Julia Hippisley-Cox

• Professor (Full) at University of Oxford

Cancer prediction algorithms are used in the UK to identify individuals at high probability of having a current, as yet undiagnosed cancer with the intention of improving early diagnosis and treatment. Here we develop and externally validate two diagnostic prediction algorithms to estimate the probability of having cancer for 15 cancer types. The f...

Background Sotrovimab is a neutralising monoclonal antibody (nMAB) currently available to treat extremely clinically vulnerable COVID-19 patients in England. Trials have shown it to have mild to moderate side effects, however, evidence regarding its safety in real-world settings remains insufficient. Methods Descriptive and multivariable logistic...

Background Antidepressants’ effects are established in randomised controlled trials (RCTs), but not in the real world. Aims To investigate real-world comparative effects of antidepressants for depression and compare them with RCTs. Method We performed a cohort study based on the QResearch database. We included people with a newly recorded diagnos...

Background Lung cancer is a leading cause of mortality, yet disparities in lung cancer across different sociodemographic groups in the UK remain unclear. This study investigates ethnicity and sociodemographic disparities and differences in lung cancer in a nationally representative English cohort, aiming to highlight inequalities and promote equita...

Electronic health records can be used to facilitate research in pregnancy. This work describes the construction of a novel algorithm to create a unified pregnancy cohort in the QResearch database, during the initial phases of the COVID-19 pandemic, for England. National GP records in the QResearch® database were linked to patient-level data from Ho...

Objectives To explore symptoms and symptom combinations associated with a subsequent cancer diagnosis in children, teenagers and young adults (0–24 years) and to establish their timeframe. Methods Using the QResearch Database, a nationally representative primary care database linked to secondary care data and the National Cancer Registry, we carri...

Background Childhood, teenage and young adult (CTYA, 0–24 years) cancers are rare and diverse, making timely diagnosis challenging. We aim to explore symptoms and symptom combinations associated with a subsequent cancer diagnosis and to establish their timeframe. Methods Using the QResearch Database, we carried out a matched nested case-control st...

Background Childhood, teenage and young adult (CTYA, 0-24 years) cancers are rare and diverse, making timely diagnosis challenging. Studies based on adult cancers suggest that the development and integration of clinical decision tools in primary care aid earlier cancer detection, yet, these have not been explored for CTYA cancers. Aim To develop a...

Background There is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers. Methods Women newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (G...

Background Dysmenorrhoea affects up to 94% of adolescents who menstruate; approximately one third miss school and activities. Dysmenorrhoea can occur without identified pelvic pathology (primary dysmenorrhoea) or in association with other conditions (secondary dysmenorrhoea). In adolescence, the commonest cause of secondary dysmenorrhoea is endomet...

Background The diagnosis of B-cell lymphoma, one of the commonest cancers seen in childhood and adolescence, is challenging. There is a crucial need to identify and delineate the prevalence of associated symptoms in order to improve early diagnosis. Aims To identify clinical presentations associated with childhood and adolescent B-cell lymphomas a...

Background Immunocompromised individuals are at increased risk of severe COVID-19 outcomes, underscoring the importance of COVID-19 vaccination in this population. The lack of comprehensive real-world data on vaccine uptake, effectiveness and safety in these individuals presents a critical knowledge gap, highlighting the urgency to better understan...

The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse ev...

Background The National Institute for Health and Care Excellence (NICE) recommends that people aged 60+ years with newly diagnosed diabetes and weight loss undergo abdominal imaging to assess for pancreatic cancer. More nuanced stratification could lead to enrichment of these referral pathways. Methods Population-based cohort study of adults aged...

Purpose Incidence of bleeding amongst warfarin and direct oral anticoagulant (DOAC) users is greater following a respiratory tract infection (RTI). It is unclear whether immediate antibiotics modify this association. We estimated the risk of bleeding amongst warfarin and DOAC users with RTI by antibiotic treatment. Methods This retrospective cohor...

QRISK algorithms use data from millions of people to help clinicians identify individuals at high risk of cardiovascular disease (CVD). Here, we derive and externally validate a new algorithm, which we have named QR4, that incorporates novel risk factors to estimate 10-year CVD risk separately for men and women. Health data from 9.98 million and 6....

Objective The QCovid 2 and 3 algorithms are risk prediction tools developed during the second wave of the COVID-19 pandemic that can be used to predict the risk of COVID-19 hospitalisation and mortality, taking vaccination status into account. In this study, we assess their performance in Scotland. Methods We used the Early Pandemic Evaluation and...

