Metabolic dysfunction–associated steatohepatitis (MASH) is a rapidly escalating global health challenge driven by complex interactions among metabolic regulation, nutrition, immune signalling, gut microbiota, and environmental exposures. Current disease-centric frameworks prioritize late-stage pathology rather than early metabolic resilience. This article aims to redefine liver health as a dynamic, multidimensional state and to propose a prevention-oriented framework centered on nutrition and lifestyle as primary therapeutic pillars. This narrative review synthesizes current evidence on liver health and MASH. Relevant literature was identified through targeted searches, reference screening, and expert knowledge. The proposed framework positions liver health as an active state of metabolic flexibility supported by nutrition, physical activity, sleep quality, and circadian alignment. Advances in microbiome profiling, single-cell analyses, and multi-omics technologies reveal early disruptions that precede irreversible hepatic injury and may serve as actionable intervention targets. Nutrition emerges as a foundational driver that modulates systemic metabolism, inflammatory tone, and host–microbiome interactions. A multidimensional, nutrition-first strategy offers scalable opportunities for early screening, individualized prevention, and public health policy reform. Preventing MASH requires a paradigm shift from disease management to proactive cultivation of hepatic resilience. Integrating nutrition-centered, multidimensional interventions into clinical practice and policy can intercept disease trajectories before histological damage occurs.

Hypertension remains a prevalent, modifiable risk factor for cardiovascular disease, with many patients failing to achieve optimal blood pressure (BP) control despite existing therapies. Pharmacometabolomics offers promise by identifying metabolic biomarkers linked to drug response and holds potential for individualizing antihypertensive treatment. We conducted a systematic review of studies from 2013 to 2023, screening 2577 articles and including five that investigated metabolomics-based biomarkers for antihypertensive drug response in cases of primary hypertension. In total, 46 metabolites were significantly associated with BP responses to diuretics, beta-blockers, and ACE inhibitors or angiotensin receptor blockers. Key predictive metabolites included arachidonic acid, sphingosine-1-phosphate, 2-oxoglutarate, and arachidonoyl-carnitine, affecting responses across fatty acid metabolism, sphingolipid metabolism, the TCA cycle, and amino acid metabolism. This review highlights the potential of pharmacometabolomics to uncover metabolites and pathways associated with individual BP response to antihypertensive drugs. Further validation in diverse populations, drug classes, and combination treatments is needed.

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is a growing clinical challenge, necessitating effective diagnostic strategies to identify advanced liver fibrosis while minimising unnecessary referrals of mild cases. Current clinical guidelines recommend care pathways utilising non-invasive tests (NITs) to stratify patients, but the optimal diagnostic algorithm across care settings remains unclear. This state-of-the-art review systematically examines studies describing clinical care pathways for detecting advanced fibrotic MASLD and stratifying patients at risk. A comprehensive literature search of MEDLINE, Embase, Cochrane Library, and Scopus, finalised in January 2026, identified nine relevant studies that met predefined criteria including structured care plans and applicability beyond diagnosis alone. Pathway populations included patients at risk for MASLD (type 2 diabetes (n = 4) or broad range cardiometabolic risk factors (n = 1)) or confirmed MASLD (n = 4). The most frequently employed NITs were FIB-4 and vibration-controlled transient elastography (VCTE). Numbers needed to screen (NNS) for hepatology referral and advanced fibrosis detection varied considerably across pathways and populations, reflecting heterogeneity in design and fibrosis assessment methods. All studies reported improved patient risk stratification; attendance rates declined at each pathway step. Findings suggest that NIT-based clinical care pathways can effectively align patient management and optimise transmural care for MASLD. Nonetheless, heterogeneity in pathway design and fibrosis determination highlights the need for standardised protocols and validation in larger, at-risk cohorts to strengthen evidence supporting widespread adoption. This review contributes to advancing MASLD management within evolving clinical frameworks.

