Secure Anonymised Information Linkage Research Articles

Health service use of infants involved in family justice care and supervision proceedings in Wales: a data linkage study

IntroductionWhen a child has suffered, or is at risk of suffering, significant harm from parents or caregivers, the local authority may issue Section 31 (s.31) Care and Supervision proceedings under the Children Act (1989). ObjectivesWe compared the healthcare use of infants less than one year old subject to s.31 proceedings in Wales (n = 1,332),to that of a comparison group of infants not subject to s.31 proceedings (n = 204,417), between January 2011 and February 2020. MethodsPopulation-based e-cohort study utilising data held in the Secure Anonymised Information Linkage (SAIL) Databank. Infants in s.31 proceedings were identified using the Children and Family Court Advisory and Support Service dataset. This was linked to demographic and healthcare datasets, to identify General Practice (GP) visits, emergency department (ED) attendances, and hospital admissions (emergency and elective); before the study end date or the child's first birthday for the comparison group, orbefore the s.31 application date.Regression analysis calculated event rate ratios [RR] and incidence rate ratios [IRR] for healthcare events, adjusting for widerdeterminants of health (e.g. perinatal factors, maternal mental health, deprivation), and investigated reasons for healthcare use. ResultsInfants in s.31 proceedings had ahigher number and incidence of healthcare events compared with the comparison group, across all healthcare settings. Differences were greatest for emergency hospital admissions (IRR = 4.03, 95% confidence interval [CI] = 3.53 - 4.59; RR = 4.60, CI = 3.90 - 5.41). "Injury and poisoning" was the main reason for emergency admissions amongst infants in s.31 proceedings. For ED presentations, emergency hospital admissions, and GP visits, there were proportionally more events for these infants across all top ten reasons for healthcare. ConclusionsFindings highlight greater healthcare utilisation for infants involved in s.31 proceedings in Wales, helping to build a better understanding of their needs and vulnerabilities.

A Harmonised Approach to Curating Research-Ready Datasets for Asthma, Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) in England, Wales and Scotland Using Clinical Practice Research Datalink (CPRD), Secure Anonymised Information Linkage (SAIL) Databank and DataLoch.

Electronic healthcare records (EHRs) are an important resource for health research that can be used to improve patient outcomes in chronic respiratory diseases. However, consistent approaches in the analysis of these datasets are needed for coherent messaging, and when undertaking comparative studies across different populations. We developed a harmonised curation approach to generate comparable patient cohorts for asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) using datasets from within Clinical Practice Research Datalink (CPRD; for England), Secure Anonymised Information Linkage (SAIL; for Wales) and DataLoch (for Scotland) by defining commonly derived variables consistently between the datasets. By working in parallel on the curation methodology used for CPRD, SAIL and DataLoch for asthma, COPD and ILD, we were able to highlight key differences in coding and recording between the databases and identify solutions to enable valid comparisons. Codelists and metadata generated have been made available to help re-create the asthma, COPD and ILD cohorts in CPRD, SAIL and DataLoch for different time periods, and provide a starting point for the curation of respiratory datasets in other EHR databases, expediting further comparable respiratory research.

Epilepsy and the risk of COVID-19-related hospitalization and death: A population study.

People with epilepsy (PWE) may be at an increased risk of severe COVID-19. It is important to characterize this risk to inform PWE and for future health and care planning. We assessed whether PWE were at higher risk of being hospitalized with, or dying from, COVID-19. We performed a retrospective cohort study using linked, population-scale, anonymized electronic health records from the SAIL (Secure Anonymised Information Linkage) databank. This includes hospital admission and demographic data for the complete Welsh population (3.1 million) and primary care records for 86% of the population. We identified 27 279 PWE living in Wales during the study period (March 1, 2020 to June 30, 2021). Controls were identified using exact 5:1 matching (sex, age, and socioeconomic status). We defined COVID-19 deaths as having International Classification of Diseases, 10th Revision (ICD-10) codes for COVID-19 on death certificates or occurring within 28 days of a positive SARS-CoV-2 polymerase chain reaction (PCR) test. COVID-19 hospitalizations were defined as having a COVID-19 ICD-10 code for the reason for admission or occurring within 28 days of a positive SARS-CoV-2 PCR test. We recorded COVID-19 vaccinations and comorbidities known to increase the risk of COVID-19 hospitalization and death. We used Cox proportional hazard models to calculate hazard ratios. There were 158 (.58%) COVID-19 deaths and 933 (3.4%) COVID-19 hospitalizations in PWE, and 370 (.27%) deaths and 1871 (1.4%) hospitalizations in controls. Hazard ratios for COVID-19 death and hospitalization in PWE compared to controls were 2.15 (95% confidence interval [CI] = 1.78-2.59) and 2.15 (95% CI = 1.94-2.37), respectively. Adjusted hazard ratios (adjusted for comorbidities) for death and hospitalization were 1.32 (95% CI = 1.08-1.62) and 1.60 (95% CI = 1.44-1.78). PWE are at increased risk of being hospitalized with, and dying from, COVID-19 when compared to age-, sex-, and deprivation-matched controls, even when adjusting for comorbidities. This may have implications for prioritizing future COVID-19 treatments and vaccinations for PWE.

