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Horby P, Mafham M, Linsell L, et al., 2020, Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 383, Pages: 2030-2040, ISSN: 0028-4793
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- Citations: 199
Riley S, Ainslie K, Eales O, et al., 2020, REACT-1 round 6 updated report: high prevalence of SARS-CoV-2 swab positivity with reduced rate of growth in England at the start of November 2020
BackgroundEngland is now in the midst of its second wave of the COVID-19 pandemic. Multiple regions of the country are at high infection prevalence and all areas experienced rapid recent growth of the epidemic during October 2020.MethodsREACT-1 is a series of community surveys of SARS-CoV-2 RT-PCR swab-positivity in England designed to monitor the spread of the epidemic and thus increase situational awareness. Round 6 of REACT-1 commenced swab-collection on 16th October. A prior interim report included data from 16th to 25th October for 85,971 participants. Here, we report data for the entire round on 160,175 participants with swab results obtained up to 2nd November 2020.ResultsOverall weighted prevalence of infection in the community in England was 1.3% or 130 people per 10,000 infected, up from 60 people per 10,000 in the round 5 report (18th September to 5th October 2020), doubling every 24 days on average since the prior round. The corresponding R number was estimated to be 1.2. Prevalence of infection was highest in North West (2.4%, up from 1.2% ), followed by Yorkshire and The Humber (2.3% up from 0.84%), West Midlands (1.6% up from 0.60%), North East (1.5% up from 1.1%), East Midlands (1.3% up from 0.56%), London (0.97%, up from 0.54%), South West (0.80% up from 0.33%), South East (0.69% up from 0.29%), and East of England (0.69% up from 0.30%). Rapid growth in the South observed in the first half of round 6 was no longer apparent in the second half of round 6. We also observed a decline in prevalence in Yorkshire and The Humber during this period. Comparing the first and second halves of round 6, there was a suggestion of decline in weighted prevalence in participants aged 5 to 12 years and in those aged 25 to 44 years. While prevalence remained high, in the second half of round 6 there was suggestion of a slight fall then rise that was seen nationally and also separately in both the North and the South.ConclusionThe impact of the second national lockdown
Riley S, Ainslie KEC, Eales O, et al., 2020, High prevalence of SARS-CoV-2 swab positivity and increasing R number in England during October 2020: REACT-1 round 6 interim report, Publisher: medRxiv
Background REACT-1 measures prevalence of SARS-CoV-2 infection in representative samples of the population in England using PCR testing from self-administered nose and throat swabs. Here we report interim results for round 6 of observations for swabs collected from the 16th to 25th October 2020 inclusive. Methods REACT-1 round 6 aims to collect data and swab results from 160,000 people aged 5 and above. Here we report results from the first 86,000 individuals. We estimate prevalence of PCR-confirmed SARS-CoV-2 infection, reproduction numbers (R) and temporal trends using exponential growth or decay models. Prevalence estimates are presented both unweighted and weighted to be representative of the population of England, accounting for response rate, region, deprivation and ethnicity. We compare these interim results with data from round 5, based on swabs collected from 18th September to 5th October 2020 inclusive. Results Overall prevalence of infection in the community in England was 1.28% or 128 people per 10,000, up from 60 per 10,000 in the previous round. Infections were doubling every 9.0 (6.1, 18) days with a national reproduction number (R) estimated at 1.56 (1.27, 1.88) compared to 1.16 (1.05, 1.27) in the previous round. Prevalence of infection was highest in Yorkshire and The Humber at 2.72% (2.12%, 3.50%), up from 0.84% (0.60%, 1.17%), and the North West at 2.27% (1.90%, 2.72%), up from 1.21% (1.01%, 1.46%), and lowest in South East at 0.55% (0.45%, 0.68%), up from 0.29% (0.23%, 0.37%). Clustering of cases was more prevalent in Lancashire, Manchester, Liverpool and West Yorkshire, West Midlands and East Midlands. Interim estimates of R were above 2 in the South East, East of England, London and South West, but with wide confidence intervals. Nationally, prevalence increased across all age groups with the greatest increase in those aged 55-64 at 1.20% (0.99%, 1.46%), up 3-fold from 0.37% (0.30%, 0.46%). In those aged over 65, prevalence was 0.81% (0.58%, 0
