All-cause and Infection-attributable Mortality Amongst Adults With Bloodstream Infection-a Population-based Study.

Background: Bloodstream infections (BSIs) are common, life-threatening infections. However, it remains unclear whether deaths following BSIs are primarily from uncontrolled infection or underlying comorbidities. We aimed to determine the overall mortality, infection-attributable mortality, and causes of death for four leading BSI pathogens. Methods: This retrospective cohort study was conducted within the Secure Anonymized Information Linkage Databank, containing anonymized population-scale electronic health record data for Wales, UK. We included adults with Escherichia coli, Klebsiella spp, Pseudomonas aeruginosa, and Staphylococcus aureus BSI between 2010 and 2022 using linked data from Public Health Wales and the Office for National Statistics. Thirty-day all-cause and sepsis-specific mortality, as a proxy for infection-attributable mortality, were compared using Cox proportional hazards and competing risk regression, respectively. Results: We identified 35 691 adults with BSI (59.6% E coli). Adjusted analyses revealed that all organisms had a higher 30-day mortality versus E coli with Pseudomonas aeruginosa the highest (hazard ratio, 1.96 [1.76-2.17], P < .001). Cancer was the leading cause of death following BSIs for all organisms, particularly deaths occurring between 30 and 90 days (35.9%). A total of 25.5% of deaths within 30 days involved sepsis. Methicillin-resistant Staphylococcus aureus was associated with the highest sepsis mortality versus E coli (hazard ratio, 2.56 [2.10-3.12], P < .001). Peak C-reactive protein was positively associated with increased sepsis mortality (P < .001). Conclusions: This population-level study challenges the assumption that most deaths following BSIs are directly attributable to uncontrolled infection, particularly subacutely more than 30 days from BSI. Our findings underscore the need for reevaluating clinical trial design and developing better preventive strategies for BSIs.

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).

The association of anxiety disorders and depression with facial scarring: population-based, data linkage, matched cohort analysis of 358 158 patients.

BACKGROUND: Estimates suggest that 1 in 100 people in the UK live with facial scarring. Despite this incidence, psychological support is limited. AIMS: The aim of this study was to strengthen the case for improving such support by determining the incidence and risk factors for anxiety and depression disorders in patients with facial scarring. METHOD: A matched cohort study was performed. Patients were identified via secondary care data sources, using clinical codes for conditions resulting in facial scarring. A diagnosis of anxiety or depression was determined by linkage with the patient's primary care general practice data. Incidence was calculated per 1000 person-years at risk (PYAR). Logistic regression was used to determine risk factors. RESULTS: Between 2009 and 2018, 179 079 patients met the study criteria and were identified as having a facial scar, and matched to 179 079 controls. The incidence of anxiety in the facial scarring group was 10.05 per 1000 PYAR compared with 7.48 per 1000 PYAR for controls. The incidence of depression in the facial scarring group was 16.28 per 1000 PYAR compared with 9.56 per 1000 PYAR for controls. Age at the time of scarring, previous history of anxiety or depression, female gender, socioeconomic status and classification of scarring increased the risk of both anxiety disorders and depression. CONCLUSIONS: There is a high burden of anxiety disorders and depression in this patient group. Risk of these mental health disorders is very much determined by factors apparent at the time of injury, supporting the need for psychological support.

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.

The psychosocial impact of microtia and ear reconstruction: A national data-linkage study.

