Uptake of COVID-19 vaccinations amongst 3,433,483 children and young people: meta-analysis of UK prospective cohorts.

SARS-CoV-2 infection in children and young people (CYP) can lead to life-threatening COVID-19, transmission within households and schools, and the development of long COVID. Using linked health and administrative data, we investigated vaccine uptake among 3,433,483 CYP aged 5-17 years across all UK nations between 4th August 2021 and 31st May 2022. We constructed national cohorts and undertook multi-state modelling and meta-analysis to identify associations between demographic variables and vaccine uptake. We found that uptake of the first COVID-19 vaccine among CYP was low across all four nations compared to other age groups and diminished with subsequent doses. Age and vaccination status of adults living in the same household were identified as important risk factors associated with vaccine uptake in CYP. For example, 5-11 year-olds were less likely to receive their first vaccine compared to 16-17 year-olds (adjusted Hazard Ratio [aHR]: 0.10 (95%CI: 0.06-0.19)), and CYP in unvaccinated households were less likely to receive their first vaccine compared to CYP in partially vaccinated households (aHR: 0.19, 95%CI 0.13-0.29).

Risk of severe COVID-19 outcomes after autumn 2022 COVID-19 booster vaccinations: a pooled analysis of national prospective cohort studies involving 7.4 million adults in England, Northern Ireland, Scotland and Wales.

Background: UK COVID-19 vaccination policy has evolved to offering COVID-19 booster doses to individuals at increased risk of severe Illness from COVID-19. Building on our analyses of vaccine effectiveness of first, second and initial booster doses, we aimed to identify individuals at increased risk of severe outcomes (i.e., COVID-19 related hospitalisation or death) post the autumn 2022 booster dose. Methods: We undertook a national population-based cohort analysis across all four UK nations through linked primary care, vaccination, hospitalisation and mortality data. We included individuals who received autumn 2022 booster doses of BNT162b2 (Comirnaty) or mRNA-1273 (Spikevax) during the period September 1, 2022 to December 31, 2022 to investigate the risk of severe COVID-19 outcomes. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CIs) for the association between demographic and clinical factors and severe COVID-19 outcomes after the autumn booster dose. Analyses were adjusted for age, sex, body mass index (BMI), deprivation, urban/rural areas and comorbidities. Stratified analyses were conducted by vaccine type. We then conducted a fixed-effect meta-analysis to combine results across the four UK nations. Findings: Between September 1, 2022 and December 31, 2022, 7,451,890 individuals ≥18 years received an autumn booster dose. 3500 had severe COVID-19 outcomes (2.9 events per 1000 person-years). Being male (male vs female, aHR 1.41 (1.32-1.51)), older adults (≥80 years vs 18-49 years; 10.43 (8.06-13.50)), underweight (BMI <18.5 vs BMI 25.0-29.9; 2.94 (2.51-3.44)), those with comorbidities (≥5 comorbidities vs none; 9.45 (8.15-10.96)) had a higher risk of COVID-19 hospitalisation or death after the autumn booster dose. Those with a larger household size (≥11 people within household vs 2 people; 1.56 (1.23-1.98)) and from more deprived areas (most deprived vs least deprived quintile; 1.35 (1.21-1.51)) had modestly higher risks. We also observed at least a two-fold increase in risk for those with various chronic neurological conditions, including Down's syndrome, immunodeficiency, chronic kidney disease, cancer, chronic respiratory disease, or cardiovascular disease. Interpretation: Males, older individuals, underweight individuals, those with an increasing number of comorbidities, from a larger household or more deprived areas, and those with specific underlying health conditions remained at increased risk of COVID-19 hospitalisation and death after the autumn 2022 vaccine booster dose. There is now a need to focus on these risk groups for investigating immunogenicity and efficacy of further booster doses or therapeutics. Funding: National Core Studies-Immunity, UK Research and Innovation (Medical Research Council and Economic and Social Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.

Understanding and reporting odds ratios as rate-ratio estimates in case-control studies.

