Publications by authors named "Nathan J Brendish"

20 Publications

  • Page 1 of 1

Influenza vaccination: protecting the most vulnerable.

Eur Respir Rev 2021 Mar 13;30(159). Epub 2021 Jan 13.

School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

Influenza virus infection causes seasonal epidemics and occasional pandemics, leading to huge morbidity and mortality worldwide. Vaccination against influenza is needed annually as protection from constantly mutating strains is required. Groups at high risk of poor outcomes include the elderly, the very young, pregnant women and those with chronic health conditions. However, vaccine effectiveness in the elderly is generally poor due to immunosenescence and may be altered due to "original antigenic sin". Strategies to overcome these challenges in the elderly include high-dose or adjuvant vaccines. Other options include vaccinating healthcare workers and children as this reduces community-level influenza transmission. Current guidelines in the UK are that young children receive a live attenuated nasal spray vaccine, adults aged >65 years receive an adjuvanted trivalent inactivated vaccine and adults aged <65 years with comorbidities receive a quadrivalent inactivated vaccine. The goal of a universal influenza vaccine targeting conserved regions of the virus and avoiding the need for annual vaccination is edging closer with early-phase trials under way.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/16000617.0258-2020DOI Listing
March 2021

Physical distancing in schools for SARS-CoV-2 and the resurgence of rhinovirus.

Lancet Respir Med 2020 12 22;8(12):e92-e93. Epub 2020 Oct 22.

School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton SO16 6YD, UK; Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK; NIHR Southampton Biomedical Research Centre, Southampton, UK; NIHR Post-Doctoral Fellowship Programme, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(20)30502-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581315PMC
December 2020

Clinical impact of a routine, molecular, point-of-care, test-and-treat strategy for influenza in adults admitted to hospital (FluPOC): a multicentre, open-label, randomised controlled trial.

Lancet Respir Med 2021 04 4;9(4):419-429. Epub 2020 Dec 4.

NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

Background: Diagnosis of influenza in patients admitted to hospital is delayed due to long turnaround times with laboratory testing, leading to inappropriate and late antiviral treatment and isolation facility use. Molecular point-of-care tests (mPOCTs) are highly accurate, easy to use, and generate results in less than 1 h, but high-quality evidence for their effect on management and clinical outcomes is needed. The aim of this study was to assess the clinical impact of an mPOCT on influenza detection, antiviral use, infection control measures, and clinical outcomes in adults admitted to hospital with acute respiratory illness.

Methods: In this multicentre, pragmatic, open-label, randomised controlled trial (FluPOC), we recruited adults admitted to hospital with acute respiratory illness during influenza seasons from two hospitals in Hampshire, UK. Eligible patients were aged 18 years and older, with acute respiratory illness of 10 days or fewer duration before admission to hospital, who were recruited within 16 h of admission to hospital. Participants were randomly assigned (1:1), using random permuted blocks of varying sizes (4, 6 and 8), to receive mPOCT for influenza or routine clinical care (control group). The primary outcome was the proportion of patients infected with influenza who were treated appropriately with antivirals (neuraminidase inhibitors) within 5 days of admission. Safety was assessed in all patients. Secondary outcomes included time to antivirals, isolation facility use, and clinical outcomes. This study is registered with the ISRCTN registry, ISRCTN17197293, and is now complete.

Findings: Between Dec 12, 2017, and May 3, 2019, over two influenza seasons, 613 patients were enrolled, of whom 307 were assigned to the mPOCT group and 306 to the control group, and all were analysed. Median age was 62 years (IQR 45-75) and 332 (54%) of 612 participants with data were female. 100 (33%) of 307 patients in the mPOCT group and 102 (33%) of 306 in the control group had influenza. 100 (100%) of 100 patients with influenza were diagnosed in the mPOCT group and 60 (59%) of 102 were diagnosed though routine clinical care in the control group (relative risk 1·7, 95% CI 1·7-1·7; p<0·0001). 99 (99%) of 100 patients with influenza in the mPOCT group were given antiviral treatment within 5 days of admission versus 63 (62%) 102 in the control group (relative risk 1·6, 95% CI 1·4-1·9; p<0·0001). Median time to antivirals was 1·0 h (IQR 0·0 to 2·0) in the mPOCT group versus 6·0 h (0·0 to 12·0) in the control group (difference of 5·0 h [95% CI 0·0-6·0; p=0·0039]). 70 (70%) of 100 patients with influenza in the mPOCT group were isolated to single-room accommodation versus 39 (38%) of 102 in the control group (relative risk 1·8 [95% CI 1·4-2·4; p<0·0001]). 19 adverse events occurred among patients with influenza in the mPOCT group compared with 34 events in the control group. No patients with influenza died in the mPOCT group and two (2%) died in the control group (p=0·16).

