Imperial College London

Professor the Lord Darzi of Denham PC KBE FRS FMedSci HonFREng

Faculty of MedicineDepartment of Surgery & Cancer

Co-Director of the IGHI, Professor of Surgery
 
 
 
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Contact

 

+44 (0)20 3312 1310a.darzi

 
 
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Location

 

Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

2002 results found

Philpott-Morgan S, Thakrar DB, Symons J, Ray D, Ashrafian H, Darzi Aet al., 2021, Characterising the nationwide burden and predictors of unkept outpatient appointments in the National Health Service in England: A cohort study using a machine learning approach, PLOS Medicine, Vol: 18, Pages: e1003783-e1003783

<jats:sec id="sec001"><jats:title>Background</jats:title><jats:p>Unkept outpatient hospital appointments cost the National Health Service £1 billion each year. Given the associated costs and morbidity of unkept appointments, this is an issue requiring urgent attention. We aimed to determine rates of unkept outpatient clinic appointments across hospital trusts in the England. In addition, we aimed to examine the predictors of unkept outpatient clinic appointments across specialties at Imperial College Healthcare NHS Trust (ICHT). Our final aim was to train machine learning models to determine the effectiveness of a potential intervention in reducing unkept appointments.</jats:p></jats:sec><jats:sec id="sec002"><jats:title>Methods and findings</jats:title><jats:p>UK Hospital Episode Statistics outpatient data from 2016 to 2018 were used for this study. Machine learning models were trained to determine predictors of unkept appointments and their relative importance. These models were gradient boosting machines. In 2017–2018 there were approximately 85 million outpatient appointments, with an unkept appointment rate of 5.7%. Within ICHT, there were almost 1 million appointments, with an unkept appointment rate of 11.2%. Hepatology had the highest rate of unkept appointments (17%), and medical oncology had the lowest (6%). The most important predictors of unkept appointments included the recency (25%) and frequency (13%) of previous unkept appointments and age at appointment (10%). A sensitivity of 0.287 was calculated overall for specialties with at least 10,000 appointments in 2016–2017 (after data cleaning). This suggests that 28.7% of patients who do miss their appointment would be successfully targeted if the top 10% least likely to attend received an intervention. As a result, an intervention targeting the top 10% of likely non-attenders, in the full population of pati

Journal article

Sounderajah V, Ashrafian H, Rose S, Shah NH, Ghassemi M, Golub R, Kahn CE, Esteva A, Karthikesalingam A, Mateen B, Webster D, Milea D, Ting D, Treanor D, Cushnan D, King D, McPherson D, Glocker B, Greaves F, Harling L, Ordish J, Cohen JF, Deeks J, Leeflang M, Diamond M, McInnes MDF, McCradden M, Abràmoff MD, Normahani P, Markar SR, Chang S, Liu X, Mallett S, Shetty S, Denniston A, Collins GS, Moher D, Whiting P, Bossuyt PM, Darzi Aet al., 2021, A quality assessment tool for artificial intelligence-centered diagnostic test accuracy studies: QUADAS-AI., Nat Med, Vol: 27, Pages: 1663-1665

Journal article

Elliott J, Whitaker M, Bodinier B, Eales O, Riley S, Ward H, Cooke G, Darzi A, Chadeau M, Elliott Pet al., 2021, Predictive symptoms for COVID-19 in the community: REACT-1 study of over one million people, PLoS Medicine, ISSN: 1549-1277

Background:Rapid detection, isolation and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and whether predictive symptoms differ between B.1.1.7 (Alpha) lineage (predominating as of April 2021in the USA, UK and elsewhere) and wild type.Methods and Findings:We obtained throat and nose swabs with valid SARS-CoV-2 polymerase chain reaction (PCR) test results from 1,147,370 volunteers aged 5 years and above (6,450 positives) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least one symptom identified seven symptoms as jointly and positively predictive of PCR positivity in rounds 2–7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss and muscle aches. The resulting model (rounds 2–7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same seven symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. Main

Journal article

Clarke J, Flott K, Crespo R, Ashrafian H, Fontana G, Benger J, Darzi A, Elkin Set al., 2021, Assessing the Safety of Home Oximetry for Covid-19: A multi-site retrospective observational study, BMJ Open, Vol: 11, Pages: 1-9, ISSN: 2044-6055

Objectives To determine the safety and effectiveness of home oximetry monitoring pathways safe for Covid-19 patients in the English NHS.Design Retrospective, multi-site, observational study of home oximetry monitoring for patients with suspected or proven Covid-19 Setting This study analysed patient data from four Covid-19 home oximetry pilot sites in England across primary and secondary care settings.Participants A total of 1338 participants were enrolled in a home oximetry programme across four pilot sites. Participants were excluded if primary care data and oxygen saturations are rest at enrolment were not available. Data from 908 participants was included in the analysis. Interventions Home oximetry monitoring was provided to participants with a known or suspected diagnosis of Covid-19. Participants were enrolled following attendance to emergency departments, hospital admission or referral through primary care services. Results Of 908 patients enrolled into four different Covid-19 home oximetry programmes in England, 771 (84.9%) had oxygen saturations at rest of 95% or more, and 320 (35.2%) were under 65 years of age and without comorbidities. 52 (5.7%) presented to hospital and 28 (3.1%) died following enrolment, of which 14 (50%) had Covid-19 as a named cause of death. All-cause mortality was significantly higher in patients enrolled after admission to hospital (OR 8.70 [2.53-29.89]), compared to those enrolled in primary care. Patients enrolled after hospital discharge (OR 0.31 [0.15-0.68]) or emergency department presentation (OR 0.42 [0.20-0.89]) were significantly less likely to present to hospital than those enrolled in primary care. ConclusionsThis study find that home oximetry monitoring can be a safe pathway for Covid-19 patients; and indicates increases in risk to vulnerable groups and patients with oxygen saturations < 95% at enrolment, and in those enrolled on discharge from hospital. Findings from this evaluation have contributed to the national

