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Publications (226)
BACKGROUND
There has been a rapid growth in the application of structured Electronic Health Records (EHRs) to healthcare systems, where huge amounts of diagnosis codes presenting the temporal event of the patient are collected. In the era of artificial intelligence, many models, especially Deep Learning (DL), are applied for patient outcome predict...
Comorbidities present considerable challenges to cancer treatment and care. However, little is known about the effect of comorbidity on cancer treatment decisions across a wide range of cancer types and treatment modalities. Harnessing a cohort of 280,543 patients spanning 19 site-specific cancers, we explored pan-cancer frequencies of 109 comorbid...
Objective
To describe hospital admissions associated with SARS-CoV-2 infection in children and adolescents.
Design
Cohort study of 3.2 million first ascertained SARS-CoV-2 infections using electronic health care record data.
Setting
England, July 2020 to February 2022.
Participants
About 12 million children and adolescents (age <18 years) who we...
A comprehensive evaluation of the total burden of morbidity endured by cancer survivors remains unavailable. This study quantified the burden of 144 health conditions and critical care admissions across 26 adult cancers and treatment modalities in 243,767 adults. By age 60, top conditions ranked by fold difference (cumulative burden in survivors di...
Despite their latent neurogenic potential, most normal parenchymal astrocytes fail to dedifferentiate to neural stem cells in response to injury. In contrast, aberrant lineage plasticity is a hallmark of gliomas, and this suggests that tumor suppressors may constrain astrocyte dedifferentiation. Here, we show that p53, one of the most commonly inac...
Background
Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.
Methods
We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases...
Objectives
To use national, pre- and post-pandemic electronic health records (EHR) to develop and validate a scenario-based model incorporating baseline mortality risk, infection rate (IR) and relative risk (RR) of death for prediction of excess deaths.
Design
An EHR-based, retrospective cohort study.
Setting
Linked EHR in Clinical Practice Resea...
Comorbidities present considerable challenges to cancer treatment and care. However, little is known about the effect of comorbidity on cancer treatment decisions across a wide range of cancer types and treatment modalities. Harnessing a cohort of 280,543 patients spanning 19 site-specific cancers, we explored pan-cancer frequencies of 109 comorbid...
Background
Globally, there is a paucity of multimorbidity and comorbidity data, especially for minority ethnic groups and younger people. We estimated the frequency of common disease combinations and identified non-random disease associations for all ages in a multiethnic population.
Methods
In this population-based study, we examined multimorbidi...
The burden of mental illness in young people with chronic liver disease is not known. In this population cohort study in England, we identified 358 individuals (aged ≤25 years) diagnosed with autoimmune hepatitis or liver disease related to cystic fibrosis and 1541 propensity-score-matched controls. By the first year of follow-up, the cumulative bu...
Background
Randomised controlled trials (RCTs) inform prescription guidelines, but stringent eligibility criteria exclude individuals with vulnerable characteristics, which we define as comorbidities, concomitant medication use, and vulnerabilities due to age. Poor external validity can result in inadequate treatment decision information. Our first...
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...
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 e...
Cancer is a life-altering event causing considerable psychological distress. However, information on the total burden of psychiatric disorders across all common adult cancers and therapy exposures has remained scarce. Here, we estimated the risk of self-harm after incident psychiatric disorder diagnosis in patients with cancer and the risk of unnat...
Cancer is a leading cause of death, accounting for almost 10 million deaths annually worldwide. Personalised therapies harnessing genetic and clinical information may improve survival outcomes and reduce the side effects of treatments. The aim of this study is to appraise published evidence on clinicopathological factors and genetic mutations (sing...
Background Throughout the pandemic, research, public health, and policy emphasised prediction and surveillance of excess deaths, which have mostly occurred in older individuals with underlying conditions, highlighting importance of baseline mortality risk, infection rate (IR) and pandemic-related relative risk (RR). We now use national, pre-and pos...
