Drug Design, Development and Therapy最新文献

{"title":"The Potential Mechanisms of <i>Althaea rosea</i> (Linn.) Cavan. Flower in Alleviating Tetrodotoxin Poisoning: An Integrated Metabolomics, Network Pharmacology and Experimental Validation.","authors":"Renjin Zheng, Youjia Wu, Lingyi Huang, Fanxiang Zeng, Liying Huang","doi":"10.2147/DDDT.S505270","DOIUrl":"https://doi.org/10.2147/DDDT.S505270","url":null,"abstract":"<p><strong>Purpose: </strong>Tetrodotoxin (TTX) poisoning manifests rapidly and severely, and there are currently no clinically effective treatments. <i>Althaea rosea</i> (Linn.) Cavan. flower, documented in the \"National Compendium of Chinese Herbal Medicines\", is traditionally recognized and clinically applied for its potential to mitigate tetrodotoxin (TTX) poisoning. This study aims to explores the pharmacodynamic components and mechanisms of the ethyl acetate extract of <i>Althaea rosea</i> flower (EAEAR) in a TTX-induced rat model.</p><p><strong>Methods: </strong>Ultra-performance liquid chromatography coupled with quadrupole Orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) was used to identify active components in EAEAR. Metabolomics combined with network pharmacology was used to explore the mechanisms underlying the mitigating effects of EAEAR in TTX-intoxicated rats. Experimental validation was performed on key targets of the pathway through Western blotting or enzyme-linked immunosorbent assay. And differential metabolites in key pathways were further validated using ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS).</p><p><strong>Results: </strong>A total of 35 active components were identified in EAEAR, 12 core components and 15 core targets were screened in network pharmacology, and metabolomics revealed 15 different metabolites. The arginine and proline metabolism pathway and the arginine biosynthesis pathway were identified as critical pathways for EAEAR's effect in alleviating TTX poisoning. Validation results indicated that EAEAR treatment led to significant alterations (<i>P</i> <0.05) in six key targets (MAOA, AOC1, ALDH7A1, NAGS, NOS2, and NOS3) and three differential metabolites (GABA, Pro, and NAG) in TTX-intoxicated rats.</p><p><strong>Conclusion: </strong>EAEAR alleviates TTX poisoning symptoms by modulating targets and metabolites in the arginine and proline metabolism pathways and the arginine biosynthesis pathway. This study provides a theoretical basis for further exploration of its therapeutic potential and mechanisms against TTX poisoning.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3657-3680"},"PeriodicalIF":4.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Population Pharmacokinetics Study of Venetoclax Concomitant with Voriconazole in Patients with Hematologic Malignancies.","authors":"Jing Yang, Haoran Wang, Dongmei Liu, Weijie Cao, Han Xing, Peile Wang","doi":"10.2147/DDDT.S514173","DOIUrl":"https://doi.org/10.2147/DDDT.S514173","url":null,"abstract":"<p><strong>Background: </strong>Venetoclax is a selective small-molecule BCL-2 inhibitor that has been approved for treating hematologic malignancies. Co-administration with CYP3A inhibitors, such as voriconazole, poses a high risk of drug-drug interactions (DDIs) that can increase venetoclax exposure. This study aimed to develop a population pharmacokinetics (PopPK) model to characterize the PK properties of venetoclax when co-administered with voriconazole.</p><p><strong>Methods: </strong>Patients (≥18 years of age) treated with venetoclax for hematologic malignancies and concomitant with voriconazole were enrolled. A PopPK model of venetoclax was developed, and Monte Carlo simulations were performed to optimize dosing regimens.</p><p><strong>Results: </strong>A total of 261 samples from 30 patients were collected as the development dataset, and 55 samples from 43 patients as the external validation dataset. Venetoclax concentrations were adequately described by a two-compartment linear model with first-order absorption and elimination and absorption lag-time. Albumin was identified as a significant covariate influencing the clearance, with a typical value of 1.31 ± 0.08 L/h. Simulation indicated that the exposure to venetoclax (75 mg/day and 100 mg/day) concomitant with voriconazole was higher than that to venetoclax (400 mg/day) alone and tended to accumulate over two weeks.