BACKGROUND AND PURPOSE:There is a paucity of available clinical tools with which to accurately predict the risk of tigecycline-associated hypofibrinogenemia, an adverse reaction with a high incidence and serious consequences. This study aimed to developed an optimal machine-learning model for predicting tigecycline-associated hypofibrinogenemia and to facilitate its clinical application. METHODS:A total of 896 inpatients who received tigecycline treatment in a large tertiary teaching hospital between 2016 and 2022 were included in the model development cohort. Subsequent temporal external validation of the models was performed on 313 patients admitted in 2023. Three robust machine-learning algorithms, including LASSO, Boruta, and VSURF were integrated to identify predictors. These features were then utilized to construct nine machine-learning models. The optimal one was identified through model evaluation and validation and was interpreted based on the SHAP method. RESULTS:The three algorithms identified five predictors, including age, treatment duration, pre-dose fibrinogen level, D-dimer level, and activated partial thromboplastin time. The XGboost model was identified as the most suitable due to its stability and excellent discrimination, calibration, and clinical utility. The area under the receiver operating characteristic curve for the model were 0.823 (0.794-0.853), 0.810 (0.746-0.873), and 0.773 (0.721-0.825) in the training, internal validation, and temporal external validation cohorts, respectively. CONCLUSIONS:Machine-learning models are promising in solving the classification prediction problem of tigecycline-associated hypofibrinogenemia. Model interpretation based on SHAP enables clinicians to visualize individualized risk and tailor prophylactic strategies, potentially improving patient safety and treatment outcomes.

Drug-induced hypofibrinogenemia has received increasing scrutiny; however, the specific drugs involved remain poorly characterized. Hypofibrinogenemia can have significant clinical implications, including increased bleeding risks. This study aimed to utilize the FDA Adverse Event Reporting System (FAERS) to identify and analyze drugs frequently implicated in drug-induced hypofibrinogenemia. A disproportionality analysis was conducted using FAERS data from January 2004 to March 2024. Various statistical tools were used, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio, Medicines and Healthcare Products Regulatory Agency metrics, and Bayesian confidence propagation neural network. The analysis included 17,627,340 cases involving 52,373,206 adverse events, with 1,661 cases identified as hypofibrinogenemia. The top five drugs associated with hypofibrinogenemia by case number were methotrexate (124 cases), tigecycline (119 cases), tocilizumab (100 cases), pegaspargase (83 cases), and alteplase (57 cases). The drugs ranked by signal strength based on ROR included eravacycline (ROR 2173.84, 95

The occurrence of hypofibrinogenemia after tocilizumab treatment has attracted increasing attention, which may cause bleeding and even life-threatening. This study aims to explore the risk factors for tocilizumab-induced hypofibrinogenemia (T-HFIB) and construct a risk prediction model. A total of 221 inpatients that received tocilizumab from 2015 to 2023 were retrospectively collected and divided into T-HFIB group or control group. The risk factors for T-HFIB were obtained by logistic regression equation and used to establish the nomogram. T-HFIB was observed in 121 of 221 patients (54.75

Drug-induced movement disorders (DIMDs) are often underrecognized and challenging to diagnose and manage in clinical practice. Sodium valproate (VPA), a widely prescribed antiepileptic drug, causes DIMDs. Predictive modeling based on electronic medical records and machine learning algorithms offers a promising approach to improve early identification of adverse drug reactions (ADRs) and enhance clinical safety. This study aimed to conduct real-world active surveillance of VPA-associated DIMDs using hospital information system data, to identify independent risk factors, and to develop a clinically applicable prediction model for early warning and intervention. In this retrospective case–control study, data were collected from hospitalized patients prescribed sodium valproate between 2018 and 2022. DIMD cases were identified through automated alerts generated by the ADE Active Surveillance and Assessment System II, and subsequently confirmed using the Naranjo scale for manual causality assessment. A clinical prediction model was developed using LASSO logistic regression and was presented as a nomogram. Model performance was evaluated using area under the receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC). Of the 6692 patients screened, 98 were confirmed to have DIMDs, yielding an incidence rate of 1.46

