Rapid determination of an individual's antibody status can be beneficial in understanding an individual's immune response to SARS-CoV-2 and for initiation of therapies that are only deemed effective ...in sero-negative individuals. Antibody lateral flow tests (LFTs) have potential to address this need as a rapid, point of care test.
Here we present a proof-of-concept evaluation of eight LFT brands using sera from 95 vaccinated individuals to determine sensitivity for detecting vaccination generated antibodies. Samples were analysed on eight different brands of antibody LFT and an automated chemiluminescent microparticle immunoassay (CMIA) that identifies anti-spike antibodies which was used as our reference standard.
All 95 (100%) participants tested positive for anti-spike antibodies by the chemiluminescent microparticle immunoassay (CMIA) reference standard post-dose two of their SARS-CoV-2 vaccine: BNT162b2 (Pfizer/BioNTech, n = 60), AZD1222 (AstraZeneca, n = 31), mRNA-1273 (Moderna, n = 2) and Undeclared Vaccine Brand (n = 2). Sensitivity increased from dose one to dose two in six out of eight LFTs with three tests achieving 100% sensitivity at dose two in detecting anti-spike antibodies.
These tests are demonstrated to be highly sensitive to detect raised antibody levels in vaccinated individuals. RDTs are low cost and rapid alternatives to ELISA based systems.
Rapid diagnostic tests (RDTs) developed for point of care detection of SARS-CoV-2 antigen are recommended by WHO to use trained health care workers to collect samples. We hypothesised that self-taken ...samples are non-inferior for use with RDTs to diagnose COVID-19. We designed a prospective diagnostic evaluation comparing self-taken and healthcare worker (HCW)-taken throat/nasal swabs to perform RDTs for SARS-CoV-2, and how these compare to RT-PCR.
Eligible participants 18 years or older with symptoms of COVID-19. 250 participants recruited at the NHS Test and Trace drive-through community PCR testing site (Liverpool, UK); one withdrew before analysis. Self-administered throat/nasal swab for the Covios® RDT, a trained HCW taken throat/nasal sample for PCR and HCW comparison throat/nasal swab for RDT were collected. RDT results were compared to RT-PCR, as the reference standard, to calculate sensitivity and specificity.
Seventy-five participants (75/249, 30.1%) were positive by RT-PCR. RDTs with self-taken swabs had a sensitivity of 90.5% (67/74, 95% CI: 83.9-97.2), compared to 78.4% (58/74, 95% CI: 69.0-87.8) for HCW-taken swabs (absolute difference 12.2%, 95% CI: 4.7-19.6, p = 0.003). Specificity for self-taken swabs was 99.4% (173/174, 95% CI: 98.3-100.0), versus 98.9% (172/174, 95% CI: 97.3-100.0) for HCW-taken swabs (absolute difference 0.6%, 95% CI: 0.5-1.7, p = 0.317). The PPV of self-taken RDTs (98.5%, 67/68, 95% CI: 95.7-100.0) and HCW-taken RDTs (96.7%, 58/60, 95% CI 92.1-100.0) were not significantly different (p = 0.262). However, the NPV of self-taken swab RDTs was significantly higher (96.1%, 173/180, 95% CI: 93.2-98.9) than HCW-taken RDTs (91.5%, 172/188, 95% CI 87.5-95.5, p = 0.003).
In conclusion, self-taken swabs for COVID-19 testing offer an accurate alternative to healthcare worker taken swabs for use with RDTs. Our results demonstrate that, with no training, self-taken throat/nasal samples can be used by lay individuals as part of rapid testing programmes for symptomatic adults. This is especially important where the lack of trained healthcare workers restricts access to testing.
•To date this is the first ever service evaluation of SARS-CoV-2 Ag-RDTs in elite professional rugby teams.•Despite the high acceptability of Ag-RDTs amongst players and staff in this the study, the ...performance needs ongoing real-world evaluation to support rapid transition to self-swabbing.•This study highlights the need for continued service evaluations for SARS-CoV-2 Ag-RDTs in elite sport settings.
