A perfect pharmacovigilance database is the core pillar of pharmacovigilance activities. At present, the United States, Japan, Europe, and the World Health Organization have all established comparatively mature pharmacovigilance databases, which have played an important role in adverse drug reaction (ADR) monitoring, ADR signal mining, and post marketing re-evaluation of drugs. This paper summarizes the data sources, data accessibility, available elements, data quality control, and data utilization status of the 4 major databases mentioned above, so as to provide references for clinical pharmacovigilance activities and improvement of the construction of pharmacovigilance database in China.

A 78-year-old female patient with atrial fibrillation developed tarry stools after regularly taking dronedarone, metoprolol, and rivaroxaban for 3 months. The patient stopped using rivaroxa- ban by herself for 7 days, and her black stools was gradually improved. After taking rivaroxaban again for 1 month, black stools appeared again, accompanied by fatigue, dizziness, and amaurosis fugax. Her blood pres- sure was 90/50-mmHg, heart rate was 80 beats/min, and hemoglobin was 55-g/L. Rivaroxaban was discon- tinued again and supportive treatments such as soft food, acid suppression, fluid replacement, and blood transfusion were given. After 3 days of treatments, the symptoms of fatigue were improved significantly, and no amaurosis recurred when sitting up. Hemoglobin was 75-g/L. After 6 days of treatments, the patient dis- charged formed yellow soft stools. After excluding gastrointestinal tumors through gastroscopy and tumor mar- ker examination, it was considered that the interaction of dronedarone and rivaroxaban caused the increase of rivaroxaban plasma concentration, which resulted in gastrointestinal bleeding in the patient. The patient′s anticoagulant medication was changed to dabigatran etexilate, and no gastrointestinal bleeding occurred.

Signal detection of adverse drug reaction (ADR) is an important research method in post marketing pharmacovigilance. In recent years, the number of literature on ADR signal detection in China has increased significantly. However, there are still many problems in this kind of research, such as unclear understanding of the concept of ADR signal, unclear purpose of signal detection research, limited signal source, inadequate processing of data in detection, unduly single data mining algorithm, unduly short time period in data selection, and no processing and analysis on bias in signal detection. This paper provides some views on these common problems in order to improve the quality of ADR signal detection research in China.

A 25-year-old woman received subcutaneous injection of semaglutide injection (semaglutide) 0.5-mg by herself for weight loss. She developed nausea and vomiting after medication but did not pay much attention to. On the 2nd week, semaglutide 1-mg was injected subcutaneously. Symptoms such as nausea and vomiting were aggravated, followed by stomach pain and distension, which could not be relieved. Laboratory tests showed alanine aminotransferase (ALT) 1-687-U/L, aspartate aminotransferase (AST) 809-U/L, alkaline phosphatase (ALP) 167-U/L, total bile acid (TBA) 178.8-μmol/L, total bilirubin (TBil) 106.3-μmol/L, direct bilirubin 64.0-μmol/L, and indirect bilirubin (IBil) 42.3-μmol/L. After excluding causes like viral hepatitis, autoimmune liver disease, obstructive jaundice, and concomitant drugs, acute liver injury caused by semaglutide was considered, and liver-protective treatments were given. Due to poor therapeutic effects, artificial liver treatment was given once, and then liver protective treatments were continued. On day 17 of treatment, laboratory tests showed ALT 579-U/L, AST 583-U/L, ALP 180-U/L, TBA 231.8-μmol/L, TBil 344.8-μmol/L, DBil 233.8-μmol/L, and IBil 111.0-μmol/L. After 6 months of treatments, the patient′s liver function returned to normal, with laboratory tests results of ALT 56-U/L, AST 33-U/L, ALP 99-U/L, TBA 2.7-μmol/L, TBil 10.5-μmol/L, DBil 3.2-μmol/L, and IBil 7.3-μmol/L.

Objective To explore the effects of pharmaceutical services through enterprise WeChat for outpatients with cancer pain.　Methods A retrospective study was conducted on patients who were first diagnosed and/or previously treated for cancer pain and visited Outpatient Department of the First Affiliated Hospital of Soochow University from January 1, 2020 to January 30, 2023. The outpatients were divided into conventional pharmaceutical services management group (conventional group) and pharmaceutical services management group through enterprise WeChat (enterprise WeChat group) based on whether they received pharmaceutical services for cancer pain through enterprise WeChat. Prescription appropriateness, changes in cancer pain and life quality evaluation indicators after treatment in patients between the 2 groups were recorded and compared.　Results A total of 174 patients were included, with 87 patients in each group. There were no significant differences in age and gender between the 2 groups (all P>0.05). Before the pharmaceutical services management for cancer pain through enterprise WeChat, the differences in the proportion of patients with pain free, mild, moderate, and severe pain after pain relief treatments between the 2 groups were not significant (all P>0.05). In the conventional group, 13 out of 87 patients (14.9%) had inappropriate prescriptions, and 2 out of 87 (2.3%) in the enterprise WeChat group, with statistically significant difference (χ2=8.828, P<0.05). After management with enterprise WeChat, the patients of pain-free increa- sed from 19 to 55 (63.2%) in the enterprise WeChat group, and from 18 to 41 (47.1%) in the conventional group. The difference in the proportion of pain-free patients between the 2 groups was statistically significant (χ2=4.555, P=0.033). The differences in the scores of various indicators of life quality between the 2 groups before management with enterprise WeChat were not significant (all P>0.05). After the management with enterprise WeChat, life quality scores in all the 8 dimensions were significantly higher than those in the conventional group (all P<0.05).　Conclusion The utilization of enterprise WeChat could improve the treatment effect of cancer pain, enhance their life quality, help improve the quality of pharmaceutical services, and have certain promotion and utilization value.

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.