Introduction: Children with visible facial differences are believed to be at increased risk of negative psychosocial behaviours which may manifest as affective disorders. The aim of this study was to determine whether a diagnosis of microtia, and the associated surgical intervention, is associated with psychosocial implications including impaired educational attainment and a diagnosis of an affective disorder. Methods: A retrospective case-control study was conducted using data linkage to identify patients in Wales with a diagnosis of microtia. Matched controls were sought on the basis of age, gender and socioeconomic deprivation status to yield a total sample size of 709. incidence was calculated using annual and geographic birth rates. Surgical operation codes were used to classify patients into those that had no surgery, autologous reconstruction or prosthetic reconstruction. Educational attainment at 11 years of age, plus a diagnosis of depression or anxiety were used as markers of adverse psychosocial outcomes and the relative risk was attained using logistic regression analyses. Results: There were no significant associations between a diagnosis of microtia and an increased risk of adverse educational attainment or a risk of an affective disorder diagnosis. Male gender and higher deprivation scores were significantly associated with poorer educational attainment, irrespective of a diagnosis of microtia. Surgical intervention of any nature was also not associated with any increased risk of adverse educational or psychosocial outcomes in microtia patients. Discussion: Microtia patients in Wales do not appear to be at greater risk of developing affective disorders or impaired academic performance as a result of their diagnosis or associated surgical intervention. Whilst reassuring, the need for appropriate support mechanisms to maintain positive psychosocial wellbeing and academic achievement in this patient cohort is reinforced.

Inequalities in colorectal cancer screening uptake in Wales: an examination of the impact of the temporary suspension of the screening programme during the COVID-19 pandemic.

BACKGROUND: Response to the early stages of the COVID-19 pandemic resulted in the temporary disruption of cancer screening in the UK, and strong public messaging to stay safe and to protect NHS capacity. Following reintroduction in services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who may benefit from tailored interventions. METHODS: Records within the BSW were linked to electronic health records (EHR) and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank. Ethnic group was obtained from a linked data method available within SAIL. We examined uptake for the first 3 months of invitations (August to October) following the reintroduction of BSW programme in 2020, compared to the same period in the preceding 3 years. Uptake was measured across a 6 month follow-up period. Logistic models were conducted to analyse variations in uptake by sex, age group, income deprivation quintile, urban/rural location, ethnic group, and clinically extremely vulnerable (CEV) status in each period; and to compare uptake within sociodemographic groups between different periods. RESULTS: Uptake during August to October 2020 (period 2020/21; 60.4%) declined compared to the same period in 2019/20 (62.7%) but remained above the 60% Welsh standard. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Compared to the pre-pandemic period in 2019/20, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most income deprived group. Uptake continues to be lower in males, younger individuals, people living in the most income deprived areas and those of Asian and unknown ethnic backgrounds. CONCLUSION: Our findings are encouraging with overall uptake achieving the 60% Welsh standard during the first three months after the programme restarted in 2020 despite the disruption. Inequalities did not worsen after the programme resumed activities but variations in CRC screening in Wales associated with sex, age, deprivation and ethnic group remain. This needs to be considered in targeting strategies to improve uptake and informed choice in CRC screening to avoid exacerbating disparities in CRC outcomes as screening services recover from the pandemic.

Patterns of Healthcare Resource Utilisation of Critical Care Survivors between 2006 and 2017 in Wales: A Population-Based Study.

In this retrospective cohort study, we used the Secure Anonymised Information Linkage (SAIL) Databank to characterise and identify predictors of the one-year post-discharge healthcare resource utilisation (HRU) of adults who were admitted to critical care units in Wales between 1 April 2006 and 31 December 2017. We modelled one-year post-critical-care HRU using negative binomial models and used linear models for the difference from one-year pre-critical-care HRU. We estimated the association between critical illness and post-hospitalisation HRU using multilevel negative binomial models among people hospitalised in 2015. We studied 55,151 patients. Post-critical-care HRU was 11-87% greater than pre-critical-care levels, whereas emergency department (ED) attendances decreased by 30%. Age ≥50 years was generally associated with greater post-critical-care HRU; those over 80 had three times longer hospital readmissions than those younger than 50 (incidence rate ratio (IRR): 2.96, 95% CI: 2.84, 3.09). However, ED attendances were higher in those younger than 50. High comorbidity was associated with 22-62% greater post-critical-care HRU than no or low comorbidity. The most socioeconomically deprived quintile was associated with 24% more ED attendances (IRR: 1.24 [1.16, 1.32]) and 13% longer hospital stays (IRR: 1.13 [1.09, 1.17]) than the least deprived quintile. Critical care survivors had greater 1-year post-discharge HRU than non-critical inpatients, including 68% longer hospital stays (IRR: 1.68 [1.63, 1.74]). Critical care survivors, particularly those with older ages, high comorbidity, and socioeconomic deprivation, used significantly more primary and secondary care resources after discharge compared with their baseline and non-critical inpatients. Interventions are needed to ensure that key subgroups are identified and adequately supported.

