139 results found
Mugwagwa T, Abubakar I, White P, 2021, Using molecular testing and whole-genome sequencing for tuberculosis diagnosis in a low-burden setting: a cost-effectiveness analysis using transmission-dynamic modelling, Thorax, Vol: 76, Pages: 281-291, ISSN: 0040-6376
Background: Despite progress in tuberculosis (TB) control in low-burden countries like England and Wales, there are still diagnostic delays. Molecular testing and/or whole-genome sequencing (WGS) provide more rapid diagnosis but their cost-effectiveness is relatively unexplored in low-burden settings. Methods: An integrated transmission-dynamic health-economic model is used to assess the cost-effectiveness of using WGS to replace culture-based drug-sensitivity testing, vs using molecular testing vs combined use of WGS and molecular testing, for routine TB diagnosis. The model accounts for the effects of faster appropriate treatment in reducing transmission, benefiting health and reducing future treatment costs. Cost-effectiveness is assessed using Incremental Net benefit (INB) over a 10-yearhorizon with a Quality-Adjusted Life-Year valued at £20,000, and discounting at 3.5%p.a.ResultsWGS shortens the time to drug-sensitivity testing, and treatment modification where necessary, reducing treatment and hospitalization costs, with an INB of £7.1M. Molecular testing shortens the time to TB diagnosis and treatment. Initially this causes an increase in annual costs of treatment, but averting transmissions and future active-TB disease subsequently resulting in cost savings and health benefits to achieve an INB of £8.6M(GeneXpert MTB/RIF) or £11.1M(Xpert-Ultra) respectively. Combined use of Xpert-Ultraand WGS is the optimal strategy we consider, with an INB of £16.5M. Conclusions: Routine use of WGS or molecular testing is cost-effective in a low-burden setting, and combined use is the most cost-effective option. Adoption of these technologies can help low-burden countries meet the WHO End TB Strategy milestones, particularly the UK, which still has relatively high TB rates.
McCabe R, Kont M, Schmit N, et al., 2021, Modelling ICU capacity under different epidemiological scenarios of the COVID-19 pandemic in three western European countries, International Journal of Epidemiology, ISSN: 0300-5771
Background: The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on intensive care units (ICUs) in Europe. Ensuring access to care, irrespective of COVID-19 status, in winter 2020/21 is essential.Methods: An integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients is used to estimate the demand for and resultant spare capacity of ICU beds, staff, and ventilators under different epidemic scenarios in France, Germany, and Italy across the 2020/21 winter period. The effect of implementing lockdowns triggered by different numbers of COVID-19 patients in ICU under varying levels of effectiveness is examined, using a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model.Results: Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource. Reactive lockdowns could lead to large improvements in ICU capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and sustained under a higher level of suppression. The success of such interventions also depends on baseline bed numbers and average non-COVID-19 patient occupancy.Conclusions: Reductions in capacity deficits under different scenarios must be weighed against the feasibility and drawbacks of further lockdowns. Careful, continuous decision-making by national policymakers will be required across the winter period 2020/21.
Didelot X, Kendall M, Xu Y, et al., 2021, Genomic Epidemiology Analysis of Infectious Disease Outbreaks Using TransPhylo., Curr Protoc, Vol: 1
Comparing the pathogen genomes from several cases of an infectious disease has the potential to help us understand and control outbreaks. Many methods exist to reconstruct a phylogeny from such genomes, which represents how the genomes are related to one another. However, such a phylogeny is not directly informative about transmission events between individuals. TransPhylo is a software tool implemented as an R package designed to bridge the gap between pathogen phylogenies and transmission trees. TransPhylo is based on a combined model of transmission between hosts and pathogen evolution within each host. It can simulate both phylogenies and transmission trees jointly under this combined model. TransPhylo can also reconstruct a transmission tree based on a dated phylogeny, by exploring the space of transmission trees compatible with the phylogeny. A transmission tree can be represented as a coloring of a phylogeny where each color represents a different host of the pathogen, and TransPhylo provides convenient ways to plot these colorings and explore the results. This article presents the basic protocols that can be used to make the most of TransPhylo. © 2021 The Authors. Basic Protocol 1: First steps with TransPhylo Basic Protocol 2: Simulation of outbreak data Basic Protocol 3: Inference of transmission Basic Protocol 4: Exploring the results of inference.
