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The physics output of modern experimental HEP collaborations hinges not only on the quality of its software but also on the ability of the collaborators to make the best possible use of it. With the COVID-19 pandemic making in-person training impossible, the training paradigm at Belle II was shifted from periodic workshops towards guided self-study. To that end, the study material was rebuilt from scratch as a series of modular and hands-on lessons tightly integrated with the software documentation using Sphinx. Each lesson contains multiple exercises that are supplemented with hints and complete solutions. Rather than duplicating information, students are systematically taught to work with the technical reference documentation to find the important sections for themselves. Unit tests ensure that all examples work with different software versions, and feedback buttons make it easy to submit comments for improvements. © Published under licence by IOP Publishing Ltd.
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Background: Blocking the C5a-C5aR axis in COVID-19 patients could improve outcomes by limiting myeloid cell infiltration in damaged organs and preventing excessive lung inflammation and endothelialitis. Aims and Objectives: Vilobelimab (VILO), an anti-C5a mAb that preserves the membrane attack complex (MAC), was tested in a Phase III adaptively designed multicenter, double-blind placebo (P)-controlled study for survival in critically ill COVID-19 patients. Method(s): COVID-19 pneumonia patients (N=369;VILO n=178, P n=191) within 48 hrs of intubation were randomly assigned to receive 6, 800 mg infusions of VILO or P on top of standard of care. Primary outcome was 28-day allcause mortality. Result(s): 28-day all-cause mortality was 31.7% VILO vs 41.6% P (Kaplan-Meier estimates;Cox regression site stratified, HR 0.73;95%CI:0.50-1.06;P=0.094) with a 22.7% relative mortality reduction to Day 60. In predefined primary outcome analysis without site stratification, VILO significantly reduced 28-day mortality (HR 0.67;95%CI:0.48-0.96;P=0.027);needed to treat number, 10 to save 1. VILO significantly reduced 28-day mortality in severe patients with baseline WHO ordinal scale score of 7 (n=237, HR 0.62;95%CI:0.40-0.95;P=0.028) or severe ARDS/PaO2/FiO2<=100 mmHg (n=98, HR 0.55;95%CI:0.30-0.98;P=0.044) or eGFR<60 mL/min/1.73m2 (n=108, HR 0.55;95%CI:0.31-0.96;P=0.036). Treatment emergent AEs were 90.9% VILO vs 91.0% P. Infections were comparable;VILO (62.9%), P (59.3%). Serious AEs were 58.9% VILO, 63.5% P. Conclusion(s): VILO reduced mortality at 28 to 60 days in severe COVID-19 pneumonia patients with no increase in infections suggesting the importance of targeting C5a while preserving MAC.
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The COVID-19 pandemic continues to affect the conduct of clinical trials globally. Complications may arise from pandemic-related operational challenges such as site closures, travel limitations and interruptions to the supply chain for the investigational product, or from health-related challenges such as COVID-19 infections. Some of these complications lead to unforeseen intercurrent events in the sense that they affect either the interpretation or the existence of the measurements associated with the clinical question of interest. In this article, we demonstrate how the ICH E9(R1) Addendum on estimands and sensitivity analyses provides a rigorous basis to discuss potential pandemic-related trial disruptions and to embed these disruptions in the context of study objectives and design elements. We introduce several hypothetical estimand strategies and review various causal inference and missing data methods, as well as a statistical method that combines unbiased and possibly biased estimators for estimation. To illustrate, we describe the features of a stylized trial, and how it may have been impacted by the pandemic. This stylized trial will then be revisited by discussing the changes to the estimand and the estimator to account for pandemic disruptions. Finally, we outline considerations for designing future trials in the context of unforeseen disruptions.Copyright © 2022 American Statistical Association.
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PURPOSE: Patients with COVID-19 have an increased risk for venous thrombo-embolism (VTE), especially pulmonary embolism. The exact prevalence of asymptomatic DVT is not known, as is the usefulness of screening for DVT in patients admitted to ward with COVID-19. We have studied the prevalence of asymptomatic DVT. METHODS: We performed a cross-sectional observational multi-center study at four university medical centers in The Netherlands. All adult patients admitted with COVID-19 to a medical ward were eligible for inclusion, including patients who were transferred back from the ICU to the ward. The study protocol consisted of weekly cross-sectional rounds of compression ultrasound. RESULTS: In total, 125 patients were included in the study. A significant proportion of patients (N = 34 (27%)) had developed a VTE during their admission for COVID-19 before the study ultrasound was performed. In most VTE cases (N = 27 (79%)) this concerned pulmonary embolism. A new asymptomatic DVT was found in 5 of 125 patients (4.0%; 95% CI 1.3-9.1%) (Table 2). Nine patients (7.2%; 95% CI 3.3-13.2%) developed a VTE (all PE) diagnosed within 28 days after the screening US was performed. CONCLUSION: We have shown a low prevalence (4%) of newly discovered asymptomatic DVT outside the ICU-setting in COVID-19 patients. Despite this low prevalence, nine patients developed PE (7%) within 28 days after ultrasound. This favors the hypothesis of local thrombus formation in the lungs. Based on our findings and literature, we do not recommend US-screening of asymptomatic patients with COVID-19 admitted to the ward.
