Assessment of prolonged proteasome inhibition through ixazomib-based oral regimen on newly diagnosed and first-relapsed multiple myeloma: A real-world Chinese cohort study.

OBJECTIVE: To evaluate the effectiveness, safety, and convenience of in-class transition (iCT) from intravenous bortezomib-based induction to ixazomib-based oral regimens. METHODS: This retrospective real-world study was conducted in 16 Chinese hospitals between October 2017 and April 2023 and analyzed newly diagnosed (NDMM) and first-line relapsed multiple myeloma (FRMM) patients who attained at least a partial response from bortezomib-based induction therapy, followed by an ixazomib-based oral regimen for 2 year or until disease progression or intolerable toxicity. RESULTS: The study enrolled 199 patients, median age: 63 years old, male 55.4%, 53% as high risk (HR), and 47% as standard risk. Cytogenetic risk stratification by metaphase fluorescence in situ hybridization (M-FISH), based on the Mayo Clinic risk stratification system. The median duration of total PI therapy was 11 months, with ixazomib-based treatment spanning 6 months. At the 20-month median follow-up, 53% of patients remained on therapy. The 24-month PFS rate was 84.3% from the initiation of bortezomib-based induction and 83.4% from the start of ixazomib-based treatment. Overall response rate (ORR) was 100% post-bortezomib induction and 90% following 6 cycles of the ixazomib-based regimen. Based on the Sankey diagrams, 89.51% of patients maintained or improved their disease response after 2 cycles of iCT, 6 cycles (90.14%), and 12 cycles (80%). The HR level of Mayo was found to be a significant independent factor in a worse remission (hazard ratio (HR) 2.55; p = 0.033). Ixazomib's safety profile aligned with previous clinical trial data, with 49% of patients experiencing at least one AE of any grade. The most common AEs included peripheral neuropathy, nausea and vomiting, diarrhea, thrombocytopenia, and granulocytopenia. CONCLUSION: In the real-world Chinese MM population, NDMM and FRMM patients responded favorably to PI-based continuous therapy, demonstrating substantial response rates. The ixazomib-based iCT allows for sustained PI-based treatment, offering promising efficacy and tolerable AEs.

Clinical Observation and Pharmacoeconomic Evaluations of Original Research Drug and Generic Drug Bortezomib in the Treatment of Multiple Myeloma.

Background: Multiple myeloma (MM) is one of the hitherto incurable malignant blood tumors. Bortezomib plays an important role in the treatment of MM. Objective: We aimed to compare effectiveness, safety, and pharmacoeconomic evaluations of the original research drug and the generic drug Bortezomib in the treatment of MM, so as to provide a reasonable basis for the selection of drugs in clinical diagnosis and treatment. Methods: A collection of 374 patients with MM were diagnosed and treated with combined Bortezomib in our hospital from July 2019 to January 2020.Two hundred and sixty nine cases met the criteria for inclusion and discharge. According to the different drug manufacturers, divided into the original research drug group (n = 149) and the generic drug group (n = 120). The effectiveness and safety were separately counted, and use the cost-minimization analysis to make the pharmacoeconomic evaluations. Results: Compared with the results of the two groups, there was no statistical difference between the two groups of treatment efficacy or adverse reaction rates (P > 0.05). The average daily cost of the original research drug group was 2954.38 Chinese yuan (CNY), the average treatment cost per cycle was 32967.69 CNY, the average daily cost of the generic drug group was 2697.29 CNY, and the average treatment cost per cycle was 29129.57 CNY. The price of the generic drug group is lower than the original drug group, and there was a statistical difference between the two groups (P < 0.05). Conclusion: There was no difference between the two groups of effectiveness or safety, and the generic drug is more economical in the treatment.

Dual-Channel Global Closed-Loop Supply Chain Network Optimization Based on Random Demand and Recovery Rate.

