Conserved longitudinal alterations of anti-S-protein IgG subclasses in disease progression in initial ancestral Wuhan and vaccine breakthrough Delta infections.

Introduction: COVID-19 has a wide disease spectrum ranging from asymptomatic to severe. While humoral immune responses are critical in preventing infection, the immune mechanisms leading to severe disease, and the identification of biomarkers of disease progression and/or resolution of the infection remains to be determined. Methods: Plasma samples were obtained from infections during the initial wave of ancestral wildtype SARS-CoV-2 and from vaccine breakthrough infections during the wave of Delta variant, up to six months post infection. The spike-specific antibody profiles were compared across different severity groups and timepoints. Results: We found an association between spike-specific IgM, IgA and IgG and disease severity in unvaccinated infected individuals. In addition to strong IgG1 and IgG3 response, patients with severe disease develop a robust IgG2 and IgG4 response. A comparison of the ratio of IgG1 and IgG3 to IgG2 and IgG4 showed that disease progression is associated with a smaller ratio in both the initial wave of WT and the vaccine breakthrough Delta infections. Time-course analysis revealed that smaller (IgG1 and IgG3)/(IgG2 and IgG4) ratio is associated with disease progression, while the reverse associates with clinical recovery. Discussion: While each IgG subclass is associated with disease severity, the balance within the four IgG subclasses may affect disease outcome. Acute disease progression or infection resolution is associated with a specific immunological phenotype that is conserved in both the initial wave of WT and the vaccine breakthrough Delta infections.

A genome wide association study of chronic spontaneous urticaria risk and heterogeneity.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a dermatologic condition that is characterized by spontaneous, pruritic hives and/or angioedema that persist for six weeks or longer with no identifiable trigger. Anti-histamines and second line therapies such as omalizumab are effective for some CSU patients, but others remain symptomatic with significant impact on quality of life. This variable response to treatment and autoantibodies levels across patients highlight clinically heterogeneous subgroups. OBJECTIVE: We aimed to highlight pathways involved in CSU by investigating the genetics of CSU risk and subgroups. METHODS: We performed a genome-wide association study (GWAS) of 679 CSU patients and 4,446 controls and a GWAS of Chronic Urticaria (CU) index, which measures IgG autoantibodies levels, by comparing 447 CU-index low to 183 CU-index high patients. We also tested whether polygenic scores for autoimmune-related disorders associate with CSU risk and CU-index. RESULTS: We identified two loci significantly associated with disease risk. The strongest association maps to position 56 of HLA-DQA1 (P=1.69x10-9), where the arginine residue was associated with increased risk (OR=1.64). The second association signal colocalizes with expression-quantitative trait loci for ITPKB in whole blood (probabilitycolocalization=0.997). The arginine residue at position 56 of HLA-DQA1 was also associated with increased risk of CU-index high (P=6.15x10-5, OR=1.86), while the ITKPB association was not (P=0.64). Polygenic scores for three autoimmune-related disorders (hypothyroidism, type-1 diabetes, and vitiligo) are associated with CSU risk and CU-index (P<2.34x10-3, OR>1.72). CONCLUSION: This GWAS of CSU identifies two genome-wide significant loci and highlights the shared genetics between CU-index and autoimmune disorders.

Severity of SARS-CoV-2 Omicron XBB subvariants in Singapore (preprint)

Several XBB subvariants such as XBB.1.5, XBB.1.9, XBB.1.16 and XBB.2.3 co-circulate in Singapore. Despite the different viral properties of XBB.1.16 as compared to other XBB subvariants, comparison on their severity is limited. In this study, we investigate the outcomes of hospitalisation and severe COVID-19 infection in individuals infected with different XBB subvariants, adjusted for potential confounders such as age and vaccination history. Overall, our preliminary analysis showed no difference in the severity of different XBB variants.

A qualitative study to explore the acceptability and feasibility of implementing person-focused evidence-based pain education concepts in pre-registration physiotherapy training.

