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.
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.
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.
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 2×10 9/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.
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.
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.
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.
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.
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.
Objective:To investigate the prevalence, clinical characteristics, risk factors, and prognosis of chronic drug-induced liver injury (DILI).Methods:A multicenter, open, retrospective, non-interventional epidemiological survey was conducted. According to the inclusion criteria, patients with DILI and hospitalized in 308 hospitals in China from January 1, 2012 to December 31, 2014 were enrolled, and medical records of the patients were collected. The patients with DILI were divided into chronic and acute DILI groups. The clinical characteristics, laboratory tests, and prognosis in patients of the 2 groups were compared, and the suspected drugs that induced the liver injury were analyzed. Univariate and multivariate logistic regression analyses were used to analyze the influencing factors of chronic DILI.Results:A total of 25 927 patients were enrolled in the study, including 22 556 (87%) with acute DILI (acute DILI group) and 3 371 (13%) with chronic DILI (chronic DILI group). In the chronic DILI group, there were high proportion of women and the patients were older in age; more patients were with a history of liver disease and the time from medication to DILI was longer; more patients had digestive system symptoms (including loss of appetite, abdominal distension, nausea, vomiting, etc.), fatigue, jaundice, pruritus, liver pain/discomfort, bleeding tendency; the alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and international normalized ratio were higher, while the serum albumin and platelet counts were lower; the proportion of patients with model for end-stage liver disease score ≥ 15 was higher; the all-cause mortality rate and liver disease-related mortality rate were higher, compared with the acute DILI group. The differences above-mentioned were statistically significant (all P<0.05). Multivariate logistic regression analysis showed that male was protective factor [odds ratio ( OR)=0.76, 95% confidence interval ( CI): 0.69-0.83], while previous liver disease history ( OR=2.00, 95% CI: 1.82-2.19) and hypoalbuminemia ( OR=0.96, 95% CI: 0.95-0.96) were independent risk factors for chronic DILI. Conclusions:In the study period, the proportion of chronic DILI among DILI inpatients is 13.0% in the 308 hospitals. Compared with those with acute DILI, more chronic DILI patients were female, and patients with chronic DILI have higher ages, severer conditions, and poorer prognoses; female, previous liver disease history, and hypoalbuminemia are independent risk factors for chronic DILI.
A 20-year-old female patient took compound Zaoren capsules (containing processed ziziphi Spinosae Semen and L-tatrahydropal matine, 1 capsule at bedtime, 12 capsules in total) by herself intermittently due to insomnia. Fifteen days later, she developed fatigue and dark yellow urine. Laboratory tests showed total bilirubin (TBil) 62 μmol/L, direct bilirubin (DBil) 49 μmol/L, alanine aminotransferase (ALT) 1 658 U/L, aspartate aminotransferase (AST) 1 525 U/L, γ-glutamic trans-ferase (GGT) 160 U/L, alkaline phosphatase (ALP) 149 U/L, and total bile acid (TBA) 90.2 μmol/L. She received liver-protective treatments. After 30 days, the symptoms of fatigue and dark yellow urine were relieved, and laboratory tests showed TBil 24 μmol/L, DBil 13 μmol/L, ALT 54 U/L, AST 68 U/L, GGT 170 U/L, and ALP 90 U/L. Nine months later, the patient took compound Zaoren capsules (1 capsule/4 d, 3 capsules in total) again due to insomnia. Fourteen days later, the patient developed yellow sclera and dark yellow urine, and laboratory tests showed TBil 44 μmol/L, DBil 29 μmol/L, ALT 2 041 U/L, AST 1 152 U/L, GGT 110 U/L, ALP 155 U/L, and TBA 28.0 μmol/L. The liver-protective treatments were given again, and the symptoms of yellow sclera and urine were relieved 18 days later. Laboratory tests showed ALT 199 U/L, AST 78 U/L, and GGT 55 U/L. The liver injury is considered to be caused by tetrahydropalmatine in compound Zaoren capsules.
