Imperial College London

DrSophieYacoub

Faculty of MedicineDepartment of Infectious Disease

Honorary Clinical Research Fellow
 
 
 
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s.yacoub

 
 
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Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

86 results found

Chanh HQ, Ming DK, Nguyen QH, Duc TM, An LP, Trieu HT, Karolcik S, Hernandez B, Perez J, Van Nuil J, Lyle NN, Kestelyn E, Thwaites L, Georgiou P, Paton C, Holmes A, Chau NVV, Yacoub Set al., 2023, Applying artificial intelligence and digital health technologies, Viet Nam, BULLETIN OF THE WORLD HEALTH ORGANIZATION, Vol: 101, Pages: 487-492, ISSN: 0042-9686

Journal article

Karolcik S, Ming D, Yacoub S, Holmes A, Georgiou Pet al., 2023, A multi-site, multi-wavelength PPG platform for continuous non-invasive health monitoring in hospital settings, IEEE Transactions on Biomedical Circuits and Systems, Vol: 17, Pages: 349-361, ISSN: 1932-4545

This paper presents a novel PPG acquisition platform capable of synchronous multi-wavelength signal acquisition from two measurement locations with up to 4 independent wavelengths from each in parallel. The platform is fully configurable and operates at 1ksps, accommodating a wide variety of transmitters and detectors to serve as both a research tool for experimentation and a clinical tool for disease monitoring. The sensing probes presented in this work acquire 4 PPG channels from the wrist and 4 PPG channels from the fingertip, with wavelengths such that surrogates for pulse wave velocity and haematocrit can be extracted.For conventional PPG sensing, we have achieved the mean error of 4.08 ± 3.72 bpm for heart-rate and a mean error of 1.54 ± 1.04% for SpO2 measurement, with the latter lying within the FDA limits for commercial pulse oximeters. We have further evaluated over 700 individual peak-to-peak time differences between wrist and fingertip signals, achieving a normalized weighted average PWV of 5.80 ± 1.58 m/s, matching with values of PWV found for this age group in literature. Lastly, we introduced and computed a haematocrit ratio (Rhct) between the deep IR and deep red wavelength from the fingertip sensor, finding a significant difference between male and female values (median of 1.9 and 2.93 respectively) pointing to devices sensitivity to Hct.

Journal article

Kien DTH, Edenborough K, Goncalves DDS, Vi TT, Casagrande E, Duyen HTL, Long VT, Dui LT, Nhu VTT, Giang NT, Trang HTX, Lee E, Donovan-Banfield I, Van HTT, Nguyet NM, Phong NT, Chau NVV, Wills B, Yacoub S, Flores H, Simmons Cet al., 2023, Genome evolution of dengue virus serotype 1 under selection by Wolbachia pipientis in Aedes aegypti mosquitoes, VIRUS EVOLUTION, Vol: 9

Journal article

Rosenberger KD, Khanh LP, Tobian F, Chanpheaktra N, Kumar V, Lum LCS, Sathar J, Sandoval EP, Maron GM, Laksono IS, Mahendradhata Y, Sarker M, Rahman R, Caprara A, Benevides BS, Marques ETA, Magalhaes T, Brasil P, Calvet GA, Tami A, Bethencourt SE, Hoai TDT, Thanh KNT, Van NT, Tran NN, Do Chau V, Yacoub S, Van KN, Guzman MG, Martinez PA, Ha QNT, Simmons CP, Wills BA, Geskus RB, Jaenisch Tet al., 2023, Early diagnostic indicators of dengue versus other febrile illnesses in Asia and Latin America (IDAMS study): a multicentre, prospective, observational study, LANCET GLOBAL HEALTH, Vol: 11, Pages: e361-e372, ISSN: 2214-109X

Journal article

Hernandez Perez B, Stiff O, Ming D, Ho Quang C, Vuong Nguyen L, Tuan Nguyen M, Chau Nguyen VV, Nguyet Nguyen M, Huy Nguyen Q, Lam Phung K, Tam Dong Thi H, Trung Dinh T, Trieu Huynh T, Wills B, Cameron Paul S, Holmes A, Yacoub S, Georgiou Pet al., 2023, Learning meaningful latent space representations for patient risk stratification: model development and validation for dengue and other acute febrile illness, Frontiers in Digital Health, Vol: 5, Pages: 1-16, ISSN: 2673-253X

