A 63-year-old female with non-Hodgkin's lymphoma was treated with a chemotherapeutic regimen composed of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). She was given  rituximab 600 mg plus 750 ml of 0.9% sodium chloride injection intravenous drip on the first day, at the same time treatments for hydration, alkalization, protecting visceral function, prevention of adverse reactions were given. On day 2, the patient developed an involuntary shaking limbs, a lower limbs weakness, a slightly slow reaction and an unsteady gait. MRI of the brain did not show any significant finding. On day 3, she had a fever, cognitive impairment and confusion. On day 4, the patient could not have independent feeding and defecation. Methyl prednisolone, drugs for improving microcirculation and rehydration therapy were applied. Two days later, the patient's consciousness restored. He can eat independently, defecate by himself, and his limbs and neuropsychological symptoms were relieved. Five days later, the symptoms were apparently   improved.

Two female patients, aged 61 and 48 years old, received a combined chemotherapy of irinotecan 200 mg and lonaplatin 50 mg for cervical cancer. Patient 1 developed diarrhea, grade IV arrest of bone marrow and septicemia, accompanied by septic shock on the ninth day after the second cycle of chemotherapy. Patient 2 developed diarrhea, grade IV arrest of bone marrow, accompanied by fever on the sixth day after the first cycle of chemotherapy, and then developed secondary septicemia. Antidiarrhea, anti-infection, and immune support treatment were given. Five days later, diarrhea was controlled. Ten days later for patient 1 and six days later for patients 2, white blood cell, hemoglobin and platelet count were within normal range. After twenty days for patient 1 and six days later for patients 2, septicemia was controlled.

The proton pump inhibitors (PPI) are widely used as the treatment of choice in acid-related diseases in clinic. Long term use of PPI may further induce abnormal absorption of nutrition (vitamin B12, calcium, iron, magnesium and other minerals), abnormal proliferation of gastrointestinal mucosa, infection, and abnormal bone metabolism (osteoporosis and bone fracture), and so on. Most studies on safety of long term use of PPI are retrospective cohorts or case-control studies. More prospective randomized controlled trials should be performed and good clinical evidences should be obtained for reasonable and safe use of PPI.

ObjectiveTo develop a list of potentially inappropriate medication (PIM) for the Chinese aged people and provide reference for prevention and reduce the medication risk of the aged people.MethodsBased on the PIM lists of the United States, Canada, Japan, France, Norway, Germany, South Korea and Austria, and combined with the data of serious adverse drug reactions (ADR) in the aged people collected from China National Center for ADR Monitoring, ADR monitoring center in the People′s Liberation Army, Beijing Center for ADR Monitoring and ADR data from Beijing 22 hospitals, we created a preliminary PIM list for the Chinese aged people. Using Delphi technique experts consultation was made for the initial list. Round 1 consultantation invited 32 experts, according to the expert advice to adjust the initial list, and form a revised list. Round 2 consultantation invited 38 experts, according to the expert advice to adjust revised list, and the final version of the PIM list formed. ResultsA total of 13-class 72 medications or medication classes were selected as the Chinese aged people PIM list, each medicine had 1-6 risk points. The list was divided according to the result of expert evaluation into 35 kinds of high risk medications and 37 kinds of low risk medications. In addition, according to the frequency of drug use, the medications were divided into A and B two categories, including 24 medications or medication classes as the preferred alert medications (A), 48 medications or medication classes as routinely alert medications (B).ConclusionPIM list for the Chinese aged people have been developed, which can be taken as reference to intervention and evaluation of China′s elderly medication.

ObjectiveTo analyze the clinical characteristics and risk factors of lansoprazole-induced microscopic colitis (MC).MethodsPubMed, Da-Yi medical search, CHKD and Wanfang databases were searched and articles related to MC induced by lansoprazole were collected. The patients′primary diseases, coexisting diseases, the dosage, the way of administration, combination drugs, latent period, clinical manifestations, colonoscopic findings, the treatment measures, and the outcomes were recorded and the clinical characteristics, the risk factors of MC induced by lansoprazole were analyzed.ResultsA total of 30 articles and 62 patients with MC induced by lansoprazole were retrieved. All articles were case reports and no randomized controlled trials were found. Of all the 62 patients, 22 were male (35.5%) and 40 were female (64.5%) with age from 36 to 92 years and the average age was (69±12) years; 57 patients (91.9%) were >50 years; 43 patients were with collagenous colitis (CC) (69.4%) , 18 patients (29%) were with lymphocytic colitis (LC), and one patient with LC changed into CC (1.6%). All patients were treated with oral lansoprazole. The latent period of MC induced by lansoprazole were 5d-6 years and within 1-6 months in 31 patients (60.8%) . The most common clinical manifestations were non-bloody watery diarrhea (3-10 times daily in 59 patients, >10 times daily in 3 patients). Intestinal mucosal screening was performed for all the patients and mild abnormalities or edema were observed in 37 patients, mucosal defect and mucosal laceration in 11 patients, epithelial collagen layer thickening, inflammatory cells infiltration in lamina propria, increased lymphocytes in intraepithelial spaces in 18 patients. High-risk drugs for drug-induced MC were combined use in 20 patients and the combination drugs in 13 patients were non steroidal anti-inflammatory drugs. Fifty-eight patients with mild or moderate drug-induced MC returned to normal after withdrawl of lansoprazole and treatment with omeprazole or rabeprazole sodium and 4 patients with severe drug-induced MC recovered after withdrawl of lansoprazole and treatment with glucocorticoids.ConclusionsThe clinical characteristics in patients with MC induced by lansoprazole are watery diarrhea, mild abnormality or edema of colon mucosa, and thickening in the epithelium of colonic mucosa in histopathology. Age, gender, and combined use of drugs may be related to occurrence of MC induced by lansoprazole.

ObjectiveTo observe the adverse reactions of zoledronic acid in the treatment of osteoporosis combined with rheumatic diseases and analyze the potential risk factors.MethodsMedical record data of patients with rheumatic diseases and osteoporosis who were treated with zoledronic acid during hospitalization in Xuanwu Hospital of Capital Medical University from January 2011 to December 2014 were collected and a retrospective analysis was conducted. The patients were grouped according to the occurrence of adverse reactions and their demographic characteristics, types of rheumatic diseases and medication regimen of zoledronic acid were compared. The screened risk factors for adverse reactions were analyzed by multivariate logistic regression. The results were expressed by odds ratio (OR) and 95% confidence intervals (CI).ResultsA total of 120 patients were enrolled into the study. There were 41 males and 79 females. Their ages ranged from 23 to 85 years. Of 120 patients, 64 cases (53.3%) received first infusion of zoledronic acid, 66 cases (55.0%) received the treatment with corticosteroids during hospitalization, 58 cases (48.3%) were given antipyretic analgesics before infusion of zoledronic acid and 64 cases (53.3%) received sufficient hydration before and after the infusion; 49 (40.8%) of the 120 patients were reported to have adverse reactions. All adverse reactions were of acute phase responses, including fever in 32 (65.3%), flu-like symptoms in 21 (42.9%), headache in 17 (34.7%), fatigue in 12 (24.5%), myalgia in 10 (20.4%), arthralgia in 8 (16.3%), chills in 6 (12.2%), nausea in 5 (10.2%), vomiting in 4 (8.2%), and dry cough in 1 (2.0%). No severe adverse events occurred. The incidence of adverse reactions in initial infusion patients was significantly higher than that in non-initial infusion patients［51.6% (33/64) vs. 28.6% (16/56), P=0.011］. The incidence of adverse reactions in patients with  corticosteroid therapy was significantly lower than that in patients with no corticosteroid therapy［24.2% (16/66) vs. 61.1% (33/54), P<0.001］. The patients who were given sufficient hydration before and after the infusion also had significantly lower incidence of adverse reactions than those without sufficient hydration treatments［31.2% (20/64) vs. 51.8% (29/56), P=0.023］. Multivariate logistic regression analysis suggested that initial infusion was a risk factor for adverse reactions (OR=2.631, 95%CI: 1.132-6.116, P=0.025). However, oral corticosteroid and sufficient hydration treatments before and after the infusion were protective factors (OR=0.232, 95%CI: 0.102-0.526, P<0.001; OR=0.379, 95%CI: 0.164-0.874, P=0.023).ConclusionsAcute phase responses related to zoledronic acid are common in the treatment of patients with rheumatic diseases and osteoporosis. Iniaial infusion is closely associated with adverse reactions of zoledronic acid, but oral corticosteroid and sufficient hydration treatments before and after the infusion might decrease the incidence of adverse reactions.