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 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 provide a basis for the selection of antiemetic regimen by establishing an artificial intelligence model for predicting chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving platinum-based chemotherapy with high emetic risk.　Methods The clinical information on cancer patients who received cisplatin or carboplatin with area under the blood concentration-time curve (AUC) ≥4 and registered in the Department of Oncology, Tianjin Medical University General Hospital from January 2018 to December 2022 was collected, including gender, age, history of alcohol consumption, history of vomiting in pregnancy, chemotherapy cycle, patient expects to have CINV, chemotherapeutic agents, antiemetic regimen, out-of-hospital antiemetic treatment, sleep of less than 7 hours on the night before chemotherapy, occurrence of CINV in the previous cycle, and creatinine clearance (Ccr). After pre-proces- sing, the data were randomly divided into the training set and the test set. The training set was used to construct the prediction model, and the test set was used to evaluate the prediction efficiency of the model. Three algorithms, gradient boosting decision tree (GBDT), random forest (RF), and logistic regression (LR), were used to build a prediction model and evaluate the model performance, respectively. The evaluation metrics included accuracy, sensitivity, recall, F1 value (the reconciled mean of sensitivity and recall), and area under the receiver operating characteristic curve (AUROC). Finally, Shapley Additive exPlanation (SHAP) was applied to analyze the interpretability of the clinical features with predictive significance.　Results A total of 698 patients, 439 males (62.9%) with a median age of 64 (21, 84) years, were included in this study and received a total of 1-654 cycles of chemotherapy. The chemotherapy regimen contained cisplatin in 364 cases with 864 cycles of chemotherapy, and carboplatin with AUC ≥4 in 361 cases with 790 cycles of chemotherapy. The number of treatment cycles in which neurokinin-1 receptor antagonist (NK-1 RA), 5-hydroxytryptamine-3 receptor antagonist (5-HT3 RA), and dexamethasone were selected as the antiemetic regimen was 1 347, and in those with the selection of 5-HT3 RA and dexamethasone was 307. The Spearman′s correlation analysis showed no strong correlation between the feature variables in the patients, and all of them could be used for model building. GBDT optimal hyperparameters n_estimators=500, max_depth=9; RF optimal hyperparameters max_depth=5; LR optimal hyperparameters penalty=L2. Three prediction models, GBDT, RF and LR, were established based on the optimal hyperparameter training data, respectively. The accuracy of GBDT model was 0.903, sensitivity was 0.882, recall was 0.903, F1 value was 0.883, and AUROC was 0.778±0.036 (95%CI: 0.739-0.814); the accuracy of RF model was 0.885, sensitivity was 0.861, recall was 0.885, F1 value was 0.870, and AUROC was 0.679±0.041 (95%CI: 0.636- 0.720); the LR model had an accuracy of 0.817, a sensitivity of 0.851, a recall of 0.817, an F1 value of 0.832, and an AUROC of 0.682±0.042 (95%CI: 0.639-0.723). Ccr, age, chemotherapy cycle, history of alcohol consumption, and patient expects to have CINV were the main features predicted by the model. The risk of CINV was negatively associated with Ccr, age, and chemotherapy cycle. And the risk of CINV was lower in patients with no history of drinking alcohol and patient expects to have CINV.　Conclusion The GBDT, RF, and LR models could all predict the risk of CINV in patients receiving platinum-based chemotherapy with high emetic risk, with the GBDT model having the best predictive effect.

A 66-year-old male patient with chronic bronchitis for more than 50 years received 0.1 g of aminophylline once or twice daily orally. Because of cough and runny nose, he took 1 compound parace- tamol and amantadine hydrochloride tablet twice daily orally and added the dose of aminophylline to 0.2 g twice daily by himself. After 3 days of medication, the patient experienced sudden unconsciousness and limb convulsions without any triggering factors, with a total of 6 episodes. The results of brain magnetic resonance imaging and electroencephalography were normal. The possibility of intracranial infection could be ruled out through cerebrospinal fluid examination. Laboratory test showed creatine kinase (CK) 1-574-U/L. After 4 days of experimental treatments with haloperidol, piperacillin sodium, tazobactam sodium, budesonide suspen- sion, etc., his CK was 217-U/L and no further seizures occurred. The patient′s seizures were considered to be related to combination of compound paracetamol and amantadine hydrochloride, and aminophylline.

The theme of World Patient Safety Day 2023 is "Engaging Patients for Patient Safety". Encouraging patients (including patients′ families, caregivers, etc.) to voice in medication safety is one of the important measures of medication safety management and pharmacovigilance, which conforms to the principles of ethics and science and is adapted to the development of society. It has been widely recognized in the world that patients participate in the safety monitoring in drug clinical trial, adverse drug reaction reporting， and information communicating and safety supervising of drug safety, and act as partners with doctors and drug regulatory agencies in drug safety. China should also attach importance to and address the obstacles in patient participation in management of medication safety, and accelerate the process of patient participation in management of medication safety.

Objective To explore the risk signals of montelukast-related adverse events (AEs) in pediatric patients and provide reference for the safe use.　Methods AE reports of children with montelukast as the primary suspect drug from the first quarter of 2004 to the third quarter of 2022 were collected by searching the US FDA Adverse Event Reporting System database （FAERS）. AEs were standardized and classified according to the preferred terms (PT) and system organ class (SOC) of Medical Dictionary for Regulatory Activities 23.0. Proportional reporting odds ratio (PRR) method was used to mine the AE risk signals of montelukast. An AE with reports ≥3, PRR≥2, and χ2>4 was defined as a positive signal, which were analyzed using descriptive method.　Results A total of 5-179 AE reports were included in the analysis, involving 1-295 PTs, and 233 positive PTs were obtained by PRR method. The top 10 PTs in AE reports were aggres- sive behavior, anxiety, suicidal ideation, abnormal behavior, depression, anger, nightmares, insomnia, crying loudly and night terrors. Except crying loudly, all of them were adverse reactions recorded in the label. The top 10 PTs in signal intensity were sensory overload, arrhythmia, separation anxiety disorder, loneliness phobia, dust allergy, Mille-Fisher syndrome, eosinophilic granuloma complicated with polyangitis, personality disorder in children, night terrors and decreased platelet adhesion. Among them, abnormal heart rate, Mille-Fisher syndrome and decreased platelet adhesion were not recorded in the label. A total of 59 of the 233 positive PTs were not recorded in the label, involving 10 SOCs. The top 5 SOCs were social environment, mental illness, injury, poisoning and surgical complications, general conditions and administration site, and respiratory, thoracic and mediastinal diseases.　Conclusion The main AEs of pediatric patients receiving montelukast treatment in the US FAERS are aggressive behavior, anxiety, depression, insomnia, night terrors, etc., all of which are adverse reactions recorded in the label; adverse reactions not recorded in the drug label include abnormal heart rate, Miller-Fisher syndrome， and decreased platelet adhesion.

