Proposal summaries
B3530 - Health and wellbeing in surviving congenital heart disease patients - 14/05/2020
Patients with congenital heart (CHD) disease now live longer and therefore they are more likely to experience common aging condition.
One of these are cardiovascular disease (CVD) with relative morbidity and mortality.However, whether the established risk factors for CVD in the general population are the same with CHD is unclear.
In addition, there is a substantial evidence that risk for CVD begins in early life and that risk factors (e.g. obesity, high blood pressure, dyslipidaemia)measured in childhood and adolescence track and relate to adult risk, but the prevalence of these in children with CHD and their future risk on CVD is unknown and may differ from the general population.
Another issue for the aging CHD population is regarding their educational achievement. Academic performance represent a main area of interest as this is anticipated to have major impact in their quality of life. It's well recognised that some children with CHD can present neurocognitive impairment when compared to the general population. However, whether this has a significant effect in their overall academic performance remains unclear with discordant results reported.
To our knowledge there are no study that investigate the trajectories of cardiovascular risk factor and neurocognitive development (in term of educational achievement)from early childhood to adulthood life.
B3532 - The role of neighbourhood conditions in mental health responses to the Covid-19 lockdown - 15/05/2020
The Covid-19 lockdown has shone a light on the importance of where we live for our health and wellbeing. Living in the countryside; having a garden; living in a cohesive neighbourhood; being within walking distance of a park: these factors create very different lockdown experiences, even between neighbours living a stoneâs throw apart.
Research into neighbourhood factors and mental health is not new. However, lockdown has created a natural experiment in which peopleâs activities outside the home are largely being confined to their immediate neighbourhoods. Lockdown has thus amplified the potential detrimental â and protective â effects of neighbourhood conditions on our mental health. Investigating this relationship is not simple. It is important to take into consideration potential factors that might confound associations (e.g., prior mental health). It is also important to take into consideration how individual-level factors such as housing type might modify any associations of neighbourhood characteristics with mental health.
The current project will explore the relationship between neighbourhood characteristics during lockdown â including population density, greenspace, deprivation, and social fragmentation â and peopleâs symptoms of anxiety and depression during and after lockdown. Analyses will control for key confounders of the association. Moderation of associations according to household composition, housing type, garden access, and perceived access to nature will be explored.
B3527 - Serological testing for COVID19 - 26/05/2020
There is currently a pandemic of a new disease, COVID19, which is caused by a virus called SARS-CoV-2.
B3524 - The association between different modes of delivery for childbirth and sexual health a studying using ALSPAC data - 04/05/2020
Sexual health can impact upon a personâs quality of life. Being pregnant and having a child can affect a womanâs body and mind in a way that may affect their sexual health. We know that when couples have babies, their sexual activity is likely be low in the first few months after the birth. Yet what we don't know is if the mode of delivery (in other words having a vaginal or a ceasrean delivery) affects female sexual health, particularly in the medium to long-term.
B3525 - Young adults gambling behaviour in lockdown - 12/05/2020
The ALSPAC Gambling study is an ongoing investigation of gambling behaviour in young people, and the antecedents and consequences of problem gambling. The young participants in ALSPAC have previously completed gambling questionnaires and the Problem Gambling Severity Index, at 17, 20- and 24-years.
This proposal will survey the ALSPAC cohort again during the COVID 19 lockdown. This is an excellent opportunity to investigate in real time the effects of COVID-19 mitigation on gambling activities at home by young adults, and to compare individualâs behaviour with what was previously reported at 24 years.
B3526 - Linking research and routine data to explore childhood asthma eczema and allergic rhinitis in the Born in Bradford birth cohort - 13/05/2020
Asthma, eczema and hay fever and are common diseases in childhood and responsible for a significant burden on families and health services. Atopic eczema, hay fever (allergic rhinitis) and atopic asthma often co-exist. Early diagnosis and appropriate management can reduce progression and severity of these diseases.
The Born in Bradford (BiB) birth cohort includes over 13,500 children born between 2007 and 2011, with around half born to women of Pakistani ethnicity. Linked primary care and hospital admission data are available for 97% of BiB children. Two sub-studies within BiB, the Allergy and Infection Study (ALL IN, n=2559) and Mechanisms of the Development of ALLergy (MeDALL, n=1814), have collected detailed parental questionnaire data at age 1 and 2 years (ALL IN) and at 4 years (MeDALL). The current data collection phase for the whole BiB cohort, Growing Up, at ages 7-11 years is ongoing and also includes questions on these outcomes.
The BiB data provide an opportunity to investigate trajectories of allergic disease and asthma through childhood, by ethnic group. The linked primary care and hospital electronic health records (EHR) will contribute a wealth of data which can be analysed with machine learning methods. There is uncertainty over the validity of routine data but the extensive BiB questionnaire data at different ages provide a rare opportunity to test this.