In the process of globalization, customer demand is usually difficult to predict, and product recycling is generally difficult to achieve accurately. It is also urgent to deal with increased inventory while avoiding shortages, with the purpose of reducing supply chain risks. This study analyzes the integrated supply chain decision-making problem in the random product demand and return environment. It proposes a multi-objective optimization model, which is an effective tool to solve the design and planning problems of the global closed-loop supply chain. It consists of a multi-period, single-product and multi-objective mixed integer linear programming model, which can solve some strategic decision problems, including the network structure, entity capacities, flow of products and components, and collection levels, as well as the inventory levels. From the perspective of economic, environmental and social benefits, three objective functions are defined, including maximizing the net present value (NPV) of the system, minimizing the total CO2e emissions of supply chain activities, and maximizing social sustainability indicators. Finally, a numerical example is provided to verify the advantages of this model, and sensitivity analysis results are provided. The results show that changes in product demand and return rate will have a great impact on economic and social performance.

Farmer-Led Irrigation and its Impacts on Smallholder Farmers' Crop Income: Evidence from Southern Tanzania.

Irrigation projects in sub-Saharan Africa are mostly unsustainable because of lack of maintenance by their users or government planners. By contrast, evidence shows that the smallholder farmers are developing and expanding the irrigated land, using their initiatives. Farmer-led irrigation, a revolutionary agricultural intensification approach, is already in progress with the magnitude to significantly transform the living standards of smallholder farmers. However, a rigorous assessment of its impact on household welfare to ascertain this is lacking. This paper bridges this gap by assessing factors influencing the adoption of this particular approach as well as its effects on the farmers' per capita net crop income. Our data set consists of 608 smallholder farmers in Southern Tanzania and used propensity score matching to estimate the effects of adoption on the per capita net crop income. Our results indicate that the uptake of farmer-led irrigation practices is influenced by drought experience, water user group membership, farmer organization membership, and government extension, as well as the sex of the household head. Further, there was a positive and significant effect on the adopters' per capita net crop income, thus encouraging the need to promote farmer-led irrigation as a complement to externally promoted innovations in achieving sustainable food security. This study, therefore, recommends that the government should support the farmers' initiative by improving roads, removing market barriers, and helping farmers who have not yet taken up the initiative. Also, the government should enact regulations to make sure farmer-led irrigation initiatives do not harm the eco-environment such as protecting domestic water users. Finally, the government should leverage microservices to the farmers such as promoting affordable and appropriate credit facilities. It is necessary to continue pursuing this vein of research to gain information regarding the definite impact of the farmer-led irrigation on household welfare.

The Evaluation Method of Low-Carbon Scenic Spots by Combining IBWM with B-DST and VIKOR in Fuzzy Environment.

With the concept of sustainability gaining popularity, low-carbon tourism has been widely considered. In this paper, a multicriteria group decision making (MCGDM) process based on an uncertain environment is proposed to study the evaluation problem of low-carbon scenic spots (LSSs). In order to minimize the influence of subjective and objective factors, the traditional Vlse Kriterjumska Optimizacija I Kompromisno Resenje (VIKOR) method is expanded, using the improved best and worst method (IBWM) and Bayes approximation method, based on Dempster-Shafer Theory (B-DST). First, in order to make the evaluation process more professional, a number of evaluation criteria are established as effective systems, followed by the use of triangular intuitionistic fuzzy numbers (TIFNs) to evaluate alternatives of LSSs. Next, according to the evaluation results, the weights of the criteria are determined by the IBWM method, and the weights of the expert panels (Eps) are determined by B-DST. Finally, a weighted averaging algorithm of TIFN is used to integrate the above results to expand the traditional VIKOR and obtain the optimal LSS. The applicability of this method is proven by example calculation. The main conclusions are as follows: tourist facilities and the eco-environment are the two most important factors influencing the choice of LSSs. Meanwhile, the roles of management and participant attitudes in LSS evaluations cannot be ignored.