</p><p><strong>Conclusion: </strong>Co-administration of voriconazole contributed to elevated venetoclax exposure. These potential DDIs suggest the need for therapeutic drug monitoring of venetoclax.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3681-3690"},"PeriodicalIF":4.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12065538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison Between Low-Dose Esketamine and Dexmedetomidine on Postoperative Recovery Quality Among Patients Undergoing Humeral Trauma Surgery in Interscalene Brachial Plexus Block: A Randomized, Double-Blind, Controlled Trial.","authors":"Jiao Chen, Yu Qi, Jun Zhang, Bin Sun, Meng Zhang, Xiangdi Meng, Meiyan Zhou, Liwei Wang","doi":"10.2147/DDDT.S507427","DOIUrl":"10.2147/DDDT.S507427","url":null,"abstract":"<p><strong>Purpose: </strong>Patients with humeral fracture often suffer from post-traumatic neuropsychiatric sequelae, which can cause immense anxiety or fear and worsen recovery. In this report, we examined the effect of low-dose esketamine versus dexmedetomidine on postsurgical recovery among patients who underwent humerus surgery with interscalene brachial plexus block.</p><p><strong>Patients and methods: </strong>In this prospective, randomized, controlled study, 141 patients aged 18 to 65 years who underwent humerus reduction and internal fixation were recruited. Patients were randomly assigned to two groups: esketamine (Group E: received 0.2 mg/kg (i.v.) esketamine administration, with subsequent continuous 0.15mg/kg/h infusion); dexmedetomidine (Group D: received 10-min 0.8µg/kg dexmedetomidine infusion, with 0.4ug/kg/h maintenance infusion). All infusions were terminated at closure of surgical incisions. Our major endpoint was the Quality of Recovery-40 (QoR-40) score on postoperative day 1 (POD-1). The secondary outcomes were QoR-40 POD-3, the intraoperative modified observer's assessment of alert/Sedation (MOAA/S) scores at 5 min (T1) and 10 min (T2) post i.v. administration, at operation initiation (T3), at 10 min interval (T4), 30 min interval (T5) post operation, and at the end of operation (T6), Numeric Rating Scale (NRS) at POD-1, additional postoperative analgesic usage and hospital stays. In addition, we analyzed safety indices, such as hemodynamic profile, postoperative nausea and vomiting, adverse events (AEs) involving the central nervous system.</p><p><strong>Results: </strong>The QoR-40 scores on POD-1 for Group E were substantially elevated relative to Group D. The T4 and T5 MOAA/S scores of Group D were lower relative to Group E. In comparison to Group E, Group D exhibited reduced T1 and T2 Mean arterial pressure (MAP) and T1-T6 Heart rate (HR). Lastly, we observed no marked alteration in other postsurgical AEs between the two patient cohorts.</p><p><strong>Conclusion: </strong>Continuous low-dose esketamine infusion seems safely and tolerably, it significantly improves the postoperative recovery quality among patients with ASA I or II receiving elective humeral trauma surgery.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3645-3655"},"PeriodicalIF":4.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of High-Dose Methotrexate Blood Concentration in Osteosarcoma Patients Using Machine Learning.","authors":"Jin Zhao, Shuqi Dai, Jiali He, Na Liu, Baowanze Zhang, Su Li","doi":"10.2147/DDDT.S515535","DOIUrl":"https://doi.org/10.2147/DDDT.S515535","url":null,"abstract":"<p><strong>Introduction: </strong>High-dose methotrexate is a typical chemotherapy that is widely used in the treatment of osteosarcoma. However, the unique dose-response relationship of methotrexate makes its treatment window relatively narrow, and its clinical use is in a dilemma: either the drug concentration in the patient's body cannot reach the effective concentration level, or adverse reactions may occur due to drug overdose. For this circumstance, monitoring and predicting the drug concentration in the patient's body is well founded and necessary. While pharmacokinetic models exist, they often oversimplify patient-specific covariates. This study addresses the unmet need for early-exposure prediction through interpretable machine learning, enabling data-driven decisions before toxicity manifestation.