The aims of this proposed study are:
1) to link research and routine data to explore early life and childhood longitudinal trajectories and describe clinical phenotypes of asthma, eczema and hay fever;
2) to investigate ethnic inequalities in access to care and presentation of these diseases
3) to investigate early life risk factors for these diseases
Questionnaire data are available from the BiB ALL IN sub-study at age 1 year, including questions on pets, family history of asthma/eczema/hay fever, housing conditions (damp, heating, flooring, bedding etc.), and at 2 years (as for age 1 plus eczema, hay fever, food allergy). Detailed data relevant to asthma, eczema and hay fever are available for the MeDALL sub-study participants at 4 years, including skin prick testing for 2269.
BiB receive regular extracts of primary care EHR data on diagnoses and prescriptions for BiB children, which will be linked to the BiB maternal baseline questionnaire data, including socio-demographic and household characteristics. Linked hospital admissions data are available from the Bradford Royal Infirmary. We will also compare EHR data and questionnaire data from the Avon Longitudinal Study of Parents and Children (ALSPAC).
Latent class analysis or other cluster methods, such as k-means clustering, will be used to identify clinical phenotypes of asthma, eczema and hay fever. Longitudinal extensions of these cluster methods will be used to describe trajectories over age.
This study will provide important data on the validity of routine primary care EHR for asthma and allergic diseases, which is relevant as EHR are increasingly used for research studies. The comparison of questionnaire and EHR data will indicate whether there are ethnic differences in access to primary care for these diseases. Identification of clinical phenotypes of asthma, eczema and hay fever will inform appropriate treatment and management and the identification of factors associated with disease progression or severity could indicate potential prevention strategies.
B3522 - The Healthier Together Population Data Platform - 01/05/2020
Health and care services are increasingly planned and provided using patient data shared securely across multiple health-care settings. However, we know that peopleâs health is influenced by a wide range of things, including social, cultural, and economic factors. Unfortunately, we donât currently have data resources that link information about these things to improve service planning, individual care and research.
Our project will fund the information technology and people to bring together information from multiple sources, including, local councils and other services such as the police, as well as the detailed data collected as part of research studies. We will do this using secure technologies and protecting patientsâ confidentiality.
By combining and analysing data, we will be able to work with public services to help identify people at higher risk of a condition or disease, and deliver better, more joined up care that is both more effective and offers better value.
B3523 - Fine-mapping of vascular reactivity loci using human artery multi-omics analyses - 01/05/2020
Vascular diseases such as hypertension, migraine, and atherosclerosis (hardening of arteries) involve changes in vascular cell function with reduced ability to contract and relax in response to different stresses. This results in chronic alterations in artery blood flow and maladaptive structural changes to the vascular wall leading to injury, tissue damage, and increased risk for life-threatening diseases such as stroke and heart attacks. Given that naturally occurring genetic variation contributes to changes in vascular function along with environmental risk from early life stages, it is now critical to evaluate the effects of these genetic associations at this stage using more systematic approaches. We plan to integrate these vascular phenotype data with high resolution molecular data to better understand how these genetic risk factors impact vascular disease risk at an early age.
B3518 - Using a machine learning approach to develop and validate a prediction model for the onset of hypomania - 12/05/2020
Bipolar disorder (BD) is a debilitating mental health condition, characterised by severe shifts in mood, that can range from disabling highs (i.e., mania/hypomania) to extreme lows (i.e., depression). Approximately 1% of the population are affected by bipolar (Pini et al., 2005), with most people experiencing the onset of mood symptoms prior to their 20s (Geoffroy et al., 2013). Despite this, little is known about the predictors to bipolar disorder and hypomania symptoms, particularly among young people. Intervening early in the development of bipolar is a top clinical priority, and one that may have the potential to limit its functional and symptomatic impact on those affected. Thus, predicting the onset of bipolar/hypomania prior to its onset, may help clinicians/researchers to develop novel, tailored preventative strategies and interventions for young people.
B3521 - HDR-UK South West Better Care Partnership - 01/05/2020
Better Care South-West Partnership is a collaboration of NHS commissioners, primary, secondary, community and mental health care providers, local authorities, and academia. They look to address real-world health problems using the Bristol, North Somerset and South Gloucestershire (BNSSG) Systemwide health and social care dataset and have an ambition to use individual-level, linked routine care and administrative data to deliver a learning, Integrated Care System for the local population.
The Partnership represents a step change in using advanced analytics to deliver Better Care Loops across a care system and benefit patients and partner organisations. Its results will be scalable across the region and nationally.