ObjectiveTo analyze the characteristics of highly cited papers published in Adverse Drug Reactions Journal (our journal) during 2009 to 2013， understand the hot spots of subject development and demands of readers, and improve impact and quality of our journal. MethodsThe citation frequency of papers published in our journal from 2009 to 2013 was searched in China Academic Journal Network Publishing Database (as of April 30, 2015). Price law was used to determine the highly cited papers. The main statistical parameters included total citation frequency of papers published in our journal, average citation frequency of papers, citation frequency of highly cited papers, and average citation frequency of highly cited papers. The distribution of subjects of highly cited papers, regional distribution of authors, distribution of article types, and funding  sources were analyzed descriptively.ResultsA total of 1 052 articles were searched and 736 articles were entered into the study, including 147 original articles, 85 reviews, and 504 case reports. Of the 736 articles, 517 were cited (70.2%) and the total citation frequency was 2 170 times and average citation frequency of papers was 4 times. According to the Price law, the papers which were cited ≥5 times were considered as highly cited papers in our journal during the study period. The citation frequency of 138 highly cited papers was 1 388 times which accounted for 64.0% of total frequency (2  170 times) during the study period and average citation frequency of highly cited papers was 10 times. The subjects of highly cited 138 papers are relatively centered and the top 5 subjects were antimicrobial agents (44 papers, 31.9%), Chinese Medicine (22, 15.9%), cardiovascular system drugs (19, 13.8%), antineoplastic drugs (11, 8.0%), and endocrine system drugs (5, 3.6%); there were 87 papers (63.0%) distributed in Beijing and 51 papers (37.0%) distributed in other 17 provinces or municipality directly under the central government; 33 of the highly cited 138 papers were original articles (23.9%), 29 were reviews (21.0%), and 76 were case reports (55.1%), their citation frequency was 390, 354, and 643, respectively which accounted for 28.1%, 25.5% and 46.3% of total citation frequency 1 388 times, respectively, and the average citation frequency of original articles, reviews, or case reports were 12,12, and 9, respectively. There was 1 paper supported by National funds at top 20 highly cited papers.ConclusionsAs highly cited papers published in our journal, distribution of subjects and regions were relatively centered; distribution of authors were dispersive; reviews and case reports made more contributions; and average citation frequency of original articles and reviews was higher. It is valuable to understand the above mentioned characteristics to make measures for improvement of impact and quality of our journal.

A 76-year-old male patient with acute coronary syndrome received regularly aspirin (0.1 g once daily), clopidogrel (50 mg once daily), atorvastatin calcium (20 mg once daily), and isosorbide mononitrate (10 mg twice daily) by mouth after undergoing percutaneous coronary intervention. He suffered from left lumbago with gross hematuria after 2 months of treatments. Laboratory tests showed the following values：urine occult blood(+++)，235 red blood cells per microlitre and 17 red blood cells per high power field. Urinary system ultrasonography and renal function detection showed no abnormalities. Aspirin and clopidogel were withdrawn and the symptomatic treatments were given. Two days later, the patient′s urine recovered to normal，his left lumbago was alleviated, and the red blood cell in his urine was negative. Gene polymorphism detection of cytochrome P-450(CYP)2C19 showed that the patient carried CYP2C19*17(CT) allele and CYP2C19 enzyme had ultra rapid metabolism. Aspirin was given orally and the hematuria did not appear again.

A 45-year-old man with about 10 years of drug abuse history took 96 tablets of sodium valproate sustained-release (48 g) and about 20 capsules of ziprasidone hydrochloride (＞400 mg) by himself one time. He appeared comatous and had no response to being called, then he was sent to the hospital by his family members. He presented no autonomous respiration, hypotonia of the four limbs and neck (2 level) on admission. He received symptomatic supportive treatments including tracheal intubation and ventilator assisted breathing, gastric lavage, coloclyster, fluid infusion,  diuresis, and central nervous system stimulant, immediately. Two hours later, the patient awoke. Laboratory tests revealed the following results: arterial oxygen partial pressure (PaO2) 292 mmHg (1 mmHg=0.133 kPa), lactic acid 5.70 mmol/L, D-dimer 7.8 mg/L, plasma fibrinogen degradation product (FDP) 45 mg/L. Twenty-four hours later, laboratory tests revealed the following results:  PaO2  98 mmHg, lactic acid 1.7 mmol/L, D-dimer 2.2 mg/L, FDP 19 mg/L. The trachea cannula was removed. Forty-eight hours later, his consciousness returned to normal. He could finish the common action. But he still had the symptom of  drowsiness. Seven days later, the patient could answer questions accurately. His muscular tension returned to normal. He had light drowsiness occasionally.

ObjectiveTo explore the relationships between active systemic allergic reaction induced by breviscapine injection and the drug dose and the sensitization time.MethodsActive systemic allergic reaction in guinea pigs was used as experimental method. Forty-eight guinea pigs were divided into 6 groups according to random number table: breviscapine injection 1, 5, 25 and 50 mg/kg group (the breviscapine injection group 1, 2, 3, 4), 0.9% sodium chloride injection group (the negative control group) and bovine serum albumin (BSA) control group (the positive control group). Each group comprised 8 guinea pigs. Sensitization: the guinea pigs in group 1 to 4 were given the breviscapine injection  at doses of 1, 5, 25 and 50 mg/kg (0.5 ml) by intraperitoneal injection every other day for three times, respectively. The the guinea pigs in the negative control group and the positive control group were given 0.9% sodium chloride injection (0.5 ml) and bovine serum albumin (BSA) 20 mg/kg by intraperitoneal injection every other day for 3 times, respectively. Excitation: the sensitized guinea pigs in each group were divided into 2 subgroups, each subgroup comprised 4 guinea pigs. On the 14 and 21 days after the last sensitization, the guinea pigs in breviscapine 1 to 4 subgroups received 2 times of breviscapine injection intravenously (1.0 ml), respectively. The guinea pigs in the negative and the positive control subgroups  received 2 times of control articles intravenously, respectively. The symptoms of anaphylactic reaction (pilo-erection, shiver, scratching nose, sneeze, cough, vomiturition, cyanosis, dyspnea, urinary and fecal incontinence, instability of gait or tumble, convulsion or hyperspasmia, shock and death) were observed every day during the sensitization phase. The guinea pigs′ reactions which appeared in 30 min after intravenous injections were observed and the occurrence time of allergic symptoms/signs were recorded attentively. The anaphylactic reaction was determined according to the Chinese Pharmacopoeia′s allergic reaction test. ResultsThe guinea pigs in 6 groups did not show any allergic symptoms in the sensitization phase. Within 30 min in fourteenth days′ excitation,  2, 4, 4, 4 guinea pigs developed allergic reactions in the breviscapine 1 to 4 groups, respectively. But none of them were identified as allergic reaction. The 4 guinea pigs in the positive control group were judged to have positive allergic reaction. Within 30 min of 21 days′ excitation, 4、3、4、4 guinea pigs developed allergic reactions in the breviscapine 1 to 4 groups, respectively. Only one guinea pig in the breviscapine 4 group was identified as allergic reaction. The 4 guinea pigs in the positive control group were all judged positive allergic reaction. The guinea pigs in the negative control group did not develop any allergic reactions during the 2 times of excitation. The occurrence time of allergic reactions in the breviscapine groups (within 20 min after excitation) on 21 days′ excitation was shorter than those (within 25 min after excitation) occurred on 14 days′ excitation, but the difference was not statistically significant.ConclusionsThe active systemic allergic reactions induced by breviscapine injection are associated with drug dose and sensitization time. The larger dose and longer sensitization time can increase the risk of allergic reaction and shorten the latency of allergic reaction.

As stated by article 12 of the Drug Administration Law of the People′s Republic of China, the state shall construct pharmacovigilance regulations to monitor, identify, assess, and control adverse drug reactions and other harmful events related to medication. Pharmacovigilance runs throughout the whole life cycle of drug from research and development to clinical use, and the core idea is to prevent and control medication risks and ensure the safety of patients and the general public. As the main places for drug consumption and the key participants in pharmacovigilance activities, the construction of pharmacovigilance system in health facilities is an important part in the construction of national pharmacovigilance regulations. At present, we are at the initial stage of the implementation of national pharmacovigilance regulations. In order to promote the establishment of pharmacovigilance system in health facilities, domestic pharmacovigilance monitoring institutions, relevant academic groups, medical colleges and universities, periodical offices, and social welfare organizations jointly initiate the compilation of Expert consensus on construction of pharmacovigilance system in health facilities by inviting experts and scholars in relevant fields to discuss, distinguish, and analyze the important concepts on adverse drug reactions/events, medication safety, pharmacovigilance, etc., in combination with cutting-edge developments. The consensus puts forward systematic principles and methods on establishing pharmacovigilance system, expecting to provide reference to health facilities in pharmacovigilance system establishment.