Cardiac interventions in Wales: A comparison of benefits between NHS Wales specialties.

The study aimed to assess if specialised healthcare service interventions in Wales benefit the population equitably in work commissioned by the Welsh Health Specialised Services Committee (WHSSC). The study utilised anonymised individual-level, population-scale, routinely collected electronic health record (EHR) data held in the Secure Anonymised Information Linkage (SAIL) Databank to identify patients resident in Wales receiving specialist cardiac interventions. Measurement was undertaken of associated patient outcomes 2-years before and after the intervention (minus a 6-month clearance period on either side) by measuring events in primary care, hospital attendance, outpatient and emergency department. The analysis controlled for comorbidity (Charlson) and deprivation (Welsh Index of Multiple Deprivation), stratified by admission type (elective or emergency) and membership of top 5% post-intervention costs. Costs were estimated by multiplying events by mean person cost estimates. We identified 5,999 percutaneous coronary interventions (PCI) and 1,640 coronary artery bypass graft (CABG) between 2014-06-01 to 2020-02-29. The ratio of emergency to elective interventions was 2.85 for PCI and 1.04 for CABG. In multivariate analysis significant associations were identified for comorbidity (OR = 1.52, CI = (1.01-2.27)), deprivation (OR = 1.34, CI = (1.03-1.76)) and rurality (OR = 0.81, CI = (0.70-0.95)) for PCI interventions, and comorbidity (OR = 1.47, CI = (1.10-1.98)) for CABG. Higher costs post-intervention were associated with increased comorbidity for PCI and CABG in the top 5% cost groups, but for PCI this was not seen outside the top 5%. For PCI, moderate cost increase was associated with increased deprivation, but the picture was more mixed following CABG interventions. For both interventions, lower costs post intervention were seen in rural locations. We identified and compared health outcomes for selected specialist cardiac interventions amongst patients resident in Wales, with these methods and analyses, providing a template for comparing other cardiac interventions.

Cohort profile: Born in Wales—a birth cohort with maternity, parental and child data linkage for life course research in Wales, UK

PurposeUsing Wales’s national dataset for maternity and births as a core dataset, we have linked related datasets to create a more complete and comprehensive entire country birth cohort. Data of...

Correlations between comorbidities in trials and the community: An individual-level participant data meta-analysis.

People with comorbidities are under-represented in randomised controlled trials, and it is unknown whether patterns of comorbidity are similar in trials and the community. Individual-level participant data were obtained for 83 clinical trials (54,688 participants) for 16 index conditions from two trial repositories: Yale University Open Data Access (YODA) and the Centre for Global Clinical Research Data (Vivli). Community data (860,177 individuals) were extracted from the Secure Anonymised Information Linkage (SAIL) databank for the same index conditions. Comorbidities were defined using concomitant medications. For each index condition, we estimated correlations between comorbidities separately in trials and community data. For the six commonest comorbidities we estimated all pairwise correlations using Bayesian multivariate probit models, conditioning on age and sex. Correlation estimates from trials with the same index condition were combined into a single estimate. We then compared the trial and community estimates for each index condition. Despite a higher prevalence of comorbidities in the community than in trials, the correlations between comorbidities were mostly similar in both settings. On comparing correlations between the community and trials, 21% of correlations were stronger in the community, 10% were stronger in the trials and 68% were similar in both. In the community, 5% of correlations were negative, 21% were null, 56% were weakly positive and 18% were strongly positive. Equivalent results for the trials were 11%, 33%, 45% and 10% respectively. Comorbidity correlations are generally similar in both the trials and community, providing some evidence for the reporting of comorbidity-specific findings from clinical trials.

