Publications
153 results found
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, Vol: 2020, Pages: 1-11, ISSN: 1058-4838
Background: Emerging evidence suggests ethnic minorities are disproportionatelyaffected by COVID-19. Detailed clinical analyses of multi-cultural hospitalized patientcohorts remain largely undescribed.Methods: We performed regression, survival andcumulative competing risk analyses to evaluate factors associated with mortality inpatients admitted for COVID-19 in three large London hospitals between February 25and April 5, censored as of May 1, 2020.Results: Of 614 patients (median age 69years, (IQR 25) and 62% male), 381 (62%) had been discharged alive, 178 (29%)died and 55 (9%) remained hospitalized at censoring. Severe hypoxemia (aOR 4.25,95%CI 2.36-7.64), leukocytosis (aOR 2.35, 95%CI 1.35-4.11), thrombocytopenia (aOR1.01, 95%CI 1.00-1.01, increase per 10x9decrease), severe renal impairment (aOR5.14, 95%CI 2.65-9.97), and low albumin (aOR 1.06, 95%CI 1.02-1.09, increase per gdecrease) were associated with death. Forty percent (244) were from black, Asian andother minority ethnic (BAME) groups, 38% (235) white and for 22% (135) ethnicity wasunknown. BAME patients were younger and had fewer comorbidities. Whilst theunadjusted odds of death did not differ by ethnicity, when adjusting for age, sex andcomorbidities, black patients were at higher odds of death compared to whites (aOR1.69, 95%CI 1.00-2.86). This association was stronger when further adjusting foradmission severity (aOR 1.85 95% CI 1.06-3.24). Conclusions: BAME patients were over-represented in our cohort and, whenaccounting for demographic and clinical profile of admission, black patients were atincreased odds of death. Further research is needed into biologic drivers of differencesin COVID-19 outcomes by ethnicity.
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
Grassly N, Pons Salort M, Parker E, et al., 2020, Report 16: Role of testing in COVID-19 control
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
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, Response to Kounali et al.’s letter of response, Epidemiology and Infection, Vol: 147, ISSN: 0950-2688
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
Story A, Garber E, Aldridge RW, et al., 2019, Management and control of tuberculosis control in socially complex groups: A research programme including three RCTs, Programme Grants for Applied Research, Vol: 8, Pages: 7-75, ISSN: 2050-4322
Background: 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. Objective: To assess a series of interventions to improve tuberculosis control in socially complex groups. Design: A series of observational surveys, evaluations and trials of interventions. Setting: The pan-London Find & Treat service, which supports tuberculosis screening and case management in socially complex groups across London. Participants: 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. Interventions and main outcome measures: 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 screening of people experiencing homelessness. The costs of video-observed treatment and directly observed treatment wer
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.
Takwoingi Y, Whitworth H, Rees-Roberts M, et al., 2019, Interferon gamma release assays for diagnostic evaluation of active tuberculosis (IDEA): test accuracy study and economic evaluation, Health Technology Assessment, Vol: 23, ISSN: 1366-5278
BackgroundInterferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice.ObjectivesTo compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB® (Oxford Immunotec, Abingdon, UK) and QuantiFERON® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs.DesignProspective within-patient comparative diagnostic accuracy study.SettingSecondary care.ParticipantsAdults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB.InterventionsThe index tests [T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results.Main outcome measuresSensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test.ResultsA total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT.TB was mor
Whittles L, White P, Didelot X, 2019, A dynamic power-law sexual network model of gonorrhoea outbreaks, PLoS Computational Biology, Vol: 15, ISSN: 1553-734X
Human networks of sexual contacts are dynamic by nature, with partnerships forming and breaking continuously over time. Sexual behaviours are also highly heterogeneous, so that the number of partners reported by individuals over a given period of time is typically distributed as a power-law. Both the dynamism and heterogeneity of sexual partnerships are likely to have an effect in the patterns of spread of sexually transmitted diseases. To represent these two fundamental properties of sexual networks, we developed a stochastic process of dynamic partnership formation and dissolution, which results in power-law numbers of partners over time. Model parameters can be set to produce realistic conditions in terms of the exponent of the power-law distribution, of the number of individuals without relationships and of the average duration of relationships. Using an outbreak of antibiotic resistant gonorrhoea amongst men have sex with men as a case study, we show that our realistic dynamic network exhibits different properties compared to the frequently used static networks or homogeneous mixing models. We also consider an approximation to our dynamic network model in terms of a much simpler branching process. We estimate the parameters of the generation time distribution and offspring distribution which can be used for example in the context of outbreak reconstruction based on genomic data. Finally, weinvestigate the impact of a range of interventions against gonorrhoea, including increased condom use, more frequent screening and immunisation, concluding that the latter shows great promise to reduce the burden of gonorrhoea, even if the vaccine was only partially effective or applied to only a random subset of the population.