Simmonds P, Cuypers L, Irving WL, et al., 2020, Impact of virus subtype and host <i>IFNL4</i> genotype on large-scale RNA structure formation in the genome of hepatitis C virus, RNA, Vol: 26, Pages: 1541-+, ISSN: 1355-8382
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- Citations: 3
Gibani MM, Toumazou C, Sohbati M, et al., 2020, Assessing a novel, lab-free, point-of-care test for SARS-CoV-2 (CovidNudge): a diagnostic accuracy study., The Lancet Microbe, Vol: 1, Pages: e300-e307, ISSN: 2666-5247
Background: Access to rapid diagnosis is key to the control and management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Laboratory RT-PCR testing is the current standard of care but usually requires a centralised laboratory and significant infrastructure. We describe our diagnostic accuracy assessment of a novel, rapid point-of-care real time RT-PCR CovidNudge test, which requires no laboratory handling or sample pre-processing. Methods: Between April and May, 2020, we obtained two nasopharyngeal swab samples from individuals in three hospitals in London and Oxford (UK). Samples were collected from three groups: self-referred health-care workers with suspected COVID-19; patients attending emergency departments with suspected COVID-19; and hospital inpatient admissions with or without suspected COVID-19. For the CovidNudge test, nasopharyngeal swabs were inserted directly into a cartridge which contains all reagents and components required for RT-PCR reactions, including multiple technical replicates of seven SARS-CoV-2 gene targets (rdrp1, rdrp2, e-gene, n-gene, n1, n2 and n3) and human ribonuclease P (RNaseP) as sample adequacy control. Swab samples were tested in parallel using the CovidNudge platform, and with standard laboratory RT-PCR using swabs in viral transport medium for processing in a central laboratory. The primary analysis was to compare the sensitivity and specificity of the point-of-care CovidNudge test with laboratory-based testing. Findings: We obtained 386 paired samples: 280 (73%) from self-referred health-care workers, 15 (4%) from patients in the emergency department, and 91 (23%) hospital inpatient admissions. Of the 386 paired samples, 67 tested positive on the CovidNudge point-of-care platform and 71 with standard laboratory RT-PCR. The overall sensitivity of the point-of-care test compared with laboratory-based testing was 94% (95% CI 86-98) with an overall specificity of 100% (99-100). The sensitivity of the test varied
Tsang O, Brar I, Spinner C, et al., 2020, IMPACT OF BASELINE ALANINE AMINOTRANSFERASE LEVELS ON THE SAFETY AND EFFICACY OF REMDESIVIR IN MODERATE COVID-19 PATIENTS, Liver Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD), Publisher: WILEY, Pages: 88A-89A, ISSN: 0270-9139
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- Citations: 2
Daunt A, Perez-Guzman PN, Cafferkey J, et al., 2020, Factors associated with reattendance to emergency services following COVID-19 hospitalization, Journal of Medical Virology, Vol: 93, Pages: 1250-1252, ISSN: 0146-6615
Thompson CP, Grayson NE, Paton RS, et al., 2020, Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020., Euro Surveillance, Vol: 25, Pages: 1-9
BackgroundThe progression and geographical distribution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United Kingdom (UK) and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland in the spring of 2020 to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.AimOur objective was to determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.MethodsA pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study comprised samples from 3,500 blood donors collected in Scotland between 17 March and 18 May 2020. Controls were collected from 100 donors in Scotland during 2019.ResultsAll samples collected on 17 March 2020 (n = 500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in six of 500 donors from 23 to 26 March. The number of samples containing neutralising antibodies did not significantly rise after 5-6 April until the end of the study on 18 May. We found that infections were concentrated in certain postcodes, indicating that outbreaks of infection were extremely localised. In contrast, other areas remained comparatively untouched by the epidemic.ConclusionAlthough blood donors are not representative of the overall population, we demonstrated that serosurveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic such as the SARS-CoV-2 outbreak.
