Prediabetes: An overlooked risk factor for major adverse cardiac and cerebrovascular events in atrial fibrillation patients

BACKGROUND Prediabetes is a well-established risk factor for major adverse cardiac and cerebrovascular events(MACCE).However,the relationship between prediabetes and MACCE in atrial fibrillation(AF)patients has not been extensively studied.Therefore,this study aimed to establish a link between prediabetes and MACCE in AF patients.AIM To investigate a link between prediabetes and MACCE in AF patients.METHODS We used the National Inpatient Sample(2019)and relevant ICD-10 CM codes to identify hospitalizations with AF and categorized them into groups with and without prediabetes,excluding diabetics.The primary outcome was MACCE(all-cause inpatient mortality,cardiac arrest including ventricular fibrillation,and stroke)in AF-related hospitalizations.RESULTS Of the 2965875 AF-related hospitalizations for MACCE,47505(1.6%)were among patients with prediabetes.The prediabetes cohort was relatively younger(median 75 vs 78 years),and often consisted of males(56.3%vs 51.4%),blacks(9.8%vs 7.9%),Hispanics(7.3%vs 4.3%),and Asians(4.7%vs 1.6%)than the non-prediabetic cohort(P<0.001).The prediabetes group had significantly higher rates of hypertension,hyperlipidemia,smoking,obesity,drug abuse,prior myocardial infarction,peripheral vascular disease,and hyperthyroidism(all P<0.05).The prediabetes cohort was often discharged routinely(51.1%vs 41.1%),but more frequently required home health care(23.6%vs 21.0%)and had higher costs.After adjusting for baseline characteristics or comorbidities,the prediabetes cohort with AF admissions showed a higher rate and significantly higher odds of MACCE compared to the non-prediabetic cohort[18.6%vs 14.7%,odds ratio(OR)1.34,95%confidence interval 1.26-1.42,P<0.001].On subgroup analyses,males had a stronger association(aOR 1.43)compared to females(aOR 1.22),whereas on the race-wise comparison,Hispanics(aOR 1.43)and Asians(aOR 1.36)had a stronger association with MACCE with prediabetes vs whites(aOR 1.33)and blacks(aOR 1.21).CONCLUSION This population-based study found a significant association between prediabetes and MACCE in AF patients.Therefore,there is a need for further research to actively screen and manage prediabetes in AF to prevent MACCE.

Impact of body mass index on adverse kidney events in diabetes mellitus patients: A systematic-review and meta-analysis

BACKGROUND The incidence of chronic kidney disease among patients with diabetes mellitus(DM)remains a global concern.Long-term obesity is known to possibly influence the development of type 2 diabetes mellitus.However,no previous meta-analysis has assessed the effects of body mass index(BMI)on adverse kidney events in patients with DM.AIM To determine the impact of BMI on adverse kidney events in patients with DM.METHODS A systematic literature search was performed on the PubMed,ISI Web of Science,Scopus,Ovid,Google Scholar,EMBASE,and BMJ databases.We included trials with the following characteristics:(1)Type of study:Prospective,retrospective,randomized,and non-randomized in design;(2)participants:Restricted to patients with DM aged≥18 years;(3)intervention:No intervention;and(4)kidney adverse events:Onset of diabetic kidney disease[estimated glomerular filtration rate(eGFR)of<60 mL/min/1.73 m2 and/or microalbuminuria value of≥30 mg/g Cr],serum creatinine increase of more than double the baseline or end-stage renal disease(eGFR<15 mL/min/1.73 m2 or dialysis),or death.RESULTS Overall,11 studies involving 801 patients with DM were included.High BMI(≥25 kg/m2)was significantly associated with higher blood pressure(BP)[systolic BP by 0.20,95%confidence interval(CI):0.15–0.25,P<0.00001;diastolic BP by 0.21 mmHg,95%CI:0.04–0.37,P=0.010],serum albumin,triglycerides[standard mean difference(SMD)=0.35,95%CI:0.29–0.41,P<0.00001],low-density lipoprotein(SMD=0.12,95%CI:0.04–0.20,P=0.030),and lower high-density lipoprotein(SMD=–0.36,95%CI:–0.51 to–0.21,P<0.00001)in patients with DM compared with those with low BMIs(<25 kg/m2).Our analysis showed that high BMI was associated with a higher risk ratio of adverse kidney events than low BMI(RR:1.22,95%CI:1.01–1.43,P=0.036).CONCLUSION The present analysis suggested that high BMI was a risk factor for adverse kidney events in patients with DM.