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The Covid-19 pandemic escalated demand for scientific explanations and guidance, creating opportunities for scientists to become publicly visible. In this study, we compared characteristics of visible scientists during the first year of the Covid-19 pandemic (January to December 2020) across 16 countries. We find that the scientists who became visible largely matched socio-cultural criteria that have characterised visible scientists in the past (e.g., age, gender, credibility, public image, involvement in controversies). However, there were limited tendencies that scientists commented outside their areas of expertise. We conclude that the unusual circumstances created by Covid-19 did not change the phenomenon of visible scientists in significant ways.
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Background. SARS-CoV-2 induces endothelial damage and activates the complement system. In severe COVID-19 patients, complement split factor C5a is highly elevated leading to inflammation that contributes to multiorgan failure. The anti-C5a monoclonal antibody, Vilobelimab (Vilo), which preserves the membrane attack complex (MAC), was investigated in an adaptively designed, randomized doubleblind, placebo (P)-controlled Phase 3 international multicenter study for survival in critically ill COVID-19 patients (pts). Methods. COVID-19 pneumonia pts (N=368;Vilo n=177, P n=191), mechanically ventilated within 48 hrs before treatment, received up to 6, 800 mg infusions of Vilo or P on top of standard of care. The primary and main secondary endpoints were 28-day (d) and 60-d all-cause mortality. Results. Pts enrolled in the study were on corticosteroids (97%) and anticoagulants (98%) as standard of care. A smaller proportion (20%) were either continuing or had taken immunomodulators such as tocilizumab and baricitinib prior to receiving Vilo. The 28-d all-cause mortality was 31.7% with Vilo vs 41.6% with P (Kaplan-Meier estimates;Cox regression site-stratified, HR 0.73;95% CI:0.50-1.06;P=0.094), representing a 23.8% relative mortality reduction. In predefined primary outcome analysis without site stratification, however, Vilo significantly reduced mortality at 28 (HR 0.67;95% CI:0.48-0.96;P=0.027) and 60 days (HR 0.67;95% CI:0.48-0.92;P=0.016). Vilo also significantly reduced 28-d mortality in more severe pts with baseline WHO ordinal scale score of 7 (n=237, HR 0.62;95% CI:0.40-0.95;P=0.028), severe ARDS/PaO2/FiO2 <= 100 mmHg (n=98, HR 0.55;95% CI:0.30-0.98;P=0.044) and eGFR < 60 mL/min/1.73m2 (n=108, HR 0.55;95% CI:0.31-0.96;P=0.036). Treatment-emergent AEs were 90.9% Vilo vs 91.0% P. Infections were comparable: Vilo 62.9%, P 59.3%. Infection incidence per 100 Pt days were equal. No meningococcal infections were reported. Serious AEs were 58.9% Vilo, 63.5% P. Conclusion. Vilo significantly reduced mortality at 28 and 60 days in critically ill COVID-19 pts with no increase in infections suggesting the importance of targeting C5a while preserving MAC. Vilo targets inflammation which may represent an approach to treat sepsis and ARDS caused by other respiratory viruses. (Figure Presented).
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Background. Rapid COVID-19 tests can offer significant advantages and reduce health disparities. The LumiraDx SARS-CoV-2 platform can perform microfluidic fluorescence assays for the rapid detection of SARS-CoV-2 antigen (Ag) and antibodies (Ab). We evaluated both tests in a longitudinal cohort to evaluate performance during acute SARS-CoV-2 infection and recovery. Methods. We collected nasal samples from 71 unique participants at four clinic visits spanning 0-21 days since symptom onset (DSSO);blood samples were collected from the same participants over six visits spanning 0-87 DSSO. For Ag testing, 232 anterior nasal swabs were assayed by: 1) the LumiraDx Ag test, 2) a laboratory-based electrochemiluminescence immunoassay for N Ag, 3) RT-PCR (Hologic Panther Fusion), and 4) culture (growth in VeroE6AT cells). For Ab testing, 308 serum samples were assayed by: 1) the LumiraDx Ab test and 2) Roche Elecsys Anti-S SARS-CoV-2 total Ab test. Measures of concordance [positive predictive agreement (PPA), negative predictive agreement (NPA), and Cohen's Kappa (K)] were estimated for qualitative results of the LumiraDx tests versus corresponding lab reference tests. Confidence intervals were estimated via bootstrapping. Results. LumiraDx Ag results had strong agreement with lab N-Ag results (K > 0.80) across all samples. Between 0-5 days, agreement was perfect, except for one sample resulting positive by LumiraDx Ag and negative by lab Ag. Agreement with PCR results was moderate overall (K=0.60), though substantial (K > 0.6) for both 0-5 DSSO (PPA=0.96/NPA=0.80) and 6-10 DSSO (PPA=0.96/NPA=0.59). Agreement with culture results was moderate overall (K=0.46): substantial (K=0.6) between 0-5 DSSO (PPA=0.96/NPA=0.60) and fair (K=0.29) between 6-10 DSSO (PPA=1.0/NPA=0.32). LumiraDx Ab results showed almost perfect agreement with lab Ab results across all samples (K=0.88), with substantial agreement (K > 0.7) for samples collected 0-10 DSSO (PPA=0.93/NPA=0.89) and 11-28 DSSO (PPA=0.99/NPA=0.69). Longitudinal agreement of LumiraDx antigen test result and culture positivity, by PCR Ct value. Nasal samples grouped by participant (lines) and agreement of results between LumiraDx antigen test result and culture positivity (proxy for infectiousness). Conclusion. LumiraDx rapid tests perform well compared to more costly and time-consuming lab methods of Ag and Ab detection. The rapid Ag test may be helpful in identifying patients infectious between 0-5 DSSO, given the substantial concordance of the rapid Ag test and culture positivity.
