Publications
414 results found
Martinello M, Orkin C, Cooke G, et al., 2020, Short duration pan‐genotypic therapy with glecaprevir‐pibrentasvir for six weeks among people with recent HCV infection, Hepatology, Vol: 72, Pages: 7-18, ISSN: 0270-9139
Among treatment‐naïve individuals with chronic HCV infection and without cirrhosis, glecaprevir‐pibrentasvir for eight weeks is recommended. The aim of this analysis was to evaluate the efficacy of glecaprevir‐pibrentasvir for six weeks in people with acute and recent HCV infection. In this open‐label single‐arm multicentre international pilot study, adults with recent HCV (duration of infection <12 months) received glecaprevir‐pibrentasvir 300mg‐120mg daily for six weeks. Primary infection was defined by first positive anti‐HCV antibody and/or HCV RNA within six months of enrolment and either acute clinical hepatitis within the past 12 months (symptomatic seroconversion illness or ALT>10xULN) or anti‐HCV antibody seroconversion within 18 months. Reinfection was defined as new positive HCV RNA within six months of enrolment and evidence of prior spontaneous or treatment‐induced clearance. The primary endpoint was sustained virologic response at 12 weeks post‐treatment (SVR12). Thirty men (median age 43 years, 90% men‐who‐have‐sex‐with‐men) received treatment, of whom 77% (n=23) were HIV‐positive, 47% (n=14) had ever injected drugs, and 13% (n=4) had HCV reinfection. The majority had HCV genotype 1 (83%, n=25), followed by genotype 4 (10%, n=3) and genotype 3 (7%, n=2). At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log10 IU/mL (range 0.9, 7.7). SVR12 in the intention‐to‐treat and per‐protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively. There was one case of relapse and two cases of non‐virological failure (death, n=1; loss to follow up, n=1). No treatment‐related serious adverse events were seen.
Vollmer M, Radhakrishnan S, Kont M, et al., 2020, Report 29: The impact of the COVID-19 epidemic on all-cause attendances to emergency departments in two large London hospitals: an observational study
The health care system in England has been highly affected by the surge in demand due to patients afflicted by COVID-19. Yet the impact of the pandemic on the care seeking behaviour of patients and thus on Emergency department (ED) services is unknown, especially for non-COVID-19 related emergencies. In this report, we aimed to assess how the reorganisation of hospital care and admission policies to respond to the COVID-19 epidemic affected ED attendances and emergency hospital admissions. We performed time-series analyses of present year vs historic (2015-2019) trends of ED attendances between March 12 and May 31 at two large central London hospitals part of Imperial College Healthcare NHS Trust (ICHNT) and compared these to regional and national trends. Historic attendances data to ICHNT and publicly available NHS situation reports were used to calibrate time series auto-regressive integrated moving average (ARIMA) forecasting models. We thus predicted the (conterfactual) expected number of ED attendances between March 12 (when the first public health measure leading to lock-down started in England) to May 31, 2020 (when the analysis was censored) at ICHNT, at all acute London Trusts and nationally. The forecasted trends were compared to observed data for the same periods of time. Lastly, we analysed the trends at ICHNT disaggregating by mode of arrival, distance from postcode of patient residence to hospital and primary diagnosis amongst those that were subsequently admitted to hospital and compared these data to an average for the same period of time in the years 2015 to 2019.During the study period (January 1 to May 31, 2020) there was an overall decrease in ED attendances of 35% at ICHNT, of 50% across all London NHS Trusts and 53% nationally. For ICHNT, the decrease in attendances was mainly amongst those aged younger than 65 and those arriving by their own means (e.g. personal or public transport). Increasing distance (km) from postcode of residence to hospi
Bradshaw D, Vasylyeva T, Davis C, et al., 2020, Transmission of hepatitis C virus in HIV-positive and PrEP-using MSM in England, JOURNAL OF VIRAL HEPATITIS, Vol: 27, Pages: 721-730, ISSN: 1352-0504
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- Citations: 13
Rawson TM, Moore LSP, Zhu N, et al., 2020, Response to Dudoignon et al., Clin Infect Dis
