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OBJECTIVES: CDK4/6 inhibitors dalpiciclib and abemaciclib have been approved by the Chinese National Medical Products Administration as first-line treatment for postmenopausal females with hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer (ABC). We aimed to assess the cost-effectiveness of dalpiciclib plus letrozole/anastrozole (non-steroidal aromatase inhibitor [NSAI]) compared with abemaciclib plus NSAI as a first-line treatment for HR+/HER2- ABC in China. METHODS: We constructed a Markov model with three health states to evaluate health and economic outcomes of first-line treatment with dalpiciclib plus NSAI and abemaciclib plus NSAI for HR+/HER2- ABC. Efficacy data was obtained from MONARCH3 and DAWNA-2 trials. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: Compared with abemaciclib plus NSAI, dalpiciclib plus NSAI resulted in 4.27 additional QALYs, with an ICER of $14827.4/QALY. At a willingness-to-pay threshold of 3 times gross domestic product per capita in China for 2023 ($37721.5/QALY), the cost-effectiveness probability of dalpiciclib plus NSAI was 77.42%. CONCLUSIONS: From the perspective of Chinese payers, dalpiciclib plus NSAI appears to be a cost-effective strategy compared with abemaciclib plus NSAI for the first-line treatment of patients with HR+/HER2- ABC in China. CLINICAL TRIAL REGISTRATION: MONARCH3, www.clinicaltrials.gov, identifier is NCT02246621 and DAWNA-2, www.clinicaltrials.gov, identifier is NCT03966898.
Asunto(s)
Aminopiridinas , Bencimidazoles , Neoplasias de la Mama , Piperidinas , Piridinas , Pirimidinas , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Inhibidores de la Aromatasa/uso terapéutico , Análisis Costo-Beneficio , Protocolos de Quimioterapia Combinada Antineoplásica , Receptor ErbB-2/metabolismoRESUMEN
BACKGROUND: Immunotherapy shows promise as a treatment option for various cancers. However, there is growing concern over potential complications from hepatitis B virus (HBV) reactivation after checkpoint blockade immunotherapy. Although most of the previous clinical trials on immune checkpoint inhibitors (ICIs) excluded patients with HBV, a few case reports and retrospective studies of HBV reactivation have been published. The aim of this study is to assess the risk of hepatitis B virus reactivation (HBVr) in patients receiving ICIs for advanced cancer. METHODS: English and Chinese language literature published prior to April 30, 2023, was searched in PubMed, EMBASE, Web of Science, Cochrane, SinoMed, CNKI and Wanfang Data for studies reporting HBVr rates in cancer patients treated with ICIs. A pooled risk estimate was calculated for HBVr rates with 95% confidence intervals (CI). RESULTS: Data from 34 studies including 7126 patients were retrieved and analyzed. The pooled HBVr rate in cancer patients treated with ICIs was 1.3% (I2 = 90.44%, 95% CI: 0.2-2.9%, P < 0.001). Subgroup analysis revealed that patients diagnosed with hepatocellular carcinoma (HCC), HBV carriers, and patients from Asian regions or in developing countries have a higher rate of HBVr. CONCLUSIONS: Our meta-analysis demonstrated a low risk of HBVr in patients treated with ICIs for advanced cancer. ICI treatment may be safely used in patients with existing HBV infection or chronic hepatitis B, accompanied by regular monitoring and appropriate antiviral prophylaxis if necessary.
Asunto(s)
Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Estudios Retrospectivos , Virus de la Hepatitis BRESUMEN
Massive production of efficient, durable, and low-cost electrocatalysts toward oxygen reduction reaction (ORR) is urgently desired for the development of energy storage and conversion devices. In this study, a facile and cost-effective strategy is proposed for the scalable synthesis of atomically dispersed FeNC derived from petroleum asphalt (FeNC@PA) as a reinforced catalyst for ORR. The FeNC@PA is fabricated through a layer-by-layer cladding template and subsequent pyrolysis method. Intercalating appropriate amount of petroleum asphalt not only improves the graphitic degree to reinforce the atomic Fe-Nx active sites, but also increases mass yield of the catalyst (~220%) compared with the FeNC counterpart. Serving as an ORR electrocatalyst, the optimized FeNC@PA-1:4 provides almost a four-electron transfer pathway (3.96) and exhibits superior electrocatalytic activity with a half-wave potential (E1/2) of 0.90 V to the commercial Pt/C catalyst (E1/2 = 0.86 V), as well as promoted durability and methanol tolerance in alkaline medium. Moreover, the zinc-air battery based on FeNC@PA-1:4 cathode delivers a high power density of 166.7 mW cm-2. This work may help the massive production of robust atomically dispersed non-noble metal catalysts for ORR and provide a new avenue for the high value-added utilization of petroleum asphalt.
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BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for preventing and treating gastrointestinal ulcers. In patients with advanced cancer, it is unclear whether concomitant use of immune checkpoint inhibitors (ICIs) and PPIs could result in poorer outcomes. This study investigates the impact of PPIs on the survival of cancer patients treated with ICIs. METHODS: PubMed, MEDLINE, EMBASE, and the Cochrane Library databases were searched from January 1, 1970 to June 2, 2020 for studies reporting the prognoses of cancer patients receiving antitumor therapies including ICIs with or without PPIs. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Hazard ratios (HRs) with a 95% confidence interval (CI) were reported to express the effectiveness of ICIs in PPI users compared to non-PPI users, using a random effects model. RESULTS: Five studies were identified comprising 1,167 cancer patients. Concomitant use of PPIs with ICIs did not result in statistically significant changes in OS (HR 0.996; 95% CI: 0.486-1.447) and PFS (HR 0.858; 95% CI: 0.388-1.328). Statistical testing suggested heterogeneity among studies. Sensitivity analyses confirmed the stability of our results. CONCLUSIONS: Concomitant ICI-PPI therapy does not appear to be significantly associated with OS or PFS, and further research on the effect of individual ICIs in different cancer patients is needed.
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In this paper, we develop an angles-centroids fitting (ACF) system and the centroid algorithm to calibrate the reverse Hartmann test (RHT) with sufficient precision. The essence of ACF calibration is to establish the relationship between ray angles and detector coordinates. Centroids computation is used to find correspondences between the rays of datum marks and detector pixels. Here, the point spread function of RHT is classified as circle of confusion (CoC), and the fitting of a CoC spot with 2D Gaussian profile to identify the centroid forms the basis of the centroid algorithm. Theoretical and experimental results of centroids computation demonstrate that the Gaussian fitting method has a less centroid shift or the shift grows at a slower pace when the quality of the image is reduced. In ACF tests, the optical instrumental alignments reach an overall accuracy of 0.1 pixel with the application of laser spot centroids tracking program. Locating the crystal at different positions, the feasibility and accuracy of ACF calibration are further validated to 10-6-10-4 rad root-mean-square error of the calibrations differences.