This study evaluated the validity and utility of antigen-detection rapid diagnostic tests (Ag-RDTs) for SARS-CoV-2 in elite sports. The data on utility, ease of use and application for Ag-RDTs as a new testing format were positive from players and staff. This evaluation was limited by the low prevalence of SARS-CoV-2 circulating within the three squads. This study highlights the need for continued service evaluations for SARS-CoV-2 Ag-RDTs in elite sport settings.
In order to generate independent performance data regarding accuracy of COVID-19 antigen-based rapid diagnostic tests (Ag-RDTs), prospective diagnostic evaluation studies across multiple sites are ...required to evaluate their performance in different clinical settings. This report describes the clinical evaluation the GENEDIA W COVID-19 Ag Device (Green Cross Medical Science Corp., Chungbuk, Korea) and the ActiveXpress+ COVID-19 Complete Testing Kit (Edinburgh Genetics Ltd, UK), in two testing sites Peru and the United Kingdom.
Nasopharyngeal swabs collected from 456 symptomatic patients at primary points of care in Lima, Peru and 610 symptomatic participants at a COVID-19 Drive-Through testing site in Liverpool, England were analyzed by Ag-RDT and compared to RT-PCR. Analytical evaluation of both Ag-RDTs was assessed using serial dilutions of direct culture supernatant of a clinical SARS-CoV-2 isolate from the B.1.1.7 lineage.
For GENEDIA brand, the values of overall sensitivity and specificity were 60.4% 95% CI 52.4-67.9%, and 99.2% 95% CI 97.6-99.7% respectively; and for Active Xpress+ the overall values of sensitivity and specificity were 66.2% 95% CI 54.0-76.5%, and 99.6% 95% CI 97.9-99.9% respectively. The analytical limit of detection was determined at 5.0 x 102 pfu/ml what equals to approximately 1.0 x 104 gcn/ml for both Ag-RDTs. The UK cohort had lower median Ct values compared to that of Peru during both evaluations. When split by Ct, both Ag-RDTs had optimum sensitivities at Ct<20 (in Peru; 95% 95% CI 76.4-99.1% and 100.0% 95% CI 74.1-100.0% and in the UK; 59.2% 95% CI 44.2-73.0% and 100.0% 95% CI 15.8-100.0%, for the GENDIA and the ActiveXpress+, respectively).
Whilst the overall clinical sensitivity of the Genedia did not meet WHO minimum performance requirements for rapid immunoassays in either cohort, the ActiveXpress+ did so for the small UK cohort. This study illustrates comparative performance of Ag-RDTs across two global settings and considers the different approaches in evaluation methods.
Clostridioides difficile-associated diarrhoea (CDAD) has emerged as a leading healthcare-associated infection of great clinical and economic significance. The infection is not only characterised by ...debilitating symptoms but is also complicated with a high incidence of recurrence and is increasingly found in the community. C. difficile spores are resistant to many chemical and physical agents, as a result spores shed in faecal matter are very difficult to eradicate, leading to infection, or re-infection, of cohabiting individuals through ingestion of spores from contaminated surfaces. Interventions that target sporulation could, therefore, have an enormous impact on disease transmission. Nonetheless, it is the toxin-producing vegetative cells that subsequently arise following germination that cause disease and so intervention at the stage of germination would be an effective means of disease prevention. In this study various methods where employed towards the elucidation of ribotype prevalence and spore phenotypes of clinical isolates derived from 151 patients enrolled on a trial to assess the use of Rifaximin as a measure to control relapse of Clostridioides difficile infection (CDI). Genomic characterisation of a subset of isolates was performed to differentiate incidence of reinfection from relapse. Pangenome analysis together with genetic variation analysis of 23 key genes implicated in the colonisation, sporulation, germination and outgrowth of C. difficile was conducted to elucidate whether genotypic and phenotypic characteristics of isolates could be implicated as significant virulence or risk factors of recurrence in CDAD. A subset of 35 isolates were presented in this research. In this subset, 23 isolates are from 9 patients, who clinically presented with recurrent CDI, and 12 isolates from 6 patients, who clinically presented with non-recurrent CDI. Specific research questions included, whether variations of spore phenotypes and within the genomes among isolates over the infection period of CDI and recurrence could be observed. To further support associations with data from clinical isolates, sporulation and germination phenotypes where screened by