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Introduction: The COVID-19 pandemic has led to an increased psychological strain on public mental health and may impact behavioural, mental, and physical health, presumably with effects on patients with severe mental disorders. Objective(s): This study examines pandemic-related physical and mental health and (compensatory) behavioural changes, in patients with BD as compared to healthy control individuals. Method(s): Physical and mental health and self-reported changes in daily structure and behaviour due to pandemic were assessed using a self-constructed questionnaire and the brief symptom inventory (BSI) from outpatient clinics in Germany, Austria, and Denmark in individuals with BD and a healthy control group. Result(s): The present study included 118 individuals with BD and 215 healthy controls. Individuals with BD reported statistically significant higher physical risk burden, increased weight gain, more physical comorbidities, and a decrease in physical activity and they further reported higher rate of COVID-19 testing, had more worries concerning health and experienced more anxiety but less social distancing. Conclusion(s): The COVID-19 pandemic seems to have a greater impact on physical health in individuals with BD than in healthy controls. Individuals with BD appear to be having more difficulties compensating their behaviour due to the pandemic which could amplify the effect of risk factors associated with poorer physical health. This highlights the necessity for optimising and targeting the overall treatment of both mental and physical health in patients with BD during periods with far-reaching changes such as COVID- 19 pandemic.
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Objective: To evaluate the difference in time from hospital admission to delivery when undergoing inpatient versus outpatient cervical ripening with a transcervical Foley catheter. Study Design: This was a randomized controlled trial of patients with singleton pregnancies, Bishop Score ≤ 6 and at least 37 weeks’ gestation, undergoing labor induction at Sinai Hospital of Baltimore and Thomas Jefferson University Hospital. Patients were randomized to outpatient or inpatient cervical ripening with a Foley catheter. Inpatients received concurrent oxytocin. Outpatients returned 12 hours after Foley placement, and on arrival oxytocin was initiated if the balloon was still in place. Foleys were removed if in place after 12-18 hours, and labor induction initiated with oxytocin as needed. The primary outcome was the difference in time from admission to delivery. A maternal satisfaction survey was also administered. Unpaired t-tests, chi-square tests, and Fisher’s exact test were performed to estimate differences in outcomes between the inpatient and outpatient arms of the study. Results: Enrollment commenced January 2016 and continued until November 2020, after randomizing 30 patients (n=15 per group). The study was terminated prematurely due to low enrollment and temporary suspension during COVID-19. There was no significant difference in time from admission to delivery between outpatient and inpatient groups (14.5 ± 6.1 versus 18.9 ± 8.2 hours, P=.11). The total induction time was shorter for the inpatient group (24.9 ± 6.8 versus 17.3 ± 9.4 hours, P=.02). There were no differences in other maternal or neonatal outcomes (P>.05). Maternal satisfaction was similar between groups on a 1-10 scale (8.6 ± 1.7 versus 8.9 ± 1.0, P=.53), and all patients felt safe. Conclusion: No difference in the primary outcome of time from admission to delivery was noted between inpatient and outpatient cervical ripening with a Foley catheter;however, this may be a result of inadequate power related to early termination. Consistent with past studies, outpatient balloon cervical ripening appears to be safe, and overall satisfaction was high. [Formula presented] [Formula presented]
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The article presents the results of a survey of science journalists from six world regions about their work during the COVID-19 pandemic. The responses show perception of increasing workload for most participants. Local scientists and peer-reviewed articles are the main sources. According to the respondents, scientists have become more available during the pandemic. The use of preprint articles was a frequent practice, but a considerable proportion declared they did not adopt different procedures when reporting them. Most also said they take fake news into account when writing their stories.
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The current outbreak of coronavirus disease (COVID-19) has reached Germany. The majority of people infected present with mild disease, but there are severe cases that need intensive care. Unlike other acute infectious diseases progressing to sepsis, the severe courses of COVID19 seemingly show prolonged progression from onset of first symptoms to life-threatening deterioration of (primarily) lung function. Diagnosis relies on PCR using specimens from the respiratory tract. Severe ARDS reflects the hallmark of a critical course of the disease. Preventing nosocomial infections (primarily by correct use of personal protective equipment) and maintenance of hospitals' operational capability are of utmost importance. Departments of Anaesthesia, Intensive Care and emergency medicine will envisage major challenges.