The early detection and treatment of neoplasms, and in particular the malignant, can save lives. However, identifying those most at risk of developing neoplasms remains challenging. Electronic Health Records (EHR) provide a rich source of “big” data on large numbers of patients. We hypothesised that in the period preceding a definitive diagnosis, t...
Background
People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes.
Methods
We employed population-wide electronic health records (EHRs; from 1998 to...
Background
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....
Background
Children, teenagers and young adults who survived cancer are prone to developing late effects. The burden of late effects across a large number of conditions, in-patient hospitalisation and critical care admissions have not been described using a population-based dataset. We aim to systematically quantify the cumulative burden of late ef...
Patients and public have sought mortality risk information throughout the pandemic, but their needs may not be served by current risk prediction tools. Our mixed methods study involved: (1) systematic review of published risk tools for prognosis, (2) provision and patient testing of new mortality risk estimates for people with high-risk conditions...
Background
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 contraindicatio...
Background
People with liver disease are at increased risk of developing cardiovascular disease (CVD), however, there has yet been an investigation of incidence burden, risk, and premature mortality across a wide range of liver conditions and cardiovascular outcomes.
Methods
We employed population-wide electronic health records (EHRs; from 1998-20...
Background
Cancer is a life-altering event causing considerable psychological distress. However, population-representative variations in the total burden of psychiatric episodes across cancer types and treatment modalities have not been examined. We sought to estimate the risk of self-harm after incident psychiatric disorder diagnosis in patients w...
Objective
The objective of this study was to employ ensemble clustering and tree-based risk model approaches to identify interactions between clinicogenomic features for colorectal cancer using the 100,000 Genomes Project.
Results
Among the 2211 patients with colorectal cancer (mean age of diagnosis: 67.7; 59.7% male), 16.3%, 36.3%, 39.0% and 8.4%...
Background:
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 and BM...
Background:
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.
Methods:
We estimated the effect of 2-y weight change interventions on 7-y risk of CVD (CVD death, myocardial infarction, stroke, hospitalization from cor...
Background
Patients with liver disease have complex haemostasis and due to such contraindications, landmark randomised controlled trials investigating antithrombotic medicines have often excluded these patients. As a result, there has been limited consensus on the safety, efficacy and monitoring practices of anticoagulant and antiplatelet therapy i...
Objectives
The purpose of this scoping review is to: (1) identify existing supervised machine learning (ML) approaches on the prediction of cancer in asymptomatic adults; (2) to compare the performance of ML models with each other and (3) to identify potential gaps in research.
Design
Scoping review using the population, concept and context approa...
TALE class genes are a group of developmentally conserved transcription factors found in animals. Here, we describe the identification and phylogenetic analysis of TALE class genes in amphipod crustaceans. We identified 241 putative TALE class genes from 56 amphipod crustacean species. Phylogenetic analysis of the genes revealed six subclasses. We...
Objective
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.
Design
Data resource comprising linked person level records from national healthcare settings for the English population,...
Aims
Cardiovascular diseases (CVDs) increase mortality risk from coronavirus infection (COVID-19). There are also concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both ‘direct’, through infection, and ‘indirect’, through changes in healthcare.
Methods and result...
Background: Adult obesity prevention policies, which are largely untargeted, have met with limited success globally. Population groups with the highest risk of weight gain, if they could be reliably identified using readily available information, might benefit from targeted policy. The relative importance of age, sex, ethnicity, geographical region...
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, with return of results in clinical timescales. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a trea...
Estimating the effect of a change in a particular risk factor and a chronic disease requires information on the risk factor from two time points; the enrolment and the first follow-up. When using observational data to study the effect of such an exposure (change in risk factor) extra complications arise, namely (i) when is time zero? and (ii) which...
Objectives
Obesity is a modifiable risk factor for coronavirus(COVID-19)-related mortality. We estimated excess mortality in obesity, both “direct”, through infection, and “indirect”, through changes in healthcare, and also due to potential increasing obesity during lockdown.