Journal article

Che Bakri NA, Kwasnicki RM, Dhillon K, Khan N, Ghandour O, Cairns A, Darzi A, Leff DRet al., 2021, ASO visual abstract: objective assessment of postoperative morbidity following breast cancer treatments with wearable activity monitors: The "BRACELET" study., Annals of Surgical Oncology, ISSN: 1068-9265

Journal article

Moussa O, Ardissino M, Eichhorn C, Reddy RK, Khan O, Ziprin P, Darzi A, Collins P, Purkayastha Set al., 2021, Atrial fibrillation and obesity: long-term incidence and outcomes after bariatric surgery, European Journal of Preventive Cardiology, Vol: 28, Pages: e22-e24, ISSN: 2047-4873

Journal article

Nazarian S, Lam K, Darzi A, Ashrafian Het al., 2021, The diagnostic accuracy of smartwatches for the detection of cardiac arrhythmia: a systematic review and meta-analysis, Journal of Medical Internet Research, Vol: 23, ISSN: 1438-8871

Background:A significant morbidity, mortality and financial burden is associated with cardiac rhythm abnormalities. Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Conventional screening tools are often unsuccessful at detecting AF due to its episodic nature. Smartwatches have gained popularity in recent years as a health screening tool.Objective:The aim of our study was to systematically review and meta-analyse the diagnostic accuracy of smartwatches in the detection of cardiac arrhythmias.Methods:A comprehensive literature search was undertaken using the databases of EMBASE, Medline and the Cochrane Library. PRISMA guidance was followed. Studies reporting use of a smartwatch for detection of cardiac arrythmia were included. Independent proportion and their differences were calculated and pooled through DerSimonian and Laird random-effects modelling. Quality was assessed using the QUADAS-2 tool.Results:A total of 18 studies were analysed, measuring diagnostic accuracy in 424, 371 subjects in total. The overall sensitivity, specificity and accuracy of smartwatches to detect cardiac arrhythmias was 100% (95% CI 0.99-1.00), 95% (95% CI 0.93-0.97) and 97% (95% CI 0.96-0.99), respectively. The pooled PPV and NPV for detecting cardiac arrythmias was 85% 85% (95% CI 0.79-0.90) and 100% (95% CI 1.0-1.0), respectively.Conclusions:This review demonstrates the evolving field of digital disease screening and the increased role of machine learning in healthcare. The current diagnostic accuracy of smartwatch technology for detection of cardiac arrhythmias is high. Whilst the innovative drive of digital devices in healthcare screening will continue to gain momentum, the process of accurate evidence accrual and regulatory standards ready to accept their introduction is strongly needed. Clinical Trial: PROSPERO registration number: CRD42020213237

Journal article

Neves AL, Li E, Serafini A, Gimenez GL, Lingner H, Koskela T, Hoffman RD, Collins C, Petek D, Claveria A, Tsopra R, Irving G, Gusso G, O'Neill BG, Hoedebecke K, Espitia SM, Ungan M, Nessler K, Lazic V, Laranjo L, Ensieh M, Fernandez MJ, Ghafur S, Fontana G, Majeed A, Car J, Darzi Aet al., 2021, Evaluating the impact of COVID-19 on the adoption of virtual care in general practice in 20 countries (inSIGHT): rationale and study protocol, Journal of Medical Internet Research, Vol: 10, ISSN: 1438-8871

Background: In recent decades, virtual care has emerged as a promising option to support primary care delivery. However, despite the potential, adoption rates remained low. With the outbreak of COVID-19, it has suddenly been pushed to the forefront of care delivery. As we progress into the second year of the COVID-19 pandemic, there is a need and opportunity to review the impact remote care had in primary care settings and reassess its potential future role. This study aims to explore the perspectives of General Practitioners (GPs) / Family Doctors on a.) use of virtual care during the COVID-19 pandemic; b.) perceived impact on quality and safety of care; c.) essential factors for high-quality and sustainable use of virtual care in the future. Methods: Online cross-sectional questionnaire of GPs, distributed across 20 countries. The survey was hosted in Qualtrics and distributed using email, social media, and the researchers’ personal contact networks. General Practitioners were eligible for the survey if they were working mainly in primary care during the period of the COVID-19 pandemic. Descriptive statistical analysis will be performed for quantitative variables, and relationships between the use of virtual care and perceptions on impact on quality and safety of care, and participants’ characteristics, may be explored. Qualitative data (free-text responses) will be analysed using framework analysis. Results: Data collection took place from June to September 2020. As of this manuscript’s submission, a total of 1,605 GP respondents participated in the questionnaire. Further data analysis is currently ongoing. Discussion: The study will provide a comprehensive overview of the availability of virtual care technologies, perceived impact on quality and safety of care and essential factors for high-quality future use. In addition, a description of the under

Journal article

Kedrzycki MS, Leiloglou M, Chalau V, Chiarini N, Thiruchelvam PTR, Hadjiminas DJ, Hogben KR, Rashid F, Ramakrishnan R, Darzi AW, Elson DS, Leff DRet al., 2021, ASO visual abstract: the impact of temporal variation in indocyanine green administration on tumor identification during fluorescence-guided breast surgery, Annals of Surgical Oncology, ISSN: 1068-9265

Journal article

Neves AL, Li E, Gupta PP, Fontana G, Darzi Aet al., 2021, Virtual primary care in high-income countries during the COVID-19 pandemic: policy responses and lessons for the future, European Journal of General Practice, Vol: 27, Pages: 241-247, ISSN: 1381-4788

