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BackgroundIncreasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021–March 2022 when the Omicron variant was spreading in multiple countries: high-income countries = 600 tests/100 000 people/day; LMICs = 14 tests/100 000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear.MethodsWe used Propelling Action for Testing and Treating (PATAT), an LMIC-focused agent-based model to simulate coronavirus disease 2019 (COVID-19) epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from individuals without SARS-CoV-2 and measured impact based on the number of infections averted due to test-and-isolate.ResultsTesting symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires at least 200–400 tests/100 000 people/day, on average, as symptomatic testing demand is highly influenced by individuals without SARS-CoV-2. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yield the largest additional infections averted.ConclusionsTesting strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.

Diagnostic assays for various infectious diseases, including COVID-19, have been challenged for their utility as standalone point-of-care diagnostic tests due to suboptimal accuracy, complexity, high cost or long turnaround times for results. It is therefore critical to optimise their use to meet the needs of users. We used a simulation approach to estimate diagnostic outcomes, number of tests required and average turnaround time of using two-test algorithms compared with singular testing; the two tests were reverse transcription polymerase chain reaction (RT-PCR) and an antigen-based rapid diagnostic test (Ag-RDT). A web-based application of the model was developed to visualise and compare diagnostic outcomes for different disease prevalence and test performance characteristics (sensitivity and specificity). We tested the model using hypothetical prevalence data for COVID-19, representing low- and high-prevalence contexts and performance characteristics of RT-PCR and Ag-RDTs. The two-test algorithm when RT-PCR was applied to samples negative by Ag-RDT predicted gains in sensitivity of 27% and 7%, respectively, compared with Ag-RDT and RT-PCR alone. Similarly, when RT-PCR was applied to samples positive by Ag-RDT, specificity gains of 2.9% and 1.9%, respectively, were predicted. The algorithm using Ag-RDT followed by RT-PCR as a confirmatory test for positive patients limited the requirement of RT-PCR testing resources to 16,400 and 3,034 tests when testing a population of 100,000 with an infection prevalence of 20% and 0.05%, respectively. A two-test algorithm comprising a rapid screening test followed by confirmatory laboratory testing can reduce false positive rate, produce rapid results and conserve laboratory resources, but can lead to large number of missed cases in high prevalence setting. The web application of the model can identify the best testing strategies, tailored to specific use cases and we also present some examples how it was used as part of the Access to Covid-19 Tools (ACT) Accelerator Diagnostics Pillar.

Background Testing remains critical to controlling the COVID-19 pandemic. Antigen-detecting rapid diagnostic tests (Ag-RDTs), which can be used at the point of care, have the potential to increase access to COVID-19 testing, particularly in settings with limited laboratory capacity. This systematic review synthesized literature on specific use cases and performance of Ag-RDTs for detecting SARS-CoV-2, for the first comprehensive assessment of Ag-RDT use in real-world settings. Methods We searched three databases (PubMed, EMBASE and medRxiv) up to 12 April 2021 for publications on Ag-RDT use for large-scale screening and surveillance of COVID-19, excluding studies of only presumptive COVID-19 patients. We tabulated data on the study setting, populations, type of test, diagnostic performance, and operational findings. We assessed risk of bias using QUADAS-2 and an adapted tool for prevalence studies. Results From 4313 citations, 39 studies conducted in asymptomatic and symptomatic individuals were included. Of 39 studies, 37 (94.9%) investigated lateral flow Ag-RDTs and 2 (5.1%) investigated multiplex sandwich chemiluminescent enzyme immunoassay Ag-RDTs. Six categories of testing initiatives were identified: mass screening (n=13), targeted screening (n=11), healthcare entry testing (n=6), at-home testing (n=4), surveillance (n=4) and prevalence survey (n=1). Sensitivity and specificity values by testing category are shown in the table. Ag-RDTs were noted as convenient, easy-to-use, and low cost, with a rapid turnaround time and high user acceptability. Risk of bias was generally low or unclear across studies. Conclusion During the first year of the COVID-19 pandemic, Ag-RDTs were used across a wide range of real-world settings for screening and surveillance of COVID-19 in both symptomatic and asymptomatic individuals. Ag-RDTs were fast and simple to run, but due to their often low sensitivity, careful consideration must be given to their implementation and interpretation. Ag-RDTs have subsequently been rolled out more broadly and recommended for COVID-19 self-testing. Disclosures Talya Underwood, MPhil, Oncotherapeutics: Medical writing.

