Evidence from routine clinical practice: EMPRISE provides a new perspective on CVOTs

EMPA-REG OUTCOME is recognised by international guidelines as a landmark study that showed a significant cardioprotective benefit with empagliflozin in patients with type 2 diabetes (T2D) and cardiovascular disease. To assess the impact of empagliflozin in routine clinical practice, the ongoing EMPRISE study is collecting real-world evidence to compare effectiveness, safety and health economic outcomes between empagliflozin and DPP-4 inhibitors. A planned interim analysis of EMPRISE was recently published, confirming a substantial reduction in hospitalisation for heart failure with empagliflozin across a diverse patient population. In this commentary article, we discuss the new data in the context of current evidence and clinical guidelines, as clinicians experienced in managing cardiovascular risk in patients with T2D. We also look forward to what future insights EMPRISE may offer, as evidence is accumulated over the next years to complement the important findings of EMPA-REG OUTCOME

Polyphase zircon in ultrahigh-temperature granulites (Rogaland, SW Norway): constraints for Pb diffusion in zircon

SHRIMP U-Pb ages have been obtained for zircon in granitic gneisses from the aureole of the Rogaland anorthosite-norite intrusive complex, both from the ultrahigh temperature (UHT; >900 C pigeonite-in) zone and from outside the hypersthene-in isograd. Magmatic and metamorphic segments of composite zircon were characterised on the basis of electron backscattered electron and cathodoluminescenceimages plus trace element analysis. A sample from outside the UHT zone has magmatic cores with an age of 1034 + or- 7 Ma (2r, n= 8) and 1052 + or - 5 Ma (1r, n=1) overgrown by M1 metamorphic rims giving ages between 1020 + or- 7 and 1007 + or - 5 Ma. In contrast, samples from the UHT zone exhibitfour major age groups: (1) magmatic cores yielding ages over 1500 Ma (2) magmatic cores giving ages of 1034 + or - 13 Ma (2r, n=4) and 1056 + or - 10 Ma (1r, n=1) (3) metamorphic overgrowths ranging in age between 1017 + or - 6 Ma and 992 + or - 7 Ma (1r) corresponding to the regional M1 Sveconorwegiangranulite facies metamorphism, and (4) overgrowths corresponding to M2 UHTcontact metamorphism giving values of 922 + or - 14 Ma (2r, n=6). Recrystallized areas in zircon from both areas define a furtherage group at 974 + or - 13 Ma (2r, n=4). This study presents the first evidence from Rogaland for newgrowth of zircon resulting from UHT contact metamorphism. More importantly, it shows the survival of magmatic and regional metamorphic zircon relics in rocks that experienced a thermal overprint of c.950 C for at least 1 Myr. Magmatic and different metamorphic zones in the same zircon are sharply bounded and preserve original crystallization age information, a result inconsistent with some experimental data on Pb diffusion in zircon which predict measurable Pb diffusion under suchconditions. The implication is that resetting of zircon ages by diffusion during M2 was negligible in thesedry granulite facies rocks. Imaging and Th/U-Y systematics indicate that the main processes affecting zircon were dissolution-reprecipitation in a closed system and solid-state recrystallization during andsoon after M1