Yaru Han, Xianxiang Bai, Si Wu, Xiurong Luan, Liwen Ren, Jinhua Wang, Zhanfei She, Bin Xiao, Guanhua Du
What Is Known and Objective. Novel coronavirus disease (COVID-19) is still ravaging globally since its first discovery in 2019. With the continuous emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) mutant strains, therapeutic entities are still needed to be discovered. This study was to explore SARS-CoV-2 inhibitors and therapeutic entities for COVID-19. Methods. Based on Lipinski’s rule of 5, a small-scale “old” drug database (clinical drugs being used in Ordos Central Hospital) was established, and in silico screening of Mpro inhibitors was conducted. Binding affinity and interaction as well as structure-affinity relationship were analyzed. Furthermore, molecular dynamic (MD) simulation of the selected drugs was performed to understand the conformational changes in docked complex. In vitro Mpro inhibition tests were performed according to established methods. Finally, literature review of potential “old” drug for the treatment of COVID-19 was conducted. Results and Discussion. The antibiotic minocycline, an inhibitor of bacterial ribosomal RNA, was screened out which showed the highest binding affinity (−9.6 kcal/mol). Beside the hydrogen bond with Cys145 and hydrophobic interactions, minocycline formed a pi-cation with His41, which strongly supported minocycline as a Michael addition acceptor to bind with the catalytic site of Mpro. MD simulation results show that minocycline displayed less conformational changes. The structure-affinity relationship was summarized based on minocycline analogs, and minocycline showed in vitro Mpro inhibitory activity with IC50 of 5 mM. More importantly, the literature review found that minocycline had both in vitro and in vivo broad-spectrum antiviral as well as anti-inflammatory activities, and the levels of a broad spectrum of biological markers during minocycline administration were opposed to those of COVID-19 conditions (both severe and nonsevere). What is New and Conclusion. Minocycline deserves an adjunctive therapeutic option for COVID-19 condition (both severe and nonsevere). This study shed a new light on drug-repurposing strategy for the viral disease.
{"title":"In Silico Screening, In Vitro Mpro Inhibitory, and Adjunctive Therapy Value of Minocycline for the Treatment of COVID-19","authors":"Yaru Han, Xianxiang Bai, Si Wu, Xiurong Luan, Liwen Ren, Jinhua Wang, Zhanfei She, Bin Xiao, Guanhua Du","doi":"10.1155/2023/9955105","DOIUrl":"https://doi.org/10.1155/2023/9955105","url":null,"abstract":"What Is Known and Objective. Novel coronavirus disease (COVID-19) is still ravaging globally since its first discovery in 2019. With the continuous emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) mutant strains, therapeutic entities are still needed to be discovered. This study was to explore SARS-CoV-2 inhibitors and therapeutic entities for COVID-19. Methods. Based on Lipinski’s rule of 5, a small-scale “old” drug database (clinical drugs being used in Ordos Central Hospital) was established, and in silico screening of Mpro inhibitors was conducted. Binding affinity and interaction as well as structure-affinity relationship were analyzed. Furthermore, molecular dynamic (MD) simulation of the selected drugs was performed to understand the conformational changes in docked complex. In vitro Mpro inhibition tests were performed according to established methods. Finally, literature review of potential “old” drug for the treatment of COVID-19 was conducted. Results and Discussion. The antibiotic minocycline, an inhibitor of bacterial ribosomal RNA, was screened out which showed the highest binding affinity (−9.6 kcal/mol). Beside the hydrogen bond with Cys145 and hydrophobic interactions, minocycline formed a pi-cation with His41, which strongly supported minocycline as a Michael addition acceptor to bind with the catalytic site of Mpro. MD simulation results show that minocycline displayed less conformational changes. The structure-affinity relationship was summarized based on minocycline analogs, and minocycline showed in vitro Mpro inhibitory activity with IC50 of 5 mM. More importantly, the literature review found that minocycline had both in vitro and in vivo broad-spectrum antiviral as well as anti-inflammatory activities, and the levels of a broad spectrum of biological markers during minocycline administration were opposed to those of COVID-19 conditions (both severe and nonsevere). What is New and Conclusion. Minocycline deserves an adjunctive therapeutic option for COVID-19 condition (both severe and nonsevere). This study shed a new light on drug-repurposing strategy for the viral disease.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135092819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. Vonoprazan is a novel selective and noncompetitive oxidative-reduction state proton pump inhibitor (PPI), known as a potassium-competitive acid blocker (P-CAB). Due to its novelty, the clinical application of vonoprazan is relatively limited, and its long-term safety and adverse effects still need to be further studied and confirmed. Methods. We used the data from the FDA adverse eventreporting system (FAERS) from 2015 to 2022. Disproportionality method including calculation of the reporting odds ratio (ROR) and calculation of the information component (IC) was used to detect potential adverse drug reactions (ADRs). In preferred terms, the significant signals are ranked in the following order: Plateletcrit increased (ROR 1447.3 IC 36.62), benign duodenal neoplasm (ROR 11157.84 IC 36.40), gallbladder volvulus (ROR 964.77 IC 36.20), myopathy endocrine (ROR 723.58 IC 35.88), pernio-like erythema (ROR 723.58 IC 35.88), septic coagulopathy (ROR 723.58 IC 35.88), and so on. In SOCs, the significant signals are ranked in the following order: hepatobiliary disorders (ROR 5.65 IC 29.15), metabolism and nutrition disorders (ROR 2.78 IC 28.12), blood and lymphatic system disorders (ROR 2.73 IC 28.12), investigations (ROR 2.19 IC 27.76), endocrine disorders (ROR 2.09 IC27.76), gastrointestinal disorders (ROR 1.87 IC 27.52), and so on. Conclusion. Despite its potential advantages, there is still limited clinical experience with vonoprazan, and the long-term safety and adverse effects of this drug are not fully understood. Further studies are needed to confirm its safety and efficacy in a larger patient population and to establish its role in the management of acid-related disorders. In the meantime, careful monitoring and patient education are recommended for those who are prescribed vonoprazan.
