Background-Observational studies and randomized trials have reported increased cardiovascular risk associated with cyclooxygenase-2 inhibitors. Prior placebo-controlled randomized studies had limited ability to assess the relationship of either celecoxib dose or pretreatment cardiovascular status to risk associated with celecoxib. Our aim was to assess the cardiovascular risk associated with celecoxib in 3 dose regimens and to assess the relationship between baseline cardiovascular risk and effect of celecoxib on cardiovascular events. Methods and Results-We performed a patient-level pooled analysis of adjudicated data from 7950 patients in 6 placebo-controlled trials comparing celecoxib with placebo for conditions other than arthritis with a planned follow-up of at least 3 years. Patients were administered celecoxib in 3 dose regimens: 400 mg QD, 200 mg BID, or 400 mg BID.From the pooled data, we calculated a hazard ratio for all dose regimens combined and individual hazard ratios for each dose regimen and examined whether celecoxib-related risk was associated with baseline cardiovascular risk. The primary end point was the combination of cardiovascular death, myocardial infarction, stroke, heart failure, or thromboembolic event. With 16 070 patient-years of follow-up, the hazard ratio for the composite end point combining the tested doses was 1.6 (95% CI, 1.1 to 2.3). The risk, which increased with dose regimen (Pϭ0.0005), was lowest for the 400-mg-QD dose (hazard ratio, 1.1; 95% CI, 0.6 to 2.0), intermediate for the 200-mg-BID dose (hazard ratio, 1.8; 95% CI, 1.1 to 3.1), and highest for the 400-mg-BID dose (hazard ratio, 3.1; 95% CI, 1.5 to 6.1). Patients at highest baseline risk demonstrated disproportionately greater risk of celecoxib-related adverse events (P for interactionϭ0.034). Conclusions-We observed evidence of differential cardiovascular risk as a function of celecoxib dose regimen and baseline cardiovascular risk. By further clarifying the extent of celecoxib-related cardiovascular risk, these findings may help guide treatment decisions for patients who derive clinical benefit from selective cyclooxygenase-2 inhibition.

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We present comprehensive measurements of the structural, magnetic and electronic properties of layered van-der-Waals ferromagnet VI3 down to low temperatures. Despite belonging to a wellstudied family of transition metal trihalides, this material has received very little attention. We outline, from high-resolution powder x-ray diffraction measurements, a corrected room-temperature crystal structure to that previously proposed and uncover a structural transition at 79 K, also seen in the heat capacity. Magnetization measurements confirm VI3 to be a hard ferromagnet (9.1 kOe coercive field at 2 K) with a high degree of anisotropy, and the pressure dependence of the magnetic properties provide evidence for the two-dimensional nature of the magnetic order. Optical and electrical transport measurements show this material to be an insulator with an optical band gap of 0.67 eV -the previous theoretical predictions of d-band metallicity then lead us to believe VI3 to be a correlated Mott insulator. Our latest band structure calculations support this picture and show good agreement with the experimental data. We suggest VI3 to host great potential in the thriving field of low-dimensional magnetism and functional materials, together with opportunities to study and make use of low-dimensional Mott physics.Two-dimensional van-der-Waals (vdW) magnetic materials have in recent years become the subject of a wide range of intense research 1 . While a large portion of research into two-dimensional materials has centered on graphene, the addition of magnetism into such a system leads to many interesting fundamental questions and opportunities for device applications 2-6 . Particularly for future spintronics applications, semiconducting or metallic materials which exhibit ferromagnetism down to monolayer thickness are an essential ingredient. This has led to a large volume of recent publications on two-dimensional honeycomb ferromagnet CrI 3 7-12 . CrI 3 and VI 3 belong to a wider family of MX 3 transition metal trihalides, with X = Cl, Br, I, which were synthesized in the 60s 13,14 but have since seen little interest until recently 15 . VI 3 is an insulating two-dimensional ferromagnet with a Curie Temperature, T c , given as 55 K and reported to have the layered crystal structure of BiI 3 with space group R-3 [16][17][18] . As shown in a recent review 15 , there is very little available information on VI 3 other than the structure and the expected S = 1 from the 3d 2 configuration of the vanadium sites. Calculations using density functional theory, which additionally yield the exchange constants, have suggested VI 3 to not only remain ferromagnetic down to a single crystalline layer, but to also exhibit Dirac half-metallicity, of interest for spintronic applications 19 .In these vdW materials, hydrostatic pressure forms an extremely powerful tuning parameter. Given the weak mechanical forces between the crystal planes, the application of pressure will dominantly have the effect of pressing the ab planes together, and gradually an...