Covid-19: Rest and PPE reassurance are needed before NHS services can restart, MPs hear

At a Health and Social Care Select Committee evidence session on 14 May the King's Fund, the Nuffield Trust, and the Health Foundation warned that it would take many more months before core health and care services were able to fully restart. Limited capacity Jennifer Dixon, chief executive officer at the Health Foundation, told the committee that capacity within hospitals would be severely limited because of the need for social distancing, separating out covid and non-covid patients, and more time for deep cleaning of equipment and facilities. Chris Hopson, chief executive officer at NHS Providers, told the committee that NHS staff had worked incredibly hard in the past few months, with leave cancelled, and were very tired as a result.

Improving Clinical Decisions Via Remote Blood Sampling

3 An important component for the provision of patient-centric healthcare is the ability to collect blood samples remotely in a manner that delivers samples of a quality comparable to that of current standard phlebotomy collection, enabling routine clinical testing, monitoring disease progression and testing drug concentrations.2-4-г, This blood sampling could be performed at the patient's home, at a nearby pharmacy, or at a local clinic, rather than a centralized facility. Examples of commercially available devices include the Neoteryx Mitra,13 Tasso-M20, SST and Tasso+,14 SeventhSense TAP and TAP II,15 Trajan hemaPEN,16 Labcorp Pixel,17 Capitainer qDBS,1" HemaXis DB10 and DX,19 and Drawbridge OneDraw.20 These devices are capable of collecting from as little as 20 microliters (approximately half a drop) to several hundred microliters of blood and have been widely used to determine clinical parameters,21 drug concentrations,5'22 therapeutic drug monitoring,23 and, more recently, COVID antibody levels.24,25 Some of these devices enable the collection of a fixed volume of blood, collected as dried blood, which can then be shipped and handled at room temperatures-avoiding the need for freezers and dry ice for storing and shipping samples-enabling its adoption even in remote areas with limited infrastructure. Patient-centric blood sampling techniques have been gaining popularity for use in pharmaceutical drug development;however, to date they have not been broadly accessible to the general public.26 This can be partially attributed to the "cliniccentric" healthcare model, where reimbursement is dependent on in-person visits and sample collection. [...]the status quo remains and anyone who needs a blood test is required to go to the doctor's office or clinic. [...]studies have demonstrated that the overall cost to society will be lower, by improving health outcomes and allowing broader access and patient convenience.27 The availability and adoption of patient-centric approaches can provide access and treatment options to clinical trial participants not geographically co-located with the investigative sites and improving access in rural or lesser developed communities, globally, potentially improving the health of the general population.

DEBATE ACCELERATES OVER WHO GETS COVID VACCINE FIRST

At the agencies' request, the National Academy of Sciences, Engineering and Medicine iNASEMi has formed a blue-ribbon committee of leading bioethicists, economists, geneticists, and public health authorities to quickly develop a framework for priority vaccine access to assist policymakers in the U.S. and other nations achieve equitable distribution of anticipated vaccines (see: https://bit.ly/33jTCds). Individuals at higher risk will include those in higher age groups, with underlying health conditions, engaged in high-risk occupations, affected by racial and ethnic disparities, and in hardhit geographic locations. State and public health officials are wary of federal pandemic planning efforts so fair given the lack of coordination and effectiveness in distributing COVID-19 test kits and personal protective equipment to healthcare providers and facilities.

CLINICAL TRIAL REFORM

[...]CURES' BILL PROMOTES PANDEMIC PREPAREDNESS Congressional leaders are developing the next version of the 21st Century Cures Act, including provisions to advance research related to the COVID-19 crisis as part of initiatives for bringing innovative therapies to market faster (see https://bit.ly/2SKfA4S). Cures 2.0 continues and updates some of the main themes of the first Cures Act: support development of treatments for rare diseases, patient-focused drug development, diversity in clinical trials, expanded use of digital health systems, increased health literacy, and utilization of real-world data. A public education campaign, moreover, would aim to counter concerns about the safety of vaccines to promote widespread vaccination. Because these treatments are costly and unprofitable for biopharma companies to test and market, the legislation proposes additional financial support for both pre-market studies and post-market production and subsidized higher reimbursement rates for antibiotics that address critical needs.

New care settings and innovation will usher diagnostic testing into the future

The article focuses on the future of diagnostic testing in healthcare, highlighting the importance of testing in tracking and treating diseases like COVID-19. It discusses the advancements in diagnostic technology, including combination tests for multiple respiratory diseases and the rise of at-home testing, which will increase access to testing and empower patients to manage their health.