Background: We noted that there remains some confusion in the health-science literature on reporting sample odds ratios as estimated rate ratios in case-control studies. Methods: We recap historical literature that definitively answered the question of when sample odds ratios (ORs) from a case-control study are consistent estimators for population rate ratios. We use numerical examples to illustrate the magnitude of the disparity between sample ORs in a case-control study and population rate ratios when sufficient conditions for them to be equal are not satisfied. Results: We stress that in a case-control study, sampling controls from those still at risk at the time of outcome event of the index case is not sufficient for a sample OR to be a consistent estimator for an intelligible rate ratio. In such studies, constancy of the exposure prevalence together with constancy of the hazard ratio (HR) (i.e., the instantaneous rate ratio) over time is sufficient for this result if sampling time is not controlled; if time is controlled, constancy of the HR will suffice. We present numerical examples to illustrate how failure to satisfy these conditions adds a small systematic error to sample ORs as estimates of population rate ratios. Conclusions: We recommend that researchers understand and critically evaluate all conditions used to interpret their estimates as consistent for a population parameter in case-control studies.

The impact of the COVID-19 pandemic on community prescription of opioid and antineuropathic analgesics for cancer patients in Wales, UK.

PURPOSE: Public health measures instituted at the onset of the COVID-19 pandemic in the UK in 2020 had profound effects on the cancer patient pathway. We hypothesise that this may have affected analgesic prescriptions for cancer patients in primary care. METHODS: A whole-nation retrospective, observational study of opioid and antineuropathic analgesics prescribed in primary care for two cohorts of cancer patients in Wales, using linked anonymised data to evaluate the impact of the pandemic and variation between different demographic backgrounds. RESULTS: We found a significant increase in strong opioid prescriptions during the pandemic for patients within their first 12 months of diagnosis with a common cancer (incidence rate ratio (IRR) 1.15, 95% CI: 1.12-1.18, p < 0.001 for strong opioids) and significant increases in strong opioid and antineuropathic prescriptions for patients in the last 3 months prior to a cancer-related death (IRR = 1.06, 95% CI: 1.04-1.07, p < 0.001 for strong opioids; IRR = 1.11, 95% CI: 1.08-1.14, p < 0.001 for antineuropathics). A spike in opioid prescriptions for patients diagnosed in Q2 2020 and those who died in Q2 2020 was observed and interpreted as stockpiling. More analgesics were prescribed in more deprived quintiles. This differential was less pronounced in patients towards the end of life, which we attribute to closer professional supervision. CONCLUSIONS: We demonstrate significant changes to community analgesic prescriptions for cancer patients related to the UK pandemic and illustrate prescription patterns linked to patients' demographic background.

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.

Trends in SARS-CoV-2 infection and vaccination in school staff, students and their household members from 2020 to 2022 in Wales, UK: an electronic cohort study.

OBJECTIVES: We investigated SARS-CoV-2 infection trends, risk of SARS-CoV-2 infection and COVID-19 vaccination uptake among school staff, students and their household members in Wales, UK. DESIGN: Seven-day average of SARS-CoV-2 infections and polymerase chain reaction tests per 1000 people daily, cumulative incidence of COVID-19 vaccination uptake and multi-level Poisson models with time-varying covariates. SETTING: National electronic cohort between September 2020 and May 2022 when several variants were predominant in the UK (Alpha, Delta and Omicron). PARTICIPANTS: School students aged 4 to 10/11 years (primary school and younger middle school, n = 238,163), and 11 to 15/16 years (secondary school and older middle school, n = 182,775), school staff in Wales (n = 47,963) and the household members of students and staff (n = 697,659). MAIN OUTCOME MEASURES: SARS-CoV-2 infection and COVID-19 vaccination uptake. RESULTS: School students had a sustained period of high infection rates compared with household members after August 2021. Primary schedule vaccination uptake was highest among staff (96.3%) but lower for household members (72.2%), secondary and older middle school students (59.8%), and primary and younger middle school students (3.3%). Multi-level Poisson models showed that vaccination was associated with a lower risk of SARS-CoV-2 infection. The Delta variant posed a greater infection risk for students than the Alpha variant. However, Omicron was a larger risk for staff and household members. CONCLUSIONS: Public health bodies should be informed of the protection COVID-19 vaccines afford, with more research being required for younger populations. Furthermore, schools require additional support in managing new, highly transmissible variants. Further research should examine the mechanisms between child deprivation and SARS-CoV-2 infection.

An external validation of the QCOVID3 risk prediction algorithm for risk of hospitalisation and death from COVID-19: An observational, prospective cohort study of 1.66m vaccinated adults in Wales, UK.