Background Over time, the performance of clinical prediction models may deteriorate due to changes in clinical management, data quality, disease risk and/or patient mix. Such prediction models must be updated in order to remain useful. In this study, we investigate dynamic model updating of clinical survival prediction models. In contrast to discre...

Background There is an increasing demand for mental health services for young people, which may vary across the year. Objective To determine whether there are seasonal patterns in primary care antidepressant prescribing and mental health issues in adolescents and young adults. Methods This cohort study used anonymised electronic health records fr...

Background: Identifying female individuals at highest risk of developing life-threatening breast cancers could inform novel stratified early detection and prevention strategies to reduce breast cancer mortality, rather than only considering cancer incidence. We aimed to develop a prognostic model that accurately predicts the 10-year risk of breast...

Immunocompromised individuals face increased risks of severe COVID-19 outcomes, underscoring the importance of receiving COVID-19 vaccination. However, there's a lack of comprehensive real-world data on their COVID-19 vaccine uptake, effectiveness, and safety profile. We analysed data in the QResearch UK database from 01/12/2020 to 11/04/2022. We i...

Background: Methods to identify patients at increased risk of oesophageal cancer are needed to better identify those for targeted screening. We aimed to derive and validate novel risk prediction algorithms (CanPredict) to estimate the 10-year risk of oesophageal cancer and evaluate performance against two other risk prediction models. Methods: P...

Background: Weather and seasons, or stressful periods associated with their education could affect young people's mental health. Members of a young person's advisory group asked us to investigate whether there are particular periods in the year when adolescents have more mental health issues. Aim: To examine whether there are different seasonal...

Objectives To derive and validate risk prediction algorithms (QCOVID4) to estimate the risk of covid-19 related death and hospital admission in people with a positive SARS-CoV-2 test result during the period when the omicron variant of the virus was predominant in England, and to evaluate performance compared with a high risk cohort from NHS Digita...

Introduction At the start of the COVID-19 pandemic there was an urgent need to identify individuals at highest risk of severe outcomes, such as hospitalisation and death following infection. The QCOVID risk prediction algorithms emerged as key tools in facilitating this which were further developed during the second wave of the COVID-19 pandemic to...

Objective To develop a clinically useful model that estimates the 10 year risk of breast cancer related mortality in women (self-reported female sex) with breast cancer of any stage, comparing results from regression and machine learning approaches. Design Population based cohort study. Setting QResearch primary care database in England, with ind...

Background Liver cancer has one of the fastest rising incidence and mortality rates among all cancers in the UK, but it receives little attention. This study aims to understand the disparities in epidemiology and clinical pathways of primary liver cancer and identify the gaps for early detection and diagnosis of liver cancer in England. Methods Th...

Over time, the performance of clinical prediction models may deteriorate due to changes in clinical management, data quality, disease risk and/or patient mix. Such prediction models must be updated in order to remain useful. Here, we investigate methods for discrete and dynamic model updating of clinical survival prediction models based on refittin...

Background: Lung cancer is the second most common cancer in incidence and the leading cause of cancer deaths worldwide. Meanwhile, lung cancer screening with low-dose CT can reduce mortality. The UK National Screening Committee recommended targeted lung cancer screening on Sept 29, 2022, and asked for more modelling work to be done to help refine...

Objectives Uptake of influenza, pneumococcal and shingles vaccines in older adults vary across regions and socioeconomic backgrounds. In this study, we study the coverage and factors associated with vaccination uptake, as well as refusal in the unvaccinated population and their associations with ethnicity, deprivation, household size and health con...

Background: HBV is the leading global cause of cirrhosis and primary liver cancer. However, the UK HBV population has not been well characterised, and estimates of UK HBV prevalence and/or incidence vary widely between sources. We aimed to i) extract and summarise existing national HBV prevalence estimates, ii) add a new estimate based on primary c...

Heterogeneous studies have demonstrated ethnic inequalities in the risk of SARS-CoV-2 infection and adverse COVID-19 outcomes. This study evaluates the association between ethnicity and COVID-19 outcomes in two large population-based cohorts from England and Canada and investigates potential explanatory factors for ethnic patterning of severe outco...

