Albert Prats-Uribe

Background and aims: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. However, large-scale epidemiological evidence remains scarce due to challenges in real-world disease recognition. This study aimed to characterize clinically recognized HCM and obstructive HCM (oHCM) across six European countries regarding prevalence, demographics, and clinical characteristics. Methods: We conducted a retrospective cohort study using routinely collected healthcare data from six European countries, all mapped to the Observational Medical Outcomes Partnership (OMOP) Common Data Model within the DARWIN EU® network: CPRD-GOLD (UK), DK-DHR (Denmark), InGef RDB (Germany), NAJS (Croatia), NLHR (Norway), and SIDIAP (Spain). Clinically recognized HCM was defined based on recorded diagnoses captured in routine healthcare data, rather than on imaging-, haemodynamic-, or genotype-confirmed population screening. Adults (≥18 years) with a first recorded HCM or oHCM diagnosis after 2010 were included. We estimated annual period prevalence and described recorded comorbidities, diagnostic measurements, and treatments before, at, and after diagnosis. Results: Among 40 277 individuals with HCM, 12 363 (31%) were first diagnosed with oHCM. Females were older than males at diagnosis (median 67–78 vs 57–68 years). Annual period prevalence increased over time, ranging from 0.04% (95% Confidence interval: 0.04–0.05) to 0.24% (0.23–0.24) in recent years. Prevalence was higher in males, but differences diminished among those aged ≥80 and with oHCM. Cardiovascular comorbidities were frequently recorded before and at the time of first diagnosis, especially hypertension, cardiac arrhythmias, ischaemic heart disease, and heart failure. Beta-blockers, diuretics, and angiotensin-converting enzyme inhibitors were the most common treatments. Most comorbidities and treatments were recorded over a year before HCM diagnosis. Conclusions: An increase in the prevalence of clinically recognized HCM across Europe was observed over time. This trend is likely multifactorial and may reflect changes in disease recognition, clinical practice, demographics, database-related factors, and potentially the underlying disease burden. Cardiovascular comorbidities and treatments were frequently recorded prior to diagnosis, which may suggest that some patients would benefit from increased diagnostic awareness.

Objectives: To characterise the use of intra-articular corticosteroid injections (IACIs) in a large patient cohort with OA in UK primary care from 2005 to 2020. We sought to evaluate IACI practices, identify patterns of administration across different joints, assess regional variation and examine potential demographic factors influencing IACI utilisation for managing OA. Methods: This retrospective cohort study used data from the UK Clinical Practice Research Datalink GOLD, a database of primary care health records. Data from other healthcare settings were not included. Patients ≥20 years of age with a first diagnosis of OA between 2005 and 2019 were included. OA and IACIs were identified through Read and Gemscript codes, respectively. Results: Of 220 125 patients with OA, 11% received at least one IACI. The anatomical location was only specified in 56% of IACI records. The highest proportion of injections occurred in patients with multiple joints diagnosed with OA (19.0%), followed by the shoulder (14.9%) and knee (12.5%). The median time from OA diagnosis to first injection was 0.9 years and was shortest for the shoulder (0.3 years) and longest for the elbow (2.1 years). We observed substantial regional variation, with incidence rates ranging from 1.2 injections per 100 patient-years in the South East Coast to 3.8 in Yorkshire and the Humber. Conclusion: This study observed notable variation in the median time from OA diagnosis to injection, across different joints, with substantial heterogeneity in the incidence of IACIs across UK regions.