A 79-year-old man received an intravenous (IV) infusion of cefoperazone sodium and sulbactam sodium 1.5 g every 12 hours with concomitant use of levofloxacin 0.5 g once daily，doxofylline injection 0.2 g via pump twice daily, and an IV push of 45 mg ambroxol injection twice daily for acute exacerbation of chronic obstructive pulmonary disease. Levofloxacin was discontinued after 7 days of treatments ambroxol and doxofylline were discontinued after 13 days of treatments. Just after completion of the infusion of cefoperazone sodium and sulbactam sodium on day 16 of treatment, the patient suddenly experienced unconsciousness, convulsion of extremities, gnathospasmus, and eyes gazing rightwards, which lasted about one minute. An IV injection of methylprednisolone sodium succinate 40 mg was given immediately and 1 minute later, his consciousness restored and symptoms relieved. And then an IV injection of sodium valproate 400 mg and sodium valproate 30 mg/h via a pump were given. On day 17, 2 hours after completion of the infusion of cefoperazone sodium and sulbactam sodium, the symptoms mentioned above appeared again. An IV push of diazepam 5 mg and sodium valproate 80 mg/h were given and 2 minutes later, the symptoms alleviated gradually. Subsequently, cefoperazone sodium and sulbactam sodium was discontinued, an IV push of sodium valproate 400 mg once daily and an oral sodium valproate 0.5 g twice daily were given. After that, he didn′t experience epilepsy seizure again.

An 81-year-old female patient with pulmonary infection was given cefoxitin 2 g by intravenous drip. After 1.5 hours of treatment, the patient self-medicated with compound glycyrrhiza oral solution 10 ml for cough. About 10 minutes later, she experienced chest tightness, dyspnea, facial flushing, hyperhidrosis, weakness of limbs and rash. Disulfiram reaction was considered. Intravenous dexamethasone 10 mg and continuous low flow oxygen were given. About 30 minutes later, the patient′s condition improved. After 2 hours, the symptoms disappeared.

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 74-year-old female patient received oral carbamazepine 0.1g thrice daily because of epilepsy after acute ischemic stroke. On the third day, the patient suddenly presented drowsiness which gradually aggravated to a state of mild coma within 30 minutes. The electrocardiogram showed that sick sinus syndrome and junctional rhythm with a heart rate of 34 beats per minute. The patient was diagnosed as Adams-Stokes syndrome which may be induced by carbamazepine. She was given an intravenous injection of atropine sulfate 0.5 mg immediately. Then atropine sulfate 1 mg in 5% glucose injection 500 ml was slowly given by intravenous drip. Two hours later, the patient regained consciousness. The electrocardiogram showed restoration of sinus rhythm with a heart rate of 48 beats per minute. Carbamazepine was withdrawn and disturbance of consciousness did not recur.

A 67-year-old male patient received immunotherapy with intravenous infusion of sintili- mab 200-mg once every 3 weeks due to postoperative recurrence of liver cancer, and the efficacy and tolerance was good. After 12 doses of sintilimab treatment, the patient developed a bright red skin rashes on the chest, abdomen, and extremities with itching. Oral loratadine and topical halometasone cream were given, and the rashes were improved slightly. The rashes did not spread in the next 2 doses of sintilimab treatment. But after the 3rd dose of continuing sintilimab, the patient suddenly developed a large-area rashes all over the body, which rapidly developed into blisters, ulcers, accompanied by oozing blood and fluid on the skin, itching, and pain. Drug eruptions were diagnosed, which was considered to be induced by sintilimab. The drug was stopped. After 1 week of treatments with intravenous infusion of methylprednisolone 60-mg once daily, anti-allergy, anti-infection, mucosal protection, and skin care, the rashes were repeated. Then the dose of methylprednisolone was increased, the rashes were still not relieved 1 week later, and gastrointesting bleeding occurred. After liver cancer surgery, the patient was accompanied by hypoproteinemia, liver dysfunction, and long-term high-dose glucocorticoid use. Therefore, despite active treatment measures, the patient still died of ineffective rescue.

Chemotherapy-induced peripheral neuropathy (CIPN) usually manifests as persistent pain and sensory abnormalities, and in severe cases, loss of vibration and joint position sensation, autonomic and motor dysfunction may occur, severely affecting patients′ quality of life. Mitochondrial dysfunction may be one of the mechanisms by which chemotherapeutic drugs induce peripheral neuropathy. Different mitochondrial dysfunction caused by different chemotherapy agents are reviewed from 5 aspects in this paper, including abnormal neuronal mitochondrial morphology, activation of mitochondrial permeability transition pore and its associated calcium imbalance, dysfunction of mitochondrial bioenergetics, oxidative stress, and abnormal axonal mitochondrial transport. Avoiding or improving mitochondrial dysfunction is the main strategy to prevent or mitigate CIPN.

From March 2013 to December 2018, Japan, the United Kingdom, Canada, Australia, and China successively issued guidelines on therapeutic drug monitoring of voriconazole. It is recommended in guidelines at home and abroad that voriconazole should be given a loading dose, and the blood drug concentration of patients should be monitored on the third day; when adjusting the dose, adverse events occurrence or poor efficacy, increasing or stopping the drugs that may interact, and sequential administration, the blood drug concentration should be monitored again. The clinical characteristics of voricona- zole-related adverse events have been clearly defined. After adverse reactions occur during the treatment period, the drug can be stopped or reduced according to its severity. Voriconazole is not only the substrate of cytochrome P450 (CYP) 2C9, CYP2C19 and CYP3A4, but also an inhibitor of them. We should pay attention to the interaction between voriconazole and other drugs.  In the future, further research is needed to accumulate more evidence-based medical evidences for the use of the drug in different medication purposes, different diseases or different fungal infections, Child-Pugh grade C severe liver disease, and children <2 years old, so as to provide reference for clinical individualized treatment.

A 25yearold male patient took about 60 tablets of phenobarbital and scopolamine hydrobromide by himself (each tablet contains 30mg phenobarbital and 0.2mg scopolamine hydrobromide). About 1 hour later, he developed coma with paroxysmal limb convulsions. Drug poisoning was diagnosed. The patient received gastric lavage, catharsis, and intravenous injection of midazolam 10mg for epilepsy. Six hours later, his heart rate was 53 beats/min, breathing rate was 11 times/min, and occasional convulsions and hematuria occurred. Laboratory tests showed indirect bilirubin 16.97μmol/L, total protein 54g/L, albumin 27.6g/L, and thrombin time 25.0s. Multiple organ injury was considered and blood purification treatment was given. One day later, the patient′s consciousness was restored, heart rate was 68 beats/min, breathing rate was 16 times/min, and no convulsion occurred. Laboratory tests showed indirect bilirubin 8.69μmol/L, total protein 54.7g/L, albumin 34.0g/L, and thrombin time 16.7s.

A 77-year-old female patient was given combined chemotherapy with paclitaxel for injection (albumin bound) and nedaplatin for ovarian malignant tumor with peritoneal metastasis. When paclitaxel for injection (albumin bound) 100-mg dissolved in 0.9% sodium chloride injection 250-ml was given intravenously for the first time, the infusion was not smooth and the drip rate was slow. After stopping infusion, the infusion device was checked and white flocculent sediment above the filter was found. Clinical pharmacists ruled out the possibility of precipitation caused by drug preparation and incompatibility contraindications, and found that the infusion device used by this patient was a precision one (the pore diameter of microporous filter was 5-μm). However, in the drug label of paclitaxel for injection (albumin bound), it was pointed out that "Use of filters with a pore size less than 15-μm may result in blockage of the filter and should not be used." On the second day, a general infusion device (filter with 20-μm pore size) was used for IV infusion of paclitaxel for injection (albumin bound) and the process was smooth and no blockage recurred.

A 50-year-old male patient grinded his self-purchased blister-beetle (Mylabris) body into powder and then made it into paste for large area external use on his body skin for psoriasis. A few minutes later, the patient developed erythema and blisters on the site of medication; a few hours later, the purplish-red patches and blisters spread throughout the body, epidermis relaxed and exfoliated, and symptoms of systemic poisoning appeared. One day later, the patient developed multiple organ failure, such as respiratory failure, liver injury, kidney injury, severe hypoproteinemia, and abnormal coagulation function. Epidermolysis bullosa induced by externally application of Mylabris was diagnosed, and treatments of high-doses of pulsetherapy methylprednisolone, intravenous infusions of human immunoglobulin and human albumin, bedside hemofiltration, ventilator-assisted ventilation, and etc. were given. However, the patient′s condition deteriorated rapidly and finally he died of multiple organ failure 12-hours later.