Background: Increased data availability has prompted the creation of clinical decision support systems. These systems utilise clinical information to enhance health care provision, both to predict the likelihood of specific clinical outcomes or evaluate the risk of further complications. However, their adoption remains low due to concerns regarding the quality of recommendations, and a lack of clarity on how results are best obtained and presented.Methods: We used autoencoders capable of reducing the dimensionality of complex datasets in order to produce a 2D representation denoted as latent space to support understanding of complex clinical data. In this output, meaningful representations of individual patient profiles are spatially mapped in an unsupervised manner according to their input clinical parameters. This technique was then applied to a large real-world clinical dataset of over 12,000 patients with an illness compatible with dengue infection in Ho Chi Minh City, Vietnam between 1999 and 2021. Dengue is a systemic viral disease which exerts significant health and economic burden worldwide, and up to 5% of hospitalised patients develop life-threatening complications.Results: The latent space produced by the selected autoencoder aligns with established clinical characteristics exhibited by patients with dengue infection, as well as features of disease progression. Similar clinical phenotypes are represented close to each other in the latent space and clustered according to outcomes broadly described by the World Health Organisation dengue guidelines. Balancing distance metrics and density metrics produced results covering most of the latent space, and improved visualisation whilst preserving utility, with similar patients grouped closer together. In this case, this balance is achieved by using the sigmoid activation function and one hidden layer with three neurons, in addition to the latent dimension layer, which produces the output (Pearson, 0.840; Spearman

Journal article

Ming D, Nguyen QH, An LP, Chanh HQ, Tam DTH, Truong NT, Huy VX, Hernandez B, Van Nuil JI, Paton C, Georgiou P, Nguyen NM, Holmes A, Tho PV, Yacoub Set al., 2023, Mapping patient pathways and understanding clinical decision-making in dengue management to inform the development of digital health tools, BMC Medical Informatics and Decision Making, Vol: 23, Pages: 1-9, ISSN: 1472-6947

BackgroundDengue is a common viral illness and severe disease results in life-threatening complications. Healthcare services in low- and middle-income countries treat the majority of dengue cases worldwide. However, the clinical decision-making processes which result in effective treatment are poorly characterised within this setting. In order to improve clinical care through interventions relating to digital clinical decision-support systems (CDSS), we set out to establish a framework for clinical decision-making in dengue management to inform implementation.MethodsWe utilised process mapping and task analysis methods to characterise existing dengue management at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. This is a tertiary referral hospital which manages approximately 30,000 patients with dengue each year, accepting referrals from Ho Chi Minh city and the surrounding catchment area. Initial findings were expanded through semi-structured interviews with clinicians in order to understand clinical reasoning and cognitive factors in detail. A grounded theory was used for coding and emergent themes were developed through iterative discussions with clinician-researchers.ResultsKey clinical decision-making points were identified: (i) at the initial patient evaluation for dengue diagnosis to decide on hospital admission and the provision of fluid/blood product therapy, (ii) in those patients who develop severe disease or other complications, (iii) at the point of recurrent shock in balancing the need for fluid therapy with complications of volume overload. From interviews the following themes were identified: prioritising clinical diagnosis and evaluation over existing diagnostics, the role of dengue guidelines published by the Ministry of Health, the impact of seasonality and caseload on decision-making strategies, and the potential role of digital decision-support and disease scoring tools.ConclusionsThe study highlights the contemporary priorities i

Journal article

Nguyen LV, Cheung K-W, Periaswamy B, Tran TV, Le Duyen HT, Leong YS, Hamis ZNB, Gregorova M, Ooi EE, Sessions O, Rivino L, Yacoub Set al., 2022, Hyperinflammatory Syndrome, Natural Killer Cell Function, and Genetic Polymorphisms in the Pathogenesis of Severe Dengue, JOURNAL OF INFECTIOUS DISEASES, Vol: 226, Pages: 1338-1347, ISSN: 0022-1899

Journal article

McBride A, Nguyen LV, Nguyen VH, Nguyen QH, Ho QC, Nguyen TXC, Nguyen MN, Ming DK, Nguyen TN, Phung THN, Nguyen TP, Luong THT, Phan VT, Dinh TT, Dong THT, Huynh TT, Geskus RB, Llewelyn MJ, Thwaites CL, Yacoub Set al., 2022, A modified Sequential Organ Failure Assessment score for dengue: development, evaluation and proposal for use in clinical trials, BMC INFECTIOUS DISEASES, Vol: 22

