1,720,973 research outputs found
Global extent of chloroquine-resistant Plasmodium vivax
Full text linkI wish to thank Ric Price and colleagues1 for highlighting the under-studied chloroquine resistance in Plasmodium vivax in their systematic review and meta-analysis. However, I would question their study inclusion criteria: the primary outcome was “the risk of recurrent P vivax parasitaemia at day 28” when table 1 lists four studies with follow-up periods of less than 27 days. I would also suggest that it seems a shame that two author-reviewers, independently, did not extract and analyse the studies and data for inclusion, as seems standard practice for good systematic reviews. 2 Lastly, although the paper underlines the extent and importance of chloroquine-resistant P vivax, I am none the wiser on what management I should offer in practice to patients from different areas given the prevalence of resistance.I declare no competing interests.<br/
Neisseria meningitidis serogroup B bivalent factor H binding protein vaccine
No full textWith the successful development of meningococcal vaccines against other serogroups, disease caused by Neisseria meningitidis serogroup B now accounts for a disproportionate frequency compared with other serogroups, particularly in the US and Europe. Infants and adolescents bear the highest incidence of disease, which typically manifests as meningitis and septicemia. This vaccine profile article examines a bivalent factor H binding protein (fHbp; also known as LP2086) vaccine that has now been approved by the US FDA for use in 10- to 25-year olds. The manufacturer has shelved plans for further investigation of its use in infants because of high rates of fever in Phase I and II trials in that age group
Point-of-care testing for respiratory viruses in adults: The current landscape and future potential
No full textRespiratory viruses are responsible for a large proportion of acute respiratory illness in adults as well as children, and are associated with a huge socio-economic burden worldwide. Development of accurate point-of-care tests (POCT) for respiratory viruses has been listed as a priority by the World Health Organisation and replacing the current paradigm of empirical antimicrobial use with directed use is a listed goal of the movement for reduction in antimicrobial resistance. POCTs for respiratory viruses have previously been limited by the poor sensitivity of antigen detection based tests and by a limited range of detectable viruses. Highly accurate molecular platforms are now able to test for a comprehensive range of viruses, can be operated by non-laboratory staff and can generate a result in approximately 1 h, making them potentially deployable as POCTs. The potential clinical benefits of POC testing for respiratory viruses in adults include a reduction in unnecessary antibiotic use, improved antiviral prescribing for influenza and rationalisation of isolation facilities. We review here the burden of disease, the currently available molecular platforms with potential for POCT use and the existing evidence for clinical and economic benefits of testing for respiratory viruses in adults
Re: 'syndromic panels or “panel syndrome”? A perspective through the lens of respiratory-tract infections' by Zanella et al
No full textIncrease in circulation of non-SARS-CoV-2 respiratory viruses following easing of social distancing is associated with increasing hospital attendance
No full textIn this Journal we recently reported that the appearance of SARS-CoV-2 and the accompanying social restrictions were associated with a dramatic reduction in circulation of non-SARS-CoV-2 viruses.1 We have also previously reported on the resurgence of rhinovirus circulation following the re-opening of schools in the United Kingdom in September 2020.2 Apprehension now surrounds the effects of complete cessation of social distancing measures in the United Kingdom on the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory viruses. The effect of social distancing on suppressing respiratory viruses are well documented and as these restrictions ease multiple routes of transmission increase.3 At University Hospital Southampton NHS Foundation Trust (UHSFT), UK, we have tested all adult medical patients admitted to hospital using point-of-care multiplex PCR testing (using the QIAstat-Dx Respiratory SARS-CoV-2 panel and the BioFire Respiratory Panel 2.1 plus) for a wide range of respiratory viruses, since the start of the SARS-CoV-2 pandemic.4 From 20th March 2020 to the 30th June 2021, 17804 adult patients have been tested. There was a near absence of detection of non-SARS-CoV-2 respiratory viruses following introduction of social distancing measuring during the first wave of the pandemic. In addition to the increases seen in rhinovirus detection after September 