OBJECTIVES:People with HIV (PWH) have an increased risk of cardiovascular disease (CVD), but longitudinal data from middle-income settings remain limited. This study examined the association between HIV, antiretroviral therapy (ART), and pulse wave velocity (PWV), a marker of arterial stiffness and CVD risk. DESIGN:A longitudinal analysis from the Ndlovu Cohort Study, South Africa. METHODS:The study included 705 participants (325 PWH, 81% on ART at baseline, 19% initiating ART at baseline, and 380 HIV-negative people. Demographic data, HIV/ART status, and covariates were collected at baseline, while PWV was measured at 12 and 36  months. Mixed-effects models were used to analyze PWV changes over time, adjusting for age, sex, and systolic blood pressure (SBP). Results were reported as beta coefficients ( β ) with 95% confidence intervals (CIs). RESULTS:At baseline, PWH were older and predominantly female (67%) compared to HIV-negative people. At 12  months, median PWV was higher in PWH (7.3  m/s) than in HIV-negative people (7.0  m/s, P = 0.001). Over 36  months, PWV increased by 0.30  m/s in PWH and 0.20 m/s in HIV-negative people ( P  = 0.002). ART-naïve individuals had the largest PWV increase after starting ART (6.8  m/s at 12  months to 7.4  m/s at 36  months, P  = 0.001). HIV ( β = 0.65, 95% CI: 0.24-1.06, P  = 0.002) and time ( β = 0.31 m/s per year, P  < 0.001) were significantly associated with higher PWV. CONCLUSIONS:PWV increased over time, particularly in PWH, with ART initiation linked to rapid increases. These findings highlight the need for early CVD risk monitoring, especially post-ART initiation, in resource-limited settings.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes (T2DM) have been associated with dyslipidemia. This study aimed to investigate the association between lipid values and markers of hepatic steatosis and fibrosis in patients with T2DM. Methods: This is a post hoc analysis of the AleCardio randomized controlled trial in patients with T2DM and recent acute coronary syndrome. Risk of liver steatosis was estimated with the Hepatic Steatosis Index (HSI), risk of liver fibrosis with the NAFLD Fibrosis Score (NFS). Results: Of 7226 participants, 526 were untreated with lipid-lowering medication and formed the analysis cohort. Mean age was 61 ± 10 years, and body mass index (BMI) was 28.5 ± 5.8 kg/m2. A total of 75% of individuals had an HSI score > 36, associated with high risk of liver steatosis, elevated NFS scores > 0.67, associated with high risk of liver fibrosis, were present in 15%. Patients with elevated HSI scores had higher BMI, HOMA IR, triglycerides, remnant cholesterol, and lower high-density lipoprotein compared to those with lower scores. Patients with elevated NFS scores had greater BMI and HOMA IR, and had lower triglycerides, remnant cholesterol, and apolipoprotein B in linear regression analyses. Conclusion: Patients with T2DM, cardiovascular disease, and blood-based indices suggesting liver steatosis or fibrosis differed significantly with respect to the lipid profile. An elevated HSI score, suggesting steatosis, was associated with dyslipidemia, an elevated NFS score, suggesting fibrosis, was not. A possible explanation for the latter findings is reduced very-low-density lipoprotein (VLDL-C) synthesis or secretion accompanying advanced hepatocellular dysfunction.

