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Association of COVID-19 with arterial and venous vascular diseases: a population-wide cohort study of 48 million adults in England and Wales

Rochelle Knight, Venexia Walker, Samantha Ip, Jennifer Cooper, Thomas Bolton, Spencer Keene, Rachel Denholm, Ashley Akbari, Hoda Abbasizanjani, Fatemeh Torabi, Efosa Omigie, Sam Hollings, Teri-Louise North, Renin Toms, Emanuele Di Angelantonio, Spiros Denaxas, Johan Thygesen, Christopher Tomlinson, Ben Bray, Craig Smith, Mark Barber, George Davey Smith, Nishi Chaturvedi, Cathie Sudlow, William Whiteley, Angela Wood, Jonathan Sterne, ,

<h4>Importance</h4> The long-term effects of COVID-19 on the incidence of vascular diseases are unclear. <h4>Objective</h4> To quantify the association between time since diagnosis of COVID-19 and vascular disease, overall and by age, sex, ethnicity, and pre-existing disease. <h4>Design</h4> Cohort study based on population-wide linked electronic health records, with follow up ... Read more >>

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Understanding COVID-19 trajectories from a nationwide linked electronic health record cohort of 56 million people: phenotypes, severity, waves & vaccination

Johan Thygesen, Christopher Tomlinson, Sam Hollings, Mehrdad Mizani, Alex Handy, Ashley Akbari, Amitava Banerjee, Jennifer Cooper, Alvina Lai, Ken Li, Bilal Mateen, Naveed Sattar, Reecha Sofat, Ana Torralbo, Honghan Wu, Angela Wood, Jonathan Sterne, Christina Pagel, William Whiteley, Cathie Sudlow, Harry Hemingway, Spiros Denaxas,

<h4>Background</h4> Updatable understanding of the onset and progression of individuals COVID-19 trajectories underpins pandemic mitigation efforts. In order to identify and characterize individual trajectories, we defined and validated ten COVID-19 phenotypes from linked electronic health records (EHR) on a nationwide scale using an extensible framework. <h4>Methods</h4> Cohort study of 56.6 ... Read more >>

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Vaccinating adolescents against SARS-CoV-2 in England: a risk-benefit analysis.

Deepti Gurdasani, Samir Bhatt, Anthony Costello, Spiros Denaxas, Seth Flaxman, Trisha Greenhalgh, Stephen Griffin, Zoë Hyde, Aris Katzourakis, Martin McKee, Susan Michie, Oliver Ratmann, Stephen Reicher, Gabriel Scally, Christopher Tomlinson, Christian Yates, Hisham Ziauddeen, Christina Pagel,

<h4>Objective</h4>To offer a quantitative risk-benefit analysis of two doses of SARS-CoV-2 vaccination among adolescents in England.<h4>Setting</h4>England.<h4>Design</h4>Following the risk-benefit analysis methodology carried out by the US Centers for Disease Control, we calculated historical rates of hospital admission, Intensive Care Unit admission and death for ascertained SARS-CoV-2 cases in children aged 12-17 ... Read more >>

J R Soc Med (Journal of the Royal Society of Medicine)
[2021, :1410768211052589]

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Association of Enzyme-Inducing Antiseizure Drug Use With Long-term Cardiovascular Disease.

Colin B Josephson, Samuel Wiebe, Guillermo Delgado-Garcia, Arturo Gonzalez-Izquierdo, Spiros Denaxas, Tolulope T Sajobi, Mubasiru Lamidi, Meng Wang, Mark R Keezer,

<h4>Importance</h4>Enzyme-inducing antiseizure medications (eiASMs) have been hypothesized to be associated with long-term risks of cardiovascular disease.<h4>Objective</h4>To quantify and model the putative hazard of cardiovascular disease secondary to eiASM use.<h4>Design, setting, and participants</h4>This cohort study covered January 1990 to March 2019 (median [IQR] follow-up, 9 [4-15], years). The study linked primary ... Read more >>

JAMA Neurol (JAMA neurology)
[2021, 78(11):1367-1374]

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An informatics consult approach for generating clinical evidence for treatment decisions.

