Drug-induced liver injury(DILI) is a leading reason for preclinical safety attrition and postmarket drug withdrawals.Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DIL...Drug-induced liver injury(DILI) is a leading reason for preclinical safety attrition and postmarket drug withdrawals.Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI,especially in idiosyncratic liver injury.This study examined liver injury reports submitted to the Food and Drug Administration(FDA) Adverse Event Reporting System(FAERS) for drugs associated with hepatotoxicity via mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity.The frequency of hepatotoxicity was determined at a group level and individual drug level.A reporting odds ratio(ROR) was calculated as the measure of effect.Between the two DILI groups,reports for DILI involving mitochondrial mechanisms of toxicity had a 1.43(95% CI 1.42-1.45;P <0.0001) times higher odds compared to drugs associated with non-mitochondrial mechanisms of toxicity.Antineoplastic,antiviral,analgesic,antibiotic,and antimycobacterial drugs were the top five drug classes with the highest ROR values.Although the top 20 drugs with the highest ROR values included drugs with both mitochondrial and non-mitochondrial injury mechanisms,the top four drugs(ROR values> 18:benzbromarone,troglitazone,isoniazid,rifampin) were associated with mitochondrial mechanisms of toxicity.The major demographic influence for DILI risk was also examined.There was a higher mean patient age among reports for drugs that were associated with mitochondrial mechanisms of toxicity [56.1±18.33(SD)] compared to non-mitochondrial mechanisms [48±19.53(SD)](P <0.0001),suggesting that age may play a role in susceptibility to DILI via mitochondrial mechanisms of toxicity.Univariate logistic regression analysis showed that reports of liver injury were 2.2(odds ratio:2.2,95% CI 2.12-2.26) times more likely to be associated with older patient age,as compared with reports involving patients less than 65 years of age.Compared to males,female patients were 37% less likely(odds ratio:0.63,95% CI 0.61-0.64) to be subjects of liver injury reports for drugs associated with mitochondrial toxicity mechanisms.Given the higher proportion of severe liver injury reports among drugs associated with mitochondrial mechanisms of toxicity,it is essential to understand if a drug causes mitochondrial toxicity during preclinical drug development when drug design alternatives,more clinically relevant animal models,and better clinical biomarkers may provide a better translation of druginduced mitochondrial toxicity risk assessment from animals to humans.Our findings from this study align with mitochondrial mechanisms of toxicity being an important cause of DILI,and this should be further investigated in real-world studies with robust designs.展开更多
Objective:To develop nursing adverse events’reporting content of hospital.Methods:The study included two phases.The first phase was to develop the category and definition of nursing adverse events that need to be rep...Objective:To develop nursing adverse events’reporting content of hospital.Methods:The study included two phases.The first phase was to develop the category and definition of nursing adverse events that need to be reported through an expert meeting.The second phase was to develop every nursing adverse event’s reporting content by using the Delphi method.In total,8 experts attended the meeting and 15 experts conducted two rounds of consultation letter.Results:Nursing adverse events that need to be reported of hospital include pressure sore,fall/falling from bed,unplanned extubation,medication error,and accident.Reporting content of these events in detail had also been obtained,which was helpful for cause analysis systematically.Conclusions:The reporting content of the nursing adverse event of hospital is established,and it is a basis for further study of the development of nursing adverse event reporting and feedback system.展开更多
Background: The Spontaneous Reporting System (SRS) of the Food and Drugs Administration (FDA) of the United States of America (US), known as the FDA Adverse Event Reporting System (FAERS), is a mechanism for collectin...Background: The Spontaneous Reporting System (SRS) of the Food and Drugs Administration (FDA) of the United States of America (US), known as the FDA Adverse Event Reporting System (FAERS), is a mechanism for collecting information on safety concerns associated with the use of drugs for redress, as they are used on large scale. The data which is the subject of this paper came from the FAERS database. This paper reports on the analysis of data covering 2013 to 2018 period, but compares the observed trends in the variables during this period with that of the 2007 to 2012 period to ascertain whether the trends change over time;as this paper is, in a sense, a sequel to an earlier one with a similar title as this but covering the period 2007 to 2012. Objectives: The objectives of the study reported in this paper were to: i) explore the trends in the variables involved with the adverse events problem in the 2013 to 2018 period and compare these trends with that found in the study covering the 2007 to 2012 period;ii) determine whether or not the level of missing variable values in the 2013 to 2018 period is lower than, the same or higher than it was in the 2007 to 2012 