2023 Volume 25 Issue 11 Published: 28 November 2023
  

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  • Cui Jiali, Niu Yurong, Liu Ning, Wang Huiyun, Song Shanai, Zhang Chuantao, Zhang Xiaochun, Hou Helei
    Abstract ( ) PDF ( )
    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.
  • Wang Xinyu, Zhang Yundi, Li Yue, Zong Huiying, Han Wenqian, Liu Lun, Wang Qian, Guo Lubo, Di Huifeng, Zhen Xiaohui, Sun Deqing, Su Ying, Zhang Zonglin, Peng Jing, Cao Xiaofu, Liu Ning, Liu Jian, Lu Cuicui, Wang Li, Geng Tao, Li Rongji, Sun Guodong, Zhang Fan, Zhang Lin, Ma Chuanjiang, Tan Siyuan, Qian Dongfang, Li Yan
    Abstract ( ) PDF ( )
    Objective To compare the efficacy and safety of insulin degludec and insulin glargine U100 in patients with type 2 diabetes mellitus. Methods This study was a retrospective cohort study. The subjects were patients with type 2 diabetes mellitus who were hospitalized in 13-3A-level general hospitals in Shandong Province from September 2018 to December 2021. According to the type of basal insulin used, the patients were divided into insulin degludec group and insulin glargine U100 group. The basic information and laboratory test results in patients in the 2 groups were collected, the differences of fasting blood glucose level and incidence of hypoglycemia between the 2 groups were compared. The patients with complete blood glucose monitoring data in the 2 groups were selected and their blood glucose fluctuations were compared. Results A total of 1-152 patients were entered in the study, including 552 patients in the insulin degludec group and 600 patients in the insulin glargine U100 group. The difference in the basic conditions in patients in the 2 groups was not statistically significant (all P>0.05). After treatment, the fasting blood glucose levels in patients in the 2 groups were lower than those before treatment, with statistically significant differences [10.2 (8.8, 12.5) mmol/L vs. 7.5 (6.6, 8.7) mmol/L, Z=-19.443, P<0.001; 10.0 (8.6, 11.7) mmol/L vs. 7.8 (6.6, 9.0) mmol/L, Z=-15.449, P<0.001], but the difference in fasting blood glucose levels between the 2 groups after treatment was not statistically significant (Z=-1.427, P>0.05). The incidence of hypoglycemia in the insulin degludec group was lower than that in the insulin glargine U100 group [1.09% (6/552) vs. 2.83% (17/600), Z=4.481, P=0.032]. The intraday blood glucose standard deviation, maximum blood glucose fluctuation range, postprandial blood glucose fluctuation range, and average blood glucose fluctuation range in patients with complete blood glucose monitoring data in the insulin degludec group were significantly lower than those in the insulin glargine U100 group [(1.7±0.6) mmol/L vs. (2.4±1.0) mmol/L, (4.5±1.6) mmol/L vs. (6.7±2.9) mmol/L, (1.8±1.0) mmol/L vs. (3.3±1.2) mmol/L, (2.9±1.3) mmol/L vs. (4.6±2.1) mmol/L; all P<0.001]. Conclusion The efficacy of insulin degludec in the treatment of type 2 diabetes mellitus is equivalent to that of insulin glargine U100, but the risk of hypoglycemia and blood glucose fluctuation is lower.
  • Zhang Yalan, Hong Wencong, Chen Qiying
    Abstract ( ) PDF ( )
    Objective To mine the risk signals of ipilimumab-related adverse events (AEs) and provide reference for the safe use in clinical practice. Methods AE reports with ipilimumab as the primary suspect drug were collected from US FDA Adverse Event Reporting System database during March 1, 2011 to September 30, 2022. AEs were standardized and classified according to the preferred term (PT) and system organ class (SOC) in Medical Dictionary for Regulatory Activites version 26.0. The AE risk signals of ipilimumab were mined using reporting odds ratio (ROR) method. An AE with reports≥3, ROR≥2, 95% confidence interval (CI) lower limit of ROR>1 was defined as a risk signal. Risk signals were analyzed using descriptive method. Results A total of 12-329 AE reports were entered in the analysis, involving 1-915 PTs. Two hundred and sixty-eight risk signals (PTs) were obtained using ROR method, involving 21 SOCs. The top 10 PTs in report number were diarrhea, colitis, rash, fever, hypophysitis, adrenal insufficiency, decreased appetite, hypothyroidism, liver disease, and dehydration, all of which were common AEs in the labels. The top 10 PTs in signal intensity were hypophysitis, lymphocytic hypophysitis, immune-mediated dermatitis, immune-mediated adrenal insufficiency, hypopituitarism, immune-mediated liver disease, adrenocorticotropic hormone deficiency, immune-mediated encephalitis, autoimmune colitis, and immune-mediated hyperthyroidism. The SOCs involved were endocrine system diseases, skin and subcutaneous tissue diseases, hepatobiliary system diseases, gastrointestinal system diseases, and nervous system diseases. A total of 36 PTs were not included in the labels, and the top 5 in signal intensity were intracranial tumor hemorrhage, radiation necrosis, malignant pleural effusion, pulmonary granuloma, and lichenoid keratosis. Conclusions The main AEs of ipilimumab are diarrhea, colitis, rash, etc. In addition, ipilimumab might cause adverse reactions such as intracranial tumor hemorrhage, radiation necrosis, and malignant pleural effusion that are not recorded in label, which should be vigilant in clinical practice.