Objectives: The purpose of this study was to engage with physiotherapy clinicians, academics, physiotherapy students and patients to explore the acceptability, feasibility, and practical considerations of implementing person-focused evidence-based pain education concepts, identified from our previous research, in pre-registration physiotherapy training. Design: This qualitative study took a person-focused approach to ground pain education in the perspectives and experiences of people who deliver and use it. Data was collected via focus groups and in-depth semi-structured interviews. Data was analysed using the seven stage Framework approach. Setting: Focus groups and interviews were conducted either face to face, via video conferencing or via telephone. This depended on geographical location, participant preference, and towards the end of data collection the limitations on in-person contact due to the Covid-19 pandemic. Participants: UK based physiotherapy clinicians, physiotherapy students, academics and patients living with pain were purposively sampled and invited to take part. Results: Five focus groups and six semi-structured interviews were conducted with twenty-nine participants. Four key dimensions evolved from the dataset that encapsulate concepts underpinning the acceptability and feasibility of implementing pain education in pre-registration physiotherapy training. These are (1) make pain education authentic to reflect diverse, real patient scenarios, (2) demonstrate the value that pain education adds, (3) be creative by engaging students with content that requires active participation, (4) openly discuss the challenges and embrace scope of practice. Conclusions: These key dimensions shift the focus of pain education towards practically engaging content that reflects people experiencing pain from diverse sociocultural backgrounds. This study highlights the need for creativity in curriculum design and the importance of preparing graduates for the challenges that they will face in clinical practice.

Conserved longitudinal alterations of anti-S-protein IgG subclasses in disease progression in initial ancestral Wuhan and vaccine breakthrough Delta infections

Introduction COVID-19 has a wide disease spectrum ranging from asymptomatic to severe. While humoral immune responses are critical in preventing infection, the immune mechanisms leading to severe disease, and the identification of biomarkers of disease progression and/or resolution of the infection remains to be determined. Methods Plasma samples were obtained from infections during the initial wave of ancestral wildtype SARS-CoV-2 and from vaccine breakthrough infections during the wave of Delta variant, up to six months post infection. The spike-specific antibody profiles were compared across different severity groups and timepoints. Results We found an association between spike-specific IgM, IgA and IgG and disease severity in unvaccinated infected individuals. In addition to strong IgG1 and IgG3 response, patients with severe disease develop a robust IgG2 and IgG4 response. A comparison of the ratio of IgG1 and IgG3 to IgG2 and IgG4 showed that disease progression is associated with a smaller ratio in both the initial wave of WT and the vaccine breakthrough Delta infections. Time-course analysis revealed that smaller (IgG1 and IgG3)/(IgG2 and IgG4) ratio is associated with disease progression, while the reverse associates with clinical recovery. Discussion While each IgG subclass is associated with disease severity, the balance within the four IgG subclasses may affect disease outcome. Acute disease progression or infection resolution is associated with a specific immunological phenotype that is conserved in both the initial wave of WT and the vaccine breakthrough Delta infections.

SARS-CoV-2 Omicron variant emerged under immune selection.

The SARS-CoV-2 Omicron variant (B.1.1.529 lineage) escapes antibodies that neutralize the ancestral virus. We tested human serum panels from participants with differing infection and vaccination status using a multiplex surrogate virus neutralization assay targeting 20 sarbecoviruses. We found that bat and pangolin sarbecoviruses showed significantly less neutralization escape than the Omicron variant. We propose that SARS-CoV-2 variants have emerged under immune selection pressure and are evolving differently from animal sarbecoviruses.

Impact of the COVID-19 pandemic on surgical care in the Netherlands.