Dimensions of equality in uptake of COVID-19 vaccination in Wales, UK: A multivariable linked data population analysis

Vaccination has proven to be effective at preventing severe outcomes of COVID-19 infection, and uptake in the population has been high in Wales. However, there is a risk that high-level vaccination coverage statistics may mask hidden inequalities in under-served populations, many of whom may be at increased risk of severe outcomes of COVID-19 infection.The study population included 1,436,229 individuals aged 18 years and over, alive and residence in Wales as at 31st July 2022, and excluded immunosuppressed or care home residents. We compared people who had received one or more vaccinations to those with no vaccination using linked data from nine datasets within the Secure Anonymised Information Linkage (SAIL) databank. Multivariable analysis was undertaken to determine the impact of a range of sociodemographic characteristics on vaccination uptake, including ethnicity, country of birth, severe mental illness, homelessness and substance use.We found that overall uptake of first dose of COVID-19 vaccination was high in Wales (92.1 %), with the highest among those aged 80 years and over and females. Those aged under 40 years, household composition (aOR 0.38 95 %CI 0.35–0.41 for 10+ size household compared to two adult household) and being born outside the UK (aOR 0.44 95 %CI 0.43–0.46) had the strongest negative associations with vaccination uptake. This was followed by a history of substance misuse (aOR 0.45 95 %CI 0.44–0.46).Despite high-level population coverage in Wales, significant inequalities remain across several underserved groups. Factors associated with vaccination uptake should not be considered in isolation, to avoid drawing incorrect conclusions. Ensuring equitable access to vaccination is essential to protecting under-served groups from COVID-19 and further work needs to be done to address these gaps in coverage, with focus on tailored vaccination pathways and advocacy, using trusted partners and communities.

OR26-06 Cardiovascular Morbidity And Mortality In Patients With Resistance to THYROID Hormone (RTH): A Linked Record Study

Abstract Disclosure: O. Okosieme: None. D. Usman: None. P. Taylor: None. C. Dayan: None. G. Lyons: None. C.M. Moran: None. V.K. Chatterjee: None. A. Rees: None. Introduction: Individuals with Resistance to Thyroid Hormone β (RTH-β) may develop cardiac disease, including cardiomyopathy or arrhythmia. Long-term survival outcomes in this group of patients have not been systematically evaluated. Objectives: We investigated all-cause mortality and cardiovascular event risk in a cohort of patients with RTH-β in endocrine clinics in Wales. Methods: In a retrospective cohort study using linked datasets within the Welsh Secure Anonymised Information Linkage (SAIL) Databank, Welsh patients with genetically-proven RTH-β were identified from laboratory records (n=55), matched to population controls by age and sex (n=2750), and linked to outcomes in SAIL. We used Kaplan-Meier and Cox regression models to analyse the association of RTH-β with all-cause mortality, acute myocardial infarction, atrial fibrillation, heart failure, strokes and major adverse cardiovascular events (MACE; a composite of cardiovascular death, acute myocardial infarction, heart failure, and strokes). We also investigated any association between baseline thyroid hormone concentrations and outcomes using restricted cubic splines. Results: Compared to controls, patients had an increased risk of all-cause mortality (Hazard ratio [HR] 2.84, 95% Confidence Interval [95%CI] 1.59-5.08), MACE (HR 3.49, 95%CI 2.04-5.99), atrial fibrillation (HR 10.56, 95%CI 4.72-23.63), and heart failure (HR 6.35, 95%CI 2.26-17.86). Positive associations between FT4 concentration at diagnosis and subsequent cardiovascular morbidity or death were observed, with a 7% increased risk of death per pmol/L increase in FT4. The relationship between FT4 and outcomes was non-linear, with increased risk associated with FT4 concentration exceeding 30 pmol/L. When compared to no intervention, treatment with antithyroid drugs, radioiodine/surgical ablation or levothyroxine, alone or in combination, did not effectively control thyroid hormone excess in the long-term. Conclusion: Patients with RTH-β have increased mortality and cardiovascular outcomes that correlates with high, circulating thyroid hormone levels. Ideal future therapies would target both thyroid hormone excess and tissue resistance and could potentially reduce cardiovascular risk in this disorder. Presentation: Saturday, June 17, 2023

Detection and evaluation of signals associated with exposure to individual and combination of medications in pregnancy: a signal detection study protocol

IntroductionConsidering the high prevalence of polypharmacy in pregnant women and the knowledge gap in the risk–benefit safety profile of their often-complex treatment plan, more research is needed to optimise prescribing....