Middleton P, Perez-Guzman PN, Cheng A, et al., 2021, Characteristics and outcomes of clinically diagnosed RT-PCR swab negative COVID-19: a retrospective cohort study, Scientific Reports, Vol: 11, Pages: 1-7, ISSN: 2045-2322
Patients with strong clinical features of COVID-19 with negative real time polymerase chain reaction (RT-PCR) SARS-CoV-2 testing are not currently included in official statistics. The scale, characteristics and clinical relevance of this group are not well described. We performed a retrospective cohort study in two large London hospitals to characterize the demographic, clinical, and hospitalization outcome characteristics of swab-negative clinical COVID-19 patients. We found 1 in 5 patients with a negative swab and clinical suspicion of COVID-19 received a clinical diagnosis of COVID-19 within clinical documentation, discharge summary or death certificate. We compared this group to a similar swab positive cohort and found similar demographic composition, symptomology and laboratory findings. Swab-negative clinical COVID-19 patients had better outcomes, with shorter length of hospital stay, reduced need for >60% supplementary oxygen and reduced mortality. Patients with strong clinical features of COVID-19 that are swab-negative are a common clinical challenge. Health systems must recognize and plan for the management of swab-negative patients in their COVID-19 clinical management, infection control policies and epidemiological assessments.
Surey J, Stagg HR, Yates TA, et al., 2021, An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study., BMC Infect Dis, Vol: 21
BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current tr
Christen P, D'Aeth J, Lochen A, et al., 2021, The J-IDEA pandemic planner: a framework for implementing hospital provision interventions during the COVID-19 pandemic, Medical Care, Pages: 1-8, ISSN: 0025-7079
Background : Planning for extreme surges in demand for hospital care of patientsrequiring urgent life-saving treatment for COVID-19, whilst retaining capacity for otheremergency conditions, is one of the most challenging tasks faced by healthcareproviders and policymakers during the pandemic. Health systems must be wellpreparedto cope with large and sudden changes in demand by implementinginterventions to ensure adequate access to care. We developed the first planning toolfor the COVID-19 pandemic to account for how hospital provision interventions (suchas cancelling elective surgery, setting up field hospitals, or hiring retired staff) will affectthe capacity of hospitals to provide life-saving care.Methods : We conducted a review of interventions implemented or considered in 12 European countries in March-April 2020, an evaluation of their impact on capacity, anda review of key parameters in the care of COVID-19 patients. This information wasused to develop a planner capable of estimating the impact of specific interventions ondoctors, nurses, beds and respiratory support equipment. We applied this to ascenario-based case study of one intervention, the set-up of field hospitals in England,under varying levels of COVID-19 patients.Results : The J-IDEA pandemic planner is a hospital planning tool that allows hospitaladministrators, policymakers and other decision-makers to calculate the amount ofcapacity in terms of beds, staff and crucial medical equipment obtained byimplementing the interventions. Flexible assumptions on baseline capacity, the numberof hospitalisations, staff-to-beds ratios, and staff absences due to COVID-19 make theplanner adaptable to multiple settings. The results of the case study show that whilefield hospitals alleviate the burden on the number of beds available, this intervention isfutile unless the deficit of critical care nurses is addressed first.Discussion : The tool supports decision-makers in delivering a fast and effectiveresponse to
Knock E, Whittles L, Lees J, et al., 2020, Report 41: The 2020 SARS-CoV-2 epidemic in England: key epidemiological drivers and impact of interventions
England has been severely affected by COVID-19. We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional 2020 surveillance data. Only national lockdown brought the reproduction number below 1 consistently; introduced one week earlier in the first wave it could have reduced mortality by 23,300 deaths on average. The mean infection fatality ratio was initially ~1.3% across all regions except London and halved following clinical care improvements. The infection fatality ratio was two-fold lower throughout in London, even when adjusting for demographics. The infection fatality ratio in care homes was 2.5-times that in the elderly in the community. Population-level infection-induced immunity in England is still far from herd immunity, with regional mean cumulative attack rates ranging between 4.4% and 15.8%.