背景。Vonoprazan是一种新型的选择性非竞争性氧化还原态质子泵抑制剂(PPI)，被称为钾竞争性酸阻滞剂(P-CAB)。由于其新颖性，vonoprazan的临床应用相对有限，其长期安全性和不良反应仍需进一步研究和证实。方法。我们使用了2015年至2022年FDA不良事件报告系统(FAERS)的数据。采用计算报告优势比(ROR)和计算信息分量(IC)的歧化法检测潜在药物不良反应(adr)。优先考虑的重要信号依次为:血小板升高(ROR 1447.3 IC 36.62)、十二指肠良性肿瘤(ROR 11157.84 IC 36.40)、胆囊扭转(ROR 964.77 IC 36.20)、肌病内分泌(ROR 723.58 IC 35.88)、肠壁样红斑(ROR 723.58 IC 35.88)、脓毒性凝血病(ROR 723.58 IC 35.88)等。在soc中，重要信号依次为:肝胆疾病(ROR 5.65 IC 29.15)、代谢和营养疾病(ROR 2.78 IC 28.12)、血液和淋巴系统疾病(ROR 2.73 IC 28.12)、调查疾病(ROR 2.19 IC27.76)、内分泌疾病(ROR 2.09 IC27.76)、胃肠道疾病(ROR 1.87 IC 27.52)等。结论。尽管具有潜在的优势，但vonoprazan的临床经验仍然有限，并且该药物的长期安全性和不良反应尚未完全了解。需要进一步的研究来证实其在更大患者群体中的安全性和有效性，并确定其在酸相关疾病管理中的作用。与此同时，建议对服用vonoprazan的患者进行仔细的监测和患者教育。
{"title":"Adverse Reaction Signals Mining of Vonoprazan: A Pharmacovigilance Study Based on FAERS","authors":"Zhenfei Chi, Xuesong Bai, Zhe Zhang","doi":"10.1155/2023/7588085","DOIUrl":"https://doi.org/10.1155/2023/7588085","url":null,"abstract":"Background. Vonoprazan is a novel selective and noncompetitive oxidative-reduction state proton pump inhibitor (PPI), known as a potassium-competitive acid blocker (P-CAB). Due to its novelty, the clinical application of vonoprazan is relatively limited, and its long-term safety and adverse effects still need to be further studied and confirmed. Methods. We used the data from the FDA adverse eventreporting system (FAERS) from 2015 to 2022. Disproportionality method including calculation of the reporting odds ratio (ROR) and calculation of the information component (IC) was used to detect potential adverse drug reactions (ADRs). In preferred terms, the significant signals are ranked in the following order: Plateletcrit increased (ROR 1447.3 IC 36.62), benign duodenal neoplasm (ROR 11157.84 IC 36.40), gallbladder volvulus (ROR 964.77 IC 36.20), myopathy endocrine (ROR 723.58 IC 35.88), pernio-like erythema (ROR 723.58 IC 35.88), septic coagulopathy (ROR 723.58 IC 35.88), and so on. In SOCs, the significant signals are ranked in the following order: hepatobiliary disorders (ROR 5.65 IC 29.15), metabolism and nutrition disorders (ROR 2.78 IC 28.12), blood and lymphatic system disorders (ROR 2.73 IC 28.12), investigations (ROR 2.19 IC 27.76), endocrine disorders (ROR 2.09 IC27.76), gastrointestinal disorders (ROR 1.87 IC 27.52), and so on. Conclusion. Despite its potential advantages, there is still limited clinical experience with vonoprazan, and the long-term safety and adverse effects of this drug are not fully understood. Further studies are needed to confirm its safety and efficacy in a larger patient population and to establish its role in the management of acid-related disorders. In the meantime, careful monitoring and patient education are recommended for those who are prescribed vonoprazan.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"47 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135093329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. There is a narrow therapeutic window for sodium valproate, and the blood concentration is too low to control epilepsy, while it is easy to poison the body if the concentration is too high. It is therefore necessary to monitor drug concentration reasonably in order to control epilepsy. The purpose of this study was to establish a model for predicting concentrations of sodium valproate below 50 μg/mL in children with epilepsy. Methods. The clinical data and biochemical examination results of children with epilepsy treated in the pediatric outpatient department of our hospital from June 2019 to March 2022 were retrospectively collected and divided into a development group and a validation group according to a patient ratio of 8 to 2. Five machine learning algorithms were used to identify the key variable factors, and a risk prediction model for sodium valproate blood concentrations lower than the standard concentration was established. The area under the curve (AUC), calibration curve, GiViTi calibration band, and clinical influence curve were used to evaluate the diagnostic efficacy and clinical application value of the model. Results. A total of 525 children with epilepsy were enrolled. In the development group, the random forest algorithm performed best in predicting that the blood concentration of sodium valproate was lower than the standard concentration, showing the highest AUC (1.00). Six factors were determined as a nomogram to predict the incidence of low concentrations. In the validation group and the development group, the calibration curve, GiViTi calibration band, and clinical influence curve all performed well in the evaluation of the diagnostic efficacy and clinical application value of the model. Conclusions. This finding highlights the importance of examining biochemical indices in patients when data regarding the blood concentration of sodium valproate are lacking.