Active travel to schools in Wales

ObjectivesActive travel to school (ATS), such as walking and cycling, not only reduces carbon emissions and air pollution but also contributes to a myriad of health benefits. Understanding the ‘potential’ for ATS across Wales is poorly understood yet vital to inform policy and practice aimed at increasing ATS.
 MethodsUsing geospatial techniques, network distances have been calculated for all residences to all schools in Wales. Distances for each residence were de-identified and imported into the Secure Anonymised Information Linkage (SAIL) databank using SAIL’s split file approach. Within SAIL, anonymised distances were linked to encrypted school locations and a cohort of approximately 440,000 children attending a state school in Wales as recorded in the Education Wales (EDUW) dataset. Travel distance to school was subsequently filtered for each child within our cohort.
 ResultsThe incorporation of geospatial network derived origin-destination pairs (n=2,205,000,000) allows us to explore how households can engage in ATS, and how this varies by primary/secondary school, welsh-speaking, urban/rural, and socioeconomic status. Initially we will present findings based on distance alone, with future refinements to encompass other factors influencing ATS including: active travel routes, road safety, and topography. We will link our results to anonymised ATS survey responses in SAIL, to calculate specific ATS distance thresholds by age, deprivation, and urban/rural status, including social indicators such as household composition.
 ConclusionCurrently there is limited local or national comparable information on the potential for ATS in Wales. This baseline information is urgently needed to inform ATS policy and planning, and to ensure appropriate ATS interventions are prioritised for schools and communities where need is greatest.

Keeping children within the family: Changing patterns in the use of special guardianship orders

Special Guardianship Orders (SGOs) provide family courts with an alternative to adoption, typically through permanent placement within the extended family. Using court administrative data, this study charts the use of SGOs as a way of promoting stability and recovery for these vulnerable children who cannot remain safely with their parents.
 The study cohort is based on administrative population data produced routinely by Cafcass and accessed via the Secure Anonymised Information Linkage (SAIL) Databank at Swansea University. The unit of analysis is children subject to s.31 care and supervision proceedings in England between 2007/08 and 2021/22, providing a retrospective observational window of fifteen years. Descriptive statistics were used to compare SGOs to other permanency final legal orders (placement, child arrangements, supervision and no order), and survival modelling was employed to look at stability over time and return to court. Finally, regional and over time variations in the data were examined.
 The percentage of children placed on a SGO as a proportion of all children subject to s.31 proceedings rose from 12% to 18% between 2011/12 and 2021/22. Over the same period the percentage of children with a placement order that frees the way for adoption fell from 24% to 14%. This shift in pattern was more pronounced than for any other legal order we examined for children unable to remain with birth parents. The highest usage per region was in the North East and London and the lowest was in the Midlands. We estimate that 9% of children on SGOs would return to court within 10 years. Older children (5-17 years old) were more likely to return to court after SGOs than younger children.
 The study showed that SGOs have become a main route out of public care, outstripping the use of placement orders. These findings have major implications for policy and practice. They demonstrate that special guardianship provides a stable and sustainable permanency option for children unable to remain with their birth parents.

The adoption paradox: Exploring the role of ethnicity, deprivation, and co-ethnic density in care proceedings in England

The study objectives were to (1) examine the association between children’s ethnicity and final legal orders at the end of family care proceedings (section 31 of the 1989 Children Act), and (2) test whether residential context, such as co-ethnic density and area-level deprivation, moderates this association.
 Two sources of data were used for this study. The first consisted of records routinely generated by Cafcass (England) and stored in the Secure Anonymised Information Linkage (SAIL) databank, and the second was the 2021 England Census. The focus was on children whose initial care proceedings took place between 2015/2016 and 2020/2021 and concluded with a recorded final legal order outcome (N = 98,161). Three-level logistic regression models were employed to estimate the relationship between children's ethnicity and adoption, along with the potential moderating effects of co-ethnic density and area-level deprivation.
 Children's ethnicity is significantly associated with placement for adoption, with white children being more likely to be subject to placement orders compared to children from all other ethnic groups combined (Asian, black, mixed or multiple, and other ethnic groups). Higher local authority co-ethnic density considerably reduces the likelihood of adoption for children of other ethnicities besides white, but not for white children. Moreover, white children living in the most deprived LSOAs are more likely to be placed for adoption than those residing in the least deprived LSOAs. However, the likelihood of placement for adoption remains consistent across all LSOA deprivation quintiles for children from ethnicities other than white. Local authority-level deprivation does not appear to moderate the relationship between children's ethnicity and adoption.
 This study sheds light on the intricate relationship between ethnicity, residential context, and adoption. While previous research has indicated that white children are more likely to be adopted, the findings enhance our understanding of the underlying mechanisms influencing adoption, paving the way for a more equitable family justice system.