The first step in SARS-CoV-2 genomic surveillance is testing to identify people who are infected. However, global testing rates are falling as we emerge from the acute health emergency and remain low in many low- and middle-income countries (mean = 27 tests per 100,000 people per day). We simulated COVID-19 epidemics in a prototypical low- and middle-income country to investigate how testing rates, sampling strategies and sequencing proportions jointly impact surveillance outcomes, and showed that low testing rates and spatiotemporal biases delay time to detection of new variants by weeks to months and can lead to unreliable estimates of variant prevalence, even when the proportion of samples sequenced is increased. Accordingly, investments in wider access to diagnostics to support testing rates of approximately 100 tests per 100,000 people per day could enable more timely detection of new variants and reliable estimates of variant prevalence. The performance of global SARS-CoV-2 genomic surveillance programs is fundamentally limited by access to diagnostic testing.

Increasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries; high-income countries = 600 tests/100,000 people/day; LMICs = 14 tests/100,000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear.We used PATAT, an LMIC-focused agent-based model to simulate COVID-19 epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from non-SARS-CoV-2 infected individuals and measured impact based on the number of infections averted due to test-and-isolate.Testing symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested. Meeting symptomatic testing demand likely requires at least 200-400 tests/100,000 people/day on average as symptomatic testing demand is highly influenced by non-SARS-CoV-2 infected individuals. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yields the largest additional infections averted.Testing strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.

SummaryBackgroundIncreasing the availability of antigen rapid diagnostic tests (Ag-RDTs) in low- and middle-income countries (LMICs) is key to alleviating global SARS-CoV-2 testing inequity (median testing rate in December 2021-March 2022 when the Omicron variant was spreading in multiple countries; high-income countries=600 tests/100,000 people/day; LMICs=14 tests/ 100,000 people/day). However, target testing levels and effectiveness of asymptomatic community screening to impact SARS-CoV-2 transmission in LMICs are unclear.MethodsWe used PATAT, an LMIC-focused agent-based model to simulate COVID-19 epidemics, varying the amount of Ag-RDTs available for symptomatic testing at healthcare facilities and asymptomatic community testing in different social settings. We assumed that testing was a function of access to healthcare facilities and availability of Ag-RDTs. We explicitly modelled symptomatic testing demand from non-SARS-CoV-2 infected individuals and measured impact based on the number of infections averted due to test-and-isolate.ResultsTesting symptomatic individuals yields greater benefits than any asymptomatic community testing strategy until most symptomatic individuals who sought testing have been tested.Meeting symptomatic testing demand likely requires at least 200-400 tests/100,000 people/day on average as symptomatic testing demand is highly influenced by non-SARS-CoV-2 infected individuals. After symptomatic testing demand is satisfied, excess tests to proactively screen for asymptomatic infections among household members yields the largest additional infections averted.ConclusionsTesting strategies aimed at reducing transmission should prioritize symptomatic testing and incentivizing test-positive individuals to adhere to isolation to maximize effectiveness.