McCabe L, White IR, Nguyen VVC, et al., 2020, The design and statistical aspects of VIETNARMS: a strategic post-licensing trial of multiple oral direct-acting antiviral hepatitis C treatment strategies in Vietnam, Trials, Vol: 21, Pages: 1-12, ISSN: 1745-6215
BackgroundEliminating hepatitis C is hampered by the costs of direct-acting antiviral treatment and the need to treat hard-to-reach populations. Access could be widened by shortening or simplifying treatment, but limited research means it is unclear which approaches could achieve sufficiently high cure rates to be acceptable. We present the statistical aspects of a multi-arm trial designed to test multiple strategies simultaneously and a monitoring mechanism to detect and stop individual randomly assigned groups with unacceptably low cure rates quickly.MethodsThe VIETNARMS trial will factorially randomly assign patients to two drug regimens, three treatment-shortening strategies or control, and adjunctive ribavirin or no adjunctive ribavirin with shortening strategies (14 randomly assigned groups). We will use Bayesian monitoring at interim analyses to detect and stop recruitment into unsuccessful strategies, defined by more than 0.95 posterior probability that the true cure rate is less than 90% for the individual randomly assigned group (non-comparative). Final comparisons will be non-inferiority for regimens (margin 5%) and strategies (margin 10%) and superiority for adjunctive ribavirin. Here, we tested the operating characteristics of the stopping guideline for individual randomly assigned groups, planned interim analysis timings and explored power at the final analysis.ResultsA beta (4.5, 0.5) prior for the true cure rate produces less than 0.05 probability of incorrectly stopping an individual randomly assigned group with a true cure rate of more than 90%. Groups with very low cure rates (<60%) are very likely (>0.9 probability) to stop after about 25% of patients are recruited. Groups with moderately low cure rates (80%) are likely to stop (0.7 probability) before overall recruitment finishes. Interim analyses 7, 10, 13 and 18 months after recruitment commences provide good probabilities of stopping inferior individua
Huttner B, Cappello B, Cooke G, et al., 2020, 2019 Community-acquired Pneumonia Treatment Guidelines: There Is a Need for a Change toward More Parsimonious Antibiotic Use, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 201, Pages: 1315-1316, ISSN: 1073-449X
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- Citations: 7
Rawson TM, Moore L, Zhu N, et al., 2020, Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing, Clinical Infectious Diseases, Vol: 71, Pages: 2459-2468, ISSN: 1058-4838
BackgroundTo explore and describe the current literature surrounding bacterial/fungal co-infection in patients with coronavirus infection.MethodsMEDLINE, EMBASE, and Web of Science were searched using broad based search criteria relating to coronavirus and bacterial co-infection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-COV-2, and other coronavirus) and bacterial/fungal co-infection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal co-infections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-COV-2 even in the absence of co-infection was performed.Results1007 abstracts were identified. Eighteen full texts reported bacterial/fungal co-infection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140;61%). 9/18 (50%) studies reported on COVID-19, 5/18 (28%) SARS-1, 1/18 (6%) MERS, and 3/18 (17%) other coronavirus.For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal co-infection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described.For non-COVID-19 cases bacterial/fungal co-infection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported.ConclusionsDespite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal co-infection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic are urgently requi
Perez Guzman PN, Daunt A, Mukherjee S, et al., 2020, Report 17: Clinical characteristics and predictors of outcomes of hospitalised patients with COVID-19 in a London NHS Trust: a retrospective cohort study