Background: A number of studies indicated the benefits and safety of Endostar in combination with chemotherapy in cancer, but the exact real-life safety of Endostar is poorly known. This study aimed to assess the safety of Endostar in combination with chemotherapy in patients with cancer in a real-life setting in China. Methods: This was a retrospective study of patients treated with Endostarin combination with chemotherapy in the Chinese PLA General Hospital (Beijing, China) from 1 st January 2006to 31 st December 2017. All data were obtained from the Hospital Information System(HIS). Laboratory abnormalities were evaluated according to Common Terminology Criteria for Adverse Events(CTCAE) 4.0.Bleeding events and wound healing complications after surgery associated with Endostar were evaluated based on case records. Results: A total of 825 patients were included. There were no patients used Endostar alone in real-life settings. Overall, anemia occurred in 74.5% of the assessed patients, thrombocytopenia occurred in 29.0%, abnormal white blood cell count occurred in 54.5%, abnormal liver function occurred in 13.8%, and increased creatinine occurred in 1.2%. No definite bleeding events and wound healing complications after surgery associated with Endostar were found based on case records. Most laboratory AEs were of grade 1-2. Lung cancer, osteosarcoma and doxorubicin-based chemotherapy was associated with an increased risk of grade≥3 abnormal white blood cell count ( P <0.05). The total dose of Endostar was not associated with severe AEs(grade≥3)of thrombocytopenia and abnormal white blood cell count. Conclusion: The occurrence of AEs during treatment with Endostar in combination with chemotherapy differed across different tumor types and chemotherapy regimens. No new unexpected AEs relating to Endostar were observed from this study. The total dose of Endostar was not associated with increased risk of severe AEs (grade≥3)of thrombocytopenia and abnormal white blood cell count when used in combination with chemotherapy in the real-life setting.

BACKGROUND:To investigate the incidence and clinical characteristics of drug-induced movement disorders(DIMDs)in a large group of hospitalized patients. RESEARCH DESIGN AND METHODS:A retrospective study was conducted among hospitalized patients in 2022, utilizing the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II). After the operation and manual selection, DIMDs cases were identified for analysis of incidence, associated drugs, and clinical characteristics. RESULTS:Among 102,914 hospitalized patients, 504 cases were identified as DIMDs, with an incidence of 0.49%. There were more males than females.Most patients were over 65 years old.A total of 158 associated drugs across 15 classes were identified, with the top three classes being antibiotics(12.10%), antiepileptics(8.13%), and calcium channel blockers (7.14%).The top three drugs were sodium valproate(1.67%),meropenem(0.58%)and pregabalin (0.55%).The clinical manifestations were primarily shakiness, tremor and tic. Different manifestations are difficult to distinguish.It's necessary to make a thorough record and consult specialists. CONCLUSION:For the first time, this study found that the incidence of DIMDs in hospitalized patients in general hospitals was 0.49%, occurs occasionally. Clinicians should pay close attention to the manifestations and identification of involuntary movements. Enhanced monitoring is recommended when using valproate, meropenem and pregabalin.

The use of cefoperazone/sulbactam (CPZ/SAM) could commonly cause vitamin K-dependent coagulation disorders and even hemorrhage sometimes. However, there is a lack of prediction tools estimating the risk for this. This study aimed at developing and internally validating a model for predicting CPZ/SAM-associated coagulation disorders in Chinese inpatients. A case-control study was conducted in 11,092 adult inpatients admitted to a Chinese general hospital between 2020 and 2021 and treated with CPZ/SAM. Patients with CPZ/SAM-associated coagulation disorders were identified through the Adverse Drug Events Active Surveillance and Assessment System-II and subsequent manual evaluation. Controls were selected from eligible patients who didn’t develop coagulation disorders after CPZ/SAM therapy, with a 1:1 propensity score matching. The final predictors were obtained by univariable and multivariable logistic regression analyses. Internal validation and calibration for the model were performed using 1000 bootstrap resamplings. 258 patients were identified as CPZ/SAM-associated coagulation disorders in 2184 patients eligible for inclusions and exclusions and the incidence was 11.8

