COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Fault-Tolerant Cycle-Embedding of Crossed Cubes

Abstract The crossed cube CQ n introduced by Efe has many properties similar to those of the popular hypercube. However, the diameter of CQ n is about one half of that of the hypercube. Failures of links and nodes in an interconnection network are inevitable. Hence, in this paper, we consider the hybrid fault-tolerant capability of the crossed cube. Letting f e and f v be the numbers of faulty edges and vertices in CQ n , we show that a cycle of length l, for any 4 l |V (CQ n )| − f v , can be embedded into a wounded crossed cube as long as the total number of faults (f v + f e ) is no more than n − 2, and we say that CQ n is (n − 2)-fault-tolerant pancyclic. This result is optimal in the sense that if there are n − 1 faults, there is no guarantee of having a cycle of a certain length in it

Comparisons of clinical impacts on individuals with Brugada electrocardiographic patterns defined by ISHNE criteria or EHRA/HRS/APHRS criteria: a nationwide community-based study

<p><b>Introduction:</b> Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac death. Two different diagnostic criteria proposed by International Society for Holter and Noninvasive Electrocardiography (ISHNE) and Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society (HRS/EHRA/APHRS) were widely used in clinical practice. The difference in prevalence and prognosis of BrP by applying the two different criteria was never studied before.</p> <p><b>Methods:</b> This study was prospectively conducted in a nationwide large-scale stratified random sampling community-based cohort (HALST) from Han Chinese population in Taiwan from December 2008 to December 2012. We compared the prevalence and prognosis of BrP defined by the two diagnostic criteria.</p> <p><b>Results:</b> A total of 5214 adults were enrolled (2530 men) with mean age of 69.3 years. Four had spontaneous type 1 BrP (0.077%). By the HRS/EHRA/APHRS criteria, 68 individuals have type 2 BrP (1.30%) and 101 have type 3 BrP (1.94%) whereas by the ISHNE criteria, 46 individuals exhibited type 2 BrP (0.88%). When applying the ISHNE criteria, the number of individuals with BrP decreased by 71%. However, all-cause mortality and cardiovascular mortality were not different between individuals with or without BrP, irrespective of the criteria used.</p> <p><b>Conclusions:</b> The two different criteria may impact the diagnostic yield of individuals with BrP, but do not affect the prognosis of the individuals with BrP.Key messages</p><p>Comparing with the use of HRS/EHRA/APHRS criteria, the number of individuals with Brugada ECG patterns was decreased by 71% when applying the ISHNE criteria.</p><p>The prognosis of individuals with Brugada ECG patterns defined by 2012 ISHNE or 2013 HRS/EHRA/APHRS criteria were not different.</p><p></p> <p>Comparing with the use of HRS/EHRA/APHRS criteria, the number of individuals with Brugada ECG patterns was decreased by 71% when applying the ISHNE criteria.</p> <p>The prognosis of individuals with Brugada ECG patterns defined by 2012 ISHNE or 2013 HRS/EHRA/APHRS criteria were not different.</p

Comparisons of clinical impacts on individuals with Brugada electrocardiographic patterns defined by ISHNE criteria or EHRA/HRS/APHRS criteria: A nationwide community-based study

[[abstract]]INTRODUCTION: Identifying Brugada electrocardiographic pattern (BrP) early is crucial to prevent sudden cardiac death. Two different diagnostic criteria proposed by International Society for Holter and Noninvasive Electrocardiography (ISHNE) and Heart Rhythm Society/European Heart Rhythm Association/Asia-Pacific Heart Rhythm Society (HRS/EHRA/APHRS) were widely used in clinical practice. The difference in prevalence and prognosis of BrP by applying the two different criteria was never studied before. METHODS: This study was prospectively conducted in a nationwide large-scale stratified random sampling community-based cohort (HALST) from Han Chinese population in Taiwan from December 2008 to December 2012. We compared the prevalence and prognosis of BrP defined by the two diagnostic criteria. RESULTS: A total of 5214 adults were enrolled (2530 men) with mean age of 69.3 years. Four had spontaneous type 1 BrP (0.077%). By the HRS/EHRA/APHRS criteria, 68 individuals have type 2 BrP (1.30%) and 101 have type 3 BrP (1.94%) whereas by the ISHNE criteria, 46 individuals exhibited type 2 BrP (0.88%). When applying the ISHNE criteria, the number of individuals with BrP decreased by 71%. However, all-cause mortality and cardiovascular mortality were not different between individuals with or without BrP, irrespective of the criteria used. CONCLUSIONS: The two different criteria may impact the diagnostic yield of individuals with BrP, but do not affect the prognosis of the individuals with BrP. Key messages Comparing with the use of HRS/EHRA/APHRS criteria, the number of individuals with Brugada ECG patterns was decreased by 71% when applying the ISHNE criteria. The prognosis of individuals with Brugada ECG patterns defined by 2012 ISHNE or 2013 HRS/EHRA/APHRS criteria were not different

Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration

Neoadjuvant systemic therapy (NAST) provides the unique opportunity to assess response to treatment after months rather than years of follow-up. However, significant variability exists in methods of pathologic assessment of response to NAST, and thus its interpretation for subsequent clinical decisions. Our international multidisciplinary working group was convened by the Breast International Group-North American Breast Cancer Group (BIG-NABCG) collaboration and tasked to recommend practical methods for standardized evaluation of the post-NAST surgical breast cancer specimen for clinical trials that promote accurate and reliable designation of pathologic complete response (pCR) and meaningful characterization of residual disease. Recommendations include multidisciplinary communication; clinical marking of the tumor site (clips); and radiologic, photographic, or pictorial imaging of the sliced specimen, to map the tissue sections and reconcile macroscopic and microscopic findings. The information required to define pCR (ypT0/is ypN0 or ypT0 yp N0), residual ypT and ypN stage using the current AJCC/UICC system, and the Residual Cancer Burden system were recommended for quantification of residual disease in clinical trials

A multi-country analysis of COVID-19 hospitalizations by vaccination status

Background: Individuals vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), when infected, can still develop disease&nbsp;that requires hospitalization. It remains unclear whether these patients differ from hospitalized unvaccinated patients with regard to presentation, coexisting comorbidities, and outcomes. Methods: Here, we use data from an international consortium to study this&nbsp;question and assess whether differences between these groups are&nbsp;context specific. Data from 83,163 hospitalized COVID-19 patients (34,843 vaccinated, 48,320 unvaccinated) from 38 countries were analyzed. Findings: While typical symptoms were more often reported in unvaccinated patients, comorbidities, including some associated with worse prognosis in previous studies, were more common in vaccinated patients. Considerable between-country variation in both in-hospital fatality risk and vaccinated-versus-unvaccinated difference in this outcome was observed. Conclusions: These findings will inform allocation of healthcare resources in future surges as well as design of longer-term international studies to characterize changes in clinical profile of hospitalized COVID-19 patients related to vaccination history. Funding: This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome (215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z, and 220757/Z/20/Z); the Bill&nbsp;&amp; Melinda Gates&nbsp;Foundation (OPP1209135); and the philanthropic support of the donors&nbsp;to the University of Oxford's COVID-19 Research Response Fund (0009109). Additional funders are listed in the "acknowledgments" section

Paediatric COVID-19 mortality: a database analysis of the impact of health resource disparity

Background The impact of the COVID-19 pandemic on paediatric populations varied between high-income countries (HICs) versus low-income to middle-income countries (LMICs). We sought to investigate differences in paediatric clinical outcomes and identify factors contributing to disparity between countries.Methods The International Severe Acute Respiratory and Emerging Infections Consortium (ISARIC) COVID-19 database was queried to include children under 19 years of age admitted to hospital from January 2020 to April 2021 with suspected or confirmed COVID-19 diagnosis. Univariate and multivariable analysis of contributing factors for mortality were assessed by country group (HICs vs LMICs) as defined by the World Bank criteria.Results A total of 12 860 children (3819 from 21 HICs and 9041 from 15 LMICs) participated in this study. Of these, 8961 were laboratory-confirmed and 3899 suspected COVID-19 cases. About 52% of LMICs children were black, and more than 40% were infants and adolescent. Overall in-hospital mortality rate (95% CI) was 3.3% [=(3.0% to 3.6%), higher in LMICs than HICs (4.0% (3.6% to 4.4%) and 1.7% (1.3% to 2.1%), respectively). There were significant differences between country income groups in intervention profile, with higher use of antibiotics, antivirals, corticosteroids, prone positioning, high flow nasal cannula, non-invasive and invasive mechanical ventilation in HICs. Out of the 439 mechanically ventilated children, mortality occurred in 106 (24.1%) subjects, which was higher in LMICs than HICs (89 (43.6%) vs 17 (7.2%) respectively). Pre-existing infectious comorbidities (tuberculosis and HIV) and some complications (bacterial pneumonia, acute respiratory distress syndrome and myocarditis) were significantly higher in LMICs compared with HICs. On multivariable analysis, LMIC as country income group was associated with increased risk of mortality (adjusted HR 4.73 (3.16 to 7.10)).Conclusion Mortality and morbidities were higher in LMICs than HICs, and it may be attributable to differences in patient demographics, complications and access to supportive and treatment modalities