Abstract Background Ethnic disparities in ischemic stroke are substantial and differences in exposure to air pollution have been demonstrated as well. However, the role of air pollution in mediating ethnic disparities in risk of ischemic stroke remains unclear. Understanding this relationship is crucial, as air pollution is a major modifiable risk factor for ischemic stroke. This study aims to determine whether air pollution exposure mediates ischemic stroke risk differences between Indonesian, Surinamese, Dutch Caribbean, and ethnic Dutch populations. Methods We carried out a nationwide cohort study in the Netherlands (2014–2019), including 9,248,484 residents aged 30 or older, free of ischemic stroke at baseline, of Dutch, Surinamese, Indonesian, or Dutch Caribbean ethnicity. Ethnicity was defined based on the country of birth of the individual and their parents. Air pollution exposure was measured via annual residential estimates of particulate matter < 2.5 micrometers (PM2.5) and nitrogen dioxide (NO2) for 2014. The study outcome was time to ischemic stroke occurrence or mortality, identified from nationwide hospital discharge and death registries using ICD-9/ICD-10 codes. Results The cohort included 314,082 (3.4%) Indonesian, 204,158 (2.2%) Surinamese, 69,580 (0.8%) Dutch Caribbean and 8,660,664 (93.7%) ethnic Dutch individuals. Air pollution levels were highest among Surinamese and lowest among Dutch. For Surinamese, NO2 mediated 13.8% (11.0-17.5%) and PM2.5 mediated 7.9% (6.3–9.9%) of the ischemic stroke difference compared to ethnic Dutch. For Dutch Caribbeans, NO2 mediated 14.7% (9.8–26.7%) and PM2.5 mediated 8.0% (8.1–23.3%). Percentages could not be calculated for Indonesians. Conclusion Air pollution substantially mediates the increased ischemic stroke risk in Surinamese and Dutch Caribbean populations. These findings emphasize the urgent need for air pollution reduction strategies to mitigate the disproportionate ischemic stroke burden in these populations.

Objectives To explore differences in preferences for participation in trials with varying degrees of decentralisation among individuals with type 2 diabetes mellitus (T2DM) and to show how personal, disease specific, digital and trial experience factors influence these preferences as well as impact potential trial participation rates.Design A discrete choice experiment was conducted, including 16 choice tasks, with each two trial options and an opt-out.Setting Preference data was collected in the Netherlands between July 2023 and July 2024.Participants A total of 276 individuals with T2DM aged ≥18 years took part in the study.Outcome measures Trial options comprised six attributes: contact with the study team, activities to perform yourself, use of digital technologies, number of scheduled contacts, trial duration, safety and efficacy of the drug. Preference heterogeneity was explored using a latent class analysis.Results Four classes were identified displaying differences in preferences for trial designs. Younger female participants were more likely to have a strong preference for decentralised trials in any form. Two different classes of elderly participants were identified: elderly males who were more likely to accept any trial design including decentralisation versus elderly who were more likely to be averse to participation in all trials. The latter class showed an increase in participation probability for a home-based trial including video consultation, but still was not very likely to join.Conclusions Decentralisation in trials was overall preferred over site-based trials, but variation in preferences was identified and associated with age and gender. This may impact the choice for decentralisation in trials, especially since women and the elderly are often under-represented in trials. Understanding patient preferences may help to overcome participation challenges and to increase diversity in future trials.

Background/Objectives: Street and restaurant foods constitute a major component of daily diets in low-resource settings due to their affordability, accessibility, and convenience. However, they are frequently characterised by high sodium content, posing significant public health risks, particularly for hypertension and cardiovascular diseases. Empirical data on sodium levels in Nigerian street and restaurant foods remain limited. This study assessed the sodium content of commonly consumed street and restaurant foods in Kano and Ogun States and the Federal Capital Territory in Nigeria using a multilevel analytical framework. Methods: A total of 2583 food samples were collected from street vendors and three categories of restaurants (self-service, quick-service, and hotel restaurants) between August and October 2024. Sodium concentration was measured using a validated digital salt meter. In all three states, rice-based dishes were the most commonly available street and restaurant foods. Results: More than half (55.4%) were classified as high-sodium (>600 mg/100 g), while only 4.1% were classified as low-sodium (<120 mg/100 g). Median sodium content was highest in the FCT (720 mg/100 g), followed by Kano (650 mg/100 g) and Ogun (600 mg/100 g). Soups and stews had the highest median sodium levels (1360 mg/100 g), with several traditional dishes exceeding 1000 mg/100 g. Multilevel mixed-effects modelling demonstrated that sodium exposure was driven primarily by food type (p < 0.001) and vendor environment (p = 0.009), rather than geographic location (state effect: p = 0.217), indicating structurally embedded issues with sodium content throughout the Nigerian food system. Conclusions: These findings support multilevel sodium reduction interventions targeting high-sodium food categories, vendor preparation practices, and strengthened surveillance to monitor progress toward World Health Organization population sodium reduction targets.