Clinical characteristics and determinants of outcomes for hospitalised COVID-19 patients in the UK remain largely undescribed and emerging evidence suggests ethnic minorities might be disproportionately affected. We describe the characteristics and outcomes of patients hospitalised for COVID-19 in three large London hospitals with a multi-ethnic catchment population.We performed a retrospective cohort study on all patients hospitalised with laboratory-confirmed SARS-CoV-2 infection at Imperial College Healthcare NHS Trust between February 25 and April 5, 2020. Outcomes were recorded as of April 19, 2020. Logistic regression models, survival analyses and cumulative competing risk analyses were performed to evaluate factors associated with COVID-19 hospital mortality.Of 520 patients in this cohort (median age 67 years, (IQR 26) and 62% male), 302 (68%) had been discharged alive, 144 (32%) died and 74 (14%) were still hospitalised at the time of censoring. Increasing age (adjusted odds ratio [aOR] 2·16, 95%CI 1·50-3·12), severe hypoxia (aOR 3·75, 95%CI 1·80-7·80), low platelets (aOR 0·65, 95%CI 0.49·0·85), reduced estimated glomerular filtration rate (aOR 4·11, 95%CI 1·58-10·69), bilirubin >21mmol/L (aOR 2·32, 95%CI 1·05-5·14) and low albumin (aOR 0·77, 9%%CI 0·59-1·01) were associated with increased risk of in-hospital mortality. Individual comorbidities were not independently associated with risk of death. Regarding ethnicity, 209 (40%) were from a black and Asian minority, for 115 (22%) ethnicity was unknown and 196 (38%) patients were white. Compared to the latter, black patients were significantly younger and had less comorbidities. Whilst the crude OR of death of black compared to white patients was not significant (1·14, 95%CI 0·69-1·88, p=0.62), adjusting for age and comorbidity showed a trend towards significance
Joshi M, Archer S, Morbi A, et al., 2020, Short-Term Wearable Sensors for In-Hospital Medical and Surgical Patients: Mixed Methods Analysis of Patient Perspectives (Preprint)
<sec> <title>BACKGROUND</title> <p>Continuous vital sign monitoring using wearable sensors may enable early detection of patient deterioration and sepsis.</p> </sec> <sec> <title>OBJECTIVE</title> <p>This study aimed to explore patient experiences with wearable sensor technology and carry out continuous monitoring through questionnaire and interview studies in an acute hospital setting.</p> </sec> <sec> <title>METHODS</title> <p>Patients were recruited for a wearable sensor study and were asked to complete a 9-item questionnaire. Patients responses were evaluated using a Likert scale and with continuous variables. A subgroup of surgical patients wearing a Sensium Vital Sign Sensor was invited to participate in semistructured interviews. The Sensium wearable sensor measures the vital signs: heart rate, respiratory rate, and temperature. All interview data were subjected to thematic analysis.</p> </sec> <sec> <title>RESULTS</title> <p>Out of a total of 500 patients, 453 (90.6%) completed the questionnaire. Furthermore, 427 (85.4%) patients agreed that the wearable sensor was comfortable, 429 (85.8%) patients agreed to wear the patch again when in hospital, and 398 (79.6%) patients agreed to wear the patch at home. Overall, 12 surgical patients consented to the interviews. Five main themes of interest to patients emerged from the interviews: (1) centralized monitoring, (2) enhanced feelings of patient safety, (3) impact on nursing staff, (4) comfort and usability, and (5) future use and views on technology.</p> </se
Ross SA, Pintilie H, Hatcher J, et al., 2020, <i>Strongyloides stercoralis</i> infection in HIV-positive men who have sex with men, INTERNATIONAL JOURNAL OF STD & AIDS, Vol: 31, Pages: 398-401, ISSN: 0956-4624
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Honeyford K, Cooke GS, Kinderlerer A, et al., 2020, Evaluating a digital sepsis alert in a London multisite hospital network: a natural experiment using electronic health record data (vol 27, pg 274, 2020), JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION, Vol: 27, Pages: 501-501, ISSN: 1067-5027
Fawsitt CG, Vickerman P, Cooke GS, et al., 2020, Cost-effectiveness analysis of baseline testing for resistance-associated polymorphisms to optimize treatment outcome in genotype 1 noncirrhotic treatment-naïve patients with chronic Hepatitis C virus, Value in Health, Vol: 23, Pages: 180-190, ISSN: 1098-3015