There are risks in the use and management of perioperative analgesics, which may be caused by analgesic methods, individual patient factors, or medication errors. In order to reduce the risk in perioperative analgesics use and improve the level of safe drug use, Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs, Chinese Pharmacological Society Professional Committee of Drug-induced Diseases, Adverse Drug Reactions Journal Agency, Beijing Municipal Health Commission Clinical Safety Medication Working Group organize the domestic pharmacy experts and anesthesiology experts to formulate the guideline. The risks prevention and management measures of perioperative analgesics were described from 3 aspects including management, drugs, and special populations. The management- related risks include the risks during the formulation of analgesia plan, the risks in information/goods/drugs transmission, the risks in the use of intraoperative analgesics and analgesia pumps, which can be prevented by formulating rules and regulations, strengthening training, and improving information technology. Drug-related risks are inherent properties of drugs. Analgesics are classified into narcotic analgesics, antipyretic analgesics, and analgesic auxiliary drugs. Corresponding prevention strategies can be formulated according to the risk points of specific drugs. Special populations including the elderly, pregnant and lacta- ting women, and children, etc. have their own physiological and pharmacokinetic characteristics and countermeasures can be formulated according to specific conditions. Through comprehensive monitoring of perioperative analgesics use, the risk can be predicted, the circumvention plan can be formulated, and the pharmaceutical care can be implemented, so as to ensure the medication safety of patients. This guideline is applicable to all medical personnel who use and monitor perioperative analgesics.

 A small amount of commonly used and first-aid drugs stored in the inpatient wards can facilitate the temporary treatment of patients and save precious time for the treatment of critically ill patients. But there is a risk of medication errors in the link of drug storage in the inpatient wards. In order to strengthen the management of drug storage in the inpatient wards and reduce medication errors, experts in medicine, pharmacy, nursing, hospital management, and etc., were organized by Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs, Chinese Pharmacological Society Professional Committee of Drug-induced Diseases, and Adverse Drug Reactions Journal Agency, to formulate the guideline for prevention of medication errors in the link of drug storage in inpatient wards based on the Expert Consensus on Medication Error Management in China. The medication errors in the link of drug storage in the inpatient wards include improper storage of drugs, wrong drug specifications, wrong drug quantity, and wrong drug placement. The risk factors include management factors (unsound management system, no designated person or post management, or no regular inspections and supervision), process factors (no corresponding standard operation process, or only imperfect or unreasonable operation process), environmental factors (unqualified drug storage space and equipment, or no special labels), human factors (no training for personnel involved in drug use, or unreasonable staff arrangement), and drug factors (too many types and quantity of drugs in inpatient wards). The prevention strategies include technical strategies (enforcement and constraint management policies, implement of informatization and intelligence management, and formulation of standardized marks and processes, and establishment of standard catalog list and audit project list) and management strategies (establishment of management systems, provision of sufficient human resources, and enhancement of training).

An 87-year-old female patient with hypertension was given 3 Suhuang Zhike capsules (0.45 g/capsule) for cough. Half an hour after medication, the patient suddenly developed limbs tremor, accompanied by palpitation and sweating. The symptoms lasted for about 10-minutes and relieved spontaneously. Her blood pressure was 145/79-mmHg. Her nervous system examination showed no abnormality; blood glucose, electrolyte, thyroid function, and liver and kidney function were all normal; and electroencephalogram and cranial computed tomography showed no obvious abnormality. Ephedrine in Suhuang Zhike capsules was considered to be related to her symptoms. The drug was stopped and oral alprazolam 0.4-mg was given twice daily. The symptoms of limbs tremor did not recur in the patient.

Allergic diseases have serious influence on human health and quality of life. Cytokines secreted by T-helper cell type 2 (Th2), such as interleukin (IL)-4 and IL-13, play a pivotal role in the pathogenesis of allergic diseases. By recognizing and binding to IL-4 and IL-13 receptors, dupilumab can block the signal transduction pathways of IL-4 and IL-13, inhibit Th2 inflammatory reaction, and thus play a therapeutic role in allergic diseases. At present, dupilumab has been on the market in many countries and regions around the world, yet with different indications approved, mainly including atopic dermatitis, moderate-to- severe eosinophilic asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, etc. In addition, this drug may also have better curative effect on IgE-mediated allergic reactions and other dermal diseases. Meanwhile, the safety profile of dupilumab is generally good and the common adverse reactions mainly include injection site reactions (pain, ecchymosis and swelling at the injection site), ocular diseases (conjunctivitis, keratitis, itchiness of eyes and dry eyes), oral herpes, headache, and other herpes simplex virus infections. In China, dupilumab has been approved for the treatment of moderate-to-severe atopic dermatitis in patients aged ≥6 years, showing good efficacy and no obvious safety problems.

A 38-year-old female patient with recurrence of breast cancer accompanied by liver metastasis received intravenous infusion of sintilimab 200-mg on the first day and 21 days was a cycle. Before the immunotherapy, her function of liver, kidney, and thyroid was normal. Three days after the medication, the patient developed rash and itching on skin of waist. After that, diffuse erythema and desquamation appeared on skin of her whole body and blisters appeared on both upper limbs and back. At the same time, she developed blurred vision, increased eye secretions, and foreign-body sensation. Laboratory tests showed alanine aminotransferase (ALT) 123-U/L, aspartate aminotransferase (AST) 342 UL, γ-Glutamyltransferase (γ-GT) 907-U/L, alkaline phosphatase (ALP) 424-U/L, serum creatinine (Scr) 95.6-μmol/L, uric acid 691.0-μmol/L, and thyroid-stimulating hormone (TSH) 20.87 mU/L. She was diagnosed with rash, hypothy- roidism, kidney injury, conjunctivitis, and liver injury, which were considered to be associated with sintilimab. After 16 days of symptomatic treatments such as IV infusions of methylprednisolone sodium succinate for injection and magnesium isoglycyrrhizinate injection, oral administration of levothyroxine sodium and Haikun Shenxi capsules (海昆肾喜胶囊), levofloxacin eye drops, and skin care, her rash was subsided, blisters were absorbed, and the discomfort in the eyes disappeared. Laboratory tests showed ALT 111 UL, AST 122-U/L, γ-GT 1-430-U/L, ALP 321-U/L, Scr 56.0-μmol/L, uric acid 243.0-μmol/L, and TSH 13.60 mU/L.

Objective To understand the clinical characteristics of rivaroxban- related adverse events (AE) in perioperative patients.　Methods The relevant databases at home and abroad (as of April 20, 2020) were searched and the case reports of AE associated with rivaroxban used during perioperative period were collected. Relevant information in patients (nationality, gender, age, medical history, application of rivaroxaban, combined drugs, and the occurrence, treatment, and outcome of AE, etc.) was extracted and analyzed descriptively.　Results A total of 42 case reports of AE caused by rivaroxban during perioperative period were collected, involving 46 patients from 11 countries. Of the 46 patients，25 (54.3%) were male and 21 (45.7%) were female with an age of 16-96 years. In terms of the reasons for medication, 34 patients used rivaroxban before operation for prevention of postoperative venous thrombosis, 7 used rivaroxban after operation for prevention atrial fibrillation, stroke, or systemic thrombosis after operation, 4 discontinued rivaroxban during perioperative period, and 1 did not explain the reason for using rivaroxban. Past medical history were described in 21 patients, including hypertension, hyperlipidemia, and diabetes, etc. Combined medication was described in 22 patients, including antibiotics, non-steroidal anti-inflammatory drugs, analgesics, cardiovascular and cerebrovascular drugs, etc. The onset time of AE was recorded in 31 patients, which was 2 hours to 2 months after medication and most within 1 month. AE associated with rivaroxban were bleeding in 29 patients, liver injury in 7 patients, anaphylaxis in 6 patients, kidney injury in 3 patients, thrombosis in 3 patients, thrombocythemia in 2 patients, thrombocytopenia, pulmonary embolism, acute attack of coronary atherosclerotic heart disease, and visual loss in 1 patient each. After the occurrence of AE, 31 patients were improved after rivaroxban withdrawn, switching to other anticoagulants, and receiving symptomatic treatment; 1 patient improved after changing concomitant medications as well as reducing the dose of rivaroxban; 2 patients did not stop the drug in time and developed new allergic reaction; 2 patients were improved after using rivaroxban again; 1 patient died of hemorrhagic shock due to gastrointestinal bleeding; 9 patients′ outcome were unknown. Among the 46 patients, 18-had medication errors, of which 16-had dose error and 2 had compatibility errors.　Conclusions Hemorrhage is the most common AE related to rivaroxban in the perioperative use of rivaroxban, which mainly occurs within 1 month after medication. The overall prognosis is good after rivaroxban withdrawal, switching to other anticoagulants, and symptomatic treatment. Medication error is one of the causes of AE related to rivaroxban in perioperative period.