construction and characterisation of insertional ClosTron mutations in CD19300, CD05460, CD07730, CD07750, CD29630, CD08670 and CD24700, seven hypothetical genes, in the non-epidemic C. difficile 630Δerm strain. Targets where proposed to be involved in sporulation and germination pathways, particularly CD24700, encoding the germination protease (GPR). A recombinant GPR was produced to further asses its role along with the crude extraction of acid soluble spore proteins hypothesised to contain the GPR substrates, small acid soluble proteins (SASPs). It was hypothesised that germination and outgrowth redundancies of strains relate to prolonged spore dormancy and persistence and thus these specific phenotypes would act as an explanation/virulence factor of relapse. Whereas reinfection would be predicted to be a result of competitive outgrowth of each co-infecting isolate, where antibiotic activity would disturb the faster outgrowing more so than the slower counterpart. The data collected in this study showed evidence to support these hypotheses. Interestingly, mutations leading to amino acid changes were detected in the germinant receptor, CspC, proline reductase, PrdB and exosporium glycoproteins, BclA1 and BclA3, for all isolates included in further genetic characterisation, whilst the initiation of spore germination was found to be significantly reduced in comparison to reference strain for all clinical isolates tested, indicating a higher level of control for Taurocholate-mediated germination. Additionally, levels of spore dormancy were detected in all clinical isolates tested, indicating the potential for relapse in all isolates. The inactivation of a hypothetical gene, CD24700, hypothesised to encode a germination protease (GPR), was revealed to have significant phenotypes supporting a clear role in spore viability, outgrowth and dormancy. Together, this study has contributed and expanded our knowledge of germination and outgrowth of spores of the non-epidemic C. difficile 630Δerm strain and of clinical isolates. It is hoped that sustained study will reveal further virulence factors of relapse and targets to prevent and tackle recurrent CDI.
The emergence of severe acute respiratory syndrome 2 (SARS-CoV-2) variants of concern (VOCs), with mutations linked to increased transmissibility, vaccine escape and virulence, has necessitated the ...widespread genomic surveillance of SARS-CoV-2. This has placed a strain on global sequencing capacity, especially in areas lacking the resources for large scale sequencing activities. Here we have developed three separate multiplex high-resolution melting assays to enable the identification of Alpha, Beta, Delta and Omicron VOCs. The assays were evaluated against whole genome sequencing on upper-respiratory swab samples collected during the Alpha, Delta and Omicron BA.1 waves of the UK pandemic. The sensitivities of the eight individual primer sets were all 100%, and specificity ranged from 94.6 to 100%. The multiplex HRM assays have potential as a tool for high throughput surveillance of SARS-CoV-2 VOCs, particularly in areas with limited genomics facilities.
The COVID-19 pandemic has led to the commercialization of many antigen-based rapid diagnostic tests (Ag-RDTs), requiring independent evaluations. This report describes the clinical evaluation of the ...Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom. The collected samples (446 nasal swabs from Brazil and 246 nasopharyngeal samples from the UK) were analyzed by the Ag-RDT and compared to reverse transcription-quantitative PCR (RT-qPCR). Analytical evaluation of the Ag-RDT was performed using direct culture supernatants of SARS-CoV-2 strains from the wild-type (B.1), Alpha (B.1.1.7), Delta (B.1.617.2), Gamma (P.1), and Omicron (B.1.1.529) lineages. An overall sensitivity and specificity of 88.2% (95% confidence interval CI, 81.3 to 93.3) and 100.0% (95% CI, 99.1 to 100.0), respectively, were obtained for the Brazilian and UK cohorts. The analytical limit of detection was determined as 1.0 × 10
PFU/mL (Alpha), 2.5 × 10
PFU/mL (Delta), 2.5 × 10
PFU/mL (Gamma), and 1.0 × 10
PFU/mL (Omicron), giving a viral copy equivalent of approximately 2.1 × 10
copies/mL, 9.0 × 10
copies/mL, 1.7 × 10
copies/mL, and 1.8 × 10
copies/mL for the Ag-RDT, respectively. Overall, while a higher sensitivity was claimed by the manufacturers than that found in this study, this evaluation finds that the Ag-RDT meets the WHO minimum performance requirements for sensitivity and specificity of COVID-19 Ag-RDTs. This study illustrates the comparative performance of the Hotgen Ag-RDT across two global settings and considers the different approaches in evaluation methods.