Study design
Retrospective cohort study and causal inference methods.
M...
Objectives:
To estimate the impact of the COVID-19 pandemic on cancer care services and overall (direct and indirect) excess deaths in people with cancer.
Methods:
We employed near real-time weekly data on cancer care to determine the adverse effect of the pandemic on cancer services. We also used these data, together with national death registr...
Over the past three decades, the number of people globally with diabetes mellitus has more than doubled. It is estimated that by 2030, 439 million people will be suffering from the disease, 90-95% of whom will have type 2 diabetes (T2D). In 2017, 5 million deaths globally were attributable to T2D, placing it in the top 10 global causes of death. Be...
Background:
The AMP-activated protein kinase (AMPK) is an evolutionarily conserved regulator of cellular energy homeostasis. As a nexus for transducing metabolic signals, AMPK cooperates with other energy-sensing pathways to modulate cellular responses to metabolic stressors. With metabolic reprogramming being a hallmark of cancer, the utility of...
Objectives
We aimed to model the impact of coronavirus (COVID-19) on the clinical academic response in England, and to provide recommendations for COVID-related research.
Design
A stochastic model to determine clinical academic capacity in England, incorporating the following key factors which affect the ability to conduct research in the COVID-19...
Background: Obesity is a modifiable risk factor for coronavirus(COVID-19)-related mortality. We estimated excess mortality in obesity, both 'direct', through infection, and 'indirect', through changes in healthcare, and also due to potential increasing obesity during lockdown.
Methods: In population-based electronic health records for 1 958 638 ind...
Background: Cardiovascular diseases(CVD) increase mortality risk from coronavirus infection(COVID-19), but there are concerns that the pandemic has affected supply and demand of acute cardiovascular care. We estimated excess mortality in specific CVDs, both direct, through infection, and indirect, through changes in healthcare.
Methods: We used pop...
Background:
Cancer and multiple non-cancer conditions are considered by the Centers for Disease Control and Prevention (CDC) as high risk conditions in the COVID-19 emergency. Professional societies have recommended changes in cancer service provision to minimize COVID-19 risks to cancer patients and health care workers. However, we do not know the...
Background: 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.
Methods: We estimated the effect of 2 year weight change interventions on 7 year risk of CVD, by emulating hypothetical target trials using electronic health...
Dating back to the seminal work of Paul Ehrlich, the idea of harnessing our immune system to eliminate cancerous cells is now over a century old. In the presence of a functional immune system that so efficiently guards the host against developing neoplasms, tumour cells must evolve sophisticated strategies to escape immune destruction in order to g...
Predicted estimate of excess deaths in cancer patients related to the Covid-19 emergency. Data from England, Northern Ireland and US.
Beyond the profound challenges presented by coronavirus (COVID-19) to health systems around the world, the pandemic will lead to major shortages of clinical academics. Clinical academics are doctors at the interface of clinical care and research and are particularly needed to ensure that timely advances in prevention and treatment can be achieved,...
Background:
Since its discovery almost three decades ago, the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway has paved the road for understanding inflammatory and immunity processes related to a wide range of human pathologies including cancer. Several studies have demonstrated the importance of JAK-STAT pathway...
Cancer stem cells (CSCs) have innate abilities to resist even the harshest of therapies. To eradicate CSCs, parallels can be drawn from signalling modules that orchestrate pluripotency. Notch-Hedgehog hyperactivation are seen in CSCs, yet, not much is known about their conserved roles in tumour progression across cancers.
Employing a comparative ap...
The AMP-activated protein kinase (AMPK) is an evolutionarily conserved regulator of cellular energy homeostasis. As a nexus for transducing metabolic signals, AMPK cooperates with other energy-sensing pathways to modulate cellular responses to metabolic stressors. With metabolic reprogramming being a hallmark of cancer, the utility of agents target...