A 77-year-old male patient with rheumatoid arthritis was given methotrexate 10-mg once a week, tripterygium glycosides 20-mg twice daily, and methylprednisolone 8-mg once daily orally. However, the patient confused the medication frequency of methotrexate with tripterygium glycosides and mistakenly took methotrexate 5-mg twice daily. After 4 days of medication (taking methotrexate 7 times, 35-mg in total), the patient developed severe oral ulcers, generalized rash, fever, cough, and expectoration. Laboratory tests showed white blood cell count 1.21×109/L, serum creatinine 288-μmol/L, γ-glutamyl- transferase 163-U/L, alanine transaminase 82-U/L, and alkaline phosphatase 235-U/L. After 6 days of medi- cation, laboratory tests showed white blood cell count 0.13×109/L, neutrophil count 0.01×109/L, serum creatinine 317-μmol/L, estimated glomerular filtration rate 18-ml/(min·1.73 m2), C-reactive protein 233.8-mg L, and procalcitonin 14.31-μg/L. The patient was diagnosed as having methotrexate poisoning, myelosuppres- sion, renal insufficiency, and pulmonary infection. All drugs were discontinued immediately. Blood perfusion, intravenous injection of calcium folinate, and symptomatic treatments such as anti-infection, elevation of white blood cells, blood transfusion, rehydration, and mouth care were given. However, the patient′s infection and myelosuppression continued to worsen, and he died of multiple organ failure 12 days later.

A 4 years and 7 months old boy was treated with IV infusions of azithromycin 0.16 g once daily and methylprednisolone sodium succinate 32-mg once daily and oral amoxicillin and clavulanate potassium for suspension 228.5-mg twice daily for bronchopneumonia complicated with multiple co-infections with mycoplasma, viruses, and bacteria. After 6 days of treatments, the boy′s symptoms were improved and his body temperature returned to normal. On the 7th day of treatments, the boy developed rash with itching, which subsided on the same day after symptomatic treatments. Amoxicillin and clavulanate potassium and azithromycin were discontinued, but the child still developed rash every time after IV infusion of methylprednisolone sodium succinate, which could subside later that day. After withdrawal of methylprednisolone sodium succinate, the boy′s rash did not recur.

In 2022, a total of 22-868 cases of medication error (ME) from 315-hospitals in 26 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 14.55% compared with that in 2021 (275-hospitals), and the number of reported ME cases increased by 16.76% compared with that in 2021 (19-585 cases). In 22-868 cases of ME reports, 155 (0.68%) were classified as grade A, 18-981 (83.00%) as grade B, 3-076 (13.45%) as grade C, 422 (1.85%) as grade D, 75 (0.33%) as grade E, 156 (0.68%) as grade F, 1 (<0.01%) as grade G, and 2 (0.01%) as grade H; no MEs of grade I occurred. Among the 22-713 patients involved in MEs of grade B to I, 12-668 (55.77%) were male and 10-045 (44.23%) were female; their ages were from 1 day to 102 years; 2-453 (10.80%) were children (<18 years old), 11-374 (50.08%) were young and middle-aged adults (≥18 to <60 years old), and 8-886 (39.12%) were elderly (≥60 years old). A total of 234 patients were involved in serious MEs (grade E-I), including 134 (57.27%) males and 100 (42.73%) females, aged from 4 days to 94 years, of which 37 (15.81%) were children, 83 (35.47%) were young and middle-aged adults, 114(48.72%) were elderly. The serious MEs (grade E-I) mainly occurred in the administration link ［74.36% (174/234)］. The 155 grade A MEs did not involve person who triggered the ME and place where ME occurred. Among the 22-713 grade B-I MEs, 17-102 (75.30%) were triggered by physicians, 4-072 (17.93%) by pharmacists, 764 (3.36%) by nurses, 461 (2.03%) by patients and their family members, and 314 (1.38%) by other persons; the proportion of MEs triggered by physicians increased year by year for 4 consecutive years; the triggers of serious MEs were mainly patients and their family members ［61.97% (145/234)］. Among these MEs, 9-238 (40.67%) occurred in clinics, 7-183 (31.63%) in hospital wards, 4-620 (20.34%) in pharmacies, 1-063 (4.68%) in pharmacy intravenous admixture services, 213 (0.94%) in the nurse stations, 321 (1.41%) in patients′ home, 6 (0.03%) in the community health service stations, and 69 (0.30%) in other places. Among the 234-severe MEs, 129 (55.13%) occurred in the patient′s home, and the proportions of MEs and serious MEs occurred in the home increased year by year for 4 consecutive years. The top 3 contents of ME were wrong drug class (4-285, 18.40%), wrong dosage (4-115, 17.67%), and wrong administration frequency (2-808, 12.06%). The top 3 persons who discovered the ME were pharmacists (17-575, 74.74%), patients and their family members (2-654, 11.29%), and physicians (1-752, 7.45%). The top 3 factors causing ME were lack of related pharmacologic knowledge (8-665, 31.94%), tiredness (4-249, 15.66%), and insufficient training of medical workers (3-502, 12.91%).

An 82-year-old female patient with severe osteoporosis received an IV infusion of zoledronic acid 5 mg after the right hip artificial femoral head replacement. About 4 hours after the end of IV infusion, the patient presented chill, fatigue, myalgia and high fever. About 6 hours later the patient occurred nausea and vomiting. About 14 hours later the patient developed dyspnea, convulsions, loss of consciousness, and tachycardia. The results of laboratory tests showed the following results: carbon dioxide-combining power (CO2-CP)14 mmol/L, B-type natriuretic peptide (BNP) 1374.07 ng/L, prothrombin time (PT) 20 s, activated partial thromboplastin time (APTT) 37 s , alanine aminotransferase (ALT) 269 U/L, aspartate aminotransferase (AST) 279 U/L, blood urea nitrogen (BUN) 34.6 nmol/L, serum creatinine (Scr) 273 μmol/L. She was diagnosed as respiratory failure, multiple organ failure due to zoledronic acid. She was transferred to ICU, and was given a tracheal intubation with ventilator assisted breathing, she received   symptomatic treatments including those to keep heart rate and blood pressure stable, to protect the functions of liver and kidney. On day 7 in ICU, the patient recovered consciousness. The laboratory tests showed the following results: ALT 135 U/L, AST 137 U/L, BUN 35.3 nmol/L, Scr 217 μmol/L, CK-MB 2.1 μg/L. On day 53 in ICU, her heart rate was 55-86 beats/min, respiration rate was 21-25 times/min, blood pressure was 102-122/51- 69 mmHg (1 mmHg= 0.133 kPa), pulse oxygen saturation was 0.97-1.00. The results of laboratory tests were: ALT 38 U/L, AST 45 U/L, BUN 7.1 nmol/L, Scr 60 μmol/L, CK-MB 1.19 μg/L, myoglobin 0.03 μg/L and BNP 401 ng /L. On day 85 in ICU, the patient regained spontaneous respiration.

A 78-year-old female patient with hypertension （196/93-mmHg） received a slow IV infusion of urapidil injection 100-mg diluted into 250-ml of 0.9% sodium chloride injection to reduce blood pressure. The infusion rate was controlled at 40 drops/min. If the blood pressure dropped to the target value, the drug would be stopped temporarily. The blood pressure dropped to 152/70-mmHg when urapidil injection was intravenously infused for 40-min (about 80-ml). Then the drug was stopped temporarily. The nurse on duty did not introduce the patient′s condition and the use of urapidil to the nurse who would take turn on duty. The successive nurse did not check the doctor′s order and mistakenly infused the remained urapidil  170-ml within 60-min (60 drops/min). Five minutes later, the patient developed dizziness, fatigue, and severe vomiting, and the blood pressure dropped to 136/66-mmHg. Rehydration treatment was given imme- diately. About 2 hours later, the patient′s blood pressure increased to 158/76-mmHg and the symptoms were relieved.

近年,甘露醇静脉及口服给药的不良反多有报告,其中过敏反应较为常见,严重者可发生过敏性休克。还可致肾损害、心血管系统损害、肺水肿、中枢神经系统反应等严重不良反应,本文仅对近五年来甘露醇应用时有关不良反应的文献进行回顾,探讨导致不良反应的相关因素,以期引起临床工作者的注意。

An 87-year-old male patient was scheduled for electronic laryngoscopy examination due to pharyngeal discomfort. Before the examination, he was anesthetized locally with 10-ml dyclonine hydrochloride mucilage in his mouth and vomited out 5-minutes later. After spitting out the medicine, the patient developed shortness of breath, fatigue, and dyspnea suddenly 5-minutes later; cold sweat and syncope appeared 20-minutes later; his pulse oximeter oxygen saturation (SpO2) decreased to 0.50 and unconsciousness appeared 30-minutes later. Severe allergic reaction was diagnosed, which mainly manifested as acute respiratory failure and might be related to dyclonine hydrochloride mucilage. Endotracheal intubation and ventilator assisted ventilation were performed immediately, and anti-infection, expectorant, nutritional support, stable internal environment maintaining treatments were given at the same time. After 6 days′ treatments, the endotracheal intubation was removed and the nasal tube was used for oxygen inhalation. Then the SpO2 was 0.99 and the above-mentioned symptoms disappeared.