INTRODUCTION:We estimated vaccine effectiveness (VE) of JN.1 COVID-19 vaccination against SARS-CoV-2 infection by (sub)variant between 23 September 2024 and 23 February 2025. METHODS:JN.1 vaccine-eligible participants of an ongoing prospective cohort study (VAccine Study COvid-19; VASCO) were included: individuals aged ≥60 years, and individuals aged <60 years with a medical risk condition or who were healthcare workers. In VASCO, questionnaire and serology data are regularly collected and self-tests are provided. SARS-CoV-2 infection was based on reported positive self-tests and/or anti-nucleoprotein serology results. The variant of infection was determined by whole genome sequencing of viral genetic material in positive self-tests. VE against infection was estimated using Cox regression with JN.1-vaccination as time-varying exposure, and VE against JN.1 subvariants KP.3.1.1 and XEC using multinomial logistic regression with matching of infected and uninfected participants by calendar week. Models were adjusted for age group, sex, education level, medical risk condition and SARS-CoV-2 infection history. RESULTS:Of 4490 JN.1-vaccine eligible participants <60 years, 1283 (29%) were vaccinated. Of 19,349 participants ≥60 years, 14,400 (74%) were vaccinated. During follow-up 2142 infections occurred, of which the majority was self-reported (72%). VE was 16% (95%CI: -11-36) in participants <60 years and 13% (95%CI: 2-23) in participants ≥60 years. VE against KP.3.1.1 (n = 251;27%) did not differ significantly from the VE against XEC (n = 195;5%)(OR:1.3; 0.8-2.1). CONCLUSION:We found that, during a 5-month study period with low incidence, JN.1-vaccination provided limited added protection in preventing SARS-CoV-2 infection. The observed VE estimates indicate potentially lower protection against XEC than KP.3.1.1, but the power to detect such a difference was low.

BACKGROUND:For patients with heart failure (HF), hyperkalemia (HK) may prevent optimal renin-angiotensin system inhibitor (RASi) use. Randomized trials show that patiromer, a contemporary potassium binder, reduces serum potassium (sK+) concentrations and HK, potentially enabling RASi optimization. We sought to assess the real-world effectiveness of patiromer in facilitating RASi optimization in HF patients at increased risk of HK. METHODS AND RESULTS:The CARE-HK in HF (Cardiovascular and Renal Treatment in HF Patients with HK or at High Risk of HK) (NCT04864795) was a prospective registry of patients with chronic HF at increased risk of HK (prior or current HK or estimated glomerular filtration rate of <45 mL/min/1.73 m²). Patients treated with patiromer were propensity score matched with others not receiving potassium binders. HK episodes, sK+, and RASi optimization (≥50% target doses) were evaluated prospectively and retrospectively. Among 2558 patients, 234 (9.1%) received patiromer for a median of 12.0 months (interquartile range 6.0-19.4 months). Propensity matching yielded 211 patients treated with patiromer and 361 matched controls. The median patient age was 73 years (interquartile range 64-79 years); 79.4% were men, 50.2% had diabetes, and 44.9% had an estimated glomerular filtration rate of <45 mL/min/1.73 m². At patiromer initiation, the median sK+ was 5.5 mEq/L (interquartile range 5.4-5.7 mEq/L) and declined by 0.21 mEq/L (95% confidence interval 0.30-0.12 mEq/L) (P < .0001). However, RASi/mineralocorticoid receptor antagonist optimization within 2 years remained at ≤40% and did not increase with patiromer. CONCLUSIONS:In contemporary clinical practice, patiromer was associated with reducing sK+ but rates of RASi/mineralocorticoid receptor antagonist optimization remain low. Overcoming clinical inertia, including the addition of patiromer when appropriate, is required to optimize RASi/mineralocorticoid receptor antagonist therapy in patients with HF at high risk of HK.