{"title":"Development and Internal Validation of Machine Learning Algorithms for Determining Sodium Valproate Concentrations below the Standard Level Using a Risk Prediction Model of Children with Epilepsy","authors":"Yinhui Yao, Jingyi Zhao, Ying Wang, Wei Qiu, Yingxue Lin, Yaru Zang","doi":"10.1155/2023/9996553","DOIUrl":"https://doi.org/10.1155/2023/9996553","url":null,"abstract":"Background. There is a narrow therapeutic window for sodium valproate, and the blood concentration is too low to control epilepsy, while it is easy to poison the body if the concentration is too high. It is therefore necessary to monitor drug concentration reasonably in order to control epilepsy. The purpose of this study was to establish a model for predicting concentrations of sodium valproate below 50 μg/mL in children with epilepsy. Methods. The clinical data and biochemical examination results of children with epilepsy treated in the pediatric outpatient department of our hospital from June 2019 to March 2022 were retrospectively collected and divided into a development group and a validation group according to a patient ratio of 8 to 2. Five machine learning algorithms were used to identify the key variable factors, and a risk prediction model for sodium valproate blood concentrations lower than the standard concentration was established. The area under the curve (AUC), calibration curve, GiViTi calibration band, and clinical influence curve were used to evaluate the diagnostic efficacy and clinical application value of the model. Results. A total of 525 children with epilepsy were enrolled. In the development group, the random forest algorithm performed best in predicting that the blood concentration of sodium valproate was lower than the standard concentration, showing the highest AUC (1.00). Six factors were determined as a nomogram to predict the incidence of low concentrations. In the validation group and the development group, the calibration curve, GiViTi calibration band, and clinical influence curve all performed well in the evaluation of the diagnostic efficacy and clinical application value of the model. Conclusions. This finding highlights the importance of examining biochemical indices in patients when data regarding the blood concentration of sodium valproate are lacking.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"243 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136061432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. The kidney is the main excretory organ after diquat absorption. Acute kidney injury (AKI) is a common complication in diquat poisoning patients. Objectives. To identify the value of combined detection of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and neutrophil-lymphocyte ratio (NLR) in the early diagnosis of diquat-induced AKI. Materials and Methods. The retrospective cohort study included 42 diquat poisoning patients. Results. Forty-two patients with diquat poisoning were included, of which 20 had fulminant poisoning (47.6%). At admission (0 h), levels of KIM-1, NGAL, NLR, and acute physiology and chronic health evaluation (APACHE) II scores in the fulminant poisoning group were higher than that of the moderate to severe poisoning group ( < 0.05), and they were all higher than in the control group ( < 0.05), while blood urea nitrogen (BUN) and uric acid (UA) levels did not significantly differ across the three groups ( > 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores of patients in the fulminant poisoning group were higher than those in the moderate to severe poisoning group ( < 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h ( < 0.05). Among 42 patients with diquat poisoning, 28 had AKI (66.7%). At 0 h, the AKI group had higher levels of KIM-1, NGAL, NLR, and APACHE II scores than in the non-AKI (NAKI) group ( < 0.05), while there was no significant difference in BUN and UA levels between the two groups ( > 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores in the AKI group were higher than those in the NAKI group ( < 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h ( < 0.05). KIM-1, NGAL, and NLR are independent risk markers for AKI in diquat poisoning patients. At admission (0 h), the combined application of KIM-1, NGAL, and NLR’s sensitivity, specificity, and area under the curve (AUC) for predicting AKI in diquat poisoning patients was 0.893, 0.859, and 0.903, respectively. Conclusions. KIM-1, NGAL, and NLR can be employed as early diagnostic indicators for the clinical prediction of AKI in diquat poisoning patients. Our findings may help clinicians reduce the occurrence of AKI.
{"title":"Early Diagnostic Value of KIM-1, NGAL, and NLR in Acute Kidney Injury Caused by Diquat Poisoning","authors":"Tiezhen Liu, Qian Liu, Hongna Qi, Wenpin Xu, Xun Gao, Weizhan Wang, Baoyue Zhu","doi":"10.1155/2023/8213247","DOIUrl":"https://doi.org/10.1155/2023/8213247","url":null,"abstract":"Background. The kidney is the main excretory organ after diquat absorption. Acute kidney injury (AKI) is a common complication in diquat poisoning patients. Objectives. To identify the value of combined detection of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and neutrophil-lymphocyte ratio (NLR) in the early diagnosis of diquat-induced AKI. Materials and Methods. The retrospective cohort study included 42 diquat poisoning patients. Results. Forty-two patients with diquat poisoning were included, of which 20 had fulminant poisoning (47.6%). At admission (0 h), levels of KIM-1, NGAL, NLR, and acute physiology and chronic health evaluation (APACHE) II scores in the fulminant poisoning group were higher than that of the moderate to severe poisoning group ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M1\"> <mi>P</mi> </math> < 0.05), and they were all higher than in the control group ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M2\"> <mi>P</mi> </math> < 0.05), while blood urea nitrogen (BUN) and uric acid (UA) levels did not significantly differ across the three groups ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M3\"> <mi>P</mi> </math> > 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores of patients in the fulminant poisoning group were higher than those in the moderate to severe poisoning group ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M4\"> <mi>P</mi> </math> < 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M5\"> <mi>P</mi> </math> < 0.05). Among 42 patients with diquat poisoning, 28 had AKI (66.7%). At 0 h, the AKI group had higher levels of KIM-1, NGAL, NLR, and APACHE II scores than in the non-AKI (NAKI) group ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M6\"> <mi>P</mi> </math> < 0.05), while there was no significant difference in BUN and UA levels between the two groups ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M7\"> <mi>P</mi> </math> > 0.05). At 12 h and 24 h, the levels of KIM-1, NGAL, NLR, UA, BUN, and APACHE II scores in the AKI group were higher than those in the NAKI group ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M8\"> <mi>P</mi> </math> < 0.05), 12 h were higher than 0 h, and 24 h were higher than 12 h ( <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M9\"> <mi>P</mi> </math> < 0.05). KIM-1, NGAL, and NLR are independent risk markers for AKI in diquat poisoning patients. At admission (0 h), the combined application of KIM-1, NGAL, and NLR’s sensitivity, specificity, and area under the curve (AUC) for predicting AKI in diquat poisoning patients was 0.893, 0.859, and 0.903, respectively. Conclusions. KIM-1, NGAL, and NLR can be employed as early diagnostic indicators for the clinical prediction of AKI in diquat poisoning patients. Our findings may help clinicians reduce the occurrence of AKI.