Objective:To explore the occurrence and clinical characteristics of liver injury caused by immune checkpoint inhibitors (ICI) in cancer patients.Methods:Medical records of cancer patients with normal liver function who used ICI during hospitalization in Beijing Friendship Hospital from January 2017 to December 2022 were collected, and those with liver injury related to ICI were screened out. The basic information of patients with ICI-related liver injury, treatment regime of ICI, concomitant medication, liver function before and after medication, intervention measures and outcomes were extracted, and the clinical characteristics of ICI-related liver injury were analyzed descriptively.Results:A total of 155 patients with solid tumors were treated with ICI within the set time, of which 15 (9.7%) were diagnosed with ICI-related liver injury. Among the 15 patients, there were 6 males and 9 females, with a median age of 59 (41, 76) years. The suspected drug causing liver injury was camrelizumab in 5 patients, sugemalimab in 2 patients, serplulimab in 2 patients, toripalimab in 2 patients, sintilimab in 2 patients, penpulimab in 1 patient, and cadonilimab in 1 patient. All 15 patients received combined medication, such as traditional chemotherapy drugs, receptor tyrosine kinases inhibitors, and/or other ICIs. The median time from suspected ICI administration to liver injury in 15 patients was 22 (4-64) days, and the liver injury occurred after the first cycle of ICI treatment in 9 patients. The medians of peak value of alanine aminotransferase and aspartate aminotransferase were 157 (15-508) U/L and 131 (77-696) U/L, respectively; the total bilirubin was more than 2 times of the upper limit of normal in 3 patients. The liver injury was classified as hepatocellular type in 6 patients, cholestasis type in 5 patients, and mixed type in 3 patients; the type was unable to be determined due to lack of data in 1 patient. Among the 15 patients, 8 had liver injury of grade 2 and 7 had liver injury of grade 3; the suspected medication were discontinued after liver injury occurrence in 9 patients and did not discontinue in 6 patients. Seven and 5 patients recovered or basically had normal liver function after 1-4 months, respectively among those who stopped and did not stop ICI; the liver function did not return to normal in the other 3 patients at 2 to 9 months of follow-up.Conclusions:ICI-related liver injury usually occurs after the first cycle of ICI treatment (within 1-2 months of medication), and the severity is mostly grade 2 or 3. The 3 clinical types of drug-induced liver injury (hepatocellular type, cholestatic type, and mixed type) are clinically visible. After the occurrence of liver injury, most patients have a good prognosis through timely discontinuation and/or treatments.
A 77-year-old male patient with lung cancer developed creatine kinase (CK) 887 U/L, CK-MB 89 μg/L, and high-sensitivity troponin I (hs-TnI) 43 750.1 ng/L, and ECG showed multilead ST-segment elevation after 2 cycles of combination chemotherapy with camrelizumab. The patient did not undergo the 3rd cycle of anti-tumor treatment. Clinical pharmacists participated in consultations and assisted physicians in analyzing the patient's medication. The causality between camrelizumab and the adverse event was considered as "possible" and the patient was diagnosed as immune myocarditis grade G3, receiving intravenous injection of 1 000 mg methylprednisolone pulse therapy once daily. Clinical pharmacists assisted physicians in reviewing data and developing glucocorticoid reduction plans. The dosage was reduced to 500 mg once daily after 2 days of pulse therapy. The patient's myocardial enzymes continued to decrease after glucocorticoid reduction. After 3 days, the dosage of methylprednisolone was reduced to 40 mg by intravenous injection once every 12 hours for 7 days. The patient's hs-TnI decreased to 2 248.6 ng/L. Methylprednisolone was changed to prednisone 40 mg twice daily orally. The physician's advice for prednisone dose reduction: reduce the dosage by 10-20 mg per week, monitor myocardial enzymes every week, and when the dosage is reduced to 10 mg/d, and if the myocardial enzymes return to normal, maintain it for 1-2 weeks before discontinuation. The patient followed the doctor's advice and successfully stopped medication, and no glucocorticoid-related adverse reactions and cardiac discomfort recurred. The patient did not receive immunotherapy again.
