Dowlingsutherland9224
Sensitivity analysis indicated that the cost of atezolizumab was the most influential factor in both countries.
In the United States, which had a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per QALY, atezolizumab was a cost-effective strategy for first-line treatment in metastatic NSCLC patients with high PD-L1 expression when compared to chemotherapy. For China, with a WTP threshold of $33,210 per QALY, atezolizumab was not considered good-value treatment for NSCLC, and a price reduction of 52% appeared to be justified.
In the United States, which had a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per QALY, atezolizumab was a cost-effective strategy for first-line treatment in metastatic NSCLC patients with high PD-L1 expression when compared to chemotherapy. For China, with a WTP threshold of $33,210 per QALY, atezolizumab was not considered good-value treatment for NSCLC, and a price reduction of 52% appeared to be justified.
Pharmacoeconomic information for pembrolizumab as a second-line lung cancer treatment is insufficient in China, so we aimed to assess its cost-effectiveness versus docetaxel as a second-line treatment for patients with non-small cell lung cancer (NSCLC) in China.
A partitioned survival model was developed to assess the cost-effectiveness of pembrolizumab versus docetaxel in the treatment of NSCLC patients. A phase III clinical trial (KEYNOTE-010) was used as the clinical data. Long-term survival data were extrapolated based on the clinical study data. Lifetime cost and utility were calculated with a discount set at 3%. One-way deterministic sensitivity analyses and probabilistic sensitivity analysis were used to test the robustness of incremental cost-effectiveness ratios (ICER).
In the base-case scenario, the ICERs were $107,846/quality-adjusted life year (QALY) and $448,414/QALY for pembrolizumab (2 and 10 mg/kg) groups, respectively. Both ICER values were 3-fold higher than the threshold of China's per-capita GDP in 2019 ($30,055.01). One-way deterministic sensitivity analyses showed that the price of pembrolizumab is the main factor affecting the result of ICER. Median ICERs were $108,658/QALY ($107,005/QALY-$110,089/QALY) for the pembrolizumab 2 mg/kg group and $451,590/QALY ($443,685/QALY-$457,496/QALY) for the pembrolizumab 10 mg/kg group using the current price in China. Bemcentinib For patients receiving regimens with 2 mg/kg pembrolizumab, the probabilities will be exceeding 95% when the price of pembrolizumab decreases by 25% in a high-income region (willing to pay setting as $71,406/QALY).
The results suggest that for it to become a second-line treatment of NSCLC in China, a reduction in the cost of pembrolizumab is needed.
The results suggest that for it to become a second-line treatment of NSCLC in China, a reduction in the cost of pembrolizumab is needed.
The International Pharmaceutical Federation (FIP) has established an interim guidance of coronavirus disease 2019 (COVID-19) for pharmacists worldwide. The aim of this study was to identify the implementation of FIP guidance in China and provide applicable strategies for further actions.
A nationwide cross-sectional survey on Chinese pharmacists was distributed electronically through groups of WeChat between 9 December 2020 and 18 December 2020. The 29-item questionnaire for the survey was designed based on the FIP guidance and knowledge, attitudes, and practices (KAP) framework.
A total of 237 responses from 237 pharmacists (69.20% females) were received. Most pharmacists (81.86%) participated in work related to COVID-19. link2 Respondents referred to other guidelines or consensus more than they did to FIP guidance. Most participants were qualified for the knowledge-based questions regarding COVID-19 (67.51%), had positive attitudes towards pharmacists' roles and actions (61.18%), and were qualified in the practices of prevention measures, infection risk monitoring, and pharmacists' advice (50.63%). Several factors were revealed as having impact on pharmacists' KAP, such as the relevance of participating in work related to COVID-19, work entailments, and information source.
The FIP guidance has a certain degree of dissemination and implementation in China, which can be improved through effective actions directed towards impact factors.
The FIP guidance has a certain degree of dissemination and implementation in China, which can be improved through effective actions directed towards impact factors.
Venous thromboembolism (VTE) and postoperative bleeding are important complications of lung resection surgery. We investigated the preventive effect of mechanical prophylaxis versus pharmacological prophylaxis after lobectomy, and evaluated the effect of both on the incidence of hemorrhagic events.
A prospective study of 424 lobectomies with moderate to high risk of VTE (Caprini risk score <5) in a single center was performed from April 2020 to March 2021. Patients were 11 randomly allocated to mechanical prophylaxis or to the low-molecular-weight heparin (LMWH)-combination-prophylaxis. The incidence of postoperative thrombotic and bleeding events and relevant factors of the two groups were analyzed.
A total of 410 participants, with 202 and 208 in the mechanical prophylaxis and LMWH-combination-prophylaxis groups respectively, were selected for analysis. Both groups had similar baseline and clinical characteristics. There were no cases of VTE or major bleeding during the study, but the incidence rate of minor bleeding in the LMWH-combination-prophylaxis group was significantly higher than mechanical prophylaxis group [odds ratio (OR) 0.035, 95% confidence interval (CI) 0.011-0.113].
A case-by-case risk assessment of VTE and hemorrhage remains necessary to determine the most appropriate method of thrombosis prophylaxis for patients undergoing pulmonary surgery. Mechanical prophylaxis may be preferable for lung cancer patients with moderate to high risk of VTE (Caprini risk score <5) undergoing lobectomy.