Riley S, Ainslie KEC, Eales O, et al., 2020, High and increasing prevalence of SARS-CoV-2 swab positivity in England during end September beginning October 2020: REACT-1 round 5 updated report
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>REACT-1 is quantifying prevalence of SARS-CoV-2 infection among random samples of the population in England based on PCR testing of self-administered nose and throat swabs. Here we report results from the fifth round of observations for swabs collected from the 18th September to 5th October 2020. This report updates and should be read alongside our round 5 interim report.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Representative samples of the population aged 5 years and over in England with sample size ranging from 120,000 to 175,000 people at each round. Prevalence of PCR-confirmed SARS-CoV-2 infection, estimation of reproduction number (R) and time trends between and within rounds using exponential growth or decay models.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>175,000 volunteers tested across England between 18th September and 5th October. Findings show a national prevalence of 0.60% (95% confidence interval 0.55%, 0.71%) and doubling of the virus every 29 (17, 84) days in England corresponding to an estimated national R of 1.16 (1.05, 1.27). These results correspond to 1 in 170 people currently swab-positive for the virus and approximately 45,000 new infections each day. At regional level, the highest prevalence is in the North West, Yorkshire and The Humber and the North East with strongest regional growth in North West, Yorkshire and The Humber and West Midlands.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Rapid growth has led to high prevalence of SARS-CoV-2 virus in England, with highest rates in the North of England. Prevalence has increased in all age groups, including those at highest risk. Improved compliance with existing policy and, as necessar
Boncea E, Expert P, Honeyford K, et al., 2020, Association between intrahospital transfers and hospital-acquired infection among elderly patients: A retrospective case-control study in one urban UK hospital trust, Publisher: BMJ Publishing Group
<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Intrahospital transfers have become more common as hospital staff balance patient needs with bed availability. However, this may leave patients more vulnerable to potential pathogen transmission routes via increased exposure to contaminated surfaces and contacts with individuals.</jats:p></jats:sec><jats:sec><jats:title>Objective</jats:title><jats:p>This study aimed to quantify the association between the number of intrahospital transfers undergone during a hospital spell and the development of a hospital-acquired infection (HAI).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A retrospective case-control study was conducted using data extracted from electronic health records and microbiology cultures of non-elective, medical admissions to a large urban hospital trust comprising 3 hospital sites between 2016 and 2018 (<jats:italic>n</jats:italic>=24,239). As elderly patients comprise a large proportion of hospital users and are a high-risk population for HAIs, the analysis focused on those over 65-years old. Logistic regression was conducted to obtain the odds ratio (OR) for developing a HAI as a function of intrahospital transfers until onset of HAI for cases, or hospital discharge for controls, while controlling for age, gender, time-at-risk, Elixhauser comorbidities, hospital site of admission, dominant treatment function code, intensive care admission, total number of procedures, and discharge destination.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Of the 24,239 spells, 2879 cases were included in the analysis. 72.2% of spells contained at least one intrahospital transfer. On multivariable analysis, each additional intrahospital transfer increased the odds of acquiring a HAI by
Riley S, Ainslie KEC, Eales O, et al., 2020, High prevalence of SARS-CoV-2 swab positivity in England during September 2020: interim report of round 5 of REACT-1 study, Publisher: Cold Spring Harbor Laboratory Press