Research Projects
· P-NEWS: personalised early warning scores for preventing unplanned critical care admission
· Precision antimicrobial prescribing: safeguarding patient outcomes and preserving future efficacy
· Using operation research methods to improve flow between acute and social care: modelling the responsiveness of system-level expenditure to changes in social care capacity
· Improving hospital efficiency by forecasting demand for hospital beds
· Underpinning infrastructure to the BNSSG Systemwide dataset
B3519 - The impact of COVID-19 Lockdown on family interactions and infant behaviours - 30/04/2020
The impact of the public health measures adopted to control the COVID-19 pandemic on young infants and family interactions is unknown. New information is vital to inform future policies and recovery for families and aid infant development. Infants may show more unsettled and
restless behaviours even if they are not aware of the situation, however, they may also show positive behaviours benefiting from more parental attention if parents are home. Understanding of both is important to manage further transitions in an ever changing home environment. Furthermore , young children will have been separated from wider family and friends. Online chats may provide a helpful substitute to retain attachments, but how young infants respond to such interactions is unknown . Using our existing methods to code indepeth parent and infant verbal and non-verbal behaviours we can compare parent and infant behaviours in interactions at this time to already collected and coded interactions of ALSPAC-G2 families pre-pandemic. We can also compare infant behaviours towards parents in the same room and a mimicked online interaction (where the one parent joins a chat from another room).
B3517 - Longitudinal prevalence of covid-19 symptoms in the ALSPAC cohorts - 28/04/2020
Infection by the sars-cov-2 virus (coronavirus) causes a range of flu-like symptoms which can be mild or serious. To date, testing for coronavirus in the Bristol area has focussed on people with severe symptoms. This means that existing test results do not give a full picture of how many people in the Bristol area have already had coronavirus infection.
Rather than using tests, it may be possible to track the spread of coronavirus over time by looking at how many people are experiencing flu-like symptoms. This analysis plans to divide flu-like symptoms into two groups (those which are specific to coronavirus and those which are common in many types of cold or flu) and compare how the rate of these has changed between October 2019 and June 2020. This may give more information about the posible true rate of mild infection in the Bristol area, as well as how the number of people with coronavirus is changing over time.
B3520 - Host genetic effects on covid-19 susceptibility and outcomes - 01/05/2020
It is not clear why some people who are exposed to sars-cov-2 (the coronavirus) only develop mild symptoms while others go on to have life-threatening infections. Age and pre-existing medical problems are important, but it is likely that genetic factors also explain why some people are more susceptible to infection. One way to identify the most relevant genetic factors is to screen millions of points across the whole human genome and see which markers are more or less common in people with infection.
This type of analysis (called a genome-wide association study) needs very large studies to generate reliable results, and it is common to run the anlaysis in multiple different studies and then combine results. A global consortium has recently been set up to co-ordinate analysis of host genetic factors and coronavirus. This proposal plans to run genome-wide analysis in ALSPAC and share the results of this anlaysis which can then be combined with other studies globally. To do this it will be necessary to re-impute (re-process) the existing ALSPAC genetic data into an updated format so the results of analysis matches other studies.
B3515 - Non-invasive Characterisation Diagnosis Prognosis of COVID-19 Respiratory Infection - 27/04/2020
B3514 - Quantifying social contact patterns during the COVID-19 epidemic - 24/04/2020
Quantifying social contacts is essential for understanding how a disease will spread in a population. We have measured contact patterns using surveys that have formed the basis of predictive modelling presented at the UK Government Modelling advisory group on COVID-19. Here, we will measure social contact patterns during this unprecedented time of social distancing in the UK and compare to other studies and settings.
B3516 - Exploring the associations between paternal postnatal depression aspects of involvement and parenting and child development - 24/04/2020
There is strong epidemiological evidence to suggest that paternal postnatal depression (PPD) is associated with adverse offspring developmental outcomes in early childhood. However, few large prospective longitudinal studies have examined whether these adverse outcomes persist into later childhood (7 years of age). Furthermore, the offspring outcomes are heterogenous and effect sizes are small to moderate. Thus, it is important to elucidate putative mechanisms, i.e. mediating factors, that underly associations between PPD and offspring adverse developmental outcomes. Such insights are crucial to highlight those at greater risk and develop targeted interventions to reduce adverse outcomes in offspring of depressed fathers. A substantial body of evidence suggests that an important potential mediator is the quality of parenting. Specifically, evidence suggests that PPD disrupts paternal levels of involvement with the offspring and quality of parenting (e.g., bonding, enjoyment, confidence), which, in turn, is associated with adverse offspring outcomes, including emotional and behavioural problems. However, few population-based studies have examined potential explanatory role of fathersâ involvement and parenting in the association between PPD and offspring development using longitudinal mediation models.
