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.

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.

Clustering long-term health conditions among 67728 people with multimorbidity using electronic health records in Scotland.

There is still limited understanding of how chronic conditions co-occur in patients with multimorbidity and what are the consequences for patients and the health care system. Most reported clusters of conditions have not considered the demographic characteristics of these patients during the clustering process. The study used data for all registered patients that were resident in Fife or Tayside, Scotland and aged 25 years or more on 1st January 2000 and who were followed up until 31st December 2018. We used linked demographic information, and secondary care electronic health records from 1st January 2000. Individuals with at least two of the 31 Elixhauser Comorbidity Index conditions were identified as having multimorbidity. Market basket analysis was used to cluster the conditions for the whole population and then repeatedly stratified by age, sex and deprivation. 318,235 individuals were included in the analysis, with 67,728 (21·3%) having multimorbidity. We identified five distinct clusters of conditions in the population with multimorbidity: alcohol misuse, cancer, obesity, renal failure, and heart failure. Clusters of long-term conditions differed by age, sex and socioeconomic deprivation, with some clusters not present for specific strata and others including additional conditions. These findings highlight the importance of considering demographic factors during both clustering analysis and intervention planning for individuals with multiple long-term conditions. By taking these factors into account, the healthcare system may be better equipped to develop tailored interventions that address the needs of complex patients.

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.

BACKGROUND: Multimorbidity, 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. METHODS: This 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. RESULTS: Within 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). CONCLUSION: Younger 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.

Rationale for the shielding policy for clinically vulnerable people in the UK during the COVID-19 pandemic: a qualitative study.

INTRODUCTION: Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the first year of the pandemic from March 2020. As the first stage in the EVITE Immunity evaluation (Effects of shielding for vulnerable people during COVID-19 pandemic on health outcomes, costs and immunity, including those with cancer:quasi-experimental evaluation), we generated a logic model to describe the programme theory underlying the shielding intervention. DESIGN AND PARTICIPANTS: We reviewed published documentation on shielding to develop an initial draft of the logic model. We then discussed this draft during interviews with 13 key stakeholders involved in putting shielding into effect in Wales and England. Interviews were recorded, transcribed and analysed thematically to inform a final draft of the logic model. RESULTS: The shielding intervention was a complex one, introduced at pace by multiple agencies working together. We identified three core components: agreement on clinical criteria; development of the list of people appropriate for shielding; and communication of shielding advice. In addition, there was a support programme, available as required to shielding people, including food parcels, financial support and social support. The predicted mechanism of change was that people would isolate themselves and so avoid infection, with the primary intended outcome being reduction in mortality in the shielding group. Unintended impacts included negative impact on mental and physical health and well-being. Details of the intervention varied slightly across the home nations of the UK and were subject to minor revisions during the time the intervention was in place. CONCLUSIONS: Shielding was a largely untested strategy, aiming to mitigate risk by placing a responsibility on individuals to protect themselves. The model of its rationale, components and outcomes (intended and unintended) will inform evaluation of the impact of shielding and help us to understand its effect and limitations.

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.

Health care utilization outcomes in patients with blunt chest wall trauma following discharge from the emergency department: A retrospective, observational data-linkage study.

BACKGROUND: Although much is published reporting clinical outcomes in the patients with blunt chest wall trauma who are admitted to hospital from the ED, less is known about the patients' recovery when they are discharged directly without admission. The aim of this study was to investigate the health care utilization outcomes in adult patients with blunt chest wall trauma, discharged directly from ED in a trauma unit in the United Kingdom. METHODS: This was a longitudinal, retrospective, single-center, observational study incorporating analysis of linked datasets, using the Secure Anonymised Information Linkage databank for admissions to a trauma unit in the Wales, between January 1, 2016, and December 31, 2020. All patients 16 years or older with a primary diagnosis of blunt chest wall trauma discharged directly home were included. Data were analyzed using a negative binomial regression model. RESULTS: There were 3,205 presentations to the ED included. Mean age was 53 years, 57% were male, with the predominant injury mechanism being a low velocity fall (50%). 93% of the cohort sustained between 0 and 3 rib fractures. Four percent of the cohort were reported to have chronic obstructive pulmonary disease, and 4% using preinjury anticoagulants. On regression analysis, inpatient admissions, outpatient appointments and primary care contacts all significantly increased in the 12-week period postinjury, compared with the 12-week period preinjury (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.33-1.99; p < 0.001; OR, 1.28; 95% CI, 1.14-1.43; p < 0.001; OR, 1.02; 95% CI, 1.01-1.02; p < 0.001, respectively). Risk of health care resource utilization increased significantly with each additional year of age, chronic obstructive pulmonary disease and preinjury anticoagulant use (all p < 0.05). Social deprivation and number of rib fracture did not impact outcomes. CONCLUSION: The results of this study demonstrate the need for appropriate signposting and follow-up for patients with blunt chest wall trauma presenting to the ED, not requiring admission to the hospital. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

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.