A 5-year-old and 4-month-old boy took duloxetine about 1-000-mg mistakenly. After 30-minutes, symptoms such as listlessness, vomiting, muscle tremor, disturbance of consciousness, agitation delirium, high fever, tachycardia, convulsions etc. occurred successively. Severe serotonin syndrome caused by duloxetine poisoning was diagnosed and treatments such as gastric lavage, catharsis, hemoperfusion, cyproheptadine, midazolam, and physical cooling were given. Twelve hours later, laboratory tests showed creatine kinase 674-U/L, myoglobin 247-mg/L, blood urea nitrogen 9.5-mmol/L, uric acid 452-μmol/L, serum creatinine 55-μmol/L; 36-hours later, the results were creatine kinase 674-U/L, blood urea nitrogen 10.3-mmol/L, uric acid 350-μmol/L, and serum creatinine 70-μmol/L. Coenzyme Q10 and vitamin C were given to protect organ function. Eight days later, the boy′s symptoms disappeared. Laboratory tests showed creatine kinase 149-U/L, myoglobin 66-mg/L, urea nitrogen 4.3-mmol/l, uric acid 75-μmol/L, and serum creatinine 34-μmol/L.

A 73-year-old male patient was treated with tacrolimus 2.5-mg twice daily combined with prednisone 5-mg once daily orally for anti-rejection after lung transplantation. Due to pulmonary aspergillus fumigatus infection, the patient received voriconazole 400-mg orally twice daily on the first day and then 200-mg twice daily from the next day. During this period, the patient continued to receive anti- rejection treatments. Three days after the application of voriconazole, the patient developed decreased urine output and fatigue, serum creatinine was 196-μmol/L, and tacrolimus trough concentration was 49.0-μg/L. Acute kidney injury caused by tacrolimus poisoning was considered. Under the monitoring of blood drug concentration, tacrolimus was discontinued intermittently for 3 days, then tacrolimus was reduced to 0.5-mg once daily and voriconazole was reduced to 150-mg twice daily. Seventeen days later, the patient had a 24- hour urine output of 950-ml, serum creatinine of 154-μmol/L, and tacrolimus trough concentration of 7.7-μg/L. Twenty-two days later, his serum creatinine decreased to 142-μmol/L. It was considered that the abnormal increase of tacrolimus blood trough concentration was related to the inhibited metabolism after combined use with voriconazole.

Objective To understand the current situation and problems of research design in adverse drug reaction (ADR) signal detection study in China.　Methods The literature on ADR signal detection study in SinoMed, CNKI, WanFang Data and VIP databases were retrieved (up to May 30, 2022). The research purpose, research direction (target drug, target ADR), source database of signals, target drug role, reference drug, signal detection algorithm, and bias control of the literature were analyzed descriptively one by one.　Results A total of 165 articles were included, of which 146 (88.5%) were published in core journals. From 2013 to 2022 (January to May, 2022), there were 4, 3, 2, 7, 8, 11, 20, 29, 55, and 26 relevant articles, respectively. Problems in these studies were as follows: research purposes were not clear in 6.7% (11/165) of the literature; target ADRs were selected as non targeted in 80.6% (133/165) of the literature; the domestic database was less utilized ［only 9.7% (16/165)］; did the selection range of the target drug role were not mentioned in 33.9% (56/165) of the literature; only a single algorithm for signal detection was used in 36.4% (60/165) of the literature; bias analysis was not conducted in 85.5% (141/165) of the literature.　Conclusions The domestic literature on ADR signal detection has problems of poor standardization in research design, such as unclear research purpose and direction, incomplete research items, etc. Chinese scholars should further improve the quality of research design while strengthening the research on ADR signal detection.

A 34-year-old male patient received a subcutaneous injection of 300 mg of secukinumab once a week for 5 times, subsequently 300-mg once every 4 weeks for 3 times because of psoriasis. Then the patient developed bloody purulent stool. Electronic colonoscopy revealed diffuse mucosal congestion and edema in the sigmoid colon at a distance of 25 cm from the anus. The pathological examination results of tissue biopsy showed severe chronic inflammation, erosion, and shallow ulcer formationin the sigmoid colon. Inflammatory bowel disease caused by secukinumab was considered. Then the drug was stopped, and mesalazine enema solution 60 g once daily was given. After half a month of treatment, the patient′s bloody purulent stool was improved significantly, and after 2 months, it disappeared. Electronic colonoscopy showed that the mucosa of the sigmoid colon was rough, granular, and scattered with small patches of bleeding at a distance of 20-cm to 25-cm from the anus, which was diagnosed as having ulcerative colitis (in remission). Mesalazine enema was discontinued and changed to mesalazine suppository 0.5 g once daily.

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.