Story A, Aldridge RW, Smith CM, et al., 2019, Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: a multicentre, analyst-blinded, randomised, controlled superiority trial, Lancet, Vol: 393, Pages: 1216-1224, ISSN: 0140-6736
BACKGROUND: Directly observed treatment (DOT) has been the standard of care for tuberculosis since the early 1990s, but it is inconvenient for patients and service providers. Video-observed therapy (VOT) has been conditionally recommended by WHO as an alternative to DOT. We tested whether levels of treatment observation were improved with VOT. METHODS: We did a multicentre, analyst-blinded, randomised controlled superiority trial in 22 clinics in England (UK). Eligible participants were patients aged at least 16 years with active pulmonary or non-pulmonary tuberculosis who were eligible for DOT according to local guidance. Exclusion criteria included patients who did not have access to charging a smartphone. We randomly assigned participants to either VOT (daily remote observation using a smartphone app) or DOT (observations done three to five times per week in the home, community, or clinic settings). Randomisation was done by the SealedEnvelope service using minimisation. DOT involved treatment observation by a health-care or lay worker, with any remaining daily doses self-administered. VOT was provided by a centralised service in London. Patients were trained to record and send videos of every dose ingested 7 days per week using a smartphone app. Trained treatment observers viewed these videos through a password-protected website. Patients were also encouraged to report adverse drug events on the videos. Smartphones and data plans were provided free of charge by study investigators. DOT or VOT observation records were completed by observers until treatment or study end. The primary outcome was completion of 80% or more scheduled treatment observations over the first 2 months following enrolment. Intention-to-treat (ITT) and restricted (including only patients completing at least 1 week of observation on allocated arm) analyses were done. Superiority was determined by a 15% difference in the proportion of patients with the primary outcome (60% vs 75%). This trial
Halliday A, Jain P, Hoang L, et al., 2019, Validation of new technologies for the diagnostic evaluation of active tuberculosis (VANTDET), Efficacy and Mechanism Evaluation, ISSN: 2050-4365
Background: Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed. Objective: To validate promising new technologies (namely whole blood transcriptomics, proteomics, flow cytometry and qRT-PCR) and existing signatures for detection of active TB in samples obtained from individuals suspected of active TB. Design: Four sub-studies, each of which used the samples from biobank collected as part of the IDEA study, which was a prospective cohort of patients recruited with suspected TB. Setting: secondary care Participants: Adults (aged ≥ 16 years old) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. Interventions: New tests using either: genome-wide gene expression microarray (transcriptomics); SELDI TOF/ LC-MS (proteomics), flow cytometry, qRT-PCR. Main outcome measures: Area under the curve (AUC), sensitivity and specificity, were calculated to determine diagnostic accuracy. Positive and negative predictive values were calculated in some cases. A decision tree model was developed to calculate the incremental costs and quality-adjusted life-years (QALYs) of changing from current practice to using the novels tests. Results: The project and 4 sub-studies which assessed the previous published signatures measured using each of the new technologies, and a health economic analysis where the best performing tests were evaluated for cost effectiveness. The diagnostic accuracy of the transcriptomic tests ranged from AUC=0.81-0.84 for detecting all TB in our cohort. The performance for detecting culture confirmed TB or pulmonary TB (PTB) was better than for highly probable TB or extrapulmonary TB (EPTB) respectively, but not high enough to be clinically useful. None of the previously described serum proteomic signatures for active TB provided good diagnostic accuracy, not did the candidate rule-out tests. Four of six previously described cell
Story A, Aldridge RW, Smith CM, et al., 2018, Smartphone-enabled video observed versus directly observed treatment for tuberculosis: a randomised controlled trial, Lancet, ISSN: 0140-6736
BackgroundDirectly observed treatment (DOT) has been the standard of care for tuberculosissince the early 1990s, but delivery entails substantial inconvenience to patients andservice providers. Remote video observed therapy (VOT) has recently beenconditionally recommended by the WHO as an alternative to DOT. We testedwhether levels of treatment observation were improved with VOT.MethodsWe conducted a randomised controlled trial of VOT (daily remote observation using asmartphone app) compared to DOT (three or five-weekly observation in home,community or clinic settings). Tuberculosis patients eligible for DOT at 22 clinics inEngland were allocated to trial arms by the SealedEnvelopeTM service usingrandomisation by minimisation. The primary outcome was completion of 80% or morescheduled treatment observations over the first two months following enrolment.Intention-to-treat and restricted (including only patients with at least one week ofobservation on allocated arm) analyses were conducted. The trial is registered withthe ISRCTN, number ISRCTN26184967.FindingsBetween September 1, 2014 and October 1, 2016, we enrolled 226 patients; 112randomised to VOT and 114 to DOT. Overall, 58% (131 of 226) had a history ofhomelessness, imprisonment, drug use, alcohol problems or mental health problems.Seventy percent of patients on VOT (78 of 112) had the primary outcome comparedto 31% (35 of 114) of those on DOT (adjusted odds ratio 5·48; 95% confidenceinterval 3·10-9·68; p<0·0001). Drop-out during the first week of observation was lessfor VOT (10%, 11 of 112) than DOT (51%, 58 of 114). High observation levels weresustained throughout treatment for VOT patients, but declined rapidly for DOTpatients.4InterpretationVOT is a more effective approach to observation of tuberculosis treatment than clinic-, community- or home-based DOT.