BACKGROUND: The COVID-19 pandemic caused disruption of regular healthcare leading to reduced hospital attendances, repurposing of surgical facilities, and cancellation of cancer screening programmes. This study aimed to determine the impact of COVID-19 on surgical care in the Netherlands. METHODS: A nationwide study was conducted in collaboration with the Dutch Institute for Clinical Auditing. Eight surgical audits were expanded with items regarding alterations in scheduling and treatment plans. Data on procedures performed in 2020 were compared with those from a historical cohort (2018-2019). Endpoints included total numbers of procedures performed and altered treatment plans. Secondary endpoints included complication, readmission, and mortality rates. RESULTS: Some 12 154 procedures were performed in participating hospitals in 2020, representing a decrease of 13.6 per cent compared with 2018-2019. The largest reduction (29.2 per cent) was for non-cancer procedures during the first COVID-19 wave. Surgical treatment was postponed for 9.6 per cent of patients. Alterations in surgical treatment plans were observed in 1.7 per cent. Time from diagnosis to surgery decreased (to 28 days in 2020, from 34 days in 2019 and 36 days in 2018; P < 0.001). For cancer-related procedures, duration of hospital stay decreased (5 versus 6 days; P < 0.001). Audit-specific complications, readmission, and mortality rates were unchanged, but ICU admissions decreased (16.5 versus 16.8 per cent; P < 0.001). CONCLUSION: The reduction in the number of surgical operations was greatest for those without cancer. Where surgery was undertaken, it appeared to be delivered safely, with similar complication and mortality rates, fewer admissions to ICU, and a shorter hospital stay.

COVID-19 has had a significant impact on healthcare worldwide. Hospital visits were reduced, operating facilities were used for COVID-19 care, and cancer screening programmes were cancelled. This study describes the impact of the COVID-19 pandemic on Dutch surgical healthcare in 2020. Patterns of care in terms of changed or delayed treatment are described for patients who had surgery in 2020, compared with those who had surgery in 2018­2019. The study found that mainly non-cancer surgical treatments were cancelled during months with high COVID-19 rates. Outcomes for patients undergoing surgery were similar but with fewer ICU admissions and shorter hospital stay. These data provide no insight into the burden endured by patients who had postponed or cancelled operations.

Exploring COVID-19 circuit breaker (CB) restrictions at a migrant worker dormitory in Singapore: a case study and nested mixed-method analysis of stress management and mental health

Introduction Measures to mitigate the COVID-19 outbreak in the migrant worker dormitories in Singapore included lockdown and isolation of residents for prolonged periods. In this paper, we explore efforts to ease tensions and support mental health under these conditions. Methods Case study of dormitory residents under lockdown from April to August 2020 comprises a nested mixed-method approach using an online questionnaire (n=175) and semistructured interviews (n=23) of migrant workers sampled from the survey (August to September 2020). Logistic regression models were used to analyse survey data. Semistructured interviews were analysed using applied thematic analysis. Results Survey and interview data showed that mental health was largely protected despite initial rising tensions over restrictions during lockdown. Sources of tension negatively affecting low stress responses included job related worries, OR=0.07 (95% CI 0.03 to 0.18, p<0.001), poor communication with employers, OR=0.12 (95% CI 0.03 to 0.44, p<0.001) and loneliness, OR=0.24 (95% CI 0.10 to 0.55, p<0.001). Interview narratives concurrently revealed themes around job insecurity and the effects of the lockdown ‘not being good for mind and body’, the imposition of new rules and regulations compounded by the most emphasised concern—worry about family back home. Interviewees shared how their adaptive capability played a pivotal protective role alongside social support and solidarity;aided by regular use of messaging applications, which supported mental health, OR=4.81 (95% CI 1.54 to 15.21, p<0.01). Employers were described as central to alleviating tensions, providing feedback loops to improve dorm conditions. Employees feeling their employers cared about their health and well-being was especially protective to mental health, OR=17.24 (95% CI 4.00 to 85.74, p<0.001). Gratitude and trust in government and healthcare provision was widely acknowledged. Concurrently, related attitudes such as believing in the timeliness and appropriateness of the lockdown also protected mental health, OR 2.85 (95% CI 1.08 to 7.39, p=0.03). Conclusion Tensions are mapped to protective solutions informing guidelines for future outbreak stress management response.