COVID-19 vaccination in pregnancy: the impact of multimorbidity and smoking status on vaccine hesitancy, a cohort study of 25,111 women in Wales, UK

BackgroundMultimorbidity, smoking status, and pregnancy are identified as three risk factors associated with more severe outcomes following a SARS-CoV-2 infection, thus vaccination uptake is crucial for pregnant women living with multimorbidity and a history of smoking. This study aimed to examine the impact of multimorbidity, smoking status, and demographics (age, ethnic group, area of deprivation) on vaccine hesitancy among pregnant women in Wales using electronic health records (EHR) linkage.MethodsThis cohort study utilised routinely collected, individual-level, anonymised population-scale linked data within the Secure Anonymised Information Linkage (SAIL) Databank. Pregnant women were identified from 13th April 2021 to 31st December 2021. Survival analysis was employed to examine and compare the length of time to vaccination uptake in pregnancy by considering multimorbidity, smoking status, as well as depression, diabetes, asthma, and cardiovascular conditions independently. The study also assessed the variation in uptake by multimorbidity, smoking status, and demographics, both jointly and separately for the independent conditions, using hazard ratios (HR) derived from the Cox regression model.ResultsWithin the population cohort, 8,203 (32.7%) received at least one dose of the COVID-19 vaccine during pregnancy, with 8,572 (34.1%) remaining unvaccinated throughout the follow-up period, and 8,336 (33.2%) receiving the vaccine postpartum. Women aged 30 years or older were more likely to have the vaccine in pregnancy. Those who had depression were slightly but significantly more likely to have the vaccine compared to those without depression (HR = 1.08, 95% CI 1.03 to 1.14, p = 0.002). Women living with multimorbidity were 1.12 times more likely to have the vaccine compared to those living without multimorbidity (HR = 1.12, 95% CI 1.04 to 1.19, p = 0.001). Vaccine uptakes were significantly lower among both current smokers and former smokers compared to never smokers (HR = 0.87, 95% CI 0.81 to 0.94, p < 0.001 and HR = 0.92, 95% CI 0.85 to 0.98, p = 0.015 respectively). Uptake was also lower among those living in the most deprived areas compared to those living in the most affluent areas (HR = 0.89, 95% CI 0.83 to 0.96, p = 0.002).ConclusionYounger women, living without multimorbidity, current and former smokers, and those living in the more deprived areas are less likely to have the vaccine, thus, a targeted approach to vaccinations may be required for these groups. Pregnant individuals living with multimorbidity exhibit a slight but statistically significant reduction in vaccine hesitancy towards COVID-19 during pregnancy.

Antipsychotic drug prescribing and mortality in people with dementia before and during the COVID-19 pandemic: a retrospective cohort study in Wales, UK

Concerns have been raised that antipsychotic drug prescribing, which has been associated with increased mortality in people with dementia, might have increased during the COVID-19 pandemic due to social restrictions imposed to limit the spread of SARS-CoV-2. We used multisource, routinely collected health-care data from Wales, UK to investigate prescribing and mortality variations in people with dementia before and during the COVID-19 pandemic. In this retrospective cohort study, we used individual-level, anonymised, population-scale linked health data to identify adults aged 60 years and older with a diagnosis of dementia in Wales, UK. We used the CVD-COVID-UK initiative to access Welsh routinely collected electronic health record data from the Secure Anonymised Information Linkage (SAIL) Databank. Patients who were alive and registered with a SAIL general practice on Jan 1, 2016, and who received a dementia diagnosis before the age of 60 years and before or during the study period were included. We explored antipsychotic drug prescribing rate changes over 67 months, between Jan 1, 2016, and Aug 1, 2021, overall and stratified by age and dementia subtype. We used time-series analyses to examine all-cause and myocardial infarction and stroke mortality over the study period and identified the leading causes of death in people with dementia between Jan 1, 2020, and Aug 1, 2021. Of 3 106 690 participants in SAIL between Jan 1, 2016 and Aug 1, 2021, 57 396 people (35 148 [61·2%] women and 22 248 [38·8%] men) met inclusion criteria for this study and contributed 101 428 person-years of follow-up. Of the 57 396 people with dementia, 11 929 (20·8%) were prescribed an antipsychotic drug at any point during follow-up. Accounting for seasonality, antipsychotic drug prescribing increased during the second half of 2019 and throughout 2020. However, the absolute difference in prescribing rates was small, ranging from 1253 prescriptions per 10 000 person-months in March, 2019, to 1305 per 10 000 person-months in September, 2020. All-cause mortality and stroke mortality increased throughout 2020, while myocardial infarction mortality declined. From Jan 1, 2020, to Aug 1, 2021, 1286 (17·1%) of 7508 participants who died had COVID-19 recorded as the underlying cause of death. During the COVID-19 pandemic, antipsychotic drug prescribing in people with dementia in the UK increased slightly; however, it is unlikely that this was solely related to the pandemic and this increase was unlikely to be a major factor in the substantial increase in mortality during 2020. The long-term increase in antipsychotic drug prescribing in younger people and in those with Alzheimer's disease warrants further investigation using resources with access to more granular clinical data. Although deprescribing antipsychotic medications remains an essential aspect of dementia care, the results of this study suggest that changes in prescribing and deprescribing practices as a result of the COVID-19 pandemic are not required. British Heart Foundation (via the British Heart Foundation Data Science Centre led by Health Data Research UK), and the Scottish Neurological Research Fund.

