Population aging has shifted the burden of cardiovascular disease toward older adults living with multimorbidity, frailty, cognitive vulnerability, functional impairment, and treatment burden. Yet much of the contemporary cardiovascular evidence still derives from randomized clinical trials (RCTs) designed around biologically homogeneous participants, limiting applicability to real-world geriatric cardiology. Our objective was to perform a comparative methodological analysis of two contemporary European cardiovascular RCTs, HI-COR-65 and SENEKA, as illustrative cases and to propose a geriatric-oriented framework for improving trial design in older adults with cardiovascular multimorbidity. We qualitatively compared both trials across five domains: population representativeness, clinical objectives and outcome hierarchy, exclusion criteria, multidisciplinarity, and patient perspective, including participation burden and patient-reported outcomes. Both trials represent important progress by explicitly enrolling older adults with clinically relevant cardiovascular multimorbidity. However, the analysis identified recurring limitations: geriatric complexity is acknowledged but not operationalized through comprehensive geriatric assessment or vulnerability-based stratification; safety and participation requirements may preferentially select robust older adults; outcome hierarchies remain variably aligned with patient priorities; and intervention models are predominantly pharmacological and monodisciplinary. Future cardiovascular trials in older adults should move from chronological inclusion toward pragmatic, complexity-sensitive design. We propose the Comprehensive Geriatric Cardiology (COMGERCARDIO) framework, which integrates baseline geriatric assessment, vulnerability-adaptive interventions, hierarchical patient-centered outcomes, stratified analysis, and implementation evaluation to generate evidence that is scientifically robust, clinically usable, and equitable for aging populations.

Hydrocortisone (cortisol) is a normal component of breastmilk, but it has not been studied in milk after exogenous administration in pharmacologic amounts. Although it is unlikely that dangerous amounts of hydrocortisone would reach the infant, a better studied corticosteroid might be preferred. Maternal use of hydrocortisone as an enema would not be expected to cause any adverse effects in breastfed infants. Local maternal injections, such as for tendinitis, would not be expected to cause any adverse effects in breastfed infants. Medium to large doses of corticosteroids given systemically or injected into joints or the breast have been reported to cause temporary reduction of lactation. See also Hydrocortisone, Topical. Cortisol in breastmilk might have a role in intestinal maturation, the intestinal microbiome, growth, body composition or neurodevelopment, but adequate studies are lacking.[1] Concentrations follow a diurnal rhythm, with the highest concentrations in the morning at about 7:00 am and the lowest concentrations in the late afternoon and evening.[2,3] Cortisol concentration in milk also increase with infant age and decrease with complementary feeding and infant illness.[4] Cortisol in milk may protect against later infant obesity, especially in girls;[5] however, in another study, milk glucocorticoid levels were positively associated with percent fat mass, adiposity and head circumference at 1 year of age.[6] Maternal stress can increase breastmilk cortisol levels, especially with preterm births.[7,8] Some information indicates that maternal adverse childhood experiences may decrease cortisol concentration in their breastmilk.[9]

Topical hydrocortisone has not been studied during breastfeeding. Since only extensive application of the most potent corticosteroids may cause systemic effects in the mother, it is unlikely that short-term application of topical hydrocortisone would pose a risk to the breastfed infant by passage into breastmilk. However, it would be prudent to use the least potent drug on the smallest area of skin possible. It is important to ensure that the infant's skin does not come into direct contact with the areas of skin that have been treated. Current guidelines allow topical corticosteroids to be applied to the nipples just after nursing for eczema, with the nipples cleaned gently before nursing.[1,2] Only water-miscible cream or gel products should be applied to the breast because ointments may expose the infant to high levels of mineral paraffins via licking.[3] Maternal use rectally with a cream or by suppository poses little to no risk to the breastfed infant.