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 identify groups of people at highest risk of severe COVID-19 related outcomes following one or two doses of vaccine. OBJECTIVES: To externally validate the QCOVID3 algorithm based on primary and secondary care records for Wales, UK. METHODS: We conducted an observational, prospective cohort based on electronic health care records for 1.66m vaccinated adults living in Wales on 8th December 2020, with follow-up until 15th June 2021. Follow-up started from day 14 post vaccination to allow the full effect of the vaccine. RESULTS: The scores produced by the QCOVID3 risk algorithm showed high levels of discrimination for both COVID-19 related deaths and hospital admissions and good calibration (Harrell C statistic: ≥ 0.828). CONCLUSION: This validation of the updated QCOVID3 risk algorithms in the adult vaccinated Welsh population has shown that the algorithms are valid for use in the Welsh population, and applicable on a population independent of the original study, which has not been previously reported. This study provides further evidence that the QCOVID algorithms can help inform public health risk management on the ongoing surveillance and intervention to manage COVID-19 related risks.

Harmonising electronic health records for reproducible research: challenges, solutions and recommendations from a UK-wide COVID-19 research collaboration.

BACKGROUND: The CVD-COVID-UK consortium was formed to understand the relationship between COVID-19 and cardiovascular diseases through analyses of harmonised electronic health records (EHRs) across the four UK nations. Beyond COVID-19, data harmonisation and common approaches enable analysis within and across independent Trusted Research Environments. Here we describe the reproducible harmonisation method developed using large-scale EHRs in Wales to accommodate the fast and efficient implementation of cross-nation analysis in England and Wales as part of the CVD-COVID-UK programme. We characterise current challenges and share lessons learnt. METHODS: Serving the scope and scalability of multiple study protocols, we used linked, anonymised individual-level EHR, demographic and administrative data held within the SAIL Databank for the population of Wales. The harmonisation method was implemented as a four-layer reproducible process, starting from raw data in the first layer. Then each of the layers two to four is framed by, but not limited to, the characterised challenges and lessons learnt. We achieved curated data as part of our second layer, followed by extracting phenotyped data in the third layer. We captured any project-specific requirements in the fourth layer. RESULTS: Using the implemented four-layer harmonisation method, we retrieved approximately 100 health-related variables for the 3.2 million individuals in Wales, which are harmonised with corresponding variables for > 56 million individuals in England. We processed 13 data sources into the first layer of our harmonisation method: five of these are updated daily or weekly, and the rest at various frequencies providing sufficient data flow updates for frequent capturing of up-to-date demographic, administrative and clinical information. CONCLUSIONS: We implemented an efficient, transparent, scalable, and reproducible harmonisation method that enables multi-nation collaborative research. With a current focus on COVID-19 and its relationship with cardiovascular outcomes, the harmonised data has supported a wide range of research activities across the UK.

COVID-19 booster vaccination uptake and infection breakthrough amongst health care workers in Wales: A national prospective cohort study.

BACKGROUND: From September 2021, Health Care Workers (HCWs) in Wales began receiving a COVID-19 booster vaccination. This is the first dose beyond the primary vaccination schedule. Given the emergence of new variants, vaccine waning vaccine, and increasing vaccination hesitancy, there is a need to understand booster vaccine uptake and subsequent breakthrough in this high-risk population. METHODS: We conducted a prospective, national-scale, observational cohort study of HCWs in Wales using anonymised, linked data from the SAIL Databank. We analysed uptake of COVID-19 booster vaccinations from September 2021 to February 2022, with comparisons against uptake of the initial primary vaccination schedule. We also analysed booster breakthrough, in the form of PCR-confirmed SARS-Cov-2 infection, comparing to the second primary dose. Cox proportional hazard models were used to estimate associations for vaccination uptake and breakthrough regarding staff roles, socio-demographics, household composition, and other factors. RESULTS: We derived a cohort of 73,030 HCWs living in Wales (78% female, 60% 18-49 years old). Uptake was quickest amongst HCWs aged 60 + years old (aHR 2.54, 95%CI 2.45-2.63), compared with those aged 18-29. Asian HCWs had quicker uptake (aHR 1.18, 95%CI 1.14-1.22), whilst Black HCWs had slower uptake (aHR 0.67, 95%CI 0.61-0.74), compared to white HCWs. HCWs residing in the least deprived areas were slightly quicker to have received a booster dose (aHR 1.12, 95%CI 1.09-1.16), compared with those in the most deprived areas. Strongest associations with breakthrough infections were found for those living with children (aHR 1.52, 95%CI 1.41-1.63), compared to two-adult only households. HCWs aged 60 + years old were less likely to get breakthrough infections, compared to those aged 18-29 (aHR 0.42, 95%CI 0.38-0.47). CONCLUSION: Vaccination uptake was consistently lower among black HCWs, as well as those from deprived areas. Whilst breakthrough infections were highest in households with children.