Journal article

Choisy M, McBride A, Chambers M, Ho Quang C, Nguyen Quang H, Xuan Chau NT, Thi GN, Bonell A, Evans M, Ming D, Ngo-Duc T, Quang Thai P, Dang Giang DH, Dan Thanh HN, Ngoc Nhung H, Lowe R, Maude R, Elyazar I, Surendra H, Ashley EA, Thwaites L, van Doorn HR, Kestelyn E, Dondorp AM, Thwaites G, Vinh Chau NV, Yacoub Set al., 2022, Climate change and health in Southeast Asia – defining research priorities and the role of the Wellcome Trust Africa Asia Programmes, Wellcome Open Research, Vol: 6, Pages: 278-278

<ns4:p>This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region.</ns4:p>

Journal article

Garcia-Gallo E, Merson L, Kennon K, Kelly S, Citarella BW, Fryer DV, Shrapnel S, Lee J, Duque S, Fuentes YV, Balan V, Smith S, Wei J, Goncalves BP, Russell CD, Sigfrid L, Dagens A, Olliaro PL, Baruch J, Kartsonaki C, Dunning J, Rojek A, Rashan A, Beane A, Murthy S, Reyes LFet al., 2022, ISARIC-COVID-19 dataset: a prospective, standardized, global dataset of patients hospitalized with COVID-19, Scientific Data, Vol: 9, Pages: 1-22, ISSN: 2052-4463

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.

Journal article

Hung TM, Van Hao N, Yen LM, McBride A, Dat VQ, van Doorn HR, Loan HT, Phong NT, Llewelyn MJ, Nadjm B, Yacoub S, Thwaites CL, Ahmed S, Van Vinh Chau N, Turner HCet al., 2022, Direct medical costs of tetanus, dengue, and sepsis patients in an intensive care unit in vietnam, Frontiers in Public Health, Vol: 10, ISSN: 2296-2565

Background: Critically ill patients often require complex clinical care by highly trained staff within a specialized intensive care unit (ICU) with advanced equipment. There are currently limited data on the costs of critical care in low-and middle-income countries (LMICs). This study aims to investigate the direct-medical costs of key infectious disease (tetanus, sepsis, and dengue) patients admitted to ICU in a hospital in Ho Chi Minh City (HCMC), Vietnam, and explores how the costs and cost drivers can vary between the different diseases.Methods: We calculated the direct medical costs for patients requiring critical care for tetanus, dengue and sepsis. Costing data (stratified into different cost categories) were extracted from the bills of patients hospitalized to the adult ICU with a dengue, sepsis and tetanus diagnosis that were enrolled in three studies conducted at the Hospital for Tropical Diseases in HCMC from January 2017 to December 2019. The costs were considered from the health sector perspective. The total sample size in this study was 342 patients.Results: ICU care was associated with significant direct medical costs. For patients that did not require mechanical ventilation, the median total ICU cost per patient varied between US$64.40 and US$675 for the different diseases. The costs were higher for patients that required mechanical ventilation, with the median total ICU cost per patient for the different diseases varying between US$2,590 and US$4,250. The main cost drivers varied according to disease and associated severity.Conclusion: This study demonstrates the notable cost of ICU care in Vietnam and in similar LMIC settings. Future studies are needed to further evaluate the costs and economic burden incurred by ICU patients. The data also highlight the importance of evaluating novel critical care interventions that could reduce the costs of ICU care.

Journal article

Trieu HT, Khanh LP, Ming DKY, Quang CH, Phan TQ, Van VCN, Deniz E, Mulligan J, Wills BA, Moulton S, Yacoub Set al., 2022, The compensatory reserve index predicts recurrent shock in patients with severe dengue, BMC Medicine, Vol: 20, ISSN: 1741-7015