Background: Telemedicine, once defined merely as the treatment of certain conditions remotely, has now often been supplanted in use by broader terms such as ‘virtual care’, in recognition of its increasing capability to deliver a diverse range of healthcare services from afar. With the unexpected onset of COVID-19, virtual care (e.g., telephone, video, online) has become essential to facilitating the continuation of primary care globally. Over several short weeks, existing healthcare policies have adapted quickly and empowered clinicians to use digital means to fulfil a wide range of clinical responsibilities which until then, have required face-to-face consultations. Objective: This paper aims to explore the virtual care policies and guidance material published during the initial months of the pandemic and examine their potential limitations and impact on transforming the delivery of primary care in high-income countries. Methods: A rapid review of publicly available national policies guiding the use of virtual care in General Practice was conducted. Documents were included if issued in the first six months of the pandemic (March to August of 2020) and focused primarily on high-income countries. Documents must have been issued by a national health authority, accreditation body, or professional organisation, and directly refer to the delivery of primary care. Results: We extracted six areas of relevance: primary care transformation during COVID-19, the continued delivery of preventative care, the delivery of acute care, remote triaging, funding & reimbursement, and security standards.Conclusion: Virtual care use in primary care saw a transformative change during the pandemic. However, despite the advances in the various governmental guidance offered, much work remains in addressing the shortcomings exposed during COVID-19 and strengthening viable policies so as to better incorporate novel technologies into the modern primary care clinical

Journal article

Che Bakri NA, Kwasnicki RM, Dhillon K, Khan N, Ghandour O, Cairns A, Darzi A, Leff DRet al., 2021, ASO author reflections: Improving management of upper limb complications after breast cancer treatments, Annals of Surgical Oncology, ISSN: 1068-9265

Journal article

Eales O, Walters C, Wang H, Haw D, Ainslie K, Atchison C, Page A, Prosolek S, Trotter A, Viet TL, Alikhan N-F, Jackson LM, Ludden C, COG UK TCGUKC, Ashby D, Donnelly C, Cooke G, Barclay W, Ward H, Darzi A, Elliott P, Riley Set al., 2021, Characterising the persistence of RT-PCR positivity and incidence in a community survey of SARS-CoV-2

BackgroundCommunity surveys of SARS-CoV-2 RT-PCR swab-positivity provide prevalence estimates largely unaffected by biases from who presents for routine case testing. The REal-time Assessment of Community Transmission-1 (REACT-1) has estimated swab-positivity approximately monthly since May 2020 in England from RT-PCR testing of self-administeredthroat and nose swabs in random non-overlapping cross-sectional community samples. Estimating infection incidence from swab-positivity requires an understanding of the persistence of RT-PCR swab positivity in the community.MethodsDuring round 8 of REACT-1 from 6 January to 22 January 2021, of the 2,282 participants who tested RT-PCR positive, we recruited 896 (39%) from whom we collected up to two additional swabs for RT-PCR approximately 6 and 9 days after the initial swab. We estimated sensitivity and duration of positivity using an exponential model of positivity decay, for all participants and for subsets by initial N-gene cycle threshold (Ct) value, symptom status, lineage and age. Estimates of infection incidence were obtained for the entire duration of the REACT-1 study using P-splines.ResultsWe estimated the overall sensitivity of REACT-1 to detect virus on a single swab as 0.79 (0.77, 0.81) and median duration of positivity following a positive test as 9.7 (8.9, 10.6) days. We found greater median duration of positivity where there was a low N-gene Ct value, in those exhibiting symptoms, or for infection with the Alpha variant. The estimated proportionof positive individuals detected on first swab, was found to be higher ­ŁĹâ for those with an 0 initially low N-gene Ct value and those who were pre-symptomatic. When compared to swab-positivity, estimates of infection incidence over the duration of REACT-1 included sharper features with evident transient increases around the time of key changes in socialdistancing measures.DiscussionHome self-swabbing for RT-PCR based on a single swab, as implemented in REACT-1, has hig

Working paper

Mason SE, Manoli E, Alexander JL, Poynter L, Ford L, Paizs P, Adebesin A, McKenzie JS, Rosini F, Goldin R, Darzi A, Takats Z, Kinross JMet al., 2021, Lipidomic profiling of colorectal lesions for real-time tissue recognition and risk-stratification using rapid evaporative ionisation mass spectrometry., Annals of Surgery, ISSN: 0003-4932

OBJECTIVE: Rapid Evaporative Ionisation Mass Spectrometry (REIMS) is a metabolomic technique analysing tissue metabolites, which can be applied intra-operatively in real-time. The objective of this study was to profile the lipid composition of colorectal tissues using REIMS, assessing its accuracy for real-time tissue recognition and risk-stratification. SUMMARY BACKGROUND DATA: Metabolic dysregulation is a hallmark feature of carcinogenesis, however it remains unknown if this can be leveraged for real-time clinical applications in colorectal disease. METHODS: Patients undergoing colorectal resection were included, with carcinoma, adenoma and paired-normal mucosa sampled. Ex vivo analysis with REIMS was conducted using monopolar diathermy, with the aerosol aspirated into a Xevo G2S QToF mass spectrometer. Negatively charged ions over 600-1000m/z were used for univariate and multivariate functions including linear discriminant analysis. RESULTS: 161 patients were included, generating 1013 spectra. Unique lipidomic profiles exist for each tissue type, with REIMS differentiating samples of carcinoma, adenoma and normal mucosa with 93 1% accuracy and 96 1% negative predictive value for carcinoma. Neoplasia (carcinoma or adenoma) could be predicted with 96 0% accuracy and 91 8% negative predictive value. Adenomas can be risk-stratified by grade of dysplasia with 93 5% accuracy, but not histological subtype. The structure of 61 lipid metabolites was identified, revealing that during colorectal carcinogenesis there is progressive increase in relative abundance of phosphatidylglycerols, sphingomyelins and mono-unsaturated fatty acid containing phospholipids. CONCLUSIONS: The colorectal lipidome can be sampled by REIMS and leveraged for accurate real-time tissue recognition, in addition to risk-stratification of colorectal adenomas. Unique lipidomic features associated with carcinogenesis are described.