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 hospitali- zation 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 investigate the risk of adverse event (AE) associated with inclisiran and to provide reference for the safe use in clinical practice.　Methods The AE reports in the US FDA Adverse Event Reporting System (FAERS) database from the 4th quarter of 2004 to the 2nd quarter of 2023 with inclisiran as the primary suspect drug were collected. AE was standardized and classified using the preferred terminology (PT) and the system organ class (SOC) of the Medical Dictionary for Regulatory Activities 26.0. AE risk signal mining was performed using the report odds ratio (ROR) method and the UK Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method. PT that was considered as an AE risk signal in both methods were defined as AE risk signals ［ROR method: ≥3 reports  and the lower limit of the 95% confidence interval (CI) of the ROR>1; MHRA comprehensive standard method: ≥3 reports、PRR ≥2 and χ2≥4]. A descriptive statistical analysis was performed.　Results A total of 1 888 AE reports were collected with inclisiran as the primary suspect drug, involving 1-888 patients and 835 PTs. The AE was predominantly reported in the United States (88.7%, 1 675/1 888), and predominantly by the consumer (62.1%, 1 171/1 886); there were a total of 484 reports (25.6%) about serious AE. Excluding non-drug and indication-related PTs, 85 PTs (involving 15 SOCs) met the criteria in both the ROR method and the MHRA comprehensive standard method, and defined as AE risk signals. The top 5 PTs ranked by the number of reports were arthralgia (248 cases), injection site pain (237 cases), limb pain (170 cases), myalgia (158 cases), and diarrhea (132 cases); the top 5 PTs ranked by the signal intensity included bladder discomfort (ROR=28.87, PRR=28.85), injection site discomfort (ROR=24.48, PRR=24.40), sinus pain (ROR=23.20, PRR=23.19), injection site vesicles (ROR=17.63, PRR=17.61), and injection site rash (ROR=12.51, PRR=12.45). Among the top 20 PTs ranked according to the number of reports and signal intensity respectively, 8 and 13 PTs were not documented in domestic and international specifications, of which myalgia and hypoacusis had more reports and stronger signal intensity.　Conclusion The main AE  of inclisiran in the US FAERS database were injection site reactions, followed by musculoskeletal-related AEs (arthralgia, myalgia, and myospasm, etc.) and infection-related AEs (such as urinary tract infections and bronchitis), which require clinical attention.

A 31-year-old woman received semaglutide injection subcutaneously for weight loss. Three months later, the electrocardiogram showed sinus tachycardia, and the laboratory tests showed triiodothyronine (T3) 2.75-nmol/L, thyroxine (T4) 199.86-nmol/L, free triiodothyronine (FT3) 11.31-pmol/L, free thyroxine (FT4) 46.63-pmol/L, thyroid-stimulating hormone (TSH)<0.005 mU/L. Considering the sinus tachycardia and hyperthyroidism caused by semaglutide injection, the drug was discontinued, and methimazole 10-mg orally, twice daily and metoprolol 25-mg orally twice daily were given. After treatment for more than 1 month, the electrocardiogram of the patient was normal, and the thyroid function examination showed T3-1.79-nmol/L, T4-127.33-nmol/L, FT3-4.94-pmol/L, FT4-15.87-pmol/L, and TSH<0.005 mU/L. However, there were elevated liver enzymes, showing alanine aminotransferase 327-U/L, aspartate aminotransferase 148-U/L, and γ-glutamyl transpeptidase 123.4-U/L. Then, methimazole and metoprolol were stopped, and silibinin 140-mg orally thrice daily combined with bicyclol 50-mg thrice daily were given. More than 1 month after treatments, the patient′s thyroid function and liver function were normal, and silibinin and bicyclol were stopped. After that, the thyroid function, liver function and electrocardiogram were all normal in repeated examinations.

Objective To mine and compare the adverse event (AE) signals of allopurinol and febuxostat and provide reference for the rational and safe use of the 2 drugs in clinic.　Methods The AE reports on allopurinol and febuxostat from January 1, 2009 to December 31, 2021 were collected by searching the US Food and Drug Administration Public Data Open Project (openFDA) database. AEs were classified using preferred term (PT) and systemic organ class (SOC) of the International Medical Terminology Dictionary 25.0. The AE risk signals of allopurinol and febuxostat were mined using the reporting odds ratio (ROR) method. The number of AE reports ≥3 and the lower limit of the 95% confidence interval (CI) of the ROR>1 was defined as a positive signal. The new AE risk signals of allopurinol and febuxostat were screened according to the drug labels. The radar chart was drawn according to the number of allopurinol and febuxostat risk signals. The positive PT signals were descriptively and statistically analyzed.　Results The number of AE reports of allopurinol and febuxostat were 105-532 and 9-949, respectively. The analysis of the top 100 AE reports were as follows. There were 82 positive PT signals of allopurinol, involving 14 SOCs, and 61 AEs were not recorded in the drug labels; there were 86 positive PT signals of febuxostat, involving 18 SOCs, and 25 AEs were not recorded in the drug labels. The top 5 PTs in the signal strength of allopurinol were drug reaction with eosinophilia and systemic symptoms, end-stage renal disease, hypercalcemia, acute kidney injury, and chronic kidney disease; the top 5 PTs in the signal strength of febuxostat were enthesopathy, granu- loma skin, blood parathyroid hormone decreased, tenosynovitis and alanine aminotransferase abnormal. The 2 drugs had a total of 49 overlapping signals. More AE signals of allopurinol were detected in SOCs of meta- bolic and nutritional diseases, blood and lymphatic system diseases etc.; more AE signals of febuxostat were detected in SOCs of skin and subcutaneous tissue diseases, various musculoskeletal, and connective tissue diseases, etc.　Conclusions Allopurinol has a higher risk of causing AEs related to kidney and urinary system, blood and lymphatic system, and metabolic system, while febuxostat has a higher risk of causing AEs related to skin and subcutaneous tissue, musculoskeletal and connective tissue, and hepatobiliary system. It is suggested that patients with gout accompanied by renal insufficiency, urinary system diseases or blood disea- ses should be careful with allopurinol, and the patients with gout accompanied by liver dysfunction should be careful with febuxostat.

