Cost-Utility Analysis of Vericiguat in Heart Failure with Reduced Ejection Fraction After Worsening Heart Failure Events in China.

OBJECTIVE: Vericiguat is a new medication to demonstrate clinical efficacy in heart failure with reduced ejection fraction (HFrEF) after worsening heart failure (WHF) events, but its cost-utility was unknown. We aimed to assess the cost-utility of combining the application of vericiguat with standard treatment in HFrEF patients who had WHF events. METHODS: A multistate Markov model was implemented to mimic the economic results of HFrEF patients who had WHF events in China after receiving vericiguat or placebo. An analysis of cost-utility was conducted; most parameters were set according to the published studies and related databases. All the utilities and costs were decreased at a rate of 5% annually. The incremental cost-effectiveness ratios (ICERs) were the primary outcome measure. We also conducted sensitivity analyses. RESULTS: Over a 20 year lifetime horizon, additional use of vericiguat led to an elevated cost from US$9725.03 to US$20,660.76 at the current vericiguat costs. This was related to increased quality-adjusted life years (QALYs) from 2.50 to 2.66, along with an ICER of US$65,057.24 per QALY, which was over the willingness-to-pay (WTP) threshold of US$36,096.30 per QALY. If the vericiguat costs were discounted at 80%, it contributed to an ICER of US$12,226.77 per QALY. Additional use of vericiguat for patients with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) of ≤ 5314 pg per ml produced an ICER of US$23,688.46 per QALY. The outcomes of the one-way sensitivity analysis showed the risk of death from cardiovascular disease in both groups was variable with the highest sensitivity. The probabilistic sensitivity analysis showed that 41.6% of the mimicked population receiving vericiguat combined with standard therapy was cost-effective at the WTP threshold of US$36,096.30 per QALY. CONCLUSIONS: From the perspective of Chinese public healthcare system, the combined use of vericiguat and standard treatment in patients with HFrEF following WHF events did not generate advantages in cost-utility in China but was a cost-effective therapeutic strategy for those who with plasma NT-proBNP of ≤ 5314 pg per ml.

Can green finance promote urban green development? Evidence from green finance reform and innovation pilot zone in China.

This study aims to evaluate the effect of the green finance reform and innovation pilot zone (GFPZ) policy on urban green development. Based on city-level panel data in China from 2012 to 2019, a difference-in-differences model was employed to examine the effects of China's GFPZ policy on the city's green total factor productivity (GTFP). Results show that (1) the GFPZ policy has promoted the GTFP of pilot cities, a conclusion that still holds after performing multiple robustness tests. (2) Compared to non-pilot cities, the GFPZ policy can increase urban GTFP by promoting urban green innovation and reducing urban energy intensity. (3) The GFPZ policy had a more significant impact on mega cities and resource-based cities than on medium and big-sized cities and non-resource-based cities. This study provides new empirical evidence on how green finance influences urban green development and offers China's experience to policymakers worldwide to develop green finance in top-level policy design and practice.

[Instant response of individual size inequality indices to thinning regimes in plantation].

Four kinds of thinning treatments were designed including thinning from below, thinning from above, mechanical thinning and crop tree release with the same thinning intensity on the 14-year-old pure Cunninghamia laceolata and Pinus massoniana plantations in Guangxi, and 6 kinds of size inequality indices were applied including stand deviation, variation coefficient, skewness, Gini coefficient, Kuznetz coefficient and Lorenz asymmetry coefficient to evaluate the change of individual volume inequality after the 4 kinds of thinning regimes applied. The results showed that stand deviation, variation coefficient, Gini coefficient and Kuznetz coefficient decreased and skewness increased after thinning from below or above compared with before thinning, while after crop tree release these four indices increased and skewness was uncertain. Lorenz asymmetry coefficient increased after thinning from below while it decreased after thinning from above or crop tree release compared with before thinning. There was no distinct rule for the 6 kinds of size inequality indices after mechanical thinning. The size inequality increased after crop tree release while it decreased af- ter thinning from above or below. The study suggested that Lorenz curve, Gini coefficient and Lorenz asymmetry coefficient could be used to compare the size inequality statically and dynamically among different stands, and could be discriminated the difference of size inequality caused by the different thinning regimes. Lorenz asymmetry coefficient even could be applied to tell the size inequality was mainly from the larger or smaller individuals. Crop tree release method in close-to-nature management could lessen the competition pressures of crop trees and increase the size inequality of the stand effectively which would be helpful to maintain the dominant position of crop trees.