Waning of first- and second-dose ChAdOx1 and BNT162b2 COVID-19 vaccinations: a pooled target trial study of 12.9 million individuals in England, Northern Ireland, Scotland and Wales.

BACKGROUND: Several SARS-CoV-2 vaccines have been shown to provide protection against COVID-19 hospitalization and death. However, some evidence suggests that notable waning in effectiveness against these outcomes occurs within months of vaccination. We undertook a pooled analysis across the four nations of the UK to investigate waning in vaccine effectiveness (VE) and relative vaccine effectiveness (rVE) against severe COVID-19 outcomes. METHODS: We carried out a target trial design for first/second doses of ChAdOx1(Oxford-AstraZeneca) and BNT162b2 (Pfizer-BioNTech) with a composite outcome of COVID-19 hospitalization or death over the period 8 December 2020 to 30 June 2021. Exposure groups were matched by age, local authority area and propensity for vaccination. We pooled event counts across the four UK nations. RESULTS: For Doses 1 and 2 of ChAdOx1 and Dose 1 of BNT162b2, VE/rVE reached zero by approximately Days 60-80 and then went negative. By Day 70, VE/rVE was -25% (95% CI: -80 to 14) and 10% (95% CI: -32 to 39) for Doses 1 and 2 of ChAdOx1, respectively, and 42% (95% CI: 9 to 64) and 53% (95% CI: 26 to 70) for Doses 1 and 2 of BNT162b2, respectively. rVE for Dose 2 of BNT162b2 remained above zero throughout and reached 46% (95% CI: 13 to 67) after 98 days of follow-up. CONCLUSIONS: We found strong evidence of waning in VE/rVE for Doses 1 and 2 of ChAdOx1, as well as Dose 1 of BNT162b2. This evidence may be used to inform policies on timings of additional doses of vaccine.

Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales.

BACKGROUND: Current UK vaccination policy is to offer future COVID-19 booster doses to individuals at high risk of serious illness from COVID-19, but it is still uncertain which groups of the population could benefit most. In response to an urgent request from the UK Joint Committee on Vaccination and Immunisation, we aimed to identify risk factors for severe COVID-19 outcomes (ie, COVID-19-related hospitalisation or death) in individuals who had completed their primary COVID-19 vaccination schedule and had received the first booster vaccine. METHODS: We constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data on 30 million people. We included individuals who received primary vaccine doses of BNT162b2 (tozinameran; Pfizer-BioNTech) or ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccines in our initial analyses. We then restricted analyses to those given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a severe COVID-19 outcome between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant). We fitted time-dependent Poisson regression models and calculated adjusted rate ratios (aRRs) and 95% CIs for the associations between risk factors and COVID-19-related hospitalisation or death. We adjusted for a range of potential covariates, including age, sex, comorbidities, and previous SARS-CoV-2 infection. Stratified analyses were conducted by vaccine type. We then did pooled analyses across UK nations using fixed-effect meta-analyses. FINDINGS: Between Dec 8, 2020, and Feb 28, 2022, 16 208 600 individuals completed their primary vaccine schedule and 13 836 390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0·4%) of the primary vaccine group and 26 100 (0·2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster (rate change: 8·8 events per 1000 person-years to 7·6 events per 1000 person-years). Older adults (≥80 years vs 18-49 years; aRR 3·60 [95% CI 3·45-3·75]), those with comorbidities (≥5 comorbidities vs none; 9·51 [9·07-9·97]), being male (male vs female; 1·23 [1·20-1·26]), and those with certain underlying health conditions-in particular, individuals receiving immunosuppressants (yes vs no; 5·80 [5·53-6·09])-and those with chronic kidney disease (stage 5 vs no; 3·71 [2·90-4·74]) remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected ≥9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29-0·58]). INTERPRETATION: Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics. FUNDING: National Core Studies-Immunity, UK Research and Innovation (Medical Research Council), Health Data Research UK, the Scottish Government, and the University of Edinburgh.

Risk of thrombocytopenic, haemorrhagic and thromboembolic disorders following COVID-19 vaccination and positive test: a self-controlled case series analysis in Wales.