Journal article

Runciman M, Avery J, Darzi A, Mylonas Get al., 2021, Open loop position control of soft hydraulic actuators for minimally invasive surgery, Applied Sciences-Basel, Vol: 11, Pages: 1-16, ISSN: 2076-3417

Minimally invasive surgery (MIS) presents many constraints on the design of robotic devices that can assist medical staff with a procedure. The limitations of conventional, rigid robotic devices have sparked interest in soft robotic devices for medical applications. However, problems still remain with the force exertion and positioning capabilities of soft robotic actuators, in conjunction with size restrictions necessary for MIS. In this article we present hydraulically actuated soft actuators that demonstrate highly repeatable open loop positioning and the ability to exert significant forces in the context of MIS. Open loop position control is achieved by changing the actuator volume, which causes contraction. In one degree of freedom (DOF) configurations, root mean square error (RMSE) values of 0.471 mm, 1.506 mm, and 0.350 mm were recorded for a single actuator against gravity, a single actuator with a pulley, and a horizontal antagonistic configuration, respectively. Hysteresis values of 0.711 mm, 0.958 mm, and 0.515 mm were reported in these experiments. In addition, different numbers of soft actuators were used in configurations two and three DOFs to demonstrate position control. When deactivated, the soft actuators are low-profile and flexible as they are constructed from thin films. As such, a robot with a deployable structure and three soft actuators was constructed. The robot is therefore able to reversibly transition from low to high volume and stiffness, which has potential applications in MIS. A user successfully controlled the deployable robot in a circle tracing task.

Journal article

Acharya A, Lam K, Danielli S, Ashrafian H, Darzi Aet al., 2021, COVID-19 vaccinations among Black Asian and Minority Ethnic (BAME) groups: Learning the lessons from influenza, International Journal of Clinical Practice, Vol: 75, Pages: 1-3, ISSN: 1368-5031

BackgroundThe COVID-19 vaccination roll-out continues to grow at significant pace around the world. There is, however, growing concern regarding vaccine hesitancy amongst Black, Asian and Minority Ethnic (BAME) populations. Such inequalities have the potential for exposing, an already at-risk population, further. Whilst the COVID-19 vaccination programme is in its infancy, influenza programmes have been undertaken for over 50 years, and may provide invaluable insights. In this commentary, we aim to examine the lessons from influenza vaccinations, and how this can help reduce inequalities with COVID-19 vaccinations.Main TextSeveral factors have been associated with both seasonal and pandemic influenza vaccine hesitancy amongst BAME groups. One of the most prevalent barriers in both types of immunisation programmes is the mistrust of medical organisations. This is often a multi-faceted issue, with previous negative healthcare discrimination, and historical unethical practices contributing towards this scepticism. This mistrust, however, is predominantly aimed towards healthcare systems, as opposed to individual physicians. In fact, physician endorsement is often a strong driver to vaccination, with Black patients who receive this support 8 times more likely to receive seasonal influenza vaccination. On the other hand, with H1N1 pandemic influenza vaccination, social norms or community influence, was an important determinant. In both seasonal and pandemic immunisation programmes, a significant amount of concern regarding side-effects, including misinformation, was reported amongst BAME groups.ConclusionsThe use of community-based approaches, with local advocacy, has the potential to counteract misinformation, and concerns regarding side-effects. Moreover, using consistent physician endorsement not only in media campaigns but also through messaging would potentially help to address longstanding healthcare mistrust amongst minority ethnic groups. Close attention regardin

Journal article

Elliott P, Haw D, Wang H, Eales O, Walters C, Ainslie K, Atchison C, Fronterre C, Diggle P, Page A, Trotter A, Prosolek S, COG-UK TCGUKC, Ashby D, Donnelly C, Barclay W, Cooke G, Ward H, Darzi A, Riley Set al., 2021, REACT-1 round 13 final report: exponential growth, high prevalence of SARS-CoV-2 and vaccine effectiveness associated with Delta variant in England during May to July 2021

BackgroundThe prevalence of SARS-CoV-2 infection continues to drive rates of illness andhospitalisations despite high levels of vaccination, with the proportion of cases caused by theDelta lineage increasing in many populations. As vaccination programs roll out globally andsocial distancing is relaxed, future SARS-CoV-2 trends are uncertain.MethodsWe analysed prevalence trends and their drivers using reverse transcription-polymerasechain reaction (RT-PCR) swab-positivity data from round 12 (between 20 May and 7 June2021) and round 13 (between 24 June and 12 July 2021) of the REal-time Assessment ofCommunity Transmission-1 (REACT-1) study, with swabs sent to non-overlapping randomsamples of the population ages 5 years and over in England.ResultsWe observed sustained exponential growth with an average doubling time in round 13 of 25days (lower Credible Interval of 15 days) and an increase in average prevalence from 0.15%(0.12%, 0.18%) in round 12 to 0.63% (0.57%, 0.18%) in round 13. The rapid growth acrossand within rounds appears to have been driven by complete replacement of Alpha variant byDelta, and by the high prevalence in younger less-vaccinated age groups, with a nine-foldincrease between rounds 12 and 13 among those aged 13 to 17 years. Prevalence amongthose who reported being unvaccinated was three-fold higher than those who reported beingfully vaccinated. However, in round 13, 44% of infections occurred in fully vaccinatedindividuals, reflecting imperfect vaccine effectiveness against infection despite high overalllevels of vaccination. Using self-reported vaccination status, we estimated adjusted vaccineeffectiveness against infection in round 13 of 49% (22%, 67%) among participants aged 18to 64 years, which rose to 58% (33%, 73%) when considering only strong positives (Cyclethreshold [Ct] values < 27); also, we estimated adjusted vaccine effectiveness againstsymptomatic infection of 59% (23%, 78%), with any one of three common COVID-19symptoms reported