Post-COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection.

Importance: Little is known about the risk factors for, and the risk of, developing post-COVID-19 conditions (PCCs) among children. Objectives: To estimate the proportion of SARS-CoV-2-positive children with PCCs 90 days after a positive test result, to compare this proportion with SARS-CoV-2-negative children, and to assess factors associated with PCCs. Design, Setting, and Participants: This prospective cohort study, conducted in 36 emergency departments (EDs) in 8 countries between March 7, 2020, and January 20, 2021, included 1884 SARS-CoV-2-positive children who completed 90-day follow-up; 1686 of these children were frequency matched by hospitalization status, country, and recruitment date with 1701 SARS-CoV-2-negative controls. Exposure: SARS-CoV-2 detected via nucleic acid testing. Main Outcomes and Measures: Post-COVID-19 conditions, defined as any persistent, new, or recurrent health problems reported in the 90-day follow-up survey. Results: Of 8642 enrolled children, 2368 (27.4%) were SARS-CoV-2 positive, among whom 2365 (99.9%) had index ED visit disposition data available; among the 1884 children (79.7%) who completed follow-up, the median age was 3 years (IQR, 0-10 years) and 994 (52.8%) were boys. A total of 110 SARS-CoV-2-positive children (5.8%; 95% CI, 4.8%-7.0%) reported PCCs, including 44 of 447 children (9.8%; 95% CI, 7.4%-13.0%) hospitalized during the acute illness and 66 of 1437 children (4.6%; 95% CI, 3.6%-5.8%) not hospitalized during the acute illness (difference, 5.3%; 95% CI, 2.5%-8.5%). Among SARS-CoV-2-positive children, the most common symptom was fatigue or weakness (21 [1.1%]). Characteristics associated with reporting at least 1 PCC at 90 days included being hospitalized 48 hours or more compared with no hospitalization (adjusted odds ratio [aOR], 2.67 [95% CI, 1.63-4.38]); having 4 or more symptoms reported at the index ED visit compared with 1 to 3 symptoms (4-6 symptoms: aOR, 2.35 [95% CI, 1.28-4.31]; ≥7 symptoms: aOR, 4.59 [95% CI, 2.50-8.44]); and being 14 years of age or older compared with younger than 1 year (aOR, 2.67 [95% CI, 1.43-4.99]). SARS-CoV-2-positive children were more likely to report PCCs at 90 days compared with those who tested negative, both among those who were not hospitalized (55 of 1295 [4.2%; 95% CI, 3.2%-5.5%] vs 35 of 1321 [2.7%; 95% CI, 1.9%-3.7%]; difference, 1.6% [95% CI, 0.2%-3.0%]) and those who were hospitalized (40 of 391 [10.2%; 95% CI, 7.4%-13.7%] vs 19 of 380 [5.0%; 95% CI, 3.0%-7.7%]; difference, 5.2% [95% CI, 1.5%-9.1%]). In addition, SARS-CoV-2 positivity was associated with reporting PCCs 90 days after the index ED visit (aOR, 1.63 [95% CI, 1.14-2.35]), specifically systemic health problems (eg, fatigue, weakness, fever; aOR, 2.44 [95% CI, 1.19-5.00]). Conclusions and Relevance: In this cohort study, SARS-CoV-2 infection was associated with reporting PCCs at 90 days in children. Guidance and follow-up are particularly necessary for hospitalized children who have numerous acute symptoms and are older.

Injury-Related Pediatric Emergency Department Visits in the First Year of COVID-19.