</p><p><strong>Methods: </strong>In this article, 68 osteosarcoma patients' information including demography, administration and assay was gathered. We analyzed medical data and selected 10 important features using a random forest, including hydration status, red blood cell distribution width coefficient of variation, platelet distribution width, creatinine, γ-glutamyl transferase, large platelet ratio, serum potassium, lactate dehydrogenase, weight, and prealbumin. Then, cross-validation and SHAP has been conducted to confirm the robust and interpretation of the model.</p><p><strong>Results: </strong>On this basis, 7 machine learning regression models was built to predict the blood concentration of methotrexate. R², MSE, RMSE, MAE are the evaluation metrics. Finally, LightGBM was selected as the best prediction model with a performance of R²=0.87, MSE=0.020, RMSE=0.141, MAE=0.065.</p><p><strong>Discussion: </strong>This machine learning framework addresses a critical gap in high-dose methotrexate therapeutic monitoring by achieving early and personalized blood drug concentration prediction, allowing for personalized dosing of patients based on predicted concentrations. The interpretability of SHAP-derived feature importance enhances clinical utility, offering a paradigm shift from reactive toxicity management to proactive precision dosing in osteosarcoma therapy.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3631-3643"},"PeriodicalIF":4.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyodeoxycholic Acid Ameliorates Metabolic Syndrome Through Pathways of Primary Bile Acid Synthesis and Fatty Acid Degradation: Insights From a Rat Model.","authors":"Meimei Chen, Kaiyue Huang, Wenqian Luo, Fei Zhang, Huijuan Gan, Zhaoyang Yang","doi":"10.2147/DDDT.S514189","DOIUrl":"https://doi.org/10.2147/DDDT.S514189","url":null,"abstract":"<p><strong>Background: </strong>Bile acids (BAs) play a crucial role in metabolic regulation, but their specific functions in metabolic syndrome (MS) remain unclear. Hyodeoxycholic acid (HDCA) has shown potential effects in non-alcoholic fatty liver disease (NAFLD), yet its role in MS is unexplored.</p><p><strong>Aim: </strong>This study aims to assess whether HDCA is a characteristic BA of MS and to investigate its intervention effects and potential mechanisms.</p><p><strong>Methods: </strong>We employed 16S rDNA sequencing and UHPLC-MS/MS to investigate the dynamics of the gut microbiota and BA profiles in rats and conducted a correlation study between indices, identifying HDCA as the potential characteristic BA. We then examined its interventional effects in MS rats comparing efficacy with the positive drug of MS (metformin). Subsequently, liver RNA sequencing (RNA-seq), gene set enrichment analysis (GSEA), and Wes Automated Simple Western assays were employed to investigate mechanisms of HDCA ameliorating MS.</p><p><strong>Results: </strong> HDCA was identified as a characteristic BA for MS, exhibiting a significant positive correlation with beneficial gut bacteria and a negative correlation with harmful bacteria, and highly inversely related to various abnormal MS indexes. HDCA treatment led to significant improvements in metabolic abnormalities in MS rats, with a central role in altering serum BA profiles and profoundly modifying the gut microbiome composition. The results of RNA-seq and GSEA indicated that HDCA influenced the expression of genes related to primary bile acid synthesis and fatty acid degradation (p<0.05). Wes assays validated that FXR, CYP7A1, CYP7B1, PPARα, CPT1, CPT2, FABP1, HMGCS1 and HMGCS2 proteins in MS rats exhibited significant changes after HDCA treatment (<i>p</i><0.05), and this was more effective than metformin treatment.