A Health Technology Assessment Based on Chinese Guideline: Active Vitamin D and Its Analogs in the Treatment of Osteoporosis.

Objective: To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals. Methods: In this study, three active vitamin D and its analogs were evaluated by quantitative scoring in five dimensions, including pharmaceutical properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points). Results: The final scores of quantitative assessment for the selection of alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets, alfacalcidol capsules, alfacalcidol oral drops, calcitriol injection, and eldecalcitol soft capsules were 73.17, 72.06, 71.52, 71.29, 69.62, 68.86, 65.60, 64.05 points. Conclusion: Based on the scoring results, alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets can be entered into the medication list of medical institutions as strongly recommended drugs. This study offers guidance on selecting and using active vitamin D and its analogs in hospitals, with consideration for the patient's needs.

Comparison of the efficacy and safety of domestically produced tislelizumab, camrelizumab, and imported pembrolizumab in the treatment of advanced NSCLC: a real-world retrospective study.

BACKGROUND: Since the imported PD-1 inhibitor pembrolizumab was listed in China in 2018, China has opened up the era of immunotherapy for malignant tumors, with several domestically produced PD-1 inhibitors coming onto the market one after another. To find out whether there are differences in the efficacy and safety of domestic and imported PD-1 inhibitors in patients with advanced non-small cell lung cancer, we conducted this retrospective study in two tertiary hospitals in China. METHODS: Patients with advanced NSCLC treated with tislelizumab or camrelizumab or pembrolizumab who met the inclusion criteria were screened through the electronic medical record system. A total of 259 patients were screened, but due to the unbalanced baseline, we performed propensity score matching and finally included 149 patients in three groups: pembrolizumab (n = 38), tislelizumab (n = 38), and camrelizumab (n = 73), which had very balanced baseline characteristics in each group after propensity score matching treatment. RESULTS: The results showed that the median progression-free period was 11.3 m vs 10.1 m vs 8.9 m; p = 0.754; and the objective response rate was 63.2% vs 50% vs 57.5%; P = 0.510 for pembrolizumab, tislelizumab, and carrelizumab, respectively. There was no significant difference in median PFS between PD-L1 expression subgroups. In terms of safety, only skin toxicity of any grade of carrelizumab was higher than that of the other two groups (p = 0.034), and the incidence of grade ≥ 3 adverse reactions was not statistically significant among the three groups. CONCLUSION: In this real-world study, the efficacy and safety of the domestically produced tislelizumab, camrelizumab, and the imported pembrolizumab were comparable.

YOLOv8-MU: An Improved YOLOv8 Underwater Detector Based on a Large Kernel Block and a Multi-Branch Reparameterization Module.

Underwater visual detection technology is crucial for marine exploration and monitoring. Given the growing demand for accurate underwater target recognition, this study introduces an innovative architecture, YOLOv8-MU, which significantly enhances the detection accuracy. This model incorporates the large kernel block (LarK block) from UniRepLKNet to optimize the backbone network, achieving a broader receptive field without increasing the model's depth. Additionally, the integration of C2fSTR, which combines the Swin transformer with the C2f module, and the SPPFCSPC_EMA module, which blends Cross-Stage Partial Fast Spatial Pyramid Pooling (SPPFCSPC) with attention mechanisms, notably improves the detection accuracy and robustness for various biological targets. A fusion block from DAMO-YOLO further enhances the multi-scale feature extraction capabilities in the model's neck. Moreover, the adoption of the MPDIoU loss function, designed around the vertex distance, effectively addresses the challenges of localization accuracy and boundary clarity in underwater organism detection. The experimental results on the URPC2019 dataset indicate that YOLOv8-MU achieves an mAP@0.5 of 78.4%, showing an improvement of 4.0% over the original YOLOv8 model. Additionally, on the URPC2020 dataset, it achieves 80.9%, and, on the Aquarium dataset, it reaches 75.5%, surpassing other models, including YOLOv5 and YOLOv8n, thus confirming the wide applicability and generalization capabilities of our proposed improved model architecture. Furthermore, an evaluation on the improved URPC2019 dataset demonstrates leading performance (SOTA), with an mAP@0.5 of 88.1%, further verifying its superiority on this dataset. These results highlight the model's broad applicability and generalization capabilities across various underwater datasets.