Sandmann FG, White PJ, Ramsay M, et al., 2020, Optimising benefits of testing key workers for infection with SARS-CoV-2: A mathematical modelling analysis., Clinical Infectious Diseases, Vol: 71, Pages: 3196-3203, ISSN: 1058-4838
BACKGROUND: Internationally, key workers such as healthcare staff are advised to stay at home if they or household members experience coronavirus disease 2019 (COVID-19)-like symptoms. This potentially isolates / quarantines many staff without SARS-CoV-2, whilst not preventing transmission from staff with asymptomatic infection. We explored the impact of testing staff on absence durations from work and transmission risks to others. METHODS: We used a decision-analytic model for 1,000 key workers to compare the baseline strategy of (S0) no RT-PCR testing of workers to testing workers (S1) with COVID-19-like symptoms in isolation, (S2) without COVID-19-like symptoms but in household-quarantine, and (S3) all staff. We explored confirmatory re-testing scenarios of repeating all initial tests, initially-positive tests, initially-negative tests; or no re-testing. We varied all parameters, including the infection rate (0.1%-20%), proportion asymptomatic (10%-80%), sensitivity (60%-95%), and specificity (90%-100%). RESULTS: Testing all staff (S3) changes the risk of workplace transmission by -56.9 to +1.0 workers per 1,000 tests (with reductions throughout at RT-PCR sensitivity of ≥65%), and absences by 0.5 to +3.6 days per test but at heightened testing needs of 989.6-1995.9 tests per 1,000 workers. Testing workers in household-quarantine (S2) reduces absences the most by 3.0-6.9 days per test (at 47.0-210.4 tests per 1,000 workers), while increasing risk of workplace transmission by 0.02-49.5 infected workers per 1,000 tests (which can be minimised when re-testing initially-negative tests). DISCUSSION: Based on optimising absence durations or transmission risk our modelling suggests testing staff in household-quarantine or all staff, depending on infection levels and testing capacities.
Lewis J, White PJ, Price MJ, 2020, Per-partnership transmission probabilities for Chlamydia trachomatis infection: Evidence synthesis of population-based survey data, International Journal of Epidemiology, ISSN: 0300-5771
Grassly NC, Pons-Salort M, Parker EPK, et al., 2020, Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study, Lancet Infectious Diseases, Vol: 20, Pages: 1381-1389, ISSN: 1473-3099
BACKGROUND: WHO has called for increased testing in response to the COVID-19 pandemic, but countries have taken different approaches and the effectiveness of alternative strategies is unknown. We aimed to investigate the potential impact of different testing and isolation strategies on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and PCR test sensitivity over time since infection. We estimated the reduction in the effective reproduction number (R) achieved by testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols. The expected effectiveness of different testing strategies was defined as the percentage reduction in R. We reviewed data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics and examined their implications for the use of so-called immunity passports. FINDINGS: If all individuals with symptoms compatible with COVID-19 self-isolated and self-isolation was 100% effective in reducing onwards transmission, self-isolation of symptomatic individuals would result in a reduction in R of 47% (95% uncertainty interval [UI] 32-55). PCR testing to identify SARS-CoV-2 infection soon after symptom onset could reduce the number of individuals needing to self-isolate, but would also reduce the effectiveness of self-isolation (around 10% would be false negatives). Weekly screening of health-care workers and other high-risk groups irrespective of symptoms by use of PCR testing is estimated to reduce their contribution to SARS-CoV-2 transmission by 23% (95% UI 16-40), on top of reductions achieved by self-isolation following symptoms, assuming results are available at 24 h. The effectiveness of test and trace depends strongly on coverage and the timelines
Lewer D, Braithwaite I, Bullock M, et al., 2020, COVID-19 among people experiencing homelessness in England: a modelling study, The Lancet Respiratory Medicine, Vol: 8, Pages: 1181-1191, ISSN: 2213-2600