Alvina G Lai, Wai Hoong Chang, Constantinos A Parisinos, Michail Katsoulis, Ruth M Blackburn, Anoop D Shah, Vincent Nguyen, Spiros Denaxas, George Davey Smith, Tom R Gaunt, Krishnarajah Nirantharakumar, Murray P Cox, Donall Forde, Folkert W Asselbergs, Steve Harris, Sylvia Richardson, Reecha Sofat, Richard J B Dobson, Aroon Hingorani, Riyaz Patel, Jonathan Sterne, Amitava Banerjee, Alastair K Denniston, Simon Ball, Neil J Sebire, Nigam H Shah, Graham R Foster, Bryan Williams, Harry Hemingway,

<h4>Background</h4>An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication ... Read more >>

BMC Med Inform Decis Mak (BMC medical informatics and decision making)
[2021, 21(1):281]

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Development and Validation of a Primary Care Electronic Health Record Phenotype to Study Migration and Health in the UK

Neha Pathak, Claire Zhang, Yamina Boukari, Rachel Burns, Rohini Mathur, Arturo Gonzalez-Izquierdo, Spiros Denaxas, Pam Sonnenberg, Andrew Hayward, Robert Aldridge,

International migrants comprised 14% of the UK population in 2020, but migrant health in the UK has rarely been studied at a population level using primary care electronic health records (EHRs). Given the difficulty of determining migration status using EHRs, this study developed a migration phenotype and assessed its validity. ... Read more >>

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'We have been in lockdown since he was born': a mixed methods exploration of the experiences of families caring for children with intellectual disability during the COVID-19 pandemic in the UK.

Jeanne Wolstencroft, Laura Hull, Lauren Warner, Tooba Nadeem Akhtar, William Mandy, , David Skuse,

<h4>Objectives</h4>This study aimed to explore the experiences of parents caring for children with intellectual and developmental disabilities (IDD) during the UK national lockdown in spring 2020, resulting from the COVID-19 pandemic.<h4>Design</h4>Participants were identified using opportunity sampling from the IMAGINE-ID national (UK) cohort and completed an online survey followed by a ... Read more >>

BMJ Open (BMJ open)
[2021, 11(9):e049386]

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A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the Remote Early Detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial.

Timo B Brakenhoff, Billy Franks, Brianna Mae Goodale, Janneke van de Wijgert, Santiago Montes, Duco Veen, Eskild K Fredslund, Theo Rispens, Lorenz Risch, Ariel V Dowling, Amos A Folarin, Patricia Bruijning, Richard Dobson, Tessa Heikamp, Paul Klaver, Maureen Cronin, Diederick E Grobbee, ,

<h4>Objectives</h4>It is currently thought that most-but not all-individuals infected with SARS-CoV-2 develop symptoms, but the infectious period starts on average 2 days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals before ... Read more >>

Trials (Trials)
[2021, 22(1):694]

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Emergency department attendance after telephone triage

Spiros Denaxas, Holger Kunz, Liam Smeeth, Arturo Gonzalez-Izquierdo, Harry Boutselakis, Maria Pikoula, Harry Hemingway,

Int J Popul Data Sci (International journal of population data science)
[0, 1(1):]

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Evaluation of antithrombotic use and COVID-19 outcomes in a nationwide atrial fibrillation cohort

Alex Handy, Amitava Banerjee, Angela Wood, Caroline Dale, Cathie Sudlow, Christopher Tomlinson, Daniel Bean, Johan Thygesen, Mehrdad Mizani, Michail Katsoulis, Reecha Sofat, Richard Dobson, Rohan Takhar, Sam Hollings, Spiros Denaxas, Venexia Walker,

<h4>ABSTRACT</h4> <h4>Objective</h4> Evaluate antithrombotic (AT) use in individuals with atrial fibrillation (AF) and high stroke risk (CHA 2 DS 2 -VASc score>=2) and investigate whether pre-existing AT use may improve COVID-19 outcomes. <h4>Methods</h4> Individuals with AF and a CHA 2 DS 2 -VASc score>=2 on January 1 st 2020 were ... Read more >>

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Desiderata for the development of next-generation electronic health record phenotype libraries.