OBJECTIVES: To describe the epidemiology of pediatric injury-related visits to children's hospital emergency departments (EDs) in the United States during early and later periods of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: We conducted a cross-sectional study using the Pediatric Health Information System, an administrative database to identify injury-related ED visits at 41 United States children's hospitals during the SARS-CoV-2 pandemic period (March 15, 2020 to March 14, 2021) and a 3 year comparator period (March 15-March 14, 2017-2020). For these 2 periods, we compared patient characteristics, injury type and severity, primary discharge diagnoses, and disposition, stratified by early (March 15, 2020 to June 30, 2020), middle (July 1, 2020 to October 31, 2020), and late (November 1, 2020 to March 14, 2021) pandemic periods. RESULTS: Overall, ED injury-related visits decreased by 26.6% during the first year of the SARS-CoV-2 pandemic, with the largest decline observed in minor injuries. ED injury-related visits resulting in serious-critical injuries increased across the pandemic (15.9% early, 4.9% middle, 20.6% late). Injury patterns with the sharpest relative declines included superficial injuries (41.7% early) and sprains/strains (62.4% early). Mechanisms of injury with the greatest relative increases included (1) firearms (22.9% early; 42.8% middle; 37% late), (2) pedal cyclists (60.4%; 24.9%; 32.2%), (3) other transportation (20.8%; 25.3%; 17.9%), and (4) suffocation/asphyxiation (21.4%; 20.2%; 28.4%) and injuries because of suicide intent (-16.2%, 19.9%, 21.8%). CONCLUSIONS: Pediatric injury-related ED visits declined in general. However, there was a relative increase in injuries with the highest severity, which warrants further investigation.

VIRTUAL LEARNING IN PSYCHIATRY: A GUIDE FOR EDUCATORS

The global COVID-19 pandemic has had a profound impact on the delivery of undergraduate psychiatry in medical schools across the world. This session will share the key findings on a report jointly produced by the Association of University Teachers of Psychiatry (AUTP) and the World Psychiatric Association (WPA) entitled 'Virtual learning in psychiatry: a guide for educators'. The session will be an interactive session that will provide undergraduate medical educators with an experiential update on delivering undergraduate psychiatry teaching virtually. At the end of the session, delegates will learn how to: •• Promote asynchronous learning through the use of artificial intelligence, online webinars, media and films. •• Deliver synchronous learning through the use of virtual ward rounds and virtual outpatient clinics, use of virtual expert patient sessions, teaching in specific psychiatric settings (e.g. forensic, eating disorders, CAMHS) and online simulation. •• Conduct virtual formative and summative assessments for medical undergraduates. •• Arrange a virtual psychiatry placement for medical undergraduates (including the provision of online Balint groups). •• Maintain a supportive and caring virtual learning environment, with space and time for delivery of the 'hidden curriculum'. •• Recognise the challenges of delivering effective online supervision to medical undergraduates, including international undergraduates.

Respiratory virus testing and clinical outcomes among children hospitalized with pneumonia.

BACKGROUND: Despite the increased availability of diagnostic tests for respiratory viruses, their clinical utility for children with community-acquired pneumonia (CAP) remains uncertain. OBJECTIVE: To identify patterns of respiratory virus testing across children's hospitals prior to the COVID-19 pandemic and to determine whether hospital-level rates of viral testing were associated with clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study of children hospitalized for CAP at 19 children's hospitals in the United States from 2010-2019. MAIN OUTCOMES AND MEASURES: Using a novel method to identify the performance of viral testing, we assessed time trends in the use of viral tests, both overall and stratified by testing method. Adjusted proportions of encounters with viral testing were compared across hospitals and were correlated with length of stay, antibiotic and oseltamivir use, and performance of ancillary laboratory testing. RESULTS: There were 46,038 hospitalizations for non-severe CAP among children without complex chronic conditions. The proportion with viral testing increased from 38.8% to 44.2% during the study period (p < .001). Molecular testing increased (27.2% to 40.0%, p < .001) and antigen testing decreased (33.2% to 7.8%, p < .001). Hospital-specific adjusted proportions of testing ranged from 10.0% to 83.5% and were not associated with length of stay, antibiotic use, or antiviral use. Hospitals that performed more viral testing did not have lower rates of ancillary laboratory testing. CONCLUSIONS: Viral testing practices varied widely across children's hospitals and were not associated with clinically important process or outcome measures. Viral testing may not influence clinical management for many children hospitalized with CAP.