ObjectivesDirect-acting antivirals containing nonstructural protein 5A (NS5A) inhibitors administered over 8 to 12 weeks are effective in ∼95% of patients with hepatitis C virus. Nevertheless, patients resistant to NS5A inhibitors have lower cure rates over 8 weeks (<85%); for these patients, 12 weeks of treatment produces cure rates greater than 95%. We evaluated the lifetime cost-effectiveness of testing for NS5A resistance at baseline and optimizing treatment duration accordingly in genotype 1 noncirrhotic treatment-naïve patients from the perspective of the UK National Health Service.MethodsA decision-analytic model compared (1) standard 12-week treatment (no testing), (2) shortened 8-week treatment (no testing), and (3) baseline testing with 12-/8-week treatment for those with/without NS5A polymorphisms. Patients who failed first-line therapy were retreated for 12 weeks. Model inputs were derived from published studies. Costs, quality-adjusted life-years, and the probability of cost-effectiveness were calculated.ResultsBaseline testing had an incremental net monetary benefit (INMB) of £11 838 versus standard 12 weeks of therapy (no testing) and low probability (31%) of being the most cost-effective, assuming £30 000 willingness to pay. Shortened 8 weeks of treatment (no testing) had an INMB of £12 294 and the highest probability (69%) of being most cost-effective. Scenario analyses showed baseline testing generally had the highest INMB and probability of being most cost-effective if first- and second-line drug prices were low (<£20k).ConclusionsOptimizing treatment duration based on NS5A polymorphisms for genotype 1 noncirrhotic treatment-naive patients in the United Kingdom is not cost-effective if the drug costs are high; the strategy is generally most cost-effective when drug prices are low (<£20k).
Elliott T, Cooke GS, Garvey L, 2020, Interventions to reduce acute hepatitis C virus in HIV-positive MSM., Curr Opin Infect Dis, Vol: 33, Pages: 1-9
PURPOSE OF REVIEW: The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets. RECENT FINDINGS: With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM. Recent evidence demonstrates that treatment in early infection is well tolerated, cost effective and may reduce the risk of onward transmission. Modelling studies suggest that to reduce incidence, a combination approach including behavioural interventions and access to early treatment, targeting both HIV+ and negative high-risk groups, will be required. HCV vaccine trials have not yet demonstrated efficacy in human studies, however phase one and two studies are ongoing. SUMMARY: Some progress towards the WHO HCV elimination targets has been reported. Achieving sustained HCV elimination is likely to require a combination approach including early access to DAAs in acute infection and reinfection, validated and reproducible behavioural interventions and an efficacious HCV vaccine.
Honeyford C, Cooke G, Kinderlerer A, et al., 2020, Evaluating a digital sepsis alert in a London multi-site hospital network: a natural experiment using electronic health record data, Journal of the American Medical Informatics Association, Vol: 27, Pages: 274-283, ISSN: 1067-5027
Objective: To determine the impact of a digital sepsis alert on patient outcomes in a UK multi-site hospital network. Methods:A natural experiment utilising the phased introduction (without randomisation) of a digital sepsis alert into a multi-site hospital network. Sepsis alerts were either visible to clinicans (patients in the ‘intervention’ group) or running silently and not visible (the control group). Inverse probability of treatment weighted multivariable logistic regression was used to estimate the effect of the intervention on individual patient outcomes.Outcomes:In-hospital 30-day mortality (all inpatients), prolonged hospital stay (≥7 days) and timely antibiotics (≤60minutes of the alert) for patients who alerted in the Emergency Department. Results: The introduction of the alert was associated with lower odds of death (OR:0.76; 95%CI:(0.70, 0.84) n=21183); lower odds of prolonged hospital stay ≥7 days (OR:0.93; 95%CI:(0.88, 0.99) n=9988); and in patients who required antibiotics, an increased odds of receiving timely antibiotics (OR:1.71; 95%CI:(1.57, 1.87) n=4622).Discussion: Current evidence that digital sepsis alerts are effective is mixed. In this large UK study a digital sepsis alert has been shown to be associated with improved outcomes, including timely antibiotics. It is not known whether the presence of alerting is responsible for improved outcomes, or whether the alert acted as a useful driver for quality improvement initiatives.Conclusions: These findings strongly suggest that the the introduction of a network-wide digital sepsis alert is associated with improvements in patient outcomes, demonstrating that digital based interventions can be successfully introduced and readily evaluated.