Martin Chapman, Shahzad Mumtaz, Luke V Rasmussen, Andreas Karwath, Georgios V Gkoutos, Chuang Gao, Dan Thayer, Jennifer A Pacheco, Helen Parkinson, Rachel L Richesson, Emily Jefferson, Spiros Denaxas, Vasa Curcin,

<h4>Background</h4>High-quality phenotype definitions are desirable to enable the extraction of patient cohorts from large electronic health record repositories and are characterized by properties such as portability, reproducibility, and validity. Phenotype libraries, where definitions are stored, have the potential to contribute significantly to the quality of the definitions they host. In ... Read more >>

Gigascience (GigaScience)
[2021, 10(9):]

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The genomics of heart failure: design and rationale of the HERMES consortium.

R Thomas Lumbers, Sonia Shah, Honghuang Lin, Tomasz Czuba, Albert Henry, Daniel I Swerdlow, Anders Mälarstig, Charlotte Andersson, Niek Verweij, Michael V Holmes, Johan Ärnlöv, Per Svensson, Harry Hemingway, Neneh Sallah, Peter Almgren, Krishna G Aragam, Geraldine Asselin, Joshua D Backman, Mary L Biggs, Heather L Bloom, Eric Boersma, Jeffrey Brandimarto, Michael R Brown, Hans-Peter Brunner-La Rocca, David J Carey, Mark D Chaffin, Daniel I Chasman, Olympe Chazara, Xing Chen, Xu Chen, Jonathan H Chung, William Chutkow, John G F Cleland, James P Cook, Simon de Denus, Abbas Dehghan, Graciela E Delgado, Spiros Denaxas, Alexander S Doney, Marcus Dörr, Samuel C Dudley, Gunnar Engström, Tõnu Esko, Ghazaleh Fatemifar, Stephan B Felix, Chris Finan, Ian Ford, Francoise Fougerousse, René Fouodjio, Mohsen Ghanbari, Sahar Ghasemi, Vilmantas Giedraitis, Franco Giulianini, John S Gottdiener, Stefan Gross, Daníel F Guðbjartsson, Hongsheng Gui, Rebecca Gutmann, Christopher M Haggerty, Pim van der Harst, Åsa K Hedman, Anna Helgadottir, Hans Hillege, Craig L Hyde, Jaison Jacob, J Wouter Jukema, Frederick Kamanu, Isabella Kardys, Maryam Kavousi, Kay-Tee Khaw, Marcus E Kleber, Lars Køber, Andrea Koekemoer, Bill Kraus, Karoline Kuchenbaecker, Claudia Langenberg, Lars Lind, Cecilia M Lindgren, Barry London, Luca A Lotta, Ruth C Lovering, Jian'an Luan, Patrik Magnusson, Anubha Mahajan, Douglas Mann, Kenneth B Margulies, Nicholas A Marston, Winfried März, John J V McMurray, Olle Melander, Giorgio Melloni, Ify R Mordi, Michael P Morley, Andrew D Morris, Andrew P Morris, Alanna C Morrison, Michael W Nagle, Christopher P Nelson, Christopher Newton-Cheh, Alexander Niessner, Teemu Niiranen, Christoph Nowak, Michelle L O'Donoghue, Anjali T Owens, Colin N A Palmer, Guillaume Paré, Markus Perola, Louis-Philippe Lemieux Perreault, Eliana Portilla-Fernandez, Bruce M Psaty, Kenneth M Rice, Paul M Ridker, Simon P R Romaine, Carolina Roselli, Jerome I Rotter, Christian T Ruff, Marc S Sabatine, Perttu Salo, Veikko Salomaa, Jessica van Setten, Alaa A Shalaby, Diane T Smelser, Nicholas L Smith, Kari Stefansson, Steen Stender, David J Stott, Garðar Sveinbjörnsson, Mari-Liis Tammesoo, Jean-Claude Tardif, Kent D Taylor, Maris Teder-Laving, Alexander Teumer, Guðmundur Thorgeirsson, Unnur Thorsteinsdottir, Christian Torp-Pedersen, Stella Trompet, Danny Tuckwell, Benoit Tyl, Andre G Uitterlinden, Felix Vaura, Abirami Veluchamy, Peter M Visscher, Uwe Völker, Adriaan A Voors, Xiaosong Wang, Nicholas J Wareham, Peter E Weeke, Raul Weiss, Harvey D White, Kerri L Wiggins, Heming Xing, Jian Yang, Yifan Yang, Laura M Yerges-Armstrong, Bing Yu, Faiez Zannad, Faye Zhao, , Jemma B Wilk, Hilma Holm, Naveed Sattar, Steven A Lubitz, David E Lanfear, Svati Shah, Michael E Dunn, Quinn S Wells, Folkert W Asselbergs, Aroon D Hingorani, Marie-Pierre Dubé, Nilesh J Samani, Chim C Lang, Thomas P Cappola, Patrick T Ellinor, Ramachandran S Vasan, J Gustav Smith,