Hypertension remains a major public health concern. Diet is a well established modifiable risk factor for hypertension and may interact with antihypertensive drugs. This scoping review aimed to identify dietary factors that modify the blood pressure (BP) lowering effects of antihypertensive drugs. The review protocol was preregistered on Zenodo and was guided by PRISMA-ScR. Studies were included when participants were treated with a specified antihypertensive drug class and a dietary intervention. Of 7346 screened reports, 43 met inclusion criteria and investigated 16 dietary factors across five antihypertensive drug classes. Evidence for effect modification was available for eight dietary factors in ten drug-diet combinations. Of these, seven combinations suggested modification of the BP lowering effect of antihypertensive drugs, either a trend toward enhancement or attenuation. In addition, sodium restriction, potassium and magnesium supplementation showed consistent BP-lowering effects when added to drug therapy. These findings support the potential of integrating dietary considerations into antihypertensive treatment strategies to improve BP control.

AIMS:Hypertension is a highly common cardiovascular risk factor, and a large proportion of patients with coronary heart disease (CHD) have uncontrolled hypertension. We report on the distribution and determinants of hypertension awareness, treatment, and control in CHD hypertensive patients. METHODS:The EUROASPIRE V survey included 8261 CHD patients from 27 countries. Awareness was defined as patients reporting being told by a health professional to have raised blood pressure (BP), being aware of their BP target and latest measurement. Patients using antihypertensive medication to lower BP were considered treated. Controlled hypertension was defined as BP <140/90mmHg (<140/85mmHg in patients with diabetes). Factors associated with hypertension awareness, treatment and control were identified with logistic regression. RESULTS:A total of 6496 EUROASPIRE V patients were considered hypertensive, from which 60.4% were aware, 91.7% were on treatment, and 46.8% were controlled. Number of antihypertensive drugs and adherence were independently associated with awareness (OR 1.23, 95%CI 1.16-1.31, and 2.18, 1.74-2.74 respectively) and control (1.11, 1.05-1.17 and 1.93, 1.57-2.37 respectively). Secondary (1.32, 1.03-1.68) and tertiary (1.70, 1.32-2.17) education and undertaking lifestyle changes (1.60, 1.37-1.87) were associated with awareness. Controlled patients were more often aware (1.43, 1.23-1.65) and had a healthier risk factor profile (BMI >25kg/m2 0.73, 0.61-0.87, diabetes 0.67, 0.59-0.76, LDL ≥1.8mmol/L 0.75, 0.65-0.86) than uncontrolled patients. CONCLUSION:Hypertension control remains poor in hypertensive CHD patients, despite high treatment and reasonable awareness levels. Communication with CHD hypertensive patients, especially those from vulnerable groups, needs to improve to facilitate change of health behaviours.

High intake of processed foods, especially those with high sodium content, is a contributor to hypertension and cardiovascular disease. This study aimed to compare the sodium content of packaged foods and beverages in Nigeria to WHO Global Sodium Benchmarks and similar products in Kenya and South Africa. The study examined packaged foods from major retail stores in the capital cities of the Federal Capital Territory, Kano, and Ogun states in Nigeria from November 2020 to March 2021. Benchmark values were based on the 2021 WHO Global Sodium Benchmarks. We used secondary data from packaged food surveys conducted in South Africa (2015, 2016 and Kenya 2019). Approximately 40.0% (n = 36) of subcategories of packaged foods were captured in the WHO global sodium benchmark. Of these, 64.0% (n = 23) exceeded the benchmarks, including ‘processed meat’ (912.0 vs. 250.0 mg/100 g), cheese (776.0 vs. 190 mg/100 g), and ‘wholegrain chips’ (930.0 vs. 470 mg/100 g). Exactly 36.0% (n = 13) had lower sodium content, such as ‘rice-based snacks’ (113.0 vs. 520 mg/100 g) and ‘dried seafood’ (400 vs. 800 mg/100 g). In seven out of eleven main food categories (64%), Nigeria had a higher sodium content compared to Kenya. Similarly, Nigeria exhibited higher sodium content than South Africa in six out of eleven food categories (55.0%). With 64.0% of Nigerian subcategories exceeding WHO benchmarks and higher sodium levels than South Africa and Kenya in most categories. These findings highlight the urgent need for targeted sodium reduction and product reformulation to align Nigeria’s packaged foods with international benchmarks.