BACKGROUND: People experiencing homelessness are vulnerable to COVID-19 due to the risk of transmission in shared accommodation and the high prevalence of comorbidities. In England, as in some other countries, preventive policies have been implemented to protect this population. We aimed to estimate the avoided deaths and health-care use among people experiencing homelessness during the so-called first wave of COVID-19 in England-ie, the peak of infections occurring between February and May, 2020-and the potential impact of COVID-19 on this population in the future. METHODS: We used a discrete-time Markov chain model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that included compartments for susceptible, exposed, infectious, and removed individuals, to explore the impact of the pandemic on 46 565 individuals experiencing homelessness: 35 817 living in 1065 hostels for homeless people, 3616 sleeping in 143 night shelters, and 7132 sleeping outside. We ran the model under scenarios varying the incidence of infection in the general population and the availability of prevention measures: specialist hotel accommodation, infection control in homeless settings, and mixing with the general population. We divided our scenarios into first wave scenarios (covering Feb 1-May 31, 2020) and future scenarios (covering June 1, 2020-Jan 31, 2021). For each scenario, we ran the model 200 times and reported the median and 95% prediction interval (2·5% and 97·5% quantiles) of the total number of cases, the number of deaths, the number hospital admissions, and the number of intensive care unit (ICU) admissions. FINDINGS: Up to May 31, 2020, we calibrated the model to 4% of the homeless population acquiring SARS-CoV-2, and estimated that 24 deaths (95% prediction interval 16-34) occurred. In this first wave of SARS-CoV-2 infections in England, we estimated that the preventive measures imposed might have avoided 21 092 infections (19 777-22 147)
McCabe R, Kont M, Schmit N, et al., 2020, Report 36: Modelling ICU capacity under different epidemiological scenarios of the COVID-19 pandemic in three western European countries
The coronavirus disease 2019 (COVID-19) pandemic has placed enormous strain on healthcare systems, particularly intensive care units (ICUs), with COVID-19 patient care being a key concern of healthcare system planning for winter 2020/21. Ensuring that all patients who require intensive care, irrespective of COVID-19 status, can access it during this time is essential. This study uses an integrated model of hospital capacity planning and epidemiological projections of COVID-19 patients to estimate the spare capacity of key ICU resources under different epidemic scenarios in France, Germany and Italy across the winter period of 2020/21. In particular, we examine the effect of implementing suppression strategies of varying effectiveness, triggered by different numbers of COVID-19 patients in ICU. The use of a ‘dual-demand’ (COVID-19 and non-COVID-19) patient model and the consideration of multiple ICU resources that determine capacity (beds, doctors, nurses and ventilators) and the interdependencies between them, provides a detailed insight into potential capacity constraints this winter. Without sufficient mitigation, we estimate that COVID-19 ICU patient numbers will exceed those seen in the first peak, resulting in substantial capacity deficits, with beds being consistently found to be the most constrained resource across countries. Lockdowns triggered based on ICU capacity could lead to large improvements in spare capacity during the winter season, with pressure being most effectively alleviated when lockdown is triggered early and implemented at a higher level of suppression. In many cases, maximum deficits are reduced to lower levels which can then be managed by expanding supply-side hospital capacity, to ensure that all patients can receive treatment. The success of such interventions also depends on baseline ICU bed numbers and average non-COVID-19 patient occupancy. We find that lockdowns of longer duration reduce the total number of days in defic
Haw D, Forchini G, Christen P, et al., 2020, Report 35: How can we keep schools and universities open? Differentiating closures by economic sector to optimize social and economic activity while containing SARS-CoV-2 transmission
There is a trade-off between the education sector and other economic sectors in the control of SARS-Cov-2 transmission. Here we integrate a dynamic model of SARS-CoV-2 transmission with a 63-sector economic model reflecting sectoral heterogeneity in transmission and economic interdependence between sectors. We identify COVID-19 control strategies which optimize economic production while keeping schools and universities operational and constraining infections such that emergency hospital capacity is not exceeded. The model estimates an economic gain of between £163bn and £205bn for the United Kingdom compared to a blanket lockdown of non-essential activity over six months, depending on hospital capacity. Sectors identified as potential priorities for closure are contact-intensive and/or less economically productive.