<h4>Aims</h4>The HERMES (HEart failure Molecular Epidemiology for Therapeutic targetS) consortium aims to identify the genomic and molecular basis of heart failure.<h4>Methods and results</h4>The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected ... Read more >>

ESC Heart Fail (ESC heart failure)
[2021, :]

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The association between mechanical ventilator compatible bed occupancy and mortality risk in intensive care patients with COVID-19: a national retrospective cohort study.

Harrison Wilde, Thomas Mellan, Iwona Hawryluk, John M Dennis, Spiros Denaxas, Christina Pagel, Andrew Duncan, Samir Bhatt, Seth Flaxman, Bilal A Mateen, Sebastian J Vollmer,

<h4>Background</h4>The literature paints a complex picture of the association between mortality risk and ICU strain. In this study, we sought to determine if there is an association between mortality risk in intensive care units (ICU) and occupancy of beds compatible with mechanical ventilation, as a proxy for strain.<h4>Methods</h4>A national retrospective ... Read more >>

BMC Med (BMC medicine)
[2021, 19(1):213]

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Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records.

Michail Katsoulis, Alvina G Lai, Karla Diaz-Ordaz, Manuel Gomes, Laura Pasea, Amitava Banerjee, Spiros Denaxas, Kostas Tsilidis, Pagona Lagiou, Gesthimani Misirli, Krishnan Bhaskaran, Goya Wannamethee, Richard Dobson, Rachel L Batterham, Dimitra-Kleio Kipourou, R Thomas Lumbers, Lan Wen, Nick Wareham, Claudia Langenberg, Harry Hemingway,

<h4>Background</h4>Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight ... Read more >>

Lancet Diabetes Endocrinol (The lancet. Diabetes & endocrinology)
[2021, 9(10):681-694]

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Weight Change and the Onset of Cardiovascular Diseases: Emulating Trials Using Electronic Health Records.

Michail Katsoulis, Bianca D Stavola, Karla Diaz-Ordaz, Manuel Gomes, Alvina Lai, Pagona Lagiou, Goya Wannamethee, Konstantinos Tsilidis, R Thomas Lumbers, Spiros Denaxas, Amitava Banerjee, Constantinos A Parisinos, Rachel Batterham, Riyaz Patel, Claudia Langenberg, Harry Hemingway,

<h4>Background</h4>Cross-sectional measures of body mass index (BMI) are associated with cardiovascular disease (CVD) incidence, but less is known about whether weight change affects the risk of CVD.<h4>Methods</h4>We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from coronary heart disease, ... Read more >>