Cramér-Rao bound for Intravoxel Incoherent Motion Diffusion Weighted Imaging fitting.

The precision of parameter estimation for Intravoxel Incoherent Motion Diffusion Weighted Imaging (IVIM-DWI) was investigated by examining their Cramér-Rao bounds (CRBs) under the presence of Rician noise. Monte Carlo (MC) simulation was also conducted to validate the CRB results. The estimation uncertainties of true diffusion coefficient (D) and perfusion fraction (f0) could reach 3.89% and 11.65% respectively with typical parameter values at a moderate signal-to-noise ratio (SNR) of 40. However, to estimate pseudo diffusion coefficient (D*) within 10% uncertainty requires SNR>122. The results also showed that the estimation precision of each parameter is not only dependent on SNR but also their true values, while this mutual dependency is complicated. Under some particular cases, estimation uncertainty for certain parameters might be smaller than 5% at a moderate SNR of 40. However, the simultaneous precise estimation for all three parameters is theoretically difficult and highly SNR demanding.

Accuracy and uncertainty of asymmetric magnetization transfer ratio quantification for amide proton transfer (APT) imaging at 3T: a Monte Carlo study.

Amide proton transfer (APT) imaging offers a novel and powerful MRI contrast mechanism for quantitative molecular imaging based on the principle of chemical exchange saturation transfer (CEST). Asymmetric magnetization transfer ratio (MTR(asym)) quantification is crucial for Z-spectrum analysis of APT imaging, but is still challenging, particularly at clinical field strength. This paper studies the accuracy and uncertainty in the quantification of MTR(asym) for APT imaging at 3T, by using high-order polynomial fitting of Z-spectrum through Monte Carlo simulation. Results show that polynomial fitting is a biased estimator that consistently underestimates MTR(asym). For a fixed polynomial order, the accuracy of MTR(asym) is almost constant with regard to signal-to-noise ratio (SNR) while the uncertainty decreases exponentially with SNR. The higher order polynomial fitting increases both the accuracy and the uncertainty of MTR(asym). For different APT signal intensity levels, the relative accuracy and the absolute uncertainty keep constant for a fixed polynomial order. These results indicate the limitations and pitfalls of polynomial fitting for MTR(asym) quantification so better quantification technique for MTR(asym) estimation is warranted.

Quantification of T(1ρ) relaxation by using rotary echo spin-lock pulses in the presence of B(0) inhomogeneity.

T(1ρ) relaxation is traditionally described as a mono-exponential signal decay with spin-lock time. However, T(1ρ) quantification by fitting to the mono-exponential model can be substantially compromised in the presence of field inhomogeneities, especially for low spin-lock frequencies. The normal approach to address this issue involves the development of dedicated composite spin-lock pulses for artifact reduction while still using the mono-exponential model for T(1ρ) fitting. In this work, we propose an alternative approach for improved T(1ρ) quantification with the widely-used rotary echo spin-lock pulses in the presence of B(0) inhomogeneities by fitting to a modified theoretical model which is derived to reveal the dependence of T(1ρ)-prepared magnetization on T(1ρ), T(2ρ), spin-lock time, spin-lock frequency and off-resonance, without involving complicated spin-lock pulse design. It has potentials for T(1ρ) quantification improvement at low spin-lock frequencies. Improved T(1ρ) mapping was demonstrated on phantom and in vivo rat spin-lock imaging at 3 T compared to the mapping using the mono-exponential model.

DL-3-n-Butylphthalide, an anti-oxidant agent, prevents neurological deficits and cerebral injury following stroke per functional analysis, magnetic resonance imaging and histological assessment.