Immunisation status of children receiving care and support in Wales: a national data linkage study.

In the UK, a robust childhood immunisation programme ensures children are offered protection against serious infections; identifying inequalities in vaccination coverage is essential. This is one of the first data linkage studies to examine coverage of primary, as well as pre-school booster and second dose of MMR vaccines, in children receiving support from social care services across Wales. By accessing records held within the Secure Anonymised Information Linkage (SAIL) Databank, vaccination status of children receiving social care and support between April 2016 and March 2021 (n = 24,540) was ascertained. This was achieved through linkage of the Children Receiving Care and Support (CRCS) Census and National Community Child Health Database which holds vaccination records for all children in Wales registered for NHS care. This sample was split into three groups - those children who had never been recorded on the Child Protection Register (CPR) or as 'Looked After' but in CRCS (n = 12,480), children ever on the CPR (n = 6,225) and those ever recorded as 'Looked After' but who were never on the CPR (n = 5,840). The comparison group of children and young people (CYP) never receiving welfare support consisted of 624,905 children. Children receiving care or support were more likely to be up-to-date with all six vaccines (no recorded vaccines: 0.6-6.3%) compared to children in the comparison group (no recorded vaccines: 3-10.3%). However, of those who were vaccinated, they were less likely to be vaccinated in a timely manner; both early (5.2% vs. 22.2%; margin of error [ME] = 0.52, 95% CI [confidence interval] = -0.18 - -0.17, p < 0.001) and delayed vaccinations were more common (62.7% vs. 71.3%; ME = 0.58, 95% CI = 0.08-0.09, p < 0.001). Validation of the CRCS immunisation flag showed moderate levels of accuracy. Around 70% of immunisation flags were correct across all three groups. Findings suggest a positive association between receiving services under a care and support plan and being up-to-date with immunisations; children receiving support under a care and support plan were more likely to have experienced early or late vaccinations, demonstrating that there is still more inter-disciplinary co-ordination and planning needed to improve these outcomes. Thus, identifying inequalities in vaccination coverage is essential to target interventions and to prioritise geographic areas for catch-up.

Cardiovascular morbidity and mortality in patients in Wales, UK with resistance to thyroid hormone β (RTHβ): a linked-record cohort study

Individuals with resistance to thyroid hormone owing to mutations in the thyroid hormone receptor β gene (RTHβ) exhibit impaired tissue sensitivity to thyroid hormones, but retain sensitivity in cardiac tissue. Long-term health and survival outcomes in this rare disorder have not been evaluated. We investigated all-cause mortality and cardiovascular event risk in a cohort of patients with RTHβ, followed-up in UK endocrine clinics. In a retrospective cohort design, we linked genetically confirmed patients with RTHβ and age-matched and sex-matched population controls to outcomes in datasets within the Welsh Secure Anonymised Information Linkage (SAIL) Databank. Kaplan-Meier and Cox regression models analysed associations of RTHβ with all-cause mortality and cardiovascular events. We identified 61 patients with a genetic diagnosis of RTHβ between Jan 1, 1997, and Dec 31, 2019, and matched them with 2750 controls. Compared with controls, patients exhibited increased risks for all-cause mortality (hazard ratio [HR] 2·84, 95% CI 1·59-5·08), atrial fibrillation (10·56, 4·72-23·63), heart failure (HR 6·35, 95% CI 2·26-17·86), and major adverse cardiovascular events (MACE), comprising cardiovascular death, acute myocardial infarction, heart failure, or strokes (HR 3·49, 95% CI 2·04-5·99). The median age of first occurrence of any adverse event was 11 years earlier in patients (56 years, 95% CI 44-65) compared with controls (67 years, 65-70). Cubic spline analyses showed positive associations between FT4 concentrations at diagnosis and mortality or MACE, with FT4 concentration of 30 pmol/L or greater conferring increased risk. Compared with no intervention, treatment with antithyroid drugs, surgery or radioiodine gland ablation, or thyroxine did not control thyroid hormone excess. We have documented reduced survival and increased cardiovascular morbidity in a cohort of patients with RTHβ for the first time. These outcomes might be driven by lifelong cardiac exposure to thyroid hormone excess; and effective therapies, targeting hormone resistant pathways, could potentially curtail this risk. Royal College of Physicians, Wellcome Trust Investigator Award, and NIHR Cambridge Biomedical Research Centre.

