Imperial College London

ProfessorPeterWhite

Faculty of MedicineSchool of Public Health

Professor of Public Health Modelling
 
 
 
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p.white Website

 
 
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Praed StreetSt Mary's Campus

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Summary

 

Publications

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151 results found

Rangaka MX, Hamada Y, Duong T, Bern H, Calvert J, Francis M, Clarke AL, Ghanouni A, Layton C, Hack V, Owen-Powell E, Surey J, Sanders K, Booth HL, Crook A, Griffiths C, Horne R, Kunst H, Lipman M, Mandelbaum M, White PJ, Zenner D, Abubakar Iet al., 2022, Evaluating the effect of short-course rifapentine-based regimens with or without enhanced behaviour-targeted treatment support on adherence and completion of treatment for latent tuberculosis infection among adults in the UK (RID-TB: Treat): protocol for an open-label, multicentre, randomised controlled trial, BMJ Open, Vol: 12, Pages: 1-11, ISSN: 2044-6055

Introduction The successful scale-up of a latent tuberculosis (TB) infection testing and treatment programme is essential to achieve TB elimination. However, poor adherence compromises its therapeutic effectiveness. Novel rifapentine-based regimens and treatment support based on behavioural science theory may improve treatment adherence and completion.Methods and analysis A pragmatic multicentre, open-label, randomised controlled trial assessing the effect of novel short-course rifapentine-based regimens for TB prevention and additional theory-based treatment support on treatment adherence against standard-of-care. Participants aged between 16 and 65 who are eligible to start TB preventive therapy will be recruited in England. 920 participants will be randomised to one of six arms with allocation ratio of 5:5:6:6:6:6: daily isoniazid +rifampicin for 3 months (3HR), routine treatment support (control); 3HR, additional treatment support; weekly isoniazid +rifapentine for 3 months (3HP), routine treatment support; weekly 3HP, additional treatment support ; daily isoniazid +rifapentine for 1 month (1HP), routine treatment support; daily 1HP, additional treatment support. Additional treatment support comprises reminders using an electronic pillbox, a short animation, and leaflets based on the perceptions and practicalities approach. The primary outcome is adequate treatment adherence, defined as taking ≥90% of allocated doses within the pre-specified treatment period, measured by electronic pillboxes. Secondary outcomes include safety and TB incidence within 12 months. We will conduct process evaluation of the trial interventions and assess intervention acceptability and fidelity and mechanisms for effect and estimate the cost-effectiveness of novel regimens. The protocol was developed with patient and public involvement, which will continue throughout the trial.Ethics and dissemination Ethics approval has been obtained from The National Health Service Health Research

Journal article

White P, Nikitin D, Whittles L, 2022, We need estimates of gonorrhoea vaccine protection and symptomaticity by sex and anatomical site, Lancet Infectious Diseases, Vol: 22, Pages: 937-937, ISSN: 1473-3099

Journal article

Rahman A, Thangaratinam S, Copas A, Zenner D, White PJ, Griffiths C, Abubakar I, McCourt C, Kunst Het al., 2022, A feasibility study evaluating the uptake, effectiveness and acceptability of routine screening of pregnant migrants for latent tuberculosis infection in antenatal care: a research protocol., BMJ Open, Vol: 12, Pages: 1-7, ISSN: 2044-6055

INTRODUCTION: Globally, tuberculosis (TB) is a leading cause of death in women of reproductive age and there is high risk of reactivation of latent tuberculosis infection (LTBI) in pregnancy. The uptake of routine screening of migrants for LTBI in the UK in primary care is low. Antenatal care is a novel setting which could improve uptake and can lend insight into the feasibility and acceptability of offering opt-out screening for LTBI. METHODS AND ANALYSIS: This is an observational feasibility study with a nested qualitative component. The setting will be the antenatal clinics in three hospitals in East London, UK . Inclusion criteria are pregnant migrant women aged 16-35 years attending antenatal clinics who are from countries with a TB incidence of greater than 150/100 000 including sub-Saharan Africa, and who have been in the UK for less than 5 years. Participants will be offered LTBI screening with an opt-out interferon gamma release assay blood test, and be invited to complete a questionnaire. Both participants and healthcare providers will be invited to participate in semistructured interviews or focus groups to evaluate understanding, feasibility and acceptability of routine opt-out LTBI screening. The primary analysis will focus on estimating the uptake of the screening programme along with the corresponding 95% CI. Secondary analysis will focus on estimating the test positivity. Qualitative analysis will evaluate the acceptability of offering routine opt-out LTBI screening to participants and healthcare providers. ETHICS AND DISSEMINATION: The study has received the following approvals: Health Research Authority (IRAS 247388) and National Health Service Ethics Committee (19/LO/0557). The results will be made available locally to antenatal clinics and primary care physicians, nationally to NHS England and Public Health England and internationally through conferences and journals. TRIAL REGISTRATION NUMBER: NCT04098341.