Working paper

Kedrzycki MS, Leiloglou M, Chalau V, Chiarini N, Thiruchelvam PTR, Hadjiminas DJ, Hogben KR, Rashid F, Ramakrishnan R, Darzi AW, Elson DS, Leff DRet al., 2021, The impact of temporal variation in indocyanine green administration on tumor identification during fluorescence guided breast surgery., Annals of Surgical Oncology, Vol: 28, Pages: 5617-5625, ISSN: 1068-9265

BACKGROUND: On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system. METHODS: In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected ~ 25 min prior to tumor excision, and in the second 'angiography' cohort, ~ 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts. RESULTS: The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 ± 1.74 vs 2.10 ± 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099). DISCUSSION: ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer.

Journal article

Neves AL, Pereira Rodrigues P, Mulla A, Glampson B, Willis T, Mayer Eet al., 2021, Using electronic health records to develop and validate a machine learning tool to predict type 2 diabetes outcomes: a study protocol, BMJ Open, Vol: 11, Pages: 1-5, ISSN: 2044-6055

Introduction: Type 2 diabetes (T2DM) is a major cause of blindness, kidney failure, myocardial infarction, stroke and lower limb amputation. We are still unable, however, to accurately predict or identify which patients are at a higher risk of deterioration. Most risk stratification tools do not account for novel factors such as socio-demographic determinants, self-management ability, or access to healthcare. Additionally, most tools are based in clinical trials, with limited external generalisability.Objective: The aim of this work is to design and validate a machine learning-based tool to identify patients with T2DM at high risk of clinical deterioration, based on a comprehensive set of patient level characteristics retrieved from a population health linked dataset.Sample and design: Retrospective cohort study of patients with diagnosis of T2DM on Jan 1st, 2015, with a 5-year follow-up. Anonymised electronic health care records from the Whole System Integrated Care (WSIC) database will be used. Preliminary outcomes: Outcome variables of clinical deterioration will include retinopathy, chronic renal disease, myocardial infarction, stroke, peripheral arterial disease, or death. Predictor variables will include sociodemographic and geographic data, patients’ ability to self-manage disease, clinical and metabolic parameters and healthcare service usage. Prognostic models will be defined using multi-dependence Bayesian networks (BN). The derivation cohort, comprising 80% of the patients, will be used to define the prognostic models. Model parameters will be internally validated by comparing the area under the receiver operating characteristic (ROC) curve (AUC) in the derivation cohort with those calculated from a leave-one-out and a 10 times 2-fold cross-validation. Ethics and dissemination: The study has received approvals from the Information Governance Committee at the Whole Systems Integrated Care. Results will be made available to people with type 2 diabetes

Journal article

Stalteri Mastrangelo R, Santesso N, Bognanni A, Darzi A, Karam S, Piggott T, Baldeh T, Sch├╝nemann F, Ventresca M, Morgano GP, Moja L, Loeb M, Schunemann Het al., 2021, Consideration of antimicrobial resistance and contextual factors in infectious disease guidelines: a systematic survey., BMJ Open, Vol: 11, Pages: 1-10, ISSN: 2044-6055

OBJECTIVES: Guidelines that include antimicrobial recommendations should explicitly consider contextual factors that influence antimicrobial resistance and their downstream effects on resistance selection. The objectives were to analyse (1) how, and to what extent, tuberculosis, gonorrhoea and respiratory tract infection guidelines are considering antimicrobial resistance; (2) are of acceptable quality and (3) if they can be easily contextualised to fit the needs of specific populations and health systems. METHODS: We conducted a systematic review and searched Ovid MEDLINE and Embase from 1 January 2007 to 7 June 2019 for tuberculosis, gonorrhoea and respiratory tract infection guidelines published in English. We also searched guideline databases, key websites and reference lists. We identified guidelines and recommendations that considered contextual factors including antimicrobial resistance, values, resource use, equity, acceptability and feasibility. We assessed quality of the guidelines using the Appraisal of Guidelines for Research and Evaluation II tool focusing on the domains scope and purpose, rigour of development, and editorial independence. RESULTS: We screened 10 365 records, of which 74 guidelines met inclusion criteria. Of these guidelines, 39% (n=29/74) met acceptable quality scores. Approximately two-thirds of recommendations considered antimicrobial resistance at the population and/or outcome level. Five of the 29 guidelines reported all factors required for recommendation contextualisation. Equity was the least considered across guidelines. DISCUSSION: Relatively few guidelines for highly prevalent infectious diseases are considering resistance at a local level, and many do not consider contextual factors necessary for appropriate antimicrobial use. Improving the quality of guidelines targeting specific regional areas is required. PROSPERO REGISTRATION NUMBER: CRD42020145235.

Journal article

Williams SP, Purkayastha S, Chaturvedi S, Darzi Aet al., 2021, The GP-OH (General Practice - Organizational Health) Survey: Development and Validation of a Novel Instrument to Measure Organizational Health in General Practice., Hosp Top, Pages: 1-11

Primary care healthcare organizations are complex and multidimensional, and there has been much discussion about the potential dangers of focusing on outcomes as quality indicators in isolation without understanding the processes and system characteristics that drive them. Organizational health, as a concept, shifts the focus of measurement upstream and considers the elements needed for sustainable long-term success. This study has both designed and tested the first survey seeking to measure organizational health specifically within the context of primary care. A stepwise approach was taken to ensure that the validity and reliability of the survey was examined at multiple stages.Supplemental data for this article is available online at https://doi.org/10.1080/00185868.2021.1947164.