Predicting major adverse cardiovascular events after orthotopic liver transplantation using a supervised machine learning model:A cohort study

BACKGROUND Liver transplant(LT)patients have become older and sicker.The rate of post-LT major adverse cardiovascular events(MACE)has increased,and this in turn raises 30-d post-LT mortality.Noninvasive cardiac stress testing loses accuracy when applied to pre-LT cirrhotic patients.AIM To assess the feasibility and accuracy of a machine learning model used to predict post-LT MACE in a regional cohort.METHODS This retrospective cohort study involved 575 LT patients from a Southern Brazilian academic center.We developed a predictive model for post-LT MACE(defined as a composite outcome of stroke,new-onset heart failure,severe arrhythmia,and myocardial infarction)using the extreme gradient boosting(XGBoost)machine learning model.We addressed missing data(below 20%)for relevant variables using the k-nearest neighbor imputation method,calculating the mean from the ten nearest neighbors for each case.The modeling dataset included 83 features,encompassing patient and laboratory data,cirrhosis complications,and pre-LT cardiac assessments.Model performance was assessed using the area under the receiver operating characteristic curve(AUROC).We also employed Shapley additive explanations(SHAP)to interpret feature impacts.The dataset was split into training(75%)and testing(25%)sets.Calibration was evaluated using the Brier score.We followed Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines for reporting.Scikit-learn and SHAP in Python 3 were used for all analyses.The supplementary material includes code for model development and a user-friendly online MACE prediction calculator.RESULTS Of the 537 included patients,23(4.46%)developed in-hospital MACE,with a mean age at transplantation of 52.9 years.The majority,66.1%,were male.The XGBoost model achieved an impressive AUROC of 0.89 during the training stage.This model exhibited accuracy,precision,recall,and F1-score values of 0.84,0.85,0.80,and 0.79,respectively.Calibration,as assessed by the Brier score,indicated excellent model calibration with a score of 0.07.Furthermore,SHAP values highlighted the significance of certain variables in predicting postoperative MACE,with negative noninvasive cardiac stress testing,use of nonselective beta-blockers,direct bilirubin levels,blood type O,and dynamic alterations on myocardial perfusion scintigraphy being the most influential factors at the cohort-wide level.These results highlight the predictive capability of our XGBoost model in assessing the risk of post-LT MACE,making it a valuable tool for clinical practice.CONCLUSION Our study successfully assessed the feasibility and accuracy of the XGBoost machine learning model in predicting post-LT MACE,using both cardiovascular and hepatic variables.The model demonstrated impressive performance,aligning with literature findings,and exhibited excellent calibration.Notably,our cautious approach to prevent overfitting and data leakage suggests the stability of results when applied to prospective data,reinforcing the model’s value as a reliable tool for predicting post-LT MACE in clinical practice.

Performance of the EDACS-ADP incorporating high-sensitivity troponin assay:Do components of major adverse cardiac events matter?

BACKGROUND:The accelerated diagnostic protocol(ADP)using the Emergency Department Assessment of Chest pain Score(EDACS-ADP),a tool to identify patients at low risk of a major adverse cardiac event(MACE)among patients presenting with chest pain to the emergency department,was developed using a contemporary troponin assay.This study was performed to validate and compare the performance of the EDACS-ADP incorporating high-sensitivity cardiac troponin I between patients who had a 30-day MACE with and without unstable angina(MACE I and II,respectively).METHODS:A single-center prospective observational study of adult patients presenting with chest pain suggestive of acute coronary syndrome was performed.The performance of EDACS-ADP in predicting MACE was assessed by calculating the sensitivity and negative predictive value.RESULTS:Of the 1,304 patients prospectively enrolled,399(30.6%;95%confidence interval[95%CI]:27.7%–33.8%)were considered low-risk using the EDACS-ADP.Among them,the rates of MACE I and II were 1.3%(5/399)and 1.0%(4/399),respectively.The EDACS-ADP showed sensitivities and negative predictive values of 98.8%(95%CI:97.2%–99.6%)and 98.7%(95%CI:97.0%–99.5%)for MACE I and 98.7%(95%CI:96.8%–99.7%)and 99.0%(95%CI:97.4%–99.6%)for MACE II,respectively.CONCLUSION:EDACS-ADP could help identify patients as safe for early discharge.However,when unstable angina was added to the outcome,the 30-day MACE rate among the designated lowrisk patients remained above the level acceptable for early discharge without further evaluation.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