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.

Evaluating the cost of managing patients with cellulitis in Wales, UK: A 20-year population-scale study.

This study aimed to estimate costs associated with managing patients with cellulitis from the UK National Health Service (NHS) perspective. The analysis was undertaken through the Secure Anonymised Information Linkage Databank, which brings together population-scale, individual-level anonymised linked data from a wide range of sources, including 80% of primary care general practices within Wales (population coverage ~3.2 million). The data covered a 20-year period from 1999 to 2019. All patients linked to the relevant codes were tracked through primary care settings, recording the number of general practice visits (number of days with an event recorded) and number of in-patient stays. Resources were valued in monetary terms (£ sterling), with costs determined from national published sources of unit costs. These resources were then extrapolated out to reflect UK NHS costs. This is the first attempt to estimate the financial burden of cellulitis using routine data sources on a national scale. The estimated direct annual costs to the Welsh NHS (£28 554 338) are considerable. In-Patient events and length of stay costs are the main cost drivers, with annual Welsh NHS estimates of £19 664 126 with primary care events costing £8 890 212. Initiatives to support patients and healthcare professionals in identifying early signs/risks of cellulitis, improve the accuracy of initial diagnosis, prevent cellulitis recurrence, and improve evidence-based treatment pathways would result in major financial savings, to both the Welsh and UK NHS. In light of these findings, Wales has developed the innovative National Lymphoedema cellulitis Improvement Programme to address these burdens; providing a proactive model of cellulitis care.

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.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.

The epidemiology, healthcare and societal burden of basal cell carcinoma in Wales 2000-2018: a retrospective nationwide analysis.

BACKGROUND: Basal cell carcinoma (BCC) represents the most commonly occurring cancer worldwide within the white population. Reports predict 298 308 cases of BCC in the UK by 2025, at a cost of £265-366 million to the National Health Service (NHS). Despite the morbidity, societal and healthcare pressures brought about by BCC, routinely collected healthcare data and global registration remain limited. OBJECTIVES: To calculate the incidence of BCC in Wales between 2000 and 2018 and to establish the related healthcare utilization and estimated cost of care. METHODS: The Secure Anonymised Information Linkage (SAIL) databank is one of the largest and most robust health and social care data repositories in the UK. Cancer registry data were linked to routinely collected healthcare databases between 2000 and 2018. Pathological data from Swansea Bay University Health Board (SBUHB) were used for internal validation. RESULTS: A total of 61 404 histologically proven BCCs were identified within the SAIL Databank during the study period. The European age-standardized incidence for BCC in 2018 was 224.6 per 100 000 person-years. Based on validated regional data, a 45% greater incidence was noted within SBUHB pathology vs. matched regions within SAIL between 2016 and 2018. A negative association between deprivation and incidence was noted with a higher incidence in the least socially deprived and rural dwellers. Approximately 2% travelled 25-50 miles for dermatological services compared with 37% for plastic surgery. Estimated NHS costs of surgically managed lesions for 2002-2019 equated to £119.2-164.4 million. CONCLUSIONS: Robust epidemiological data that are internationally comparable and representative are scarce for nonmelanoma skin cancer. The rising global incidence coupled with struggling healthcare systems in the post-COVID-19 recovery period serve to intensify the societal and healthcare impact. This study is the first to demonstrate the incidence of BCC in Wales and is one of a small number in the UK using internally validated large cohort datasets. Furthermore, our findings demonstrate one of the highest published incidences within the UK and Europe.