IntroductionTesting is critical to controlling the COVID-19 pandemic. Antigen-detecting rapid diagnostic tests (Ag-RDTs) that can be used at the point of care have the potential to increase access to COVID-19 testing, particularly in settings with limited laboratory capacity. This systematic review synthesized literature on specific use cases and performance of Ag-RDTs for detecting SARS-CoV-2, for the first comprehensive assessment of Ag-RDT use in real-world settings.MethodsWe searched three databases (PubMed, EMBASE and medRxiv) up to 12 April 2021 for publications on Ag-RDT use for large-scale screening, irrespective of symptoms, and surveillance of COVID-19, excluding studies of only presumptive COVID-19 patients. We tabulated data on the study setting, populations, type of test, diagnostic performance and operational findings. We assessed risk of bias using QUADAS-2 and an adapted tool for prevalence studies.ResultsFrom 4313 citations, 39 studies conducted in asymptomatic and symptomatic adults were included. Study sample sizes varied from 40 to >5 million. Of 39 studies, 37 (94.9%) investigated lateral flow Ag-RDTs and two (5.1%) investigated multiplex sandwich chemiluminescent enzyme immunoassay Ag-RDTs. Six categories of testing (screening/surveillance) initiatives were identified: mass screening (n=13), targeted screening (n=11), healthcare entry testing (n=6), at-home testing (n=4), surveillance (n=4) and prevalence survey (n=1). Across studies, Ag-RDT sensitivity varied from 40% to 100%. Ag-RDTs were noted as convenient, easy-to-use and low cost, with a rapid turnaround time and high user acceptability. Risk of bias was generally low or unclear across the studies.ConclusionThis systematic review demonstrates the use of Ag-RDTs across a wide range of real-world settings for screening and surveillance of COVID-19 in both symptomatic and asymptomatic individuals. Ag-RDTs were overall found to be easy-to-use, low cost and rapid tools, when consideration is given to their implementation and interpretation. The review was funded by FIND, the global alliance for diagnostics.SUMMARYWhat is already known?Antigen-detecting rapid diagnostic tests (Ag-RDTs) have the potential to substantially improve access to timely testing for COVID-19 and are being deployed in a variety of settings around the worldWhile studies have investigated the diagnostic accuracy of Ag-RDTs, less is known about how and in what settings Ag-RDTs are being used around the world and their performance in these different settingsWhat are the new findings?Ag-RDTs are being used in a diverse range of real-world settings for mass screening and surveillance of COVID-19 among symptomatic and asymptomatic individualsThe sensitivity of Ag-RDTs is variable - ranging from 40% to 100% - and in some cases low compared with RT-PCR, meaning that the value of testing with Ag-RDTs needs to be carefully evaluated for each use case taking into account factors such as the prevalence of COVID-19 in the population, the consequences of false positive or false negative results, and whether confirmatory testing of positive or negative Ag-RDT results with RT-PCR is requiredNevertheless, Ag-RDTs are generally reported as being easy to use and low cost, with a rapid turnaround time that enables timely identification of cases and subsequent interventions to prevent onward transmission of COVID-19What do the new findings imply?The evidence indicates that Ag-RDTs can be effectively deployed across a broad range of settings when consideration is given to how they are implemented and interpretedThe development of more detailed, evidence-based testing policies for Ag-RDTs will be important to help countries implement effective testing programmes and make the best use of Ag-RDTs as part of the COVID-19 testing toolkit

Abdominal radiography and computed tomography scans are standard tests to diagnose pneumoperitoneum. With the growing availability of point-of-care ultrasound, pneumoperitoneum may be diagnosed in settings without easy access to radiography or computed tomography, such as in overcrowded emergency departments or resource-poor environments. The use of point-of-care ultrasound to diagnose or monitor pneumoperitoneum has been described in adult but not pediatric patients. We present a case of point-of-care ultrasound detection of pneumoperitoneum and monitoring for tension pneumoperitoneum, after failed air enema reduction for intussusception in an infant.

Background Stent-assisted coiling in the setting of subarachnoid hemorrhage remains controversial. Currently, there is a paucity of data regarding the utility of this procedure and the risks of hemorrhagic and ischemic complications. Objective To assess the utility of stent-assisted coil embolization and pretreatment with antiplatelet agents in the management of ruptured wide-necked aneurysms. Methods A retrospective study of 65 patients with ruptured wide-necked aneurysms treated with stent-assisted coiling. Patients with hydrocephalus or a Hunt and Hess grade ≥ III received a ventriculostomy before endovascular intervention. Patients were treated intraoperatively with 600 mg of clopidogrel and maintained on daily doses of 75 mg of clopidogrel and 81 mg of aspirin. The Glasgow outcome scale (GOS) score was recorded at the time of discharge. We identified major bleeding complications secondary to antiplatelet therapy and cases of in-stent thrombosis that required periprocedural thrombolysis. Results Of the aneurysms, 66.2% arose within the anterior circulation; 69.2% of patients presented with hydrocephalus or a Hunt and Hess grade ≥ III and required a ventriculostomy. A good outcome (GOS of 4 or 5) was achieved in 63.1% of patients, and the overall mortality rate was 16.9%. There were 10 (15.38%) major complications associated with bleeding secondary to antiplatelet therapy (5 patients, 7.7%) or intraoperative in-stent thrombosis (5 patients, 7.7%). Three (4.6%) patients had a fatal hemorrhage. Conclusion Our findings suggest that stent-assisted coiling and routine treatment with antiplatelet agents is a viable option in the management of ruptured wide-necked aneurysms.