An 83-year-old male patient received moxifloxacin hydrochloride (moxifloxacin) 400-mg once daily orally for acute attack of chronic obstructive pulmonary disease. He developed scattered red rashes, accompanied by itching, on his both lower limbs 5 hours after the first dose. Next day, the rashes involved skin on the trunk, and purpura appeared on the multiple skin below the knees. Laboratory tests showed platelet count (PLT) 1×109/L，and thrombocytopenia related to moxifloxacin was considered. Moxi- floxacin was stopped and the treatments including hemostasis, anti-allergy, regulation of immune function, and platelet transfusion were given. On day 2 of drug withdrawal, his PLT was 3×109/L, and on day 4 the PLT was 35×109/L. He was transferred to a superior hospital and received the therapy including anti-immune response, platelet-raising, and hemostasis for 5 days. Then his PLT increased to 244×109/L.

Immune effector cell-associated neurotoxicity syndrome （ICANS） is a common adverse reaction of chimeric antigen receptor T-cell （CAR-T） immunotherapy. Its mechanism is mainly related to the destruction of brain mural cells, increase of cytokine level, the inflammation mediated by natural killer cells, and the activation of endothelial cells. The main clinical manifestations of ICANS are aphasia, tremor, dysgraphia, drowsiness, and epilepsy. In severe cases, asphyxia, coma, or brain edema may occur, and sometimes it is even life-threatening. The factors affecting ICANS include age, peak value of CAR-T amplification, product type, and disease type, etc. American Society for Blood and Marrow Transplantation recommends symptomatic and supportive treatments for mild ICANS and hormonal shock therapy for severe cases.

A 56-year-old male patient received an IV infusion of methylprednisolone 500-mg/d, which was changed to oral prednisone 40-mg/d after 3 days, for thyroid associated ophthalmopathy. Calcium carbonate, calcitriol, alendronate sodium, and esomeprazole magnesium enteric-coated tablets were given orally to prevent hormone-related adverse reactions. The renal function of the patient was normal in the past, but continued to decline after 1 month of medication. And at the end of 3 months after medication, the lowest estimated glomerular filtration rate (eGFR) was 33.1-ml/(min·1.73 m2). Renal diseases and urinary tract obstruction were excluded by routine urine analysis and color Doppler ultrasound examination of the kidneys. Kidney injury caused by esomeprazole magnesium enteric-coated tablets was considered. Then the drug was replaced by famotidine and the other drugs were continued. After 9 days, the renal function of the patient gradually recovered, with the eGFR of 74.0 ml/(min·1.73 m2) at discharge.

The recommendations of Guideline for Emergency Management of Anaphylaxis  answered 15 clinical questions about diagnosis, preparation for treatment, treatment measures, and post-treatment management of anaphylaxis and a total of 26 recommendations were formed. In the recommendations, the quality of evidence was divided into 4 levels: high, moderate, low, and very low. And the strength of recommendation was divided into 2 levels: strong and weak. The strength of recommendations was mainly determined by weighing the advantages and disadvantages, instead of relying on the quality of evidence. Emergency management of anaphylaxis in clinical practice could be carried out with reference to the recommendations of this guideline.

盐酸西布曲明是20世纪90年代后期开发的新型减肥药,其相关不良反应临床报道较少。本文综述了国内外对西布曲明安全性评价的有关文献,对该药的常见、少见不良反应,与其他药物的相互作用以及防治措施作一介绍,以供临床参考。

Insulin switching is very common in the treatment of diabetes mellitus, which is an important link that affects the safe use of insulin. At present, insulin switching, including selection of different insulin products, dosage adjustment, and patient education has been explained in the guidelines issued by the United States, the United Kingdom, Canada, and China. Relevant information on insulin switching is various and scattered and there is a lack of systemicity and comprehensiveness. It is suggested to refer to the guidelines of other countries, fully analyze the clinical characteristics of diabetes mellitus in China, and base on the real-world research data to formulate a systematic insulin switching guideline in line with China′s national conditions, in which the selection of insulin products, dose adjustment, patient education, dietary advice, and blood glucose monitoring, etc. can be described in detail. In addition, strengthening patient tracking and medication monitoring is also a necessary mean to ensure the safety in insulin switching.

A 60-year-old woman with connective tissue disease received  cyclosporine 300 mg once daily . On day 2 of adding cyclosporine, the patient  developed pharyngalgia. On day 3, she developed hematochezia, abdominal distension and abdominal pain. On day 14, she lost her vision of both eyes,  developed attacks of binoculus transient upper left gaze twice, a slight headache, and the elevated blood pressure (150/90 mmHg). Laboratory tests showed that the cyclosporine blood concentration was 372.4 μg/L. The results of cranial MRI showed bilateral frontal, parietal, occipital and temporal lobes symmetrical multiple patchy long T1, long T2 signals, the fluid attenuated inversion recovery sequence showed high signal, which suggested the vascular edema.  The patient was diagnosed as reversible posterior encephalopathy syndrome due to cyclosporine. Cyclosporine was stopped immediately. She received an IV infusion of methylprednisolone 40 mg once daily and other symptomatic supportive treatments including deprivation of body fluids, anti-epileptic, and blood pressure control, etc. On day 5 of treatment, her vision began to recover, but she had blurred vision and visual hallucinations. On day 7 of treatment, the degree of abdominal distension and abdominal pain was relieved, vision was recovered obviously, visual hallucination disappeared. Her blood pressure returned to normal (125/86 mmHg). The result of laboratory tests showed the cyclosporine blood concentration 139.2 μg/L. The result of MRI reexamination showed that the original focus disappeared.

Monoclonal antibody (mAb) drugs belong to protein drugs, which are characterized by high relative molecular weight, strong polarity, and limited transmembrane. Their pharmacokinetics have certain particularity and complexity, and problems such as large individual differences in therapeutic effects, diverse biological effects, and loss of therapeutic response exist in clinical application. The blood concentration of mAb drugs is affected by many factors including the number of receptors at the target site, the level of anti-drug antibody, and the interaction between drugs. Early monitoring is helpful to timely adjust the dose of mAb drugs, improve the efficacy, and avoid or reduce the occurrence of adverse reactions. Clinical monitoring should be actively carried out to improve the level of rational use of mAb drugs and the ability of early warning of adverse reactions, so as to reduce the drug-induced injury in patients.

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 56-year-old male patient with nasopharyngeal carcinoma had progressed disease after receiving radiotherapy, chemotherapy, and targeted therapy, etc. Then he received chemotherapy combined with immunotherapy (capecitabine and sintilimab). Before receiving the 3rd immunotherapy, no abnormality was found in the relevant examination in the patient. On the 3rd day of treatment, he developed cough, shortness of breath, and other symptoms, and chest CT imaging indicated inflammatory lesion of both lungs. The results of sputum culture, sputum smear examination, G test, GM test, and autoantibody examination were all negative. Infectious pneumonia and interstitial pneumonia with autoimmune features were excluded. The common respiratory adverse reaction to capecitabine was pharyngeal discomfort, and no large-scale pneumonia caused by capecitabine was reported. Therefore, it was considered to be immune- associated pneumonitis cause by sintilimab. Treatments such as intravenous injection of methylprednisolone, IV infusion of cefoperazone sodium and sulbactam sodium and moxifloxacin were given and the patient′s condition was improved. After that, methylprednisolone dose was gradually reduced, and then changed to oral prednisone. On the 10th day of oral prednisone, the symptom of shortness of breath worsened. Chest CT imaging indicated that the pneumonitis was more severe than before. Intravenous methylprednisolone was re-given but the condition was not improved.

A 60-year-old male patient with lung cancer received IV infusions of toripalimab 200-mg, bevacizumab 500-mg, and pemetrexed 1 g (the treatment was given on day 1 and 21 days was a cycle) due to the progression of tumor after 26 months of first-line and second-line chemotherapy successively. His thyroid function was normal before treatment. After the second medication of toripalimab (on day 30 after the first medication), the patient developed symptoms such as increased heart rate, fear of heat, hyperhidrosis, and weight loss. The reexamination of thyroid function showed triiodothyronine (T3) 3.4-nmol/L, thyroxine (T4) 305.0-nmol/L, free triiodothyronine (FT3) 13.1-pmol/L, free thyroxine (FT4) 55.7-pmol/L, thyroid stimula- ting hormone (TSH) 0.02 mU/L, thyroglobulin (Tg) 32.7-μg/L, antithyroglobulin antibody (TgAb) 531.0 kU/L, antithyroid peroxidase antibody (TPOAb) 318.0 kU/L, and thyroid stimulating hormone receptor antibody (TRAb) 1.00-U/L. Hyperthyroidism was considered, anti-tumor treatment was suspended, and symptoms were improved after metoprolol treatment. Ninety-seven days after the first toripalimab treatment, the patient developed symptoms such as chills, dizziness, fatigue, eyelid edema, weight gain, etc. The laboratory tests showed  T3-0.3-nmol/L, T4-20-nmol/L, FT3-1.0-pmol/L, FT4-1.8-pmol/L, TSH>100.00 mU/L, and carcinoembryonic antigen 251-μg/L. Hypothyroidism was considered, but the tumor progressed, so the treatment of toripalimab was restarted and thyroxine was supplemented at the same time. The patient′s thyroid function was gradually improved and then remained normal. More than 13 months after the first medication of toripalimab, the laboratory tests showed T3-1.3-nmol/L, T4-137.0-nmol/L, FT3-3.8-pmol/L, FT4-21.1-pmol/L, TSH 6.03 mU/L, Tg 3.9-μg/L, TgAb 432.0 kU/L, and TPOAb 222.0 kU/L.