Predictive Effect of CA125 on Adverse Cardiovascular Events in Patients with Chronic Heart Failure

Objective: To study the expression of CA125 in the serum of patients with CHF and the relationship between CA125 level and the occurrence of adverse cardiovascular events. Methods: The clinical data of 132 patients with CHF admitted to Shizuishan Second People’s Hospital from January 2023 to December 2023 were collected and divided into heart function II group, heart function III group, heart function IV group according to cardiac function. 44 healthy subjects who underwent physical examination during the same period were selected as the control group. The clinical data of CA125, NT-proBNP, echocardiography and other clinical data of the four groups were compared, and the incidence of major adverse cardiovascular events was followed up for 12 months. Results: Compared with the control group, the CA125 level in the CHF group was significantly increased (P Conclusion: Serum CA125 level is related to the cardiac function level in CHF patients and increases with the deterioration of cardiac function. The increase of the index is related to the mortality rate and re-hospitalization rate, suggesting that CA125 can be used as an indicator to reflect the severity of heart failure and prognosis monitoring.

Value of improved nursing measures and enhanced nursing management to reduce the occurrence of adverse events in pediatric infusion

BACKGROUND Intravenous infusion is a common method of drug administration in clinical practice.Errors in any aspect of the infusion process,from the verification of medical orders,preparation of the drug solution,to infusion by nursing staff,may cause adverse infusion events.AIM To analyzed the value of improving nursing measures and enhancing nursing management to reduce the occurrence of adverse events in pediatric infusion.METHODS The clinical data of 130 children who received an infusion in the pediatric department of our hospital from May 2020 to May 2021 were analyzed and divided into two groups according to the differences in nursing measures and nursing management:65 patients in the control group received conventional nursing and nursing management interventions,while 65 patients in the observation group received improved nursing measure interventions and enhanced nursing management.The occurrence of adverse events,compliance of children,satisfaction of children’s families,and complaints regarding the transfusion treatment were recorded in both groups.RESULTS The incidence of fluid extravasation and infusion set dislodgement in the observation group were 3.08%and 1.54%,respectively,which were significantly lower than 12.31%and 13.85%in the control group(P<0.05),while repeated punctures and medication addition errors in the observation group were 3.08%and 0.00%,respectively,which were lower than 9.23%and 3.08%in the control group,but there was no significant difference(P>0.05).The compliance rate of children in the observation group was 98.46%(64/65),which was significantly higher than 87.69%(57/65)in the control group,and the satisfaction rate of children’s families was 96.92%(63/65),which was significantly higher than 86.15%(56/65)in the control group(P<0.05).The observation group did not receive any complaints from the child’s family,whereas the control group received four complaints,two of which were due to the crying of the child caused by repeated punctures,one due to the poor attitude of the nurse,and one due to medication addition errors,with a cumulative complaint rate of 6.15%.The cumulative complaint rate of the observation group was significantly lower than that of the control group(P<0.05).CONCLUSION Improving nursing measures and enhancing nursing management can reduce the incidence of fluid extravasation and infusion set dislodgement in pediatric patients,improve children’s compliance and satisfaction of their families,and reduce family complaints.

