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Background and aims: Atrial fibrillation (AF) causes at least one-fifth of ischaemic strokes, with a high risk of early recurrence. Oral anticoagulation is highly effective for reducing the long-term risk of recurrent ischaemic stroke in patients with AF. However, its benefit in the acute phase is unclear. OPTIMAS is an RCT aiming to establish the safety and efficacy of early anticoagulation with a direct oral anticoagulant (DOAC). Methods: OPTIMAS will enrol 3,478 participants with ischaemic stroke and AF from 100+ stroke services in the UK. Participants are randomised 1:1 to early (within 4 days) or standard (day 7 to 14 after stroke) initiation of anticoagulation. Follow-up is at 90 days, blinded to treatment allocation. The primary outcome is the incidence of stroke of any cause, and systemic arterial embolism. Results: OPTIMAS opened in June 2019 and is recruiting from 87 sites. 1,714 participants have been randomised. Recruitment and site-set up were reduced during the COVID-19 pandemic, due to national lockdowns and hospital staff being reallocated to COVID-related trials. We rapidly developed a contingency plan to face these challenges, implementing strategies, such as collecting the 90-day follow-ups and obtaining consents over the phone, and encouraging sites to sign up to the NIHR Associate PI Scheme to help with trial-related activities. The trial has consistently been recruiting 80+ patients per month. Conclusions: OPTIMAS will determine the efficacy and safety of early anticoagulation in patients with ischaemic strokes and AF. The trial is recruiting successfully despite COVID-19.
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Introduction: The emergence of the SARS-CoV-2 virus, the cause of the COVID-19 pandemic, in late 2019 put every country on high alert and led to major changes in global diagnostic testing capability in infectious disease. From the outset it was apparent that local health authorities were under-prepared and under-staffed to cope with the rapid onset and spread of the disease. Demand for SAR-CoV-2 testing soared, highlighting the limitations of capacity in existing infectious disease laboratories along with requests from governments to support growing testing need. We partnered with US and UK Governments to establish, supply, staff and operate three large-scale, high-throughput SARS-CoV-2 testing facilities. These were ultimately established in Valencia, CA, offering testing of up to 150k samples per day, and in Loughborough and Newport, UK, offering a combined testing of up to 70k samples per day. The biggest challenge faced globally was the unprecedented scale of testing required and the timeframe to deliver a reliable and sensitive high-throughput assay. The benefits of industry and government partnerships become evident along with having a dedicated supply chain to feed the reagent and consumable needs for high-throughput testing as well as a highly accurate test with a fast turnaround time. Experts from multiple divisions, including R&D, Genomics, Enterprise, and regional centres were bought into the project, resulting in the establishment of SARS-CoV-2 testing within the three facilities in approximately eight weeks. Clinical testing experts in high-throughput, newborn screening, and rare disease testing, built molecular testing pipelines for the facilities based around the use of real-time polymerase chain reaction (RT-PCR) assays and sequencing. Laboratories were setup to meet the requirements set by various regulatory and accreditation agencies such as Clinical Laboratory Improvement Amendments, College of American Pathologies, the UK National Health Service validation group and ISO15189. Methods: Underpinning the testing was the massive IT and bioinformatics effort to enable reporting of the testing outcomes to the relevant authorities. We were able to deploy a novel LIMS system that is used throughout the laboratories to maintain sample chain of custody from arrival at the facility to reporting of results and incorporating interpretive software to support clinical interpretation of the resulting RT-PCR data. The LIMS systems are constantly undergoing improvement to support interpretation and troubleshooting. Local experts in clinical interpretation and reporting were onboarded to augment data analysis and ensure high-quality and reliable reporting whilst ensuring that clinical governance remains at the centre of all activities. Results: Before any SARS-CoV-2 testing was able to commence, several significant challenges were overcome by combining the expertise of our global teams with the local knowledge and support of the respective Governments. Experts in logistics and program management were able to convert three empty facilities with no pre-existing laboratory infrastructure into fully functional clinical testing laboratories within eight weeks. Our assay manufacturing capacity was majorly expanded to accommodate the requirements of SARS-CoV-2 testing, with all three facilities operating on automated platforms and utilizing chemistry with a dedicated secure supply chain. The final major challenge was rapid onboarding and training of staff for the facilities, and a year out, the two active facilities are currently employing over 600 individuals. Conclusion: To date the three facilities have performed over 12 million SARS-CoV-2 RT-PCR assays and SARS-CoV-2 testing will continue into 2022. The number of cases is again growing globally, and with the emergence of new variants and continual uncertainty about the impact on existing vaccines, there is an ongoing requirement for this scale of testing. From the experience of the SARS-CoV-2 global pandemic, the benefits of industry and government collaboration or the public has become much clearer, including greater access to large-scale testing options, significant reductions in time-to-testing and reporting and the rapid deployment of modern, cutting edge technology in diagnostic and monitoring programmes and eventually reduced costs to health services from mass-production. Ultimately the longevity of the individual testing facilities is unclear, but the future of large-scale clinical testing has changed forever and the legacy of this is the clear benefit to everybody when industry and governments work together to provide the public high quality and reliable testing operations.