Educational achievements of children aged 10-11 years with cystic fibrosis. A data linkage study in Wales.

Introduction: As people with cystic fibrosis (CF) lead longer, healthier lives, educational qualifications and employment prospects are increasingly important. However, little is known about the social consequences of CF, in particular, any impact on educational achievements and the support children with CF receive in schools. Objectives: To assess the educational achievements of children with CF in Wales compared to the general Welsh population, and the additional learning support children with CF receive in schools. Methods: We conducted a population-scale data linkage study of all children born in Wales using the Secure Anonymised Information Linkage (SAIL) Databank. We used anonymised individual-level population-scale health and administrative data sources to identify children with CF born between 2000 - 2015, linked to educational attainment records. We calculated the percentage of children that reached expected levels in statutory assessment at age 10-11, Key Stage 2 (KS2), and compared this to educational outcomes in the general population. We also assessed the percentage of children with CF that received extra learning support. Results: Out of 150 eligible children, 119 had KS2 results. 77% (95% CI: 69%-84%) of children achieved expected levels in English, 81% (95% CI: 73% -87%) in Mathematics and 82% (95% CI: 75% - 88%) in Science. In the comparable general Welsh population, 83.4% to 91.1% achieved the expected level in English, 84.9% to 91.6% in Maths, and 87.1% to 92.2% in Science across the years of the study. 70% of children with CF received extra learning support. Conclusions: Children with CF in Wales may have worse educational achievements than the general population. More research is needed to inform policies and interventions to better support children with CF to reach their full educational potential and employment opportunities.

SARS-CoV-2 infection risk among 77,587 healthcare workers: a national observational longitudinal cohort study in Wales, United Kingdom, April to November 2020.

OBJECTIVES: To better understand the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers, leading to recommendations for the prioritisation of personal protective equipment, testing, training and vaccination. DESIGN: Observational, longitudinal, national cohort study. SETTING: Our cohort were secondary care (hospital-based) healthcare workers employed by NHS Wales (United Kingdom) organisations from 1 April 2020 to 30 November 2020. PARTICIPANTS: We included 577,756 monthly observations among 77,587 healthcare workers. Using linked anonymised datasets, participants were grouped into 20 staff roles. Additionally, each role was deemed either patient-facing, non-patient-facing or undetermined. This was linked to individual demographic details and dates of positive SARS-CoV-2 PCR tests. MAIN OUTCOME MEASURES: We used univariable and multivariable logistic regression models to determine odds ratios (ORs) for the risk of a positive SARS-CoV-2 PCR test. RESULTS: Patient-facing healthcare workers were at the highest risk of SARS-CoV-2 infection with an adjusted OR (95% confidence interval [CI]) of 2.28 (95% CI 2.10-2.47). We found that after adjustment, foundation year doctors (OR 1.83 [95% CI 1.47-2.27]), healthcare support workers [OR 1.36 [95% CI 1.20-1.54]) and hospital nurses (OR 1.27 [95% CI 1.12-1.44]) were at the highest risk of infection among all staff groups. Younger healthcare workers and those living in more deprived areas were at a higher risk of infection. We also observed that infection rates varied over time and by organisation. CONCLUSIONS: These findings have important policy implications for the prioritisation of vaccination, testing, training and personal protective equipment provision for patient-facing roles and the higher risk staff groups.

Impact of the SARS-CoV-2 pandemic on female breast, colorectal and non-small cell lung cancer incidence, stage and healthcare pathway to diagnosis during 2020 in Wales, UK, using a national cancer clinical record system.