A Cross-Sectional Time Course of COVID-19 Related Worry, Perceived Stress, and General Anxiety in the Context of Post-Traumatic Stress Disorder-like Symptomatology.

The COVID-19 pandemic within the United States of America resulted in over 800,000 deaths as of February 2022 and has been addressed by social distancing or stay-at-home measures. Collective prolonged multimodal trauma on this scale is likely to elicit symptomatology in the general population consistent with post-traumatic stress disorder (PTSD), somatization, anxiety, and stress. The psychological component of this response contributes substantially to the burden of this disease worldwide. This cross-sectional study examines the relationship between COVID-19-related concern, anxiety, and perceived stress on PTSD-like symptomatology over the course of the COVID-19 pandemic. Participants were recruited via social media within the United States of America between 8th May 2020 and 11th August 2021 to complete an internet questionnaire including mood, personality, and COVID-19-specific scales. General anxiety and PTSD-like symptomatology were above the screening cutoffs for most respondents. These measures increased in severity over the pandemic, with the change point of our Concern scale preceding that of the other significant measures. Measures of COVID-19-related concern, generalized anxiety, and PTSD-like symptomatology were strongly correlated with each other. Anxiety, perceived stress, and PTSD-like symptomatology are strongly interrelated, increase with pandemic length, and are linked to reported levels of concern over COVID-19. These observations may aid future research and policy as the pandemic continues.

Complement blockade with eculizumab for treatment of severe Coronavirus Disease 2019 in pregnancy: A case series.

PROBLEM: We evaluated eculizumab, a complement protein C5 inhibitor, for treatment of severe COVID-19 in pregnant and postpartum individuals. METHOD OF STUDY: Protocol ECU-COV-401 (clinicaltrials.gov NCT04355494) is an open label, multicenter, Expanded Access Program (EAP), evaluating eculizumab for treatment of severe COVID-19. Participants enrolled at our center from August 2020 to February 2021. Hospitalized patients were eligible if they had severe COVID-19 with bilateral pulmonary infiltrates and oxygen requirement. Eculizumab was administered on day 1 (1200 mg IV) with additional doses if still hospitalized (1200 mg IV on Days 4 and 8; 900 mg IV on Days 15 and 22; optional doses on Days 12 and 18). The primary outcome was survival at Day 15. Secondary outcomes included survival at Day 29, need for mechanical ventilation, and duration of hospital stay. We evaluated pharmacokinetic and pharmacodynamic data, safety, and adverse outcomes. RESULTS: Eight participants were enrolled at the Cedars-Sinai Medical Center, six during pregnancy (mean 30 ± 4.0 weeks) and two in the postpartum period. Baseline oxygen requirement ranged from 2 L/min nasal cannula to 12 L/min by non-rebreather mask. The median number of doses of eculizumab was 2 (range 1-3); the median time to hospital discharge was 5.5 days (range 3-12). All participants met the primary outcome of survival at Day 15, and all were alive and free of mechanical ventilation at Day 29. In three participants we demonstrated that free C5 and soluble C5b-9 levels decreased following treatment. There were no serious adverse maternal or neonatal events attributed to eculizumab at 3 months. CONCLUSION: We describe use of eculizumab to treat severe COVID-19 in a small series of pregnant and postpartum adults. A larger, controlled study in pregnancy is indicated.

Corticosteroids and Other Treatments Administered to Children Tested for SARS-CoV-2 Infection in Emergency Departments.