OBJECTIVE:To analyze the clinical characteristics, incidence, and distribution of drug-associated muscle adverse reactions (DAMAR) in real-world inpatients, to provide valuable references for clinical medication use.METHODS:We conducted an automatic retrospective monitoring of inpatients from May 1, 2022, to April 30, 2023, to collect information on adverse drug reactions (ADR) of patients and conducted subsequent analyses.RESULTS:Among 102,430 hospitalizations, 1106 cases of DAMARs were identified, yielding an incidence of 1.08%, including 125 cases of rhabdomyolysis at an incidence of 0.12%. Seventy-five percent of the patients experienced muscle adverse reactions within 5 days after taking medication, with a median elevated creatine kinase (CK) value of 420.4 IU/L. Risk factors of DAMAR include age ≥ 65, male sex, obesity, hypertension, hepatic and renal insufficiency, and anemia. No significant correlation was observed between the duration of surgery and CK elevation, while the surgical procedure itself had an impact. The 114 drugs associated were predominantly nervous system drugs, anti-infectives for systemic use, and cardiovascular system drugs, with levofloxacin, pregabalin, and parecoxib being the most frequently associated drugs.CONCLUSION:Healthcare professionals should be vigilant with patients exhibiting the identified risk factors. Monitoring creatine kinase and related indices when using myotoxic drugs is crucial to preventing serious adverse reactions, ultimately preserving patients' quality of life.

This study aimed to analyze the incidence, clinical characteristics, and risk factors of moxifloxacin-related arrhythmias and electrocardiographic alterations in hospitalized patients using real-world data. Concurrently, a nomogram was established and validated to provide a practical tool for prediction. Retrospective automatic monitoring of inpatients using moxifloxacin was performed in a Chinese hospital from January 1, 2017, to December 31, 2021, to obtain the incidence of drug-induced arrhythmias and electrocardiographic alterations. Propensity score matching was conducted to balance confounders and analyze clinical characteristics. Based on the risk and protective factors identified through logistic regression analysis, a prediction nomogram was developed and internally validated using the Bootstrap method. Arrhythmias and electrocardiographic alterations occurred in 265 of 21,711 cases taking moxifloxacin, with an incidence of 1.2%. Independent risk factors included medication duration (odds ratio [OR] 1.211, 95% confidence interval [CI] 1.156-1.270), concomitant use of meropenem (OR 4.977, 95% CI 2.568-9.644), aspartate aminotransferase >40 U/L (OR 3.728, 95% CI 1.800-7.721), glucose >6.1 mmol/L (OR 2.377, 95% CI 1.531-3.690), and abnormally elevated level of amino-terminal brain natriuretic peptide precursor (OR 2.908, 95% CI 1.640-5.156). Concomitant use of cardioprotective drugs (OR 0.430, 95% CI 0.220-0.841) was a protective factor. The nomogram showed good differentiation and calibration, with enhanced clinical benefit. The incidence of moxifloxacin-related arrhythmias and electrocardiographic alterations is in the range of common. The nomogram proves valuable in predicting the risk in the moxifloxacin-administered population, offering significant clinical applications.

Abstract Background and aim: Long-term use of cefoperazone/sulbactam (CPZ/SAM) may lead to vitamin K-dependent coagulation dysfunction which is significantly associated with increased risks of major bleeding and death. However, there is a lack of prediction models estimating the risk for this adverse drug reaction. This study aimed at developing and internally validating a risk prediction model for coagulation-related adverse reactions in Chinese inpatients treated with CPZ/SAM. Methods: A case-control study was conducted in 11,092 adult inpatients admitted to our hospital from 2020 to 2021. We selected patients reporting coagulation-related adverse reactions through the Adverse Drug Events Active Surveillance and Assessment System-2 developed by our team. The final predictors were obtained by using the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm. The prediction model was visualized as a static nomogram and a web-based dynamic nomogram. Internal validation and calibration were performed using bootstrap enhanced procedure with 1000 resampling. Results: We found 215 coagulation-related adverse reactions (5.1%) in 4212 patients treated with CPZ/SAM. A final population of 208 cases and 624 controls was considered for model development and validation. Malnutrition, renal insufficiency, parenteral nutrition, longer treatment duration and red blood cell count were identified as final predictors. There is a nonlinear relationship between treatment duration and coagulation disorder. The model shows good discrimination and calibration, with the validated area under the receiver operating characteristic curve (AUROC)being 0.739 (0.699-0.779), p for Hosmer-lemeshow more than 0.05 and Brier score being 0.152. The decision curve analysis reveals that the net benefit of the model is higher, compared with the hypothesis that coagulopathy occurs in all patients with medication or no coagulopathy occurs. Conclusions: The nomogram model quantifies the risk for coagulation-related adverse reactions in Chinese inpatients treated with CPZ/SAM, supporting individual assessment and interventions to mitigate the risk.