Chinese Clinical Trial Registry ChiCTR2100051073.
Chinese Clinical Trial Registry ChiCTR2100051073.
This study aimed to explore the effects of voriconazole on population pharmacokinetics and optimization of the initial dose of tacrolimus in children with chronic granulomatous disease (CGD) undergoing hematopoietic stem cell transplantation (HSCT).
Thirty-four children with CGD undergoing HSCT were assessed to establish a population pharmacokinetic model (PPM) using the non-linear mixed effect. Tacrolimus concentrations were simulated by the Monte Carlo method in children weighing <25 kg at different doses.
In the final model, weight and concomitant use of voriconazole were included as covariates. With the same weight, the relative value of tacrolimus clearance was 10.388 in children not taking voriconazole children taking voriconazole. Compared with children not taking voriconazole, the measured tacrolimus concentrations were all higher in children taking voriconazole (P<0.01); however, these were not corrected by dose or body weight for concentration differences. link3 Thus, we simulated the tacrolimonazole significantly increased tacrolimus concentrations. In addition, the initial dose of tacrolimus in children with CGD undergoing HSCT was recommended.
Human infertility is caused by many factors, among which thin endometrium is the main reason for poor embryo implantation. Currently, stem cell therapy could be a potential approach in treating human endometrial disorder like thin endometrium. In this study, we aimed to explore the influence of menstrual stem cells from non-thin endometrium (NTE-MenSCs) and thin endometrium (TE-MenSCs) on the phenotype of endometrial epithelial cells (EECs).
The MenSCs were isolated from women with and without thin endometria, characterized and co-cultured with the EECs. The expression of cytokeratin 7 (CK7) was verified by immunofluorescence while the detection stem cell markers was determined flow cytometry. Osteogenic and adipogenic differentiation were induced in appropriate media. The quantitative real-time PCR and western blotting were respectively used for detecting the mRNA and protein expression levels, respectively. The CCK-8 assay was used for cell viability analysis whereas ELISA was used for the detection of cytokine levels.
The results showed that the co-culture of NTE-MenSCs or TE-MenSCs and EECs promoted the proliferation, migration, and angiogenesis of endothelial progenitor cells differently. Furthermore, the TE-MenSCs promoted the expression of inflammation, vascularized adipose, and extracellular matrix related proteins. The epidermal growth factor (EGF)/Ras p21 pathway was found to mediate the influence of MenSCs on EECs.
These findings are vital in that they may promote stem cell therapy of thin endometrium and enable embryo implantation in humans with thin endometrium.
These findings are vital in that they may promote stem cell therapy of thin endometrium and enable embryo implantation in humans with thin endometrium.
Immune checkpoint inhibitors (ICIs) have brought clinical benefits to patients with various histological types of lung cancer. Previous studies have shown an association between mesenchymal-epithelial transition (MET) and the immunotherapy response in non-small cell lung cancer (NSCLC) but there is a lack of clinical data on the correlation of MET amplification with the ICI response in NSCLC.
Copy number alteration (CNA), somatic mutation, and clinical data from two immunotherapy cohorts (Rizvi
cohort and our local cohort) were collected and pooled to further investigate the key role of MET amplification in patients with NSCLC receiving ICIs. The correlations between MET amplification and tumor immunogenicity and antitumor immunity were further investigated in The Cancer Genome Atlas (TCGA)-NSCLC [lung adenocarcinoma (LUAD)/lung squamous cell carcinoma (LUSC)] data-set.
In the immunotherapy cohorts, MET amplification was associated with longer progression-free survival (PFS) times in patients receiving ICI treatment (P=0.039; HR =0.37; 95% CI 0.18-0.73). In the TCGA-NSCLC data-set, MET amplification was associated with high MET mRNA and protein levels, tumor mutation burden (TMB), neoantigen load (NAL), immune-activated cell patterns, immune-related gene expression levels, and the number of gene alterations in the DNA damage response and repair (DDR) pathway. Gene set enrichment analysis (GSEA) results indicated significant up-regulation of the immune response-related pathways in the MET-amplification group.
Our results suggest that MET amplification may be a novel predictive marker for immunotherapy efficacy in NSCLC.
Our results suggest that MET amplification may be a novel predictive marker for immunotherapy efficacy in NSCLC.
Lysyl oxidase (LOX) has been identified to modulate osteoclast activity, so we explored the role of LOX
, the highest frequency single nucleotide polymorphism in LOX, in osteoclast formation and its potential relationship to autophagy.
The ability of the LOX mutant, LOX
, to promote autophagy and osteoclast formation was evaluated in the pre-osteoclast cell line RAW264.7. Furthermore, autophagy-related protein expression and autophagosomes were detected by western blot and electron microscopy, respectively. Simultaneously, osteoclast formation and resorption ability were also detected using TRAP staining assay and bone resorption assay. In addition, the osteoclast-related proteins and mRNAs, as well as p-AMPKα and p-mTOR proteins, were further evaluated by western blot and qPCR assays.
Autophagy inhibitor 3-MA suppressed the Beclin-1 and ATG5 protein levels and the ratio of LC3-II to LC3-I, as well as autophagosome formation in RAW264.7 transfected with the MUT plasmid and enhanced p62 protein expression.