Journal article

Haw D, Forchini G, Doohan P, Christen P, Pianella M, Johnson R, Bajaj S, Hogan A, Winskill P, Miraldo M, White P, Ghani A, Ferguson N, Smith P, Hauck Ket al., 2022, Optimizing social and economic activity while containing SARS-CoV-2 transmission using DAEDALUS, Nature Computational Science, Vol: 2, Pages: 223-233, ISSN: 2662-8457

To study the trade-off between economic, social and health outcomes in the management of a pandemic, DAEDALUS integrates a dynamic epidemiological model of SARS-CoV-2 transmission with a multi-sector economic model, reflecting sectoral heterogeneity in transmission and complex supply chains. The model identifies mitigation strategies that optimize economic production while constraining infections so that hospital capacity is not exceeded but allowing essential services, including much of the education sector, to remain active. The model differentiates closures by economic sector, keeping those sectors open that contribute little to transmission but much to economic output and those that produce essential services as intermediate or final consumption products. In an illustrative application to 63 sectors in the United Kingdom, the model achieves an economic gain of between £161 billion (24%) and £193 billion (29%) compared to a blanket lockdown of non-essential activities over six months. Although it has been designed for SARS-CoV-2, DAEDALUS is sufficiently flexible to be applicable to pandemics with different epidemiological characteristics.

Journal article

Evans S, Stimson J, Pople D, Bhattacharya A, Hope R, White PJ, Robotham JVet al., 2022, Quantifying the contribution of pathways of nosocomial acquisition of COVID-19 in English hospitals, International Journal of Epidemiology, Vol: 51, Pages: 393-403, ISSN: 0300-5771

BACKGROUND: Despite evidence of the nosocomial transmission of novel coronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in hospitals worldwide, the contributions of the pathways of transmission are poorly quantified. METHODS: We analysed national records of hospital admissions and discharges, linked to data on SARS-CoV-2 testing, using an individual-based model that considers patient-to-patient, patient-to-healthcare worker (HCW), HCW-to-patient and HCW-to-HCW transmission. RESULTS: Between 1 March 2020 and 31 December 2020, SARS-CoV-2 infections that were classified as nosocomial were identified in 0.5% (0.34-0.74) of patients admitted to an acute National Health Service trust. We found that the most likely route of nosocomial transmission to patients was indirect transmission from other infected patients, e.g. through HCWs acting as vectors or contaminated fomites, followed by direct transmission between patients in the same bay. The risk of transmission to patients from HCWs over this time period is low, but can contribute significantly when the number of infected inpatients is low. Further, the risk of a HCW acquiring SARS-CoV-2 in hospital is approximately equal to that in the community, thereby doubling their overall risk of infection. The most likely route of transmission to HCWs is transmission from other infected HCWs. CONCLUSIONS: Current control strategies have successfully reduced the transmission of SARS-CoV-2 between patients and HCWs. In order to reduce the burden of nosocomial COVID-19 infections on health services, stricter measures should be enforced that would inhibit the spread of the virus between bays or wards in the hospital. There should also be a focus on inhibiting the spread of SARS-CoV-2 between HCWs. The findings have important implications for infection-control procedures in hospitals.