OBJECTIVE: We sought to determine if corticosteroid administration is associated with a SARS-CoV-2 nucleic acid test-positive result and to describe therapies administered to SARS-CoV-2 infected children. METHODS: We collected cross-sectional data from participants recruited in 41 pediatric emergency departments (ED) in 10 countries between March 2020 and June 2021. Participants were <18 years old, had signs or symptoms of, or risk factors for acute SARS-CoV-2 infection, and had nucleic acid testing performed. To determine if SARS-CoV-2 test status was independently associated with corticosteroid administration, we used a multivariable conditional logistic regression model matched by study site to compare treatments administered based on SARS-CoV-2 test and disposition status. This analysis was repeated for the subgroup of study participants who were hospitalized. RESULTS: 30.3% (3,121/10,315) of participants were SARS-CoV-2-positive. Although remdesivir was more commonly administered to SARS-CoV-2-positive children, use was infrequent (25/3120 [0.8%] vs 1/7188 [0.01%]; P = .001). Corticosteroid use was less common among SARS-CoV-2-positive children (219/3120 [7.0%] vs 759/7190 [10.6%]; P < .001). Among hospitalized children, there were no differences in provision of inotropes, respiratory support, chest drainage or extracorporeal membrane oxygenation between groups. Corticosteroid administration was associated with age, history of asthma, wheezing, study month, hospitalization and intensive care unit admission; it was not associated with a positive SARS-CoV-2 test result overall (aOR: 0.91; 95%CI: 0.74, 1.12) or among the subgroup of those hospitalized (aOR: 1.04; 95%CI: 0.75, 1.44). CONCLUSIONS: Few disease-specific treatments are provided to SARS-CoV-2-positive children; clinical trials evaluating therapies in children are urgently needed.

Cybersecurity educational games: a theoretical framework

Purpose>Computer games that teach cybersecurity concepts have been developed to help both individuals and organizations shore up their defence against cybercrimes. Evidence of the effectiveness of these games has been rather weak, however. This paper aims to guide the design and testing of more effective cybersecurity educational games by developing a theoretical framework.Design/methodology/approach>A review of the literature is conducted to explore the dependent variable of this research stream, learning outcomes and its relationship with four independent variables, game characteristics, game context, learning theory and user characteristics.Findings>The dependent variable can be measured by five learning outcomes: information, content, strategic knowledge, eagerness to learn/time spent and behavioral change. Game characteristics refer to features that contribute to a game’s usefulness, interactivity, playfulness or attractiveness. Game context pertains to factors that determine how a game is used, including the target audience, the skill involved and the story. Learning theory explains how learning takes place and can be classified as behaviorism, cognitivism, humanism, social learning or constructivism. User characteristics including gender, age, computer experience, knowledge and perception, are attributes that can impact users’ susceptibility to cybercrimes and hence learning outcomes.Originality/value>The framework facilitates taking stock of past research and guiding future research. The use of the framework is illustrated in a critique of two research streams. Multiple research directions are discussed for continued research into the design and testing of next-generation cybersecurity computer games.

Outcomes of SARS-CoV-2-Positive Youths Tested in Emergency Departments: The Global PERN-COVID-19 Study.