Health Technology Assessment: Evaluation of 7 Glucagon-Like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes Mellitus.

Purpose: This study provides a reference for healthcare organizations in the selection and rational use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), based on the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition). Methods: According to the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition) released in 2023, relevant databases such as PubMed, Cochrane, and Embase, drug labels, and clinical guidelines were searched for drug information. We systematically evaluated 7 GLP-1RAs marketed in China for safety, efficacy, economy, pharmacological properties, and other attributes using a percentage scoring method. Results: The final assessment result scores from highest to lowest were semaglutide (71.5 points), dulaglutide (68.9 points), liraglutide (68.7 points), exenatide (62.5 points), lixisenatide (59.9 points), polyethylene glycol loxenatide (55.9 points), and benaglutide (45.1 points). Conclusion: When a healthcare organization introduces GLP-1RAs to their hospital, they can refer to the assessment results and use the top three recommended medications: semaglutide, dulaglutide, and liraglutide.

Efficacy and potential mechanism of atherosclerosis prevention by the active components of leech based on network pharmacology combined with animal experiments.

Introduction: Leeches are flesh-eating and bloodsucking parasitic worms. They are being used as a traditional Chinese medicine for centuries in activating blood and dissolving statis, dreging the meridims and tick. Hirudin, an active peptide product present in leech, has blood anticoagulant property and can assist in the treatment of thrombosis and diseases related to blood circulation. The efficacy and potential mechanism of action of leeches in such diseases should be further explored. Materials and methods: First, network pharmacology was used to screen the predicted potential targets of the active constituents of leech and AS. The common targets of the active constituents of leech and AS were obtained using Venn diagram. Further, the drug-active-constituent-target network diagram, protein-protein interaction, and GO and KEGG pathway enrichment analyses were used to construct the active-constituent-AS target-pathway network diagram. Subsequently, the protein-drug molecule docking model was drawn. Finally, the results of network pharmacology were validated using a mouse model of AS. Results: In total, 34 active constituents of leech and 1172 AS-related gene targets were selected, took the drug action targets and potential disease targets to get the common targets, and took the top 10 of degree value as the main active constituents for the treatment of atherosclerosis. There were 89 common targets and 12 core targets. The main targets included MAPK, EGFR, PIK3CB, etc. Potential regulatory pathways included cancer pathways, EGFR tyrosine kinase inhibitor resistance, Rap1 signaling pathway, PPAR signaling pathway, PI3K-Akt signaling pathway, C-type lectin receptor signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Animal experiments using mouse model of AS confirmed that AS plaques were smaller after treatment with leeches. SRC level was measured using western blotting. Expression of SRC in myocardial tissue was remarkably lower in the mice treated with leech than in the mice from model group fed on high-fat chow. Conclusions: To the best of our knowledge, this is the first study to explore the mechanism of action of the active components of leech in AS prevention. The active components of leeches play a coordinated role in preventing AS through multicomponent, multitarget, and multichannel mechanism of action related to inflammatory response, oxidative stress, and lipid metabolism. This study provided a reference for subsequent cellular and animal experiments.

Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis.