Background REACT-1 is a community survey of PCR confirmed swab-positivity for SARS-CoV-2 among random samples of the population in England. This interim report includes data from the fifth round of data collection currently underway for swabs sampled from the 18th to 26th September 2020.Methods Repeated cross-sectional surveys of random samples of the population aged 5 years and over in England with sample size ranging from 120,000 to 160,000 people in each round of data collection. Collection of self-administered nose and throat swab for PCR and questionnaire data. Prevalence of swab-positivity by round and by demographic variables including age, sex, region, ethnicity. Estimation of reproduction number (R) between and within rounds, and time trends using exponential growth or decay model. Assessment of geographical clustering based on boundary-free spatial model.Results Over the 9 days for which data are available, we find 363 positives from 84,610 samples giving a weighted prevalence to date of 0.55% (0.47%, 0.64%) in round 5. This implies that 411,000 (351,000, 478,000) people in England are virus-positive under the assumption that the swab assay is 75% sensitive. Using data from the most recent two rounds, we estimate a doubling time of 10.6 (9.4, 12.0) days covering the period 20th August to 26th September, corresponding to a reproduction number R of 1.47 (1.40, 1.53). Using data only from round 5 we estimate a reproduction number of 1.06 (0.74, 1.46) with probability of 63% that R is greater than 1. Between rounds 4 and 5 there was a marked increase in unweighted prevalence at all ages. In the most recent data, prevalence was highest in the 18 to 24 yrs age group at 0.96% (0.68%, 1.36%). At 65+ yrs prevalence increased 7-fold between rounds 4 and 5 from 0.04% (0.03%, 0.07%) to 0.29% (0.23%, 0.37%). Prevalence increased in all regions between rounds 4 and 5, giving the highest unweighted prevalence in round 5 in the North West at 0.86% (0.69%, 1.06%). In Lond
Drake TM, Docherty AB, Harrison EM, et al., 2020, Outcome of hospitalization for COVID-19 in patients with interstitial lung disease: an international multicenter study., American Journal of Respiratory and Critical Care Medicine, Vol: 202, Pages: 1656-1665, ISSN: 1073-449X
RATIONALE: The impact of COVID-19 on patients with Interstitial Lung Disease (ILD) has not been established. OBJECTIVES: To assess outcomes in patients with ILD hospitalized for COVID-19 versus those without ILD in a contemporaneous age, sex and comorbidity matched population. METHODS: An international multicenter audit of patients with a prior diagnosis of ILD admitted to hospital with COVID-19 between 1 March and 1 May 2020 was undertaken and compared with patients, without ILD obtained from the ISARIC 4C cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished IPF from non-IPF ILD and used lung function to determine the greatest risks of death. MEASUREMENTS AND MAIN RESULTS: Data from 349 patients with ILD across Europe were included, of whom 161 were admitted to hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity-score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching ILD patients with COVID-19 had higher mortality (HR 1.60, Confidence Intervals 1.17-2.18 p=0.003) compared with age, sex and co-morbidity matched controls without ILD. Patients with a Forced Vital Capacity (FVC) of <80% had an increased risk of death versus patients with FVC ≥80% (HR 1.72, 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR 2.27, 1.39-3.71). CONCLUSIONS: Patients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Daunt A, Perez-Guzman PN, Liew F, et al., 2020, Validity of the UK early access to medicines scheme criteria for Remdesivir use in patients with COVID-19 disease, Journal of Infection, Vol: 81, Pages: 666-668, ISSN: 0163-4453
Palayew A, Razavi H, Hutchinson S, et al., 2020, Do the most heavily burdened countries have the right policies to eliminate viral hepatitis B and C?, LANCET GASTROENTEROLOGY & HEPATOLOGY, Vol: 5, Pages: 948-953
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- Citations: 14
Hanley B, Naresh KN, Roufosse C, et al., 2020, Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study, The Lancet Microbe, Vol: 1, Pages: e245-e253, ISSN: 2666-5247
BackgroundSevere COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19.MethodsIn this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.FindingsThe median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of
Nguyen HA, Cooke GS, Day JN, et al., 2020, The direct-medical costs associated with interferon-based treatment for Hepatitis C in Vietnam, Wellcome Open Research, Vol: 4, Pages: 129-129