Objective:To investigate the current status of polypharmacy among elderly outpatients with 4 types of chronic diseases such as hypertension, diabetes mellitus, coronary atherosclerotic heart disease, and cerebrovascular disease.Methods:A retrospective study was conducted on the drug use of elderly (≥65 years old) outpatients with hypertension, diabetes mellitus, coronary atherosclerotic heart disease, and cerebrovascular disease with data of Beijing Municipal Health Insurance Centre database from July 2017 to September 2017. The included patients had at least 1 of 4 types of chronic diseases. Polypharmacy was defined as ≥5 different types of medication at the first visit, and non-polypharmacy was defined as <5 types of medication. The number and severity of comorbidity were quantified using the Charlson Comorbidity Index (CCI), and the prognosis of patient was evaluated at 4 levels of 0, 1, 2, and ≥3 scores. The larger the value, the more severe the disease. Based on the Beers Criteria 2015, the potential inappropriate medication (PIM) was identified using the prescription review system of Puhua Health.Results:A total of 405 608 patients were included in this study, with a median age of 74 (65-107) years, and 204 219 patients (50.35%) were female. According to the type of medication used by patients, they were divided into polypharmacy group (113 594 cases, 28.01%) and non-polypharmacy group (292 014 cases, 71.99%). The CCI of the polypharmacy group was significantly higher than that of the non-polypharmacy group ( P<0.001). The proportion of patients with 0, 1, 2, and ≥3 scores in the polypharmacy group was significantly higher than that of the non-polypharmacy group, and the differences were statistically significant (all P<0.001). In terms of comorbidity, the proportions of patients among the 4 types of chronic diseases were higher in the polypharmacy group than in the non-polypharmacy group ( P<0.001). In terms of concomitant diseases, the proportion of patients with hyperlipidemia, cognitive impairment, heart failure, and osteoporosis in the polypharmacy group was higher than that in the non-polypharmacy group (all P<0.001). In terms of medical treatment behaviour, the median number of medical visits was higher in the polypharmacy group than in the non-polypharmacy group [2(1,3) vs. 1(1,2), P<0.001]. In terms of evaluating the unsuitability of medication, the proportion of patients with PIM in the polypharmacy group was higher than that in the non-polypharmacy group, including repeated medication [4.60% (5 227/113 594) vs. 1.64% (4 486/292 014)], contraindications [2.97% (3 376/113 594) vs. 1.13% (3 294/292 014)], interactions [6.51% (7 399/113 594) vs. 1.94% (5 658/292 014)], and lack of indications [22.39% (25 432/113 594) vs. 13.54% (39 543/292 014)], and the differences were all significant (all P<0.001). In terms of drug use categories, the top 5 most commonly prescribed drugs in the polypharmacy group were HMG-CoA reductase inhibitors (68 318 cases, 60.14%), dihydropyridines (60 951 cases, 53.66%), angiotensin receptor antagonists(45 050 cases, 39.66%), β-receptor blockers (25 675 cases, 22.60%) and sulfonylureas (16 023 cases, 14.11%). Conclusions:Polypharmacy is common in elderly patients with hypertension, diabetes mellitus, coronary artery disease, and cerebrovascular disease. The elderly patients with polypharmacy have a worse baseline status and more problems with PIM.