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis. A total of 66 patients were included, with a median age of 68 years. The median onset time of myocarditis is 11.5 days. The main organs affected in persons presented with myocarditis are heart (100.0%) and skeletal muscle (22.7%). The main clinical manifestations are dyspnea (49.2%), fatigue (47.6%), and myalgias (25.4%). The levels of troponin, troponin T, troponin I, creatine kinase, creatine kinase myocardial band, creatine phosphokinase, C-reactive protein, brain natriuretic peptide, and N-terminal brain natriuretic peptide precursor were significantly increased. Histopathology often shows lymphocyte infiltration, myocardial necrosis, and fibrosis. Myocardial immunological parameters usually present positive. Cardiac imaging often suggests complete heart block, intraventricular conduction delay, arrhythmia, myocardial infarction, edema, left ventricular ejection fractions reduction, ventricular dysfunction, and other symptoms of myocarditis. Forty-two (63.6%) patients achieved remission within a median time of 8 days after discontinuation of nivolumab and treatment with systemic corticosteroids, immunoglobulins, plasmapheresis, and immunosuppressant. Thirty-five patients eventually died attributed to myocarditis (68.6%), cancer (20.0%), respiratory failure (5.7%), and other reasons (5.7%). Nivolumab-induced myocarditis should be comprehensively diagnosed based on clinical symptoms, histopathological manifestations, immunological parameters, and cardiac function imaging examinations. Nivolumab should be discontinued immediately, plasmapheresis and systemic corticosteroids combined with immunoglobulins or immunosuppressants may be an effective treatment.

The association between atherosclerosis and nonalcoholic fatty liver disease.

Atherosclerosis (AS) is closely related to nonalcoholic fatty liver disease (NAFLD), which promotes and exacerbates the development of AS. However, it is uncertain how the precise underlying mechanism occurs. Here, we attempted to further explore the association underlying atherosclerosis and nonalcoholic fatty liver disease through integrated bioinformatics analysis. Microarray data for atherosclerosis and nonalcoholic fatty liver disease were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify the genes related to atherosclerosis and nonalcoholic fatty liver disease showing co-expression. Additionally, the common gene targets associated with atherosclerosis and nonalcoholic fatty liver disease were also analyzed and screened using data from 3 public databases [comparative toxicogenomics database (CTD), DISEASES, and GeneCards]. The Gene Ontology (GO) enrichment analysis and the Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed using Metascape R, respectively. The protein-protein interaction networks (PPI) network was constructed using Cytoscape. According to the results of an analysis of common genes, matrix metalloproteinase 9 (MMP9) is co-expressed up-regulated in AS and NAFLD and is enriched in inflammatory and immune-related collaterals. Consequently, MMP9 may work together through immunity and inflammation to treat AS and NAFLD and may be a potential therapeutic target in the future. The findings of this study provide new insights into the shared association between AS and NAFLD. MMP9 is co-expressed up-regulated in AS and NAFLD, which be able to reveal the presence of co-expressed genes in atherosclerosis and NAFLD.

Intrathecal or intraventricular antimicrobial therapy for post-neurosurgical Gram-negative bacillary meningitis or ventriculitis: a systematic review and meta-analysis.

PURPOSE: Extensively-drug-resistant Gram-negative bacteria (XDR GNB)-related post-neurosurgical infection is closely related to mortality, which represents a major challenge for neurosurgeons. There is an urgent need to review and evaluate methods to reduce mortality. METHODS: Both international and Chinese databases were searched independently from their inception to 15 June 2023. A meta-analysis was conducted using RevMan 5.4 to compare the efficacy and safety of intravenous (IV) treatment in combination with intrathecal or intraventricular (ITH/IVT) treatment with IV treatment alone for post-neurosurgical meningitis or ventriculitis due to GNB. Mortality, microbiological clearance and adverse events were considered as primary outcomes. RESULTS: In total, 18 eligible studies involving 602 patients were included in the meta-analysis. The IV + ITH/IVT group was associated with significantly lower mortality (especially in the XDR GNB subgroup) and acceptable safety. In terms of microbiological clearance, a significant decrease was shown in the XDR GNB subgroup. Significant benefits were shown in laboratory parameters and clinical symptoms after patients were treated with ITH/IVT. CONCLUSION: Additional ITH/IVT treatment may promote XDR GNB clearance and reduce mortality. In addition, ITH/IVT administration can improve clinical symptoms and cerebrospinal fluid indicators of patients with post-neurosurgical infections. Significantly, ITH/IVT treatment does not increase the incidence of adverse events at the recommended dose.

Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review.