Riley S, Atchison C, Ashby D, et al., 2020, REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol [version 1; peer review: 1 approved, 1 approved with reservations], Wellcome Open Research, Vol: 5, Pages: 1-17
Background: England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. Protocol: The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). Ethics and dissemination: The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. Conclusions: This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered testing for SARS-CoV-2 antibody in a home-based setting, not done before at
Ward H, Cooke G, Atchison C, et al., 2020, Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365,000 adults
Background The prevalence and persistence of antibodies following a peak SARS-CoV-2 infection provides insights into its spread in the community, the likelihood of reinfection and potential for some level of population immunity.Methods Prevalence of antibody positivity in England, UK (REACT2) with three cross-sectional surveys between late June and September 2020. 365104 adults used a self-administered lateral flow immunoassay (LFIA) test for IgG. A laboratory comparison of LFIA results to neutralization activity in panel of sera was performed.Results There were 17,576 positive tests over the three rounds. Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% [5.8, 6.1], to 4.8% [4.7, 5.0] and 4.4% [4.3, 4.5], a fall of 26.5% [-29.0, −23.8] over the three months of the study. There was a decline between rounds 1 and 3 in all age groups, with the highest prevalence of a positive result and smallest overall decline in positivity in the youngest age group (18-24 years: −14.9% [-21.6, −8.1]), and lowest prevalence and largest decline in the oldest group (75+ years: −39.0% [-50.8, −27.2]); there was no change in antibody positivity between rounds 1 and 3 in healthcare workers (+3.45% [-5.7, +12.7]).The decline from rounds 1 to 3 was largest in those who did not report a history of COVID-19, (−64.0% [-75.6, −52.3]), compared to −22.3% ([-27.0, −17.7]) in those with SARS-CoV-2 infection confirmed on PCR.Discussion These findings provide evidence of variable waning in antibody positivity over time such that, at the start of the second wave of infection in England, only 4.4% of adults had detectable IgG antibodies using an LFIA. Antibody positivity was greater in those who reported a positive PCR and lower in older people and those with asymptomatic infection. These data suggest the possibility of decreasing population immunity and increasing risk of rei
Ward JW, Wiktor SZ, Cooke GS, 2020, Launch of the Coalition for Global Hepatitis Elimination: a recommendation of the Lancet Gastroenterology & Hepatology Commission, Lancet Gastroenterology and Hepatology, Vol: 5, Pages: 8-10, ISSN: 2468-1253
Riley S, Atchison C, Ashby D, et al., 2020, REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol., Wellcome open research, Vol: 5, ISSN: 2398-502X
<b>Background:</b> England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. <b>Protocol:</b> The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). <b>Ethics and dissemination:</b> The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. <b>Conclusions:</b> This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered
Manalan K, Green N, Arnold A, et al., 2020, A cost comparison of amikacin therapy with bedaquiline, for drug-resistant tuberculosis in the UK, JOURNAL OF INFECTION, Vol: 80, Pages: 38-41, ISSN: 0163-4453
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Riley S, Atchison C, Ashby D, et al., 2020, REal-time Assessment of Community Transmission (REACT) of SARS-CoV-2 virus: Study protocol., Wellcome Open Res, Vol: 5, ISSN: 2398-502X