</p><p><strong>Conclusion: </strong>These study is the first to highlight HDCA as a therapeutic candidate for MS and provides new insights into the BA-MS axis, though further validation is needed.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3611-3630"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Median Effective Dose of Ciprofol Combined with Sufentanil for Inhibiting Responses to Gastroscope Insertion in Obese Patients: A Prospective, Single-Center Study.","authors":"Zhouya Xue, Xiang Liu, Weisheng Qian, Nan Yang, Yongyi Pan, Yong Zhou, Wei Jiang, Feng Li, Bin Qian","doi":"10.2147/DDDT.S494972","DOIUrl":"https://doi.org/10.2147/DDDT.S494972","url":null,"abstract":"<p><strong>Background: </strong>Ciprofol, a recently developed intravenous anesthetic, whereas sufentanil is a widely used adjuvant for gastroenteroscopy sedation. The recommended dosage of ciprofol for obese patients remains unclear. Our study aimed to determine the median effective dose (ED₅₀) of ciprofol in combination with sufentanil for obese patients undergoing gastroscopy sedation.</p><p><strong>Methods: </strong>A total of 70 patients undergoing painless gastroscopy from July 2024 to September 2024 were recruited. Patients were assigned to the obese group (body mass index [BMI]≥28 kg/m², n=34) and non-obese group (18.5 kg/m² ≤BMI<24 kg/m², n=36). All patients received 0.1 μg/kg of sufentanil, and the ciprofol dose was determined by the modified Dixon sequential method with an initial dose of 0.4 mg/kg and a dose gradient of 0.01 mg/kg. The dose of ciprofol administered to the subsequent patient was determined by the response of the preceding patient. The response referred to the patient's cough, swallowing, and body movement during gastroscope insertion. The primary outcome was the ED₅₀ of ciprofol in each group, while the secondary outcomes comprised the incidences of hypoxemia, hypotension, bradycardia, postoperative nausea and vomiting (PONV), and hemodynamic parameters.</p><p><strong>Results: </strong>The ED₅₀ of ciprofol was 0.278 mg/kg (95% confidence interval [CI]: 0.226-0.297 mg/kg) in the obese group and 0.347 mg/kg (95% CI: 0.329-0.360 mg/kg) in the non-obese group for gastroscopy sedation. The ED₅₀ of ciprofol in the obese group was significantly lower than that in the non-obese group (<i>P</i><0.05). The incidence of hypoxemia in the obese group was significantly higher than that in the non-obese group (<i>P</i><0.05).</p><p><strong>Conclusion: </strong>Obesity affected the ED₅₀ of ciprofol, suggesting that the ciprofol dosage should be adjusted in obese patients.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3577-3587"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143997110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimized Sampling Strategies for Isoniazid in East Asian Pediatric Populations Using Population Pharmacokinetics-Informed Approaches.","authors":"Gehang Ju, Xin Liu, Yeheng Peng, Wenyu Yang, Nuo Xu, Qingfeng He, Chenchen Zhang, Lulu Chen, Nan Yang, Gufen Zhang, Chao Li, Pan Su, Xiao Zhu, Dongsheng Ouyang","doi":"10.2147/DDDT.S503987","DOIUrl":"10.2147/DDDT.S503987","url":null,"abstract":"<p><strong>Objective: </strong>Isoniazid exposure in vivo is significantly affected by NAT2 genotypes and has ethnic differences. To optimize the sampling strategy for isoniazid in East Asian pediatric populations. We employed a model-informed optimization approach based on INH population pharmacokinetic (PopPK) models.</p><p><strong>Methods: </strong>We selected PopPK models for children and East Asian adults and optimized the sampling strategy using PopED (Population Experimental Design), a method that helps identify the most efficient sampling points for maximizing parameter estimation accuracy. Virtual patients with varying NAT2 phenotypes were created, and real-world pediatric scenarios were evaluated using questionnaire data, sampling windows, and stochastic simulations.