Interpretation: Routine mPOCT for influenza was associated with improved influenza detection and improvements in appropriate and timely antiviral and isolation facility use. Routine mPOCT should replace laboratory-based diagnostics for acute admissions to hospital during the influenza season.

Funding: National Institute for Health Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(20)30469-0DOI Listing
April 2021

SARS-CoV-2 has displaced other seasonal respiratory viruses: Results from a prospective cohort study.

J Infect 2020 12 15;81(6):966-972. Epub 2020 Nov 15.

NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust Southampton, UK; Department of Infection, University Hospital Southampton NHS Foundation Trust Southampton, UK; School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; NIHR Post-Doctoral Fellowship Programme, UK.

Objectives: The effect of SARS-CoV-2 on existing respiratory viruses in circulation and the overall burden of viral respiratory disease remains uncertain. Traditionally, severe viral respiratory disease disproportionally affects those with underlying chronic lung diseases. This study aimed to assess the impact of SARS-CoV-2 on the prevalence and clinical characteristics of respiratory virus disease in hospitalised adults.

Methods: Data for this cohort study were from hospitalised adults who had multiplex PCR testing for respiratory viruses over several seasons in Hampshire, UK. Respiratory virus detection during the first epidemic peak of SARS-CoV-2 was compared to detection during the same time period across previous years.

Results: 856 patients had multiplex PCR for respiratory viruses between March and May over 5 years. Before 2020, a non-SARS-CoV-2 virus was detected in 54% patients (202/371) compared to 4.1% (20/485) in 2020 (p < 0.0001). SARS-CoV-2 was associated with asthma or COPD exacerbations in a smaller proportion of infected patients compared to other viruses (1.0% vs 37%, p < 0.0001).

Conclusions: The emergence of SARS-CoV-2 was associated with substantial reductions in the circulation of seasonal respiratory viruses and large differences in the characteristics of viral-associated disease, including illness in a greater proportion of patients without underlying lung disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2020.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666810PMC
December 2020

Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): a prospective, interventional, non-randomised, controlled study.

Lancet Respir Med 2020 12 8;8(12):1192-1200. Epub 2020 Oct 8.

School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. Electronic address:

Background: The management of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals, these delays lead to poor patient flow and nosocomial transmission. Rapid, accurate tests are therefore urgently needed in preparation for the next wave of the pandemic.

Methods: We did a prospective, interventional, non-randomised, controlled study of molecular point-of-care testing in patients aged 18 years or older presenting with suspected COVID-19 to the emergency department or other acute areas of Southampton General Hospital during the first wave of the pandemic in the UK. Nose and throat swab samples taken at admission from patients in the point-of-care testing group were tested with the QIAstat-Dx Respiratory SARS-CoV-2 Panel. Samples taken from patients in a contemporaneous control group were tested by laboratory PCR. The primary outcome was time to results in the full cohort. This study is registered with ISRCTN (ISRCTN14966673) and is completed.

Findings: Between March 20 and April 29, 2020, 517 patients were assessed for eligibility, of whom 499 were recruited to the point-of-care testing group and tested by the QIAstat-Dx Respiratory SARS-CoV-2 Panel. 555 contemporaneously identified patients were included in the control group and tested by laboratory PCR. The two groups were similar with regard to the distribution of sex, age, and ethnicity. 197 (39%) patients in the point-of-care testing group and 155 (28%) in the control group tested positive for COVID-19 (difference 11·5% [95% CI 5·8-17·2], p=0·0001). Median time to results was 1·7 h (IQR 1·6-1·9) in the point-of-care testing group and 21·3 h (16·0-27·9) in the control group (difference 19·6 h [19·0-20·3], p<0·0001). A Cox proportional hazards regression model controlling for age, sex, time of presentation, and severity of illness also showed that time to results was significantly shorter in the point-of-care testing group than in the control group (hazard ratio 4023 [95% CI 545-29 696], p<0·0001).

Interpretation: Point-of-care testing is associated with large reductions in time to results and could lead to improvements in infection control measures and patient flow compared with centralised laboratory PCR testing.