HIV majorly contributes to the disease burden in South Africa. Depressive symptoms are common in people living with HIV (PLHIV). Few studies compared depressive symptoms between PLHIV and those without HIV. The aim of the study was to examine the association of HIV status and depressive symptoms. Moreover, the study aimed to explore the comparison between HIV-negative participants and the different HIV-positive sub-groups regarding their depressive symptoms. A cross-sectional analysis was conducted among PLHIV and HIV-negative participants in rural South Africa, using the baseline data of the Ndlovu Cohort study. Data was collected on demographics, socioeconomic status, and depressive symptoms using the PHQ-9 questionnaire. A score of 10 and above indicated depressive symptoms. Logistic regression analysis on the relationship between HIV status and depressive symptoms was used while adjusting for age, sex, level of education, employment status, income, and ever smoking. The study included 1,927 participants; 46% were PLHIV and 239 (12.5%) had depressive symptoms. PLHIV were more likely to have depressive symptoms than HIV-negative participants (OR 1.34, 95% CI 1.01–1.77). This association was not statistically significant after adjusting for confounders (OR 1.22, 95% CI 0.92–1.63). Compared to HIV-negative participants, ART (antiretroviral treatment) naïve participants had statistically significant higher odds of depressive symptoms (OR 1.84, 95% CI 1.20–2.78). This association remained after adjusting for confounders (OR 1.72, 95% CI 1.11–2.61). There was no statistically significant difference in depressive symptoms between HIV-negative participants and those on ART, regardless of treatment regimen. In general, higher odds of depressive symptoms in ART-naïve PLHIV could reflect poor coping with diagnosis of HIV. Future research to investigate the relation between ART regimen and depressive symptoms, to establish causality and to identify changes over time, is warranted.

INTRODUCTION:Multimorbidity, defined as the coexistence of two or more chronic diseases, is common. It is not well-understood how multimorbidity differs by sex and socioeconomic status. METHODS:Cross-sectional data from the UK Biobank in 2006-10 were used. Socioeconomic status was determined from area-based deprivation and individual education level. Multimorbidity was defined as having two or more chronic diseases, identified through linked hospital-admission data between 1995 and 2022. Modified Poisson regression was used to estimate age-adjusted prevalence relative risks (RRs) and women-to-men ratio of RRs with 95 % confidence intervals (CIs) for association of socioeconomic status with multimorbidity. RESULTS:A total of 502,364 individuals (54 % women) were included. Forty two percent of women and 48 % of men had multimorbidity, with the most common disease combination being cancer and hypertension, and hypertension being the most common single condition in both sexes (68 % of men and 58 % of women). The age-adjusted risk of multimorbidity was higher in men than in women (RR, 1.12, 95 % CI, 1.11-1.13). Compared to those in the least deprived areas, the age-adjusted risk of multimorbidity in the most deprived areas was 1.36 (95% CI, 1.33 1.38) in women, and 1.29 (95% CI, 1.27-1.31) in men, with a women-to-men ratio of RRs of 1.05 (95 % CI, 1.02-1.08). CONCLUSION:Multimorbidity is more common in individuals with lower socioeconomic status, and men have a higher age-adjusted risk than women. The association between area-based deprivation and multimorbidity is stronger in women than men, emphasizing the need for tailored interventions that address both sex and socioeconomic disparities in multimorbidity.