Peroxisome proliferator‐activated receptors (PPARs) are a family of nuclear receptors that regulate lipid metabolism and bioenergetic demands within living systems. Consequently, aberrant expression of PPAR genes could predispose individuals to diseases, including cancer. PPAR signaling exerts pleiotropic functions in cancer, yet little is known ab...
Background:
Tumor hypoxia is associated with metastasis and resistance to chemotherapy and radiotherapy. Genes involved in oxygen-sensing are clinically relevant and have significant implications for prognosis. In this study, we examined the pan-cancer prognostic significance of oxygen-sensing genes from the 2-oxoglutarate-dependent oxygenase fami...
Background
The circadian clock governs a large variety of fundamentally important physiological processes in all three domains of life. Consequently, asynchrony in timekeeping mechanisms could give rise to cellular dysfunction underpinning many disease pathologies including human neoplasms. Yet, detailed pan-cancer evidence supporting this notion h...
Chronic hepatitis B is one of the world’s unconquered diseases with more than 240 million infected subjects at risk of developing liver disease and hepatocellular carcinoma. Hepatitis B virus reverse transcribes pre-genomic RNA to relaxed circular DNA (rcDNA) that comprises the infectious particle. To establish infection of a naïve target cell, the...
Cancer stem cells pose significant obstacles to curative treatment contributing to tumor relapse and poor prognosis. They share many signaling pathways with normal stem cells that control cell proliferation, self-renewal, and cell fate determination. One of these pathways known as Wnt is frequently implicated in carcinogenesis where Wnt hyperactiva...
Overactive DNA repair contributes to therapeutic resistance in cancer. However, pan-cancer comparative studies investigating the contribution of all DNA repair genes in cancer progression employing an integrated approach have remained limited. We performed a multi-cohort retrospective analysis to determine the prognostic significance of 138 DNA rep...
Since its discovery almost three decades ago, the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway has paved the road for understanding inflammatory and immunity processes related to a wide range of human pathologies including cancer. Several studies have demonstrated the importance of JAK-STAT pathway components i...
Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear receptors that regulate lipid metabolism and bioenergetic demands within living systems. Consequently, aberrant expression of PPAR genes could predispose individuals to diseases including cancer. PPAR signaling exerts pleiotropic functions in cancer, yet, little is known ab...
Background: The circadian clock governs a large variety of fundamentally important physiological processes in all three domains of life. Consequently, asynchrony in timekeeping mechanisms could give rise to cellular dysfunction underpinning many disease pathologies including human neoplasms. Yet, detailed pan-cancer evidence supporting this notion...
The circadian clock regulates immune responses to microbes and affects pathogen replication, but the underlying molecular mechanisms are not well understood. Here we demonstrate that the circadian components BMAL1 and REV-ERBα influence several steps in the hepatitis C virus (HCV) life cycle, including particle entry into hepatocytes and RNA genome...
Background: Cancer stem cells (CSCs) have innate abilities to resist even the harshest of therapies. To eradicate CSCs, parallels can be drawn from signalling modules that orchestrate pluripotency. Notch-Hedgehog hyperactivation are seen in CSCs, yet, not much is known about their conserved roles in tumour progression across cancers.
Methods: Emplo...
Overactive DNA repair contributes to therapeutic resistance in cancer. However, pan-cancer comparative studies investigating the contribution of all DNA repair genes in cancer progression employing an integrated approach have remained limited. We performed a multi-cohort retrospective analysis to determine the prognostic significance of 138 DNA rep...
Cancer stem cells pose significant obstacles to curative treatment contributing to tumor relapse and poor prognosis. They share many signaling pathways with normal stem cells that control cell proliferation, self-renewal and cell fate determination. One of these pathways known as Wnt is frequently implicated in carcinogenesis where Wnt hyperactivat...
Background:
Despite much progress in cancer research, its incidence and mortality continue to rise. A robust biomarker that would predict tumor behavior is highly desirable and could improve patient treatment and prognosis.
Methods:
In a retrospective bioinformatics analysis involving patients with liver cancer (n = 839), we developed a prognost...