Contemporary nationwide trends in major adverse cardiovascular events in young cannabis users without concomitant tobacco,alcohol,cocaine use

BACKGROUND Cannabis use has increased among young individuals in recent years.Although dependent cannabis use disorder(CUD)has been associated with various cardiac events,its effects on young adults without concurrent substance use remain understudied.AIM To examine trends in hospitalizations for major adverse cardiac and cerebrovascular events(MACCE)in this cohort.METHODSWe used the National Inpatient Sample(2016-2019)to identify hospitalized young individuals(18-44 years),excluding those with concurrent substance usage(tobacco,alcohol,and cocaine).They were divided into CUD+and CUD-.Using International Classification of Diseases-10 codes,we examined the trends in MACCE hospitalizations,including all-cause mortality(ACM),acute myocardial infarction(AMI),cardiac arrest(CA),and acuteischemic stroke(AIS).RESULTSOf 27.4 million hospitalizations among young adults without concurrent substance abuse,4.2%(1.1 million)hadco-existent CUD.In CUD+group,hospitalization rates for MACCE(1.71%vs 1.35%),AMI(0.86%vs 0.54%),CA(0.27%vs 0.24%),and AIS(0.49%vs 0.35%)were higher than in CUD-group(P<0.001).However,rate of ACMhospitalizations was lower in CUD+group(0.30%vs 0.44%).From 2016 to 2019,CUD+group experienced arelative rise of 5%in MACCE and 20%in AMI hospitalizations,compared to 22%and 36%increases in CUDgroup(P<0.05).The CUD+group had a 13%relative decrease in ACM hospitalizations,compared to a 10%relative rise in CUD-group(P<0.05).However,when adjusted for confounders,MACCE odds among CUD+cohort remain comparable between 2016 and 2019.CONCLUSIONThe CUD+group had higher rates of MACCE,but the rising trends were more apparent in the CUD-group overtime.Interestingly,the CUD+group had lower ACM rates than the CUD-group.

Adverse Events following AstraZeneca COVID-19 Vaccination: A Case Study in Abidjan, Côte d’Ivoire

Introduction: Pharmaceutical companies have boosted vaccine production following the global COVID-19 pandemic. In Côte d’Ivoire, the first vaccination campaign with the AstraZeneca vaccine began on March 1, 2021, as part of the Covax program. Despite the positive benefit/risk balance, the adverse effects of vaccination should not be minimized. Objective: To identify adverse events of AstraZeneca’s COVID-19 vaccination for better management. Materials and Methods: This is a case of a 57-year-old obese (BMI = 39 kg/m2) female health care worker who experienced adverse events in March 2021 after the second dose of AstraZeneca vaccine administered 4 weeks apart. These were subject to mandatory case reporting. Results: Major post-vaccination events occurred in a noisy systemic picture with parameters showing significant disturbances. Biological surveillance remains costly and makes the accountability of the vaccine complex. Conclusion: Vaccination remains the ultimate weapon in the fight against endemic diseases but should not overshadow the reporting of adverse events.

Biomarkers associated with immune-related adverse events induced by immune checkpoint inhibitors

Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irAEs),significantly affecting the efficacy and survival rates of patients undergoing ICI therapy.While conventional hematological and imaging tests are adept at detecting organ-specific toxicities,distinguishing adverse reactions from those induced by viruses,bacteria,or immune diseases remains a formidable challenge.Consequently,there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs.Thus,a thorough review of existing studies on irAEs biomarkers is indispensable.Our review commences by providing a succinct over-view of major irAEs,followed by a comprehensive summary of irAEs biomarkers across various dimensions.Furthermore,we delve into innovative methodologies such as machine learning,single-cell RNA sequencing,multiomics analysis,and gut microbiota profiling to identify novel,robust biomarkers that can facilitate precise irAEs diagnosis or prediction.Lastly,this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction,diagnosis,and treatment strategies.

Gender Effects on Statin-Associated Muscular Adverse Events: An Analysis of the FDA AERS Database

Objective: The reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) from 1997 to 2011 were reviewed to assess the gender effects on muscular adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). Methods: After the deletion of duplicated submissions and the revision of arbitrary drug names, the reports involving pravastatin, simvastatin, atorvastatin, rosuvastatin, and cerivastatin were analyzed. Data mining algorithms were applied for the quantitative detection of signals, where a signal means a drug-associated adverse event, including the proportional reporting ratio, the reporting odds ratio, the information component, and the empirical Bayes geometric mean. Myopathy, myalgia, myositis, rhabdomyolysis, and an increase in creatine phosphokinase level were focused on as the muscular adverse events. Results: The total number of reports was 3,472,494. The signal scores suggested that all 5 statins were associated with 5 muscular adverse events in both male and female patients. The scores varied among statins, but were more noteworthy for cerivastatin. Conclusion: The data strongly suggested the necessity of well-organized clinical studies on statin-associated muscular adverse events.