Funding: University Hospitals Southampton NHS Foundation Trust.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(20)30454-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544498PMC
December 2020

Clinical characteristics, symptoms and outcomes of 1054 adults presenting to hospital with suspected COVID-19: A comparison of patients with and without SARS-CoV-2 infection.

J Infect 2020 12 28;81(6):937-943. Epub 2020 Sep 28.

School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS, Foundation Trust, Southampton, UK; NIHR Post Doctoral Fellowship Programme, UK.

Objectives: Most reports describing the characteristics of patients hospitalised with COVID-19 lack a comparator group. We compared clinical characteristics, symptoms, and outcomes of adults presenting to hospital during the pandemic first wave, who tested positive and negative for SARS-CoV-2.

Methods: Detailed patient data was obtained from a large, controlled, non-randomised trial of molecular point-of-care testing versus laboratory RT-PCR for SARS-CoV-2 in adults presenting to a large UK hospital with suspected COVID-19.

Results: 1054 patients were included: 352 (33.4%) tested positive and 702 (66.6%) negative. 13.4% (47/352) COVID-19-positive patients had COPD versus 18.7% (131/702) of COVID-19-negative patients (difference=5.3% [95%CI -9.7% to -0.5%], p = 0.0297). 5.7% (20/352) of COVID-19-positive patients were smokers versus 16.5% (116/702) of negative patients (difference=-10.8% [-14.4% to -7.0%], p = 0.0001). 70.5% (248/352) of COVID-19-positive patients were White-British versus 85.5% (600/702) of negative patients (difference=-15.0% [-20.5% to -9.7%], p<0.0001). 20.9% (39/187) of COVID-19-positive patients were healthcare workers versus 5.2% (15/287) of negative patients (p<0.0001). Anosmia was reported in 33.1% (47/142) versus 8.8% (19/216) of COVID-19-positive and negative patients respectively (p<0.0001). Non-SARS-CoV-2 respiratory viruses or atypical bacteria were detected in 2.5% (5/197) of COVID-19 patients versus 7.9% (24/302) of COVID-19-negative patients (p = 0.0109). Hospitalisation duration and 30-day-mortality were higher in COVID-19 patients and invasive ventilation was more frequent (11.1% vs 2.8%, p<0.0001), and longer (14.5 vs 4.7 days, p = 0.0015).

Conclusions: There were substantial differences between patients with and without COVID-19 in terms of ethnicity, healthcare worker-status, comorbidities, symptoms, and outcomes. These data can inform healthcare planning for the next phase of the pandemic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2020.09.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521430PMC
December 2020

Diagnostic accuracy of the FebriDx host response point-of-care test in patients hospitalised with suspected COVID-19.

J Infect 2020 10 21;81(4):607-613. Epub 2020 Jun 21.

Southampton Clinical Trials Unit, University of Southampton, UK.

Introduction: Management of the COVID-19 pandemic is hampered by long delays associated with centralised laboratory PCR testing. In hospitals this leads to poor patient flow and nosocomial transmission and so rapid, accurate diagnostic tests are urgently required. The FebriDx is a point-of-care test that detects an antiviral host response protein in finger prick blood within 10 min, but its accuracy for the identification of COVID-19 is unknown.

Methods: We performed a real-world diagnostic accuracy study of FebriDx in hospitalised patients during the first wave of the pandemic. Measures of diagnostic accuracy were calculated based on FebriDx results compared to the reference standard of SARS-CoV-2 PCR on combined nose and throat swabs. A multivariable predictive model including FebriDx, age, sex, and clinical characteristics was developed and underwent internal validation.

Results: FebriDx was performed on 251 patients and gave a valid result in 248. 118 of 248 (48%) were PCR positive for COVID-19. FebriDx results were available after 10 min compared with 1.7 (1.6 to 2.1) hours with point-of-care PCR testing and 23.4 (17.2 to 31.1) hours with laboratory PCR testing. Sensitivity of FebriDx for the identification of COVID-19 was 93% (110/118; 95% CI 87 to 97%) and specificity was 86% (112/130; 95%CI 79 to 92%). Positive and negative likelihood ratios were 6.73 (95%CI 4.37 to 10.37) and 0.08 (95%CI 0.04 to 0.15) respectively. In the multivariate model age, sex and other clinical features did not contribute significantly to the effect of the FebriDx result in distinguishing patients with and without COVID-19.

Conclusions: During the first wave of the pandemic, FebriDx had high accuracy for the identification of COVID-19 in hospitalised adults and could be deployed as a front door triage tool.