<ns4:p><ns4:bold>Background:</ns4:bold> Injectable interferon-based therapies have been used to treat hepatitis C virus (HCV) infection since 1991. International guidelines have now moved away from interferon-based therapy towards direct-acting antiviral (DAA) tablet regimens, because of their superior efficacy, excellent side-effect profiles, and ease of administration. Initially DAA drugs were prohibitively expensive for most healthcare systems. Access is now improving through the procurement of low-cost, generic DAAs acquired through voluntary licenses. However, HCV treatment costs vary widely, and many countries are struggling with DAA treatment scale-up. This is not helped by the limited cost data and economic evaluations from low- and middle-income countries to support HCV policy decisions. We conducted a detailed analysis of the costs of treating chronic HCV infection with interferon-based therapy in Vietnam. Understanding these costs is important for performing necessary economic evaluations of novel treatment strategies.</ns4:p><ns4:p> <ns4:bold>Methods:</ns4:bold> We conducted an analysis of the direct medical costs of treating HCV infection with interferon alpha (IFN) and pegylated-interferon alpha (Peg-IFN), in combination with ribavirin, from the health sector perspective at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, in 2017.</ns4:p><ns4:p> <ns4:bold>Results:</ns4:bold> The total cost of the IFN treatment regimen was estimated to range between US$1,120 and US$1,962. The total cost of the Peg-IFN treatment regimen was between US$2,156 and US$5,887. Drug expenses were the biggest contributor to the total treatment cost (54-89%) and were much higher for the Peg-IFN regimen.</ns4:p><ns4:p> <ns4:bold>Conclusions:</ns4:bold> We found that treating HCV with IFN or Peg-IFN resulted in significant direct medical costs. Of concern, we found that all patie
Riley S, Ainslie KEC, Eales O, et al., 2020, Resurgence of SARS-CoV-2 in England: detection by community antigen surveillance
<jats:title>Summary</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Based on cases and deaths, transmission of SARS-CoV-2 in England peaked in late March and early April 2020 and then declined until the end of June. Since the start of July, cases have increased, while deaths have continued to decrease.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We report results from 594,000 swabs tested for SARS-CoV-2 virus obtained from a representative sample of people in England over four rounds collected regardless of symptoms, starting in May 2020 and finishing at the beginning of September 2020. Swabs for the most recent two rounds were taken between 24th July and 11th August and for round 4 between 22nd August and 7th September. We estimate weighted overall prevalence, doubling times between and within rounds and associated reproduction numbers. We obtained unweighted prevalence estimates by sub-groups: age, sex, region, ethnicity, key worker status, household size, for which we also estimated odds of infection. We identified clusters of swab-positive participants who were closer, on average, to other swab-positive participants than would be expected.</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>Over all four rounds of the study, we found that 72% (67%, 76%) of swab-positive individuals were asymptomatic at the time of swab and in the week prior. The epidemic declined between rounds 1 and 2, and rounds 2 and 3. However, the epidemic was increasing between rounds 3 and 4, with a doubling time of 17 (13, 23) days corresponding to an R value of 1.3 (1.2, 1.4). When analysing round 3 alone, we found that the epidemic had started to grow again with 93% probability. Using only the most recent round 4 data, we estimated a doubling time of 7.7 (5.5, 12.7) days, corresponding to an R value of 1.7 (1.4, 2.0). Cy
Knight SR, Ho A, Pius R, et al., 2020, Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score, BMJ, Vol: 370, ISSN: 1759-2151
Objective To develop and validate a pragmatic risk score to predict mortality in patients admitted to hospital with coronavirus disease 2019 (covid-19).Design Prospective observational cohort study.Setting International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study (performed by the ISARIC Coronavirus Clinical Characterisation Consortium—ISARIC-4C) in 260 hospitals across England, Scotland, and Wales. Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited after model development between 21 May and 29 June 2020.Participants Adults (age >=18 years) admitted to hospital with covid-19 at least four weeks before final data extraction.Main outcome measure In-hospital mortality.Results 35 463 patients were included in the derivation dataset (mortality rate 32.2%) and 22 361 in the validation dataset (mortality rate 30.1%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea level, and C reactive protein (score range 0-21 points). The 4C Score showed high discrimination for mortality (derivation cohort: area under the receiver operating characteristic curve 0.79, 95% confidence interval 0.78 to 0.79; validation cohort: 0.77, 0.76 to 0.77) with excellent calibration (validation: calibration-in-the-large=0, slope=1.0). Patients with a score of at least 15 (n=4158, 19%) had a 62% mortality (positive predictive value 62%) compared with 1% mortality for those with a score of 3 or less (n=1650, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (area under the receiver operating characteristic curve range 0.61-0.76), with sco