Purpose: This study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin that is approved for use worldwide in patients with type 2 diabetes and to provide evidence-based support and reference for the selection of clinical treatment. Methods: Three databases (PubMed, Embase, and Cochrane Library) were searched from their respective inception until September 30, 2022. Only randomized controlled trials comparing the efficacy and safety of GLP-1RAs for treating type 2 diabetes (T2D) were included. The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide. Results: 34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA). According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200µg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively. There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg. PEX168-200µg, tirzepatide 15mg, and oral semaglutide 14mg had Surface Under the Cumulative Ranking (SUCRA) values greater than placebo, and only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events. All GLP-1RA did not lead to increased incidence of hypoglycemia. Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal. Finally, the sensitivity analysis and publication bias analysis results indicate that the study results are reliable. Conclusion: This study's results showed that GLP-1RAs were effective in lowering HbA1c and reducing body weight without increased incidence of hypoglycemic reactions. In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred.

A multicenter real-world study comparing the clinical equivalence of trastuzumab biosimilar HLX02 and reference trastuzumab in the treatment of HER-2-positive breast cancer.

As the first trastuzumab biosimilar introduced in China, there are few studies on the clinical application of HLX02, especially in combination with other antitumour drugs, for the treatment of HER-2-positive breast cancer. A multicenter retrospective study was conducted in three hospitals in China to select patients with HER-2-positive breast cancer who met the inclusion criteria and received HLX02 or the reference trastuzumab. Ninety-six patients diagnosed with HER-2-positive breast cancer were finally included and divided into two groups and treated with HLX02 or the reference trastuzumab. The results showed no significant differences in pathological complete response (70.0% vs. 76.2%; P=1.000) and overall response rate (91.9% vs. 94.9%; P=0.673) between the two groups. Kaplan-Meier survival curves also showed no significant difference in time-to-event variables between the two groups (log-rank P=0.48). Safety was also comparable in both groups. In conclusion, among patients with HER2-positive breast cancer, HLX02 demonstrated equivalent efficacy and safety to its reference trastuzumab, both in neoadjuvant chemotherapy and in postoperative adjuvant therapy. However, clinical equivalence studies between HLX02 and the original trastuzumab drug remain challenging. Future research should focus on the clinical exchange between biosimilars and original drugs, as well as the extrapolation of biosimilars' indications.

Plutonium in sediments of the Eastern Guangdong coast-its sources and their contribution.

The 239+240Pu activities and 240Pu/239Pu atom ratios of surface sediments from the Eastern Guangdong coast (EGDC) were determined by sector field ICP-MS in order to examine the sources of plutonium (Pu) and quantify their contributions. The 239+240Pu activities in the EGDC ranged from 0.113 to 0.451 Bq kg-1, with an average of 0.225 ± 0.090 Bq kg-1 (n = 17). Consistently high 240Pu/239Pu atom ratios, ranging from 0.218 to 0.274 (average = 0.254 ± 0.014, n = 17), indicate a non-global fallout Pu source in the EGDC. The horizontal distribution of the 240Pu/239Pu atom ratios in the EGDC sediment suggests the non-global fallout Pu is sourced from close-in fallout from the Pacific Proving Grounds (PPG). Using a simple two end-member mixing model, we calculated the relative proportions of Pu from the PPG and global fallout in the EGDC to be 57 ± 9 % and 43 ± 9 %, respectively. Moreover, from the well-defined relationship between 239+240Pu activity and total organic carbon content in sediments and a two end-member mixing model using δ13C, we further calculated the Terr-global fallout (riverine input) and Mar-global fallout (direct atmospheric deposition) to be 11 ± 2 % and 32 ± 6 %, respectively. Finally, from the activity levels and atom ratios of Pu isotopes in the EGDC, we established a baseline for future use in environmental risk assessment related to nuclear power plant operations.

Surgical Pharmacy for Optimizing Medication Therapy Management Services within Enhanced Recovery after Surgery (ERAS®) Programs.