基于FAERS数据库的白消安不良事件信号挖掘与分析

目的 利用美国食品药品管理局不良事件报告系统(FAERS)数据库对白消安的药品不良事件(ADE)进行研究,挖掘潜在的ADE信号,为临床安全用药提供参考。方法 检索FAERS数据库中2004年第1季度至2023年第1季度的数据,通过数据清洗、目标药物名称标准化,获得以白消安为首要怀疑药物的ADE记录。采用报告比值比法、比例报告比值法和综合标准法挖掘白消安ADE信号,并利用信息成分法进行信号强弱判断。以《国际医学用语词典》对ADE进行系统器官分类(SOC),并按照ADE发生频次和信号强度分别排序。结果 共获得20 326份以白消安为首要怀疑药物的ADE报告,涉及患者5 615例,男性患者比例高于女性(40.71%vs.30.74%);年龄小于18岁占31.56%;上报人群主要为医师(33.71%)、其他健康专业人员(24.35%)以及药师(23.86%);上报国家主要为美国(29.69%)、日本(15.78%)、法国(11.79%)。共挖掘出白消安相关ADE信号556个,其中117个ADE信号未被药品说明书收载。556个ADE信号中,发生频次前五位ADE分别为产品用于未经批准的适应证、肝小静脉闭塞症、黏膜炎症、巨细胞病毒感染和移植物抗宿主病;信号强度排名前五位ADE分别为肝小静脉闭塞症、急性移植物抗宿主病、静脉闭塞性疾病、移植物抗宿主病以及慢性移植物抗宿主病。挖掘的ADE信号共累及23个SOC,数量排名前三的SOC分别为感染及侵染类疾病,各类检查,良性、恶性及性质不明的肿瘤(包括囊状和息肉状)。结论 白消安临床应用中,应警惕肝小静脉闭塞症、感染、移植物抗宿主病、神经相关毒性和血栓性微血管病等易造成严重后果的ADE,临床药师协助医师做好ADE的预防方案,提高白消安的使用安全性。

基于FAERS数据库的喹硫平不良事件信号挖掘与分析

目的基于美国食品药品监督管理局(FDA)不良事件报告系统(FAERS)数据库挖掘喹硫平的药物不良事件(ADE)信号,为该药的临床安全使用提供参考。方法检索FAERS数据库中2004年至2023年共79个季度关于喹硫平的不良反应报告,同时采用报告比值比法、比例报告比值法、贝叶斯置信区间神经网络传播法、多重伽马-泊松收缩估计法,按药物不良事件术语集的首选术语(PT)和系统器官分类(SOC)对纳入的ADE报告进行分类并计算风险信号。结果共收集主要怀疑药物为喹硫平的ADE报告261725份,涉及的患者有68012例,其中以女性(37495份,55.13%)及老年患者(>65岁)(35312份,占51.9%)居多,报告国家以美国为主,结局多为其他严重后果、住院、死亡和危及患者生命。共挖掘出喹硫平阳性风险信号PT 713个,涉及SOC 27个,所得信号基本与药品说明书一致,其中报告数最多的ADE为糖尿病,且信号强度较高。报告数超过500例的ADE中,共挖掘47个阳性风险信号PT,其中横纹肌溶解为说明书中未收载的ADE。喹硫平引起ADE发生的时间不一,常在用药后30 d内或用药一年以上发生。结论临床在使用喹硫平时除应在全程关注药品说明书收录的ADE外,还应警惕说明书未提及的ADE,并且根据性别、年龄等制订个体化的用药监护方案。