Maternal Mental Health and Children’s Problem Behaviours: A Bi-directional Relationship?

Transactional theory and the coercive family process model have illustrated how the parent-child relationship is reciprocal. Emerging research using advanced statistical methods has examined these theories, but further investigations are necessary. In this study, we utilised linked health data on maternal mental health disorders and explored their relationship with child problem behaviours via the Strengths and Difficulties Questionnaire for over 13 years. We accessed data from the Millennium Cohort Study, linked to anonymised individual-level population-scale health and administrative data within the Secure Anonymised Information Linkage (SAIL) Databank. We used Bayesian Structural Equation Modelling, specifically Random-Intercept Cross-Lagged Panel Models, to analyse the relationships between mothers and their children. We then explored these models with the addition of time-invariant covariates. We found that a mother’s mental health was strongly associated over time, as were children’s problem behaviours. We found mixed evidence for bi-directional relationships, with only emotional problems showing bi-directional associations in mid to late childhood. Only child-to-mother pathways were identified for the overall problem behaviour score and peer problems; no associations were found for conduct problems or hyperactivity. All models had strong between-effects and clear socioeconomic and sex differences. We encourage the use of whole family-based support for mental health and problem behaviours, and recommend that socioeconomic, sex and wider differences should be considered as factors in tailoring family-based interventions and support.

#5476 SEX DIFFERENCES IN INCIDENT KIDNEY FAILURE AND THE IMPACT OF RISK FACTORS IN A POPULATION STUDY

Abstract Background and Aims Chronic kidney disease (CKD) has different effects on women and men. Women are more likely to have CKD, but men are more likely to develop kidney failure requiring treatment (KFRT: dialysis or transplantation). Recent studies have highlighted sex differences in CKD progression and there is a need to determine if this relates to differential effects of risk factors. Method We used primary care data stored within the electronic health records repository Secure Anonymised Information Linkage Databank (SAIL) for adults with CKD stages G3/4 (estimated glomerular filtration rate (eGFR) 15-59 mL/min/1.73 m2) living in Wales, UK. We studied the relationship between sex and the development of kidney failure (KFRT or incident eGFR&amp;lt;15 mL/min/1.73 m2 for ≥3 months). Sex-specific rates of kidney failure were compared using an event plot with patients censored on the date of death. Cox proportional hazards models tested associations between sex and kidney failure, before and after adjustment for other known risk factors (age, baseline eGFR, smoking, social deprivation, diabetes mellitus and hypertension). Interactions between sex and risk factors were sought and interaction terms were retained if these were statistically significant (p-value&amp;lt;0.05). Models were then stratified by sex to compare the impact of risk factors in men and women. Results 135,635 patients (median age 78 years, 57% female, median baseline eGFR 50 mL/min/1.73 m2) were followed up for a median of 6.8 years, representing a total of 782,237 patient years. 1.1% of women and 2.3% of men developed kidney failure. An unadjusted Cox model including both sexes showed a hazard ratio of 2.06 (95% confidence interval 1.89-2.24) for men. After adjustment for all risk factors and inclusion of interaction terms (between sex and baseline eGFR and sex and age), men were not more likely to develop kidney failure (aHR 0.91, 0.60-1.38) (Figure 1A). In sex-stratified models, kidney failure was most likely to develop in those with low baseline eGFR, younger age, current and ex-smokers, patients with diabetes mellitus and patients with hypertension (Figure 1B). Diabetes was a more important risk factor for kidney failure in women (aHR in women 1.73 (1.51-1.98) compared with men (aHR 1.56, 1.39-1.74). Hazard ratios for other risk factors were similar in men and women. Conclusion We found that sex differences in rates of kidney failure are related to a differential impact of risk factors – in particular diabetes – on CKD progression. These results warrant further investigation with a need to determine whether risk reduction strategies should be different in men and women with CKD, or whether current diagnosis, monitoring and treatment strategies are either applied differentially or have different benefit and harms by sex.