Introduction Dysmenorrhoea affects up to 70%–91% of adolescents who menstruate, with approximately one-third experiencing severe symptoms with impacts on education, work and leisure. Dysmenorrhoea can occur without identifiable pathology, but can indicate underlying conditions, including congenital genital tract anomalies or endometriosis. There is...

Background: People with blood cancers have increased risk of severe outcomes from COVID-19 and were prioritised for vaccination. Methods: Individuals in the QResearch database aged 12 years and above on 1st December 2020 were included in the analysis. Kaplan-Meier analysis described time to COVID-19 vaccine uptake in people with blood cancer and...

Background The COVID-19 pandemic has affected millions of people globally with major health, social and economic consequences, prompting development of vaccines for use in the general population. However, vaccination uptake is lower in some groups, including in pregnant women, because of concerns regarding vaccine safety. There is evidence of incre...

Importance Evidence indicates that preexisting neuropsychiatric conditions confer increased risks of severe outcomes from COVID-19 infection. It is unclear how this increased risk compares with risks associated with other severe acute respiratory infections (SARIs). Objective To determine whether preexisting diagnosis of and/or treatment for a neu...

Objective To evaluate the benefit of combining polygenic risk scores with the QCancer-10 (colorectal cancer) prediction model for non-genetic risk to identify people at highest risk of colorectal cancer. Design Population based cohort study. Setting Data from the UK Biobank study, collected between March 2006 and July 2010. Participants 434 587...

Background and research aim The incidence and mortality of liver cancer have been increasing in the UK in recent years. However, liver cancer is still under-studied. The Early Detection of Hepatocellular Liver Cancer (DeLIVER-QResearch) project aims to address the research gap and generate new knowledge to improve early detection and diagnosis of p...

Introduction This study aims to explore the impact of COVID-19 vaccination on critical care by examining associations between vaccination and admission to critical care with COVID-19 during England's Delta wave, by age group, dose, and over time. Methods We used linked routinely-collected data to conduct a population cohort study of patients admitt...

Background Concerns have been raised that angiotensin-converting enzyme-inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) might facilitate transmission of severe acute respiratory syndrome coronavirus 2 leading to more severe coronavirus disease (COVID-19) disease and an increased risk of mortality. We aimed to investigate the association...

Objectives To explore associations between COVID-19 vaccination and admission to critical care with COVID-19 in England, by age group, dose, and over time. ApproachWe conducted a population cohort study by linking the Case Mix Programme national clinical audit of adult intensive care to the National Immunisation Management System, combined with pop...

OBJECTIVE: To assess the risk of COVID-19 death following infection from Omicron BA.1 relative to Delta (B.1.617.2). DESIGN: Retrospective cohort study. SETTING: England, UK, 1 December 2021 to 30 December 2021. PARTICIPANTS: 1,035,149 people aged 18-100 years who tested positive for SARS-CoV-2 in the national surveillance programme, and had an inf...

Background: Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain. Methods: A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December...

Sotrovimab is a neutralising monoclonal antibody (nMAB), currently administrated in England to treat extremely clinically vulnerable COVID-19 patients. Trials have shown it to have mild or moderate side effects, however safety in real-world settings has not been yet evaluated. We used national databases to investigate its uptake and safety in commu...

To (a) derive and validate risk prediction algorithms (QCovid4) to estimate risk of COVID-19 mortality and hospitalisation in UK adults with a SARS-CoV-2 positive test during the Omicron pandemic wave and (b) evaluate performance with earlier versions of algorithms developed in previous pandemic waves and the high-risk cohort identified by NHS Digi...

Background: HBV is the leading global cause of cirrhosis and primary liver cancer. However, the UK HBV population has not been well characterised, and estimates of UK HBV prevalence and/or incidence vary widely between sources. We summarised datasets that are available to represent UK CHB epidemiology, considering differences between sources, and d...

Objective: To assess the risk of covid-19 death after infection with omicron BA.1 compared with delta (B.1.617.2). Design: Retrospective cohort study. Setting: England, United Kingdom, from 1 December 2021 to 30 December 2021. Participants: 1 035 149 people aged 18-100 years who tested positive for SARS-CoV-2 under the national surveillance...

Background: A high BMI has been associated with a reduced immune response to vaccination against influenza. We aimed to investigate the association between BMI and COVID-19 vaccine uptake, vaccine effectiveness, and risk of severe COVID-19 outcomes after vaccination by using a large, representative population-based cohort from England. Methods:...