基于FAERS数据库对塞来昔布不良事件信号的分析

目的基于美国食品药品监督管理局(FDA)不良事件报告系统(FAERS)数据库,挖掘塞来昔布的不良事件(ADE)信号,为临床安全用药提供参考。方法采用报告比值比法、综合标准法和信息成分法挖掘FAERS数据库2004年第1季度至2022年第4季度的报告数据。结果ADE报告人主要为45岁以上人群,以女性居多,上报国家主要是美国。获得塞来昔布ADE报告37020例,涉及ADE 4068种,挖掘ADE信号406个,经筛选后得到有效信号285个,累及23个系统-器官(SOC)。根据信号强度,排名前5位的信号分别为:食管纤维化、与性活动有关的原发性头痛、脑血管疾病、胃肠道腺癌、心血管障碍。说明书未载明的ADE信号主要有:视网膜静脉血栓形成、失明、健忘、过敏性休克等。结论所得ADE信号基本与说明书一致;信号提示塞来昔布ADE主要集中在心脏疾病、神经系统疾病、免疫系统疾病、胃肠道疾病等;说明书黑框警告心血管血栓事件,胃肠道出血、溃疡和穿孔均有相关ADE信号检出。在使用该药时,除注意患者心脑血管、胃肠道不适症状以外,还应关注患者视网膜病变,并做好相关监护,以保证临床用药的安全。

基于美国FAERS数据库的利奈唑胺抗结核治疗不良事件分析

目的分析美国FDA不良事件报告系统(FAERS)数据库中利奈唑胺在抗结核治疗中的不良事件(AEs),评估其安全性特征,为临床合理用药提供科学依据。方法提取2016年第1季度至2024年第1季度间与利奈唑胺相关的抗结核治疗不良事件报告。数据经过清洗和预处理,采用报告比值比(ROR)和信息成分法(IC)进行信号挖掘。结果研究共筛选出1135例利奈唑胺相关AEs,主要不良事件类型为住院(18.46%)和死亡(10.99%)。结果显示,利奈唑胺的AEs主要涉及血液及淋巴系统疾病和肝胆系统疾病。常见不良反应包括贫血、周围神经病、视神经病等。此外,发现了一些说明书未提及的不良反应信号,如多发神经病(ROR=75.25,IC_(025)=5.8)、中毒性视神经病(ROR=776.95,IC_(025)=8.86)和耳聋(ROR=14.66,IC_(025)=3.26)。结论本研究表明,利奈唑胺在抗结核治疗中可能伴随一些严重不良反应,建议对长期使用利奈唑胺的患者进行定期的神经系统、眼科和听力检查,为临床合理用药提供更充足的依据。

基于FAERS的儿童奥司他韦不良事件信号挖掘与分析

目的 为临床安全使用奥司他韦提供参考。方法 检索美国食品和药物管理局不良事件报告系统(FAERS)数据库中2004年第1季度至2023年第1季度以奥司他韦为首要怀疑药物、发生于0~17岁患儿的药品不良事件(ADE)报告,采用报告比值比(ROR)法、比例报告比值比(PRR)法进行信号挖掘,采用《国际医学用语词典》中的首选语(PT)及系统器官分类(SOC)进行编码和归类。结果 共挖掘到奥司他韦相关ADE报告3 100份,检测到阳性信号76个,主要集中在精神病类(34个)、各类神经系统疾病(13个)、胃肠系统疾病(7个)、全身性疾病及给药部位各种反应(6个)、免疫系统疾病(3个)等12个SOC。发生频次排前20位的ADE有幻觉(455次)、异常行为(428次)、呕吐(410次)、谵妄(120次)、意识模糊状态(111次)等,信号强度排前20位的ADE仍以精神病类、各类神经系统疾病、胃肠系统疾病为主。发生频次和信号强度均排前20位的ADE有尖叫、恐惧、睡惊症,药品说明书中均未提及。结论 患儿临床应用奥司他韦时,应关注精神疾病、神经系统和胃肠道系统,以及皮肤和眼部的ADE。