Trial Registration: ISRCTN14966673.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2020.06.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7306108PMC
October 2020

Impact of point-of-care testing for respiratory viruses on antibiotic use in adults with exacerbation of airways disease.

J Infect 2019 10 21;79(4):357-362. Epub 2019 Jun 21.

Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; Department of Infection, University Hospital Southampton NHS Foundation Trust, LF101, South Academic block, Southampton General Hospital, Southampton SO16 6YD, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; NIHR Post-Doctoral Fellowship Programme, UK. Electronic address:

Background: The ResPOC study demonstrated that syndromic molecular point-of-care testing (POCT) for respiratory viruses was associated with early discontinuation of unnecessary antibiotics compared to routine clinical care. Subgroup analysis suggests these changes occur predominantly in patients with exacerbation of airways disease. Use of molecular POCT for respiratory viruses is becoming widespread but there is a lack of evidence to inform the choice between multiplex syndromic panels versus POCT for influenza only.

Materials/methods: We evaluated patients from the ResPOC study with exacerbation of asthma or COPD who were treated with antibiotics. The duration of antibiotics and proportion with early discontinuation were compared between patients testing positive and negative for viruses by POCT, and controls. Patients testing positive for viruses by POCT were compared according to virus types.

Results: 118 patient with exacerbation of airways disease received antibiotics in the POCT group and 111 in the control group. In the POCT group 49/118 (42%) patients tested positive for viruses. Of those testing positive for viruses 17/49 (35%) had early discontinuation of antibiotics versus 9/69 (13%) testing negative and 7/111 (6%) of controls, p<0.0001. Of those positive for viruses by POCT 10/49 (20%) were positive for influenza, 21/49 (43%) for rhinovirus and 18/49 (37%) for other viruses. The proportion with early discontinuation of antibiotics was not different between the virus types (p = 0.34).

Conclusions: This data suggests that syndromic molecular POCT for respiratory viruses should be favoured over POCT for influenza alone in adults with exacerbation of airways disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2019.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112619PMC
October 2019

Hospitalised adults with pneumonia are frequently misclassified as another diagnosis.

Respir Med 2019 04 21;150:81-84. Epub 2019 Feb 21.

Academic Unit of Clinical and Experimental Sciences, University of Southampton, Southampton, UK; Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; NIHR Post-Doctoral Fellowship Programme, UK.

Using data from a large randomised controlled trial of adults hospitalised with acute respiratory illness, we examined the reliability of pneumonia diagnosis on discharge documentation. 50 (28.2%) of 177 patients with a pneumonia diagnosis had no radiological evidence of pneumonia. 67 (34.9%) of 192 patients with clinico-radiological evidence of pneumonia did not have a diagnosis of pneumonia listed; 'COPD exacerbation' or 'lower respiratory tract infection' was often listed instead. These patients more frequently had a respiratory comorbidity and lower oxygen saturations, CRP and temperature at presentation. Pneumonia diagnoses misclassification on discharge documentation may have clinical, financial, and research data implications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmed.2019.02.013DOI Listing
April 2019

Molecular Point-of-care Testing for Influenza to Improve Early Neuraminidase Inhibitor Treatment and Outcomes in Hospitalized Adults.

Clin Infect Dis 2019 05;68(12):2154-2155

Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciy1042DOI Listing
May 2019

Treatment of influenza with neuraminidase inhibitors.

Curr Opin Infect Dis 2018 12;31(6):514-519

Academic Unit of Clinical and Experimental Sciences, University of Southampton.

Purpose Of Review: Seasonal and pandemic influenza are major causes of morbidity and mortality globally. Neuraminidase inhibitors (NAIs) are the only class of antiviral agent recommended for the treatment of currently circulating strains of influenza. There has previously been controversy over the level of evidence for patient benefit with NAIs. We review here the current evidence base for the clinical impact of treatment of influenza with NAIs.

Recent Findings: Meta-analysis of pharma-sponsored studies (including previously unpublished data) shows that NAIs reduce the duration of illness in influenza-infected patients, and suggest a possible reduction in the rate of complications and hospitalization. Meta-analysis of observational studies examining oseltamivir use during the H1N1 2009 pandemic, suggest a reduction in hospitalization rate in community-dwelling patients and a reduction in mortality in hospitalized adults treated with NAIs. Current NAI use in the community and hospitals varies widely but in general they are underutilized.

