Hepatotoxicity reports in the FDA adverse event reporting system database:A comparison of drugs that cause injury via mitochondrial or other mechanisms

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.

Establishing nursing adverse events’reporting content of hospital:using the Delphi method

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.

Analysis of the adverse reactions of atezolizumab: A real-world study based on FAERS database

Objective In this study,we aimed to determine the incidence of adverse drug reactions(ADRs)of atezolizumab,identify ADR signals that are significantly related to atezolizumab,and provide a reference for the rational use of atezolizumab in the clinic through the statistical analysis of its adverse drug events(ADEs)reported in the American Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database.Methods In total,4796 cases of atezolizumab ADEs reported in the American FAERS database from 2017 to 2019 were retrospectively analyzed.Results The top three ADEs were febrile neutropenia(3.7%),anemia(2.9%),and acute renal failure(2.3%).In addition,the incidence rates of some ADEs were significantly different according to sex and age.The systematic organ classification of atezolizumab ADEs involved 32 systems,among which the top three were blood and lymphatic system disorders(585 cases,12.2%),gastrointestinal disorders(433 cases,9.0%),and infections and infestations(401 cases,8.4%).The reporting odds ratio(ROR)method was used to detect the ADR signals of atezolizumab.The ROR(95%confidence interval)of the top ADE,febrile neutropenia,was 39.236(33.757–45.604).In addition,we found 121 cases of complications associated with immune-related ADEs.Conclusion The ADRs of atezolizumab reported in the FAERS database were consistent with those mentioned in the instructions for atezolizumab use,suggesting that atezolizumab has an acceptable and controllable drug effect.