2020, detections of parainfluenza viruses and non-SARS-CoV-2 coronaviruses were seen to increase after the 18th April 2021, corresponding with the opening of non-essential retail and outdoor hospitality in England on the 12th April 2021. There was a further sharp increase following the resumption of indoor socialising and hospitality which started on the 17th May 2021 (figure 1). At peak circulation, 13% of admitted adult patients had parainfluenza viruses detected and 5% had non-SARS-CoV-2 coronaviruses detected. These findings are consistent with national surveillance data.5 Concurrently, Emergency Department attendances for acute respiratory illness increased at UHSFT following schools returning after the Easter holidays on the 8th March 2021 corresponding with an increase in rhinovirus detection. Thereafter, a further sustained increase in attendances has been seen coinciding with increased parainfluenza and non-SARS-CoV-2 detection (figure 2).Our data is aligned with previous research supporting the impact of social distancing on reducing the circulation of non-SARS-CoV-2 respiratory viruses, and that non-enveloped viruses such as rhinovirus, re-emerge initially as social distancing is eased followed by other viruses.1,2 The increase in detection of non-SARS-CoV-2 coronaviruses is in keeping with other reports of increased respiratory virus detections outside of the normal viral epidemiological cycles.6 These findings might have important implications for the complete relaxing of social distancing measures in the coming months and particularly on the forthcoming circulation of respiratory syncytial virus (RSV) and influenza viruses. <br/
Phase I studies: the role of publicly funded academic-healthcare partnerships
Full text linkEmanuel and colleagues’ meta-analysis found that phase I studies are very safe.1 However, the accompanying editorial mentioned that phase I studies are a “secret realm” and that “most studies are conducted outside academic medical centres at private facilities run by pharmaceutical companies or contract research organisations.”2After a major safety problem at a commercial phase I facility in 2006,3 the UK Medicines and Healthcare products Regulatory Agency (MHRA) introduced an accreditation scheme to enhance phase I safety standards in the UK. There are now four publicly funded phase I accredited clinical research facilities in the UK that have been open to non-commercial facilities since 2013. These include one university-hospital partnership (the Southampton National Institute for Health Research (NIHR) Wellcome Trust Clinical Research Facility) funded by the National Institute for Health Research. This provides an environment for early phase studies within the heart of an acute NHS hospital along with academic input from local university investigators. Phase I studies in patient populations and healthy volunteers are a crucial part of drug development. The UK Department of Health NIHR experimental medicine infrastructure has created a setting that delivers industry and publicly funded phase I trials while allowing recruitment from the entire UK population.<br/
Emergency Department point-of-care antiviral host response testing is accurate during periods of multiple respiratory virus co-circulation
No full textObjectives: FebriDx is a CE-marked, FDA-approved point-of-care test that detects the antiviral host response protein Myxovirus Resistance Protein A (MxA), in addition to C-reactive protein, using finger-prick blood. FebriDx MxA detection had a high negative predictive value for COVID-19 in symptomatic adults presenting to hospital in the first waves of the pandemic and was used subsequently as a ‘rule out’ triage tool in Emergency departments. The diagnostic accuracy of FebriDx MxA in the current context of co-circulation of influenza, SARS-CoV-2, and Respiratory Syncytial Virus (RSV), and in the era of COVID-19 vaccination, is unknown.Methods: we retrospectively evaluated the diagnostic performance of FebriDx MxA in adults with acute respiratory symptoms presenting to the Emergency Department (ED) of a large UK teaching hospital using Reverse Transcription Polymerase Chain Reaction (RT-PCR) as the reference standard (Cepheid Xpert Xpress SARS-CoV-2/Flu/RSV). Results: between March 9th 2022 and March 8th 2023, 5426 patients had both FebriDx and RT-PCR testing with valid results. 999 (18.4%) of patients had influenza detected, 520 (9.6%) SARS-CoV-2, and 190 (3.5%) RSV. Negative Predictive Value (NPV) of MxA detection by FebriDx was 97.5% (96.9-98.0) for influenza, 97.1% (96.4-97.7) for SARS-CoV-2, 98.1% (97.5-98.6) for RSV, and 92.8% (91.8-93.7) for all viruses combined.Conclusions: in symptomatic adults FebriDx MxA had a high NPV for influenza and RSV, and retained a high NPV for SARS-CoV-2, in the context of virus co-circulation and widespread COVID-19 vaccination. FebriDx continues to be a useful ‘rule out’ triage tool in the ED and could potentially be scaled to provide a national triage solution for future viral pandemics
