A comprehensive clinical evaluation of first-line drugs for ALK-positive advanced non-small cell lung cancer.

Background: Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are mainly used in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), but a comprehensive clinical evaluation of ALK-TKIs is lacking. Hence, a comparison of ALK-TKIs for first-line treatment of ALK-positive advanced NSCLC is essential to provide rational drug use and a basis for improving national policies and systems. Methods: According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs (2021) and the Technical Guideline for the Clinical Comprehensive Evaluation of Antitumor Drugs (2022), a comprehensive clinical evaluation index system of first-line treatment drugs for ALK-positive advanced NSCLC was established by literature review and expert interviews. We conducted a systematic literature review, meta-analysis, and other relevant data analyses, combined with an indicator system, to establish a quantitative and qualitative integration analysis for each indicator and each dimension of crizotinib, ceritinib, alectinib, ensartinib, brigatinib, and lorlatinib. Results: The comprehensive clinical evaluation results of all dimensions were as follows: in terms of safety, alectinib had a lower incidence of grade 3 and above adverse reactions; for effectiveness, alectinib, brigatinib, ensartinib, and lorlatinib showed better clinical efficacy, and alectinib and brigatinib have been recommended by several clinical guidelines; in terms of economy, second-generation ALK-TKIs have more cost-utility advantages, and both alectinib and ceritinib have been recommended by the UK and Canadian Health Technology Assessment (HTA) agencies; for suitability, accessibility, and innovation, alectinib has a higher degree of physician recommendations and patient compliance. Except for brigatinib and lorlatinib, all other ALK-TKIs have been admitted to the medical insurance directory; the accessibility of crizotinib, ceritinib, and alectinib is good, meeting the needs of patients. Second- and third-generation ALK-TKIs have higher blood-brain barrier permeability, stronger inhibition ability, and innovation than first-generation ALK-TKIs. Conclusions: Compared with other ALK-TKIs, alectinib performs better across six dimensions and has a higher comprehensive clinical value. The results provide better drug choice and rational use for patients with ALK-positive advanced NSCLC.

Cost-effectiveness analysis of rhTPO and rhIL-11 in the treatment of chemotherapy-induced thrombocytopenia in hematological tumors based on real-world data.

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a common adverse reaction to chemotherapy that can lead to treatment delay, platelet transfusion, thereby increasing treatment costs, reducing chemotherapy effectiveness and affecting prognosis. Based on real-world data, this study analyzed the safety, efficacy, and economic of recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-11 (rhIL-11) in the treatment of CIT in hematological tumors from the perspective of the health care system. METHODS: We retrospectively collected the data of hematological tumor patients treated with rhTPO and rhIL-11 due to thrombocytopenia caused by chemotherapy. The propensity score matching (PSM) method was used to balance the baseline information of the two groups and they were further stratified according to the degree of thrombocytopenia (grade I-II and grade III-IV). The platelet compliance rate at 2 weeks of treatment was used as the efficacy evaluation index, and the cost-effectiveness method was used to evaluate the economic value of the two drugs in the treatment of thrombocytopenia based on drug effectiveness. Univariate and probabilistic sensitivity analyses were performed. RESULTS: A total of 1,571 patients met the inclusion and exclusion criteria, and 476 patients were included after 1:1 PSM. For patients with grade I-II thrombocytopenia, no significant difference in the platelet compliance rate was found between the two groups after 1 and 2 weeks of treatment. The platelet compliance rate in the rhTPO group was higher than that in the rhIL-11 group for patients with grade III-IV thrombocytopenia. Cost-effectiveness analysis (CEA) showed that the incremental cost-effectiveness ratio (ICER) for the rhTPO and rhIL-11 groups was 226,615.8. The ICER value was sensitive to the platelet compliance rate of the two groups, the cost of rhTPO, the cost of platelet transfusion in the rhTPO group. Probabilistic sensitivity analysis showed that when willingness to pay was less than approximately 220,000 yuan, rhIL-11 economy presented 100% better than that of rhTPO. CONCLUSIONS: In CIT treatment for hematological tumors, rhTPO yielded a higher platelet compliance rate than rhIL-11 treatment, especially for patients with grade III-IV thrombocytopenia. However, whether rhTPO has economic advantages still requires further exploration.

Assessment of cerebral infarction after transient cerebral ischemic attack by ABCD2 score combined with the position of intracranial vascular stenosis.

This study aims to investigate the value of the ABCD score combined with the position of the offending vessel stenosis in predicting the risk of transient ischemic attack (TIA) to develop into cerebral infarction.The ABCD score and head magnetic resonance imaging + magnetic resonance angiography (MRA) results of 192 patients with TIA were retrospectively analyzed. With the 7th day as the endpoint time, these patients were divided into 3 groups, according to ABCD scores: low-risk group (n = 105), moderate-risk group (n = 60), and high-risk group (n = 27). Blood vessels were screened using head MRA results, and patients were accordingly divided into 2 groups: proximal vascular stenosis group (n = 71) and nonproximal vascular stenosis group (n = 171). Then, the association of the position of the intracranial vascular stenosis and ABCD score with short-term prognosis was analyzed.Based on the ABCD score, the incidence of cerebral infarction after 1 week was significantly higher in the high-risk group (85.7%) than in the moderate-risk group (16.7%) and low-risk group (1.9%), and the differences were statistically significant (P < .05). When the ABCD score was ≥4 points, the incidence of cerebral infarction after 1 week was significantly higher in the proximal vascular stenosis group (59.1%) than in the nonproximal vascular stenosis group (30.8%), and the difference was statistically significant (P < .05). When the ABCD score was <4 points, the incidence of cerebral infarction after 1 week in the proximal stenosis group (2%) was not significantly different from that in the nonproximal stenosis group (1.9%, P > .05).The ABCD score combined with proximal offending vessel stenosis can improve the short-term prediction of cerebral infarction in patients with TIA.

Development of an industrial medium for economical 2,3-butanediol production through co-fermentation of glucose and xylose by Klebsiella oxytoca.

An industrial medium containing urea as a sole nitrogen source, low levels of corn steep liquor and mineral salts as nutrition factors to retain high 2,3-butanediol production through co-fermentation of glucose and xylose (2:1, wt/wt) by Klebsiella oxytoca was developed. Urea and corn steep liquor were identified as the most significant factors by the two-level Plackett-Burman design. Steepest ascent experiments were applied to approach the optimal region of the two factors and a central composite design was employed to determine their optimal levels. Under the optimal medium, the yield of 2,3-butanediol plus acetoin relative to glucose and xylose was up to 0.428 g/g, which was 85.6% of theoretical value. The cheap nitrogen source and nutrition factors combining the co-fermentation process using lignocellulose derived glucose and xylose as the carbon source in the developed medium would be a potential solution to improve the economics of microbial 2,3-butanediol production.