Summary: Although there has been controversy over the level of evidence for patient benefit, a growing body of evidence suggests that treatment of influenza with NAIs is associated with improved outcomes for both patients in the community and more severely unwell patients in hospital. Clinical outcomes are optimal with earlier use and strategies to improve early widespread NAI utilization are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QCO.0000000000000496DOI Listing
December 2018

Impact of turnaround time on outcome with point-of-care testing for respiratory viruses: a analysis from a randomised controlled trial.

Eur Respir J 2018 08 9;52(2). Epub 2018 Aug 9.

Academic Unit of Clinical and Experimental Sciences, University of Southampton, Southampton, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1183/13993003.00555-2018DOI Listing
August 2018

Antiviral treatment of severe non-influenza respiratory virus infection.

Curr Opin Infect Dis 2017 Dec;30(6):573-578

aClinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General HospitalbNIHR Southampton Biomedical Research CentrecNIHR Post-Doctoral Fellowship Programme, Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

Purpose Of Review: Non-influenza respiratory virus infections are a frequent cause of severe acute respiratory infections, especially in infants, the elderly, and the immunocompromised. We review here the current treatment options for non-influenza respiratory viruses and promising candidate antiviral agents currently in development.

Recent Findings: Small molecule antiviral agents active against respiratory syncytial virus (RSV), such as ALS-8176 and GS-5806, show considerable promise in challenge studies and are undergoing late-phase clinical trials in hospitalised adults and children. Monoclonal antibodies (mAbs) active against non-influenza respiratory viruses are broadly at a preclinical stage. Broad-spectrum antivirals, such as favipiravir and nitrazoxanide, have potential utility in treating illness caused by non-influenza respiratory viruses but further definitive clinical trials are needed.

Summary: Severe non-influenza respiratory virus infection is common and current treatment is largely supportive. Ribavirin is used in immunocompromised patients but its use is limited by toxicity and the evidence for its efficacy is weak. Effective antiviral treatment for RSV may shortly become available, pending the results of ongoing clinical trials. For other non-influenza viruses, effective treatments may become available in the medium term. Early detection of respiratory viruses with rapid molecular test platforms will be crucial in differentiating virus types and directing the prompt initiation of novel treatments when available.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/QCO.0000000000000410DOI Listing
December 2017

Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions.

JCI Insight 2017 11 2;2(21). Epub 2017 Nov 2.

The Jenner Institute, University of Oxford, Oxford, United Kingdom.

The development of a highly effective vaccine remains a key strategic goal to aid the control and eventual eradication of Plasmodium falciparum malaria. In recent years, the reticulocyte-binding protein homolog 5 (RH5) has emerged as the most promising blood-stage P. falciparum candidate antigen to date, capable of conferring protection against stringent challenge in Aotus monkeys. We report on the first clinical trial to our knowledge to assess the RH5 antigen - a dose-escalation phase Ia study in 24 healthy, malaria-naive adult volunteers. We utilized established viral vectors, the replication-deficient chimpanzee adenovirus serotype 63 (ChAd63), and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding RH5 from the 3D7 clone of P. falciparum. Vaccines were administered i.m. in a heterologous prime-boost regimen using an 8-week interval and were well tolerated. Vaccine-induced anti-RH5 serum antibodies exhibited cross-strain functional growth inhibition activity (GIA) in vitro, targeted linear and conformational epitopes within RH5, and inhibited key interactions within the RH5 invasion complex. This is the first time to our knowledge that substantial RH5-specific responses have been induced by immunization in humans, with levels greatly exceeding the serum antibody responses observed in African adults following years of natural malaria exposure. These data support the progression of RH5-based vaccines to human efficacy testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.96381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5752323PMC
November 2017

Routine molecular point-of-care testing for respiratory viruses in adults presenting to hospital with acute respiratory illness (ResPOC): a pragmatic, open-label, randomised controlled trial.

Lancet Respir Med 2017 05 6;5(5):401-411. Epub 2017 Apr 6.

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK; Department of Infection, University Hospital Southampton NHS Foundation Trust, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK. Electronic address:

Background: Respiratory virus infection is a common cause of hospitalisation in adults. Rapid point-of-care testing (POCT) for respiratory viruses might improve clinical care by reducing unnecessary antibiotic use, shortening length of hospital stay, improving influenza detection and treatment, and rationalising isolation facility use; however, insufficient evidence exists to support its use over standard clinical care. We aimed to assess the effect of routine POCT on a broad range of clinical outcomes including antibiotic use.