Objective:To understand the adverse event (AE) risk signals of 3 anti-disialoganglioside 2 (GD2) monoclonal antibodies, including dinutuximab, dinutuximab beta, and naxitamab, and to provide reference to clinical use.Methods:AE reports with dinutuximab, dinutuximab beta, and naxitamab as the primary and secondary suspect drug were collected from the US FDA Adverse Event Reporting System (FAERS) database during 2015 to the 2nd quarter of 2023. AEs were standardized and classified according to the preferred term (PT) and system organ classification (SOC) in the International Medical Terminology Dictionary, Version 25.0, and AE risk signals were mined using the reporting odds ratio (ROR) method and information component (IC) method. The AE reports information and AE risk signals of 3 GD2 monoclonal antibodies were descriptively analyzed.Results:A total of 630 AE reports were collected, in which the 3 GD2 monoclonal antibodies were the primary and secondary suspect drugs, including 465 reports of dinutuximab, 61 reports of dinutuximab beta, and 104 reports of naxitamab, which involved 341, 24, and 125 PTs and mapped to 19, 2, and 12 SOCs, respectively. The AEs of the 3 GD2 monoclonal antibodies were associated with the occurrence of death, life-threatening, hospitalization, or prolonged hospitalization adverse outcomes. Signal mining using ROR and IC methods detected a total of 142, 3, and 30 AE risk signals, of which 73, 0, and 6 were not documented in the corresponding drug instructions, respectively. The top PTs in report number were fever for both dinutuximab and dinutuximab beta, and hypotension and pain for naxitamab; the top PTs in signal intensity were puncture site abscess, device related bacteraemia, and wheezing for dinutuximab, dinutuximab beta, and naxitamab, respectively. The overlapping AE risk signals for the 3 drugs were fever and pain, with dinutuximab having the strongest signal intensity for fever and naxitamab having the strongest signal intensity for pain. Among the top 30 PTs in report number, naxitamab had significantly more AE risk signals than dinutuximab in respiratory, thoracic, and mediastinal disorders, skin and subcutaneous tissue disorders, immune system disorders, and vascular disorders. For naxitamab, the PTs that differed from dinutuximab′s AE risk signals and were not documented in the naxitamab drug instructions were respiration abnormal, cyanosis, and metabolic acidosis.Conclusions:Fever, pain, and hypotension are common AEs for the 3 GD2 monoclonal antibodies. Naxitamab causes significant pain; respiration abnormal, cyanosis, and metabolic acidosis are AE risk signals specific to naxitamab and not documented in the drug instruction, which warrant clinical vigilance and prompt intervention.
Objective:To explore the adherence and its influencing factors of tegafur, gimeracil and oteracil potassium (S-1) treatment in patients with tumor-node-metastasis (TNM) stage Ⅲ gastric cancer after operation.Methods:Medical records of adult patients with stage Ⅲ gastric cancer after operation in the Second Affiliated Hospital of Nanjing University of Chinese Medicine from October 2018 to April 2022 and treated with oral S-1 were collected, and the S-1 adherence and its related factors in these patients were retrospectively analyzed according to their S-1 treatment information. Good adherence was defined as completing 8 cycles of S-1 treatment within 186 days (14 days of continuous medication and 7 days of discontinuation as 1 cycle). The patients were divided into good and poor S-1 adherence groups. Univariate and multivariate logistic regression analysis were performed to analyze the factors affecting S-1 adherence of patients.Results:A total of 148 patients were entered in the study, including 116 males (78.4%) and 32 females (21.6%), with a median age of 67 (27-85) years. Sixty-nine patients (46.6%) completed ≥ 8 cycles of S-1 treatment within the set time and had good adherence; 79 (53.4%) patients had poor adherence. The reasons for interruption or failure to complete treatments as scheduled in the 79 patients were serious adverse reactions in 30 (38.0%) patients, refusal to treat in 27 (34.2%) patients, and poor curative effect in 22 (27.8%) patients. Univariate and multivariate logistic regression analysis showed that lack of or partial understanding of the disease [odds ratio ( OR)=5.368, 95% confidence interval ( CI): 1.488-19.370, P= 0.010; OR=3.393, 95% CI: 1.309-8.793, P=0.012], gastric cancer with a course of less than 1 year ( OR=10.214, 95% CI: 2.400-43.472, P=0.002), and TNM stage Ⅲa ( OR=3.879, 95% CI: 1.522-9.886, P=0.005) were the independent influencing factors of poor adherence to S-1 treatment in patients with gastric cancer. Conclusions:Less than half of the gastric cancer patients with stage Ⅲ after operation had good adherence to S-1 treatment. Insufficient understanding of the disease, short duration of gastric cancer, and TNM stage Ⅲa were independent influencing factors for poor adherence to S-1 treatment in gastric cancer patients. Increasing patients′ understanding of the disease and strengthening patient education may be important strategies to improve S-1 treatment compliance.
