Impact of national drug price negotiation policy on the accessibility and utilization of PCSK9 inhibitors in China: an interrupted time series analysis.

BACKGROUND: PCSK9 inhibitors are a novel class of lipid-lowering drugs that have demonstrated favorable efficacy and safety. Evolocumab and alirocumab have been added to China's National Reimbursement Drug List through the National Drug Price Negotiation (NDPN) policy. This study aims to evaluate the impact of the NDPN policy on the utilization and accessibility of these two PCSK9 inhibitors. METHODS: The procurement data of evolocumab and alirocumab were collected from 1,519 hospitals between January 2021 and December 2022. We determined the monthly availability, utilization, cost per daily defined dose (DDDc), and affordability of the two medicines. Single-group interrupted time series (ITS) analysis was performed to assess the impact of the NDPN policy on each drug, and multiple-group ITS analysis was performed to compare the differences between them. RESULTS: The NDPN policy led to a significant and sudden increase in the availability and utilization of PCSK9 inhibitors, along with a decrease in their DDDc. In the year following the policy implementation, there was an increase in the availability, utilization, and spending, and the DDDc remained stable. The affordability of PCSK9 inhibitors in China have been significantly improved, with a 92.97% reduction in out-of-pocket costs. The availability of both PCSK9 inhibitors was similar, and the DDDc of alirocumab was only $0.23 higher after the intervention. The market share of evolocumab consistently exceeded that of alirocumab. Regional disparities in utilization were observed, with higher utilization in the eastern region and a correlation with per capita disposable income. CONCLUSIONS: The NDPN policy has successfully improved the accessibility and utilization of PCSK9 inhibitors in China. However, regional disparities in utilization indicate the need for further interventions to ensure equitable medicine access.

Recent Advances of Carbon Materials in Anodes for Aqueous Zinc Ion Batteries.

Carbon-based materials have been successfully applied in the zinc ion batteries to improve the energy storage capability and durability of zinc anodes. In this review, four types of carbon materials (conventional carbons, fiber-like carbons, carbon nanotubes, graphene and other 2D carbon materials) are introduced based on the electrode preparation, physicochemical property and battery performance. Several modification strategies are also illustrated, such as heteroatom doping, hierarchical design and metal/carbon composites. Besides the discussion of existing issues of zinc anodes, the structure-performance relationships are analyzed in depth. Finally, conclusive remarks of this review are summarized and prospects of the future improvement are proposed.

Antiangiogenic antibody BD0801 combined with immune checkpoint inhibitors achieves synergistic antitumor activity and affects the tumor microenvironment.

BACKGROUND: Signaling through VEGF/VEGFR induces cancer angiogenesis and affects immune cells. An increasing number of studies have recently focused on combining anti-VEGF/VEGFR agents and immune checkpoint inhibitors (ICIs) to treat cancer in preclinical and clinical settings. BD0801 is a humanized rabbit anti-VEGF monoclonal antibody in the clinical development stage. METHODS: In this study, the anti-cancer activities of BD0801 and its potential synergistic anti-tumor effects when combined with different immunotherapies were assessed by using in vitro assays and in vivo tumor models. Ex vivo studies were conducted to reveal the possible mechanisms of actions (MOA) underlying the tumor microenvironment modification. RESULTS: BD0801 showed more potent antitumor activity than bevacizumab, reflected by stronger blockade of VEGF/VEGFR binding and enhanced inhibitory effects on human umbilical vein endothelial cells (HUVECs). BD0801 exhibited dose-dependent tumor growth inhibitory activities in xenograft and murine syngeneic tumor models. Notably, combining BD0801 with either anti-PD-1 or anti-PD-L1 antibodies showed synergistic antitumor efficacy in both lung and colorectal cancer mouse models. Furthermore, the mechanistic studies suggested that the MOA of the antitumor synergy involves improved tumor vasculature normalization and enhanced T-cell mediated immunity, including increased tumor infiltration of CD8+ and CD4+ T cells and reduced double-positive CD8+PD-1+ T cells. CONCLUSIONS: These data provide a solid rationale for combining antiangiogenic agents with immunotherapy for cancer treatment and support further clinical development of BD0801 in combination with ICIs.

Zeolite-based catalytic membrane reactors for thermo-catalytic conversion of CO2.

Zeolite-based catalytic membrane reactors have been successfully applied in overcoming the thermodynamic limitations of CO2 hydrogenations and dry reforming of methane (DRM) reactions. This review summarizes the zeolites as membrane reactor components regarding the permeance, permselectivity, durability, conversion, selectivity, and stability by referring to the synergy of catalyst and membrane. Also, five operation parameters (temperature, pressure, feed ratio, sweeping gas flow rate, and gas hourly space velocity) are introduced regarding their impacts on the performance of membrane reactor. Besides, synthesis methods and conditions for zeolite membranes are critically illustrated in the category. Moreover, representative surface and structure properties of zeolite membranes are discussed by relating to the synthesis-structure-performance relationships. Finally, conclusive remarks are demonstrated and possible solutions to existing challenges are proposed. So far, this is the first time to discuss the applications of zeolite membrane reactors in the CO2 adsorption, separation, activation, and conversion in reforming and hydrogenation processes.

Emerging application of metabolomics on Chinese herbal medicine for depressive disorder.