关注免疫检查点抑制剂发生irAE后免疫治疗再挑战

免疫检查点抑制剂(immune-checkpoint inhibitors,ICIs)是近年来肿瘤学领域最重要的突破之一,为不同类型的实体瘤治疗提供了新的范式。ICIs通过阻断免疫内在下调因子,如细胞毒性T淋巴细胞抗原4(CTLA-4)和程序性细胞死亡1(PD-1)或其配体程序性细胞死亡配体1(PD-L1),增加抗肿瘤免疫力[1]。然而,由于免疫应答增强和免疫系统失衡,患者可能会发生免疫相关不良事件(immune-related adverse events,irAE)。

基于FAERS数据库的依达拉奉不良事件信号挖掘

目的:挖掘美国食品药品监督管理局不良事件报告系统(FDA Adeverse Event Reporting System,FAERS)数据库中依达拉奉不良事件的相关临床报告,分析其在临床治疗中的安全性和有效性,为依达拉奉在临床中的应用提供参考。方法:从FAERS数据库中收集2017年4月—2022年12月有关依达拉奉不良事件的相关临床报告,并采用报告比值比(reporting odds ratio,ROR)法以及国际上常用ADE信号检测比例报告(proportional reportingratio,PRR)对数据进行分析。结果:共收集4367份报告,涉及全身性疾病及给药部位各种反应(43.46%)、各类神经系统疾病(13.28%)以及呼吸系统、胸及纵隔疾病(6.69%)等13类系统/器官分类项。其中,药物无效、患者疾病进展以及病情恶化的预警报告分别为239份、227份和125份,肌萎缩侧索硬化信号强度较高(PRR=1269.58),这些不良事件均未出现在说明书中。结论:依达拉奉相关报告反映出其在临床治疗中存在药效不理想的情况。因此,在依达拉奉的临床应用中,除了密切关注患者可能出现说明书包含的不良事件之外,还需根据患者实际情况采用联合用药的策略,保证临床干预的有效性。

基于FAERS数据库的达罗他胺不良反应信号挖掘与分析

目的:挖掘达罗他胺相关的不良反应风险信号,为临床安全用药提供参考。方法:利用报告比值比法(ROR)对美国FDA不良反应报告系统(FAERS)中2019年第三季度至2022年第四季度以达罗他胺为首要怀疑药物的不良反应进行挖掘,检测阈值为报告数≥3且ROR的95%置信区间下限>1的不良反应。结果及结论:共筛选出以达罗他胺为首要怀疑药物的不良反应报告1376份,去除非药品不良反应后为1013份,涉及患者589例,检测出风险信号40个,涉及16个系统器官,主要集中在全身性疾病及给药部位各种反应、胃肠系统疾病、皮肤及皮下组织类疾病、各类检查及各类神经系统疾病。达罗他胺的不良反应最常出现在服药的第1个月。挖掘出药品说明书未提及的信号21个,具体包括横纹肌溶解、谵妄、男性乳腺发育、周围神经病变和水肿等。

基于FAERS数据库的奥马珠单抗不良事件信号挖掘

目的运用数据挖掘的方法检测奥马珠单抗上市后的不良反应信号,为临床安全合理用药提供参考。方法本研究采用报告比值比法(ROR)和贝叶斯判别可信区间递进神经网络法(BCPNN)对美国FDA不良事件报告系统(FAERS)中2004年第1季度至2023年第2季度的奥马珠单抗相关不良事件(ADE)报告进行数据挖掘和信号检测。结果通过数据挖掘和信号检测,涉及奥马珠单抗的ADE报告中提取了186,353份报告,涉及45,383例患者。在这些报告中,女性(65.31%)比例远高于男性(24.97%)。主要报告国家为美国(64.93%)和加拿大(11.96%)。报告者中以消费者(41.35%)和医师(36.97%)为主要群体。研究发现了621个ADE阳性信号,涉及25个系统器官分类(SOC),主要包括呼吸系统、胸部和纵隔疾病(21.29%)以及感染和侵染类疾病(10.91%)。其中,183个信号被评定为高风险信号,其中包括57个新的高风险信号,如血压升高、易醒型失眠和心律失常等。这些发现有助于更全面地了解奥马珠单抗的安全性和潜在风险。结论在奥马珠单抗的临床应用过程中,除了要注意药品说明中提到的已知不良反应外,还需特别警惕潜在的不良药物事件,如血压升高、心率升高、中间易醒型失眠、体位性心动过速综合征等。