Journal article

Rangaka MX, Hamada Y, Duong T, Bern H, Calvert J, Francis M, Clarke AL, Ghanouni A, Hack V, Owen-Powell E, Surey J, Sanders K, Booth HL, Crook A, Griffiths C, Horne R, Kunst H, Lipman M, Mandelbaum M, White PJ, Whiting P, Zenner D, Abubakar Iet al., 2021, Randomised controlled trial to evaluate the effectiveness of using the RD-1-based C-Tb skin test as a replacement for blood-based interferon-gamma release assay for detection of, and initiation of preventive treatment for, tuberculosis infection: RID-TB:Dx study protocol, BMJ Open, Vol: 11, ISSN: 2044-6055

Introduction The predictive utility for incident tuberculosis (TB) of the purified protein derivative tuberculin skin test and region of difference 1 (RD1)-based interferon-gamma release assays (IGRA) is comparable; and either is recommended to test for latent TB infection (LTBI). Despite associated high costs of IGRA, sites participating in LTBI screening in many high-income settings pragmatically favour IGRA due to its higher specificity and simpler logistics. A new RD1-based skin test, C-Tb, could offer an acceptable and as accurate, cheaper alternative to IGRA. Evaluating the impact of C-Tb on process and patient-related outcomes would provide important information to help guide its use in LTBI testing strategies.Methods and analysis This is a pragmatic multicentre, open-label, non-inferiority, randomised controlled trial. The trial will assess the initiation of LTBI treatment following a positive result of the randomised test as the primary outcome. Participants will be randomised to receive the C-Tb test (intervention) or IGRA (usual care, control) for initiation of treatment. We will enrol 1530 participants in England aged≥16 years who are eligible for LTBI testing and treatment according to UK guidance. In the C-Tb arm, skin induration will be assessed 2–3 days after intradermal injection and measured in millimetres of induration. Results of IGRA will be obtained in line with standard practice. Behavioural studies will explore people’s experiences, perspectives and preferences of LTBI testing and treatment. Economic analysis will estimate cost-effectiveness of changes to the diagnostic algorithm for LTBI. The protocol was developed with Patient and Public Involvement (PPI), which will continue throughout the trial.Ethics and dissemination Ethics approval has been obtained from The NHS Health Research Authority (269485). We will share results of the trial in peer-reviewed journals and conferences.

Journal article

McCabe R, Kont MD, Watson O, Schmit N, Whittaker C, Lochen A, Walker PGT, Ghani AC, Ferguson NM, White PJ, Donnelly CA, Watson OJet al., 2021, Communicating uncertainty in epidemic models, Epidemics: the journal of infectious disease dynamics, Vol: 37, Pages: 1-6, ISSN: 1755-4365

While mathematical models of disease transmission are widely used to inform public health decision-makers globally, the uncertainty inherent in results are often poorly communicated. We outline some potential sources of uncertainty in epidemic models, present traditional methods used to illustrate uncertainty and discuss alternative presentation formats used by modelling groups throughout the COVID-19 pandemic. Then, by drawing on the experience of our own recent modelling, we seek to contribute to the ongoing discussion of how to improve upon traditional methods used to visualise uncertainty by providing a suggestion of how this can be presented in a clear and simple manner.

Journal article

Whittles L, Didelot X, White P, 2021, Public health impact and cost-effectiveness of gonorrhoea vaccination: an integrated transmission-dynamic health-economic modelling analysis, Lancet Infectious Diseases, Vol: 22, ISSN: 1473-3099