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135059357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. Drug use evaluation is an approach that focuses on evaluating and optimizing drug use practices to achieve the best possible patient outcomes. The purpose of this study was to assess the appropriateness of vancomycin usage patterns and their practical application in hospitalized patients. Methods. An institutional-based descriptive retrospective cross-sectional study design was carried out among 265 hospitalized patients from May 1, 2022, to July 30, 2022. The study participants were selected using a simple random sampling method. Result. Among the 265 study participants, 60.4% were male respondents, while 86.8% of vancomycin was administered for treatment; however, 13.2% was administered for prophylaxis. In addition, 41.9% and 27.5% of vancomycin were ordered for treatment of meningitis and pneumonia, respectively. The culture was performed for only 17.4% of patients, and 82.6% of vancomycin was used for empiric therapy. Most (66.8%) of vancomycin was given in the dose range of 800–1000 mg. The finding indicates that 57.36% and 39.25% were due to incorrect doses and durations, respectively. Only 17.4% of patients had sensitivity tests. Conclusions. Vancomycin inappropriateness was common with the indication, dose, frequency, and duration of therapy according to the guidelines. Vancomycin was mostly indicated as empiric therapy, even though the sensitive test was performed in a small amount. Given the widespread use of vancomycin as an empiric drug, its utilization should be monitored closely. Therefore, the usual sensitive test is recommended to identify those intermediate and resistant results and to predict the outcomes of the treatment.
{"title":"Evaluation of Vancomycin Utilization in the Medical and Gynecology Wards of Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia","authors":"Baye Yrga Adugna, Zewdu Yilma Dlie, Biset Asrade Mekonnen, Abebe Tarekegn Kassaw","doi":"10.1155/2023/2335694","DOIUrl":"https://doi.org/10.1155/2023/2335694","url":null,"abstract":"Background. Drug use evaluation is an approach that focuses on evaluating and optimizing drug use practices to achieve the best possible patient outcomes. The purpose of this study was to assess the appropriateness of vancomycin usage patterns and their practical application in hospitalized patients. Methods. An institutional-based descriptive retrospective cross-sectional study design was carried out among 265 hospitalized patients from May 1, 2022, to July 30, 2022. The study participants were selected using a simple random sampling method. Result. Among the 265 study participants, 60.4% were male respondents, while 86.8% of vancomycin was administered for treatment; however, 13.2% was administered for prophylaxis. In addition, 41.9% and 27.5% of vancomycin were ordered for treatment of meningitis and pneumonia, respectively. The culture was performed for only 17.4% of patients, and 82.6% of vancomycin was used for empiric therapy. Most (66.8%) of vancomycin was given in the dose range of 800–1000 mg. The finding indicates that 57.36% and 39.25% were due to incorrect doses and durations, respectively. Only 17.4% of patients had sensitivity tests. Conclusions. Vancomycin inappropriateness was common with the indication, dose, frequency, and duration of therapy according to the guidelines. Vancomycin was mostly indicated as empiric therapy, even though the sensitive test was performed in a small amount. Given the widespread use of vancomycin as an empiric drug, its utilization should be monitored closely. Therefore, the usual sensitive test is recommended to identify those intermediate and resistant results and to predict the outcomes of the treatment.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"202 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135060518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pengfei Yin, Xian Zhao, Chaoliang Zhang, Yi Shi, Weiwei Sheng, Binwei Hu, Hui Li, Mi Wang, Xianhui Kang
Background. Remimazolam, a benzodiazepine sedative with clinical advantages, is used for anesthesia during GI endoscopy. However, the accurate clinical dosage remains understudied. This study aims to investigate the 90% effective dose (ED90) of remimazolam in inhibiting responses to upper GI endoscopy insertion and evaluate its efficacy and safety for upper GI endoscopic diagnosis and treatment. Methods. A total of 54 adult patients undergoing upper GI endoscopy under procedural sedation were included, and they were anesthetized with an intravenous bolus of remimazolam. The first patient was given a dose of 0.3 mg/kg of remimazolam and was next randomized according to a biased coin design (BCD) method, and each patient received a dose of remimazolam depending on the response of the previous patient. A positive reaction was defined as no choking cough, nausea and vomiting, and/or motor response during placement of the upper GI endoscope into pharyngeal cavity or within 3 minutes after placement; otherwise, it was a negative reaction. If positive, randomize the next patient’s dose of remimazolam to be unchanged or decrease by 0.05 mg/kg. If negative, increase the next patient’s dose of remimazolam by 0.05 mg/kg. According to the study protocol, at least 45 patients with positive reactions were needed to suspend the trial while monitoring anesthesia-related adverse events. Results. The ED90 of remimazolam for upper gastrointestinal endoscopy insertion was 0.556 mg/kg (95% CI: 0.399–0.578). All patients maintained stable circulation and no serious adverse events were observed during sedation. Patient satisfaction was 4.89 ± 0.69 points, anesthesiologist satisfaction was 4.57 ± 0.96 points, and endoscopist satisfaction was 4.67 ± 0.87 points (full score 5 points, minimum 1 point). Conclusion. The use of remimazolam for upper gastrointestinal endoscopy was safe and effective, with a single intravenous bolus at an ED90 dose of 0.556 mg/kg inhibiting responses to the procedure.