Objective Prior studies identified clinical factors associated with increased risk of pancreatic ductal adenocarcinoma (PDAC). However, little is known regarding their time-varying nature, which could inform earlier diagnosis. This study assessed temporality of body mass index (BMI), blood-based markers, comorbidities and medication use with PDAC r...

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used...

Objectives To develop and validate the QCancer2 (10-year risk) lung model for estimation of future risk of lung cancer and to compare the model performance against other prediction models for lung cancer screening Design open cohort study using linked electronic health records (EHRs) from the QResearch database (1 January 2005 – 31 March 2020) Se...

Introduction The QCOVID algorithm is a risk prediction tool for infection and subsequent hospitalisation/death due to SARS-CoV-2. At the time of writing, it is being used in important policy-making decisions by the UK and devolved governments for combatting the COVID-19 pandemic, including deliberations on shielding and vaccine prioritisation. Ther...

Objective To confirm the symptoms and signs for motor neuron disease (MND) in the Red Flag tool; to quantify the extent to which the key symptoms and signs are associated with MND; and to identify additional factors which may be helpful within the primary care setting in recognition of possible MND and triggering timely referral to neurology specia...

Importance: Individuals surviving severe COVID-19 may be at increased risk of neuropsychiatric sequelae. Robust assessment of these risks may help improve clinical understanding of the post-COVID syndrome, aid clinical care during the ongoing pandemic, and inform postpandemic planning. Objective: To quantify the risks of new-onset neuropsychiatr...

Background HBV is the leading global cause of cirrhosis and primary liver cancer. The virus’s attributable disease burden in the UK is concentrated in vulnerable populatons including ethinic minorities, people experiencing homelessness and people born in high-prevalence countries. Despite this the UK HBV population has not been well characterised,...

Objective To investigate childhood, teenage and young adult cancer diagnostic pathways during the first wave of the COVID-19 pandemic in England. Design Population-based cohort study. Setting and participants QResearch, a nationally representative primary care database, linked to hospital admission, mortality and cancer registry data, was used to...

Background Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants. Objectives To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments. Design and setting Cohort study using anonymised English primary care...

Introduction Breast cancer is the most common cancer and the leading cause of cancer-related death in women worldwide. Risk prediction models may be useful to guide risk-reducing interventions (such as pharmacological agents) in women at increased risk or inform screening strategies for early detection methods such as screening. Methods and analys...

Objective To assess the risk of death involving COVID-19 following infection from Omicron (B.1.1.539/BA.1) relative to Delta (B.1.617.2). Design Retrospective cohort study. Setting England, UK, 1 December 2021 to 25 January 2022. Participants 1,035,163 people aged 18-100 years who tested positive for SARS-CoV-2 in the national surveillance progr...

Background: Smoking is a risk factor for most respiratory infections, but it may protect against SARS-CoV-2 infection. The objective was to assess whether smoking and e-cigarette use were associated with severe COVID-19. Methods: This cohort ran from 24 January 2020 until 30 April 2020 at the height of the first wave of the SARS-CoV-2 epidemic i...

Background: Guidelines recommend that GPs give patients lifestyle advice to manage hypertension and diabetes. Increasing evidence shows that this is an effective and practical treatment for these conditions, but it is unclear whether GPs offer this support. Aim: To investigate trends in the percentage of patients with hypertension/diabetes recei...

Introduction COVID-19 risk prediction algorithms can be used to identify at-risk individuals from short-term serious adverse COVID-19 outcomes such as hospitalisation and death. It is important to validate these algorithms in different and diverse populations to help guide risk management decisions and target vaccination and treatment programs to t...

Background Studies have reported an increased risk of mortality among people prescribed mirtazapine compared to other antidepressants. The study aimed to compare all-cause and cause-specific mortality between adults prescribed mirtazapine or other second-line antidepressants. Methods This cohort study used English primary care electronic medical r...

Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1...

Objective: This study uses three linked datasets to provide an estimate of incidence of motor neuron disease (MND) in England from 1998 to 2019. Comparison is made to previous British studies. It examines age at diagnosis and ethnicity of those affected. Methods: The literature was searched for studies of MND incidence in Great Britain from 1995 to...

Background and research aim The incidence and mortality of liver cancer have been increasing in recent years in the UK. However, liver cancer is still under-studied. The Early De tection of Hepatocellular Liver Cancer (DeLIVER-QResearch) project aims to address the research gap and generate new knowledge to improve early detection and diagnosis of...

