SPRINTT and the involvement of stakeholders: strategy and structure.

The current healthcare systems are built around the traditional paradigm of patients suffering from a single acute illness. They are, therefore, largely unprepared to face the increasing demands for health services arising from the expansion of an older population with specific medical needs related to multiple chronic disorders. As a consequence, the medical conditions of a large and growing segment of the older European population are not efficiently managed by the available healthcare services. In the context of an aging population, policy makers such as the European Commission and European Institutions, such as the European Medicines Agency (EMA), devote time and resources to study and accompany the need of the aging population. The EMA recognizes the importance of making sure that the needs of the Elderly are considered during development, approval, and use of new medicines, and, therefore, engages with healthcare professional organisations. The Sarcopenia and Physical Frailty in Older People: Multicomponent Intervention Strategies (SPRINTT) is the obvious result of these strategies. The present article describes the SPRINTT workpackage activities aimed at engaging the scientific discussion on the physical frailty and sarcopenia with the EMA as one of its interlocutor, acknowledging the need to collaborate on this topic to foster a productive dialogue.

Rationale for a preliminary operational definition of physical frailty and sarcopenia in the SPRINTT trial.

In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the adopted instruments, and the reasons for setting the relevant thresholds are explained. In SPRINTT, the concept of physical frailty is translated with a Short Physical Performance Battery score of ≥3 and ≤9. Concurrently, sarcopenia is defined according to the recent definitions of low muscle mass proposed by the Foundation for the National Institutes of Health-Sarcopenia Project. Given the preventive purpose of SPRINTT, older persons with mobility disability (operationalized as incapacity to complete a 400-m walk test within 15 min; primary outcome of the trial) at the baseline are not included within the diagnostic spectrum of PF&S.

Inhibition of retinoic acid metabolising enzymes by 2-(4-aminophenylmethyl)-6-hydroxy-3,4-dihydronaphthalen-1(2H)-one and related compounds.

In a search for inhibitors of all-trans retinoic acid (RA)-metabolising enzymes as potential agents for the treatment of skin conditions and cancer we have examined 2-(4-aminophenylmethyl)-6-hydroxy-3,4-dihydronaphthalen-1(2H)-one (5). Compound (5) is a moderate inhibitor of RA-metabolising enzymes in mammalian cadaverous tissue microsomes and homogenates as well as RA-induced enzymes in cultured human genital fibroblasts and HaCat cells. Overall (5) was more potent than or equipotent with ketoconazole, a standard inhibitor, in the cadaverous systems but less active towards the RA-induced cell culture systems. Examination of the data suggests that RA-induction generates metabolising enzymes not present in the cadaverous systems, which are more susceptible to inhibition by ketoconazole than (5).