</p><p><strong>Results: </strong>From eight analyzed models (four for East Asian adults and four for non-East Asian pediatrics), we simplified two over-parameterized models using lumping without loss of performance. The optimized clinical sampling strategy involved collecting samples at 0.25 [0-0.5], 1.5 [1-2], 6 [3-8], 12 [9-14], and 24 [22-24] hours post-dose. Simulation verification showed that re-estimated major PK parameters had acceptable relative biases and relative standard error (<30%).</p><p><strong>Conclusion: </strong>Traditional adult sampling strategies are inadequate for East Asian pediatric populations. A tailored strategy involving up to five samples can accurately estimate INH PopPK parameters and should be considered for clinical implementation to optimize treatment and reduce patient sampling burden.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3555-3576"},"PeriodicalIF":4.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12051976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Procyanidin Improves Erectile Function in Rats by Inhibiting PDE5A Activity.","authors":"Yudong Su, Jinman Shui, Danshi Qi, Jie Bai, Xiaoxia Xu, Yongchun Huang, Ruilian Li, Qiong Wu, Haiyan Wang, Chengzhu Cao, Zhanhai Su, Shoude Zhang","doi":"10.2147/DDDT.S514209","DOIUrl":"https://doi.org/10.2147/DDDT.S514209","url":null,"abstract":"<p><strong>Purpose: </strong>Erectile dysfunction (ED), a prevalent form of male sexual dysfunction, is predominantly treated with Phosphodiesterase type 5 inhibitors (PDE5Is). Our previous research highlighted procyanidin, a natural compound, as a notably effective PDE5I. In the current study, we intend to further validate the inhibitory activity of procyanidin on PDE5A through in vitro and in vivo assessments. This study aims to validate the efficacy of procyanidin as a treatment for ED.</p><p><strong>Methods: </strong>The binding affinity of procyanidin for PDE5A was assessed by molecular docking, molecular dynamics (MD) simulations, and microscale thermophoresis (MST) assay. The toxicity of procyanidin on penile corpus cavernosum smooth muscle (CCSM) cells (n=5) was evaluated. Additionally, its effects on intracellular cyclic guanosine monophosphate (cGMP) levels in CCSM cells (n=5) were evaluated. The absorption of procyanidin was evaluated by measuring plasma levels at various times after oral gavage to Sprague-Dawley (SD) rats (n=6). Subsequently, the effects of procyanidin on intracavernous pressure (ICP) and cGMP levels in penile cavernous tissue were evaluated in SD rats (n=6).</p><p><strong>Results: </strong>Procyanidin forms three hydrogen bonds with PDE5A and stabilizes the complex structure, exhibiting equilibrium dissociation constants (K_D) value of 7.77 ± 2.39 µmol/L. Additionally, procyanidin exhibits minimal cytotoxicity toward CCSM cells and significantly elevates intracellular cGMP levels compared to the control group. In vivo studies demonstrate that procyanidin is rapidly absorbed, achieving peak blood concentrations within one hour. Simultaneously, procyanidin significantly increases ICP and cGMP levels in rats compared to the control group.</p><p><strong>Conclusion: </strong>These findings indicate that procyanidin sustains elevated cGMP levels within cells by targeting PDE5A, thereby exhibiting therapeutic efficacy in improving ICP. Procyanidin emerges as a promising PDE5I for treating ED and potentially other related conditions.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3351-3361"},"PeriodicalIF":4.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143988194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lean Six Sigma as a Management Tool Helps Standardize Antimicrobial Use in Hospital Settings.","authors":"Qian Wang, Xinru Han, Xiang Zhang, Lubo Guo","doi":"10.2147/DDDT.S510926","DOIUrl":"https://doi.org/10.2147/DDDT.S510926","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to standardize antimicrobial use in a hospital setting by implementing the Lean Six Sigma (LSS)-DMAIC model (Define, Measure, Analyze, Improve, Control), addressing the irrational use of antibacterial drugs.