There is a need for better understanding of the risk of thrombocytopenic, haemorrhagic, thromboembolic disorders following first, second and booster vaccination doses and testing positive for SARS-CoV-2. Self-controlled cases series analysis of 2.1 million linked patient records in Wales between 7th December 2020 and 31st December 2021. Outcomes were the first diagnosis of thrombocytopenic, haemorrhagic and thromboembolic events in primary or secondary care datasets, exposure was defined as 0-28 days post-vaccination or a positive reverse transcription polymerase chain reaction test for SARS-CoV-2. 36,136 individuals experienced either a thrombocytopenic, haemorrhagic or thromboembolic event during the study period. Relative to baseline, our observations show greater risk of outcomes in the periods post-first dose of BNT162b2 for haemorrhagic (IRR 1.47, 95%CI: 1.04-2.08) and idiopathic thrombocytopenic purpura (IRR 2.80, 95%CI: 1.21-6.49) events; post-second dose of ChAdOx1 for arterial thrombosis (IRR 1.14, 95%CI: 1.01-1.29); post-booster greater risk of venous thromboembolic (VTE) (IRR-Moderna 3.62, 95%CI: 0.99-13.17) (IRR-BNT162b2 1.39, 95%CI: 1.04-1.87) and arterial thrombosis (IRR-Moderna 3.14, 95%CI: 1.14-8.64) (IRR-BNT162b2 1.34, 95%CI: 1.15-1.58). Similarly, post SARS-CoV-2 infection the risk was increased for haemorrhagic (IRR 1.49, 95%CI: 1.15-1.92), VTE (IRR 5.63, 95%CI: 4.91, 6.4), arterial thrombosis (IRR 2.46, 95%CI: 2.22-2.71). We found that there was a measurable risk of thrombocytopenic, haemorrhagic, thromboembolic events after COVID-19 vaccination and infection.

Methodological Issues in Using a Common Data Model of COVID-19 Vaccine Uptake and Important Adverse Events of Interest: Feasibility Study of Data and Connectivity COVID-19 Vaccines Pharmacovigilance in the United Kingdom.

BACKGROUND: The Data and Connectivity COVID-19 Vaccines Pharmacovigilance (DaC-VaP) UK-wide collaboration was created to monitor vaccine uptake and effectiveness and provide pharmacovigilance using routine clinical and administrative data. To monitor these, pooled analyses may be needed. However, variation in terminologies present a barrier as England uses the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT), while the rest of the United Kingdom uses the Read v2 terminology in primary care. The availability of data sources is not uniform across the United Kingdom. OBJECTIVE: This study aims to use the concept mappings in the Observational Medical Outcomes Partnership (OMOP) common data model (CDM) to identify common concepts recorded and to report these in a repeated cross-sectional study. We planned to do this for vaccine coverage and 2 adverse events of interest (AEIs), cerebral venous sinus thrombosis (CVST) and anaphylaxis. We identified concept mappings to SNOMED CT, Read v2, the World Health Organization's International Classification of Disease Tenth Revision (ICD-10) terminology, and the UK Dictionary of Medicines and Devices (dm+d). METHODS: Exposures and outcomes of interest to DaC-VaP for pharmacovigilance studies were selected. Mappings of these variables to different terminologies used across the United Kingdom's devolved nations' health services were identified from the Observational Health Data Sciences and Informatics (OHDSI) Automated Terminology Harmonization, Extraction, and Normalization for Analytics (ATHENA) online browser. Lead analysts from each nation then confirmed or added to the mappings identified. These mappings were then used to report AEIs in a common format. We reported rates for windows of 0-2 and 3-28 days postvaccine every 28 days. RESULTS: We listed the mappings between Read v2, SNOMED CT, ICD-10, and dm+d. For vaccine exposure, we found clear mapping from OMOP to our clinical terminologies, though dm+d had codes not listed by OMOP at the time of searching. We found a list of CVST and anaphylaxis codes. For CVST, we had to use a broader cerebral venous thrombosis conceptual approach to include Read v2. We identified 56 SNOMED CT codes, of which we selected 47 (84%), and 15 Read v2 codes. For anaphylaxis, our refined search identified 60 SNOMED CT codes and 9 Read v2 codes, of which we selected 10 (17%) and 4 (44%), respectively, to include in our repeated cross-sectional studies. CONCLUSIONS: This approach enables the use of mappings to different terminologies within the OMOP CDM without the need to catalogue an entire database. However, Read v2 has less granular concepts than some terminologies, such as SNOMED CT. Additionally, the OMOP CDM cannot compensate for limitations in the clinical coding system. Neither Read v2 nor ICD-10 is sufficiently granular to enable CVST to be specifically flagged. Hence, any pooled analysis will have to be at the less specific level of cerebrovascular venous thrombosis. Overall, the mappings within this CDM are useful, and our method could be used for rapid collaborations where there are only a limited number of concepts to pool.