BACKGROUND: COVID-19 pandemic responses impacted behaviour and health services. We estimated the impact on incidence, stage and healthcare pathway to diagnosis for female breast, colorectal and non-small cell lung cancers at population level in Wales. METHODS: Cancer e-record and hospital admission data linkage identified adult cases, stage and healthcare pathway to diagnosis (population ~2.5 million). Using multivariate Poisson regressions, we compared 2019 and 2020 counts and estimated incidence rate ratios (IRR). RESULTS: Cases decreased 15.2% (n = -1011) overall. Female breast annual IRR was 0.81 (95% CI: 0.76-0.86, p < 0.001), colorectal 0.80 (95% CI: 0.79-0.81, p < 0.001) and non-small cell lung 0.91 (95% CI: 0.90-0.92, p < 0.001). Decreases were largest in 50-69 year olds for female breast and 80+ year olds for all cancers. Stage I female breast cancer declined 41.6%, but unknown stage increased 55.8%. Colorectal stages I-IV declined (range 26.6-29.9%), while unknown stage increased 803.6%. Colorectal Q2-2020 GP-urgent suspected cancer diagnoses decreased 50.0%, and 53.9% for non-small cell lung cancer. Annual screen-detected female breast and colorectal cancers fell 47.8% and 13.3%, respectively. Non-smal -cell lung cancer emergency presentation diagnoses increased 9.5% (Q2-2020) and 16.3% (Q3-2020). CONCLUSION: Significantly fewer cases of three common cancers were diagnosed in 2020. Detrimental impacts on outcomes varied between cancers. Ongoing surveillance with health service optimisation will be needed to mitigate impacts.

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.

Impact of the temporary suspension of the Bowel Screening Wales programme on inequalities during the COVID-19 pandemic: a retrospective register-based study.

BACKGROUND: Response to the COVID-19 pandemic resulted in the temporary disruption of routine services in the UK National Health Service, including cancer screening. Following the reintroduction of services, we explored the impact on inequalities in uptake of the Bowel Screening Wales (BSW) programme to identify groups who might benefit from tailored intervention. METHODS: BSW records were linked to electronic health record and administrative data within the Secured Anonymised Information Linkage (SAIL) Databank Trusted Research Environment. We examined uptake in the first 3 months (from August to October, 2020) of invitations following the reintroduction of the BSW programme compared with the same period in the preceding 3 years. We analysed inequalities in uptake by sex, age group, income deprivation quintile, urban and rural location, ethnic group, and uptake between different periods using logistic regression models. FINDINGS: Overall uptake remained above the 60% Welsh standard during the COVID-19 pandemic period of 2020-21 but declined compared with the pre-pandemic period of 2019-20 (60·4% vs 62·7%; p<0·001). During the COVID-19 pandemic period of 2020-21, uptake declined for most demographic groups, except for older individuals (70-74 years) and those in the most deprived quintile. Variation by sex, age, income deprivation, and ethnic groups was observed in all periods studied. Among low-uptake groups, including males, younger individuals (60-64 years), those living in most deprived areas, and ethnic minorities, uptake remains below the 60% Welsh standard. INTERPRETATION: Despite the disruption, uptake remained above the Welsh standard and inequalities did not worsen after the programme resumed activities. However, variations associated with sex, age, deprivation, and ethnicity remain. These findings need to be considered in targeting strategies to improve uptake and informed choice in colorectal cancer screening such as co-producing information products with low-uptake groups and upscaling the use of GP-endorsed invitations and reminder letters for bowel screening. FUNDING: Health Data Research UK, UK Medical Research Council, Administrative Data Research UK, and Health and Care Research Wales.

A methodology to facilitate critical care research using multiple linked electronic, clinical and administrative health records at population scale.