Depressive disorder is a kind of emotional disorder that is mainly manifested with spontaneous and persistent low mood. Its etiology is complex and still not fully understood. Metabolomics, an important part of system biology characterized by its integrity and systematicness, analyzes endogenous metabolites of small molecules in vivo and examines the metabolic status of the organism. It is widely used in the field of disease research for its unique advantage in the disease molecular marker discovering Due to fewer adverse reactions and high safety, Chinese herbal medicine (CHM) has great advantages in the treatment of chronic diseases including depression. Metabolomics has been gradually applied to the efficacy evaluation of CHM in treatment of depression and the metabolomics analysis exhibits a systemic metabolic shift in amino acids (such as alanine, glutamic acid, valine, etc.), organic acids (lactic acid, citric acid, stearic acid, palmitic acid, etc.), and sugars, amines, etc. These differential metabolites are mainly involved in energy metabolism, amino acid metabolism, lipid metabolism, etc. In this review, we have exemplified the study of CHM in animals or clinics on the depression, and revealed that CHM treatment has significantly changed the metabolic disorders associated with depression, promoting metabolic network reorganization through restoring of key metabolites, and metabolic pathways, which may be the main mechanism basis of CHM's treatment on depression. Besides, we further envisioned the future application of metabolomics in the study of CHM treatment of depression.

Carbon-Based Composites as Anodes for Microbial Fuel Cells: Recent Advances and Challenges.

Owing to the low price, chemical stability and good conductivity, carbon-based materials have been extensively applied as the anode in microbial fuel cells (MFCs). In this review, apart from the charge storage mechanism and anode requirements, the major work focuses on five categories of carbon-based anode materials (traditional carbon, porous carbon, nano-carbon, metal/carbon composite and polymer/carbon composite). The relationship is demonstrated in depth between the physicochemical properties of the anode surface/interface/bulk (porosity, surface area, hydrophilicity, partical size, charge, roughness, etc.) and the bioelectrochemical performances (electron transfer, electrolyte diffusion, capacitance, toxicity, start-up time, current, power density, voltage, etc.). An outlook for future work is also proposed.

Evaluating program effects: Conceptualizing and demonstrating a typology.

Outcome evaluation is very important for program evaluation and has been becoming increasingly so in the age of accountability. Typically, outcome evaluation is conducted for a single program from a single perspective. However, in a real-life situation, many programs exist in a system, and the effects could be viewed from various perspectives. The authors illustrate a typology of program effects in a system. It moves from the paradigm of a single program's single effect to that of a set of programs' multiple effects. Methodological implications are discussed.

Using logic model and visualization to conduct portfolio evaluation.

Portfolio evaluation is the evaluation of multiple projects with a common purpose. While logic models have been used in many ways to support evaluation, and data visualization has been used widely to present and communicate evaluation findings, adopting logic models for portfolio evaluation and using data visualization to share findings simultaneously is surprisingly limited in the literature. With the data from a sample portfolio of 209 projects which aims to improve the system of early care and education (ECE), this study illustrated how to use logic model and data visualization techniques to conduct a portfolio evaluation by answering two evaluation questions: "To what extent are the elements of a logic model (strategies, sub-strategies, activities, outcomes, and impacts) reflected in the sample portfolio?" and "Which dominant paths through the logic model were illuminated by the data visualization technique?" For the first question, the visualization technique illuminated several dominant strategies, sub-strategies, activities, and outcomes. For the second question, our visualization techniques made it convenient to identify critical paths through the logic model. Implications for both program evaluation and program planning were discussed.

Reliability of Using Motion Sensors to Measure Children's Physical Activity Levels in Exergaming.

OBJECTIVES: This study examined the reliability of two objective measurement tools in assessing children’s physical activity (PA) levels in an exergaming setting. METHODS: A total of 377 children (190 girls, Mage = 8.39, SD = 1.55) attended the 30-min exergaming class every other day for 18 weeks. Children’s PA levels were concurrently measured by NL-1000 pedometer and ActiGraph GT3X accelerometer, while children’s steps per min and time engaged in sedentary, light, and moderate-to-vigorous PA were estimated, respectively. RESULTS: The results of intraclass correlation coefficient (ICC) indicated a low degree of reliability (single measures ICC = 0.03) in accelerometers. ANOVA did detect a possible learning effect for 27 classes (p < 0.01), and the single measures ICC was 0.20 for pedometers. Moreover, there was no significant positive relationship between steps per min and time spent in moderate-to-vigorous physical activity (MVPA). Finally, only 1.3% variance was explained by pedometer as a predictor using Hierarchical Linear Modeling to further explore the relationship between pedometer and accelerometer data. CONCLUSIONS: The NL-1000 pedometers and ActiGraph GT3X accelerometers have low reliability in assessing elementary school children’s PA levels during exergaming. More research is warranted in determining the reliable and accurate measurement information regarding the use of modern devices in exergaming setting.

Using WWC sanctioned rigorous methods to develop comparison groups for evaluation.

Evaluation of program impact in the field of education has been a controversial topic over the years. Although randomized control trials have great advantages in causal inference, they often raise ethical and economic concerns in practice. As an alternative, quasi-experimental designs may provide valid evidence of influence if they are well-designed. In this article, we presented an evaluation case of a district-wide early learning improvement program. To strike a balance between practicability and academic rigor, we developed comparison groups from multiple perspectives, and used a series of tests consistent with WWC 3.0 standards to reach the most valid comparisons. Implications for evaluation practice were discussed.