New Sample Prep Products and Accessories for 2023

[...]instrument-based sample preparation technologies are presented. [...]attention is turned to other sample preparation accessories and supporting technologies. First is the Swift HLB-DPX tips. First is the Thermo Scientific AccelerOme sample preparation platform automating sample preparation for liquid chroma-tography-mass spectrometry (LC-MS) proteomics.

Enhanced Role of EMA in EU Crisis Response

The regulation also sets out obligations on marketing authorization holders (MAHs) and medical devices manufacturers, authorized representatives, importers, distributors, and notified bodies duties to: * Provide information that will assist with the monitoring by the MSSG/MDSSG of shortages of medicinal products and devices contained in the critical medicines list and updating this when necessary * Provide a justification for any failure to provide the requested information by the established deadlines * Immediately provide any evidence of an actual or potential shortage of medicinal products or devices * Provide information to EMA by 2 Sep. 2022 that will enable the establishment of a Single Point of Contact (SPOC) network, and the industry Single Point of Contact (iSPOC) network, with mandates to updating this when necessary (7). Enhanced advisory role In addition to the measures designed to address medicinal and medical device shortages, an Emergency Task Force (ETF) will also be established within EMA to provide scientific advice and review evidence on medicines that have the potential to address public health emergencies, offer scientific support to facilitate clinical trials, and support existing EMA committees with their authorization and safety monitoring of medicines (8). According to the document published by EMA on Crisis Preparedness and Management, the key benefits for EMA of having these responsibilities include: * Accelerated evaluation and access to safe and effective medicines which could treat or prevent a disease causing, or likely to cause, a public health emergency * Improved quality of data and the effective use of resources through increased support at EU level towards the conducting of clinical trials in preparation for, and during a public health emergency * Improved coordination and harmonization at EU level in preparation for and during a public health emergency (7).

HOW FAR WILL EUROPEAN DRUG INDUSTRY 'COMMITMENTS' ON COVID RESONATE?

According to Jean-Christophe Tellier, EFPIA president and CEO of UCB Pharma, the industry is "continuing to donate money and in-kind support to health systems, governments, and organizations on the ground, pulling out every stop to ensure the safe supply of medicines to the patients that need them," and "working around the clock to find new vaccines, diagnostics and treatments." Industry is expanding its manufacturing capabilities and sharing available capacity to ramp up production "once a successful medicine or vaccine is developed," and in the meantime, it is directly linking with regulatory authorities to provide information about stock, manufacturing capacity, and market tensions so as to head off potential disruptions or shortages. [...]the industry commitment most likely to strike a chord with many of the industry's inveterate critics, who have not ceased to push for patent limitations and price controls in a post-COVID world, is "working with governments and health systems to ensure that when new treatments and vaccines are approved they are available and affordable."

Impact of COVID-19 on Phase I Clinical Activities

[...]to ensure a safe re-opening of the unit in alignment with rules set by the government, regulatory authorities, local hospitals, the local ethics committee and SGS's company policy, a COVID-19 risk implementation plan was created. Following evaluation, bed capacity was reduced by 20 beds, and plastic screens were put in place where applicable. [...]the number of monitors, visits, and the length of time in the monitoring room is limited to a minimum.

Thermal Shock Viral RNA Release in COVID-19 Testing

Introduction/Objective The public health emergency of the COVID-19 pandemic emphasized the crucial role of medical laboratory professionals and scientists in molecular diagnostics laboratories to ensure success in infection control strategies. The demand for laboratory testing using nucleic acid amplification tests to detect SARS-CoV-2 RNA imposed strains in laboratory supplies. Here, we explored an alternative cost-effective solution that will simplify the pre-PCR steps by using a simple heating method to release viral RNA. Methods/Case Report Samples tested using the reference automated extraction method were used:100 samples identified as positive for SARS-CoV-2 RNA and 500 samples tested negative for SARS-CoV-2 RNA were used for the study and sorted with equal distribution according to Ct values of (a) <20, (b) 20–30, and (c) >30.100 ul from swab preserved in Universal Transport Medium was treated with 30 μg of proteinase K, and another set was tested without proteinase K pre-treatment. All samples with or without proteinase K were diluted to minimize PCR inhibitors. The thermal shock protocol was set at (98°C, 5 minutes;4°C, 2 minutes) and screened for purity. Performance and method verification studies were performed. Internal extraction, positive template, and no template controls were markers used for testing quality. The experimental study was performed by qualified testing personnel and all under the same experimental conditions. Results (if a Case Study enter NA) The Ct values from the thermal shock RNA release were compared to the automated extraction method and statistically analyzed.The criteria for acceptability for validation of this new RNA extraction proceeding were set to 100% concordance compared to the commercial kit using an automated extraction. PCR efficiency was at 98% and a slope of -3.3. Within run precision of 2% and limits of detection from 200 to 20,000 copies/uL The method 100% (50/50) concordance on samples previously identified as negative by automated methods and identified 86% (86/100) with a mean difference of 3 Ct. Conclusion Our findings suggest that the thermal shock treatment of nasopharyngeal swabs in viral transport media can successfully extract viral nucleic acid for nucleic acid amplification and is a reasonable alternative for chemical extraction methods when molecular diagnostic laboratories persistently encounter supply chain issues.