BACKGROUND: Dengue shock syndrome (DSS) is one of the major clinical phenotypes of severe dengue. It is defined by significant plasma leak, leading to intravascular volume depletion and eventually cardiovascular collapse. The compensatory reserve Index (CRI) is a new physiological parameter, derived from feature analysis of the pulse arterial waveform that tracks real-time changes in central volume. We investigated the utility of CRI to predict recurrent shock in severe dengue patients admitted to the ICU. METHODS: We performed a prospective observational study in the pediatric and adult intensive care units at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. Patients were monitored with hourly clinical parameters and vital signs, in addition to continuous recording of the arterial waveform using pulse oximetry. The waveform data was wirelessly transmitted to a laptop where it was synchronized with the patient's clinical data. RESULTS: One hundred three patients with suspected severe dengue were recruited to this study. Sixty-three patients had the minimum required dataset for analysis. Median age was 11 years (IQR 8-14 years). CRI had a negative correlation with heart rate and moderate negative association with blood pressure. CRI was found to predict recurrent shock within 12 h of being measured (OR 2.24, 95% CI 1.54-3.26), P < 0.001). The median duration from CRI measurement to the first recurrent shock was 5.4 h (IQR 2.9-6.8). A CRI cutoff of 0.4 provided the best combination of sensitivity and specificity for predicting recurrent shock (0.66 [95% CI 0.47-0.85] and 0.86 [95% CI 0.80-0.92] respectively). CONCLUSION: CRI is a useful non-invasive method for monitoring intravascular volume status in patients with severe dengue.

Journal article

Urner M, Barnett AG, Li Bassi G, Brodie D, Dalton HJ, Ferguson N, Heinsar S, Hodgson CL, Peek G, Shekar K, Suen JY, Fraser JF, Fan Eet al., 2022, Venovenous extracorporeal membrane oxygenation in patients with acute covid-19 associated respiratory failure: comparative effectiveness study, BMJ-BRITISH MEDICAL JOURNAL, Vol: 377, ISSN: 0959-535X

Journal article

Ming DK, Tuan NM, Hernandez B, Sangkaew S, Vuong NL, Chanh HQ, Chau NVV, Simmons CP, Wills B, Georgiou P, Holmes AH, Yacoub Set al., 2022, The diagnosis of dengue in patients presenting with acute febrile illness using supervised machine learning and impact of seasonality, Frontiers in Digital Health, Vol: 4, ISSN: 2673-253X

Background: Symptomatic dengue infection can result in a life-threatening shock syndrome and timely diagnosis is essential. Point-of-care tests for non-structural protein 1 and IgM are used widely but performance can be limited. We developed a supervised machine learning model to predict whether patients with acute febrile illnesses had a diagnosis of dengue or other febrile illnesses (OFI). The impact of seasonality on model performance over time was examined.Methods: We analysed data from a prospective observational clinical study in Vietnam. Enrolled patients presented with an acute febrile illness of <72 h duration. A gradient boosting model (XGBoost) was used to predict final diagnosis using age, sex, haematocrit, platelet, white cell, and lymphocyte count collected on enrolment. Data was randomly split 80/20% into a training and hold-out set, respectively, with the latter not used in model development. Cross-validation and hold out set testing was used, with performance over time evaluated through a rolling window approach.Results: We included 8,100 patients recruited between 16th October 2010 and 10th December 2014. In total 2,240 (27.7%) patients were diagnosed with dengue infection. The optimised model from training data had an overall median area under the receiver operator curve (AUROC) of 0.86 (interquartile range 0.84–0.86), specificity of 0.92, sensitivity of 0.56, positive predictive value of 0.73, negative predictive value (NPV) of 0.84, and Brier score of 0.13 in predicting the final diagnosis, with similar performances in hold-out set testing (AUROC of 0.86). Model performances varied significantly over time as a function of seasonality and other factors. Incorporation of a dynamic threshold which continuously learns from recent cases resulted in a more consistent performance throughout the year (NPV >90%).Conclusion: Supervised machine learning models are able to discriminate between dengue and OFI diagnoses in patients presenting with

Journal article

Duc MT, Thwaites CL, Van Nuil JI, McKnight J, An PL, Paton Cet al., 2022, Digital Health Policy and Programs for Hospital Care in Vietnam: Scoping Review, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 24, ISSN: 1438-8871

Journal article

Ho QC, Huynh TT, Huynh NTV, Tran KH, Tu QP, Campbell J, Pley C, Yacoub Set al., 2022, Novel Clinical Monitoring Approaches for Reemergence of Diphtheria Myocarditis, Vietnam, EMERGING INFECTIOUS DISEASES, Vol: 28, Pages: 282-290, ISSN: 1080-6040