Drug-related problems (DRPs) are common among surgical patients, especially older patients with polypharmacy and underlying diseases. DRPs can potentially lead to morbidity, mortality, and increased treatment costs. The enhanced recovery after surgery (ERAS) system has shown great advantages in managing surgical patients. Medication therapy management for surgical patients (established as "surgical pharmacy" by Guangdong Province Pharmaceutical Association (GDPA)) is an important part of the ERAS system. Improper medication therapy management can lead to serious consequences and even death. In order to reduce DRPs further, and promote the rapid recovery of surgical patients, the need for pharmacists in the ERAS program is even more pressing. However, the medication therapy management services of surgical pharmacy and how surgical pharmacists should participate in ERAS programs are still unclear worldwide. Therefore, this article reviews the main perioperative medical management strategies and precautions from several aspects, including antimicrobial agents, antithrombotic agents, pain medication, nutritional therapy, blood glucose monitoring, blood pressure treatment, fluid management, treatment of nausea and vomiting, and management of postoperative delirium. Additionally, the way surgical pharmacists participate in perioperative medication management, and the relevant medication pathways are explored for optimizing medication therapy management services within the ERAS programs. This study will greatly assist surgical pharmacists' work, contributing to surgeons accepting that pharmacists have an important role in the multidisciplinary team, benefitting medical workers in treating, counseling, and advocating for their patients, and further improving the effectiveness, safety and economy of medication therapy for patients and promoting patient recovery.

Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review.

Purpose: The effect and safety of Semaglutide and Liraglutide on weight loss in people with obesity or overweight were evaluated by a Network Meta-Analysis system to provide an evidence-based reference for clinical treatment. Methods: Computer searched PubMed, Embase, and Cochrane Library databases to collect Liraglutide and Semaglutide injection monotherapy RCTs until April 2022, using Stata 16 software for Network Meta-Analysis. Results: Twenty-three RCTs study with 11,545 patients and 4 interventions (semaglutide 2.4mg, semaglutide 1.0mg, liraglutide 3.0mg and liraglutide 1.8 mg) were finally included. In terms of efficacy, semaglutide 2.4mg (-12.47 kg) had the best weight loss, followed by liraglutide 3.0mg (-5.24 kg), semaglutide 1.0mg (-3.74 kg) and liraglutide 1.8mg (-3.29 kg). In terms of decreased HbA1c, semaglutide 2.4mg (MD=-1.48%, 95% CI [-1.93, -1.04]), semaglutide 1.0mg (MD=-1.36%, 95% CI [-1.72, -1.01]), liraglutide 1.8mg (MD=-1.23%, 95%Cl [-1.66, -0.80]) more effective than placebo. In terms of safety, the total incidence of adverse events was semaglutide 2.4mg > liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 1.0mg compare to placebo, the incidence of serious adverse events was liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 2.4mg > semaglutide 1.0mg, the incidence of hypoglycemic events was semaglutide 2.4mg > liraglutide 3.0mg > semaglutide 1.0mg > liraglutide 1.8mg. Conclusion: This meta-analysis indicates that all GLP-1RAs were more efficacious than placebo in people with obesity or overweight on efficacy. Semaglutide 2.4mg has an absolute advantage in weight loss and decreased HbA1c, but the incidence of total adverse events is also the highest and can cause hypoglycemia. In addition, although liraglutide 3.0mg was less effective than semaglutide 2.4mg, serious adverse events were still the most elevated.

Efficacy and safety of proton pump inhibitors versus vonoprazan in treatment of erosive esophagitis: A PRISMA-compliant systematic review and network meta-analysis.

BACKGROUND: Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE. METHODS: Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment. RESULTS: A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo. CONCLUSIONS: Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.

Comparative efficacy and safety of antiviral traditional Chinese medicine injections for viral pneumonia: a systematic review and network meta-analysis.