Impact of personal protective equipment on the clarity of vision among trachoma survey graders and trichiasis surgeons in the context of COVID-19

Background/aimsThe COVID-19 pandemic necessitated the use of personal protective equipment for those involved in trachoma survey grading and trichiasis surgery. We sought to determine which configuration of a face shield would be less likely to impact grading accuracy and ability to conduct trichiasis surgery. The research also included assessment of comfort, ease of cleaning and robustness.MethodsThere were three research phases. In phase 1, assessment of four potential face shield configurations was undertaken with principal trachoma graders and trichiasis surgeon trainers to decide which two options should undergo further testing. In phase 2, clarity of vision and comfort (in a classroom environment) of the two configurations were assessed compared with no face shield (control), while grading trachomatous inflammation—follicular (TF). The second phase also included the assessment of impact of the configurations while performing trichiasis surgery using a training model. In phase 3, face shield ease of use was evaluated during routine surgical programmes.ResultsIn phase 2, 124 trachoma graders and 28 trichiasis surgeons evaluated the 2 face shield configurations selected in phase 1. TF agreement was high (kappa=0.83 and 0.82) for both configurations compared with not wearing a face shield. Comfort was reported as good by 51% and 32% of graders using the two configurations. Trichiasis skill scores were similar for both configurations.ConclusionThe face shield configuration that includes a cut-out for mounting the 2.5× magnifying loupes does not appear to impact the ability or comfort of trachoma graders or trichiasis surgeons to carry out their work.

Application of quality statistical tools for the evaluation of diagnostic tests for SARS-CoV-2 detection

This chapter explores the use of quality statistical tools for the development of diagnostic tests for SARS-CoV-2 and the different metrological parameters recommended to laboratories towards guaranteeing the quality assurance of the tests, according to ISO/IEC 17025. Tools such as validation, uncertainty estimation, and proficiency testing are presented and the importance of their application to the current scenario and their perspectives and scarcity in the tests developed and made available are discussed. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023. All rights reserved.

Usefulness of C-reactive protein to determine the severity of SARS-CoV-2 infection in Peru.

Background: Recently, many biomarkers have been studied to determine severe cases of COVID-19. C-reactive protein (CRP) has shown high sensitivity in identifying patients with severe disease and utility comparable to computed tomography. Aim(s): To determine the usefulness of CRP to predict the severity of SARS-CoV-2 infection in patients hospitalized at the Naval Medical Center of Peru during the period January-September in the year 2021. Method(s): A quantita-tive, observational, analytical, retrospective, and diagnostic test type design was used. A sample size of 503 patients was calculated, which were divided into two groups according to their severity. Result(s): An optimal cut-off point of 10.92 mg/L for CRP levels was determined for the diagnosis of severe COVID-19. An area under the curve (AUC) of 0.762 was calculated and sensitivity, specificity, positive and negative predictive values and diagnostic accuracy values of 78.88%, 66.4%;41.42%;87.01%;and 67.27%;respectively. Fagan's normogram showed a post-test probability of 41%. In the adjusted model, CRP (aOR = 4.853;95% CI 2.987-7.886;p = 0.001), ferritin (aOR = 1.001;95% CI: 1.001-1.002;p = 0.001) and hypothyroidism (adjusted OR = 4899;95% CI: 1272-18872;p = 0.021) showed significance. Conclusion(s): The present study showed an association between CRP and the severity of SARS-CoV-2 infection in an adjusted model, showing its potential utility and contributing to determine the cut-off point of CRP in the Peruvian population and its international comparison.Copyright © 2023, Sociedad Chilena de Infectologia. All rights reserved.

Correction of vaccine effectiveness derived from test-negative case-control studies.

