Objective:To understand the risk signal of ocular adverse events (AE) related to mycophenolate mofetil (MMF) and to provide reference for the safe clinical use of this drug.Methods:The US FDA Adverse Event Reporting System database was searched, and the AE reports on MMF as the primary suspect drug from the 1st quarter of 2004 to the 3rd quarter of 2022 were collected. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities version 24.0, and ocular AEs were screened out. The ocular AE risk signals were explored using 3 frequency methods, including reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, and Bayesian confidence propagation neural network method, and the multi-item gamma-Possion shrinker (MGPS) method. The information of the ocular AE reports and AE risk signals of MMF were analyzed descriptively. Results:A total of 402 cases of ocular AE with MMF as the primary suspect drug were collected, which involved 402 patients, 31 PTs and 5 SOCs. The 402 AE cases were reported among 33 countries, 283 of which had clinical outcome records, including death in 32 cases (11.3%), disability or blindness in 142 cases (50.2%), life-threatening in 14 cases (4.9%), and hospitalization or prolonged hospitalization in 95 cases (33.6%). Results of the frequency method showed that all 31 PTs were risk signals, while the results of the MGPS method manifested that 22 PTs were risk signals. None of the 31 PTs were recorded in the drug labels. The top 5 PTs in the number of AE reports were blindness (136 cases), cytomegalovirus chorioretinitis (37 cases), uveitis (34 cases), endophthalmitis (29 cases), and necrotising retinitis (22 cases). The ranking of signal intensity showed by the 4 methods was similar. The top 5 PTs with the high signal intensity were orbital apex syndrome [ ROR=55.84, PRR=55.83, information component ( IC)=5.58, empirical Bayesian geometric mean ( EBGM)=47.71], quadrantanopia ( ROR=43.22, PRR=43.21, IC=5.26, EBGM=38.21), retinitis viral ( ROR=40.13, PRR=40.13, IC=5.16, EBGM=35.78), optic discs blurred ( ROR=40.13, PRR=40.13, IC=5.16, EBGM=35.78), and serpiginous choroiditis ( ROR=31.07, PRR=31.07, IC=4.83, EBGM=28.41). Conclusions:The clinical manifestations of ocular AE during MMF treatment are diverse, and none of them are recorded in the drug label. The clinical outcomes are poor and can lead to blindness, which should be vigilant in clinical practice.
Objective:To compare the risk for pneumonia in antiplatelet therapy with clopidogrel and ticagrelor.Methods:The relevant databases including PubMed, Embase, Cochrane Library, CBM, CNKI, and Wanfang Med (up to March 1, 2022) were searched. The randomized controlled trials (RCTs) of clopidogrel and ticagrelor (trial group or control group to each other) in the treatment of coronary atherosclerotic heart disease were collected. The Cochrane collaboration risk of bias assessment tool was used to evaluate the methodological quality of the RCTs. RevMan 5.4 software was used for meta-analysis to compare the risk of pneumonia in patients between 2 groups. The effect sizes were the risk ratio ( RR) and its 95% confidence interval ( CI). Results:A total of 5 RCTs were enrolled in the analysis. The methodological quality evaluation results showed that 2 RCTs were with low risk of bias and the others were high. In the 5 RCTs, 36 401 patients were involved, of which 18 724 received the therapy for acute coronary syndrome, 13 842 for peripheral artery disease, 3 799 for myocardial infarct, and 36 for coma survivor with cardiac arrest. The meta-analysis results showed that the incidence of pneumonia were 1.5% (271/18 174) and 1.2% (217/18 227) in patients receiving clopidogrel and ticagrelor, respectively; the risk of pneumonia in ticagrelor-treated patients was relatively lower, and the difference was statistically significant ( RR=0.80, 95% CI: 0.67-0.95, P=0.01). Subgroup analysis showed that the risk for pneumonia was similar in patients between the 2 groups when they received short-term (several days) medication ( P=0.26), while the risk was relatively lower in ticagrelor-treated patients compared with that in clopidogrel-treated patients when the therapeutical time was more than 12 months ( RR=0.80, 95% CI: 0.67-0.96, P=0.02). And also, in the combination therapy with aspirin, the risk of pneumonia was lower in ticagrelor-treated patients than that in clopidogrel-treated patients ( RR=0.74, 95% CI: 0.56-0.98, P=0.03). Conclusion:Compared with clopidogrel, the risk for pneumonia was relatively lower in ticagrelor treatment than that in clopidogrel treatment.