A 54-year-old female patient was scheduled to undergo laparoscopic segmental resection for hepatic hemangioma. Thirty minutes before operation, an IV infusion of etimicin sulfate and sodium chloride injection 100-mg was given to prevent infection. After 2-minutes of medication, the patient developed general numbness, apathy, redness of the skin, cold sweating, and dyspnea. Her breath rate was 22 times per minute, heart rate was 110 beats per minute, blood pressure was 45/32-mmHg, and pulse oxygen saturation (SPO2) was undetectable. Anaphylactic shock due to etimicin was considered. Etimicin was discontinued immediately and treatments such as oxygen inhalation, epinephrine, methylprednisolone sodium succinate, norepinephrine, and intravenous volume expansion were administered. Twenty minutes later, the patient′s symptoms were basically relieved, with breath rate 18 times per minute, heart rate 88 times per minute, blood pressure 108/60-mmHg, and SPO2-0.99. Thirteen hours later, all symptoms disappeared.

Objective To explore the efficacy and safety of crisaborole ointment (crisaborole) treatment in children with atopic dermatitis (AD).　Methods PubMed, Embase, Medline, CNKI, Wanfang Medicine, VIP, and Chinese Medical Journal Databases were searched (up to March 2022) and the literature on randomized controlled trials (RCTs) and cohort studies of crisaborole treatment in children with AD was collected. The quality of RCTs and cohort studies was evaluated using the modified Jadad scale and Newcastle- Ottawa scale, respectively. Data on effective rate and incidence of adverse event in children treated with crisaborole were extracted. The meta-analysis of single proportions was performed with Stata 15-software.　Results A total of 8 studies (4 RCTs and 4 prospective cohort studies, respectively) were entered in the analysis, including 1-855 children (aged from 3 months to 17 years) treated with crisaborole. The 8 studies were all of high quality. The meta-analysis of single proportions showed that the effective rate of children with AD treated with crisaborole for 14-28 days was 46% ［95% confidence interval (CI): 32%-61%］, the incidence of adverse events during treatment was 28% (95%CI: 19%-38%), and the incidence of treatment discontinuation due to adverse events was 1% (95%CI: 0-2%). Most of the adverse events caused by crisaborole were local skin reactions, mainly characterized by local pain, itching, dermatitis, paresthesia, and local infection, etc. Seven of the 8 studies reported the pain at the application site, and the incidence of pain at the application site was 17% (95%CI: 11%-24%). Most adverse events were mild to moderate and could be alleviated without treatment. Serious adverse events occurred in 8 patients (0.4%), 7 of which were unrelated to the treatment drugs.　Conclusion Crisaborole has good efficacy and safety in the treatment of mild to moderate AD in children.

A 63-year-old male patient took tamsulosin hydrochloride sustained release capsules 0.2-mg daily and Qianliexin capsules 2 g thrice daily by himself for urinary urgency and urodynia. Twenty- five days later, he developed itchy skin, deep brown urine, nausea, fatigue, and loss of appetite. Laboratory tests showed alanine aminotransferase (ALT) 265-U/L, aspartate aminotransferase (AST) 163-U/L, total bilirubin (TBil) 155.1-μmol/L, direct bilirubin (DBil) 74.7-μmol/L, indirect bilirubin (IBil) 80.4-μmol/L, alkaline phosphatase (ALP) 261-U/L, and gamma-glutamyltransferase (γ-GT) 184-U/L. Liver biopsy showed the cholestatic liver injury. He was diagnosed as acute drug-induced liver injury, which might be related to the above 2 drugs. The above 2 drugs were stopped and oral ursodeoxycholic acid 250-mg thrice daily was given. On day 42 of drug withdrawal, laboratory tests showed ALT 368-U/L, AST 179-U/L,TBil 504.9-μmol/L, DBil 382.8-μmol/L, IBil 122.1-μmol/L, ALP 201-U/L, and γ-GT 58-U/L. On day 91 of drug withdrawal, laboratory tests showed ALT 78-U/L, AST 62-U/L, TBil 138.1-μmol/L, DBil 118.2-μmol/L, IBil 20.2-μmol/L, ALP 140 U/L, and γ-GT 31-U/L. The patient′s liver function returned to normal 135 days after drug withdrawal.

Based on the potentially inappropriate medication (PIM) criteria in older adults of the United States, Canada, Japan, France, Norway, Germany, South Korea, Austria, Thailand and Chinese Taiwan, and combined with the severe adverse drug reaction (ADR) data in the elderly of China National Center for ADR Monitoring, ADR monitoring center in the Chinese People′ s Liberation Army，Beijing Center for ADR Monitoring and drug data of people over 60 years from Beijing 22 hospitals, 3 rounds of Delphi expert consultation were made to accomplish the final criteria. The criteria was divided into high risk and low risk medications according to the experts evaluation and divided into A and B alert categories according to DDDs. Finally, criteria of potentially inappropriate medications for older adults in China was formed, including medication risk and medication risk under morbid state. A sum of 13 categories 72 medications or medication classes were selected in medication risk part, for example, neurologic medication，psychotropic medication，antipyretic, analgesic and anti-inflammatory medication and cardiovascular medication. The 72 medications were divided into 28 kinds of high risk and 44 kinds of low risk medications. The 72 medications were also divided into 24 kinds of preferred alert medications(A) and 48 kinds of routinely alert medications(B)．PIM in the elderly under morbid state contained 44 medications or medication classes under 27 kinds of morbid states, in which 35 medications under 25 morbid states of preferred alert medications (A) and 9 medications under 9 morbid states of routinely alert medications (B).

A 77-year-old female patient with pneumonia received an IV infusion of piperacillin sodium and tazobactam sodium 4.5 g dissolved in 0.9% sodium chloride injection 100 ml, 3 times daily. The patient′s WBC, RBC, Hb, and PLT levels were 2.0×109/L， 2.9×1012/L， 88 g/L， and 10×109/L, respectively before using the medicine. On day 4 of drug administration, her WBC, RBC, Hb and PLT were 2.0×109/L, 2.9×1012/L, 88 g/L, and 10×109/L, respectively. The result of  bone marrow smear showed decrease of nucleated cell, granulocyte series,  and  erythrocyte series′ hyperplasia. The proportion and morphology of  cells at different stages were approximately normal. She was diagnosed as acute myelosuppression associated with piperacillin sodium and tazobactam sodium. Piperacillin sodium and tazobactam sodium were stopped. On day 15 of drug withdrawal, her WBC, RBC, Hb and PLT were 4.8×109/L, 3.0×1012/L, 88 g/L, and 218×109/L, respectively.

通过检索Medline和中国医院数字图书馆数据库,对体内药物相互作用的发生率、发生机制、临床干预方法等内容进行综述,以期引起医务工作者的充分认识,减少药源性损害,提高临床治疗水平。

A 45-year-old male patient was treated with canagliflozin 100-mg once daily orally for type 2 diabetes mellitus due to poor blood sugar control. On the 4th day of medication, the patient developed slight abdominal distension and fatigue; on the 5th day, the patient felt nausea and general fatigue, and the color of urine became dark brown. The laboratory tests showed serum creatinine (Scr) 136-μmol/L, blood urea nitrogen (BUN) 9.7-mmol/L, urine protein (+), and urinary occult blood (++). Acute kidney injury induced by canagliflozin was considered. Canagliflozin was stopped, and acarbose 50-mg (before meal), 2 Haikun Shenxi capsules (海昆肾喜胶囊), and 3 Jinshuibao capsules (金水宝胶囊) orally thrice daily were given. After 2 days of drug withdrawal, the symptoms of nausea and fatigue disappeared, and the color of urine was normal. After 5 days of drug withdrawal, laboratory tests showed fasting blood glucose 5.6-mmol/L, Scr 112-μmol/L, BUN 8.5-mmol/L, urine protein (-), and urine occult blood (-). After 19 days of drug withdrawal, the patient′s renal function indexes were all within the normal range, and no discomfort symptoms recurred.