BACKGROUND: Determining the vaccine effectiveness (VE) is an important part of studying every new vaccine. Test-negative case-control (TNCC) studies have recently been used to determine the VE. However, the estimated VE derived from a TNCC design depends on the test sensitivity and specificity. Herein, a method for correction of the value of VE derived from a TNCC study is presented. METHODS: An analytical method is presented to compute the corrected VE based on the sensitivity and specificity of the diagnostic test utilized. To show the application of the method proposed, a hypothetical TNCC study is presented. In this in silico study, 100 000 individuals referring to a healthcare system for COVID-19-like illness were tested with diagnostic tests with sensitivities of 0.6, 0.8, and 1.0, and specificities ranging from 0.85 to 1.00. A vaccination coverage of 60%, an attack rate of 0.05 for COVID-19 in unvaccinated group, and a true VE of 0.70, were assumed. In this simulation, a COVID-19-like illness with an attack rate of 0.30 could also affect all the studied population regardless of their vaccination status. RESULTS: The observed VE ranged from 0.11 (computed for a test sensitivity of 0.60 and specificity of 0.85) to 0.71 (computed for a test sensitivity and specificity of 1.0). The mean computed corrected VE derived from the proposed method was 0.71 (the standard deviation of 0.02). CONCLUSIONS: The observed VE derived from TNCC studies can be corrected easily. An acceptable estimate for VE can be computed regardless of the diagnostic test sensitivity and specificity used in the study.

Feasibility, Uptake, and Results of COVID-19 Antigen Rapid Diagnostic Tests among Refugees and Migrants in a Pilot Project in North-West Syria.

North-west Syria (NWS) is a conflict-affected and unstable area. Due to its limited health infrastructure, accessing advanced COVID-19 testing services is challenging. COVID-19 antigen rapid diagnostic tests (Ag-RDTs) have the potential to overcome this barrier. A pilot project was implemented to introduce Ag-RDTs in NWS, aiming to determine the feasibility, uptake, and results of Ag-RDTs and identify facilitators and barriers to testing with Ag-RDTs. A cross-sectional study design involving secondary analysis of data collected during the project was employed. A local non-governmental organization implemented 25,000 Ag-RDTs that were conducted cross-border by trained community health workers. In total, 27,888 eligible individuals were enrolled, 24,956 (89.5%) consented to test, and 121 (0.5%) were COVID-19-positive. The highest positivity was observed among those with severe COVID-19 symptoms (12.7%), with respiratory illnesses (2.5%), enrolled at hospitals in Afrin (2.5%), and healthcare workers (1.9%). A non-random sample of 236 individuals underwent confirmatory RT-PCR testing. Observed sensitivity, specificity, and positive and negative predictive values were 80.0%, 96.1%, 91.4%, and 90.3%, respectively. Challenges included obtaining informed consent and conducting confirmatory testing. Ag-RDTs represent a feasible screening/diagnostic tool for COVID-19 infections in NWS, with nearly 90% uptake. Embedding Ag-RDTs into COVID-19 testing and screening strategies would be highly beneficial.

Estimating SARS-CoV-2 seroprevalence

Governments and public health authorities use seroprevalence studies to guide responses to the COVID-19 pandemic. Seroprevalence surveys estimate the proportion of individuals who have detectable SARS-CoV-2 antibodies. However, serologic assays are prone to misclassification error, and non-probability sampling may induce selection bias. In this paper, non-parametric and parametric seroprevalence estimators are considered that address both challenges by leveraging validation data and assuming equal probabilities of sample inclusion within covariate-defined strata. Both estimators are shown to be consistent and asymptotically normal, and consistent variance estimators are derived. Simulation studies are presented comparing the estimators over a range of scenarios. The methods are used to estimate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in New York City, Belgium, and North Carolina.

What are the health care protocols in a postpandemic world?

A brief look back On lanuary 31, 2020, US Secretary of Health & Human Services Alex Azar declared the COVID-19 virus a public health emergency and ordered all US citizens returning from the Wuhan, China, region to quarantine for 2 weeks. Rapid diagnostic tests were quickly distributed, personal protective equipment (PPE) was secured, and vaccines were developed in record time. A recent study suggests that young children mount a T-cell activation when exposed to non-COVID-19 seasonal coronavirus infections, which either prevents COVID-19 infections or provides enough protection to render most infections mild.2 In addition, despite the endorsement of the American Academy of Pediatrics (AAP) and the CDC, not many young children were vaccinated against COVID-19 once the FDA approved it use, eventually allowing it to be administered to those as young as 6 months.

A final review: How are our children doing right now?

In caring for our pediatric patients, we will continue to live with the fact that the disruptions have not been uniformly felt, with increased impact on Black and Brown children and those living in poverty;additionally, levels of access to routine pediatric health services have varied throughout the pandemic.1 For all children, though, we have to make up much lost time when it comes to physical, mental, and academic concerns, as well as socialization issues. Because schools provide another resource for identifying and addressing mental health concerns, the complete or partial shift to virtual learning likely compounded the mental health crisis. According to one study, "the prevalence of depression and anxiety symptoms during the COVID-19 pandemic has doubled, compared with prepan-demic estimates. Early childhood: A profound degree of development takes place from birth to 5 years of life. Because of the pandemic, children 5 years and younger have spent all or a significant portion of their lives in social isolation alongside parents or caregivers.