Journal article

Che Bakri NA, Kwasnicki R, Dhillon K, Ghandour O, Khan N, Cairns A, Darzi A, Leff Det al., 2021, Objective assessment of post-operative morbidity following breast cancer treatments with wearable activity monitors, Annals of Surgical Oncology, Vol: 28, Pages: 5597-5606, ISSN: 1068-9265

BackgroundCurrent validated tools to measure upper limb dysfunction after breast cancer treatment, such as questionnaires, are prone to recall bias and do not enable comparisons between patients. This study aimed to test the feasibility of wearable activity monitors (WAMs) for achieving a continuous, objective assessment of functional recovery by measuring peri-operative physical activity (PA).MethodsA prospective, single-center, non-randomized, observational study was conducted. Patients undergoing breast and axillary surgery were invited to wear WAMs on both wrists in the peri-operative period and then complete upper limb function (DASH) and quality-of-life (EQ-5D-5L) questionnaires. Statistical analyses were performed to determine the construct validity and concurrent validity of WAMs.ResultsThe analysis included 39 patients with a mean age of 55 ± 13.2 years. Regain of function on the surgically treated side was observed to be an increase of arm activity as a percentage of preoperative levels, with the greatest increase observed between the postoperative days 1 and 2. The PA was significantly greater on the side not treated by surgery than on the surgically treated side after week 1 (mean PA, 75.8% vs. 62.3%; p < 0.0005) and week 2 (mean PA, 91.6% vs. 77.4%; p < 0.005). Subgroup analyses showed differences in recovery trends between different surgical procedures. Concurrent validity was demonstrated by a significant negative moderate correlation between the PA and DASH questionnaires (R = −0.506; p < 0.05).ConclusionThis study demonstrated the feasibility and validity of WAMs to objectively measure postoperative recovery of upper limb function after breast surgery, providing a starting point for personalized rehabilitation through early detection of upper limb physical morbidity.

Journal article

Ward H, Atchison C, Whitaker M, Donnelly CA, Riley S, Ashby D, Darzi A, Barclay WS, Cooke G, Elliott Pet al., 2021, Increasing SARS-CoV-2 antibody prevalence in England at the start of the second wave: REACT-2 Round 4 cross-sectional study in 160,000 adults

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>REACT-2 Study 5 is a population survey of the prevalence of SARS-CoV-2 antibodies in the community in England.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We contacted a random sample of the population by sending a letter to named individuals aged 18 or over from the NHS GP registrations list. We then sent respondents a lateral flow immunoassay (LFIA) kit for SARS-CoV-2 antibody self-testing and asked them to perform the test at home and complete a questionnaire, including reporting of their test result. Overall, 161,537 adults completed questionnaires and self-administered LFIA tests for IgG against SARS-CoV-2 between 27 October and 10 November 2020.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The overall adjusted and weighted prevalence was 5.6% (95% CI 5.4-5.7). This was an increase from 4.4% (4.3-4.5) in round 3 (September), a relative increase of 26.9% (24.0-29.9).The largest increase by age was in the 18 to 24 year old age group, which increased (adjusted and weighted) from 6.7% (6.3-7.2) to 9.9% (9.3-10.4), and in students, (adjusted, unweighted) from 5.9% (4.8-7.1) to 12.1% (10.8-13.5). Prevalence increased most in Yorkshire and The Humber, from 3.4% (3.0-3.8) to 6.3% (5.9-6.8) and the North West from 4.5% (4.2-4.9) to 7.7% (7.2-8.1). In contrast, the prevalence in London was stable, at 9.5% (9.0-9.9) and 9.5% (9.1-10.0) in rounds 3 and 4 respectively. We found the highest prevalence in people of Bangladeshi 15.1% (10.9-20.5), Pakistani 13.9% (11.2-17.2) and African 13.5% (10.7-16.8) ethnicity, and lowest in those of white British ethnicity at 4.2% (4.0-4.3).</jats:p></jats:sec><jats:sec><jats:title>Interpretation</jats:title><jats:p>The second wave of infection in England is apparen

Journal article

Morgano GP, Wiercioch W, Anderson DR, Bro┼╝ek JL, Santesso N, Xie F, Cuker A, Nieuwlaat R, Akl EA, Darzi AJ, Yepes-Nu├▒ez JJ, Exteandia-Ikobaltzeta I, Rahman M, Rajasekhar A, Rogers F, Tikkinen KAO, Yates AJ, Dahm P, Sch├╝nemann HJet al., 2021, A modeling approach to derive baseline risk estimates for GRADE recommendations: Concepts, development, and results of its application to the American Society of Hematology 2019 guidelines on prevention of venous thromboembolism in surgical hospitalized patients., J Clin Epidemiol, Vol: 140, Pages: 69-78

OBJECTIVE: The goal of this study was to develop an approach that can be used where baseline risk estimates that are directly applicable to prioritized patient-important outcomes are not available from published studies. STUDY DESIGN: The McMaster University GRADE Centre and the ASH guideline panel for the prevention of VTE in surgical patients developed a modeling approach based on explicit assumptions about the distribution of symptoms, anatomical location, and severity of VTE events. RESULTS: We applied the approach to derive modeled estimates of baseline risk. These estimates were used to calculated absolute measures of anticipated effects that informed the discussion of the evidence and the formulation of 30 guideline recommendations. CONCLUSION: Our approach can assist guideline developers facing a lack of information about baseline risk estimates that directly apply to outcomes of interest. The use of modeled estimates increases transparency in the process and makes the baseline risk used by guideline experts explicit during their decision-making.