The characteristics of adverse reactions caused by new antineoplastic agents are significantly different from those by traditional chemotherapy drugs, especially the immune-related adverse events caused by immune checkpoint inhibitors (ICIs), in which the diagnosis and treatment often involve multiple fields such as tumor, cardiovascular, endocrine, and immunity. In order to ensure the safety of new antineoplastic agents in the clinical application, the Pharmacy Department of Army Medical Center, Army Medical University established a specialized clinical pharmacy cooperation group of tumor-chronic diseases in October 2022, which is made up of clinical pharmacists majoring in tumor, immunity, cardiovascular, digestion, endocrine, respiration, and anti-infection, to provide pharmaceutical services for managing serious and perplexing adverse drug reaction in tumor patients. As of March 2023, 20 patients have been intervened by the cooperation group, and suggestions from the cooperation group in 17 patients have been adopted and achieved good results. About 98% of the clinicians and nurses are satisfied with the working mode of the cooperation group. This article takes a case of ICI-related myocarditis as an example to illustrate that through the cooperation group model we can provide multi-dimensional, efficient, and full process pharmaceutical care in the clinic, thereby significantly alleviating the problems of insufficient allocation of clinical pharmacists and inadequate coverage of pharmasits with different pharmaceutical specialties.
他汀类药物是治疗血脂异常的主要药物，通过抑制羟甲基戊二酸单酰辅酶A（HMG-CoA）还原酶而减少胆固醇的生物合成。其不良反应主要发生在肝脏和肌肉。在肌肉不良反应中，横纹肌溶解是最严重的，有可能致命，但极少有研究对不同他汀类药物之间横纹肌溶解的风险进行比较。
Objective:To explore the clinical manifestation, treatments, and outcomes of immune checkpoint inhibitor (ICI)-induced immune-mediated liver injury (IMLI).Methods:The patients with ICI- related IMLI and hospitalized in the Department of Oncology, the Affiliated Hospital of Qingdao University from January 2018 to November 2022 were collected. The basic information, tumor treatments, clinical manifestation, treatments and outcomes of the patients with IMLI were retrospectively analyzed.Results:A total of 29 patients were included in the study, including 17 males (58.6%) and 12 females (41.4%), with a median age of 65 years. The median treatment cycle from the use of ICI to the occurrence of liver injury was 3 cycles, and the median time was 78 days. In patients with IMLI, 48.3% (14/29) had no obvious symptoms and 51.7% (15/29) had symptoms such as decreased appetite, nausea, abdominal distension, fatigue, fever and jaundice; 44.8% (13/29) were accompanied by other immune-related adverse events. The clinical classification of IMLI was hepatocellular type in 18 patients (62.1%), cholestasis type in 4 patients (13.8%), and mixed type in 7 patients (24.1%). According to the Common Terminology Criteria for Adverse Events (CTCAE) classification, severe liver injury (≥ grade 3) accounted for 86.2% (25/29), while according to the Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury (DILI guidelines) classification, severe liver injury (≥ grade 2) accounted for 34.5% (10/29). All 29 patients discontinued the treatment of ICIs after occurrence of IMLI, and 28 patients were treated with glucocorticoids, 7 of which were combined with mycophenolate mofetil and/or human immunoglobulin and artificial liver; 22 patients (75.9%) were improved. In the other 7 patients that did not recover, 4 discharged automatically, 2 died, and 1 could not be judged. ICI was rechallenged in 3 patients after liver function improvement, and IMLI did not recur. Conclusions:The IMLIs often occur 2 to 3 months after the start of ICI treatment, the most common clinical type is hepatocyte type, and the severity of clinical symptoms in patients vary from mild to severe. After discontinuing ICIs and receiving glucocorticoid treatments, most patients may have a good prognosis.
