Cost Effectiveness of Vericiguat for the Treatment of Chronic Heart Failure with Reduced Ejection Fraction Following a Worsening Heart Failure Event from a US Medicare Perspective.

OBJECTIVE: Given the high economic burden of disease among adult patients with chronic heart failure with reduced ejection fraction (HFrEF) following a worsening heart failure event in the US, this study aimed to estimate the cost effectiveness of vericiguat plus prior standard-of-care therapies (PSoCT) versus PSoCT alone from a US Medicare perspective. METHODS: A four-state Markov model (alive prior to heart failure hospitalization, alive during heart failure hospitalization, alive post-heart failure hospitalization, and death) was developed to predict clinical and economic outcomes, based on the results of the VICTORIA trial, in which patients with chronic HFrEF following a worsening heart failure were randomized to placebo or vericiguat, in addition to PSoCT, which consisted of β-blockers, renin-angiotensin-aldosterone inhibitors, mineralocorticoid receptor antagonists, and the angiotensin receptor-neprilysin inhibitor sacubitril/valsartan. Risks of heart failure hospitalization and cardiovascular mortality were based on multivariable regression models derived from VICTORIA data. Utilities were derived from VICTORIA EQ-5D data and the literature. Costs included drug acquisition, heart failure hospitalization, routine care, and terminal care. Primary outcomes included heart failure hospitalization, cardiovascular mortality, life-years, quality-adjusted life-years (QALYs), and incremental costs per QALY gained over a 30-year lifetime horizon, discounted at 3.0% annually. RESULTS: For the VICTORIA overall intent-to-treat population, compared with PSoCT, vericiguat plus PSoCT resulted in 19 fewer heart failure hospitalizations and 13 fewer cardiovascular deaths per 1000 patients, as well as 0.28 QALY gained per patient at an incremental cost of $23,322, leading to$82,448 per QALY gained. CONCLUSIONS: Based on the results of VICTORIA, patients treated with vericiguat had lower rates of heart failure hospitalization and cardiovascular death. The addition of vericiguat to PSoCT was estimated to increase QALYs and to be cost effective at a willingness-to-pay threshold of $100,000 per QALY gained

Flux-Barrier Design and Torque Performance Analysis of Synchronous Reluctance Motor with Low Torque Ripple

In this paper, an improved rotor structure with cross-shaped flux-barriers was proposed to improve the torque output capacity and reduce the torque ripple of the synchronous reluctance motor (SynRM). Firstly, an improved rotor structure of synchronous reluctance motor with cross-shaped flux-barriers, which can be described by two main parameters, is presented. Second, the improved motor is qualitatively analyzed by using magnetic equivalent circuit (MEC), and then the effects of the main parameters of the improved flux-barriers on the distribution of air-gap flux density, average torque, and torque ripple were analyzed by using the finite element method. Based on the above analysis, the rotor structure parameters of the proposed cross-shaped flux-barriers were obtained, and the performance was compared with that of the initial motor. The results show that the proposed rotor structure with cross-shaped flux-barriers can significantly reduce the torque ripple and increase the average torque

3-D Joint Inversion of Gravity and Magnetic Data Using Data-Space and Truncated Gauss-Newton Methods

Gravity and magnetic inversion are important methods for comprehensive quantitative interpretation of data obtained in, e.g., mineral, oil and gas, and geothermal exploration. At present, the 3-D joint inversion technology of gravity and magnetic data is facing challenges from large-scale data exploration applications. In this letter, a new algorithm for 3-D joint inversion of gravity and magnetic data with high accuracy and low computational cost is presented. We use the geometric trellis method to perform fast forward calculations and then introduce the sparse constraint and adaptive sensitivity matrix into the model constraint terms. The inexact structural resemblance method is then used to add the cross-gradient constraint penalty term to the objective function. Finally, an algorithm (DS-TGN) combining data-space (DS) and truncated Gauss-Newton (TGN) methods is used to solve the joint inversion objective function. Numerical experiments with synthetic data show that the proposed algorithm can significantly reduce the computational cost and obtain high accuracy density and magnetization models with structural resemblance and sharp boundaries. We also apply the DS-TGN algorithm to data obtained in the area of Greater Khingan in northwestern Heilongjiang, China. The underground density and magnetization distribution results provide a high-resolution geological model for the detection of skarn-type deposits

Preparation of High-Efficiency Fe/N-Doped Carbon Catalysts Derived from Graphite Phase Carbon Nitride for Reduction of Oxygen

Fe/N-doped carbon (Fe-NC) is an excellent base-metal catalyst for use in an electrocatalytic oxygen reduction reaction (ORR) with high activity. In this paper, graphite phase carbon nitride (g-C3N4) was first obtained from the pyrolyzing of melamine, and then different proportions of FeCl3 were separately doped into g-C3N4 to further prepare the Fe-NC catalyst. The Fe-NC catalyst was applied in an ORR reaction, and the results show that the Fe-NC catalyst doped with 0.5 mmol FeCl3 possesses exceptional electrocatalytic performance, with an onset potential of 0.96 V and a half-wave potential of 0.81 V, which approaches that of a Pt/C catalyst. Meanwhile, the Fe-NC catalyst displays high stability and methanol resistance. The results supply a new way to prepare efficient ORR electrocatalysts

IRGM/Irgm1 deficiency inhibits neutrophil-platelet interactions and thrombosis in experimental atherosclerosis and arterial injury

Background: Neutrophil extracellular traps (NETs) closely link inflammation and thrombosis. The immune-related GTPase family M protein (IRGM) and its ortholog of mouse IRGM1 are positively correlated with plaque rupture during atherosclerosis process. However, whether and how IRGM/IRGM1 affects NETs formation and atherosclerotic thrombosis remains unknown, which will further promote the development of antithrombotic treatment tools. Methods: The thrombi images, platelet activation makers and NETs makers were detected in the serum of STEMI patients and controls. To futher investigate IRGM/IRGM1 affects NETs formation and atherothrombosis in vivo, ApoE-/-Irgm1+/- and ApoE-/- mice received diets rich in fat and 2.5% FeCl3 was then used to induce experimental arterial thrombosis in an atherosclerosis background. In vitro, PMA and thrombin were used to stimulate neutrophils and platelets, respectively, and the expression of IRGM/IRGM1 were modified. To reveal the molecular mechanisms, MAPK-cPLA2 signals inhibitors were used. Results: Serum IRGM was positively correlated with PF4 and neutrophil elastase. Subsequently, Irgm1 deficient mice have a longer occlusion time and lower growth rate. In vitro, as expected, IRGM/Irgm1 deficiency inhibits platelet activation and platelet-neutrophil interaction. More importantly, IRGM promoted NETs production through activating MAPK-cPLA2 signals in PMA stimulated neuropils, whereas inhibiting the production of NETs eliminated the difference in platelet activation and thrombosis caused by IRGM/Irgm1 modification in vivo and vitro. Similarly, inhibition of platelet activation also eliminated the influence of IRGM/Irgm1 modification on NETs production. Conclusions: Overall, our data indicate that IRGM/Irgm1 deficiency in neuropils inhibits the intense interaction between neutrophils and platelets, and ultimately inhibits thrombosis