Objective To explore the clinical characteristics of mirtazapine-related thrombocytopenia.　Methods The diagnosis and treatment of a patient with mirtazapine-related thrombocytopenia who was admitted to the Aerospace Center Hospital was reported, and the main clinical data (gender, age, indications of mirtazapine use, dosage of mirtazapine, combined medication, platelet count before and after medication, time from application of mirtazapine to thrombocytopenia occurrence, clinical treatment and prognosis, etc.) of the case and similar cases collected by searching relevant databases (up to August 31, 2023) were analyzed by descriptive statistic method.　Results A total of 9 patients were enrolled in the analysis, including 4 males and 5 females; the age ranged from 28 to 74 years, with a median age of 52 years. The indication of medication was depression in 8 patients, and 1 had no record. The daily dose of mirtazapine was 15-mg in 4 patients, 30-mg in 3 patients, and no record in 2 patients. Two patients were treated with mirtazapine alone, 6 patients were treated with mirtazapine combined with other drugs, and it was not recorded in 1 patient. The time from the application of mirtazapine to occurrence of thrombocytopenia in the 9 patients ranged from 2 to 28 days, with a median time of 8 days. The severity of thrombocytopenia was grade 1, 3, and 4 in 3, 3, and 2 patients, respectively; 1 patient had no relevant record. Of the 5 patients with severe thrombocytopenia, 3 developed bleeding, and 1 had skin ecchymosis. The results of drug-dependent antiplatelet antibody test in 2 patients were positive. Nine patients stopped mirtazapine treatment after diagnosis of thrombocytopenia, 6 patients did not receive special intervention, and 3 patients were given symptomatic treatments. After drug withdrawal for 2-43 days with the median time of 9 days, platelet counts returned to the reference range in 7 patients, platelet count increased in 1 patient, and platelet count was unknown but skin symptom was improved in 1 patient.　Conclusions Mirtazapine-related thrombocytopenia usually occurs within 10 days of treatments, which can be improved after drug withdrawal. It is suggested to monitor the blood routine before and after the application of mirtazapine.

Objective To explore the neurological adverse events (AE) associated to brexucabtagene autoleucel (brexu-cel) and their risk of occurrence.　Methods Neurological AE reports related to brexu-cel were collected through the US FDA Adverse Event Reporting System database from July 1, 2020 to September 31, 2022. The AEs were classified and counted according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) 24.1. The information component (IC) method and the reporting odds ratio (ROR) method were used to perform signal mining. AEs with ≥3 reports and a lower limit of 95% confidence interval (CI) for IC>0 or that for ROR>1 were defined as positive risk signals. The proportion of patients who suffered fatal outcomes after experiencing neurological AEs related to brexu-cel was analyzed.　Results A total of 1-960 neurological AE reports related to brexu-cel were collected, involving 559 patients and 22 PTs. Fifteen positive signals (PT) were detected by using the IC and ROR methods. The top 5 PTs in the number of AE reports were immune effector cell-associated neurotoxicity syndrome (153 reports), altered mental status (32 reports), encephalopathy (29 reports), tremor (27 reports), and aphasia (25 reports); the top 5 PTs with the high signal intensity were immune effector cell-associated neurotoxicity syndrome (IC=7.81, ROR=235.74), encephalopathy (IC=4.74, ROR=26.96), aphasia (IC=4.28, ROR=19.58), cerebral edema (IC=3.35, ROR=10.24), and incontinence (IC=3.04, ROR=8.22); incontinence (6 cases, IC=3.04, ROR=8.22) was not recorded in the drug instruction. Patients involved in 17 PTs, out of the 22 PTs, had fatal outcomes, and the proportion of deaths from immune effector cell-associated neurotoxi- city syndrome was 18% (28/153). The PTs with a proportion of patient deaths >50% were unresponsive to stimuli (80%, 4/5), brain oedema (75%, 6/8), cerebrovascular accident (67%, 2/3), lethargy (60%, 3/5), and seizure (57%, 4/7).　Conclusions Neurological AEs related to brexu-cel are common, of which incontinence is not yet recorded in the drug instruction. The clinical outcomes of some AEs (unrespontive to stimulus, brain oedema, and lethargy) are poor and should be closely monitored.

A 67-year-old female patient with lymph node metastasis from lung adenocarcinoma received the treatment of chemotherapy, immunotherapy, and targeted therapy (cisplatin, pemetrexed, pembrolizumab, and lenvatinib) at the same time. After the end of the third cycle of treatment, the patient developed elevated blood pressure (160/100-mmHg), blood creatinine increase (from 90-μmol/L to 160-μmol/L), anemia (hemoglobin 90-g/L), and metabolic acidosis (total carbon dioxide 18-mmol/L). Renal histopathological exami- nation showed tubulointerstitial damage. Excluding kidney injury caused by other drugs, it was considered to be the immune adverse reaction caused by pembrolizumab. The drug was discontinued and hormone, antihypertensive, and symptomatic treatments were given. After 5 months, the patient′s blood pressure was 110-120/70-80-mmHg, serum creatinine decreased to 130-μmol/L, hemoglobin was 117-g/L, and total carbon dioxide was 26-mmol/L.

An 86-year-old male patient with acute exacerbation of chronic heart failure developed diuretic resistance due to long-term use of diuretics, and was added tolvaptan 3.75-mg once daily orally, with significant diuretic effect. The next day, the dose was increased to 7.5-mg once daily orally. After taking medication, the patient′s urine volume increased and the symptoms of heart failure were improved. On the third day, the patient developed frequent dry mouth, thirst, transient restlessness, and convulsion of extremities. Laboratory tests showed pH 7.51, partial pressure of blood oxygen (PaO2) 67.4-mmHg, standard bicarbonate concentration (SB) 28.4-mmol/L, actual bicarbonate concentration (AB) 28.5-mmol/L, blood potassium 3.0-mmol/L, blood sodium 143-mmol/L, and blood chlorine 104-mmol/L. It was considered that the metabolic alkalosis and respiratory acidosis were caused by tolvaptan. Tolvaptan was stopped and arginine injection, 0.9 % sodium chloride, potassium supplementation, and other symptomatic treatments were given, and the patient′s water drinking was not restricted. On the day of tolvaptan discontinuation, the patient′s dry mouth and thirst were significantly reduced, his mental state was improved, with no convulsion of extremities, and lower limb and facial edema subsided. After 1 day of drug withdrawal, the laboratory tests showed pH 7.49, SB 31.1-mmol/L, AB 31.4-mmol/L, and blood potassium 3.6-mmol/L. After 3 days of drug withdrawal, the patient developed drowsiness, poor mental state, and weakened breathing compared to before, which was considered that the patient suffered from metabolic alkalosis combined with respiratory acidosis and secondary type II respiratory failure. Intravenous pumping of nikethamide was given. After 5 days of drug withdrawal, the patient′s 24-hour urine volume was 3-285-ml, and the levels of AB, SB, and pH slightly decreased. However, the patient′s condition was not improved significantly. After 13 days of drug withdrawal, symptomatic and supportive treatments such as tracheal intubation and ventilation assistance were given, but the patient′s condition continue to worsen.