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INTRODUCTION AND OBJECTIVE: The severe acuterespiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created a surge of research to help better understand the breadth of possible sequelae. However, little is known regarding the impact on semen parameters and fertility potential. Our study sought to evaluate the impact of SARS-CoV-2 on male reproduction among American men. We collected semen samples from men who recovered from SARS-CoV-2 infection to evaluate for the presence of SARS-CoV-2. We also assessed the impact of SARS-CoV-2 infection on total sperm number (TSN) in ejaculate both during the acute phase after testing positive and a smaller cohort of men at follow-up. METHODS: We prospectively recruited thirty men diagnosed with acute SARS-CoV-2 infection using real-time reverse transcriptasepolymerase chain reaction (RT-PCR) of pharyngeal swab specimens. Semen samples were collected from each individual using mailed kits. Follow-up semen samples were done with mailed kits or inperson in office setting. Semen analysis and PCR was performed after samples were received. RESULTS: Thirty semen samples from recovered men were obtained 11-64 days after testing positive for SAR-CoV-2 infection. The median duration between positive SAR-CoV-2 test and semen collection was 37 days (IQR=23). The median total sperm number (TSN) in ejaculate was 12.5 million (IQR=53.1). When compared with age-matched SARS-CoV-2(-) men, TSN was lower among SARS-CoV-2(+) men (p=0.0024). Five men completed a follow-up sperm analysis (median 3 months) and had a median TSN of 18 million (IQR=21.6). No RNA was detected by means of RT-PCR in the semen in 16 samples tested. CONCLUSIONS: SARS-CoV-2 infection, though not detected in semen of recovered men, can affect TSN in ejaculate in the acute setting. Whether SARS-CoV-2 can affect spermatogenic function longterm remains to be evaluated.
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Campbell's Law warns that when measurements become consequential those whose performance is being measured may try to skew the results. This case study examines the Trump administration's efforts to present COVID-19 statistics that would discourage restricting economic activities and encourage reopening the economy. © 2021, National Numeracy Network. All rights reserved.
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BACKGROUND AND PURPOSE: There are very few studies of the characteristics and causes of ICH in COVID-19, yet such data are essential to guide clinicians in clinical management, including challenging anticoagulation decisions. We aimed to describe the characteristics of spontaneous symptomatic intracerebral haemorrhage (ICH) associated with COVID-19. METHODS: We systematically searched PubMed, Embase and the Cochrane Central Database for data from patients with SARS-CoV-2 detected prior to or within 7 days after symptomatic ICH. We did a pooled analysis of individual patient data, then combined data from this pooled analysis with aggregate-level data. RESULTS: We included data from 139 patients (98 with individual data and 41 with aggregate-level data). In our pooled individual data analysis, the median age (IQR) was 60 (53-67) years and 64% (95% CI 54-73.7%) were male; 79% (95% CI 70.0-86.9%) had critically severe COVID-19. The pooled prevalence of lobar ICH was 67% (95% CI 56.3-76.0%), and of multifocal ICH was 36% (95% CI 26.4-47.0%). 71% (95% CI 61.0-80.4%) of patients were treated with anticoagulation (58% (95% CI 48-67.8%) therapeutic). The median NIHSS was 28 (IQR 15-28); mortality was 54% (95% CI 43.7-64.2%). Our combined analysis of individual and aggregate data showed similar findings. The pooled incidence of ICH across 12 cohort studies of inpatients with COVID-19 (n = 63,390) was 0.38% (95% CI 0.22-0.58%). CONCLUSIONS: Our data suggest that ICH associated with COVID-19 has different characteristics compared to ICH not associated with COVID-19, including frequent lobar location and multifocality, a high rate of anticoagulation, and high mortality. These observations suggest different underlying mechanisms of ICH in COVID-19 with potential implications for clinical treatment and trials.
Subject(s)
COVID-19 , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/epidemiology , Cohort Studies , Humans , Male , Middle Aged , SARS-CoV-2ABSTRACT
Objective: Our aim was to evaluate the semen parameters of men with COVID-19 infection. Design: A prospective study was performed to evaluate the gross semen parameters in men with COVID-19 infection. Samples of saliva and semen were collected and analyzed. Materials and Methods: We included men age 18-70 years old who tested positive for COVID-19. Subjects were contacted about willingness to participate. Packages with sterile specimen containers were mailed to the subject’s house with a preaddressed package included to return to our lab. The semen then underwent gross semen analysis for volume, concentration, pH and motility. Results: A total of 12 men were enrolled in the study with a median age of 35.5 (IQR = 19.5) (Table 1). The median duration of infection was 37 days (IQR = 21) and 2/12 (16.7%) had associated orchitis symptoms during the infective period. For the 11/12 men who returned a semen specimen, median volume was 1.6cc (IQR = 1.65), median pH was 7.2 (IQR = 0.2), median concentration was 14 million/cc (IQR = 30.25), and median motility of 0% (IQR = 12.5). Conclusions: We evaluated 11 men’s gross semen parameters after confirmed infection with COVID-19. The median concentration for these men is abnormally low compared to World Health Organization guidelines, and further evaluation is needed to determine the impact that COVID-19 infection can have on the testis and for what duration. [Formula presented]