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.

Sunproofed study protocol: A mixed-methods scoping study of sun safety policies in primary schools in Wales.

BACKGROUND: Skin cancer, including melanoma and non-melanoma (keratinocyte), is increasing in incidence in the UK. Accounting for half of all cancers in England and Wales, the disease significantly impacts overstretched dermatology services. Research suggests that 86% of melanoma is preventable with modified sun exposure. Educating children about sun safety in schools can help prevent skin cancer and is recommended by major health organisations. In England, teaching sun safety in primary schools is compulsory, while in Wales this is left to school discretion. AIMS: Understand how primary schools in Wales are responding to growing skin cancer rates and explore the effectiveness of sun safety policies in schools on knowledge and behaviour. METHODS: Sunproofed is a mixed-methods scoping study comprising 5 work packages (WP) using survey and routine electronic health record (EHR) data supplemented by qualitative case studies. Objective(s) are to: WP1: Discover if primary schools in Wales have sun safety policies; policy characteristics; determine factors that may influence their presence and identify areas where schools need support. WP2: Determine what EHR data is available regarding the incidence of sunburn in primary school children and the feasibility of using this data to evaluate the impact of sun safety policies. WP3: Understand the impact of sun safety policies on sun-safe knowledge and behaviour amongst children, parents, teachers, and school management; identify barriers and facilitators to schools implementing sun safety policies. WP4: Co-produce guidance regarding sun safety policies and best methods for implementation in schools. WP5: Disseminate guidance and findings widely to ensure impact and uptake. DISCUSSION: Skin cancer rates are increasing in the UK, straining limited resources. Sunproofed has the potential to inform the development of future prevention activities, both in Wales and beyond. This could reduce the number of skin cancer cases in the future and keep people healthier for longer.

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.

Association of COVID-19 vaccines ChAdOx1 and BNT162b2 with major venous, arterial, or thrombocytopenic events: A population-based cohort study of 46 million adults in England.

BACKGROUND: Thromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination. METHODS AND FINDINGS: In this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age2, sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection. Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021. The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572). Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex. The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding. CONCLUSIONS: In this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group.

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.

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.

Ranking sets of morbidities using hypergraph centrality.

Multi-morbidity, the health state of having two or more concurrent chronic conditions, is becoming more common as populations age, but is poorly understood. Identifying and understanding commonly occurring sets of diseases is important to inform clinical decisions to improve patient services and outcomes. Network analysis has been previously used to investigate multi-morbidity, but a classic application only allows for information on binary sets of diseases to contribute to the graph. We propose the use of hypergraphs, which allows for the incorporation of data on people with any number of conditions, and also allows us to obtain a quantitative understanding of the centrality, a measure of how well connected items in the network are to each other, of both single diseases and sets of conditions. Using this framework we illustrate its application with the set of conditions described in the Charlson morbidity index using data extracted from routinely collected population-scale, patient level electronic health records (EHR) for a cohort of adults in Wales, UK. Stroke and diabetes were found to be the most central single conditions. Sets of diseases featuring diabetes; diabetes with Chronic Pulmonary Disease, Renal Disease, Congestive Heart Failure and Cancer were the most central pairs of diseases. We investigated the differences between results obtained from the hypergraph and a classic binary graph and found that the centrality of diseases such as paraplegia, which are connected strongly to a single other disease is exaggerated in binary graphs compared to hypergraphs. The measure of centrality is derived from the weighting metrics calculated for disease sets and further investigation is needed to better understand the effect of the metric used in identifying the clinical significance and ranked centrality of grouped diseases. These initial results indicate that hypergraphs can be used as a valuable tool for analysing previously poorly understood relationships and information available in EHR data.

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.

Examining variation in the measurement of multimorbidity in research: a systematic review of 566 studies.