Background: England, UK has one of the highest rates of confirmed COVID-19 mortality globally. Until recently, testing for the SARS-CoV-2 virus focused mainly on healthcare and care home settings. As such, there is far less understanding of community transmission. Protocol: The REal-time Assessment of Community Transmission (REACT) programme is a major programme of home testing for COVID-19 to track progress of the infection in the community. REACT-1 involves cross-sectional surveys of viral detection (virological swab for RT-PCR) tests in repeated samples of 100,000 to 150,000 randomly selected individuals across England. This examines how widely the virus has spread and how many people are currently infected. The age range is 5 years and above. Individuals are sampled from the England NHS patient list. REACT-2 is a series of five sub-studies towards establishing the seroprevalence of antibodies to SARS-CoV-2 in England as an indicator of historical infection. The main study (study 5) uses the same design and sampling approach as REACT-1 using a self-administered lateral flow immunoassay (LFIA) test for IgG antibodies in repeated samples of 100,000 to 200,000 adults aged 18 years and above. To inform study 5, studies 1-4 evaluate performance characteristics of SARS-CoV-2 LFIAs (study 1) and different aspects of feasibility, usability and application of LFIAs for home-based testing in different populations (studies 2-4). Ethics and dissemination: The study has ethical approval. Results are reported using STROBE guidelines and disseminated through reports to public health bodies, presentations at scientific meetings and open access publications. Conclusions: This study provides robust estimates of the prevalence of both virus (RT-PCR, REACT-1) and seroprevalence (antibody, REACT-2) in the general population in England. We also explore acceptability and usability of LFIAs for self-administered testing for SARS-CoV-2 antibody in a home-based setting, not done before at
Joshi M, Ashrafian H, Arora S, et al., 2019, Digital alerting and outcomes in patients with sepsis: Systematic review and meta-analysis, JMIR mHealth and uHealth, Vol: 21, ISSN: 2291-5222
Background The diagnosis and management of sepsis remains a global healthcare challenge. Digital technologies have the potential to improve sepsis care. Objective This paper systematically reviews the evidence on the impact of electronic alerting systems on sepsis related outcomes. Study Selection Embase, Medline, HMIC, Psych Info and Cochrane were searched from April 1964 to 12thFebruary 2019 with no language restriction. All full text reports of studies identified as potentially eligible after title and abstract review were obtained for further review. The search was limited to adult inpatients. Relevant articles were hand-searched for remaining studies. Only studies with clear pre-and post-alerting phases were included. Primary outcomes were hospital length of stay [LOS] and intensive care LOS, secondary outcomes were time to antibiotics and mortality. Studies based solely on intensive care, case reports, narrative reviews, editorials and commentaries were excluded. All other trial designs were included. A qualitative assessment and meta-analysis was performed. Results This review identified 72 full text articles. From these, 16 studies met the inclusion criteria and were included in the final analysis. Of these, 8 studies reviewed hospital length of stay, 12 mortality outcomes, 5 studies explored time to antibiotics, 5 studies investigated ICU length of stay. Data Synthesis Both quantitative and qualitative assessments of the studies was performed. There was evidence of a significant benefit of electronic alerting on hospital length of stay, reduced by 1.31 days[p=0.014], and ICU length of stay, reduced by 0.766 days[p=0.007]. There was no significant difference association between electronic alerts and mortality [mean decrease 11.4%,p=0.769] or time to antibiotics [mean decrease 126 minutes, p=0.134]. Conclusion This review highlights that electronic alerts can significantly reduce hospital and ICU stay in patients with sepsis. Further studies including more
Safreed-Harmon K, Blach S, Aleman S, et al., 2019, The consensus hepatitis C cascade of care: standardized reporting to monitor progress toward elimination, Clinical Infectious Diseases, Vol: 69, Pages: 2218-2227, ISSN: 1058-4838