Manalan K, Green N, Arnold A, et al., 2020, A UK cost comparison of amikacin therapy with bedaquiline, for drug resistant tuberculosis, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Lamontagne FCC, Agoritsas T, Macdonald H, et al., 2020, A living WHO guideline on drugs for covid-19, BMJ, Vol: 370
Clinical question What is the role of drug interventions in the treatment and prevention of covid-19?Recommendations The first version on this living guidance focuses on corticosteroids. It contains a strong recommendation for systemic corticosteroids in patients with severe and critical covid-19, and a weak or conditional recommendation against systemic corticosteroids in patients with non-severe covid-19. Corticosteroids are inexpensive and are on the World Health Organisation list of essential medicines.How this guideline was created This guideline reflects an innovative collaboration between the WHO and the MAGIC Evidence Ecosystem Foundation, driven by an urgent need for global collaboration to provide trustworthy and living covid-19 guidance. A standing international panel of content experts, patients, clinicians, and methodologists, free from relevant conflicts of interest, produce recommendations for clinical practice. The panel follows standards, methods, processes, and platforms for trustworthy guideline development using the GRADE approach. We apply an individual patient perspective while considering contextual factors (that is, resources, feasibility, acceptability, equity) for countries and healthcare systems.The evidence A living systematic review and network meta-analysis, supported by a prospective meta-analysis, with data from eight randomised trials (7184 participants) found that systemic corticosteroids probably reduce 28 day mortality in patients with critical covid-19 (moderate certainty evidence; 87 fewer deaths per 1000 patients (95% confidence interval 124 fewer to 41 fewer)), and also in those with severe disease (moderate certainty evidence; 67 fewer deaths per 1000 patients (100 fewer to 27 fewer)). In contrast, systemic corticosteroids may increase the risk of death in patients without severe covid-19 (low certainty evidence; absolute effect estimate 39 more per 1000 patients, (12 fewer to 107 more)). Systemic corticosteroids probably red
Flower B, Brown JC, Simmons B, et al., 2020, Clinical and laboratory evaluation of SARS-CoV-2 lateral flow assays for use in a national COVID-19 sero-prevalence survey, Thorax, Vol: 75, Pages: 1082-1088, ISSN: 0040-6376
BackgroundAccurate antibody tests are essential to monitor the SARS-CoV-2 pandemic. Lateral flow immunoassays (LFIAs) can deliver testing at scale. However, reported performance varies, and sensitivity analyses have generally been conducted on serum from hospitalised patients. For use in community testing, evaluation of finger-prick self-tests, in non-hospitalised individuals, is required.MethodsSensitivity analysis was conducted on 276 non-hospitalised participants. All had tested positive for SARS-CoV-2 by RT-PCR and were ≥21d from symptom-onset. In phase I we evaluated five LFIAs in clinic (with finger-prick) and laboratory (with blood and sera) in comparison to a) PCR-confirmed infection and b) presence of SARS-CoV-2 antibodies on two “in-house” ELISAs. Specificity analysis was performed on 500 pre-pandemic sera. In phase II, six additional LFIAs were assessed with serum.Findings95% (95%CI [92.2, 97.3]) of the infected cohort had detectable antibodies on at least one ELISA. LFIA sensitivity was variable, but significantly inferior to ELISA in 8/11 assessed. Of LFIAs assessed in both clinic and laboratory, finger-prick self-test sensitivity varied from 21%-92% vs PCR-confirmed cases and 22%-96% vs composite ELISA positives. Concordance between finger-prick and serum testing was at best moderate (kappa 0.56) and, at worst, slight (kappa 0.13). All LFIAs had high specificity (97.2% - 99.8%).InterpretationLFIA sensitivity and sample concordance is variable, highlighting the importance of evaluations in setting of intended use. This rigorous approach to LFIA evaluation identified a test with high specificity (98.6% (95%CI [97.1, 99.4])), moderate sensitivity (84.4% with fingerprick (95%CI [70.5, 93.5])), and moderate concordance, suitable for seroprevalence surveys.