BACKGROUND: Viral pneumonia (VP) is becoming a persistent and pervasive burden of disease. Traditional Chinese medicine Injections (TCMIs) have been proved effective in the treatment of patients with VP, which are now widely used in China. The evidence of TCMIs for VP is evolving rapidly. This study aims to assess the comparative efficacy and safety of TCMIs to provide more evidence and sights for the treatment selection of VP. RESEARCH DESIGN AND METHODS: Seven databases were searched from their inception up to 16 March 2022. Only randomized controlled trials (RCTs) are included to compare the efficacy and safety of antiviral TCMIs for the treatment of viral pneumonia. Clinical efficacy and rate of adverse events were considered as primary outcomes. RESULTS: A total of 76 RCTs with eight TCMIs comprising 7925 patients were included in the NMA. According to NMA, Reduning Injection combined with conventional antiviral drugs (CAD) produced superior effects in the effective outcomes and reduced the adverse event incidence rate of VP. CONCLUSIONS: This study indicated that TCMIs combined with CAD was more effective and safer than CAD monotherapy and compared different TCMIs therapies, which provided guidance and reference for the selection of clinical treatment medication.

A Health Technology Assessment Based on Chinese Guidelines: Glucagon-Like Peptide-1 Receptor Agonist in the Treatment of Type 2 Diabetes Complicated with Cardiovascular Disease.

Purpose: According to the requirements of the "Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions", this health technology assessment provides an evidence-based basis for drug selection and rational clinical use of glucagon-like peptide-1 receptor agonist drugs in medical institutions. Methods: We consult the drug instructions, clinical treatment guidelines and search relevant documents in databases such as China national knowledge infrastructure, Wanfang, PubMed, and government websites such as National Medical Products Administration, Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency to collect and sort out the relevant information of the indications, pharmacological effects, guideline recommendations, drug prices and other information of glucagon-like peptide-1 receptor agonists, using a percentile system systematically evaluate the five dimensions of glucagon-like peptide-1 receptor agonists in terms of pharmaceutical properties, efficacy, safety, economy, and other attributes. Results: The final scores of the evaluation results from high to low are semaglutide (71.00 points), dulaglutide (68.75 points), liraglutide (67.50 points), exenatide (67.00 points), lixisenatide (63.50 points), polyethylene glycol loxenatide (58.00 points) and benaglutide (49.00 points). Conclusion: In clinical practice, semaglutide and dulaglutide are the top two drugs that can be used as recommended drugs. This health technology assessment can provide an evidence-based basis for hospital selection and rational use of glucagon-like peptide-1 receptor agonists. Clinicians can rationally choose and use drugs according to the patient's conditions and needs.

Trastuzumab biosimilar HLX02 versus reference trastuzumab in patients with recurrent or metastatic HER2-positive breast cancer: a model-based economic evaluation for China.

BACKGROUND: HLX02 is a newly marketed trastuzumab biosimilar in China, but whether its price reflects a potential benefit in terms of its value remains unclear. In addition, the development of biosimilars in China is just beginning, and the state encourages health economic evaluation of newly marketed biosimilars. METHODS: Based on the previously published randomized controlled trial data, a Markov model was used to perform health economic evaluation of HLX02 and trastuzumab in the treatment of HER2-positive recurrent or metastatic breast cancer, calculate quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), and evaluate the robustness of the model with sensitivity analysis. RESULTS: The model results showed that the 5-year mortality rate was 84.4% in the HLX02 group, while the mortality rate was 91.2% in the trastuzumab group. When without accounting for the cost of second-line treatment, patients treated with HLX02 had an increased life expectancy of 0.138 QALYs and a $421.11 lower cost compared with patients in the trastuzumab group, with an ICER value of -$3,051.52/QALY. CONCLUSIONS: At the willingness-to-pay threshold of $37,653/QALY in China, HLX02 is more cost-effective than trastuzumab. However, the relevant systems for the regulation of biosimilars still need to be improved.