AIMS:Statins are widely used for the prevention and management of cardiovascular disease (CVD). Women have been shown to be less likely to receive guideline-recommended dose of statins and reach target lipid levels. This study aims to examine sex differences in titration patterns of statin therapy and in the attainment of cholesterol targets in a Dutch healthcare setting. METHODS AND RESULTS:Data on statin dispensing was extracted from the PHARMO Data Network between 2011 and 2020. New-statin users with at least two recorded statin dispenses were included. Cox proportional hazards models were used to study the association between sex and time to first uptitration of intensity and Poisson regressions were used to estimate sex differences in the attainment of cholesterol targets within 6 and 18 months after statin initiation. We identified 68 150 new users of statin therapy (46% women) with a median age of 65 years [Q1-Q3: 57-72]. The cumulative incidence of uptitration after 3 years of follow-up was 10% in women and 12% in men. After adjustment for age, CVD and other individual characteristics, women were 28% less likely to be uptitrated compared to men (adjusted hazard ratio for women vs. men 0.72 [95% confidence interval (CI) 0.69-0.75]). The adjusted risk ratio of achieving cholesterol target levels within 6 and 18 months after statin initiation in women vs. men were 0.95 (95% CI 0.93-0.97) and 0.98 (95% CI 0.97-0.99). CONCLUSION:Among new statin users, women are less likely to be uptitrated compared to men and to achieve cholesterol target levels.

Background: Myocarditis and pericarditis are recognised risks following COVID-19 vaccination, including the mRNA-1273 vaccine. Most cases occur shortly following the second dose of this vaccine, and incidence is highest among young males. However, little is known about risk factors beyond age and sex and about the longer-term clinical course. This study aims to identify possible risk factors for myocarditis and pericarditis following mRNA-1273 vaccination, to characterise the clinical course of myocarditis and pericarditis, both associated with mRNA-1273 vaccination and not associated with vaccination, and to identify risk factors for severe outcomes (i.e., cardiac or thromboembolic complications, severe hospital outcomes, all-cause hospital readmission, and death). Methods: This study is being conducted within the Vaccine Monitoring Collaboration for Europe (VAC4EU) association using routinely collected healthcare data from five data sources from four European countries (Denmark, Norway, Spain, and the United Kingdom). The study is being performed using a common data model, and all analyses are performed separately in each data source in a federated manner following a common protocol. A case–cohort analysis set is identified within each data source for identifying potential risk factors for myocarditis and pericarditis following mRNA-1273 vaccination using logistic regression analysis. The clinical course of myocarditis and pericarditis is being assessed using a cohort study design and describes all cases (i.e., cases associated with mRNA-1273 and unexposed cases). Cox regression analysis is applied to assess the associations between risk factors and several follow-up outcomes. Conclusions: This protocol describes the study methodology of an international collaborative initiative with the aim of assessing the risk factors and clinical course of myocarditis and pericarditis following mRNA-1273 vaccination using a federated network of five European data sources.

Clinical trials often face recruitment challenges. From the participant's perspective, barriers such as time commitment, travel to sites, and logistical burden, like arranging care duties or time off work, can deter enrolment. Decentralized clinical trials (DCTs) aim to address these by shifting activities closer to participants' homes and using online methods for recruitment and consent. This study explores recruitment strategies and remote eConsent implementation in a decentralized setting. The RADIAL trial, a three-arm, open-label, phase IV study in six European countries, enrolled participants with type 2 diabetes mellitus administering Insulin Glargine 300 U/ml. Recruitment strategies included online campaigns, search engine advertising, social media, and research database outreach. The remote consent process involved eConsent, telemedicine consultations, eIdentification, and eSignatures. Online recruitment campaigns generated a lot of impressions but led to very few pre-screener completions or enrolments. In contrast, outreach through research databases proved more effective, accounting for 7 of the 8 enrolled participants in the decentralized arm. Major pre-screening drop-off occurred at the initial consent step, with 69% exiting before data collection. Eleven participants successfully completed eConsent; 4 others required remote paper-based consent due to eIdentification issues. Implementing the multimedia-enhanced eConsent system was resource-intensive, complicated by country-specific layouts and differing regulatory requirements. Tailored recruitment strategies and simplified remote consent processes are needed to enhance the accessibility and efficiency of DCTs. Further research should optimize targeting and keyword use in online recruitment.