Methods: In this pragmatic, parallel-group, open-label, randomised controlled trial, we enrolled adults (aged ≥18 years) within 24 h of presenting to the emergency department or acute medical unit of a large UK hospital with acute respiratory illness or fever higher than 37·5°C (≤7 days duration), or both, over two winter seasons. Patients were randomly assigned (1:1), via an internet-based allocation sequence with random permuted blocks, to have a molecular POC test for respiratory viruses or routine clinical care. The primary outcome was the proportion of patients who received antibiotics while hospitalised (up to 30 days). Secondary outcomes included duration of antibiotics, proportion of patients receiving single doses or brief courses of antibiotics, length of stay, antiviral use, isolation facility use, and safety. Analysis was by modified intention to treat, excluding patients who declined intervention or were withdrawn for protocol violations. This study is registered with ISRCTN, number 90211642, and has been completed.

Findings: Between Jan 15, 2015, and April 30, 2015, and between Oct 1, 2015, and April 30, 2016, we enrolled 720 patients (362 assigned to POCT and 358 to routine care). Six patients withdrew or had protocol violations. 301 (84%) of 360 patients in the POCT group received antibiotics compared with 294 (83%) of 354 controls (difference 0·6%, 95% CI -4·9 to 6·0; p=0·84). Mean duration of antibiotics did not differ between groups (7·2 days [SD 5·1] in the POCT group vs 7·7 days [4·9] in the control group; difference -0·4, 95% CI -1·2 to 0·4; p=0·32). 50 (17%) of 301 patients treated with antibiotics in the POCT group received single doses or brief courses of antibiotics (<48 h) compared with 26 (9%) of 294 patients in the control group (difference 7·8%, 95% CI 2·5 to 13·1; p=0·0047; number needed to test=13). Mean length of stay was shorter in the POCT group (5·7 days [SD 6·3]) than in the control group (6·8 days [7·7]; difference -1·1, 95% CI -2·2 to -0·3; p=0·0443). Appropriate antiviral treatment of influenza-positive patients was more common in the POCT group (52 [91%] of 57 patients) than in the control group (24 [65%] of 37 patients; difference 26·4%, 95% CI 9·6 to 43·2; p=0·0026; number needed to test=4). We found no differences in adverse outcomes between the groups (77 [21%] of 360 patients in the POCT group vs 88 [25%] of 354 patients in the control group; -3·5%, -9·7 to 2·7; p=0·29).

Interpretation: Routine use of molecular POCT for respiratory viruses did not reduce the proportion of patients treated with antibiotics. However, the primary outcome measure failed to capture differences in antibiotic use because many patients were started on antibiotics before the results of POCT could be made available. Although POCT was not associated with a reduction in the duration of antibiotics overall, more patients in the POCT group received single doses or brief courses of antibiotics than did patients in the control group. POCT was also associated with a reduced length of stay and improved influenza detection and antiviral use, and appeared to be safe.

Funding: University of Southampton.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2213-2600(17)30120-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164815PMC
May 2017

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).

BMC Infect Dis 2017 02 6;17(1):128. Epub 2017 Feb 6.

Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

Background: 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 h 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 h 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12879-017-2219-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294894PMC
February 2017

Respiratory tract infection associated with seizures.

BMJ 2015 Sep 4;351:h4659. Epub 2015 Sep 4.

Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK Department of Paediatric Immunology and Infectious Diseases, University Hospital Southampton NHS Foundation Trust Institute for Life Sciences, University of Southampton, Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton NHS Foundation Trust Department of Paediatrics, University of Melbourne, Parkville, Australia

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.h4659DOI Listing
September 2015

Point-of-care testing for respiratory viruses in adults: The current landscape and future potential.

J Infect 2015 Nov 26;71(5):501-10. Epub 2015 Jul 26.

Department of Clinical and Experimental Sciences and Respiratory Biomedical Research Unit, University of Southampton, UK. Electronic address:

Respiratory 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jinf.2015.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7172689PMC
November 2015

Phase I studies: the role of publicly funded academic-healthcare partnerships.

BMJ 2015 Jul 22;351:h3889. Epub 2015 Jul 22.

Southampton National Institute for Health Research Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton SO16 6YD, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmj.h3889DOI Listing
July 2015

Global extent of chloroquine-resistant Plasmodium vivax.

Lancet Infect Dis 2015 Jun 17;15(6):630. Epub 2015 May 17.

NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(15)00017-1DOI Listing
June 2015