{"title":"Determining the 90% Effective Dose of Remimazolam Inhibiting Responses to Upper Gastrointestinal Endoscopy Insertion in Adults: A Double-Blind Study Utilizing a Biased Coin Up-and-Down Sequential Method","authors":"Pengfei Yin, Xian Zhao, Chaoliang Zhang, Yi Shi, Weiwei Sheng, Binwei Hu, Hui Li, Mi Wang, Xianhui Kang","doi":"10.1155/2023/9391407","DOIUrl":"https://doi.org/10.1155/2023/9391407","url":null,"abstract":"Background. Remimazolam, a benzodiazepine sedative with clinical advantages, is used for anesthesia during GI endoscopy. However, the accurate clinical dosage remains understudied. This study aims to investigate the 90% effective dose (ED90) of remimazolam in inhibiting responses to upper GI endoscopy insertion and evaluate its efficacy and safety for upper GI endoscopic diagnosis and treatment. Methods. A total of 54 adult patients undergoing upper GI endoscopy under procedural sedation were included, and they were anesthetized with an intravenous bolus of remimazolam. The first patient was given a dose of 0.3 mg/kg of remimazolam and was next randomized according to a biased coin design (BCD) method, and each patient received a dose of remimazolam depending on the response of the previous patient. A positive reaction was defined as no choking cough, nausea and vomiting, and/or motor response during placement of the upper GI endoscope into pharyngeal cavity or within 3 minutes after placement; otherwise, it was a negative reaction. If positive, randomize the next patient’s dose of remimazolam to be unchanged or decrease by 0.05 mg/kg. If negative, increase the next patient’s dose of remimazolam by 0.05 mg/kg. According to the study protocol, at least 45 patients with positive reactions were needed to suspend the trial while monitoring anesthesia-related adverse events. Results. The ED90 of remimazolam for upper gastrointestinal endoscopy insertion was 0.556 mg/kg (95% CI: 0.399–0.578). All patients maintained stable circulation and no serious adverse events were observed during sedation. Patient satisfaction was 4.89 ± 0.69 points, anesthesiologist satisfaction was 4.57 ± 0.96 points, and endoscopist satisfaction was 4.67 ± 0.87 points (full score 5 points, minimum 1 point). Conclusion. The use of remimazolam for upper gastrointestinal endoscopy was safe and effective, with a single intravenous bolus at an ED90 dose of 0.556 mg/kg inhibiting responses to the procedure.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"2018 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135059964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiaqin Cai, Wenhua Wu, Zhuang Jie, Guifeng Zhang, Xiaoxia Wei, Hong Sun
What Is Known? and Objective. Immune checkpoint inhibitors (ICIs) play an important role in various cancers. The efficacy and safety of rechallenge with ICIs after immune-related adverse events (irAEs) were not well known. Accumulating studies report inconsistent findings. Thus, we conducted an updated meta-analysis by including more studies. Methods. We searched PubMed, Web of Science, Embase, and Cochrane Library for studies reporting the rechallenge of ICIs after irAEs. The evaluation outcomes included the incidence of irAEs, objective response rate (ORR), and disease control rate (DCR). Results and Discussion. A total of 896 ICI rechallenge cases from 24 studies were included. Compared to the initial treatment with ICIs, rechallenge showed a higher incidence of all-grade irAEs (OR, 2.78; 95% CI, 1.51–5.10; p = 0.001 ) and high-grade irAEs (OR, 1.88; 95% CI, 1.27–2.78; p = 0.002 ), but ORR (OR, 1.01; 95% CI, 0.55–1.84; p = 0.97 ) and DCR (OR, 1.21; 95% CI, 0.68–2.15; p = 0.52 ) were not further improved after the rechallenge of ICIs. What Is New? and Conclusion. More studies are included in this paper to compare and analyze the efficacy and safety of ICIs after rechallenge, so as to update the previous meta-analyses, and finally get different conclusions from the previous meta-analyses in terms of safety. Our results suggest that rechallenged ICIs after irAEs showed similar efficacy and lower safety than initial ICIs. However, these results need to be further verified by high-quality studies with large samples. In addition, we added subgroup analysis not available in previous meta-analyses to explore the association of cancer type, age, and gender factors with the incidence of irAE after ICI rechallenge.