Epidemiology (Epidemiology (Cambridge, Mass.))
[2021, 32(5):744-755]

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Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, and thrombocytopenic events: whole population cohort study in 46 million adults in England

, William Whiteley, Samantha Ip, Jennifer Cooper, Thomas Bolton, Spencer Keene, Venexia Walker, Rachel Denholm, Ashley Akbari, Efosa Omigie, Sam Hollings, Emanuele Di Angelantonio, Spiros Denaxas, Angela Wood, Jonathan Sterne, Cathie Sudlow,

<h4>ABSTRACT</h4> <h4>Importance</h4> Thromboses after the COVID-19 vaccine ChAdOx1-S have been reported. Better understanding of population-level thrombotic risks after COVID-19 vaccination is needed. <h4>Objective</h4> Quantify associations of vaccination with ChAdOx1-S and BNT162b2 with major arterial, venous and thrombocytopenic events. <h4>Design</h4> Cohort study based on linked electronic health records, with follow up ... Read more >>

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The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus risk in people taking antidepressants and antipsychotics

Isabelle Austin-Zimmerman, Marta Wronska, Baihan Wang, Haritz Irizar, Johan Hilge Thygesen, Anjali Bhat, Spiros Denaxas, Ghazaleh Fatemifar, Chris Finan, Jasmine Harju-Seppänen, Olga Giannakopoulou, Karoline Kuchenbaecker, Eirini Zartaloudi, Andrew McQuillin, Elvira Bramon,

<h4>Background</h4> CYP2D6 and CYP2C19 enzymes are essential in the metabolism of antidepressants and antipsychotics. Genetic variation in these genes may increase risk of adverse drug reactions. Antidepressants and antipsychotics have previously been associated with risk of diabetes. We examined whether individual genetic differences in CYP2D6 and CYP2C19 contribute to these ... Read more >>

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A prospective, randomized, single-blinded, crossover trial to investigate the effect of a wearable device in addition to a daily symptom diary for the remote early detection of SARS-CoV-2 infections (COVID-RED): a structured summary of a study protocol for a randomized controlled trial.

Timo B Brakenhoff, Billy Franks, Brianna Mae Goodale, Janneke van de Wijgert, Santiago Montes, Duco Veen, Eskild K Fredslund, Theo Rispens, Lorenz Risch, Ariel V Dowling, Amos A Folarin, Patricia Bruijning, Richard Dobson, Tessa Heikamp, Paul Klaver, Maureen Cronin, Diederick E Grobbee, ,

<h4>Objectives</h4>It is currently thought that most-but not all-individuals infected with SARS-CoV-2 develop symptoms, but that the infectious period starts on average two days before the first overt symptoms appear. It is estimated that pre- and asymptomatic individuals are responsible for more than half of all transmissions. By detecting infected individuals ... Read more >>

Trials (Trials)
[2021, 22(1):412]

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Healthcare resource utilisation and mortality outcomes in international migrants to the UK: analysis protocol for a linked population-based cohort study using Clinical Practice Research Datalink (CPRD), Hospital Episode Statistics (HES) and the Office for National Statistics (ONS)

Neha Pathak, Parth Patel, Rachel Burns, Lucinda Haim, Claire Zhang, Yamina Boukari, Arturo Gonzales-Izquierdo, Rohini Mathur, Caroline Minassian, Alexandra Pitman, Spiros Denaxas, Harry Hemingway, Andrew Hayward, Pam Sonnenberg, Robert Aldridge,

An estimated 14.2% (9.34 million people) of people living in the UK in 2019 were international migrants. Despite this, there are no large-scale national studies of their healthcare resource utilisation and little is known about how migrants access and use healthcare services. One ongoing study of migration health in the ... Read more >>

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Machine learning for subtype definition and risk prediction in heart failure, acute coronary syndromes and atrial fibrillation: systematic review of validity and clinical utility.