Data resource: Children receiving care and support and children in need, administrative records in Wales.

Introduction: In Wales, the Children in Need (CIN) dataset includes information relating to needs of children and social care support. Before the Social Services and Well-being (Wales) Act 2014 came into force in April 2016, this data collection was named the Children in Need census, changing to Children Receiving Care and Support (CRCS) after this date to reflect better the children eligible for inclusion. This paper describes these datasets, their potential for research and their limitations. We describe data that researchers can access via the Secure Anonymised Information Linkage (SAIL) Databank and exploratory linkages made to health records. Methods: CIN and CRCS data were transferred to the SAIL Databank using a standardised approach to provide de-identified data with Anonymised Linking Fields (ALF) for successfully matched records. The linkage method relies on the use of Unique Pupil Numbers (UPN). As such, no records are currently available for children without a UPN, which includes most under age three. ALFs enabled linkage to individual-level health data within SAIL. Health service use was compared to non-CIN/CRCS populations. Results: CRCS data held within the SAIL Databank comprises 25,972 records, 81% of the total number of records reported by the Welsh Government. The CIN data contains 108,449 records, 79% of the Welsh Government's records for this data collection. Health service use of children in need, and children receiving care and support, was roughly equal to that of the non-CIN/CRCS population, except GP visits, where children in need had fewer consultations, and children receiving care and support had more consultations than the comparison population. Conclusion: Researchers can access Welsh CIN and CRCS datasets through the SAIL Databank, enabling research opportunities. Work is ongoing to improve records and to understand better the health and health service use among children captured by CIN and CRCS censuses.

Mental health service use among mothers involved in public family law proceedings: linked data cohort study in South London 2007-2019.

PURPOSE: Mental health problems and substance misuse are common among the mothers of children who experience court-mandated placement into care in England, yet there is limited research characterising these health needs to inform evidence-based policy. In this descriptive study, we aimed to generate evidence about the type, severity, and timing of mental health and substance misuse needs among women involved in public family law proceedings concerning child placement into care ('care proceedings'). METHODS: This is a retrospective, matched cohort study using linked family court and mental health service records for 2137 (66%) of the 3226 women involved in care proceedings between 2007 and 2019 in the South London and Maudsley NHS Mental Health Trust (SLaM) catchment area. We compared mental health service use and risk of dying with 17,096 female-matched controls who accessed SLaM between 2007 and 2019, aged 16-55 years, and were not involved in care proceedings. RESULTS: Most women (79%) were known to SLaM before care proceedings began. Women had higher rates of schizophrenia spectrum disorders (19% vs 11% matched controls), personality disorders (21% vs 11%), and substance misuse (33% vs 12%). They were more likely to have a SLaM inpatient admission (27% vs 14%) or to be sectioned (19% vs 8%). Women had a 2.15 (95% CI 1.68-2.74) times greater hazard of dying, compared to matched controls, adjusted for age. CONCLUSION: Women involved in care proceedings experience a particularly high burden of severe and complex mental health and substance misuse need. Women's increased risk of mortality following proceedings highlights that interventions responding to maternal mental health and substance misuse within family courts should offer continued, long-term support.

Variations in COVID-19 vaccination uptake among people in receipt of psychotropic drugs: cross-sectional analysis of a national population-based prospective cohort.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has disproportionately affected people with mental health conditions. AIMS: We investigated the association between receiving psychotropic drugs, as an indicator of mental health conditions, and COVID-19 vaccine uptake. METHOD: We conducted a cross-sectional analysis of a prospective cohort of the Northern Ireland adult population using national linked primary care registration, vaccination, secondary care and pharmacy dispensing data. Univariable and multivariable logistic regression analyses investigated the association between anxiolytic, antidepressant, antipsychotic, and hypnotic use and COVID-19 vaccination status, accounting for age, gender, deprivation and comorbidities. Receiving any COVID-19 vaccine was the primary outcome. RESULTS: There were 1 433 814 individuals, of whom 1 166 917 received a COVID-19 vaccination. Psychotropic medications were dispensed to 267 049 people. In univariable analysis, people who received any psychotropic medication had greater odds of receiving COVID-19 vaccination: odds ratio (OR) = 1.42 (95% CI 1.41-1.44). However, after adjustment, psychotropic medication use was associated with reduced odds of vaccination (ORadj = 0.90, 95% CI 0.89-0.91). People who received anxiolytics (ORadj = 0.63, 95% CI 0.61-0.65), antipsychotics (ORadj = 0.75, 95% CI 0.73-0.78) and hypnotics (ORadj = 0.90, 95% CI 0.87-0.93) had reduced odds of being vaccinated. Antidepressant use was not associated with vaccination (ORadj = 1.02, 95% CI 1.00-1.03). CONCLUSIONS: We found significantly lower odds of vaccination in people who were receiving treatment with anxiolytic and antipsychotic medications. There is an urgent need for evidence-based, tailored vaccine support for people with mental health conditions.