period;iii) find out how the first twenty principal suspect drugs most cited to be involved in adverse events occurring during drug use in the 2013 to 2018 period compare with that of the 2007 to 2012 period. Methods: The Food and Drugs Administration (FDA) makes extracts from the FAERS database freely available to the public on quarterly basis. Fourteen (14) out of over fifty (50) variables contained in these extracts were reckoned to be connected with the objectives of the study and were examined using the tools of frequencies, proportions and averages, on account of the nature of the data. Results: For the period 2013 to 2018, adverse events reports submitted to the FDA (US) more than doubled (2.1 times), accounting for an annual average growth rate of 15.8 %, which is considerably lower than the annual average growth rate of 22.1% for the 2007 to 2012 period. However, the reported number of cases for 2015 was 53.8% more than that of 2014. Consistent with the results for 2007 to 2012 period, the 2013 to 2018 period saw Female subjects accounting for over 60% of the annual and the overall number of reports. Overall, non-health professionals appear to have a slight edge over health professionals in reporting adverse drug events in the 2013 to 2018 period, with an indication that reports from non-health professionals are on the decline and that from health professionals is on the rise. Non-health professionals and health professionals were almost equally likely to report adverse events in the 2007 to 2012 period. Also, the findings for the 2013 to 2018 period suggest that the older one gets the more vulnerable one becomes to adverse events associated with drug use, which is consistent with the findings for the 2007 to 2012 period. Conclusion: The dangers that come with the use of drugs is an evolving one and therefore there is the need to examine SRS data from time to time so that emerging drug safety concerns can be dealt with timeously.展开更多
目的:评价和分析维泊妥珠单抗上市后的药物不良反应(adverse drug reaction,ADR)信号,为临床安全性管理提供参考。方法:通过开放性OpenVigil数据平台,收集2019年6月10日(美国FDA批准上市时间)至2023年3月31日美国FDA不良事件报告系统(FA...目的:评价和分析维泊妥珠单抗上市后的药物不良反应(adverse drug reaction,ADR)信号,为临床安全性管理提供参考。方法:通过开放性OpenVigil数据平台,收集2019年6月10日(美国FDA批准上市时间)至2023年3月31日美国FDA不良事件报告系统(FAERS)数据库中维泊妥珠单抗的ADR报告。采用比例失衡法中的报告比值比(ROR)和比例报告比(PRR)进行信号挖掘。为提高阈值,得到信号较强、较常出现的ADR,将信号进行二次筛选。结果:共检索到维泊妥珠单抗相关ADR报告2408份,经过二次筛选得到83个ADR信号。其中,脊柱磁共振成像异常、骨吸收增加、骨质溶解、天门冬氨酸氨基转移酶降低、丙氨酸氨基转移酶降低、低纤维蛋白原血症、肺栓塞等26个ADR信号在药品说明书中未提及。信号数或累积例数较多的系统器官分类包含感染及侵染类疾病(24个信号、632例),各类检查(17个信号、675例),血液及淋巴系统疾病(11个信号、734例),各类神经系统疾病(7个信号、153例),免疫系统疾病(3个信号、95例),全身性疾病及给药部位各种反应(2个信号、145例),代谢及营养类疾病(2个信号、87例)等。结论:除说明书提示的常见ADR外,本研究发现了维泊妥珠单抗新的ADR风险信号。建议临床在关注感染、骨髓抑制、周围神经病、输液相关反应、肝功能异常等已知常见ADR的同时,予以脊柱磁共振成像异常、骨吸收增加等新的风险信号更多关注。展开更多
文摘Drug-induced liver injury(DILI) is a leading reason for preclinical safety attrition and postmarket drug withdrawals.Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI,especially in idiosyncratic liver injury.This study examined liver injury reports submitted to the Food and Drug Administration(FDA) Adverse Event Reporting System(FAERS) for drugs associated with hepatotoxicity via mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity.The frequency of hepatotoxicity was determined at a group level and individual drug level.A reporting odds ratio(ROR) was calculated as the measure of effect.Between the two DILI groups,reports for DILI involving mitochondrial mechanisms of toxicity had a 1.43(95% CI 1.42-1.45;P <0.0001) times higher odds compared to drugs associated with non-mitochondrial mechanisms of toxicity.Antineoplastic,antiviral,analgesic,antibiotic,and antimycobacterial drugs were the top five drug classes with the highest ROR values.Although the top 20 drugs with the highest ROR values included drugs with both mitochondrial and non-mitochondrial injury mechanisms,the top four drugs(ROR values> 18:benzbromarone,troglitazone,isoniazid,rifampin) were associated with mitochondrial mechanisms of toxicity.The major demographic influence for DILI risk was also examined.There was a higher mean patient age among reports for drugs that were associated with mitochondrial mechanisms of toxicity [56.1±18.33(SD)] compared to non-mitochondrial mechanisms [48±19.53(SD)](P <0.0001),suggesting that age may play a role in susceptibility to DILI via mitochondrial mechanisms of toxicity.Univariate logistic regression analysis showed that reports of liver injury were 2.2(odds ratio:2.2,95% CI 2.12-2.26) times more likely to be associated with older patient age,as compared with reports involving patients less than 65 years of age.Compared to males,female patients were 37% less likely(odds ratio:0.63,95% CI 0.61-0.64) to be subjects of liver injury reports for drugs associated with mitochondrial toxicity mechanisms.Given the higher proportion of severe liver injury reports among drugs associated with mitochondrial mechanisms of toxicity,it is essential to understand if a drug causes mitochondrial toxicity during preclinical drug development when drug design alternatives,more clinically relevant animal models,and better clinical biomarkers may provide a better translation of druginduced mitochondrial toxicity risk assessment from animals to humans.Our findings from this study align with mitochondrial mechanisms of toxicity being an important cause of DILI,and this should be further investigated in real-world studies with robust designs.