Amitava Banerjee, Suliang Chen, Ghazaleh Fatemifar, Mohamad Zeina, R Thomas Lumbers, Johanna Mielke, Simrat Gill, Dipak Kotecha, Daniel F Freitag, Spiros Denaxas, Harry Hemingway,

<h4>Background</h4>Machine learning (ML) is increasingly used in research for subtype definition and risk prediction, particularly in cardiovascular diseases. No existing ML models are routinely used for cardiovascular disease management, and their phase of clinical utility is unknown, partly due to a lack of clear criteria. We evaluated ML for subtype ... Read more >>

BMC Med (BMC medicine)
[2021, 19(1):85]

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Healthcare use by people who use illicit opioids (HUPIO): development of a cohort based on electronic primary care records in England

Dan Lewer, Prianka Padmanathan, Muhammad Qummer ul Arfeen, Spiros Denaxas, Harriet Forbes, Arturo Gonzalez-Izquierdo, Matt Hickman,

Background: People who use illicit opioids such as heroin have substantial health needs, but there are few longitudinal studies of general health and healthcare in this population. Most research to date has focused on a narrow set of outcomes, including overdoses and HIV or hepatitis infections. We developed and validated ... Read more >>

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Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade.

Roy Schwartz, Alasdair Warwick, Abraham Olvera-Barrios, Maria Pikoula, Aaron Y Lee, Spiros Denaxas, Paul Taylor, Catherine Egan, Usha Chakravarthy, Peck Lin Lip, Adnan Tufail, ,

<h4>Purpose</h4>Management of neovascular age-related macular degeneration (nAMD) has evolved over the last decade with several treatment regimens and medications. This study describes the treatment patterns and visual outcomes over 10 years in a large cohort of patients.<h4>Design</h4>Retrospective analysis of electronic health records from 27 National Health Service secondary care healthcare ... Read more >>

Ophthalmol Retina (Ophthalmology. Retina)
[2021, 5(8):e11-e22]

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Relationship Between Glycemia and Cognitive Function, Structural Brain Outcomes, and Dementia: A Mendelian Randomization Study in the UK Biobank.

Victoria Garfield, Aliki-Eleni Farmaki, Ghazaleh Fatemifar, Sophie V Eastwood, Rohini Mathur, Christopher T Rentsch, Spiros Denaxas, Krishnan Bhaskaran, Liam Smeeth, Nish Chaturvedi,

We investigated the relationship between glycemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomization (MR). Data were from the UK Biobank (<i>n</i> = ∼500,000). Our exposures were genetic instruments for type 2 diabetes (157 variants) and HbA<sub>1c</sub> (51 variants) and our outcomes were reaction time (RT), ... Read more >>

Diabetes (Diabetes)
[2021, 70(10):2313-2321]

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Linked electronic health records for research on a nationwide cohort of more than 54 million people in England: data resource.

Angela Wood, Rachel Denholm, Sam Hollings, Jennifer Cooper, Samantha Ip, Venexia Walker, Spiros Denaxas, Ashley Akbari, Amitava Banerjee, William Whiteley, Alvina Lai, Jonathan Sterne, Cathie Sudlow, ,

<h4>Objective</h4>To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust.<h4>Design</h4>Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital's new trusted research ... Read more >>

BMJ (BMJ (Clinical research ed.))
[2021, 373:n826]

Cited: 4 times

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Internal-external cross-validation helped to evaluate the generalizability of prediction models in large clustered datasets.

Toshihiko Takada, Steven Nijman, Spiros Denaxas, Kym I E Snell, Alicia Uijl, Tri-Long Nguyen, Folkert W Asselbergs, Thomas P A Debray,

<h4>Objective</h4>To illustrate how to evaluate the need of complex strategies for developing generalizable prediction models in large clustered datasets.<h4>Study design and setting</h4>We developed eight Cox regression models to estimate the risk of heart failure using a large population-level dataset. These models differed in the number of predictors, the functional form ... Read more >>

J Clin Epidemiol (Journal of clinical epidemiology)
[2021, 137:83-91]

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