Objective To systematically identify and compare the performance of prognostic models providing estimates of survival or recurrence of localized renal cell cancer (RCC) in patients treated with surgery with curative intent. Materials and Methods We performed a systematic review (PROSPERO CRD42019162349). We searched Medline, EMBASE and the Cochran...

Background and research aim: Lung cancer is a research priority in the UK. Early diagnosis of lung cancer can improve patients' survival outcomes. The DART-QResearch project is part of a larger academic-industrial collaborative initiative, using big data and artificial intelligence to improve patient outcomes with thoracic diseases. There are two g...

Background Pancreatic cancer continues to have an extremely poor prognosis in part due to late diagnosis. 25% of pancreatic cancer patients have a prior diagnosis of diabetes, and hence identifying individuals at risk of pancreatic cancer in those with recently diagnosed type 2 diabetes may be a useful opportunity to identify candidates for screeni...

In an updated self-controlled case series analysis of 42,200,614 people aged 13 years or more, we evaluate the association between COVID-19 vaccination and myocarditis, stratified by age and sex, including 10,978,507 people receiving a third vaccine dose. Myocarditis risk was increased during 1-28 days following a third dose of BNT162b2 (IRR 2.02,...

Objective To estimate the association between untreated, community acquired, respiratory tract infections and bleeding in oral anticoagulant users. Design Self-controlled case series. Setting General practices in England contributing data to the Clinical Practice Research Datalink GOLD. Participants 1208 adult users of warfarin or direct oral an...

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,75...

Background The QCovid algorithm is a risk prediction tool that can be used to stratify individuals by risk of COVID-19 hospitalisation and mortality. Version 1 of the algorithm was trained using data covering 10.5 million patients in England in the period 24 January 2020 to 30 April 2020. We carried out an external validation of version 1 of the QC...

Apart from high-risk scenarios such as the presence of highly penetrant genetic mutations, breast screening typically comprises mammography or tomosynthesis strategies defined by age. However, age-based screening ignores the range of breast cancer risks that individual women may possess and is antithetical to the ambitions of personalised early det...

Objective To assess the risks of developing dementia associated with different types and durations of menopausal hormone therapy. Design Two nested case-control studies. Setting UK general practices contributing to QResearch or the Clinical Practice Research Datalink (CPRD), using all links to hospital, mortality, and social deprivation data. Pa...

Background Conflicting evidence has emerged regarding the relevance of smoking on risk of COVID-19 and its severity. Methods We undertook large-scale observational and Mendelian randomisation (MR) analyses using UK Biobank. Most recent smoking status was determined from primary care records (70.8%) and UK Biobank questionnaire data (29.2%). COVID-...

Objective While population screening programs for cancer colorectal (CRC) have proven benefit, risk-stratified approaches may improve screening outcomes further. To date, genome-wide polygenic risk scores (PRS) for CRC have not been integrated with non-genetic risk factors. We aimed to evaluate several genome-wide approaches, and the benefit of add...

Objectives To derive and validate risk prediction algorithms to estimate the risk of covid-19 related mortality and hospital admission in UK adults after one or two doses of covid-19 vaccination. Design Prospective, population based cohort study using the QResearch database linked to data on covid-19 vaccination, SARS-CoV-2 results, hospital admis...

Objective: To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults. Design: Self-controlled case series study using national data on covid-19 vaccination and hospital admissions. Setting: Patient level data were obtained for approximately 30 million people vaccinated in...

Background: Oral prednisolone is the mainstay treatment for bullous pemphigoid, an autoimmune blistering skin disorder affecting older people. Treatment with moderate-to-high doses is often initiated in secondary care, but then continued in primary care. Aim: To describe long-term oral prednisolone prescribing in UK primary care for adults with...

Introduction Hormone replacement therapy (HRT) can help women experiencing menopausal symptoms, but usage has declined due to uncertainty around risks of cancer and some cardiovascular diseases (CVD). Moreover, improved cancer survival rates mean that more women who survive cancer go on to experience menopausal symptoms. Understanding these relatio...

Acknowledgment: The authors thank the EMIS (Egton Medical Information Systems) practices that contribute to the database as well as the University of Nottingham and University of Oxford for expertise in establishing, developing, and supporting the QResearch database. QResearch acknowledges funding from the Nottingham Biomedical Research Centre fund...