Lewis J, Horner P, White P, 2020, Incidence of pelvic inflammatory disease associated with mycoplasma genitalium infection: Evidence synthesis of cohort study data, Clinical Infectious Diseases, Vol: 71, Pages: 2719-2722, ISSN: 1058-4838
We synthesized evidence from the POPI sexual-health cohort study, and estimated that 4.9% (95% credible interval 0.4-14.1%) of Mycoplasma genitalium infections in women progress to pelvic inflammatory disease, versus 14.4% (5.9-24.6%) of chlamydial infections. For validation, we predicted PID rates in four age groups that agree well with surveillance data.
Story A, Garber E, Aldridge RW, et al., 2020, Management and control of tuberculosis control in socially complex groups: a research programme including three RCTs
<h4>Background</h4>Socially complex groups, including people experiencing homelessness, prisoners and drug users, have very high levels of tuberculosis, often complicated by late diagnosis and difficulty in adhering to treatment.<h4>Objective</h4>To assess a series of interventions to improve tuberculosis control in socially complex groups.<h4>Design</h4>A series of observational surveys, evaluations and trials of interventions.<h4>Setting</h4>The pan-London Find&Treat service, which supports tuberculosis screening and case management in socially complex groups across London.<h4>Participants</h4>Socially complex groups with tuberculosis or at risk of tuberculosis, including people experiencing homelessness, prisoners, drug users and those at high risk of poor adherence to tuberculosis treatment.<h4>Interventions and main outcome measures</h4>We screened 491 people in homeless hostels and 511 people in prison for latent tuberculosis infection, human immunodeficiency virus, hepatitis B and hepatitis C. We evaluated an NHS-led prison radiographic screening programme. We conducted a cluster randomised controlled trial (2348 eligible people experiencing homelessness in 46 hostels) of the effectiveness of peer educators (22 hostels) compared with NHS staff (24 hostels) at encouraging the uptake of mobile radiographic screening. We initiated a trial of the use of point-of-care polymerase chain reaction diagnostics to rapidly confirm tuberculosis alongside mobile radiographic screening. We undertook a randomised controlled trial to improve treatment adherence, comparing face-to-face, directly observed treatment with video-observed treatment using a smartphone application. The primary outcome was completion of ≥ 80% of scheduled treatment observations over the first 2 months following enrolment. We assessed the cost-effectiveness of latent tuberculosis screening alongside radiographic scree
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
McCabe R, Schmit N, Christen P, et al., 2020, Adapting hospital capacity to meet changing demands during the COVID-19 pandemic, BMC Medicine, Vol: 18, Pages: 1-12, ISSN: 1741-7015
BackgroundTo calculate hospital surge capacity, achieved via hospital provision interventions implemented for the emergency treatment of coronavirus disease 2019 (COVID-19) and other patients through March to May 2020; to evaluate the conditions for admitting patients for elective surgery under varying admission levels of COVID-19 patients.MethodsWe analysed National Health Service (NHS) datasets and literature reviews to estimate hospital care capacity before the pandemic (pre-pandemic baseline) and to quantify the impact of interventions (cancellation of elective surgery, field hospitals, use of private hospitals, deployment of former medical staff and deployment of newly qualified medical staff) for treatment of adult COVID-19 patients, focusing on general and acute (G&A) and critical care (CC) beds, staff and ventilators.ResultsNHS England would not have had sufficient capacity to treat all COVID-19 and other patients in March and April 2020 without the hospital provision interventions, which alleviated significant shortfalls in CC nurses, CC and G&A beds and CC junior doctors. All elective surgery can be conducted at normal pre-pandemic levels provided the other interventions are sustained, but only if the daily number of COVID-19 patients occupying CC beds is not greater than 1550 in the whole of England. If the other interventions are not maintained, then elective surgery can only be conducted if the number of COVID-19 patients occupying CC beds is not greater than 320. However, there is greater national capacity to treat G&A patients: without interventions, it takes almost 10,000 G&A COVID-19 patients before any G&A elective patients would be unable to be accommodated.ConclusionsUnless COVID-19 hospitalisations drop to low levels, there is a continued need to enhance critical care capacity in England with field hospitals, use of private hospitals or deployment of former and newly qualified medical staff to allow some or all elective surge