Background Gonorrhoea is a rapidly-growing public health threat, with rising incidence andincreasing drug-resistance. Evidence that meningococcal vaccines MeNZB and 4CMenB offerprotection has created interest in using 4CMenB against gonorrhoea and in developinggonorrhoea-specific vaccines, but cost-effectiveness and how efficacy and duration of protectionaffect a vaccine’s value have not been assessed.Methods We developed an integrated transmission-dynamic health-economic model, calibratedusing Bayesian methods to surveillance data (GUMCAD: Genitourinary Medicine Clinic ActivityDataset, and GRASP: Gonococcal Resistance to Antimicrobials Surveillance Programme) on menwho-have-sex-with-men (MSM) in England. We considered vaccination of MSM from theperspective of sexual health clinics (with and without vaccination of all adolescents in schools),comparing three realistic approaches to targeting: vaccination-on-attendance for testing;vaccination-on-diagnosis with gonorrhoea; or vaccination-according-to-risk, offered to patientsdiagnosed with gonorrhoea plus those testing negative who report high numbers of partners(>5p.a.). We varied vaccine uptake (0·5-2× HPV vaccine uptake); efficacy (1-100%) and durationof protection (1-20 years); future epidemic trajectories (current trends stabilising, or continuing);and the time-horizon considered (10&20 years).Findings Adolescent vaccination has little impact with only 1·7%p.a. vaccinated. Vaccinationaccording-to-risk combines high impact and efficiency: even under conservative assumptions4CMenB would likely be cost-saving in use against gonorrhoea in MSM in England at the currentNHS price for use against infant meningitis, averting an estimated mean 110,200(95%CrI:36,500-223,600) cases, gaining 100·3(31·0-215·8) QALYs, and saving £7·9M(£0·0M-£20·5M) over 10years. A hypothetical gonorrhoea vaccine’s value is increased more by improvi

Journal article

Vollmer MAC, Radhakrishnan S, Kont MD, Flaxman S, Bhatt SJ, Costelloe C, Honeyford K, Aylin P, Cooke G, Redhead J, Sanders A, Mangan H, White PJ, Ferguson N, Hauck K, Perez Guzman PN, Nayagam Set al., 2021, The impact of the COVID-19 pandemic on patterns of attendance at emergency departments in two large London hospitals: an observational study, BMC Health Services Research, Vol: 21, Pages: 1-9, ISSN: 1472-6963

Background Hospitals in England have undergone considerable change to address the surgein demand imposed by the COVID-19 pandemic. The impact of this on emergencydepartment (ED) attendances is unknown, especially for non-COVID-19 related emergencies.Methods This analysis is an observational study of ED attendances at the Imperial CollegeHealthcare NHS Trust (ICHNT). We calibrated auto-regressive integrated moving averagetime-series models of ED attendances using historic (2015-2019) data. Forecasted trendswere compared to present year ICHNT data for the period between March 12, 2020 (whenEngland implemented the first COVID-19 public health measure) and May 31, 2020. Wecompared ICHTN trends with publicly available regional and national data. Lastly, wecompared hospital admissions made via the ED and in-hospital mortality at ICHNT duringthe present year to the historic 5-year average.Results ED attendances at ICHNT decreased by 35% during the period after the firstlockdown was imposed on March 12, 2020 and before May 31, 2020, reflecting broadertrends seen for ED attendances across all England regions, which fell by approximately 50%for the same time frame. For ICHNT, the decrease in attendances was mainly amongst thoseaged <65 years and those arriving by their own means (e.g. personal or public transport) andnot correlated with any of the spatial dependencies analysed such as increasing distance frompostcode of residence to the hospital. Emergency admissions of patients without COVID-19after March 12, 2020 fell by 48%; we did not observe a significant change to the crudemortality risk in patients without COVID-19 (RR 1.13, 95%CI 0.94-1.37, p=0.19).Conclusions Our study findings reflect broader trends seen across England and give anindication how emergency healthcare seeking has drastically changed. At ICHNT, we findthat a larger proportion arrived by ambulance and that hospitalisation outcomes of patientswithout COVID-19 did not differ from previous years. The ext

Journal article

Knock ES, Whittles LK, Lees JA, Perez-Guzman PN, Verity R, FitzJohn RG, Gaythorpe KAM, Imai N, Hinsley W, Okell LC, Rosello A, Kantas N, Walters CE, Bhatia S, Watson OJ, Whittaker C, Cattarino L, Boonyasiri A, Djaafara BA, Fraser K, Fu H, Wang H, Xi X, Donnelly CA, Jauneikaite E, Laydon DJ, White PJ, Ghani AC, Ferguson NM, Cori A, Baguelin M, Knock E, Whittles L, Lees J, Perez-Guzman P, Verity R, FitzJohn R, Gaythorpe KAM, Imai N, Hinsley W, Okell L, Rosello A, Kantas N, Walters C, Bhatia S, Watson O, Whittaker C, Cattarino L, Boonyasiri A, Djaafara B, Fraser K, Fu H, Wang H, Xi X, Donnelly C, Jauneikaite E, Laydon D, White P, Ghani A, Ferguson N, Cori A, Baguelin Met al., 2021, Key epidemiological drivers and impact of interventions in the 2020 SARS-CoV-2 epidemic in England, Science Translational Medicine, Vol: 13, Pages: 1-12, ISSN: 1946-6234