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.

Anaphylaxis is a severe, life-threatening, immediate, and systemic allergic reaction, and may lead to serious consequences due to delayed diagnose or improper treatment. Guidelines at home and abroad recommend epinephrine as a first-line treatment for anaphylaxis. But there are still some problems such as insufficient use, inappropriate administration route or dosage of epinephrine in the treatment of anaphylaxis in China. The timing (as early as possible), route (intramuscular injection is preferred), and dosage of epindphrine should strictly follow the recommendations of relevant guidlines. Epinephrine autoinjectors can win more rescue time for patients with anaphylaxis, and can be equipped and used after training by clinicians.

Objective To understand the pre-warnings of contraindicated drugs in medical advices in patients with renal insufficiency by the pre-audit system.　Methods The pre-warnings of contraindicated drugs in medical advices in patients with renal insufficiency by the pre-audit system in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 1, 2021 to December 31, 2021 were collected. The drugs involved were analyzed and determined as drugs in the correct pre- warnings and drugs in the audit rules that needed to be corrected. The drugs involved in the correct pre- warnings and the acceptance of pre-warnings by clinicians were analyzed; drugs that can be used off-label according to the evidence-based information were recorded and the proposed suggestions on the revision of the audit rules were provided.　Results A total of 259 medical advices about pre-warnings related to contraindicated drugs in patients with renal insufficiency were included in the analysis, involving 47 drugs. Among the 259 pre-warnings, 169 were correct, with the correct rate of 65.25%, and 107 (63.31%) of them were accepted by clinicians. The rate of acceptance by surgeons was higher than that by physicians, and the difference was statistically significant ［76.39% (55/72) vs. 53.61% (52/97), P<0.01］. The audit rules in the 90 pre-warnings that needed to be modified involved 12 drugs. Of them, one drug (dapagliflozin tablets) had updated instruction, thus the rules can be modified directly according to it. The other 11 drugs were recorded for off-label drug use in the system based on evidence-based information, and of them, pre-warning levels were adjusted for 6 drugs, and audit rules were adjusted for 5.　Conclusions The pre-audit system can effectively pre-warning the contraindicated drug prescriptions of CKD patients, and the correct rate of pre-warning and clinician acceptance rate are more than 60%. The audit rules of some pre-warnings need to be adjusted with the update of the instructions and additional evidence-based information for off- label drug use after recording.

Objective To explore the adverse cardiac event risk signals in arsenical for injection, improve the clinical understanding of the cardiac toxicity of arsenical.　Methods The risk signals of adverse cardiac events associated with arsenical for injection were mined using 3 methods, including reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, and the Medicines and Healthcare Products Regulatory Agency (MHRA) comprehensive standard method based on data in Shandong Provincial Center of Adverse Drug Reaction Monitoring (Shandong data) in China from the first quarter of 2003 to the fourth quarter of 2022 and the data in US FDA Adverse Event Reporting System (FAERS) database from the fourth quarter of 2003 to the third quarter of 2023. The definition of risk signal in ROR and PRR method was the number of adverse event reports ≥3 and the lower limit of 95% confidence interval (CI) of ROR and PRR >1. The definition of risk signals in MHRA comprehensive standard method was the number of adverse event reports ≥3, PRR>2, and χ2>4.　Results There were a total of 358 reports on arsenical for injection in Shandong data, of which 275 (76.8%) were related to arsenious acid and sodium chloride injection, and 83 (23.2%) were related to arsenic trioxide for injection. Among the 358 reports, adverse cardiac reactions were reported in 25 reports (7.0%), and severe cases accounted for 28.0% (7/25). There were a total of 1-294 reports on ATO in FAERS, and adverse cardiac events were reported in 418 reports (32.3%), of which severe cases accounted for 62.2% (260/418). The signal mining results form 275 reports on arsenious acid and sodium chloride injection in Shandong data showed that QT interval prolonged, chest tightness, cardiopalmus, and palpitations were risk signals. Among them, the signal strength of QT interval prolonged was the strongest. A total of 35 adverse cardiac event signals were mined in FAERS data, of which the signal strength of QT interval prolonged and long QT syndrome were the strongest. In addition, the strength of 6 arrhythmia signals (bradyarrhythmia, supraventricular premature contraction, ventricular premature contraction, torsade de pointes, ventricular tachycardia, and atrioventricular block) and 6 cardiac organic lesion signals (pericarditis, endocarditis, pericardial effusion, myocarditis, mitral regurgitation, and cardiac enlargement) also ranked high.　Conclusions Arsenical for injection is strongly associated with cardiotoxicity, and the proportion of severe cases is relatively high. The cardiotoxicity mainly affects the QT interval, and can also manifest as various types of arrhythmias and some cardiac organic lesions. 

Old drugs are generally considered as drugs that have been on the market for many years and are well known by medical workers and the public. There are still many unsolved problems about the safety of older drugs. Some adverse reactions of old drugs may not be fully understood at present, the safety of their application in special populations still needs long-term monitoring, the study on mechanism of many adverse reactions of old drugs need to be strengthened, and most adverse reactions lack specific diagnostic biomarkers and effective prevention and treatment measures. The adverse reaction content in the old drug labels needs to be continuously improved, and many safety issues in drug application still require standardized expert consensus and guidance.