Metastatic HER-2 positive breast cancer poses a considerable cost to society due to limitations in health care resources. HLX02 is the first trastuzumab biosimilar produced in China and evaluated worldwide, and its emergence has opened the door to trastuzumab biosimilars in China. Although HLX02 has been shown to be clinically equivalent to the original drug in the treatment of metastatic HER2-positive breast cancer, it remains unclear whether its price reflects the potential benefit in terms of its value. In addition, the development of biosimilars in China is just beginning, and the state encourages health economic evaluation of newly marketed biosimilars. Based on the results of Markov model, at the willingness-to-pay threshold of $37,653/QALY in China, HLX02 is more cost-effective than trastuzumab under the condition of equivalent efficacy and safety. However, it remains challenging to adjust the development of the regulation of biosimilars, such as the price difference between biosimilars and original drugs.

Rituximab biosimilar HLX01 versus reference rituximab in the treatment of diffuse large B-cell lymphoma: Real-world clinical experience.

INTRODUCTION: HLX01 is the first rituximab biosimilar produced in China and the first monoclonal antibody biosimilar marketed in China. The purpose of this study was to comprehensively evaluate whether HLX01 is clinically consistent with the original drug based on real-world data to provide evidence for the clinical substitution of biosimilars in China. METHODS: A single-center retrospective study was conducted to select patients with diffuse large B-cell lymphoma who met the inclusion criteria and were treated with HLX01 or reference rituximab. Baseline characteristics, efficacy and safety results were recorded, and the corresponding statistical analysis was performed for various indicators. RESULTS: Thirty-three patients diagnosed with diffuse large B-cell lymphoma were included and divided into two groups that received HLX01 or reference rituximab. The results showed no significant difference in the overall response rate (86.7% vs. 88.9%; p = 1.000) or complete response rate (46.7% vs. 55.6%; p = 0.889) between the two groups. Kaplan-Meier survival curves also showed no significant difference in time-to-event variables between the two groups (log-rank = 0.244). Safety was also comparable in both groups. CONCLUSIONS: HLX01 is a suitable replacement for reference rituximab in the treatment of diffuse large B-cell lymphoma and is relatively inexpensive, thereby reducing the economic burden of patients. Nevertheless, the conclusion of this study still needs to be further validated by large-sample real-world data and explored for HLX01 in other indications, such as follicular lymphoma. CLINICAL TRIAL REGISTRATION: Not applicable.

Distributions and impacts of plutonium in the environment originating from the Fukushima Daiichi Nuclear Power Plant accident: An overview of a decade of studies.

This paper reviews the current knowledge on plutonium (Pu) isotopic composition (the atom or activity ratios) and activity concentrations of 238Pu, 239Pu, 240Pu, and 241Pu resulting from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident in 2011. In this critical review, we document the characteristic values of Pu atom or activity ratios (fingerprints) and present their spatial distributions around the FDNPP site. Based on multiple Pu fingerprints (238Pu/239+240Pu activity ratio, 240Pu/239Pu atom ratio, and 241Pu/239Pu atom ratio), we clarify that Pu contamination from the FDNPP accident occurred in a restricted terrestrial area, while Pu in the Northwest Pacific Ocean is still predominately sourced from the Pacific Proving Grounds (PPG) and global fallout. Using a simple two end-member mixing model, we calculate average contributions of Pu from the FDNPP accident of 13 ± 20% (n = 180) in soil samples, 55 ± 32% (n = 38) in leaf litter samples, and 67 ± 26% (n = 129) in air dust/black substances. In the marine environment, the PPG source average contributions are 45 ± 15% (n = 76) in seawater and 42 ± 12% (n = 48) in sediments. The spatial distributions of Pu atom or activity ratios based on existing studies suggest that: 1) in the terrestrial region investigated 80 km northwest of the FDNPP site, the Pu contamination is mainly observed in an area within a 50 km distance, and 2) in the terrestrial region investigated 60 km southwest of the FDNPP site, the Pu contamination is mainly observed in an area within a 30 km distance. Studies of Cs-bearing radioactive particles indicate that Pu occurs as Pu oxide, and the fuel fragments containing Pu that were released from the reactors to the surrounding environment are associated with micron-scale Cs-bearing radioactive particles. We note that the fractionation between Pu and other radionuclides occurred after release. These new findings about the Pu fingerprints around the FDNPP site will help researchers to establish a reference background database for future environmental risk assessment and geochemical study there.