White PJ, Lewis J, 2018, Estimating chlamydia prevalence: more difficult than modelling suggests – Authors' reply, Lancet Public Health, Vol: 3, Pages: e417-e417, ISSN: 2468-2667
Whittles L, White PJ, Paul J, et al., 2018, Epidemiological trends of antibiotic resistant gonorrhoea in the United Kingdom, Antibiotics, Vol: 7, ISSN: 2079-6382
Gonorrhoea is one of the most common sexually-transmitted bacterial infections, globally and in the United Kingdom. The levels of antibiotic resistance in gonorrhoea reported in recent years represent a critical public health issue. From penicillins to cefixime, the gonococcus has become resistant to all antibiotics that have been previously used against it, in each case only a matter of years after introduction as a first-line therapy. After each instance of resistance emergence, the treatment recommendations have required revision, to the point that only a few antibiotics can reliably be prescribed to treat infected individuals. Most countries, including the UK, now recommend that gonorrhoea be treated with a dual therapy combining ceftriaxone and azithromycin. While this treatment is still currently effective for the vast majority of cases, there are concerning signs that this will not always remain the case, and there is no readily apparent alternative. Here, we review the use of antibiotics and epidemiological trends of antibiotic resistance in gonorrhoea from surveillance data over the past 15 years in the UK and describe how surveillance could be improved.
Menzies N, Wolf E, Connors D, et al., 2018, Progression from latent infection to active disease in dynamic TB transmission models: a systematic review of the validity of modelling assumptions, Lancet Infectious Diseases, Vol: 18, Pages: e228-e238, ISSN: 1473-3099
Mathematical modelling is commonly used to evaluate infectious disease control policy, and is influential in shaping policy and budgets. Mathematical models necessarily make assumptions about disease natural history, and if these assumptions are not valid the results of these studies may be biased. We conducted a systematic review of published TB transmission models, to assess the validity of assumptions about progression to active disease following initial infection (PROSPERO ID CRD42016030009). We searched PubMed, Web of Science, Embase, Biosis, and Cochrane Library, and included studies from the earliest available date (1962) to August 31st 2017. We identified 312 studies that met inclusion criteria. Predicted TB incidence varied widely across studies for each risk factor investigated. For population groups with no individual risk factors, annual incidence varied by several orders of magnitude, and 20-year cumulative incidence ranged from close to 0% to 100%. A substantial fraction of modelled results were inconsistent with empirical evidence—for 10-year cumulative incidence 40% of modelled results were more than double or less than half the empirical estimates. These results demonstrate substantial disagreement between modelling studies on a central feature of TB natural history. Greater attention to reproducing known features of TB epidemiology would strengthen future TB modelling studies, and readers of modelling studies are recommended to assess how well those studies demonstrate their validity.
Whittles L, Didelot X, Grad Y, et al., 2018, Testing for gonorrhoea should routinely include the pharynx, Lancet Infectious Diseases, Vol: 18, Pages: 716-717, ISSN: 1473-3099
The profile of Kit Fairley by Tony Kirby1 highlighted his work on the potentially important role of kissing among men who have sex with men (MSM) in gonorrhoea transmission. The role of pharyngeal infection in gonorrhoea transmission, and in the emergence and spread of antimicrobial resistance, is poorly characterised, which represents an important knowledge gap.2 Intimate kissing is a risk factor for meningococcal carriage,3 indicating other Neisseria spp can transmit via this route. Pharyngeal gonococcal infection is predominantly asymptomatic, frequently undetected, and often exposed to suboptimal antibiotic concentrations in therapy;2,4 hence infection might be persistent.