COVID-19 vaccine uptake and effectiveness in adults aged 50 years and older in Wales UK: a 1.2m population data-linkage cohort approach.

Vaccination programs against COVID-19 vary globally with estimates of vaccine effectiveness (VE) affected by vaccine type, schedule, strain, outcome, and recipient characteristics. This study assessed VE of BNT162b2 and ChAdOx1 vaccines against PCR positive SARS-CoV-2 infection, hospital admission, and death among adults aged 50 years and older in Wales, UK during the period 7 December 2020 to 18 July 2021, when Alpha, followed by Delta, were the predominant variants. We used individual-level linked routinely collected data within the Secure Anonymized Information Linkage (SAIL) Databank. Data were available for 1,262,689 adults aged 50 years and over; coverage of one dose of any COVID-19 vaccine in this population was 92.6%, with coverage of two doses 90.4%. VE against PCR positive infection at 28-days or more post first dose of any COVID-19 vaccine was 16.0% (95%CI 9.6-22.0), and 42.0% (95%CI 36.5-47.1) seven or more days after a second dose. VE against hospital admission was higher at 72.9% (95%CI 63.6-79.8) 28 days or more post vaccination with one dose of any vaccine type, and 84.9% (95%CI 78.2-89.5) at 7 or more days post two doses. VE for one dose against death was estimated to be 80.9% (95%CI 72.1-86.9). VE against PCR positive infection and hospital admission was higher for BNT162b2 compared to ChAdOx1. In conclusion, vaccine uptake has been high among adults in Wales and VE estimates are encouraging, with two doses providing considerable protection against severe outcomes. Continued roll-out of the vaccination programme within Wales, and globally, is crucial in our fight against COVID-19.

First dose ChAdOx1 and BNT162b2 COVID-19 vaccinations and cerebral venous sinus thrombosis: A pooled self-controlled case series study of 11.6 million individuals in England, Scotland, and Wales.

BACKGROUND: Several countries restricted the administration of ChAdOx1 to older age groups in 2021 over safety concerns following case reports and observed versus expected analyses suggesting a possible association with cerebral venous sinus thrombosis (CVST). Large datasets are required to precisely estimate the association between Coronavirus Disease 2019 (COVID-19) vaccination and CVST due to the extreme rarity of this event. We aimed to accomplish this by combining national data from England, Scotland, and Wales. METHODS AND FINDINGS: We created data platforms consisting of linked primary care, secondary care, mortality, and virological testing data in each of England, Scotland, and Wales, with a combined cohort of 11,637,157 people and 6,808,293 person years of follow-up. The cohort start date was December 8, 2020, and the end date was June 30, 2021. The outcome measure we examined was incident CVST events recorded in either primary or secondary care records. We carried out a self-controlled case series (SCCS) analysis of this outcome following first dose vaccination with ChAdOx1 and BNT162b2. The observation period consisted of an initial 90-day reference period, followed by a 2-week prerisk period directly prior to vaccination, and a 4-week risk period following vaccination. Counts of CVST cases from each country were tallied, then expanded into a full dataset with 1 row for each individual and observation time period. There was a combined total of 201 incident CVST events in the cohorts (29.5 per million person years). There were 81 CVST events in the observation period among those who a received first dose of ChAdOx1 (approximately 16.34 per million doses) and 40 for those who received a first dose of BNT162b2 (approximately 12.60 per million doses). We fitted conditional Poisson models to estimate incidence rate ratios (IRRs). Vaccination with ChAdOx1 was associated with an elevated risk of incident CVST events in the 28 days following vaccination, IRR = 1.93 (95% confidence interval (CI) 1.20 to 3.11). We did not find an association between BNT162b2 and CVST in the 28 days following vaccination, IRR = 0.78 (95% CI 0.34 to 1.77). Our study had some limitations. The SCCS study design implicitly controls for variables that are constant over the observation period, but also assumes that outcome events are independent of exposure. This assumption may not be satisfied in the case of CVST, firstly because it is a serious adverse event, and secondly because the vaccination programme in the United Kingdom prioritised the clinically extremely vulnerable and those with underlying health conditions, which may have caused a selection effect for individuals more prone to CVST. Although we pooled data from several large datasets, there was still a low number of events, which may have caused imprecision in our estimates. CONCLUSIONS: In this study, we observed a small elevated risk of CVST events following vaccination with ChAdOx1, but not BNT162b2. Our analysis pooled information from large datasets from England, Scotland, and Wales. This evidence may be useful in risk-benefit analyses of vaccine policies and in providing quantification of risks associated with vaccination to the general public.