Objective The purpose of this study was to analyze the occurrence characteristics, clinical manifestations, medication distribution, and incidence of drug-induced arrhythmias in a real-world inpatient population. Methods According to the inclusion and exclusion criteria as well as the ADR evaluation criteria, we retrospectively evaluated hospitalized patients in 2019 using the arrhythmia module of the Adverse Drug Event Active Surveillance and Assessment System-II (ADE-ASAS-II). A detailed analysis was performed on the demographic data, ADR manifestations, and medication distribution of 2097 patients with drug-induced arrhythmias and QT interval prolongation. Results Of the 167,546 hospitalized patients, there were 1809 cases of drug-induced arrhythmias, with an incidence of 1.08%. The ADRs in 45.35% of positive patients occurred within 3 days after medication administration, and 46.73% of the patients were 65 years old or older. The predominant ADRs identified in this study were extrasystole, tachycardia, and QT interval prolongation, of which the incidence was 0.20%. Levofloxacin was the most involved drug, and levofloxacin-associated rates of incidence of arrhythmia and QT interval prolongation were 1.24% and 0.44%, respectively. The risk factors for drug-induced arrhythmias were male sex, advanced age, emaciation, obesity, and underlying illnesses such as cardiovascular diseases, diabetes mellitus, cerebrovascular diseases, and hepatic and renal inadequacy ( P < 0.05). Conclusion The incidence of drug-induced arrhythmias was in the range of common, while QTc interval prolongation was occasional. It is necessary to pay attention to patients with risk factors.

目的 构建信息化军队药物警戒系统,强化药物安全数据的挖掘利用,促进临床安全合理用药.方法 利用数据抽取、触发器及文本分类技术逐步研发相关软件,构建起自发报告、自动监测、信息交互3个平台,并在实践应用中相辅相成、不断完善.结果 由3个平台、6个软件组成的信息化军队药物警戒系统,实现了基于军综网/互联网/局域网三网系多途径、多方式的药品不良反应数据引接、汇聚、反馈与在线查询共享,实现了相关数据来之于军、服务于军的理念;用于开展基于医院信息系统数据的临床用药风险监测评估与预警,高效快捷、精准经济.结论 基于信息化及人工智能技术支持的药物警戒系统,能够为各级药事监管决策快捷提供精准的参考数据,也是实施药物警戒制、强化药品全生命周期管理,开展大样本真实世界药物风险评价研究的高效支撑工具.

Objective To investigate the incidence and risk factors of adverse events related to liver injury induced by triazole antifungal agents in inpatients. Methods Based on the active Surveillance and Intelligent Assessment alert System of Adverse Drug Events in medical institutions（ADE-ASAS）, all eligible inpatients who received triazole antifungal injective preparation from January 2010 to June 2021 were retrospectively studied and divided into voriconazole, fluconazole and itraconazole groups, and the incidence and risk factors of liver injury in each group were analyzed. Results A total of 555 positive cases were included, and the overall incidence of adverse events of liver injury was 5.31%, among which, the incidence of voriconazole, fluconazole and itraconazole were 6.53%, 4.52% and 4.53%, respectively. The risk factors for adverse events of liver injury caused by voriconazole were hematopoietic stem cell transplantation, hypoalbuminemia, high baseline of total bilirubin（TB） and combined use of alkylation agents.the risk factors of fluconazole-induced liver injury adverse events were hematopoietic stem cell transplantation, hypoalbuminemia, high baseline of TB, surgical treatment. The risk factors of liver injury induced by itraconazole included hematopoietic stem cell transplantation and hypoalbuminemia. Conclusion Triazole antifungal drug-related liver injury is a common adverse drug reaction. When triazole antifungal agents are used clinically, the liver function of patients undergoing hematopoietic stem cell transplantation or surgical treatment during hospitalization, as well as patients with hypoalbuminemia, high baseline of TB and combined use of alkylating agents should be closely monitored.