Braham C, White P, Arinaminpathy N, 2018, Management of tuberculosis by healthcare practitioners in Pakistan: A systematic review, PLoS ONE, Vol: 13, ISSN: 1932-6203
Objective:To assess the quality of tuberculosis (TB) care in Pakistan, through determining comparison of healthcare practitioners’ knowledge and practices to national and international TB care guidelines.Methods:Studies reporting on knowledge, attitudes and practices of public and private practitioners with TB patients were selected through searching electronic databases and grey literature.Findings:Of 1458 reports, 20 full-texts were assessed, of which 11 met the eligibility and quality criteria; all studies focused on private sector care. Heterogeneity precluded meta-analysis. In 3 of 4 studies, over 50% of practitioners correctly identified a cough as the main TB symptom. However, 4 out of 6 studies showed practitioners’ compliance to be low (under 50%) for the use of sputum microscopy in diagnosis. The poorest quality care occurred in the later stages of treatment, with low compliance in prescribing practices for continuation-phase care and in monitoring and recording treatment progress, the latter of which is particularly critical for treatment success.Conclusion:TB care was variable and generally inadequate, with both a lack of knowledge and a small ‘know-do’ gap evident—practitioners did not use methods that they know they should use. A lack of recent evidence found suggests that the quality of current practices may not be fully captured and further research is needed, especially on non-allopathic, rural and public-sector contexts. Improved training of practitioners, greater availability of recommended diagnostic tools and expansion of public-private partnerships are suggestions for improving the quality of TB care in Pakistan.
Lewis JEA, White P, 2018, Changes in chlamydia prevalence and duration of infection inferred from testing and diagnosis rates in England: an evidence synthesis using surveillance data, 2000-2015, Lancet Public Health, Vol: 3, Pages: E271-E278, ISSN: 2468-2667
Background: Chlamydia screening programmes have been implemented in several countries, but the effects of screening on incidence, prevalence and reproductive sequelae remain unclear. In England, despite increases in testing with the roll-out of the National Chlamydia Screening Programme (2003-2008), prevalence estimated in population-based surveys was similar in 1999-2001 and 2010-12 – although the precision of the estimates was limited. Methods: We used newly-published annual figures for chlamydia test coverage and diagnoses in England before, during and after the scale-up of national screening, with recently-developed statistical methods which account for symptomatic chlamydia testing and asymptomatic screening, to infer changes in prevalence and average duration of infections in each year. Findings: The data provided numbers of tests and diagnoses in 15-19 and 20-24-year-old men and women in England each year from 2000 to 2015, allowing annual – rather than ten-yearly – estimates of prevalence change. We inferred reductions in prevalence and average infection duration in both sexes once screening was fully implemented. From 2008 to 2010, inferred prevalence reductions were 0.7(0.3,1.4) and 0.8(0.4-1.3) percentage points in 15-24-year-old men and women, respectively (posterior median; 95% credible interval), and average duration of infection fell by 74(17-247) days in men and 30(22-40) days in women. Progress has recently reversed with declining testing. Interpretation: Our analysis provides the first evidence for a reduction in chlamydia prevalence in England concurrent with large-scale population testing. It also shows a consistent decline in the average duration of infections: a measure of screening effectiveness that is unaffected by behavioural changes.