Atchison C, Pristerà P, Cooper E, et al., 2020, Usability and acceptability of home-based self-testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibodies for population surveillance, Clinical Infectious Diseases, Vol: 2020, Pages: 1-10, ISSN: 1058-4838
BACKGROUND: This study assesses acceptability and usability of home-based self-testing for SARS-CoV-2 antibodies using lateral flow immunoassays (LFIA). METHODS: We carried out public involvement and pilot testing in 315 volunteers to improve usability. Feedback was obtained through online discussions, questionnaires, observations and interviews of people who tried the test at home. This informed the design of a nationally representative survey of adults in England using two LFIAs (LFIA1 and LFIA2) which were sent to 10,600 and 3,800 participants, respectively, who provided further feedback. RESULTS: Public involvement and pilot testing showed high levels of acceptability, but limitations with the usability of kits. Most people reported completing the test; however, they identified difficulties with practical aspects of the kit, particularly the lancet and pipette, a need for clearer instructions and more guidance on interpretation of results. In the national study, 99.3% (8,693/8,754) of LFIA1 and 98.4% (2,911/2,957) of LFIA2 respondents attempted the test and 97.5% and 97.8% of respondents completed it, respectively. Most found the instructions easy to understand, but some reported difficulties using the pipette (LFIA1: 17.7%) and applying the blood drop to the cassette (LFIA2: 31.3%). Most respondents obtained a valid result (LFIA1: 91.5%; LFIA2: 94.4%). Overall there was substantial concordance between participant and clinician interpreted results (kappa: LFIA1 0.72; LFIA2 0.89). CONCLUSION: Impactful public involvement is feasible in a rapid response setting. Home self-testing with LFIAs can be used with a high degree of acceptability and usability by adults, making them a good option for use in seroprevalence surveys.
Perez Guzman PN, Daunt A, Mukherjee S, et al., 2020, Clinical characteristics and predictors of outcomes of hospitalized patients with COVID-19 in a multi-ethnic London NHS Trust: a retrospective cohort study, Clinical Infectious Diseases, Vol: 2020, Pages: 1-11, ISSN: 1058-4838
Background: Emerging evidence suggests ethnic minorities are disproportionatelyaffected by COVID-19. Detailed clinical analyses of multi-cultural hospitalized patientcohorts remain largely undescribed.Methods: We performed regression, survival andcumulative competing risk analyses to evaluate factors associated with mortality inpatients admitted for COVID-19 in three large London hospitals between February 25and April 5, censored as of May 1, 2020.Results: Of 614 patients (median age 69years, (IQR 25) and 62% male), 381 (62%) had been discharged alive, 178 (29%)died and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (aOR 4.25,95%CI 2.36-7.64), leukocytosis (aOR 2.35, 95%CI 1.35-4.11), thrombocytopenia (aOR1.01, 95%CI 1.00-1.01, increase per 10x9decrease), severe renal impairment (aOR5.14, 95%CI 2.65-9.97), and low albumin (aOR 1.06, 95%CI 1.02-1.09, increase per gdecrease) were associated with death. Forty percent (244) were from black, Asian andother minority ethnic (BAME) groups, 38% (235) white and for 22% (135) ethnicity wasunknown. BAME patients were younger and had fewer comorbidities. Whilst theunadjusted odds of death did not differ by ethnicity, when adjusting for age, sex andcomorbidities, black patients were at higher odds of death compared to whites (aOR1.69, 95%CI 1.00-2.86). This association was stronger when further adjusting foradmission severity (aOR 1.85 95% CI 1.06-3.24). Conclusions: BAME patients were over-represented in our cohort and, whenaccounting for demographic and clinical profile of admission, black patients were atincreased odds of death. Further research is needed into biologic drivers of differencesin COVID-19 outcomes by ethnicity.