Background: Intra-articular corticosteroid injections are an adjunct to core treatments for osteoarthritis. The National Institute for Health and Care Research Health Technology Assessment programme commissioned this research to address uncertainty around the long-term benefits and potential risks associated with recurrent intra-articular corticosteroid injections. Objectives: Characterise current intra-articular corticosteroid injection practice. Establish longer-term effects and safety of single and recurrent intra-articular corticosteroid injections. Explore views and experiences of patients and clinicians. Assess the priorities/feasibility for future research. Methods: A cohort study of incident osteoarthritis patients (2005–20) was performed using United Kingdom primary care data (Clinical Practice Research Datalink) linked to hospital data (Hospital Episode Statistics). Incidence of first intra-articular corticosteroid injection was stratified by age, calendar year, gender and geographical region. Longer-term outcomes included incident pain medication and joint replacement. Instrumental variables based on practice preference for intra-articular corticosteroid injection were used in primary analyses. Safety was assessed with propensity score matching and a self-controlled cohort, with outcomes (mortality, bleeding, hemarthrosis, wound infection, diabetes, stroke, ischaemic heart disease, myocardial infarction) assessed at 6 months. Semistructured telephone/videocall interviews were conducted (patients = 38, primary care clinicians = 19), with inductive thematic analysis used to investigate views and experiences of intra-articular corticosteroid injections. A three-round modified Delphi study with patients ( n = 41), healthcare professionals ( n = 25) and academics/researchers ( n = 25) was performed to identify future primary research priorities and feasibility. Results: There were 23,899 (10.8%) osteoarthritis patients receiving intra-articular corticosteroid injections (40% received > 1 injection). Incidence of intra-articular corticosteroid injection at 5-year follow-up was lowest for elbow (5.2%) and highest for shoulder (13.6%). Incidences remained stable for all joints between 2005 and 2019 but varied between regions {3.8 [95% confidence interval 3.4 to 4.1] to 1.4 [95% confidence interval 1.3 to 1.5] injections per 100 patient-years}. Intra-articular corticosteroid injection for knee osteoarthritis was associated with lower incident use of several pain medications at 5-year follow-up; recurrent knee intra-articular corticosteroid injections were associated with greater risk reduction. In primary analyses intra-articular corticosteroid injection was associated with a lower 5-year cumulative incidence of knee replacement (number needed to treat 17, 95% confidence interval 12 to 40), but not hip replacement. In certain analyses, incidences of diabetes, ischaemic heart disease and myocardial infarction were numerically higher with intra-articular corticosteroid injections but 95% confidence interval spanned the null; there were no significant associations with other outcomes. Qualitative interviews demonstrated clinicians were more cautious about administering intra-articular corticosteroid injections compared to patients considering receiving intra-articular corticosteroid injections. Patients valued intra-articular corticosteroid injections; however, access was variable, with contributory factors including clinician concerns about the evidence base and their individual competence and confidence performing intra-articular corticosteroid injections. The Delphi research priority list included 14 questions covering long-term effects, clinical and cost-effectiveness, outcomes measurement, comparison to other treatments, provision, safety, identifying responders, maximising benefits, patient experience, delaying joint replacement and dosage. Limitations: Observational analyses: Possibility of residual confounding. Qualitative research: Self-selecting nature of participation; and while the funding remit focussed on primary care, qualitative findings suggest orthopaedic consultants are key stakeholders. Delphi study: Unable to engage commissioners. Conclusions: Overall, in the UK, intra-articular corticosteroid injection use is unchanged over 15 years; however, there was wide regional heterogeneity. We observed a sustained reduction in usage of certain pain medications after intra-articular corticosteroid injections. Intra-articular corticosteroid injections appear generally safe, although more research is needed on potential safety signals, particularly diabetes and cardiovascular events. Future work: A Delphi study with key stakeholders identified 14 priority questions to guide future intra-articular corticosteroid injection research. Work exploring regional variation in intra-articular corticosteroid injection access would be beneficial. Study registration: This study is registered as ISRCTN32433800; Independent Scientific Advisory Committee (ISAC) for the Medicines and Healthcare Products Regulatory Agency (ISAC protocol no. 20_067RA). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR129011) and is published in full in Health Technology Assessment ; Vol. 29, No. 56. See the NIHR Funding and Awards website for further award information.

An increased risk of COVID-19 mortality risk among certain ethnic groups is well-reported, however data on ethnic disparities in COVID-19-related cardiovascular disease (CVD) are lacking. We estimated age-standardised incidence rates and adjusted hazard ratios for 28-day mortality and 30-day CVD by sex for individual ethnicity groups from England and Wales, using linked health and administrative data. We studied 6-level census-based ethnicity group classification, 10-level classification (only for Wales), and 19-level classification as well as any ethnicity sub-groups comprising >1000 individuals each (only for England). COVID-19 28-day mortality and 30-day CVD risk was increased in most non-White ethnic groups in England, and Asian population in Wales, between 23rd January 2020 and 1st April 2022. English data show mortality decreased during the Omicron variant’s dominance, whilst CVD risk [95% confidence interval] remained elevated for certain ethnic groups when compared to White populations (January-April 2022): by 120% [28-280%] in White and Asian men and 58% [32-90%] in Pakistan men, as compared to White British men; and by 75% [13-172%] in Bangladeshi women, 55% [19-102%] in Caribbean women, and 82% [31-153%] in Any Other Ethnic Group women, as compared to White British women. Ethnically diverse populations in the UK remained disproportionately affected by CVD throughout and beyond the COVID-19 pandemic.