Objective To determine the clinical characteristics and influence factors of thrombocytopenia associated with lobaplatin for injection in hospitalized population, and to provide reference for clinical safe and rational drug use. Methods Based on the adverse drug event active surveillance and assessment system（ADE-ASAS）, inpatients receiving lobaplatin for injection（10mg） in our hospital from January 1st, 2012 to December 31st, 2019 were retrospectively analyzed the occurrence and characteristics of thrombocytopenia. Propensity score matching（PSM） method was used to select the control group to determine the relevant influence factors. Results Among the 4899 inpatients receiving lobaplatin for injection, 360（7.35%） had thrombocytopenia. Logistic regression model analysis showed that the influencing factors of thrombocytopenia associated with lobaplatin for injection mainly included previous lobaplatin administration history（OR: 2.967; 95%CI: 1.676 ～ 5.250）, combined use of pirubicin（OR: 3.634; 95% CI: 1.355 ～ 9.750） and platelet base value（OR: 0.955; 95% CI: 0.947 ～ 0.962）. Conclusion ADE-ASAS can accurately and efficiently collect the real world data of large sample target drug users. Thrombocytopenia associated with lobaplatin for injection is a common adverse drug reaction. Attention should be paid to patients with clinical use of lobaplatin for injection in the past, the combination of antitumor antibiotics, especially anthracycline drugs such as pirubicin, and platelet count monitoring.

目的 基于FDA不良事件报告系统(FAERS)数据库对奥马环素相关不良事件进行信号挖掘与分析,为防范奥马环素的用药风险提供参考.方法 从FAERS数据库提取奥马环素2018年10月1日至2022年12月31日的不良事件报告,利用报告比值比法(ROR)、比例报告比法、英国药品和健康产品管理局综合标准法和贝叶斯可信区间递进神经网络法进行数据挖掘,利用国际医学用语词典术语集进行不良事件系统归类.结果 共获得319份奥马环素为首要怀疑药物的不良事件报告,涉及1049条不良事件.通过4种方法综合分析,筛选获得与奥马环素相关的有效不良反应阳性风险信号24个,主要累及胃肠系统、各类检查、皮肤及皮下组织疾病等,其中阳性风险信号的不良事件按发生频次排名前5位的依次为恶心、呕吐、住院治疗、上腹痛和腹部不适;阳性风险信号按ROR排名前5位的依次为牙齿变色(ROR=263.40)、喷射性呕吐(ROR=75.89)、伤口分泌(ROR=56.23)、粪便松软(ROR=19.98)和AST升高(ROR=13.03).结论 奥马环素引起牙齿变色、肝损伤以及胃肠系统等不良事件风险信号强度较高,用药期间应关注相关不良反应,及时干预,保证用药安全.

目的 对新型抗骨质疏松药物罗莫珠单抗相关不良反应进行分析及风险信号挖掘,为临床用药安全性提供参考依据.方法 借助美国食品药品监督管理局公共数据开放项目,调取2014年1月1日-2022年9月10日美国食品药品监督管理局不良事件报告系统收到的罗莫珠单抗的不良事件报告,应用国际医学用语词典v24.0的首选系统器官分类和首选术语对不良事件进行分类.采用报告比值比法,对报告数排名前50位的不良事件进行不良反应信号挖掘.结果 检索出不良事件报告共11118925份,其中与罗莫珠单抗相关的报告为4375份,报告主要来自日本和美国,患者75.5％为女性,患者年龄主要分布于60～89岁.在报告数排名前50的不良事件中,共检测出32个阳性信号,包括代谢及营养类疾病3个,各类检查2个,各类损伤、中毒及操作并发症1个,各种手术及医疗操作1个,肌肉骨骼及结缔组织疾病9个,泌尿及肾脏系统疾病1个,全身性疾病及给药部位各种反应8个,神经系统疾病2个及心脏器官疾病5个.其中,肾脏损害为说明书未提及的不良反应.结论 临床应关注罗莫珠单抗潜在的不良反应,尤其警惕其相关心血管不良事件、过敏或超敏反应、低钙血症、下颌骨坏死、非典型性股骨骨折及肾脏损害.对于说明书未提及的罗莫珠单抗相关肾脏损害,应给予足够重视及进一步的探究.