Riley S, Ainslie KEC, Eales O, et al., 2020, Transient dynamics of SARS-CoV-2 as England exited national lockdown
<jats:title>Abstract</jats:title><jats:p>Control of the COVID-19 pandemic requires a detailed understanding of prevalence of SARS-CoV-2 virus in the population. Case-based surveillance is necessarily biased towards symptomatic individuals and sensitive to varying patterns of reporting in space and time. The real-time assessment of community transmission antigen study (REACT-1) is designed to overcome these limitations by obtaining prevalence data based on a nose and throat swab RT-PCR test among a representative community-based sample in England, including asymptomatic individuals. Here, we describe results comparing rounds 1 and 2 carried out during May and mid June / early July 2020 respectively across 315 lower tier local authority areas. In round 1 we found 159 positive samples from 120,620 tested swabs while round 2 there were 123 positive samples from 159,199 tested swabs, indicating a downwards trend in prevalence from 0.13% (95% CI, 0.11%, 0.15%) to 0.077% (0.065%, 0.092%), a halving time of 38 (28, 58) days, and an R of 0.89 (0.86, 0.93). The proportion of swab-positive participants who were asymptomatic at the time of sampling increased from 69% (61%, 76%) in round 1 to 81% (73%, 87%) in round 2. Although health care and care home workers were infected far more frequently than other workers in round 1, the odds were markedly reduced in round 2. Age patterns of infection changed between rounds, with a reduction by a factor of five in prevalence in 18 to 24 year olds. Our data were suggestive of increased risk of infection in Black and Asian (mainly South Asian) ethnicities. Using regional and detailed case location data, we detected increased infection intensity in and near London. Under multiple sensitivity analyses, our results were robust to the possibility of false positives. At the end of the initial lockdown in England, we found continued decline in prevalence and a shift in the pattern of infection by age and occupation. Community-b
Palayew A, Stumo SR, Cooke G, et al., 2020, From stagnation to elimination: tracking hepatitis C elimination policy implementation in Europe in partnership with patient organizations, Publisher: ELSEVIER, Pages: S793-S794, ISSN: 0168-8278
Garvey L, Cooke G, Smith C, et al., 2020, Decline in HCV incidence in HIV positive MSM - progress to HCV micro-elimination in the UK?, Publisher: ELSEVIER, Pages: S32-S33, ISSN: 0168-8278
Smith DA, Wang T, Freeman O, et al., 2020, National Institute for Health Research Health Informatics Collaborative: development of a pipeline to collate electronic clinical data for viral hepatitis research, BMJ HEALTH & CARE INFORMATICS, Vol: 27
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Palayew A, Cooke G, Hutchinson S, et al., 2020, Do countries have the right policies to eliminate viral hepatitis B and C: a secondary analysis of the Lancet GastroHep viral hepatitis commission, Publisher: ELSEVIER, Pages: S811-S811, ISSN: 0168-8278
Palayew A, Stumo SR, Cooke GS, et al., 2020, The Hep-CORE policy score: A European hepatitis C national policy implementation ranking based on patient organization data, PLOS ONE, Vol: 15, ISSN: 1932-6203
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- Citations: 10
Yates T, Cooke G, MacPherson P, 2020, Rational use of SARS-CoV-2 polymerase chain reaction tests within institutions caring for the vulnerable [version1; [peer revoew: 2 approved], F1000Research, Vol: 9, Pages: 1-13, ISSN: 2046-1402
Institutions such as hospitals and nursing or long-stay residential homes accommodate individuals at considerable risk of mortality should they acquire SARS-CoV-2 infection. In these settings, polymerase chain reaction tests play a central role in infection prevention and control. Here, we argue that both false negative and false positive tests are possible and that careful consideration of the prior probability of infection and of test characteristics are needed to prevent harm. We outline evidence suggesting that regular systematic testing of asymptomatic and pre-symptomatic individuals could play an important role in reducing transmission of SARS-CoV-2 within institutions. We discuss how such a programme might be organised, arguing that frequent testing and rapid reporting of results are particularly important. We highlight studies demonstrating that polymerase chain reaction testing of pooled samples can be undertaken with acceptable loss of sensitivity, and advocate such an approach where test capacity is limited. We provide an approach to calculating the most efficient pool size. Given the current limitations of tests for SARS-CoV-2 infection, physical distancing and meticulous infection prevention and control will remain essential in institutions caring for vulnerable people.
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