Objectives: To estimate the effect of intra-articular corticosteroid injection (IACI) for osteoarthritis on longer-term incidence of pain medications. Methods: We conducted a cohort study of patients registered in the UK Clinical Practice Research Datalink (CPRD) GOLD primary care database with an incident diagnosis of knee, hip, hand or shoulder osteoarthritis between 2005 and 2019. Exposure of interest was single or repeated use of IACI (analysed separately). Main outcome measures were five-year incidence of uncombined opioids, opioid-nonopioid analgesic combinations, oral corticosteroids, paracetamol, oral non-steroidal anti-inflammatory drugs (NSAIDs) and topical NSAIDs. Instrumental variable (IV) analysis was used, given this methodology can account for strong and unmeasured confounding. Secondary analyses used propensity-score matching and Cox regression. Results: Amongst 74 527 knee osteoarthritis patients, IACI use was associated with lower subsequent prescribing of most pain medications studied, including opioid-nonopioid analgesic combinations following single IACI [number needed to treat (NNT) = 5 (95% CI: 5–6), P < 0.001] and uncombined opioids following repeat IACI [NNT = 12 (8–546), P = 0.049]. Amongst 15 092 hand osteoarthritis patients, single IACI was associated with reduced use of opioid-nonopioid combinations, paracetamol and oral NSAIDs. Secondary analyses confirmed lower incidence rates of opioid-nonopioid combinations after single IACI for knee [hazard ratio (HR) = 0.88 (0.81–0.96)], hip [HR = 0.76 (0.62–0.92)], hand [HR = 0.77 (0.61–0.98)] or shoulder [HR = 0.72 (0.53–0.99)] osteoarthritis. Conclusions: IACI for knee or hand osteoarthritis showed lower incidence of several pain medications over the longer-term relative to no IACI use. Secondary findings suggest IACI may be effective in reducing longer-term use of opioid-nonopioid analgesic combinations for patients with knee, hip, hand or shoulder osteoarthritis.

Background: European countries have included healthcare workers (HCWs) among priority groups for COVID-19 vaccination. We established a multi-country hospital network to measure the SARS-CoV-2 incidence and effectiveness of COVID-19 vaccines among HCWs against laboratory-confirmed SARS-CoV-2 infection. Methods: HCWs from 19 hospitals in 10 countries participated in a dynamic prospective cohort study, providing samples for SARS-CoV-2 testing at enrolment and during weekly/fortnightly follow-up. We measured the incidence during pre-Delta (2 May–6 September 2021), Delta (7 September–14 December 2021), and Omicron (15 December 2021–2 May 2023) waves. Using Cox regression, we measured the relative vaccine effectiveness (rVE) of the first COVID-19 booster dose versus primary course alone during Delta and Omicron waves. Results: We included a total of 3015 HCWs. Participants were mostly female (2306; 79%), with a clinical role (2047; 68%), and had a median age of 44 years. The overall incidence of SARS-CoV-2 infection was 3.01/10,000 person-days during pre-Delta, 4.21/10,000 during Delta, and 23.20/10,000 during Omicron waves. rVE was 59% (95% CI: −25; 86) during Delta and 22% (1; 39) during Omicron waves. rVE was 51% (30; 65) 7–90 days after the first booster dose during the Omicron wave. Conclusions: The incidence of SARS-CoV-2 infection among HCWs was higher during the Omicron circulation period. The first COVID-19 vaccine booster provided additional protection against SARS-CoV-2 infection compared to primary course vaccination when recently vaccinated <90 days. This multi-country HCW cohort study addressing infection as the main outcome is crucial for informing public health interventions for HCWs.

Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25–85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors.

COVID-19 vaccination recommendations include healthcare workers (HCWs). We measured COVID-19 vaccine effectiveness (CVE) of the autumn 2023 dose against laboratory-confirmed SARS-CoV-2 infection in a prospective cohort study of 1,305 HCWs from 13 European hospitals. Overall CVE was 22% (95% CI: −17 to 48), 49% (95% CI: −8 to 76) before and −11% (95% CI: −84 to 34) after the start of BA.2.86/JN.1 predominant circulation. Autumn 2023 COVID-19 vaccination led to a moderate-to-low reduction in SARS-CoV-2 infection incidence in HCWs. Monitoring of CVE is crucial for COVID-19 prevention.

Introduction: Electronic health records can be used to understand the diverse presentation of post-acute and long-term health outcomes following COVID-19 infection. In England, the UK Health Security Agency in collaboration with the University of Oxford have created the ECHOES dataset to monitor how an initial SARS-CoV-2 infection episode is associated with changes in the risk of health outcomes that are recorded in routinely collected health data. Methods: The ECHOES dataset is as a national level dataset combining national level surveillance, administrative, and healthcare data. Entity resolution and data linkages methods are used to create a cohort of individuals who have tested positive and negative for SARS-CoV-2 in England throughout the COVID-19 pandemic, alongside information on a range of health outcomes including diagnosed clinical conditions and mortality, and risk factor information. Results: The dataset contains comprehensive COVID-19 testing data and demographic, socio economic and health related information for 44 million individuals, who tested for SARS-CoV-2 between March 2020 and April 2022, representing 15,720,286 individuals who tested positive and 42,351,016 individuals who tested negative. Discussion: With the application of epidemiological and statistical methods, this dataset allows a range of clinical outcomes to be investigated, including pre-specified health conditions and mortality. Furthermore, understanding of potential determinants of health outcomes can be gained, including pre-existing health conditions, acute disease characteristics, SARS-CoV-2 vaccination status and genomic variant.