</p><p><strong>Methods: </strong>A retrospective analysis was conducted using data from a single hospital's information system in Shandong, China, covering antibacterial drug usage from January 2020 to December 2021. The LSS-DMAIC framework was applied, which involved defining problems, measuring key indicators, analyzing causes of irrational use, implementing improvement measures, and controlling outcomes. The project team comprised clinical pharmacists and healthcare professionals who evaluated antibiotic use and compliance with guidelines.</p><p><strong>Results: </strong>In the whole hospital, the management through LSS-DMAIC led to a significant reduction in the non-standard utilization rate of antibacterial drugs from 32.5% to 11.3% (P < 0.0001), achieving the set target. The intensity of antibacterial drug use decreased to 38.82 Defined Daily Doses (DDDs), meeting national standards. Additionally, the utilization rate of antibacterial drugs has dropped from 43.61% to 40.16% (P < 0.0001), and the average cost of antibacterial drugs per inpatient significantly dropped from 1909.59 RMB (known as Renminbi, which is the legal currency of China) to 1675.20 RMB (P < 0.0001), resulting in substantial annual savings.</p><p><strong>Conclusion: </strong>The application of the LSS-DMAIC model effectively improved the rational use of antibacterial drugs in the hospital, demonstrating its potential as a valuable management tool in healthcare settings. Continued efforts are necessary to sustain these improvements and further enhance clinician adherence to antimicrobial stewardship practices.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3539-3554"},"PeriodicalIF":4.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bibliometric Analysis of Non-Vitamin K Antagonist Oral Anticoagulants (NOACS) in the Prevention of Venous Thrombosis and Pulmonary Embolism.","authors":"Fangyi Zhou, Zicheng Pang, Zhuoming Chen, Kai Hu, Jian Luo, Sihui Huang, Qiang Qu","doi":"10.2147/DDDT.S505751","DOIUrl":"https://doi.org/10.2147/DDDT.S505751","url":null,"abstract":"<p><strong>Introduction: </strong>Venous thromboembolism (VTE) is a leading cause of cardiovascular-related deaths. Non-vitamin K antagonist oral anticoagulants (NOACs) offer effective therapy without injections or blood monitoring. This bibliometric analysis explores the research on NOACs for preventing VTE and pulmonary embolism.</p><p><strong>Methods: </strong>Literature up to July 20, 2024, was searched in Web of Science Core Collection. Citespace software was used for screening and analysis.</p><p><strong>Results: </strong>In this study, we analyzed 2124 articles and 767 reviews from 11,282 institutions across 528 countries and regions, encompassing 830 publications and 60 research directions. The USA led in publication count, followed by Germany and Canada. Cardiovascular System Cardiology, Hematology, and General Internal Medicine were the top research areas, while THROMBOSIS AND HAEMOSTASIS was the leading journal. From 2004 to 2024, we observed accelerated publication growth, particularly from 2008, highlighting the emergence of NOACs as a major research focus. Key contributors, including Bengt I. Eriksson, and major institutions like Harvard Medical School and University of Amsterdam, played pivotal roles in advancing anticoagulant research. Co-citation and keyword clustering analyses revealed research hotspots in NOACs, cancer-associated venous thromboembolism, stroke prevention, and COVID-19-related thrombotic events, reflecting a shift towards individualized anticoagulation therapy and the growing importance of NOACs in various clinical contexts.</p><p><strong>Conclusion: </strong>The development of NOACs has progressed rapidly, with an increasing number of publications, indicating the lead research in the United States and other Western nations. Comparative studies on the safety and efficacy of NOACs have become a significant focus, shifting from traditional anticoagulants. Pharmacogenetics-guided use of NOACS shows new hope of precision medicine.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"19 ","pages":"3589-3610"},"PeriodicalIF":4.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12050026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}