Cascade-of-care (CoC) monitoring is an important component of the response to the global hepatitis C virus (HCV) epidemic. CoC metrics can be used to communicate in simple terms the extent to which national and subnational governments are advancing on key targets, and CoC findings can inform strategic decision-making regarding how to maximize the progression of HCV-infected individuals to diagnosis, treatment and cure. The value of reporting would be enhanced if reporting entities utilized a standardized approach for generating their CoCs. We have described the Consensus HCV CoC that we developed to address this need and have presented findings from Denmark, Norway and Sweden, where it was piloted. We encourage the uptake of the Consensus HCV CoC as a global instrument for facilitating clear and consistent reporting via the World Health Organization (WHO) viral hepatitis monitoring platform and ensuring the accurate monitoring of progress toward WHO’s 2030 hepatitis C elimination targets.</jats:p>
Sharland M, Gandra S, Huttner B, et al., 2019, Encouraging AWaRe-ness and discouraging inappropriate antibiotic use-the new 2019 Essential Medicines List becomes a global antibiotic stewardship tool, Lancet Infectious Diseases, Vol: 19, Pages: 1278-1280, ISSN: 1473-3099
Bradshaw D, Mbisa JL, Geretti AM, et al., 2019, Public health England HCV resistance group: overview and consensus recommendations for resistance testing in the management of chronic hepatitis C virus infection, Journal of Infection, Vol: 79, Pages: 503-512, ISSN: 0163-4453
The treatment of hepatitis C virus (HCV) infection has been revolutionised by the advent of oral, well-tolerated, direct acting antiviral therapies (DAA), with high cure rates. However, in some scenarios, HCV resistance to antiviral therapies may have an impact on treatment success. Public Health England's HCV Resistance Group was established to support clinicians treating people with HCV, where the issue of resistance may be a factor in clinical decision-making, and this review includes the Group's current recommendations on the use of HCV resistance testing. The authors describe the principles behind and approach to HCV resistance testing and consider evidence from in vitro studies, clinical trials and real world cohorts on the impact of HCV resistance on treatment outcomes for particular DAA regimens. Five scenarios are identified in the UK and similar settings, where, in the Group's opinion, resistance testing should be performed.
Honeyford K, Cooke GS, Kinderlerer A, et al., 2019, Evaluating a digital sepsis alert in a multi-site hospital: a natural experiment, Publisher: OXFORD UNIV PRESS, ISSN: 1101-1262
Ahmad A, Atzori S, Taylor-Robinson S, et al., 2019, Spleen stiffness measurements using point shear wave elastography detects noncirrhotic portal hypertension in human immunodeficiency virus, Medicine, Vol: 98, ISSN: 0025-7974
Objectives:To assess the utility of spleen stiffness as a diagnostic tool inindividuals withHIV andnon-cirrhotic portal hypertension(NCPH).Design:The Philips EPIQ7TM, a newpoint shearwave elastography (pSWE) technique, was used to assess liver and spleen stiffnessin3 patient groups. Group1:HIV and NCPH(n=11); Group 2: HIV withpast didanosine(ddI) exposure without known liver disease or NCPH(n=5), Group 3: HIV without known liver disease or ddI exposure(n=9). Methods:Groups were matched for age, HIV chronicity and antiretroviral treatment (including cumulative ddI exposure in Groups 1 and 2). Differences in liver and spleen stiffness (in kPa) between groups were analysed using the Mann-Whiney U test.Results:Liver and spleen stiffness were both significantly higher in NCPH vs ddI-exposed (p=0.019 and p=0.006) and ddI-unexposed controls (p=0.038 and p<0.001). Spleen stiffness was more effective than liver stiffness at predicting NCPH, AUROC 0.812 vs 0.948. Combining the two variables improved the diagnostic performance, AUROC 0.961. The optimal cut-off for predicting NCPH using splenic stiffness was 25.4kPa, with sensitivity 91%, specificity 93%, PPV 91%, NPV 93%, positive likelihood ratio 12.73, negative likelihood ratio 0.10. Spleen and liver stiffness scores were strongly correlated (p=0.0004 95%CI 18,59). Conclusions:Elevated spleen stiffness is observed in HIV with NCPH and can be quantified easily using pSWE with high diagnostic accuracy. Novel strategies such as pSWE for longitudinal monitoring of patients with HIV and NCPH should be considered.