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 mine the risk signals of baloxavir marboxil-related adverse events (AEs) and provide reference for rational use in clinical practice.　Methods The report odds ratio (ROR) and proportional reporting ratio (PRR) methods were used to mine the risk signals of baloxavir marboxil-related AEs in the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the 1st quarter of 2018 to the 4th quarter of 2022. The AE with reports ≥3 and 95% confidence interval (CI) lower limit of ROR or PRR>1 was defined as a risk signal. AEs were classified according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA) 25.1 for statistical analysis.　Results A total of 1-102 AE reports were retrieved, involving 1-102 patients， and 498 were serious AE. A total of 45 AE risk signals were obtained by ROR and PRR methods. The top 10 PTs in signal intensity were febrile seizures, ischemic colitis, bacterial pneumonitis, anaphylaxis, hemorrhagic cystitis, erythema multiforme, melena, anaphylactic shock, disseminated intravascular coagulation, and anaphylactic reaction. Of them, 26 PTs were not recorded in the labels, in which the top 10 PTs were febrile seizures, ischemic colitis, bacterial pneumonia, hemorrhagic cystitis, disseminated intravascular coagulation, altered mental status, fever, rhabdomyolysis, cyanosis, and facial paralysis. The top 5 SOCs that involved more PTs were nervous system disorders, gastrointestinal disorders, respiratory system diseases, psychiatric disorders, and blood and lymphatic system disorders. Among the 498-serious AEs, a total of 5 risk signals were mined, including infectious pneumonia, diarrhea, rhabdomyolysis, allergic reactions, and abnormal behavior.　Conclusion The attention should be paid to AEs not mentioned in the drug label in clinical application of baloxavir marboxil, such as febrile seizures, bacterial pneumonia, ischemic colitis, and hemorrhagic cystitis.

    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。
    该研究基于世界卫生组织的药物警戒数据库（VigiBase），比较了7种他汀类药物（阿托伐他汀、氟伐他汀、洛伐他汀、匹伐他汀、普伐他汀、瑞舒伐他汀和辛伐他汀）横纹肌溶解的风险（不包括西立伐他汀，因其引起严重的横纹肌溶解而于2001年撤市）。该研究包括了在2022年12月31日前服用他汀类药物的成年人中出现横纹肌溶解的所有报告，结果以报告比值比（ROR）及其95%置信区间表示。结果显示，在VigiBase的3 300余万份报告所涉及的患者中，有10 657例服用他汀类药物者出现横纹肌溶解（ROR=59.33，P<0.001），第1份报告于1995年上报；其中由医师上报的占52.4%。报告所涉及的患者中男性占61.5%，73.7%的患者为“严重”横纹肌溶解（其中373例死亡，5 363例导致或延长住院治疗）。
    他汀类药物中致横纹肌溶解风险最大者为辛伐他汀（4 357例，ROR=71.80），随后为阿托伐他汀（3 346例，ROR=33.93）、瑞舒伐他汀（1 777例，ROR=33.01）、氟伐他汀（242例，ROR=31.21）、匹伐他汀（169例，ROR=27.85）、普伐他汀（472例，ROR=24.45）和洛伐他汀（295例，ROR=17.69）（均P<0.001）。当将每种他汀类药物与所有其他他汀类药物进行比较时，辛伐他汀也是风险最大者（ROR=2.20，P<0.001）。
    总之，该研究表明致横纹肌溶解风险较大的他汀类药物是辛伐他汀和阿托伐他汀，对于有横纹肌溶解风险的患者应优先考虑其他他汀类药物，如普伐他汀。除因其不被细胞色素P450系统代谢以外，普伐他汀也是该研究中致横纹肌溶解风险较低的他汀类药物之一。

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.

A 66-year-old male patient with malignant melanoma received combined treatments with apatinib (oral 250 mg once daily),temozolomide (oral 500-mg on day 1 and 400-mg/d on days 2-4),toripalimab(240 mg intravenous infusion on days 1 and 15). After 5 cycles (28 days as a cycle), the patient developed multiple rashes, which were not alleviated after reducing the dose of apatinib to 250-mg orally once every 3 days in the 6th treatment cycle. Laboratory tests showed that serum albumin was 28.5-g/L, total serum protein was 55.5-g/L, eosinophil percentage was 0.096, and venous potassium was 3.17-mmol/L. Erythroderma caused by combination of apatinib and toripalimab was considered， and the 2 drugs were stopped. The patient received the treatments of methylprednisolone,loratadine,diphenhydramine,tria- mcinolone acetonide and econazole nitrate cream and mupirocin ointment (external coating), and skin care. At the same time, symptomatic treatments such as protein supplement, diuresis, potassium supplement, and stomach protection were given. After 10 days of treatments, the rash subsided, and desquamation and itching were improved.

A 17-year-old female patient developed fever after novel coronavirus infection and took ibuprofen sustained-release capsules 0.3 g 4 times within 3 days by herself. During the medication, the patient developed the symptoms such as chest tightness, shortness of breath, limbs fatigue, sweating, muscle soreness, and dark urine successively. Laboratory tests showed creatine kinase (CK) 583-800-U/L, CK-MB 45-μg/L, lactate dehydrogenase 4-772-U/L, serum creatinine (Scr) 392-μmol/L, myoglobin 87-μg/L, and urea nitrogen 32.8-mmol/L. It was considered that rhabdomyolysis with acute kidney injury might be related to ibuprofen. The patient was given symptomatic treatments such as renal replacement therapy, hemodialysis, blood transfusion, rehydration, diuresis, etc. Thirty-three days later, the patient′s muscle soreness and other symptoms disappeared, the urine color returned to normal, laboratory tests showed CK 168-U/L, myoglobin 24-μg/L, and Scr 52-μmol/L.

