Cost-utility of transcatheter aortic valve implantation for inoperable patients with severe aortic stenosis treated by medical management: a UK cost-utility analysis based on patient-level data from the ADVANCE study.

OBJECTIVE: To use patient-level data from the ADVANCE study to evaluate the cost-effectiveness of transcatheter aortic valve implantation (TAVI) compared to medical management (MM) in patients with severe aortic stenosis from the perspective of the UK NHS. METHODS: A published decision-analytic model was adapted to include information on TAVI from the ADVANCE study. Patient-level data informed the choice as well as the form of mathematical functions that were used to model all-cause mortality, health-related quality of life and hospitalisations. TAVI-related resource use protocols were based on the ADVANCE study. MM was modelled on publicly available information from the PARTNER-B study. The outcome measures were incremental cost-effectiveness ratios (ICERs) estimated at a range of time horizons with benefits expressed as quality-adjusted life-years (QALY). Extensive sensitivity/subgroup analyses were undertaken to explore the impact of uncertainty in key clinical areas. RESULTS: Using a 5-year time horizon, the ICER for the comparison of all ADVANCE to all PARTNER-B patients was £13 943 per QALY gained. For the subset of ADVANCE patients classified as high risk (Logistic EuroSCORE >20%) the ICER was £17 718 per QALY gained). The ICER was below £30 000 per QALY gained in all sensitivity analyses relating to choice of MM data source and alternative modelling approaches for key parameters. When the time horizon was extended to 10 years, all ICERs generated in all analyses were below £20 000 per QALY gained. CONCLUSION: TAVI is highly likely to be a cost-effective treatment for patients with severe aortic stenosis

Predictors of long-term adverse events after Absorb bioresorbable vascular scaffold implantation: a 1,933-patient pooled analysis from international registries

Aims: The aim of this study was to investigate the predictors of long-term adverse clinical events after implantation of the everolimus-eluting Absorb bioresorbable vascular scaffold (BVS). Methods and results: We pooled patient-level databases derived from the large-scale ABSORB EXTEND study and five high-volume international centres. Between November 2011 and November 2015, 1,933 patients underwent PCI with a total of 2,372 Absorb BVS implanted. The median age was 61.0 (IQR 53.0 to 68.6) years, 24% had diabetes, and 68.2% presented with stable coronary artery disease. At a median follow-up of 616 days, MACE occurred in 93 (4.9%) patients, all-cause death in 36 (1.9%) patients, myocardial infarction in 47 (2.5%) patients, and target vessel revascularisation in 72 (3.8%) patients. Definite or probable scaffold thrombosis occurred in 26 (1.3%) patients. On multivariable logistic regression analysis, acute coronary syndromes (hazard ratio [HR] 2.79, 95% confidence interval [CI]: 1.47 to 5.29; p=0.002), dyslipidaemia (HR 1.43, 95% CI: 1.23 to 1.79; p=0.007), scaffold/reference diameter ratio >1.25 (HR 1.49, 95% CI: 1.18 to 1.88; p=0.001), and residual stenosis >15% (HR 1.67, 95% CI: 1.34 to 2.07; p<0.001) were independent predictors of MACE, whereas the use of intravascular imaging was independently associated with a reduction in MACE (HR 0.13, 95% CI: 0.06 to 0.28; p<0.001). Conclusions: Optimal Absorb BVS implantation and the use of intravascular imaging guidance are associated with lower rates of adverse events at long-term follow-up

Relativistic hydrodynamics on spacelike and null surfaces: Formalism and computations of spherically symmetric spacetimes

We introduce a formulation of Eulerian general relativistic hydrodynamics which is applicable for (perfect) fluid data prescribed on either spacelike or null hypersurfaces. Simple explicit expressions for the characteristic speeds and fields are derived in the general case. A complete implementation of the formalism is developed in the case of spherical symmetry. The algorithm is tested in a number of different situations, predisposing for a range of possible applications. We consider the Riemann problem for a polytropic gas, with initial data given on a retarded/advanced time slice of Minkowski spacetime. We compute perfect fluid accretion onto a Schwarzschild black hole spacetime using ingoing null Eddington-Finkelstein coordinates. Tests of fluid evolution on dynamic background include constant density and TOV stars sliced along the radial null cones. Finally, we consider the accretion of self-gravitating matter onto a central black hole and the ensuing increase in the mass of the black hole horizon.Comment: 23 pages, 13 figures, submitted to Phys. Rev.

Gravitational Waves from a Fissioning White Hole

We present a fully nonlinear calculation of the waveform of the gravitational radiation emitted in the fission of a vacuum white hole. At early times, the waveforms agree with close-approximation perturbative calculations but they reveal dramatic time and angular dependence in the nonlinear regime. The results pave the way for a subsequent computation of the radiation emitted after a binary black hole merger.Comment: 11 pages, 6 figures, RevTeX

First-order quasilinear canonical representation of the characteristic formulation of the Einstein equations

We prescribe a choice of 18 variables in all that casts the equations of the fully nonlinear characteristic formulation of general relativity in first--order quasi-linear canonical form. At the analytical level, a formulation of this type allows us to make concrete statements about existence of solutions. In addition, it offers concrete advantages for numerical applications as it now becomes possible to incorporate advanced numerical techniques for first order systems, which had thus far not been applicable to the characteristic problem of the Einstein equations, as well as in providing a framework for a unified treatment of the vacuum and matter problems. This is of relevance to the accurate simulation of gravitational waves emitted in astrophysical scenarios such as stellar core collapse.Comment: revtex4, 7 pages, text and references added, typos corrected, to appear in Phys. Rev.