Journal article

Ward H, Whitaker M, Tang SN, Atchison C, Darzi A, Donnelly C, Diggle P, Ashby D, Riley S, Barclay W, Elliott P, Cooke Get al., 2021, Vaccine uptake and SARS-CoV-2 antibody prevalence among 207,337 adults during May 2021 in England: REACT-2 study

Background The programme to vaccinate adults in England has been rapidly implementedsince it began in December 2020. The community prevalence of SARS-CoV-2 anti-spikeprotein antibodies provides an estimate of total cumulative response to natural infection andvaccination. We describe the distribution of SARS-CoV-2 IgG antibodies in adults inEngland in May 2021 at a time when approximately 7 in 10 adults had received at least onedose of vaccine.Methods Sixth round of REACT-2 (REal-time Assessment of Community Transmission-2),a cross-sectional random community survey of adults in England, from 12 to 25 May 2021;207,337 participants completed questionnaires and self-administered a lateral flowimmunoassay test producing a positive or negative result.Results Vaccine coverage with one or more doses, weighted to the adult population inEngland, was 72.9% (95% confidence interval 72.7-73.0), varying by age from 25.1% (24.5-25.6) of those aged 18 to 24 years, to 99.2% (99.1-99.3) of those 75 years and older. Inadjusted models, odds of vaccination were lower in men (odds ratio [OR] 0.89 [0.85-0.94])than women, and in people of Black (0.41 [0.34-0.49]) compared to white ethnicity. Therewas higher vaccine coverage in the least deprived and highest income households. Peoplewho reported a history of COVID-19 were less likely to be vaccinated (OR 0.61 [0.55-0.67]).There was high coverage among health workers (OR 9.84 [8.79-11.02] and care workers (OR4.17 [3.20-5.43]) compared to non-key workers, but lower in hospitality and retail workers(OR 0.73 [0.64-0.82] and 0.77 [0.70-0.85] respectively) after adjusting for age and keycovariates.

Working paper

Li E, Clarke J, Neves AL, Ashrafian H, Darzi Aet al., 2021, Electronic health records, interoperability, and patient safety in health systems of high-income countries: a systematic review protocol, BMJ Open, Vol: 11, ISSN: 2044-6055

Introduction The availability and routine use of electronic health records (EHRs) have become commonplace in healthcare systems of many high-income countries. While there is an ever-growing body ofliterature pertaining to EHR use, evidence surrounding the importance of EHR interoperability and its impact on patient safety remains less clear. There is therefore a need and opportunity to evaluate the evidence available regarding this relationship so as to better inform health informatics development and policies in the years to come. This systematic review aims to evaluate the impact of EHR interoperability on patient safety in health systems of high-income countries. Methods and analysis A systematic literature review will be conducted via a computerised search through four databases: PubMed, Embase, HMIC, and PsycInfo for relevant articles published between 2010 and 2020. Outcomes of interest will include: impact on patient safety, and the broader effects on health systems. Quality of the randomised quantitative studies will be assessed using Cochrane Risk of Bias Tool. Non-randomised papers will be evaluated with the Risk of Bias In Non Randomised Studies - of Interventions (ROBINS-I) tool. Drummond’s Checklist will be utilised for publications pertaining to economic evaluation. The National Institute for Health and Care Excellence (NICE) quality appraisal checklist will be used to assess qualitative studies. A narrative synthesis will be conducted for included studies, and the body of evidence will be summarised in a summary of findings table. Ethics and dissemination This review will summarise published studies with non-identifiable data and thus does not require ethical approval. Findings will be disseminated through preprints, open access peer reviewed publication, and conference presentations

Journal article

Nazarian S, Glover B, Ashrafian H, Darzi A, Teare Jet al., 2021, Diagnostic Accuracy of Artificial Intelligence and Computer-Aided Diagnosis for the Detection and Characterization of Colorectal Polyps: Systematic Review and Meta-analysis, JOURNAL OF MEDICAL INTERNET RESEARCH, Vol: 23, ISSN: 1438-8871

Journal article

Riley S, Eales O, Haw D, Wang H, Walters C, Ainslie K, Christina A, Fronterre C, Diggle P, Ashby D, Donnelly C, Barclay W, Cooke G, Ward H, Darzi A, Elliott Pet al., 2021, REACT-1 round 13 interim report: acceleration of SARS-CoV-2 Delta epidemic in the community in England during late June and early July 2021

BackgroundDespite high levels of vaccination in the adult population, cases of COVID-19 have risenexponentially in England since the start of May 2021 driven by the Delta variant. However,with far fewer hospitalisations and deaths per case during the recent growth in casescompared with 2020, it is intended that all remaining social distancing legislation in Englandwill be removed from 19 July 2021.MethodsWe report interim results from round 13 of the REal-time Assessment of CommunityTransmission-1 (REACT-1) study in which a cross-sectional sample of the population ofEngland was asked to provide a throat and nose swab for RT-PCR and to answer aquestionnaire. Data collection for this report (round 13 interim) was from 24 June to 5 July2021.ResultsIn round 13 interim, we found 237 positives from 47,729 swabs giving a weighted prevalenceof 0.59% (0.51%, 0.68%) which was approximately four-fold higher compared with round 12at 0.15% (0.12%, 0.18%). This resulted from continued exponential growth in prevalencewith an average doubling time of 15 (13, 17) days between round 12 and round 13.However, during the recent period of round 13 interim only, we observed a shorter doublingtime of 6.1 (4.0, 12) days with a corresponding R number of 1.87 (1.40, 2.45). There weresubstantial increases in all age groups under the age of 75 years, and especially at youngerages, with the highest prevalence in 13 to 17 year olds at 1.33% (0.97%, 1.82%) and in 18 to24 years olds at 1.40% (0.89%, 2.18%). Infections have increased in all regions with thelargest increase in London where prevalence increased more than eight-fold from 0.13%(0.08%, 0.20%) in round 12 to 1.08% (0.79%, 1.47%) in round 13 interim. Overall,prevalence was over 3 times higher in the unvaccinated compared with those reporting twodoses of vaccine in both round 12 and round 13 interim, although there was a similarproportional increase in prevalence in vaccinated and unvaccinated individuals between thetwo rounds.DiscussionWe