Whittles LK, White PJ, Didelot X, 2020, Assessment of the potential of vaccination to combat antibiotic resistance in gonorrhea: a modeling analysis to determine preferred product characteristics, Clinical Infectious Diseases, Vol: 71, Pages: 1912-1919, ISSN: 1058-4838
BACKGROUND: Gonorrhea incidence is increasing rapidly in many countries, whilst antibiotic resistance is making treatment more difficult. Combined with evidence that MeNZB and Bexsero meningococcal vaccines are likely partially-protective against gonorrhea, this has renewed interest in a gonococcal vaccine, and several candidates are in development. Key questions are how protective a vaccine needs to be, how long protection needs to last, and how should it be targeted. We assessed vaccination's potential impact, and the feasibility of achieving WHO's target 90% reduction in gonorrhea incidence 2016-2030, by comparing realistic vaccination strategies under a range of scenarios of vaccine efficacy and duration of protection, and emergence of extensively-resistant gonorrhea. METHODS: We developed a stochastic transmission-dynamic model, incorporating asymptomatic and symptomatic infection and heterogeneous sexual behavior in men-who-have-sex-with-men (MSM). We used data from England, which has a comprehensive, consistent nationwide surveillance system. Using particle Markov Chain Monte Carlo methods we fitted the model to gonorrhea incidence in 2008-17, and then used Bayesian forecasting to examine an extensive range of scenarios. RESULTS: Even in the worst-case scenario of untreatable infection emerging, the WHO target is achievable if all MSM attending sexual health clinics receive a vaccine offering ≥52% protection for ≥6 years. A vaccine conferring 31% protection (as estimated for MeNZB) for 2-4 years, could reduce incidence in 2030 by 45% in the worst-case scenario, and by 75% if >70% of resistant gonorrhea remains treatable. CONCLUSIONS: Even a partially-protective vaccine, delivered through a realistic targeting strategy, could substantially reduce gonorrhea incidence, despite antibiotic resistance.
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, 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.
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
Forchini G, Lochen A, Hallett T, et al., 2020, Report 28: Excess non-COVID-19 deaths in England and Wales between 29th February and 5th June 2020
There were 189,403 deaths from any cause reported in England from 29th February to 5th June 2020 inclusive, and 11,278 all-cause deaths in Wales over the same period. Of those deaths, 44,736 (23.6%) registered COVID-19 on the death certificate in England, and 2,294 (20.3%) in Wales, while 144,667 (76.4%) were not recorded as having been due to COVID-19 in England, and 8,984 (79.7%) in Wales. However, it could be that some of the ‘non-COVID-19’ deaths have in fact also been caused by COVID-19, either as the direct cause of death, or indirectly through provisions for the pandemic impeding access to care for other conditions. There is uncertainty in how many of the non-COVID-19 deaths were directly or indirectly caused by the pandemic. We estimated the excess deaths that were not recorded as associated with COVID-19 in the death certificate (excess non-COVID-19 deaths) as the deaths for which COVID-19 was not reported as the cause, compared to those we would have expected to occur had the pandemic not happened. Expected deaths were forecast with an analysis of historic trends in deaths between 2010 and April 2020 using data by the Office of National Statistics and a statistical time series model. According to the model, we expected 136,294 (95% CI 133,882 - 138,696) deaths in England, and 8,983 (CI 8,051 - 9,904) in Wales over this period, significantly fewer than the number of deaths reported. This means that there were 8,983 (95% CI 5,971 - 10,785) total excess non-COVID-19 deaths in England. For every 100 COVID-19 deaths during the period from 29th February to 5th June 2020 there were between 13 and 24 cumulative excess non-COVID-19 deaths. The proportion of cumulative excess non-COVID-19 deaths of all reported deaths during this period was 4.4% (95% CI 3.2% - 5.7%) in England, with small regional variations. Excess deaths were highest in the South East at 2,213 (95% CI 327 - 4,047) and in London at 1,937 (95% CI 896 - 3,010), respectively. There is no e
McCabe R, Schmit N, Christen P, et al., 2020, Report 27 Adapting hospital capacity to meet changing demands during the COVID-19 pandemic