Objective Drug-induced thrombocytopenia (DITP) is associated with increased mortality. This study aims to establish a nomogram to predict the occurrence of DITP in hospitalized patients in a multidrug environment. Methods A single-centre retrospective study among hospitalized adult patients was conducted from January 2021 to December 2021 and was based on the Adverse Drug Events Active Surveillance and Assessment System-Ⅱ (ADE-ASAS-Ⅱ). Three controls were matched for each case according to the propensity score matching algorithm to eliminate confounding bias due to individual baseline variables. Predictors of DITP were obtained by LASSO regression and were used to build the nomogram. Results Among 88151 hospitalized patients, 478 were confirmed to have DITP, which is an incidence rate of 0.54%. After matching, 382 pairs and 1146 patients were included in the study, including 1070 cases in the development group and 427 cases in the validation group. Five variables were used to construct the nomogram: hospital stay ≥ 14days, surgery before using suspected drugs, baseline platelet count < 150×10 9 /L, higher baseline BUN and combined with antibacterial. The areas under the curve (AUC) in the development group and validation group were 0.827 (95% CI 0.800-0.854) and 0.785 (95% CI 0.736–0.834), respectively, and the model also showed good calibration (P > 0.05) in the development group and validation group. Conclusion The established nomogram can help identify high-risk patients with DITP, assist doctors in decision-making, and effectively prevent DITP in the early stage.

目的 了解住院人群中氟比洛芬酯相关急性肾损伤的发生率、临床特征和危险因素.方法 依托医疗机构药物不良事件主动监测与智能评估警示系统(ADE-ASAS),回顾性监测解放军总医院2010年12月1日至2020年11月30日所有使用氟比洛芬酯的住院患者,并进行病例对照研究,分析氟比洛芬酯所致急性肾损伤的发生率、临床特征和危险因素.结果 116097例使用氟比洛芬酯的住院患者中,急性肾损伤阳性病例815例,发生率0.70％.因果关联性评价结果以可能最多见,692例(84.91％).阳性病例的严重程度分期以1期为主,449例(55.00％);转归结果主要是好转,556例(68.22％);住院科室以肝胆外科为主,575例(70.55％).合并贫血(OR=2.30;95％CI:1.80～2.94)、较低基线肾小球滤过率(OR=1.01;95％CI:1.01～1.02)、联用利尿剂(OR=3.80;95％CI:3.01～4.81)发生急性肾损伤的风险较高.结论 氟比洛芬酯相关急性肾损伤的发生率为偶见;对合并贫血、较低基线肾小球滤过率以及联用利尿剂的患者,临床应用该药时应注意监测.

OBJECTIVE: To analyze clinical characteristics, incidence, and distribution of drug associated muscle adverse reaction (DAMAR) in real world inpatients, to provide references for clinical medication use. METHODS: Automated retrospective monitored inpatients from 2022-5-1 to 2023-4-30 to obtain information about patients’ adverse reactions and analyze. RESULTS: There were 1106 DAMARs among 102430 hospitalizations, with an incidence of 1.08%, in which 125 cases of rhabdomyolysis with an incidence of 0.12%. 75% of the patients experienced muscle adverse reactions within 5 days after medication, and the median value of elevated CK was 420.4 IU/L. There was no significant correlation between duration of surgery and the elevation of CK, while the surgical procedure had an effect. Age, male sex, obesity, hypertension, hepatic and renal insufficiency, anemia, and other underlying diseases were risk factors. The 114 drugs involved were mainly nervous system drugs, antiinfectives for systemic use and cardiovascular system drugs, with levofloxacin, pregabalin and parecoxib being the drugs with the highest number of cases. CONCLUSION: Attention should be paid to patients with the above risk factors. Monitor creatine kinase and related indexes when using myotoxic drugs, to avoid the occurrence of serious adverse reactions, which may affect the patients’ quality of life.