文摘Objective:To develop nursing adverse events’reporting content of hospital.Methods:The study included two phases.The first phase was to develop the category and definition of nursing adverse events that need to be reported through an expert meeting.The second phase was to develop every nursing adverse event’s reporting content by using the Delphi method.In total,8 experts attended the meeting and 15 experts conducted two rounds of consultation letter.Results:Nursing adverse events that need to be reported of hospital include pressure sore,fall/falling from bed,unplanned extubation,medication error,and accident.Reporting content of these events in detail had also been obtained,which was helpful for cause analysis systematically.Conclusions:The reporting content of the nursing adverse event of hospital is established,and it is a basis for further study of the development of nursing adverse event reporting and feedback system.
文摘Background: The Spontaneous Reporting System (SRS) of the Food and Drugs Administration (FDA) of the United States of America (US), known as the FDA Adverse Event Reporting System (FAERS), is a mechanism for collecting information on safety concerns associated with the use of drugs for redress, as they are used on large scale. The data which is the subject of this paper came from the FAERS database. This paper reports on the analysis of data covering 2013 to 2018 period, but compares the observed trends in the variables during this period with that of the 2007 to 2012 period to ascertain whether the trends change over time;as this paper is, in a sense, a sequel to an earlier one with a similar title as this but covering the period 2007 to 2012. Objectives: The objectives of the study reported in this paper were to: i) explore the trends in the variables involved with the adverse events problem in the 2013 to 2018 period and compare these trends with that found in the study covering the 2007 to 2012 period;ii) determine whether or not the level of missing variable values in the 2013 to 2018 period is lower than, the same or higher than it was in the 2007 to 2012 period;iii) find out how the first twenty principal suspect drugs most cited to be involved in adverse events occurring during drug use in the 2013 to 2018 period compare with that of the 2007 to 2012 period. Methods: The Food and Drugs Administration (FDA) makes extracts from the FAERS database freely available to the public on quarterly basis. Fourteen (14) out of over fifty (50) variables contained in these extracts were reckoned to be connected with the objectives of the study and were examined using the tools of frequencies, proportions and averages, on account of the nature of the data. Results: For the period 2013 to 2018, adverse events reports submitted to the FDA (US) more than doubled (2.1 times), accounting for an annual average growth rate of 15.8 %, which is considerably lower than the annual average growth rate of 22.1% for the 2007 to 2012 period. However, the reported number of cases for 2015 was 53.8% more than that of 2014. Consistent with the results for 2007 to 2012 period, the 2013 to 2018 period saw Female subjects accounting for over 60% of the annual and the overall number of reports. Overall, non-health professionals appear to have a slight edge over health professionals in reporting adverse drug events in the 2013 to 2018 period, with an indication that reports from non-health professionals are on the decline and that from health professionals is on the rise. Non-health professionals and health professionals were almost equally likely to report adverse events in the 2007 to 2012 period. Also, the findings for the 2013 to 2018 period suggest that the older one gets the more vulnerable one becomes to adverse events associated with drug use, which is consistent with the findings for the 2007 to 2012 period. Conclusion: The dangers that come with the use of drugs is an evolving one and therefore there is the need to examine SRS data from time to time so that emerging drug safety concerns can be dealt with timeously.
文摘目的:评价和分析维泊妥珠单抗上市后的药物不良反应(adverse drug reaction,ADR)信号,为临床安全性管理提供参考。方法:通过开放性OpenVigil数据平台,收集2019年6月10日(美国FDA批准上市时间)至2023年3月31日美国FDA不良事件报告系统(FAERS)数据库中维泊妥珠单抗的ADR报告。采用比例失衡法中的报告比值比(ROR)和比例报告比(PRR)进行信号挖掘。为提高阈值,得到信号较强、较常出现的ADR,将信号进行二次筛选。结果:共检索到维泊妥珠单抗相关ADR报告2408份,经过二次筛选得到83个ADR信号。其中,脊柱磁共振成像异常、骨吸收增加、骨质溶解、天门冬氨酸氨基转移酶降低、丙氨酸氨基转移酶降低、低纤维蛋白原血症、肺栓塞等26个ADR信号在药品说明书中未提及。信号数或累积例数较多的系统器官分类包含感染及侵染类疾病(24个信号、632例),各类检查(17个信号、675例),血液及淋巴系统疾病(11个信号、734例),各类神经系统疾病(7个信号、153例),免疫系统疾病(3个信号、95例),全身性疾病及给药部位各种反应(2个信号、145例),代谢及营养类疾病(2个信号、87例)等。结论:除说明书提示的常见ADR外,本研究发现了维泊妥珠单抗新的ADR风险信号。建议临床在关注感染、骨髓抑制、周围神经病、输液相关反应、肝功能异常等已知常见ADR的同时,予以脊柱磁共振成像异常、骨吸收增加等新的风险信号更多关注。