We fitted a model of SARS-CoV-2 transmission in care homes and the community to regional surveillance data for England. Compared with other approaches, our model provides a synthesis of multiple surveillance data streams into a single coherent modelling framework allowing transmission and severity to be disentangled from features of the surveillance system. Of the control measures implemented, only national lockdown brought the reproduction number (Rteff ) below 1 consistently; if introduced one week earlier it could have reduced deaths in the first wave from an estimated 48,600 to 25,600 (95% credible interval [95%CrI]: 15,900-38,400). The infection fatality ratio decreased from 1.00% (95%CrI: 0.85%-1.21%) to 0.79% (95%CrI: 0.63%-0.99%), suggesting improved clinical care. The infection fatality ratio was higher in the elderly residing in care homes (23.3%, 95%CrI: 14.7%-35.2%) than those residing in the community (7.9%, 95%CrI: 5.9%-10.3%). On 2nd December 2020 England was still far from herd immunity, with regional cumulative infection incidence between 7.6% (95%CrI: 5.4%-10.2%) and 22.3% (95%CrI: 19.4%-25.4%) of the population. Therefore, any vaccination campaign will need to achieve high coverage and a high degree of protection in vaccinated individuals to allow non-pharmaceutical interventions to be lifted without a resurgence of transmission.

Journal article

McCabe R, Kont M, Schmit N, Whittaker C, Lochen A, Baguelin M, Knock E, Whittles L, Lees J, Brazeau N, Walker P, Ghani A, Ferguson N, White P, Donnelly C, Hauck K, Watson Oet al., 2021, Modelling ICU capacity under different epidemiological scenarios of the COVID-19 pandemic in three western European countries, International Journal of Epidemiology, Vol: 50, Pages: 753-767, 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.

Journal article

Gupta RK, Lule SA, Krutikov M, Gosce L, Green N, Southern J, Imran A, Aldridge RW, Kunst H, Lipman M, Lynn W, Burgess H, Rahman A, Menezes D, Rahman A, Tiberi S, White PJ, Abubakar Iet al., 2021, Screening for tuberculosis among high-risk groups attending London Emergency Departments: a prospective observational study, European Respiratory Journal, Vol: 57, Pages: 1-1, ISSN: 0903-1936

Journal article

Christen P, D'Aeth J, Lochen A, McCabe R, Rizmie D, Schmit N, Nayagam S, Miraldo M, Aylin P, Bottle A, Perez Guzman P, Donnelly C, Ghani A, Ferguson N, White P, Hauck Ket al., 2021, The J-IDEA pandemic planner: a framework for implementing hospital provision interventions during the COVID-19 pandemic, Medical Care, Vol: 59, Pages: 371-378, 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

Journal article

Lewis J, White PJ, Price MJ, 2021, Per-partnership transmission probabilities for Chlamydia trachomatis infection: Evidence synthesis of population-based survey data, International Journal of Epidemiology, Vol: 50, Pages: 510-517, ISSN: 0300-5771