DL-3-n-Butylphthalide (NBP) is a synthetic compound based on L-3-n-Butylphthalide which was isolated from seeds of Apium graveolens. The present study aims at evaluating the outcome of NBP given prior to and after the onset of ischemic stroke in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Stroke was induced by the middle cerebral artery occlusion (MCAO) in SHR and WKY. For pre-treatment, NBP was administered to SHR and WKY daily for two months prior to MCAO. For post-treatment, NBP was given daily for seven consecutive days after MCAO. Seven days post-surgery, rats were tested for the presence of neurological deficits. Magnetic resonance imaging (MRI) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to calculate the infarct volume. The cerebral cortex and corpus striatum in the ischemic penumbra area were examined microscopically for pathological changes. In SHR, NBP pre- and post-treatment significantly lowered neurological deficit scores, reduced infarct volume, and minimized pathological changes in the penumbra area when compared to oil-vehicle treated controls. In WKY, these beneficial effects were observed only in the post-treatment group. The beneficial effects of NBP post-treatment were greater in WKY than in SHR. Results indicated that NBP could exert both preventive and therapeutic effects on ischemic stroke in SHR, but only exerted therapeutic effect in WKY.

Optimized efficient liver T(1ρ) mapping using limited spin lock times.

T(1ρ) relaxation has recently been found to be sensitive to liver fibrosis and has potential to be used for early detection of liver fibrosis and grading. Liver T(1ρ) imaging and accurate mapping are challenging because of the long scan time, respiration motion and high specific absorption rate. Reduction and optimization of spin lock times (TSLs) are an efficient way to reduce scan time and radiofrequency energy deposition of T(1ρ) imaging, but maintain the near-optimal precision of T(1ρ) mapping. This work analyzes the precision in T(1ρ) estimation with limited, in particular two, spin lock times, and explores the feasibility of using two specific operator-selected TSLs for efficient and accurate liver T(1ρ) mapping. Two optimized TSLs were derived by theoretical analysis and numerical simulations first, and tested experimentally by in vivo rat liver T(1ρ) imaging at 3 T. The simulation showed that the TSLs of 1 and 50 ms gave optimal T(1ρ) estimation in a range of 10-100 ms. In the experiment, no significant statistical difference was found between the T(1ρ) maps generated using the optimized two-TSL combination and the maps generated using the six TSLs of [1, 10, 20, 30, 40, 50] ms according to one-way ANOVA analysis (p = 0.1364 for liver and p = 0.8708 for muscle).

Non-invasive MRI assessment of the articular cartilage in clinical studies and experimental settings.

Attrition and eventual loss of articular cartilage are important elements in the pathophysiology of osteoarthritis (OA). Preventing the breakdown of cartilage is believed to be critical to preserve the functional integrity of a joint. Chondral injuries are also common in the knee joint, and many patients benefit from cartilage repair. Magnetic resonance imaging (MRI) and advanced digital post-processing techniques have opened possibilities for in vivo analysis of cartilage morphology, structure, and function in healthy and diseased knee joints. Techniques of semi-quantitative scoring of human knee cartilage pathology and quantitative assessment of human cartilage have been developed. Cartilage thickness and volume have been quantified in humans as well as in small animals. MRI detected cartilage loss has been shown to be more sensitive than radiographs detecting joint space narrowing. It is possible to longitudinally study knee cartilage morphology with enough accuracy to follow the disease-caused changes and also evaluate the therapeutic effects of chondro-protective drugs. There are also several MRI methods that may allow evaluation of the glycosaminoglycan matrix or collagen network of articular cartilage, and may be more sensitive for the detection of early changes. The clinical relevance of these methods is being validated. With the development of new therapies for OA and cartilage injury, MR images will play an important role in the diagnosis, staging, and evaluation of the effectiveness of these therapies.

[Dynamic changes of ecological footprint and ecological capacity in Fujian Province].

The analysis on the dynamic changes of ecological footprint and ecological capacity in Fujian Province showed that in 1999-2003, the ecological footprint per capita in the Province increased from 1.428 hm2 to 1.658 hm2, while the ecological capacity per capita decreased from 0.683 hm2 to 0.607 hm2, with an increased ecological deficit year after year. The contradiction between the ecological footprint and ecological capacity pricked up gradually, and the ecological environment was at risk. There existed a severe imbalance in the supply and demand of ecological footprint per capita. The main body of the demands was grassland and fossil fuel, accouting for 55.74% - 63.43% of the total, while their supply only occupied 0.77% - 0.82% and next to nothing of the ecological capacity per capita, respectively. As a whole, the ecological footprint per ten thousand yuan GDP declined in the five years, indicating that the resources use efficiency in the Province was improved gradually. Based on the analysis of the present situation of the economic development and resources distribution in the Province, the strategies on reducing ecological deficit were put forward.