Journal article

Ming DK, Hernandez B, Sangkaew S, Vuong NL, Lam PK, Nguyet NM, Tam DTH, Trung DT, Tien NTH, Tuan NM, Chau NVV, Tam CT, Chanh HQ, Trieu HT, Simmons CP, Wills B, Georgiou P, Holmes AH, Yacoub Set al., 2022, Applied machine learning for the risk-stratification and clinical decision support of hospitalised patients with dengue in Vietnam, PLOS Digital Health, Vol: 1, Pages: e0000005-e0000005

BackgroundIdentifying patients at risk of dengue shock syndrome (DSS) is vital for effective healthcare delivery. This can be challenging in endemic settings because of high caseloads and limited resources. Machine learning models trained using clinical data could support decision-making in this context.MethodsWe developed supervised machine learning prediction models using pooled data from adult and paediatric patients hospitalised with dengue. Individuals from 5 prospective clinical studies in Ho Chi Minh City, Vietnam conducted between 12th April 2001 and 30th January 2018 were included. The outcome was onset of dengue shock syndrome during hospitalisation. Data underwent random stratified splitting at 80:20 ratio with the former used only for model development. Ten-fold cross-validation was used for hyperparameter optimisation and confidence intervals derived from percentile bootstrapping. Optimised models were evaluated against the hold-out set.FindingsThe final dataset included 4,131 patients (477 adults and 3,654 children). DSS was experienced by 222 (5.4%) of individuals. Predictors were age, sex, weight, day of illness at hospitalisation, indices of haematocrit and platelets over first 48 hours of admission and before the onset of DSS. An artificial neural network model (ANN) model had best performance with an area under receiver operator curve (AUROC) of 0.83 (95% confidence interval [CI], 0.76–0.85) in predicting DSS. When evaluated against the independent hold-out set this calibrated model exhibited an AUROC of 0.82, specificity of 0.84, sensitivity of 0.66, positive predictive value of 0.18 and negative predictive value of 0.98.InterpretationThe study demonstrates additional insights can be obtained from basic healthcare data, when applied through a machine learning framework. The high negative predictive value could support interventions such as early discharge or ambulatory patient management in this population. Work is underway to incorporate t

Journal article

Kerdegari H, Phung NTH, McBride A, Pisani L, Nguyen HV, Duong TB, Razavi R, Thwaites L, Yacoub S, Gomez Aet al., 2021, B-Line Detection and Localization in Lung Ultrasound Videos Using Spatiotemporal Attention, APPLIED SCIENCES-BASEL, Vol: 11

Journal article

ISARIC Clinical Characterisation Group, 2021, The value of open-source clinical science in pandemic response: lessons from ISARIC., Lancet Infectious Diseases, Vol: 21, Pages: 1623-1624, ISSN: 1473-3099

Journal article

ISARIC Clinical Characterisation Group, Hall MD, Baruch J, Carson G, Citarella BW, Dagens A, Dankwa E, Donnelly CA, Dunning J, Escher M, Kartsonaki C, Merson L, Pritchard M, Wei J, Horby PW, Rojek A, Olliaro PLet al., 2021, Ten months of temporal variation in the clinical journey of hospitalised patients with COVID-19: an observational cohort, eLife, Vol: 10, Pages: 1-30, ISSN: 2050-084X

Background: There is potentially considerable variation in the nature and duration of the care provided to hospitalised patients during an infectious disease epidemic or pandemic. Improvements in care and clinician confidence may shorten the time spent as an inpatient, or the need for admission to an intensive care unit (ICU) or high density unit (HDU). On the other hand, limited resources at times of high demand may lead to rationing. Nevertheless, these variables may be used as static proxies for disease severity, as outcome measures for trials, and to inform planning and logistics. Methods: We investigate these time trends in an extremely large international cohort of 142,540 patients hospitalised with COVID-19. Investigated are: time from symptom onset to hospital admission, probability of ICU/HDU admission, time from hospital admission to ICU/HDU admission, hospital case fatality ratio (hCFR) and total length of hospital stay. Results: Time from onset to admission showed a rapid decline during the first months of the pandemic followed by peaks during August/September and December 2020. ICU/HDU admission was more frequent from June to August. The hCFR was lowest from June to August. Raw numbers for overall hospital stay showed little variation, but there is clear decline in time to discharge for ICU/HDU survivors. Conclusions: Our results establish that variables of these kinds have limitations when used as outcome measures in a rapidly-evolving situation. Funding: This work was supported by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z] and the Bill and Melinda Gates Foundation [OPP1209135]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Journal article