Working paper

Aggarwal R, Farag S, Martin G, Ashrafian H, Darzi Aet al., 2021, Patient perceptions on data sharing and applying artificial intelligence to healthcare data: a cross sectional survey, Journal of Medical Internet Research, Vol: 23, Pages: 1-12, ISSN: 1438-8871

Background:Considerable research is being conducted as to how artificial intelligence (AI) can be effectively applied to healthcare. However, for it to be successful, large amounts of health data are required for the training and testing of algorithms. Data sharing for this purpose is controversial, therefore it is imperative to understand patient perceptions on this.Objective:To understand the perspectives and viewpoints of patients regarding the use of their health data in AI research.Methods:A cross-sectional survey with patients was conducted at a large multi-site teaching hospital in the United Kingdom. Data were collected on patient and public views about sharing health data for research and the use of AI on health data.Results:A total of 408 participants completed the survey. Respondents had low levels of prior knowledge of AI in general. Most were comfortable with sharing health data with the NHS (77·9%) or universities (65·7%), but far fewer with commercial organisations such as technology companies (26·4%). The majority endorsed AI research on healthcare data (76·8%) and healthcare imaging (76·4%) in a university setting, providing that concerns about privacy, re-identification of anonymised health care data and consent processes were addressed.Conclusions:There is significant variance in patient perceptions, levels of support, and understanding of health data research and AI. There is a need for greater public engagement and debate to ensure the acceptability of AI research and its successful integration into clinical practice in the future.

Journal article

Chan C, Sounderajah V, Daniels E, Acharya A, Clarke J, Yalamanchili S, Normahani P, Markar S, Ashrafian H, Darzi Aet al., 2021, The reliability and quality of YouTube videos as a source of public health information regarding COVID-19 vaccination: cross-sectional study, JMIR Public Health and Surveillance, Vol: 7, ISSN: 2369-2960

Background: Recent emergency authorization and rollout of COVID-19 vaccines by regulatory bodies has generated global attention. As the most popular video-sharing platform globally, YouTube is a potent medium for the dissemination of key public health information. Understanding the nature of available content regarding COVID-19 vaccination on this widely used platform is of substantial public health interest.Objective: This study aimed to evaluate the reliability and quality of information on COVID-19 vaccination in YouTube videos.Methods: In this cross-sectional study, the phrases “coronavirus vaccine” and “COVID-19 vaccine” were searched on the UK version of YouTube on December 10, 2020. The 200 most viewed videos of each search were extracted and screened for relevance and English language. Video content and characteristics were extracted and independently rated against Health on the Net Foundation Code of Conduct and DISCERN quality criteria for consumer health information by 2 authors.Results: Forty-eight videos, with a combined total view count of 30,100,561, were included in the analysis. Topics addressed comprised the following: vaccine science (n=18, 58%), vaccine trials (n=28, 58%), side effects (n=23, 48%), efficacy (n=17, 35%), and manufacturing (n=8, 17%). Ten (21%) videos encouraged continued public health measures. Only 2 (4.2%) videos made nonfactual claims. The content of 47 (98%) videos was scored to have low (n=27, 56%) or moderate (n=20, 42%) adherence to Health on the Net Foundation Code of Conduct principles. Median overall DISCERN score per channel type ranged from 40.3 (IQR 34.8-47.0) to 64.3 (IQR 58.5-66.3). Educational channels produced by both medical and nonmedical professionals achieved significantly higher DISCERN scores than those of other categories. The highest median DISCERN scores were achieved by educational videos produced by medical professionals (64.3, IQR 58.5-66.3) and the lowest median scores by indep

Journal article

Lett A, Lim A, Skinner C, Maurice J, Vergis N, Darzi A, Goldin R, Thursz M, Thompson Aet al., 2021, Rapid, non-invasive measurement of gastric emptying rate using transcutaneous fluorescence spectroscopy, Biomedical Optics Express, Vol: 12, Pages: 4249-4264, ISSN: 2156-7085

Gastric emptying rate (GER) signifies the rate at which the stomach empties following ingestion of a meal and is relevant to a wide range of clinical conditions. GER also represents a rate limiting step in small intestinal absorption and so is widely assessed for research purposes. Despite the clinical and physiological importance of gastric emptying, methods used to measure GER possess a series of limitations (including being invasive, slow or unsuitable for certain patient populations). Here, we present a new technique based on transcutaneous (through-the-skin) fluorescence spectroscopy that is fast, non-invasive, and does not require the collection of samples or laboratory-based analysis. Thus, this approach has the potential to allow immediate reporting of clinical results. Using this new method, participants receive an oral dose of a fluorescent contrast agent and a wearable probe detects the uptake of the agent from the gut into the blood stream. Analysis of the resulting data then permits the calculation of GER. We compared our spectroscopic technique to the paracetamol absorption test (a clinically approved GER test) in a clinical study of 20 participants. Results demonstrated good agreement between the two approaches and, hence, the clear potential of transcutaneous fluorescence spectroscopy for clinical assessment of GER.

Journal article

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