什么是已知的？和目标。免疫检查点抑制剂（ICIs）在各种癌症中发挥着重要作用。免疫相关不良事件（irAE）后用ICIs再激发的疗效和安全性尚不清楚。越来越多的研究报告了不一致的发现。因此，我们通过纳入更多研究进行了最新的荟萃分析。方法。我们在PubMed、Web of Science、Embase和Cochrane Library上搜索了报告irAE后ICIs再挑战的研究。评估结果包括irAE的发生率、客观反应率（ORR）和疾病控制率（DCR）。结果和讨论。共纳入24项研究中的896例ICI再激发病例。与ICIs的初始治疗相比，再次激发显示所有级别的irAE（OR，2.78；95%CI，1.51–5.10；p=0.001）和高级别irAE（OR1.88；95%CI1.27–2.78；p=0.002）的发生率更高，但再次激发ICIs后，ORR（OR，1.01；95%CI 0.55–1.84；p=0.097）和DCR（OR1.21；95%CI0.68–2.15；p=0.052）没有进一步改善。新增内容？和结论。本文纳入了更多的研究，对ICIs再激发后的疗效和安全性进行比较和分析，以更新以往的荟萃分析，最终在安全性方面得出与以往荟萃分析不同的结论。我们的结果表明，irAE后再次激发的ICIs显示出与初始ICIs相似的疗效和更低的安全性。然而，这些结果需要通过大样本的高质量研究来进一步验证。此外，我们添加了以前的荟萃分析中不可用的亚组分析，以探索癌症类型、年龄和性别因素与ICI再激发后irAE发生率的关系。
{"title":"Occurrence of irAEs after Immune Checkpoint Inhibitor Rechallenge: An Updated Meta-Analysis","authors":"Jiaqin Cai, Wenhua Wu, Zhuang Jie, Guifeng Zhang, Xiaoxia Wei, Hong Sun","doi":"10.1155/2023/9963927","DOIUrl":"https://doi.org/10.1155/2023/9963927","url":null,"abstract":"What Is Known? and Objective. Immune checkpoint inhibitors (ICIs) play an important role in various cancers. The efficacy and safety of rechallenge with ICIs after immune-related adverse events (irAEs) were not well known. Accumulating studies report inconsistent findings. Thus, we conducted an updated meta-analysis by including more studies. Methods. We searched PubMed, Web of Science, Embase, and Cochrane Library for studies reporting the rechallenge of ICIs after irAEs. The evaluation outcomes included the incidence of irAEs, objective response rate (ORR), and disease control rate (DCR). Results and Discussion. A total of 896 ICI rechallenge cases from 24 studies were included. Compared to the initial treatment with ICIs, rechallenge showed a higher incidence of all-grade irAEs (OR, 2.78; 95% CI, 1.51–5.10; \u0000 \u0000 p\u0000 =\u0000 0.001\u0000 \u0000 ) and high-grade irAEs (OR, 1.88; 95% CI, 1.27–2.78; \u0000 \u0000 p\u0000 =\u0000 0.002\u0000 \u0000 ), but ORR (OR, 1.01; 95% CI, 0.55–1.84; \u0000 \u0000 p\u0000 =\u0000 0.97\u0000 \u0000 ) and DCR (OR, 1.21; 95% CI, 0.68–2.15; \u0000 \u0000 p\u0000 =\u0000 0.52\u0000 \u0000 ) were not further improved after the rechallenge of ICIs. What Is New? and Conclusion. More studies are included in this paper to compare and analyze the efficacy and safety of ICIs after rechallenge, so as to update the previous meta-analyses, and finally get different conclusions from the previous meta-analyses in terms of safety. Our results suggest that rechallenged ICIs after irAEs showed similar efficacy and lower safety than initial ICIs. However, these results need to be further verified by high-quality studies with large samples. In addition, we added subgroup analysis not available in previous meta-analyses to explore the association of cancer type, age, and gender factors with the incidence of irAE after ICI rechallenge.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49061321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background and Aim. Daphnetin, an active monomer ingredient extracted from D. marginata, is proved to have anti-inflammatory and antioxidant effect. The aim of this study is to explore the effect and possible mechanism of daphnetin on acute lung injury (ALI) associated with acute pancreatitis (AP) in mice. Methods. A total of 36 mice were randomly assigned into three groups: control group, AP group, and daphnetin group. The mouse model of AP was induced by caerulein and lipopolysaccharide. Animals were sacrificed at 6 and 12 h after daphnetin treatment, respectively. The pathological changes of lung and pancreas were determined by hematoxylin-eosin staining and the pathological scores. Levels of IL-1β, IL-6, and TNF-α in serum and lung and the activity of myeloperoxidase (MPO) in lung tissue homogenate were detected by ELISA. The protein level of toll-like receptor 4 (TLR4), phospho-nuclear factor-kappa B p65 (p-NF-κB p65), nuclear factor-kappa B p65 (NF-κB p65), and hypoxia-inducible factor 1 alpha (HIF-1α) in the lung was detected by Western blot. Results. Results showed extensive neutrophil infiltration, hemorrhage, and edema in the pancreas tissues or lung tissues in mice with AP. The daphnetin treatment improved pathological changes in the lung tissues of AP mice. The MPO activity and the levels of inflammatory cytokines including IL-1β, TNF-α, and IL-6 of lung tissues and serum in the AP group were significantly higher than those in the control group ( P < 0.05), and daphnetin intervention significantly reversed the changes ( P < 0.05). Compared with the control mice, the protein levels of TLR4, p-NF-κB p65, and HIF-1α were significantly higher in the lung tissue of the AP mice ( P < 0.05), while daphnetin treatment decreased these protein expression levels. No significant difference was observed in the NF-κB p65 level among control, AP, and daphnetin groups ( P > 0.05). Conclusions. Daphnetin exerted a protective effect on the acute lung injury induced by SAP in mice. The mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α pathway to reduce the release of inflammatory factors.