BACKGROUND: A systematic understanding of how multimorbidity has been constructed and measured is unavailable. This review aimed to examine the definition and measurement of multimorbidity in peer-reviewed studies internationally. METHODS: We systematically reviewed studies on multimorbidity, via a search of nine bibliographic databases (Ovid [PsycINFO, Embase, Global Health, and MEDLINE], Web of Science, the Cochrane Library, CINAHL Plus, Scopus, and ProQuest Dissertations & Theses Global), from inception to Jan 21, 2020. Reference lists and tracked citations of retrieved articles were hand-searched. Eligible studies were full-text articles measuring multimorbidity for any purpose in community, primary care, care home, or hospital populations receiving a non-specialist service. Abstracts, qualitative research, and case series were excluded. Two reviewers independently reviewed the retrieved studies with conflicts resolved by discussion or a third reviewer, and a single researcher extracted data from published papers. To assess our objectives of how multimorbidity has been measured and examine variation in the chronic conditions included (in terms of number and type), we used descriptive analysis (frequencies, cross-tabulation, and negative binomial regression) to summarise the characteristics of multimorbidity studies and measures (study setting, source of morbidity data, study population, primary study purpose, and multimorbidity measure type). This systematic review is registered with PROSPERO, CRD420201724090. FINDINGS: 566 studies were included in our review, of which 206 (36·4%) did not report a reference definition for multimorbidity and 73 (12·9%) did not report the conditions their measure included. The number of conditions included in measures ranged from two to 285 (median 17 [IQR 11-23). 452 (79·9%) studies reported types of condition within a single multimorbidity measure; most included at least one cardiovascular condition (441 [97·6%] of 452 studies), metabolic and endocrine condition (440 [97·3%]), respiratory condition (422 [93·4%]), musculoskeletal condition (396 [87·6%]), or mental health condition (355 [78·5%]) in their measure of multimorbidity. Chronic infections (123 [27·2%]), haematological conditions (110 [24·3%]), ear, nose, and throat conditions (107 [23·7%]), skin conditions (70 [15·5%]), oral conditions (19 [4·2%]), and congenital conditions (14 [3·1%]) were uncommonly included. Only eight individual conditions were included by more than half of studies in the multimorbidity measure used (diabetes, stroke, cancer, chronic obstructive pulmonary disease, hypertension, coronary heart disease, chronic kidney disease, and heart failure), with individual mental health conditions under-represented. Of the 566 studies, 419 were rated to be of moderate risk of bias, 107 of high risk of bias, and 40 of low risk of bias according to the Effective Public Health Practice Project quality assessment tool. INTERPRETATION: Measurement of multimorbidity is poorly reported and highly variable. Consistent reporting of measure definitions should be required by journals, and consensus studies are needed to define core and study-dependent conditions to include in measures of multimorbidity. FUNDING: Health Data Research UK.

Microtia: A Data Linkage Study of Epidemiology and Implications for Service Delivery.

Introduction: Previous studies of microtia epidemiology globally have demonstrated significant geographical and ethnic variation, cited broadly as affecting 3-5 in 10,000 live births. The aim of this study was to determine the incidence of microtia in a largely homogeneous ethnic population in the United Kingdom (Wales) and to identify factors, such as distance and socioeconomic status, which may influence the access to surgical intervention. Materials and Methods: A retrospective cohort study was conducted using data linkage to identify patients born between 2000 and 2018 with a diagnosis of microtia. Microtia 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. Sociodemographic attributes were compared using descriptive statistics to determine differences in access to each type of surgical intervention. Results: A total of 101 patients were identified, 64.4% were male and the median age was 12 (8-16). The mean annual incidence was 2.13 microtia cases per 10,000 births over the 19-year study period. Both temporal and geographic variation was noted. The majority of patients undergoing surgery opted for autologous reconstruction (72.9%) at a median age of 9 (7-10) compared to 7 (5-8) for prosthetic reconstruction. Autologous reconstruction had a higher median number of surgeries (2, 1-3) than prosthetic (1.5, 1-2) and a higher median socioeconomic status of 3 (2-4) compared to 2 (1-4) for the prosthetic cohort. There were no statistically significant differences in the distance traveled for surgery. Discussion: This study highlights a role for data linkage in epidemiological analyses and provides a revised incidence of microtia in Wales. Although the majority of patients opted for autologous reconstruction, demographic disparities in socioeconomic status warrant further investigation, emphasizing the importance of striving for equity in accessibility to surgical intervention.