Introduction: Critical Care is a specialty in medicine providing a service for severely ill and high-risk patients who, due to the nature of their condition, may require long periods recovering after discharge. Consequently, focus on the routine data collection carried out in Intensive Care Units (ICUs) leads to reporting that is confined to the critical care episode and is typically insensitive to variation in individual patient pathways through critical care to recovery.A resource which facilitates efficient research into interactions with healthcare services surrounding critical admissions, capturing the complete patient's healthcare trajectory from primary care to non-acute hospital care prior to ICU, would provide an important longer-term perspective for critical care research. Objective: To describe and apply a reproducible methodology that demonstrates how both routine administrative and clinically rich critical care data sources can be integrated with primary and secondary healthcare data to create a single dataset that captures a broader view of patient care. Method: To demonstrate the INTEGRATE methodology, it was applied to routine administrative and clinical healthcare data sources in the Secure Anonymised Data Linking (SAIL) Databank to create a dataset of patients' complete healthcare trajectory prior to critical care admission. SAIL is a national, data safe haven of anonymised linkable datasets about the population of Wales. Results: When applying the INTEGRATE methodology in SAIL, between 2010 and 2019 we observed 91,582 critical admissions for 76,019 patients. Of these, 90,632 (99%) had an associated non-acute hospital admission, 48,979 (53%) had an emergency admission, and 64,832 (71%) a primary care interaction in the week prior to the critical care admission. Conclusion: This methodology, at population scale, integrates two critical care data sources into a single dataset together with data sources on healthcare prior to critical admission, thus providing a key research asset to study critical care pathways.

The Impact of a Centralised Pancreatic Cancer Service: a Case Study of Wales, UK.

INTRODUCTION: The centralisation of pancreatic cancer (PC) services still varies worldwide. This study aimed to assess the impact that a centralisation has had on patients in South Wales, UK. METHODS: A retrospective cohort analysis of patients in South Wales, UK, with PC prior to (2004-2009), and after (2010-2014) the formation of a specialist centre. Patients were identified using record linkage of electronic health records. RESULTS: The overall survival (OS) of all 3413 patients with PC increased from a median (IQR) 10 weeks (3-31) to 11 weeks (4-35), p = 0.038, after centralisation. The OS of patients undergoing surgical resection or chemotherapy alone did not improve (93 weeks (39-203) vs. 90 weeks (50-95), p = 0.764 and 33 weeks (20-57) vs. 33 weeks (19-58), p = 0.793). Surgical resection and chemotherapy rates increased (6.1% vs. 9.2%, p < 0.001 and 19.7% vs. 27.0%, p < 0.001). The 30-day mortality rate trended downwards (7.2% vs. 3.6%, p = 0.186). The percentage of patients who received no treatment reduced (75.2% vs. 69.6%, p < 0.001). CONCLUSION: The centralisation of PC services in South Wales is associated with a small increase in OS and a larger increase in PC treatment utilisation. It is concerning that many patients still fail to receive any treatments.

The association between immunosuppression and skin cancer in solid organ transplant recipients: a control-matched cohort study of 2,852 patients.

Skin cancer is more common in transplant recipients, although the quoted incidence is variable. This study investigated the incidence of skin cancer in solid organ transplant recipients (OTRs) in a national cohort and the effect of pharmacotherapeutic agents Transplant patients were identified from Patient Episode Database for Wales (PEDW) using Office of Population Census and Surveys Classifications of Interventions and Procedures-4 (OPCS-4) codes. Controls were matched to cases according to age, sex and socioeconomic status. Skin cancer data were obtained from linkage with other national data sources. Incidence was calculated per 100,000 person-years at risk (PYAR). Negative binomial regression was used to calculate adjusted incidence rate ratios (IRRs) for each organ type. During 2000-2018, 2,852 Welsh patients underwent solid organ transplantation. A total of 13,527 controls were matched from the general population. The incidence of skin cancer within the OTR cohort was 1203.2 per 100,000 PYAR vs 133.9 in the matched control group. Age, male gender and azathioprine use were all associated with an increased risk of skin cancer. Contemporary immunomodulators such as tacrolimus and mycophenolate were associated with a reduction in skin cancer risk when compared to their predecessors, cyclosporin and azathioprine. The highest adjusted IRR was observed in heart transplant recipients (IRR: 10.82; 95% CI: 3.64-32.19) and the lowest in liver transplant recipients (IRR: 2.86; 95% CI: 1.15-7.13). This study highlights the need for long-term routine skin cancer surveillance for all OTRs and the importance of using contemporary immunomodulators, when possible, for risk reduction.