{"title":"Effects of Daphnetin on Experimental Acute Pancreatitis-Associated Acute Lung Injury in Mice","authors":"Tao Chen, Ou Chen, Ming Zhao, Xia Chen","doi":"10.1155/2023/9822900","DOIUrl":"https://doi.org/10.1155/2023/9822900","url":null,"abstract":"Background and Aim. Daphnetin, an active monomer ingredient extracted from D. marginata, is proved to have anti-inflammatory and antioxidant effect. The aim of this study is to explore the effect and possible mechanism of daphnetin on acute lung injury (ALI) associated with acute pancreatitis (AP) in mice. Methods. A total of 36 mice were randomly assigned into three groups: control group, AP group, and daphnetin group. The mouse model of AP was induced by caerulein and lipopolysaccharide. Animals were sacrificed at 6 and 12 h after daphnetin treatment, respectively. The pathological changes of lung and pancreas were determined by hematoxylin-eosin staining and the pathological scores. Levels of IL-1β, IL-6, and TNF-α in serum and lung and the activity of myeloperoxidase (MPO) in lung tissue homogenate were detected by ELISA. The protein level of toll-like receptor 4 (TLR4), phospho-nuclear factor-kappa B p65 (p-NF-κB p65), nuclear factor-kappa B p65 (NF-κB p65), and hypoxia-inducible factor 1 alpha (HIF-1α) in the lung was detected by Western blot. Results. Results showed extensive neutrophil infiltration, hemorrhage, and edema in the pancreas tissues or lung tissues in mice with AP. The daphnetin treatment improved pathological changes in the lung tissues of AP mice. The MPO activity and the levels of inflammatory cytokines including IL-1β, TNF-α, and IL-6 of lung tissues and serum in the AP group were significantly higher than those in the control group (\u0000 \u0000 P\u0000 \u0000 < 0.05), and daphnetin intervention significantly reversed the changes (\u0000 \u0000 P\u0000 \u0000 < 0.05). Compared with the control mice, the protein levels of TLR4, p-NF-κB p65, and HIF-1α were significantly higher in the lung tissue of the AP mice (\u0000 \u0000 P\u0000 \u0000 < 0.05), while daphnetin treatment decreased these protein expression levels. No significant difference was observed in the NF-κB p65 level among control, AP, and daphnetin groups (\u0000 \u0000 P\u0000 \u0000 > 0.05). Conclusions. Daphnetin exerted a protective effect on the acute lung injury induced by SAP in mice. The mechanism may be related to the regulation of TLR4/NF-κB/HIF-1α pathway to reduce the release of inflammatory factors.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46979969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nabil Debzi, Saadi Berkane, Chafika Manouni, Nassima Amani, Sonia Hemmam, Mohamed Yousfi, Ayoub Taleb, N. Guessab, Ahlem Sarah Moulay Brahim, Sarah Helal, Ismahane Benbitour, Lynda Noual, Rafik Kerbouche, Ibtissem Ouled Cheikh, Othmane Drir, Hibat Allah Belimi, Samir Gourari, Issam Frigga, A. KASSAH-LAOUAR, Mouna Khaberi, Nawal Afredj
Background. Published data regarding the real-life application of the combination sofosbuvir/daclatasvir in Algeria are lacking. Therefore, we conducted an observational study to assess the efficacy and safety of this regimen in Algerian patients with chronic hepatitis C. Methods. We carried out a multicentric, observational, open-label study to assess the efficacy and safety of the generic fixed-dose combination (FDC) sofosbuvir/daclatasvir in patients with chronic hepatitis C. We included 100 patients with all genotypes for 12 or 24 weeks of treatment without ribavirin. The primary outcome was the proportion of patients with a sustained virologic response (SVR) 12 weeks after treatment cessation. The secondary outcome assessed the safety and occurrence of adverse events. This study is registered with ClinicalTrials.gov identifier: NCT05138523. Results. The full analysis set included 99 patients with a mean age of 51.4 ± 14.4 years and a sex ratio of M/F = 0.86. Our patients were infected with HCV genotype 1b (n = 47), 2 (n = 17), 1a (n = 3), 2a/2c (n = 2), 3 (n = 2), and 4 (n = 1). A total of 27 patients had missing genotype data. Most patients were naive noncirrhotic (n = 70) and took 12 weeks of treatment, 19 patients had cirrhosis, of which 68.42% (n = 13) were classified as Child–Pugh A, and 5 patients were treatment-experienced. Both cirrhotic and treatment-experienced patients took 24 weeks of treatment. Efficacy analysis was conducted on 95 patients, and the results showed that 91 patients achieved SVR12 with a response rate of 95.8% (95% CI: 92–100%). Six adverse events occurred and were minor and manageable. Conclusion. Our results demonstrate the efficacy and safety of sofosbuvir/daclatasvir in single tablets in treating Algerian HCV patients without ribavirin for 12 or 24 weeks. The promising results of this study warrant further trials to assess the efficacy and safety of this combination in treating special populations.
{"title":"Efficacy of Sofosbuvir/Daclatasvir in a Single Tablet for Treating Chronic Viral Hepatitis C","authors":"Nabil Debzi, Saadi Berkane, Chafika Manouni, Nassima Amani, Sonia Hemmam, Mohamed Yousfi, Ayoub Taleb, N. Guessab, Ahlem Sarah Moulay Brahim, Sarah Helal, Ismahane Benbitour, Lynda Noual, Rafik Kerbouche, Ibtissem Ouled Cheikh, Othmane Drir, Hibat Allah Belimi, Samir Gourari, Issam Frigga, A. KASSAH-LAOUAR, Mouna Khaberi, Nawal Afredj","doi":"10.1155/2023/8297332","DOIUrl":"https://doi.org/10.1155/2023/8297332","url":null,"abstract":"Background. Published data regarding the real-life application of the combination sofosbuvir/daclatasvir in Algeria are lacking. Therefore, we conducted an observational study to assess the efficacy and safety of this regimen in Algerian patients with chronic hepatitis C. Methods. We carried out a multicentric, observational, open-label study to assess the efficacy and safety of the generic fixed-dose combination (FDC) sofosbuvir/daclatasvir in patients with chronic hepatitis C. We included 100 patients with all genotypes for 12 or 24 weeks of treatment without ribavirin. The primary outcome was the proportion of patients with a sustained virologic response (SVR) 12 weeks after treatment cessation. The