Objective To explore the occurrence of rashes in healthy subjects caused by efavirenz in drug clinical trials.　Methods The occurrence of rashes related to efavirenz, which was used as an enzyme inducer, in healthy subjects in 2 clinical trials conducted by the Phase I Clinical Research Center of the Department of Pharmacy, Xuanwu Hospital, Capital Medical University (our hospital) in November 2020 and October 2021 was retrospectively analyzed. The relevant databases at home and abroad (up to November 30, 2022) were searched, and the literature, in which efavirenz was applied as trial drug or enzyme inducer in healthy subjects, were collected. The cases of efavirenz-related rashes reported in the literature were reviewed. The clinical characteristics of the cases in the literature and above 2 clinical trials in our hospital were summarized and analyzed by descriptive statistics.　Results A total of 40-healthy subjects were included in the 2 clinical trials, and 5 (12.5%) developed efavirenz-related rashes. The average time from taking the medicine to the appearance of rashes was 8 days. The initial symptom was skin itching. The rashes occurred mainly on the limbs and back, and mainly presented as maculopapular rashes, without other symptoms or laboratory abnormalities. Four subjects withdrew from the trial and the rashes subsided after 5-7 days of anti-allergic and symptomatic treatments; one subject was given calamine lotion for external use because of mild rashes, and continued to participate in the trial. His rashes subsided 17 days later (5 days after stopping efavirenz). Eighteen literature in which efavirenz was used as a trial drug or enzyme inducer in healthy subjects were retrieved. A total of 403-healthy subjects collected from 18 literature and our trials were included in the analysis. Of them, 19-subjects developed rashes, with a incidence of 4.7%. According to the daily dose of efavirenz, the incidence of rashes in the subjects of the 600-mg/d group was higher than that of the <600-mg/d group, but the difference was not statistically significant ［5.5% (18/329) vs. 1.4% (1/74), P=0.131］. According to the course of drug, the incidence of rashes was similar in subjects between the single dose group and the continuous dose group ［4.1% (4/97) vs. 4.9% (15/306), P=0.753］.　Conclusion Rashes are common adverse reactions in healthy subjects after taking efavirenz, which is generally mild and can subside after timely detection and 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.

Objective To actively monitor and analyze the safety of levofloxacin and sodium chloride injection produced by Guangzhou Green Cross Pharmaceutical Co., Ltd (generic drug). and levofloxacin and sodium chloride injection produced by Daiichi Sankyo (Beijing) Pharmaceutical Co., Ltd (original drug).　Methods The data in this study came from the adverse drug reaction reports on levofloxacin and sodium chloride injection voluntarily monitored and reported to the National Adverse Drug Reaction Monitoring System Database by the First Affiliated Hospital of Sun Yat-sen University, Guangdong Provincial People′s Hospital, and the First Affiliated Hospital of Ji'nan University from October 1, 2022, to September 30, 2023. The information on patients′ age, gender, medication use, primary disease, time from medication to the occurrence of adverse reactions, clinical manifestations, treatment and prognosis of adverse reactions, and the occurrence of serious adverse reactions were collected. The incidence of adverse reactions was calculated.　Results A total of 30 adverse reaction reports involving levofloxacin and sodium chloride injection were collected, involving 30 patients. In the generic drug group, there were 21 cases, including 8 males and 13 females, aged from 20 to 91 years with a median age of 43 years; 2 cases of serious adverse reactions were reported. In the original drug group, there were 9 cases, including 3 males and 6 females, aged from 20 to 96 years with a median age of 56 years; no serious adverse reactions were reported. In the generic drug group, a total of 36 adverse reactions occurred in 21 patients, while in the original drug group, a total of 13 adverse reactions occurred in 9 patients. These adverse reactions involved the skin and appendages, digestive system, nervous system, musculoskeletal system, urinary system, and medication site, with skin itching and rash being the most common allergic reactions (15 case time in the generic drug group, accounting for 41.7%; 6 case time in the original drug group, accounting for 46.2%). Two cases of serious adverse reactions occurred in the generic drug group, and both were anaphylactic shock. After discontinuation of the drug, switching to other antibiotics, and symptomatic treatments, 5 cases in the generic drug group were cured, 15 cases were improved, and 1 case was unknown. In the original research drug group, 2 cases were cured and 7 cases were improved. There were no deaths in either the generic or original drug groups. The incidence of adverse reactions in outpatients and/or inpatients in the generic drug group was 0.07% (21/29 557), while that in the original research drug group was 0.08% (9/10 686). There was no statistically significant difference between the 2 groups (χ2=0.183, P=0.669).　Conclusion The results of active monitoring show that there is no significant difference in safety between the generic and original drugs of levofloxacin and sodium chloride injection.

Objective To analyze the general rules and characteristics of adverse reactions of succinylated gelatin injection and provide reference for safe and rational clinical use.　Methods Adverse reaction reports related to succinylated gelatin injection in National Adverse Drug Reaction Monitoring System database from January 2004 to August 2021 were collected. Retrospective analysis of patients′ gender, age, primary disease, reason for drug use, combined drugs, and time of adverse reaction occurrence from drug use, clinical manifestations, severity and patient outcomes were performed, and classified statistics were performed according to systematic organ class (SOC) and preferred terms of Medical Dictionary for Regulatory Activities.　Results A total of 3-036 adverse reaction reports of succinylated gelatin injection were entered, including 710-serious cases (23.39%), and the top 5 SOCs involved diseases of the immune system, systemic diseases and various reactions at the administration site, skin and subcutaneous tissue diseases, vascular and lymphatic diseases, and respiratory/thoracic and mediastinal diseases. The main symptoms were anaphylactic shock, similar rapid severe allergic reaction, chills, fever, and other rapid severe allergic reactions. Among the 3-036 patients, 1-543 were cured, 1-480 were improved, 3 were not improved, 2 had sequelae, 2 died, and 6 had unknown results. The SOCs involved in adverse reactions and not recorded in labels included ocular organ diseases, various musculoskeletal and connective tissue diseases, metabolic and nutritional diseases, kidney and urinary system diseases, etc.　Conclusions The adverse reactions related to succinylated gelatin injection are mostly associated with anaphylaxis. Severe adverse reactions are consistent with the characteristics of rapid severe anaphylaxis, but there may be related risks not covered in labels.