Sangkaew S, Ming D, Boonyasiri A, Honeyford K, Kalayanarooj S, Yacoub S, Dorigatti I, Holmes Aet al., 2021, Transaminases and serum albumin as early predictors of severe dengue reply, Lancet Infectious Diseases, Vol: 21, Pages: 1489-1490, ISSN: 1473-3099

Journal article

Choisy M, McBride A, Chambers M, Ho Quang C, Nguyen Quang H, Xuan Chau NT, Thi GN, Bonell A, Evans M, Ming D, Ngo-Duc T, Quang Thai P, Dang Giang DH, Dan Thanh HN, Ngoc Nhung H, Lowe R, Maude R, Elyazar I, Surendra H, Ashley EA, Thwaites L, van Doorn HR, Kestelyn E, Dondorp AM, Thwaites G, Vinh Chau NV, Yacoub Set al., 2021, Climate change and health in Southeast Asia – defining research priorities and the role of the Wellcome Trust Africa Asia Programmes, Wellcome Open Research, Vol: 6, Pages: 278-278

<ns4:p>This article summarises a recent virtual meeting organised by the Oxford University Clinical Research Unit in Vietnam on the topic of climate change and health, bringing local partners, faculty and external collaborators together from across the Wellcome and Oxford networks. Attendees included invited local and global climate scientists, clinicians, modelers, epidemiologists and community engagement practitioners, with a view to setting priorities, identifying synergies and fostering collaborations to help define the regional climate and health research agenda. In this summary paper, we outline the major themes and topics that were identified and what will be needed to take forward this research for the next decade. We aim to take a broad, collaborative approach to including climate science in our current portfolio where it touches on infectious diseases now, and more broadly in our future research directions. We will focus on strengthening our research portfolio on climate-sensitive diseases, and supplement this with high quality data obtained from internal studies and external collaborations, obtained by multiple methods, ranging from traditional epidemiology to innovative technology and artificial intelligence and community-led research. Through timely agenda setting and involvement of local stakeholders, we aim to help support and shape research into global heating and health in the region.</ns4:p>

Journal article

Pley C, Evans M, Lowe R, Montgomery H, Yacoub Set al., 2021, Digital and technological innovation in vector-borne disease surveillance to predict, detect, and control climate-driven outbreaks, LANCET PLANETARY HEALTH, Vol: 5, Pages: E739-E745

Journal article

Kartsonaki C, 2021, Characteristics and outcomes of an international cohort of 400,000 hospitalised patients with Covid-19

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Policymakers need robust data to respond to the COVID-19 pandemic. We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, the world’s largest international, standardised cohort of hospitalised patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The dataset analysed includes COVID-19 patients hospitalised between January 2020 and May 2021. We investigated how symptoms on admission, comorbidities, risk factors, and treatments varied by age, sex, and other characteristics. We used Cox proportional hazards models to investigate associations between demographics, symptoms, comorbidities, and other factors with risk of death, admission to intensive care unit (ICU), and invasive mechanical ventilation (IMV).</jats:p></jats:sec><jats:sec><jats:title>Findings</jats:title><jats:p>439,922 patients with laboratory-confirmed (91.7%) or clinically-diagnosed (8.3%) SARS-CoV-2 infection from 49 countries were enrolled. Age (adjusted hazard ratio [HR] per 10 years 1.49 [95% CI 1.49-1.50]) and male sex (1.26 [1.24-1.28]) were associated with a higher risk of death. Rates of admission to ICU and use of IMV increased with age up to age 60, then dropped. Symptoms, comorbidities, and treatments varied by age and had varied associations with clinical outcomes. Tuberculosis was associated with an 86% higher risk of death, and HIV with an 87% higher risk of death. Case fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients.</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The size of our international database and the standardized da

Journal article

Sangkaew S, Ming D, Boonyasiri A, Honeyford K, Kalayanarooj S, Yacoub S, Dorigatti I, Holmes Aet al., 2021, Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis, Lancet Infectious Diseases, Vol: 21, Pages: 1014-1026, ISSN: 1473-3099