B3512 - What are the dietary lifestyle and socio-demographic predictors of metabolically healthy obesity in adolescence - 21/04/2020
The on-going childhood obesity epidemic is accompanied by dramatic increases in childhood metabolic disorders, such as paediatric type 2 diabetes and a cluster of metabolic complications. However, children with obesity are not all equally prone to developing these metabolic disorders; research has shown that there is a subset of obese children who have a more âfavourableâ health profile, including good insulin sensitivity and normal blood pressure, glucose regulation and blood lipid levels. This has been termed metabolically healthy obesity (MHO), which contrasts with metabolically unhealthy obesity (MUO), where excess body fat is accompanied by metabolic disorders. Since most of the research to date on MHO and MUO has focused on adults, the specific determinants of MHO and MUO in paediatric groups are still not clearly understood.
The concept of metabolically unhealthy and metabolically healthy profiles can also be applied to individuals of ânormalâ weight, since normal-weight individuals can also have the metabolic and/or inflammatory abnormalities commonly observed in obese people. This group has been termed normal-weight metabolically unhealthy (NWMU). NWMU adults are also at increased risk of cardiometabolic diseases, however, little is known about the health profile and predictive characteristics of NWMU in children.
The relatively high proportion of metabolically healthy individuals in the obese (ranging from 4-60%) and metabolically unhealthy individuals in the lean population suggests that besides from total calories, diet quality could be an important influencing factor on metabolic health. However, few studies have looked at how dietary patterns in children might influence the sub-groups of obesity. Therefore, this study aims to identify which dietary patterns, lifestyle behaviours and socio-demographic factors in children are related to MHO and MUO, as well as NWMU in adolescents. Gaining a clearer understanding of the health profile, characteristics and potential determinants of MHO and MUO in paediatric groups could be valuable in developing more efficient and targeted treatment approaches for these groups of children with obesity.
B3513 - Record Linkage to support Covid-19 Research in ALSPAC Immediate Covid-19 research objectives - 24/04/2020
ALSPAC is well-placed to contribute to the national/international Covid-19 research effort given it has an extensive archive of data about participants health and wellbeing and circumstances prior to the Covid-19 outbreak and is now collecting data specifically related to Covid-19. These data can be used with our biobank and genetic data.
This project seeks to enhance these data with NHS and other Covid-19 records. These will bring timely information about symptoms, help-seeking and care and disease outcomes. It will allow ALSPAC to look at Covid-19 specific health (i.e. the health of those with the virus) and wider general physical and mental health (which may be impacted by stretched NHS resources during the outbreak, or due to the 'lock-down' and social distancing).
This data will sit alongside the other health records ALSPAC have collected. The same security mechanisms will be used to keep the data confidential, and ALSPAC will not extract records from participants who have objected to this use of their data.
The records will be sourced from:
1) A new NHS national (English) repository of Covid-19 data (GP records, Hospital Records, Pharmacy data, NHS 111 call records, Ambulance Records, Mortality Records, Covid-19 testing records).
2) Respiratory care records from databases at NHS University Hospital Bristol Trust and NHS North Bristol Trust hospitals.
3) Records from the 'Zoe' symptom tracker app.
ALSPAC will immediately use the data to help understand more about the factors that influence the susceptibility and severity of Covid-19. We will also examine whether Blood Group and the FUT2 gene (and other genes) are associated with Covid-19 susceptibility.
B3511 - Environment DNA methylation and risk of childhood acute lymphoblastic leukaemia a novel two-sample MR study - 24/04/2020
Acute lymphoblastic leukaemia (ALL) is the most common cancer in children. Whilst a range of genetic abnormalities have been identified as crucial in disease initiation, these abnormalities alone are not sufficient for transformation. Maternal exposures during pregnancy such as smoking, or folate intake have the potential to impact on offspring DNA methylation. This epigenetic mark has also been shown to be altered in ALL. We have previously identified 5 CpG sites that have altered DNA methylation due to maternal smoking and folate intake and we aim to identify whether changes to DNA methylation at these sites affects risk of ALL.
B3508 - A robust micro-assay to determine the prevalence of COVID-19 antibodies in the general population using capillary sample collect - 24/04/2020
The Diabetes and Metabolism Unit at Southmead has a long history of measuring antibodies. Over the last three years we have focused on a particular type of assay which works on very small samples of blood. We have also good systems for sending small tubes by post which allow people to take a small blood sample from their finger and post it safely back to the laboratory for antibody testing. Since the recent COVID-19 pandemic we do not know how many people have been infected by the virus and this is a very important question. We have been working closely with a research group in Milan who have developed a test to work out who has been infected with Covid-19 because they have antibodies to the virus. Initial tests suggest that this assay works well on very small blood samples. We are now setting up this assay in Bristol and are requesting to access some samples from ALSPAC for
1. a University of Bristol study to test different assay platforms using the same samples
2. to prospectively and safely collect low volume samples by post and use the assay to estimate the infection rate in the general population and link this to questionnaire based data regarding symptoms.
This study should allow us to work out quickly and reliably how many people in the ALSPAC population have had COVID-19.