Background Commissioned by the International Epidemiological Association, this article is part of a series on burden of disease, health indicators and the challenges faced by epidemiologists in bringing their discoveries to provide equitable benefit to the populations in their regions and globally. This report covers the health status and epidemiological capacity in the North American region (USA and Canada). Methods We assessed data from country-specific sources to identify health priorities and areas of greatest need for modifiable risk factors. We examined inequalities in health as a function of social deprivation. We also reviewed information on epidemiological capacity building and scientific contributions by epidemiologists in the region. Findings The USA and Canada enjoy technologically advanced healthcare systems that, in principle, prioritize preventive services. Both countries experience a life expectancy at birth that is higher than the global mean. Health indicator measures are consistently worse in the USA than in Canada for many outcomes, although typically by only marginal amounts. Socio-economic and racial/ethnic disparities in indicators exist for many diseases and risk factors in the USA. To a lesser extent, these social inequalities also exist in Canada, particularly among the Aboriginal populations. Epidemiology is a well-established discipline in the region, with many degree-granting schools, societies and job opportunities in the public and private sectors. North American epidemiologists have made important contributions in disease control and prevention and provide nearly a third of the global scientific output via published papers. Conclusions Critical challenges for North American epidemiologists include social determinants of disease distribution and the underlying inequalities in access to and benefit from preventive services and healthcare, particularly in the USA. The gains in life expectancy also underscore the need for research on health promotion and prevention of disease and disability in older adults. The diversity in epidemiological subspecialties poses new challenges in training and accreditation and has occurred in parallel with a decrease in research funding.

Objective: Intracranial stenosis is a common culprit for stroke which has been traditionally managed with medical therapy. However, recurrent TIA or stroke symptoms often occur despite aggressive management with antiplatelet medications. As such, angioplasty and stenting of intracranial vasculature has become an attractive idea for treatment of intracranial stenosis refractory to medical treatment. Because the SAMMPRIS trial was terminated prematurely, long term data regarding efficacy is lacking. We present the results of our series of 61 patients who underwent Wingspan stent placement for intracranial stenosis and evaluate the short-term and long-term success. Methods: Sixty-one patients with high-grade, symptomatic intracranial stenosis underwent Wingspan stent embolization at Jefferson Hospital for Neuroscience from August 7, 2006 to July 13, 2011. The clinical charts were reviewed to evaluate presentation, intervention, perioperative course, and outcome. Results: Our series consisted of 61 patients who received a Wingspan stent for intracranial stenosis(41 male; 20 female; mean age 62.9). Stenotic vessels treated included the internal carotid artery(n=18), middle cerebral artery(n=13), basilar artery(n=15), vertebrobasilar junction(n=2), and vertebral artery(n=13). Failure of stent placement was the only identified intraoperative complications, occurring in 6.6% of procedures. Perioperative complications occurred in 6.6% of patients, and included myocardial infarction(n=1), TIA or stroke without in-stent thrombosis(n=1), TIA or stroke with in-stent thrombosis(n=2), and death(n=2). Mortality rate was 3.3% in the perioperative period. Follow-up data was available for 41(67.2%) patients, with a mean duration of 205 days after intervention. In this follow-up group, 9.8%(n=4) suffered delayed in-stent thrombosis, 3(7.3%) of which suffered new TIAs or stroke. There was 1(2.4%) delayed mortality related to pseudoaneurysm rupture at the site of the stent. Conclusion: We present the largest series of patients outside of SAMMPRIS to undergo Wingspan stenting for intracranial stenosis. Immediate and long-term follow-up data demonstrates the safety profile of the procedure with efficacy in preventing future strokes. Delayed in-stent thrombosis is the most common risk to observe in this patient population.