Lewis J, White PJ, 2018, Changes in chlamydia prevalence and duration of infection estimated from testing and diagnosis rates in England: a model-based analysis using surveillance data, 2000–15, Lancet Public Health, ISSN: 2468-2667
Background:Chlamydia screening programmes have been implemented in several countries, but the effects of screening on incidence, prevalence, and reproductive sequelae remain unclear. In England, despite increases in testing with the rollout of the National Chlamydia Screening Programme (NCSP; 2003–08), prevalence estimated in 10-yearly population-based surveys was similar before (1999–2001) and after (2010–12) the programme. However, the precision of these previous estimates was limited by the low numbers of infections. We aimed to establish annual, rather than 10-yearly, estimates of chlamydia prevalence and infection duration.Methods:In this model-based analysis, we used previously published minimum and maximum estimates and Public Health England data for chlamydia test coverage and diagnoses in men and women aged 15–24 years in England, before, during, and after the scale-up of national chlamydia screening. We used a mechanistic model, which accounted for symptomatic chlamydia testing and asymptomatic screening, to estimate changes in prevalence and average duration of infections for each year. We describe estimates derived from the maximum and minimum numbers of tests and diagnoses as maximum and minimum estimates, regardless of their relative magnitude.FindingsThe data included numbers of tests and diagnoses in men and women aged 15–19 years and 20–24 years in England each year from 2000 to 2015. We estimated reductions in prevalence and average infection duration in both sexes once screening was fully implemented. From 2008 to 2010, estimated posterior median prevalence reductions in people aged 15–24 years were 0·68 percentage points (95% credible interval 0·26–1·40; minimum) and 0·66 percentage points (0·25–1·37; maximum) for men and 0·77 percentage points (0·45–1·27) for women (minimum and maximum estimates were the same for women). Ove
White PJ, Abubakar I, 2018, Hepatitis C virus treatment as prevention in people who inject drugs, Lancet Infectious Diseases, Vol: 18, Pages: 379-379, ISSN: 1473-3099
Rhead R, Elmes J, Otobo E, et al., 2018, Do female sex workers have lower uptake of HIV treatment services than non-sex-workers? A cross-sectional study from East Zimbabwe, BMJ Open, Vol: 8, ISSN: 2044-6055
Objective Globally, HIV disproportionately affects female sex workers (FSWs) yet HIV treatment coverage is suboptimal. To improve uptake of HIV services by FSWs, it is important to identify potential inequalities in access and use of care and their determinants. Our aim is to investigate HIV treatment cascades for FSWs and non-sex workers (NSWs) in Manicaland province, Zimbabwe, and to examine the socio-demographic characteristics and intermediate determinants that might explain differences in service uptake.Methods Data from a household survey conducted in 2009–2011 and a parallel snowball sample survey of FSWs were matched using probability methods to reduce under-reporting of FSWs. HIV treatment cascades were constructed and compared for FSWs (n=174) and NSWs (n=2555). Determinants of service uptake were identified a priori in a theoretical framework and tested using logistic regression.Results HIV prevalence was higher in FSWs than in NSWs (52.6% vs 19.8%; age-adjusted OR (AOR) 4.0; 95% CI 2.9 to 5.5). In HIV-positive women, FSWs were more likely to have been diagnosed (58.2% vs 42.6%; AOR 1.62; 1.02–2.59) and HIV-diagnosed FSWs were more likely to initiate ART (84.9% vs 64.0%; AOR 2.33; 1.03–5.28). No difference was found for antiretroviral treatment (ART) adherence (91.1% vs 90.5%; P=0.9). FSWs’ greater uptake of HIV treatment services became non-significant after adjusting for intermediate factors including HIV knowledge and risk perception, travel time to services, physical and mental health, and recent pregnancy.Conclusion FSWs are more likely to take up testing and treatment services and were closer to achieving optimal outcomes along the cascade compared with NSWs. However, ART coverage was low in all women at the time of the survey. FSWs’ need for, knowledge of and proximity to HIV testing and treatment facilities appear to increase uptake.
Bradshaw CS, Horner PJ, Jensen JS, et al., 2018, Syndromic management of STIs and the threat of untreatable Mycoplasma genitalium, Lancet Infectious Diseases, Vol: 18, Pages: 251-252, ISSN: 1473-3099
Mugwagwa T, Stagg H, Abubakar I, et al., 2018, Comparing different technologies for active TB case-finding among the homeless: a transmission-dynamic modelling study, Scientific Reports, Vol: 8, ISSN: 2045-2322
Homeless persons have elevated risk of tuberculosis (TB) and are under-served by conventional health services. Approaches to active case-finding (ACF) and treatment tailored to their needs are required. A transmission-dynamic model was developed to assess the effectiveness and efficiency of screening with mobile Chest X-ray, GeneXpert, or both. Effectiveness of ACF depends upon the prevalence of infection in the population (which determines screening ‘yield’), patient willingness to wait for GeneXpert results, and treatment adherence. ACF is efficient when TB prevalence exceeds 78/100,000 and 46% of drug sensitive TB cases and 33% of multi-drug resistant TB cases complete treatment. This threshold increases to 92/100,000 if additional post-ACF enhanced case management (ECM) increases treatment completion to 85%. Generally, the most efficient option is one-step screening of all patients with GeneXpert, but if too many patients (>27% without ECM, >19% with ECM) are unwilling to wait the 90 minutes required then two-step screening using chest X-ray (which is rapid) followed by GeneXpert for confirmation of TB is the most efficient option. Targeted ACF and support services benefit health through early successful treatment and averting TB transmission and disease. The optimal strategy is setting-specific, requiring careful consideration of patients’ needs regarding testing and treatment.
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