BACKGROUND: The ability to accurately predict early progression of dengue to severe disease is crucial for patient triage and clinical management. Previous systematic reviews and meta-analyses have found significant heterogeneity in predictors of severe disease due to large variation in these factors during the time course of the illness. We aimed to identify factors associated with progression to severe dengue disease that are detectable specifically in the febrile phase. METHODS: We did a systematic review and meta-analysis to identify predictors identifiable during the febrile phase associated with progression to severe disease defined according to WHO criteria. Eight medical databases were searched for studies published from Jan 1, 1997, to Jan 31, 2020. Original clinical studies in English assessing the association of factors detected during the febrile phase with progression to severe dengue were selected and assessed by three reviewers, with discrepancies resolved by consensus. Meta-analyses were done using random-effects models to estimate pooled effect sizes. Only predictors reported in at least four studies were included in the meta-analyses. Heterogeneity was assessed using the Cochrane Q and I2 statistics, and publication bias was assessed by Egger's test. We did subgroup analyses of studies with children and adults. The study is registered with PROSPERO, CRD42018093363. FINDINGS: Of 6643 studies identified, 150 articles were included in the systematic review, and 122 articles comprising 25 potential predictors were included in the meta-analyses. Female patients had a higher risk of severe dengue than male patients in the main analysis (2674 [16·2%] of 16 481 vs 3052 [10·5%] of 29 142; odds ratio [OR] 1·13 [95% CI 1·01-1·26) but not in the subgroup analysis of studies with children. Pre-existing comorbidities associated with severe disease were diabetes (135 [31·3%] of 431 with vs 868 [16·0%] of 5421 witho

Journal article

McBride A, Mehta P, Rivino L, Ramanan A, Yacoub Set al., 2021, Targeting hyperinflammation in infection: can we harness the COVID-19 therapeutics momentum to end the dengue drugs drought? Comment, LANCET MICROBE, Vol: 2, Pages: E277-E278

Journal article

ISARIC Clinical Characterisation Group, 2021, COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study, Infection: journal of infectious disease, Vol: 49, Pages: 899-905, ISSN: 0300-8126

BACKGROUND: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. METHODS: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. RESULTS: 'Typical' symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. INTERPRETATION: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men.

Journal article

Nguyen LV, Phung KL, Ming DKY, Huynh TLD, Nguyet MN, Dong THT, Kien DTH, Chau NVV, Chanpheaktra N, Lum LCS, Pleites E, Simmons CP, Rosenberger KD, Jaenisch T, Bell D, Acestor N, Halleux C, Olliaro PL, Wills BA, Geskus RB, Yacoub Set al., 2021, Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes, eLife, Vol: 10, ISSN: 2050-084X

Background:Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of 10 biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).Methods:We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.Results:On days 1–3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.Conclusions:Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.Funding:This study was supported by the EU's Seventh Framework Programme (FP7-281803 IDAMS), the WHO, and the Bill and Melinda Gates Foundation.

Journal article

Nguyen LV, Nguyen THQ, Nguyen THT, Nguyen MT, Duong THK, Phung KL, Dong THT, Tran VN, Yacoub S, Jaenisch T, Geskus RB, Simmons CP, Wills BAet al., 2021, Higher Plasma Viremia in the Febrile Phase Is Associated With Adverse Dengue Outcomes Irrespective of Infecting Serotype or Host Immune Status: An Analysis of 5642 Vietnamese Cases, CLINICAL INFECTIOUS DISEASES, Vol: 72, Pages: E1074-E1083, ISSN: 1058-4838

Journal article

Li Bassi G, Suen JY, Dalton HJ, White N, Shrapnel S, Fanning JP, Liquet B, Hinton S, Vuorinen A, Booth G, Millar JE, Forsyth S, Panigada M, Laffey J, Brodie D, Fan E, Torres A, Chiumello D, Corley A, Elhazmi A, Hodgson C, Ichiba S, Luna C, Murthy S, Nichol A, Ng PY, Ogino M, Pesenti A, Huynh TT, Fraser JFet al., 2021, An appraisal of respiratory system compliance in mechanically ventilated covid-19 patients, CRITICAL CARE, Vol: 25, ISSN: 1364-8535

Journal article

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