Molecular point-of-care testing for respiratory viruses versus routine clinical care in adults with acute respiratory illness presenting to secondary care: a pragmatic randomised controlled trial protocol (ResPOC)
Full text linkBackground: Respiratory viruses are associated with a huge socio-economic burden and are responsible for a large proportion of acute respiratory illness in hospitalised adults. Laboratory PCR is accurate but takes at least 24 hours to generate a result to clinicians and antigen-based point-of-care tests (POCT) lack sensitivity. Rapid molecular platforms, such as the FilmArray Respiratory Panel, have equivalent diagnostic accuracy to laboratory PCR and can generate a result in 1 hour making them deployable as POCT. Molecular point-of-care testing for respiratory viruses in hospital has the potential to improve the detection rate of respiratory viruses, improve the use of influenza antivirals and reduce unnecessary antibiotic use, but high quality randomised trials with clinically relevant endpoints are needed.Methods: The ResPOC study is a pragmatic randomised controlled trial of molecular point-of-care testing for respiratory viruses in adults with acute respiratory illness presenting to a large teaching hospital in the United Kingdom. Eligible participants are adults presenting with acute respiratory illness to the emergency department or the acute medicine unit. Participants are allocated 1:1 by internet-based randomisation service to either the intervention of a nose and throat swab analysed immediately on the FilmArray Respiratory Panel as a POCT or receive routine clinical care. The primary outcome is the proportion of patients treated with antibiotics. Secondary outcomes include turnaround time, virus detection, neuraminidase inhibitor use, length of hospital stay and side room use. Analysis of the primary outcome will be by intention-to-treat and all enrolled participants will be included in safety analysis. Discussion: Multiple novel molecular POCT platforms for infections including respiratory viruses have been developed and licensed in the last few years and many more are in development but the evidence base for clinical benefit above standard practice is minimal. This randomised controlled trial aims to close this evidence gap by generating high quality evidence for the clinical impact of molecular POCT for respiratory viruses in secondary care and to act as an exemplar for future studies of molecular POCT for infections. This study has the potential to change practice and improve patient care for patients presenting to hospital with acute respiratory illness.Trial Registration: This study was registered with ISRCTN, number ISRCTN90211642, on 14th January 2015.<br/
Real-world performance of a single-use, analyser-free, molecular point-of-care test for COVID-19 used in the emergency department: results of a prospective trial (ED-POC)
No full textBackground: a novel single-use, analyser-free, molecular point-of-care test for SARS-CoV-2 (Veros COVID-19 test, Sherlock Biosciences) could reduce time to results and improve patient care and flow in the emergency department (ED), but its performance in this setting is unknown. Methods: adults aged ≥18 years presenting to Southampton General Hospital (UK) with suspected COVID-19 were tested with the Veros COVID-19 test in addition to standard of care near-patient PCR. Measures of diagnostic accuracy were calculated for the Veros COVID-19 test stratified by Ct value. Discrepant results underwent viral culture. Findings: between Jan 16 and May 2, 2023, 400 patients were enrolled with a median (IQR) age of 60 (34−77) and 141 (35·3%) were SARS-CoV-2 positive by PCR. The Veros test gave valid results on the first test in 384 (96·0%), and sensitivity and specificity were 127/141 (90·1%, 95%CI 83·9–94·5) and 258/259 (99·6%, 95%CI 97·9–100) overall. For those with high or moderate viral load (Ct ≤30), sensitivity was 125/129 (96·9%, 95%CI 92·3–99·2). One (7·1%) of 14 PCR positive/Veros test negative samples was culture positive. Median (IQR) time from sample collection to result was 19 (18−20) mins with the Veros test versus 73 (59−92) mins with PCR (p < 0·0001). Interpretation: the Veros COVID-19 test generated results in near real-time, around 1 h sooner than rapid, near-patient, analyser-based PCR, and accuracy was excellent for samples with moderate and high viral loads. The Veros test represents a step-change in molecular diagnostics for infection and could significantly reduce time to results and improve patient management in EDs and other settings.</p
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