The burden of COVID‐19 on all‐cause mortality in older adults living in Wales

AbstractBackgroundThe COVID‐19 pandemic has profoundly impacted the lives of people living with dementia (PLWD). Mitigating measures have led to extreme social isolation and reduced or limited capacity within routine health and social care services. Using anonymised individual‐level, population‐scale linked electronic healthcare, demographic and mortality records in Wales, we have examined the impact of the COVID‐19 pandemic on all‐cause mortality in PLWD and in older adults living with other comorbid conditions.MethodUsing the Secure Anonymised Information Linkage (SAIL) Databank (Lyons et al., 2009), we identified six cohorts of individuals aged 50‐101 and living in Wales on or before 1st February 2020, with conditions in the following domains: dementia, cardiovascular, respiratory, metabolic, renal, and cerebrovascular. For each, we identified paired samples matched by age and sex using propensity sampling. Evidence for comorbidities were extracted using ICD‐10 and READ codes. We quantified excess mortality in PLWD during the COVID‐19 period (July 2020 – May 2021 at the point of the analysis) by comparing weekly mortality to a baseline rate (2015‐2019 average) and to the population paired sample. We then extracted retrospective datasets across sixteen‐month periods from 2010‐2020. Finally, we estimated all‐cause mortality odds‐ratios for each period and comorbid domain using logistic regression, controlling for age and sex.ResultPLWD had higher risk of all‐cause mortality compared to a matched sample of individuals without dementia (Figure 1a), especially during the first wave of the pandemic (April 2020, Figure 1b), and in older PLWD (Figure 1c). Examining evidence across other comorbid conditions (Figure 2), logistic regression modelling showed the greatest increase in mortality odds among PLWD (Figure 2f) compared to people without dementia, increasing from 4.47 in 2018 to 5.61 in 2020. The magnitude of the increase in odds among people with cardiovascular, metabolic, renal, and cerebrovascular conditions from 2020‐2021 compared to previous years was smaller compared to the increase in PLWD (Figures 2a, 2c‐e).ConclusionPLWD experienced increased mortality risk compared to those living with other comorbid conditions during 2020. Further work will focus on the composition of death causes and the contribution of other comorbidities to all‐cause mortality among PLWD.

A pilot intervention to improve uptake and equality of childhood influenza vaccination in an area of Wales, through the introduction of a mixed delivery model including nursery school immunisation sessions.

The schools-based influenza vaccination programme has seen consistently high uptake in Wales, however coverage in pre-school two and three-year olds is lower. One health board area (Cwm Taf University Health Board (UHB)) developed an intervention to offer live attenuated influenza vaccine (LAIV) for three-year olds attending nursery schools alongside the existing general practice (GP) programme. During the pilot, sessions were delivered by health visitors, working with school nurses. The mixed delivery model led to vaccination data being recorded in two separate data systems. To evaluate the impact of the pilot on overall vaccine uptake, data linkage was carried out within the Secure Anonymised Information Linkage (SAIL) Databank. Overall influenza vaccine uptake was calculated for each health board in Wales for two and three-year olds for the 2015-16, 2016-17, and 2017-18 influenza programmes. Uptake in two-year olds in Cwm Taf UHB and also uptake in three-year olds in other health boards in Wales were the comparison groups. Uptake of influenza vaccine in the 2015-16 (pre-intervention) period was 41.0% for three-year olds in Cwm Taf UHB. Following the intervention, coverage increased to 70.7% and 71.5% for 2016-17 and 2017-18 respectively. The same increases in uptake were not seen in two-year olds in Cwm Taf UHB or in three-year olds in non-intervention health boards. In Cwm Taf UHB resident three-year olds in 2015-16 there was an inequality gap in the uptake of 17.4 percentage points between the most and least deprived areas. Uptake increased across all deprivation quintiles in 2016-17 and 2017-18; and the inequality gap decreased to 10.3 and 13.4 percentage points respectively. Influenza vaccination uptake and equality of uptake in three-year olds can be improved by adopting a mixed delivery model across nursery school based immunisation sessions with the additional option of influenza vaccination at GPs.