Importance: Severe outcomes among youths with SARS-CoV-2 infections are poorly characterized. Objective: To estimate the proportion of children with severe outcomes within 14 days of testing positive for SARS-CoV-2 in an emergency department (ED). Design, Setting, and Participants: This prospective cohort study with 14-day follow-up enrolled participants between March 2020 and June 2021. Participants were youths aged younger than 18 years who were tested for SARS-CoV-2 infection at one of 41 EDs across 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States. Statistical analysis was performed from September to October 2021. Exposures: Acute SARS-CoV-2 infection was determined by nucleic acid (eg, polymerase chain reaction) testing. Main Outcomes and Measures: Severe outcomes, a composite measure defined as intensive interventions during hospitalization (eg, inotropic support, positive pressure ventilation), diagnoses indicating severe organ impairment, or death. Results: Among 3222 enrolled youths who tested positive for SARS-CoV-2 infection, 3221 (>99.9%) had index visit outcome data available, 2007 (62.3%) were from the United States, 1694 (52.6%) were male, and 484 (15.0%) had a self-reported chronic illness; the median (IQR) age was 3 (0-10) years. After 14 days of follow-up, 735 children (22.8% [95% CI, 21.4%-24.3%]) were hospitalized, 107 (3.3% [95% CI, 2.7%-4.0%]) had severe outcomes, and 4 children (0.12% [95% CI, 0.03%-0.32%]) died. Characteristics associated with severe outcomes included being aged 5 to 18 years (age 5 to <10 years vs <1 year: odds ratio [OR], 1.60 [95% CI, 1.09-2.34]; age 10 to <18 years vs <1 year: OR, 2.39 [95% CI 1.38-4.14]), having a self-reported chronic illness (OR, 2.34 [95% CI, 1.59-3.44]), prior episode of pneumonia (OR, 3.15 [95% CI, 1.83-5.42]), symptoms starting 4 to 7 days prior to seeking ED care (vs starting 0-3 days before seeking care: OR, 2.22 [95% CI, 1.29-3.82]), and country (eg, Canada vs US: OR, 0.11 [95% CI, 0.05-0.23]; Costa Rica vs US: OR, 1.76 [95% CI, 1.05-2.96]; Spain vs US: OR, 0.51 [95% CI, 0.27-0.98]). Among a subgroup of 2510 participants discharged home from the ED after initial testing and who had complete follow-up, 50 (2.0%; 95% CI, 1.5%-2.6%) were eventually hospitalized and 12 (0.5%; 95% CI, 0.3%-0.8%) had severe outcomes. Compared with hospitalized SARS-CoV-2-negative youths, the risk of severe outcomes was higher among hospitalized SARS-CoV-2-positive youths (risk difference, 3.9%; 95% CI, 1.1%-6.9%). Conclusions and Relevance: In this study, approximately 3% of SARS-CoV-2-positive youths tested in EDs experienced severe outcomes within 2 weeks of their ED visit. Among children discharged home from the ED, the risk was much lower. Risk factors such as age, underlying chronic illness, and symptom duration may be useful to consider when making clinical care decisions.

Interregional Transfers for Pandemic Surges.

BACKGROUND: Hospital inpatient and intensive care unit (ICU) bed shortfalls may arise due to regional surges in volume. We sought to determine how interregional transfers could alleviate bed shortfalls during a pandemic. METHODS: We used estimates of past and projected inpatient and ICU cases of coronavirus disease 2019 (COVID-19) from 4 February 2020 to 1 October 2020. For regions with bed shortfalls (where the number of patients exceeded bed capacity), transfers to the nearest region with unused beds were simulated using an algorithm that minimized total interregional transfer distances across the United States. Model scenarios used a range of predicted COVID-19 volumes (lower, mean, and upper bounds) and non-COVID-19 volumes (20%, 50%, or 80% of baseline hospital volumes). Scenarios were created for each day of data, and worst-case scenarios were created treating all regions' peak volumes as simultaneous. Mean per-patient transfer distances were calculated by scenario. RESULTS: For the worst-case scenarios, national bed shortfalls ranged from 669 to 58 562 inpatient beds and 3208 to 31 190 ICU beds, depending on model volume parameters. Mean transfer distances to alleviate daily bed shortfalls ranged from 23 to 352 miles for inpatient and 28 to 423 miles for ICU patients, depending on volume. Under all worst-case scenarios except the highest-volume ICU scenario, interregional transfers could fully resolve bed shortfalls. To do so, mean transfer distances would be 24 to 405 miles for inpatients and 73 to 476 miles for ICU patients. CONCLUSIONS: Interregional transfers could mitigate regional bed shortfalls during pandemic hospital surges.