  • Tang Yang, Ma Yanbin, Wang Shuyun, Guo Qian, Yin Donghong, Duan Jinju
    Abstract ( ) PDF ( )
    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.
  • Li Huibo, Zhao Zhe, Yang Canyu, Cheng Yinchu, Liu Fang, Zhu Yizhun, Lu Jie, Wei Yuan, Han Tongyan, Zhao Rongsheng
    Abstract ( ) PDF ( )
    Objective To explore and establish a standardized clinical thinking mode and decision-making pathway for lactation medication consultation services and ensure the harmonization and safety of medication for lactating women. Methods Lactation medication consultation services for medical staffs conducted by pharmacists from June 2020 to August 2022 in Peking University Third Hospital were analyzed using methods of retrospective statistical analysis and root cause analysis. Application of mixed methods were used to establish a clinical thinking model for medication use during lactation and a clinical pathway for safe medication use during lactation. Lactation medication consultation service training for pharmacists was provided, questionnaire surveys before and after the training were conducted, and the effectiveness of improvement was evaluated. Results A total of 1-218 medication consultation services provided by clinical pharmacists to medical staffs were collected in the hospital, including 44 cases (3.61%) related to lactation medication. Retrospective analysis showed that clinical pharmacists did not have a clear understanding of patients′ needs, incomplete consideration of drug-maternal-infant factors, and a limited way to retrieve information in the lactation medication consultation service. Based on the root cause analysis of the problems, a clinical thinking mode of “Questions (Q), Assessment (A), Search (S), and Plan (P)" (QASP) were established. Additionally, a clinical pathway for safe medication decision-making analysis and a standard medication consultation  record template was developed. Compared with before training, clinical pharmacists made significant progress in clarifying factors related to lactation medication, evidence-based procedure, standardized documentation, and confidence in providing medication consulations (all P<0.001). Conclusion The establishment of the QASP clinical thinking model and decision analysis model, based on the 3 factors of medication, mother, and baby for the consultation service of safe medication during lactation, can help clinical pharmacists carry out standardized medication consultation services for breast-feeding  populations during lactation, and improve the quality of homogeneous pharmaceutical services.
  • Rao Zhifang, Tu Jing, Cheng Zhenling
    Abstract ( ) PDF ( )
    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.
  • Wang Xin, Liu Chen, Zhang Yanhong, Ji Bingxin, Cai Haodong
    Abstract ( ) PDF ( )
    Conducting quality evaluation of adverse drug reaction(ADR) case report and obtaining accurate, objective and scientific data is related to the level and quality of the entire monitoring work, and is an important basis for drug regulatory departments to formulate safety regulatory measures. The research progress and application status of the methodology of quality evaluation of ADR reports abroad were investigated through literature search in this paper. It mainly includes 3 different evaluation methods (WHO quality evaluation method, clinical documentation tool, ADR report quality algorithm) from Uppsala Monitoring Centre, Netherlands and Australia. There are currently 2 versions of ADR report quality evaluation methods in China, which are included in the appendices of the 2005 and 2012 editions of the "Adverse Drug Reaction Reporting and Monitoring Work Manual". Different ADR report quality evaluation methods have different focus points, and it is necessary to develop a scientific evaluation method suitable to provide reference for the quality supervision and management of ADR in China.
  • Jin Meihua, Yang Xue, Hou Min, Li Yang, Zhang Pan, Xing Haiyan
    Abstract ( ) PDF ( )
    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.