Nanofat 2.0: experimental evidence for a fat grafting rich in mesenchymal stem cells.

Different strategies have been developed in the last decade to obtain fat grafts as rich as possible of mesenchymal stem cells, so exploiting their regenerative potential. Recently, a new kind of fat grafting, called "nanofat", has been obtained after several steps of fat emulsification and filtration. The final liquid suspension, virtually devoid of mature adipocytes, would improve tissue repair because of the presence of adipose mesenchymal stem cells (ASCs). However, since it is probable that many ASCs may be lost in the numerous phases of this procedure, we describe here a novel version of fat grafting, which we call "nanofat 2.0", likely richer in ASCs, obtained avoiding the final phases of the nanofat protocol. The viability, the density and proliferation rate of ASCs in nanofat 2.0 sample were compared with samples of nanofat and simple lipoaspirate. Although the density of ASCs was initially higher in lipoaspirate sample, the higher proliferation rate of cells in nanofat 2.0 virtually filled the gap within 8 days. By contrast, the density of ASCs in nanofat sample was the poorest at any time. Results show that nanofat 2.0 emulsion is considerably rich in stem cells, featuring a marked proliferation capability

Scalar field induced oscillations of neutron stars and gravitational collapse

We study the interaction of massless scalar fields with self-gravitating neutron stars by means of fully dynamic numerical simulations of the Einstein-Klein-Gordon perfect fluid system. Our investigation is restricted to spherical symmetry and the neutron stars are approximated by relativistic polytropes. Studying the nonlinear dynamics of isolated neutron stars is very effectively performed within the characteristic formulation of general relativity, in which the spacetime is foliated by a family of outgoing light cones. We are able to compactify the entire spacetime on a computational grid and simultaneously impose natural radiative boundary conditions and extract accurate radiative signals. We study the transfer of energy from the scalar field to the fluid star. We find, in particular, that depending on the compactness of the neutron star model, the scalar wave forces the neutron star either to oscillate in its radial modes of pulsation or to undergo gravitational collapse to a black hole on a dynamical timescale. The radiative signal, read off at future null infinity, shows quasi-normal oscillations before the setting of a late time power-law tail.Comment: 12 pages, 13 figures, submitted to Phys. Rev.

High-powered Gravitational News

We describe the computation of the Bondi news for gravitational radiation. We have implemented a computer code for this problem. We discuss the theory behind it as well as the results of validation tests. Our approach uses the compactified null cone formalism, with the computational domain extending to future null infinity and with a worldtube as inner boundary. We calculate the appropriate full Einstein equations in computational eth form in (a) the interior of the computational domain and (b) on the inner boundary. At future null infinity, we transform the computed data into standard Bondi coordinates and so are able to express the news in terms of its standard $N_{+}$ and $N_{\times}$ polarization components. The resulting code is stable and second-order convergent. It runs successfully even in the highly nonlinear case, and has been tested with the news as high as 400, which represents a gravitational radiation power of about $10^{13}M_{\odot}/sec$.Comment: 24 pages, 4 figures. To appear in Phys. Rev.

Exact Solutions for the Intrinsic Geometry of Black Hole Coalescence

We describe the null geometry of a multiple black hole event horizon in terms of a conformal rescaling of a flat space null hypersurface. For the prolate spheroidal case, we show that the method reproduces the pair-of-pants shaped horizon found in the numerical simulation of the head-on-collision of black holes. For the oblate case, it reproduces the initially toroidal event horizon found in the numerical simulation of collapse of a rotating cluster. The analytic nature of the approach makes further conclusions possible, such as a bearing on the hoop conjecture. From a time reversed point of view, the approach yields a description of the past event horizon of a fissioning white hole, which can be used as null data for the characteristic evolution of the exterior space-time.Comment: 21 pages, 6 figures, revtex, to appear in Phys. Rev.

A General Definition of "Conserved Quantities" in General Relativity and Other Theories of Gravity

In general relativity, the notion of mass and other conserved quantities at spatial infinity can be defined in a natural way via the Hamiltonian framework: Each conserved quantity is associated with an asymptotic symmetry and the value of the conserved quantity is defined to be the value of the Hamiltonian which generates the canonical transformation on phase space corresponding to this symmetry. However, such an approach cannot be employed to define `conserved quantities' in a situation where symplectic current can be radiated away (such as occurs at null infinity in general relativity) because there does not, in general, exist a Hamiltonian which generates the given asymptotic symmetry. (This fact is closely related to the fact that the desired `conserved quantities' are not, in general, conserved!) In this paper we give a prescription for defining `conserved quantities' by proposing a modification of the equation that must be satisfied by a Hamiltonian. Our prescription is a very general one, and is applicable to a very general class of asymptotic conditions in arbitrary diffeomorphism covariant theories of gravity derivable from a Lagrangian, although we have not investigated existence and uniqueness issues in the most general contexts. In the case of general relativity with the standard asymptotic conditions at null infinity, our prescription agrees with the one proposed by Dray and Streubel from entirely different considerations.Comment: 39 pages, no figure