BackgroundChlamydia is the most commonly diagnosed sexually transmitted infection worldwide. Mathematical models used to plan and assess control measures rely on accurate estimates of chlamydia’s natural history, including the probability of transmission within a partnership. Several methods for estimating transmission probability have been proposed, but all have limitations.MethodsWe have developed a new model for estimating per-partnership chlamydia transmission probabilities from infected to uninfected individuals, using data from population-based surveys. We used data on sexual behaviour and prevalent chlamydia infection from the second UK National Study of Sexual Attitudes and Lifestyles (Natsal-2) and the US National Health and Nutrition Examination Surveys 2009–2014 (NHANES) for Bayesian inference of average transmission probabilities, across all new heterosexual partnerships reported. Posterior distributions were estimated by Markov chain Monte Carlo sampling using the Stan software.ResultsPosterior median male-to-female transmission probabilities per partnership were 32.1% [95% credible interval (CrI) 18.4–55.9%] (Natsal-2) and 34.9% (95%CrI 22.6–54.9%) (NHANES). Female-to-male transmission probabilities were 21.4% (95%CrI 5.1–67.0%) (Natsal-2) and 4.6% (95%CrI 1.0–13.1%) (NHANES). Posterior predictive checks indicated a well-specified model, although there was some discrepancy between reported and predicted numbers of partners, especially in women.ConclusionsThe model provides statistically rigorous estimates of per-partnership transmission probability, with associated uncertainty, which is crucial for modelling and understanding chlamydia epidemiology and control. Our estimates incorporate data from several sources, including population-based surveys, and use information contained in the correlation between number of partners and the probability of chlamydia infection. The evidence synthesis approach means that it is ea

Journal article

Halliday A, Jain P, Hoang L, Parker R, Tolosa-Wright M, Masonou T, Green N, Boakye A, Takwoingi Y, Hamilton S, Mandagere V, Fries A, Coin L, Deeks J, White PJ, Levin M, Beverley P, Kon OM, Lalvani Aet al., 2021, New technologies for diagnosing active TB: the VANTDET diagnostic accuracy study, Efficacy and Mechanism Evaluation, Vol: 8, Pages: 1-160, ISSN: 2050-4365

<jats:sec id="abs1-1"> <jats:title>Background</jats:title> <jats:p>Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed.</jats:p> </jats:sec> <jats:sec id="abs1-2"> <jats:title>Objective</jats:title> <jats:p>To validate promising new technologies [namely whole-blood transcriptomics, proteomics, flow cytometry and quantitative reverse transcription-polymerase chain reaction (qRT-PCR)] and existing signatures for the detection of active TB in samples obtained from individuals with suspected active TB.</jats:p> </jats:sec> <jats:sec id="abs1-3"> <jats:title>Design</jats:title> <jats:p>Four substudies, each of which used samples from the biobank collected as part of the interferon gamma release assay (IGRA) in the Diagnostic Evaluation of Active TB study, which was a prospective cohort of patients recruited with suspected TB.</jats:p> </jats:sec> <jats:sec id="abs1-4"> <jats:title>Setting</jats:title> <jats:p>Secondary care.</jats:p> </jats:sec> <jats:sec id="abs1-5"> <jats:title>Participants</jats:title> <jats:p>Adults aged ≥ 16 years presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham, with suspected active TB.</jats:p> </jats:sec> <jats:sec id="abs1-6"> <jats:title>Interventions</jats:title> <jats:p>New tests using genome-wide gene expression microarray

Journal article

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.

Journal article

Didelot X, Kendall M, Xu Y, White PJ, McCarthy Net al., 2021, Genomic epidemiology analysis of infectious disease outbreaks using TransPhylo., Current Protocols, Vol: 1, Pages: 1-23, ISSN: 2691-1299

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.

Journal article

Middleton P, Perez-Guzman PN, Cheng A, Kumar N, Kont M, Daunt A, Mukherjee S, Cooke G, Hallett TB, Hauck K, White PJ, Thursz MR, Nayagam Set 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.

Journal article

Surey J, Stagg HR, Yates TA, Lipman M, White PJ, Charlett A, Munoz L, Gosce L, Rangaka MX, Francis M, Hack V, Kunst H, Abubakar Iet 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 Infectious Diseases, Vol: 21, ISSN: 1471-2334

BackgroundEnding 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.MethodsAn 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.ResultsFifty-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.ConclusionIn 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-inferi

Journal article

Knock E, Whittles L, Lees J, Perez Guzman P, Verity R, Fitzjohn R, Gaythorpe K, Imai N, Hinsley W, Okell L, Rosello A, Kantas N, Walters C, Bhatia S, Watson O, Whittaker C, Cattarino L, Boonyasiri A, Djaafara A, Fraser K, Fu H, Wang H, Xi X, Donnelly C, Jauneikaite E, Laydon D, White P, Ghani A, Ferguson N, Cori A, Baguelin Met 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%.