  • Wan Suxin, Xiang Yi, Huang Gu, Xiao Yaping, Sun Qiuyan
    Abstract ( ) PDF ( )
    A 77 year-old female patient was treated with compound chlorhexidine gargle to rinse the pus cavity due to gingival abscess. After 10-minutes, the patient developed palpitation and pale face, followed by respiratory failure, undetectable blood pressure, inaccessible arterial pulsation, no spontaneous breathing, and disappearance of pupillary light reflex, which was considered as anaphylactic shock. Cardiopulmonary resuscitation, endotracheal intubation mechanical ventilation, intravenous infusion of dopamine, intravenous injection of epinephrine and other resuscitation were given immediately. About 40-minutes later, the patient returned to sinus rhythm (141 beats/min), blood pressure was 70/40-mmHg. The patient was transferred to the intensive care unit to continue the treatments such as fluid infusion, organ protection, mild hypothermia brain protection, prevention of epilepsy, correction of electrolyte disorders etc. Despite active rescue and treatments, the patient still died 6 days later due to a recurrence of cardiac arrest.
  • Huang Minjun, Bao Kun, Ma Weizhong, Yang Haifeng
    Abstract ( ) PDF ( )
    A 65-year-old male patient with stage Ⅳa lung adenocarcinoma had microscopic hema- turia for more than 10 years, and his urinary occult blood fluctuated between (+) and (++). Because his tumor target gene test showed that the epidermal growth factor receptor L858R mutation was positive, he received gefitinib 250-mg once daily orally. Laboratory tests before treatments showed albumin (ALB) 37.2-g/L, serum creatinine (Scr) 73-μmol/L, and urine occult blood (++). After 2 days of treatment, the patient developed generalized rashes, obvious foam urine, and severe edema of both lower limbs. Two weeks later, laboratory tests showed urinary occult blood (++++), urinary protein (++++), ALB 28.3-g/L, and Scr 111-μmol/L. The Scr peak value was 135-μmol/L and ALB trough value was 21.5-g/L. The drug eruptions and nephrotic syndrome caused by gefitinib were considered, gefitinib was discontinued, and symptomatic and supportive treatments were given. After 3 days, the rashes and edema gradually subsided, and the anti-tumor drug was switched to osimertinib. The pathological examination of renal puncture showed IgA nephropathy. Gefitinib-induced nephrotic syndrome on the basis of primary IgA nephropathy was considered. After 17 days, the patient′s rashes completely subsided and the edema was significantly improved. At 8 months of follow-up, the laboratory tests showed ALB 37.9-g/L, Scr 130-μmol/L, and urinary protein (++), suggesting that the renal injury had not yet fully recovered.
  • Li Anxia, Xue Shuyi, Zhao Bingqing, Ping Yaodong
    Abstract ( ) PDF ( )
    A 49-year-old male patient with primary hepatocellular carcinoma was treated with donafenib combined with tislelizumab. After 2 cycles of treatments, he developed persistent fever, poor appetite, fatigue, decreased white blood cells, hemoglobin, platelets, and fibrinogen, and significant increase of serum ferritin(91-501-μg/L) and splenomegaly. Hemophagocytic lymphohistiocytosis was diagnosed, which was consideredto be caused by tislelizumab. He received intravenous infusion of methylprednisolone 60-mg/d for 4 days, 40-mg/d for 7 days, 28-mg/d for 5 days, and at last, oral prednisone 35-mg/d was given, with dose reduction to discontinuation within 4-6 weeks. During the treatment, his laboratory tests results were improved. The patient did not use tislelizumab again and donafenib treatment was reused, and the above symptoms did not recur.
  • Yao Hairong, Liu Shikai
    Abstract ( ) PDF ( )
    A 58-year-old female patient underwent ovarian cancer tumor cell reduction surgery for advanced ovarian serous carcinoma in stage ⅣB for more than 3 years and received chemotherapy with paclitaxel and carboplatin regimen for a total of 6 cycles and chemotherapy with doxorubicin liposome and carboplatin regimen for a total of 6 cycles successively. After that, olaparib 300-mg was administered twice daily orally for maintenance treatment. Twenty-five days later, due to the occurrence of grade Ⅱ bone marrow suppression in the patient, the dose of olaparib was reduced to 150-mg in the morning and 300-mg in the evening. After 13 months of olaparib treatment, the patient developed pancytopenia, with the lowest platelet count of 2×109/L. Olaparib was stopped immediately.The symptomatic and supportive treatments such as infusion of suspended red blood cells and fresh platelets, elevation of white blood cells,iron replenishment, and platelet elevation were given, but the efficacy was not obvious. Bone marrow flow cytometry detection suggested a high possibility of myelodysplastic syndrome. After discontinuing olaparib for 47 days, the patient died of circulatory failure due to massive abdominal and pelvic bleeding and hemorrhagic shock.