Cole M, Saeed Z, Shaw A, et al., 2019, Responses to quadrivalent influenza vaccine reveal distinct circulating CD4+CXCR5+ T cell subsets in men living with HIV, Scientific Reports, Vol: 9, ISSN: 2045-2322
T cell help for B cells may be perturbed in people living with HIV (PLWH), even when HIV is suppressed, as evidenced by reports of suboptimal responses to influenza vaccination. We investigated cTFH responses to the 2017–18 inactivated quadrivalent influenza vaccine (QIV) in men living with antiretroviral therapy (ART)-suppressed HIV infection who were treated in the early or chronic phase of infection, and control subjects. Here we show that seroprotective antibody responses in serum and oral fluid correlated with cTFH activation and were equivalent in all three groups, irrespective of when ART was started. These responses were attenuated in those reporting immunisation with influenza vaccine in the preceding three years, independent of HIV infection. Measurement of influenza-specific IgG in oral fluid was closely correlated with haemagglutination inhibition titre. T-SNE and two-dimensional analysis revealed a subset of CD4+CXCR3+CXCR5+ cTFH activated at one week after vaccination. This was distinguishable from cTFH not activated by vaccination, and a rare, effector memory CD4+CXCR5hiCD32hi T cell subset. The data support the use of QIV for immunisation of PLWH, reveal distinct circulating CD4+CXCR5+ T cell subsets and demonstrate oral fluid sampling for influenza-specific IgG is an alternative to phlebotomy.
Szubert A, Bailey SL, Cooke GS, et al., 2019, Predictors of recurrence, early treatment failure and death from Staphylococcus aureus bacteraemia: observational analyses within the ARREST trial, Journal of Infection, Vol: 79, Pages: 332-340, ISSN: 0163-4453
ObjectivesAdjunctive rifampicin did not reduce failure/recurrence/death as a composite endpoint in the ARREST trial of Staphylococcus aureus bacteraemia, but did reduce recurrences. We investigated clinically-defined 14-day treatment failure, and recurrence and S. aureus-attributed/unattributed mortality by 12-weeks to further define their predictors.MethodsA post-hoc exploratory analysis using competing risks models was conducted to identify sub-groups which might benefit from rifampicin. A points-based recurrence risk score was developed and used to compare rifampicin's benefits.ResultsRecurrence was strongly associated with liver and renal failure, diabetes and immune-suppressive drugs (p < 0.005); in contrast, failure and S. aureus-attributed mortality were associated with older age and higher neutrophil counts. Higher SOFA scores predicted mortality; higher Charlson scores and deep-seated initial infection focus predicted failure. Unexpectedly, recurrence risk increased with increasing BMI in placebo (p = 0.04) but not rifampicin (p = 0.60) participants (pheterogeneity = 0.06). A persistent focus was judged the primary reason for recurrence in 23(74%). A 5-factor risk score based on BMI, Immunosuppression, Renal disease, Diabetes, Liver disease (BIRDL) strongly predicted recurrence (p < 0.001).ConclusionsRifampicin reduces recurrences overall; those with greatest absolute risk reductions were identified using a simple risk score. Source control and adequate duration of antibiotic therapy remain essential to prevent recurrence and improve outcomes.
McCabe L, White IR, Cooke GS, et al., 2019, Bayesian trial monitoring and power estimation in a complex Hepatitis C treatment trial (VIETNARMS), Publisher: BMC
Cooke G, Pett S, Jones C, et al., 2019, STRATEGIC TREATMENT OPTIMIZATION FOR HCV (STOPHCV-1): AN OPEN-LABEL RANDOMIZED CONTROLLED TRIAL OF SHORT DURATION THERAPY FOR CHRONIC HEPATITIS C, Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting, Publisher: WILEY, Pages: 905A-906A, ISSN: 0270-9139
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