Since the beginning of the SARS-CoV-2 pandemic, we have witnessed growing numbers of antigen rapid diagnostic tests (Ag-RDTs) being brought to market. In the United Kingdom, this was somewhat controlled indirectly as the government offered free tests from a small number of companies. However, as this has now ceased, individuals are responsible for their own acquisition of test kits. Similarly in Brazil, as of January 2022, pharmacies and other health care retailers are permitted to sell Ag-RDTs directly to the community. Many of these Ag-RDTs have not been externally evaluated, and results are not readily available to the public. Thus, there is now a need for a transparent evaluation of Ag-RDTs with both analytical and clinical evaluation. We present an independent review of the Novel Coronavirus 2019-nCoV Antigen Test (Colloidal Gold) (Beijing Hotgen Biotech Co., Ltd.), at two sites within Brazil and one in the United Kingdom.
Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for ...these patients.
We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973.
Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28).
No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care.
National Institute for Health Research Health Services and Delivery Research Programme.
Introduction: Parts A and B of the ICH S7 guidelines on safety pharmacology describe the in vivo studies that must be conducted prior to first time in man administration of any new pharmaceutical. ...ICH S7A requires a consideration of the sensitivity and reproducibility of the test systems used. This could encompass maintaining a dataset of historical pre-dose values, power analyses, as well as a demonstration of acceptable model sensitivity and robust pharmacological validation. During the process of outsourcing safety pharmacology studies to Charles River Laboratories, AstraZeneca set out to ensure that models were performed identically in each facility and saw this as an opportunity to review the inter-laboratory variability of these essential models. Methods: The five in vivo studies outsourced were the conscious dog telemetry model for cardiovascular assessment, the rat whole body plethysmography model for respiratory assessment, the rat modified Irwin screen for central nervous system assessment, the rat charcoal meal study for gastrointestinal assessment and the rat metabolic cage study for assessment of renal function. Each study was validated with known reference compounds and data were compared across facilities. Statistical power was also calculated for each model. Results: The results obtained indicated that each of the studies could be performed with comparable statistical power and could achieve a similar outcome, independent of facility. Discussion: The consistency of results obtained from these models across multiple facilities was high thus providing confidence that the models can be run in different facilities and maintain compliance with ICH S7A and B.
Sentenced to Treatment Finch, Emily; Brotchie, Janet; Williams, Karen ...
European addiction research,
07/2003, Volume:
9, Issue:
3
Journal Article
Peer reviewed
Drug Treatment and Testing Orders (DTTOs) were introduced in the 1998 Crime and Disorder Bill and were piloted in three areas in England over the subsequent 18 months. The orders, funded by the Home ...Office, allow drug using offenders to be coerced into attending for treatment, to have regular urine tests and to be reviewed by the courts. In Croydon an equal partnership was set up between probation, a local statutory provider of drug services and a voluntary sector agency. Treatment plans were individualised and included a variety of treatment options. Forty-eight orders were imposed mainly for persistent shoplifting. Sixty-three percent of individuals had used heroin and 54% crack cocaine in the 30 days before the order was imposed. Ethical issues raised in coerced treatment were important for the individuals providing treatment although the clients all had to consent to treatment. The pilot programme raised issues about the nature of treatment, clinical responsibility, the selection of clients for orders and the objectives of treatment. Frequent urine testing was problematic but in the vast majority of cases clients were not breached just because of positive tests. The provision of DTTOs in an area created unacceptable inequalities in access to treatment. The paper concludes that partnership working and clear objectives are vital for treatment programmes to operate effectively. More research is needed to explore the most optimum way to deliver treatment in the context of a DTTO.
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