secondary outcome assessed the safety and occurrence of adverse events. This study is registered with ClinicalTrials.gov identifier: NCT05138523. Results. The full analysis set included 99 patients with a mean age of 51.4 ± 14.4 years and a sex ratio of M/F = 0.86. Our patients were infected with HCV genotype 1b (n = 47), 2 (n = 17), 1a (n = 3), 2a/2c (n = 2), 3 (n = 2), and 4 (n = 1). A total of 27 patients had missing genotype data. Most patients were naive noncirrhotic (n = 70) and took 12 weeks of treatment, 19 patients had cirrhosis, of which 68.42% (n = 13) were classified as Child–Pugh A, and 5 patients were treatment-experienced. Both cirrhotic and treatment-experienced patients took 24 weeks of treatment. Efficacy analysis was conducted on 95 patients, and the results showed that 91 patients achieved SVR12 with a response rate of 95.8% (95% CI: 92–100%). Six adverse events occurred and were minor and manageable. Conclusion. Our results demonstrate the efficacy and safety of sofosbuvir/daclatasvir in single tablets in treating Algerian HCV patients without ribavirin for 12 or 24 weeks. The promising results of this study warrant further trials to assess the efficacy and safety of this combination in treating special populations.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42426849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective. Tyrosine kinase inhibitors are exciting new anticancer strategies. As one of the most promising oral tyrosine kinase inhibitors, cediranib has been proven effective in treating various solid malignant tumors. This study aimed to evaluate the efficacy and safety of cediranib in cancer patients. Methods. A comprehensive literature review was conducted for phase II and phase III randomized controlled trials (RCTs) up to June 31, 2021, using databases from PubMed, Cochrane Library, Embase, and Web of Science. Relevant clinical trials reporting the efficacy and toxicity characteristics of cediranib in cancer patients were analyzed using Stata 15.1. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to assess the strength of the evidence. Results. The systematic review yielded 14 eligible trials, comprising 4,387 patients with solid malignant tumors. The analysis results of RCTs showed that the cediranib-containing group had a significantly better PFS than the control group (HR: 0.75; 95% CI 0.69–0.82; < 0.001), and the pooled OS of the cediranib-containing group was significantly higher than that of the control group (HR: 0.91; 95% CI 0.84–1.00; = 0.041). The sensitivity analysis revealed that the pooled HR was stable and excluding a single study had no effect on the significance of the pooled HR. In addition, the meta-analysis passed Begg’s and Egger’s tests, indicating no publication bias. Regarding safety, the most common adverse events were diarrhea, nausea, hypertension, fatigue, sensory neuropathy, dyspnea, vomiting, headache, neutropenia, thrombocytopenia, and leukopenia. Conclusion. Cediranib treatment responds better than noncediranib therapy but can increase the risk of specific treatment-related toxicities.
目标。酪氨酸激酶抑制剂是令人兴奋的新的抗癌策略。西地尼布作为一种极具发展前景的口服酪氨酸激酶抑制剂，已被证明对多种实体恶性肿瘤的治疗有效。本研究旨在评价西地尼布对癌症患者的疗效和安全性。方法。使用PubMed、Cochrane Library、Embase和Web of Science数据库，对截至2021年6月31日的II期和III期随机对照试验(rct)进行了全面的文献综述。使用Stata 15.1分析报道cediranib在癌症患者中的疗效和毒性特征的相关临床试验。GRADE(建议、评估、发展和评价分级)系统用于评估证据的强度。结果。系统评价获得14项符合条件的试验，包括4387例实体恶性肿瘤患者。rct分析结果显示，含西地尼组PFS显著优于对照组(HR: 0.75;95% ci 0.69-0.82;P & lt;0.001)，且cediranib组的总OS显著高于对照组(HR: 0.91;95% ci 0.84-1.00;P = 0.041)。敏感性分析显示，合并的HR是稳定的，排除单个研究对合并HR的显著性没有影响。此外，meta分析通过了Begg和Egger的检验，表明没有发表偏倚。关于安全性，最常见的不良事件是腹泻、恶心、高血压、疲劳、感觉神经病变、呼吸困难、呕吐、头痛、中性粒细胞减少、血小板减少和白细胞减少。结论。西地尼治疗比非西地尼治疗效果更好，但可能增加特定治疗相关毒性的风险。
{"title":"A Systematic Review and Meta-Analysis: Safety and Efficacy of Cediranib in the Treatment of Cancer Patients","authors":"Yan Wang, Yan Cai, Qi-Ming Wang","doi":"10.1155/2023/9245663","DOIUrl":"https://doi.org/10.1155/2023/9245663","url":null,"abstract":"Objective. Tyrosine kinase inhibitors are exciting new anticancer strategies. As one of the most promising oral tyrosine kinase inhibitors, cediranib has been proven effective in treating various solid malignant tumors. This study aimed to evaluate the efficacy and safety of cediranib in cancer patients. Methods. A comprehensive literature review was conducted for phase II and phase III randomized controlled trials (RCTs) up to June 31, 2021, using databases from PubMed, Cochrane Library, Embase, and Web of Science. Relevant clinical trials reporting the efficacy and toxicity characteristics of cediranib in cancer patients were analyzed using Stata 15.1. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to assess the strength of the evidence. Results. The systematic review yielded 14 eligible trials, comprising 4,387 patients with solid malignant tumors. The analysis results of RCTs showed that the cediranib-containing group had a significantly better PFS than the control group (HR: 0.75; 95% CI 0.69–0.82; <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M1\"> <mi>P</mi> </math> < 0.001), and the pooled OS of the cediranib-containing group was significantly higher than that of the control group (HR: 0.91; 95% CI 0.84–1.00; <math xmlns=\"http://www.w3.org/1998/Math/MathML\" id=\"M2\"> <mi>P</mi> </math> = 0.041). The sensitivity analysis revealed that the pooled HR was stable and excluding a single study had no effect on the significance of the pooled HR. In addition, the meta-analysis passed Begg’s and Egger’s tests, indicating no publication bias. Regarding safety, the most common adverse events were diarrhea, nausea, hypertension, fatigue, sensory neuropathy, dyspnea, vomiting, headache, neutropenia, thrombocytopenia, and leukopenia. Conclusion. Cediranib treatment responds better than noncediranib therapy but can increase the risk of specific treatment-related toxicities.","PeriodicalId":15381,"journal":{"name":"Journal of Clinical Pharmacy and Therapeutics","volume":"25 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135671095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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