Report

Sandmann FG, White PJ, Ramsay M, Jit Met 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.

Journal article

Grassly NC, Pons-Salort M, Parker EPK, White PJ, Ferguson NM, Imperial College COVID-19 Response Team, Grassly NC, Pons Salort M, Parker EPK, White PJ, Ferguson NM, Imperial College COVID-19 Response Teamet 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

Journal article

Lewer D, Braithwaite I, Bullock M, Eyre MT, White PJ, Aldridge RW, Story A, Hayward ACet 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)

Journal article

Haw D, Forchini G, Christen P, Bajaj S, Hogan A, Winskill P, Miraldo M, White P, Ghani A, Ferguson N, Smith P, Hauck Ket 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.

Report

McCabe R, Kont M, Schmit N, Whittaker C, Lochen A, Baguelin M, Knock E, Whittles L, Lees J, Walker P, Ghani A, Ferguson N, White P, Donnelly C, Hauck K, Watson Oet 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

Report

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.

Journal article

Story A, Garber E, Aldridge RW, Smith CM, Hall J, Ferenando G, Possas L, Hemming S, Wurie F, Luchenski S, Abubakar I, McHugh TD, White PJ, Watson JM, Lipman M, Garfein R, Hayward ACet 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

Journal article

Daunt A, Perez-Guzman PN, Cafferkey J, Manalan K, Cooke G, White PJ, Hauck K, Mallia P, Nayagam Set 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

Journal article

Celma CC, Beard S, Douglas A, Wong S, Osafo N-K, Hannah M, Hale A, Huggins G, Ladhani S, Dunning J, Vegvari C, Grad Y, White P, Didelot X, Whittles L, Scangarella-Oman N, Mitrani-Gold F, Dumont E, Perry C, Gilchrist K, Hossain M, Mortimer T, Anderson R, Gardiner Det al., 2020, Retrospective analysis on confirmation rates for referred positive rotavirus samples in England, 2016 to 2017: implications for diagnosis and surveillance, Eurosurveillance, Vol: 25, Pages: 1-8, ISSN: 1025-496X

BackgroundRapid diagnostic tests are commonly used by hospital laboratories in England to detect rotavirus (RV), and results are used to inform clinical management and support national surveillance of the infant rotavirus immunisation programme since 2013. In 2017, the Public Health England (PHE) national reference laboratory for enteric viruses observed that the presence of RV could not be confirmed by PCR in a proportion of RV-positive samples referred for confirmatory detection.AimWe aimed to compare the positivity rate of detection methods used by hospital laboratories with the PHE confirmatory test rate.MethodsRotavirus specimens testing positive at local hospital laboratories were re-tested at the PHE national reference laboratory using a PCR test. Confirmatory results were compared to original results from the PHE laboratory information management system.ResultsHospital laboratories screened 70.1% (2,608/3,721) of RV samples using immunochromatographic assay (IC) or rapid tests, 15.5% (578/3,721) using enzyme immunoassays (EIA) and 14.4% (535/3,721) using PCR. Overall, 1,011/3,721 (27.2%) locally RV-positive samples referred to PHE in 2016 and 2017 failed RV detection using the PHE reference laboratory PCR test. Confirmation rates were 66.9% (1,746/2,608) for the IC tests, 87.4% (505/578) for the EIA and 86.4% (465/535) for the PCR assays. Seasonal confirmation rate discrepancies were also evident for IC tests.ConclusionsThis report highlights high false positive rates with the most commonly used RV screening tests and emphasises the importance of implementing verified confirmatory tests for RV detections. This has implications for clinical diagnosis and national surveillance.

Journal article

McCabe R, Schmit N, Christen P, D'Aeth J, Løchen A, Rizmie D, Nayagam AS, Miraldo M, Aylin P, Bottle R, Perez-Guzman PN, Ghani A, Ferguson N, White P, Hauck Ket 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

Journal article

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