To meet the growing demand for hospital care due to the COVID-19 pandemic, England implemented a range of hospital provision interventions including the procurement of equipment, the establishment of additional hospital facilities and the redeployment of staff and other resources. Additionally, to further release capacity across England’s National Health Service (NHS), elective surgery was cancelled in March 2020, leading to a backlog of patients requiring care. This created a pressure on the NHS to reintroduce elective procedures, which urgently needs to be addressed. Population-level measures implemented in March and April 2020 reduced transmission of SARS-CoV-2, prompting a gradual decline in the demand for hospital care by COVID-19 patients after the peak in mid-April. Planning capacity to bring back routine procedures for non-COVID-19 patients whilst maintaining the ability to respond to any potential future increases in demand for COVID-19 care is the challenge currently faced by healthcare planners.In this report, we aim to calculate hospital capacity for emergency treatment of COVID-19 and other patients during the pandemic surge in April and May 2020; to evaluate the increase in capacity achieved via five interventions (cancellation of elective surgery, field hospitals, use of private hospitals, and deployment of former and newly qualified medical staff); and to determine how to re-introduce elective surgery considering continued demand from COVID-19 patients. We do this by modelling the supply of acute NHS hospital care, considering different capacity scenarios, namely capacity before the pandemic (baseline scenario) and after the implementation of capacity expansion interventions that impact available general and acute (G&A) and critical care (CC) beds, staff and ventilators. Demand for hospital care is accounted for in terms of non-COVID-19 and COVID-19 patients. Our results suggest that NHS England would not have had sufficient daily capacity
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
The World Health Organization has called for increased molecular testing in response to the COVID-19 pandemic, but different countries have taken very different approaches. We used a simple mathematical model to investigate the potential effectiveness of alternative testing strategies for COVID-19 control. Weekly screening of healthcare workers (HCWs) and other at-risk groups using PCR or point-of-care tests for infection irrespective of symptoms is estimated to reduce their contribution to transmission by 25-33%, on top of reductions achieved by self-isolation following symptoms. Widespread PCR testing in the general population is unlikely to limit transmission more than contact-tracing and quarantine based on symptoms alone, but could allow earlier release of contacts from quarantine. Immunity passports based on tests for antibody or infection could support return to work but face significant technical, legal and ethical challenges. Testing is essential for pandemic surveillance but its direct contribution to the prevention of transmission is likely to be limited to patients, HCWs and other high-risk groups.
Christen P, D'Aeth J, Lochen A, et al., 2020, Report 15: Strengthening hospital capacity for the COVID-19 pandemic
Planning for extreme surges in demand for hospital care of patients requiring urgent life-saving treatment for COVID-19, and other conditions, is one of the most challenging tasks facing healthcare commissioners and care providers during the pandemic. Due to uncertainty in expected patient numbers requiring care, as well as evolving needs day by day, planning hospital capacity is challenging. Health systems that are well prepared for the pandemic can better cope with large and sudden changes in demand by implementing strategies to ensure adequate access to care. Thereby the burden of the pandemic can be mitigated, and many lives saved. This report presents the J-IDEA pandemic planner, a hospital planning tool to calculate how much capacity in terms of beds, staff and ventilators is obtained by implementing healthcare provision interventions affecting the management of patient care in hospitals. We show how to assess baseline capacity, and then calculate how much capacity is gained by various healthcare interventions using impact estimates that are generated as part of this study. Interventions are informed by a rapid review of policy decisions implemented or being considered in 12 European countries over the past few months￼ , an evaluation of the impact of the interventions on capacity using a variety of research methods, and by a review of key parameters in the care of COVID-19 patients.The J-IDEA planner is publicly available, interactive and adaptable to different and changing circumstances and newly emerging evidence. The planner estimates the additional number of beds, medical staff and crucial medical equipment obtained under various healthcare interventions using flexible inputs on assumptions of existing capacities, the number of hospitalisations, beds-to-staff ratios, and staff absences due to COVID-19. A detailed user guide accompanies the planner. The planner was developed rapidly and has limitations which we will address in future iterations. It support