Investigating the uptake, effectiveness and safety of COVID-19 vaccines: protocol for an observational study using linked UK national data.

INTRODUCTION: The novel coronavirus SARS-CoV-2, which emerged in December 2019, has caused millions of deaths and severe illness worldwide. Numerous vaccines are currently under development of which a few have now been authorised for population-level administration by several countries. As of 20 September 2021, over 48 million people have received their first vaccine dose and over 44 million people have received their second vaccine dose across the UK. We aim to assess the uptake rates, effectiveness, and safety of all currently approved COVID-19 vaccines in the UK. METHODS AND ANALYSIS: We will use prospective cohort study designs to assess vaccine uptake, effectiveness and safety against clinical outcomes and deaths. Test-negative case-control study design will be used to assess vaccine effectiveness (VE) against laboratory confirmed SARS-CoV-2 infection. Self-controlled case series and retrospective cohort study designs will be carried out to assess vaccine safety against mild-to-moderate and severe adverse events, respectively. Individual-level pseudonymised data from primary care, secondary care, laboratory test and death records will be linked and analysed in secure research environments in each UK nation. Univariate and multivariate logistic regression models will be carried out to estimate vaccine uptake levels in relation to various population characteristics. VE estimates against laboratory confirmed SARS-CoV-2 infection will be generated using a generalised additive logistic model. Time-dependent Cox models will be used to estimate the VE against clinical outcomes and deaths. The safety of the vaccines will be assessed using logistic regression models with an offset for the length of the risk period. Where possible, data will be meta-analysed across the UK nations. ETHICS AND DISSEMINATION: We obtained approvals from the National Research Ethics Service Committee, Southeast Scotland 02 (12/SS/0201), the Secure Anonymised Information Linkage independent Information Governance Review Panel project number 0911. Concerning English data, University of Oxford is compliant with the General Data Protection Regulation and the National Health Service (NHS) Digital Data Security and Protection Policy. This is an approved study (Integrated Research Application ID 301740, Health Research Authority (HRA) Research Ethics Committee 21/HRA/2786). The Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub meets NHS Digital's Data Security and Protection Toolkit requirements. In Northern Ireland, the project was approved by the Honest Broker Governance Board, project number 0064. Findings will be made available to national policy-makers, presented at conferences and published in peer-reviewed journals.

COVID-19 vaccine uptake, effectiveness, and waning in 82,959 health care workers: A national prospective cohort study in Wales.

BACKGROUND: While population estimates suggest high vaccine effectiveness against SARS-CoV-2 infection, the protection for health care workers, who are at higher risk of SARS-CoV-2 exposure, is less understood. METHODS: We conducted a national cohort study of health care workers in Wales (UK) from 7 December 2020 to 30 September 2021. We examined uptake of any COVID-19 vaccine, and the effectiveness of BNT162b2 mRNA (Pfizer-BioNTech) against polymerase chain reaction (PCR) confirmed SARS-CoV-2 infection. We used linked and routinely collected national-scale data within the SAIL Databank. Data were available on 82,959 health care workers in Wales, with exposure extending to 26 weeks after second doses. RESULTS: Overall vaccine uptake was high (90%), with most health care workers receiving theBNT162b2 vaccine (79%). Vaccine uptake differed by age, staff role, socioeconomic status; those aged 50-59 and 60+ years old were 1.6 times more likely to get vaccinated than those aged 16-29. Medical and dental staff, and Allied Health Practitioners were 1.5 and 1.1 times more likely to get vaccinated, compared to nursing and midwifery staff. The effectiveness of the BNT162b2 vaccine was found to be strong and consistent across the characteristics considered; 52% three to six weeks after first dose, 86% from two weeks after second dose, though this declined to 53% from 22 weeks after the second dose. CONCLUSIONS: With some variation in rate of uptake, those who were vaccinated had a reduced risk of PCR-confirmed SARS-CoV-2 infection, compared to those unvaccinated. Second dose has provided stronger protection for longer than first dose but our study is consistent with waning from seven weeks onwards.