Vegvari C, Grad Y, White P, et al., 2020, Using rapid point-of-care tests to inform antibiotic choice to mitigate drug resistance in gonorrhoea, Eurosurveillance, ISSN: 1025-496X
Lewis J, White PJ, 2020, Understanding relationships between chlamydial infection, symptoms and testing behavior: an analysis of data from Natsal-3, Epidemiology, Vol: 31, Pages: 263-271, ISSN: 1044-3983
Background: Genital chlamydial infection is the most commonly-diagnosed sexually- transmitted infection worldwide, and can have serious long-term sequelae. Numerous countries invest substantially in testing but evidence for programs’ effectiveness is inconclusive. The effects of testing programs in different groups of people need to be understood. Methods: We analyzed data on sexual behavior and chlamydia testing from 16-24-year-olds in Britain’s third National Survey of Sexual Attitudes and Lifestyles, considering test setting, reason and result. We conducted descriptive analysis accounting for the survey design using design variables and nonresponse weightings, and Bayesian analysis using a mathematical model of chlamydial infection and testing. Results: Most men testing due to symptoms tested in sexual health settings (63.1%; 95% confidence interval 42.5-83.6%) but most women testing due to symptoms were tested by GPs (59.3%; 42.9-75.8%). Within behavioral groups, positivity of chlamydia screens (tests not prompted by symptoms or partner notification) was similar to population prevalence. Screening rates were higher in women and in those reporting more partners: median (95% credible interval) rates per year in those reporting 0, 1 and ≥2 new partners in the last year were 0.30(0.24-0.35), 0.45(0.37-0.53) and 0.59(0.48-0.71) (men) and 0.59(0.52-0.68), 0.88(0.74-1.03) 20 and 1.16(0.97-1.39) (women). Conclusions: The proportion of testing occurring in sexual health is not a proxy for the proportion prompted by symptoms. Test positivity depends on a combination of force of infection and screening rate and does not simply reflect prevalence or behavioral risk. The analysis highlights the value of recording testing reason and behavioral characteristics to inform cost-effective control.
White P, Lewis J, 2019, Letter to editor in response to Has Chlamydia trachomatis prevalence in young women in England, Scotland and Wales changed? Evidence from national probability surveys, Epidemiology and Infection, Vol: 147, ISSN: 0950-2688
White P, Lewis J, 2019, Response to Kounali et al.’s letter of response, Epidemiology and Infection, Vol: 147, ISSN: 0950-2688
Green N, Sherrard-Smith E, Tanton C, et al., 2019, Assessing local chlamydia screening performance by combining survey and administrative data to account for differences in local population characteristics, Scientific Reports, Vol: 9, ISSN: 2045-2322
Reducing health inequalities requires improved understanding of the causes of variation. Local-level variation reflects differences in local population characteristics and health system performance. Identifying low- and high-performing localities allows investigation into these differences. We used Multilevel Regression with Post-stratification (MRP) to synthesise data from multiple sources, using chlamydia testing as our example. We used national probability survey data to identify individual-level characteristics associated with chlamydia testing and combined this with local-level census data to calculate expected levels of testing in each local authority (LA) in England, allowing us to identify LAs where observed chlamydia testing rates were lower or higher than expected, given population characteristics. Taking account of multiple covariates, including age, sex, ethnicity, student and cohabiting status, 5.4% and 3.5% of LAs had testing rates higher than expected for 95% and 99% posterior credible intervals, respectively; 60.9% and 50.8% had rates lower than expected. Residual differences between observed and MRP expected values were smallest for LAs with large proportions of non-white ethnic populations. London boroughs that were markedly different from expected MRP values (90% posterior exceedance probability) had actively targeted risk groups. This type of synthesis allows more refined inferences to be made at small-area levels than previously feasible.
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