In 2021, a total of 19-585 cases of medication error (ME) from 275-hospitals in 28 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 7.84% compared with that in 2020 (255-hospitals), and the number of reported ME cases increased by 23.57% compared with that in 2020 (15-849 cases). In 19-585 cases of ME reports, 278 (1.42%) were classified as grade A, 16-221 (82.82%) as grade B, 2-442 (12.47%) as grade C, 410 (2.09%) as grade D, 95 (0.49%) as grade E, 133 (0.68%) as grade F, 1 (<0.01%) as grade G, 4 (0.02%) as grade H, and 1 (<0.01%) as grade I. Among the 19-307 patients with ME of grade B to I, 10-528 (54.53%) were male and 8-779 (45.47%) were female; they aged from 1 day to 102 years, of which 2-236 (11.58%) were children (<18 years old), 9-794 (50.73%) were young and middle-aged people (≥18 to <60 years old), and 7-277 (37.69%) were elderly people (≥60 years old). A total of 234 patients were involved in serious MEs (grade E-I), including 129 (55.13%) males and 105 (44.87%) females, aged from 3 months to 99 years, of which 45 (19.23%) were children, 88 (37.61%) were young and middle-aged people, 101 (43.16%) were elderly people. Among the 16 patients with severe MEs caused by mistaken use of drugs, 14 were children, which was a double of the number in 2020 (7 in 2020); only 3 cases were reported for mistaken use of drugs in children from 2012 to 2019. The 278 grade A MEs did not involve person who triggered the ME and place where ME occurred. Among the 19-307 grade B-I MEs, 13-932 (72.16%) were triggered by physicians, 3-961 (20.52%) by pharmacists, 541 (2.80%) by nurses, 412 (2.13%) by patients and their family members, and 461 (2.39%) by other persons; the proportion of MEs triggered by physicians and patients and their family members increased year by year for 4 consecutive years (60.89%, 65.46%, and 68.05% in 2018, 2019, and 2020 by physicians, and 1.06%, 2.04%, and 2.08% in 2018, 2019, and 2020 by patients and their family members, respectively); 8-662 MEs (44.87%) occurred in clinics, 5-256 (27.22%) in hospital wards, 3-856 (19.97%) in pharmacies, 977 (5.06%) in pharmacy intravenous admixture services, 289 (1.50%) in the nurse stations, 239 (1.24%) in patients′ houses, 6 (0.03%) in the community health service stations, and 22 (0.11%) in other places; the proportion of ME occurred in clinics and at home increased year by year for 4 consecutive years (37.32%, 37.74%, and 43.24% in 2018, 2019, and 2020 in clinics, and 0.41%, 0.89%, and 1.02% in 2018, 2019, and 2020 at home, respectively). The top 3 contents of ME were wrong dosage, wrong drug class, and wrong administration frequency. The top 3 persons who discovered the ME were pharmacists, patients and their family members, and physicians. The top 3 factors causing ME were lack of related pharmacologic knowledge, tiredness, and insufficient training of medical workers.

In recent years, club drugs are often abused by teens and young adults, The common club drugs are gamma- hydroxybutyrate, ktamime, MDMA, and flunitrazepam. This paper describes the acute toxic effects of the four drugs in order to be beneficial to the management of their poisoning in clinical practice.

Objective To analyze the risk of diabetes mellitus related to immune checkpoint inhibitors (ICI).　Methods The adverse event (AE) reports on fulminant type 1 diabetes mellitus (FT1DM), type 1 diabetes mellitus (T1DM), diabetic ketoacidosis (DKA), which were related to duvalizumab, pabolizumab, nivolumab, and atezolizumab in the US FDA Adverse Event Reporting System from the first quarter of 2004 to the second quarter of 2021， were collected.The correlation between the 4 drugs and FT1DM, T1DM,and DKA were evaluated using proportional reporting odds ratio (PRR) method.AE with reports ≥3, PRR value≥2, and χ2≥4 were judged to have statistical correlations with drugs. The greater the PRR value, the stronger the correlation between AE and drugs and the stronger the risk signals.　Results A total of 1-468 AE reports on diabetes mellitus were collected, 53, 386, 957, and 72 of which were related toduvalizumab, pabolizumab, nivolumab, and atezolizumab, respectively. For duvalizumab, pabolizumab, nivolumab, and atezolizumab, the PRR reflecting the correlation with FT1DM were 21.97 (χ2=40.71), 71.50 (χ2=3-531.21), 294.30 (χ2=4-3915.75), and 33.58 (χ2=279.70), respectively; the PRR reflecting correlation with T1DM were 12.12 (χ2=162.08), 21.04 (χ2=3391.17), 20.99 (χ2=5816.11), and 9.71 (χ2=224.81), respectively; the PRR reflecting correlation with DKA were 6.93 (χ2=161.26), 4.78 (χ2=426.52), 6.82 (χ2=1797.15), and 3.04 (χ2=41.84), respectively. The 4 drugs were statistically correlated with their corresponding AE. The order of risk signal intensity for corresponding AE was FT1DM > T1DM > DKA. The order of risk signal intensity for FT1DM were nivolumab > pabolizumab > duvalizumab > atezolizumab, for T1DM were pabolizumab ≈ nivolumab > duvalizumab > atezolizumab, for DKA were duvalizumab ≈ nivolumab > pabolizumab > atezolizumab.　Conclusions Duvalizumab, pabolizumab, nivolumab, and atezolizumab all can cause diabetes mellitus. The risk signal intensity was the strongest for FT1DM, followed by T1DM and DKA in order.

Objective To understand the main adverse event (AE) related to denosumab and the risks and provide reference for the safe use of the drug in clinic.　Methods The AE reports on denosumab included in the US FDA Adverse Event Reporting System from the second quarter of 2010 to the first quarter of 2021 were collected, and the AE risk signals was explored using proportional reporting odds ratio (PRR) method. AEs with ≥3 reports, PRR value ≥2, and χ2≥4 were defined as positive risk signals. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities 24.0. The PTs of top 50 adverse event reports and signal intensity were selected and analyzed.　Results A total of 132-764 AE reports with denosumab as the primary suspected drug were collected, involving 5-571 PTs, and 641 positive risk signals were selected. After the second screening, the top 50 PTs in the number of AE reports and the top 50 PTs with great PRR values were obtained, and 93 PTs were included in the analysis after sifting out the repeated, involving 114-617 AE reports. The top 5 PTs in the number of AE reports were off-label use (28.7%, 32-863/114-617), death (14.2%, 16-230/114-617), osteonecrosis of the jaw (6.0%, 6-861/114-617), arthralgia (4.7%, 5-420/114-617), and limb pain (4.1%, 4-727/114-617). The top 5 PTs with the high signal intensity were giant-cell tumour of bone (PRR=402.7), malignant giant-cell tumour of bone (PRR=325.2), C-telopeptide increase (PRR=169.4), exostosis of jaw (PRR=163.2), and ionised calcium abnormal (PRR=158.1). The top 5 SOC involving AE reports were injury, poisoning and procedural complications (35.9%, 41-757/114-617), musculoskeletal and connective tissue disorders (32.7%, 37-455/114-617), general disorders and administration site conditions (18.2%, 20-814/114-617), surgical and medical procedures (4.1%, 4-744/114-617), and investigations (2.9%, 3-290/114-617). Forty-four PTs were not included in the drug instructions, of which 23 were related to the oral cavity.　Conclusions Denosumab AE with the most reports were off-label use and osteonecrosis of the jaw. The risk signals of osteonecrosis of the jaw and recurrence or deterioration of giant-cell tumor of bone was strong. Most of the AE risk signals that were not included in the instructions are oral problems.

Objective To explore the application value of radioisotope tracer technology in clinical research of biological drugs.　Methods The pharmacokinetic properties of mepuzumab in healthy volunteers were evaluated by measuring the radioactive concentrations of iodine in blood and urine samples of 3 healthy volunteers at different time points within 14 days after intravenous infusion of 131I-labeled international class I new drug mepuzumab (Trial 1). Positron emission computed tomography (PET/CT) was performed on 6 healthy volunteers after intravenous injection of 68Ga-labeled nucleic acid aptamer Sgc8, and the standard uptake values of 68Ga-Sgc8 in different organs were measured to evaluate its biodistribution in healthy humans (Trial 2). Nine patients with suspected neuroendocrine tumors underwent single photon emission and X-ray computed tomography (SPECT/CT) 4 hours after intravenous injection of 99mTc-labeled octreotide to determine the radioactive uptake level in the regions of interest; the affinity and targeting of 99mTc- labeled octreotide to somatostatin receptor subtype 2 (SSTR2) were evaluated in combination with the immunohistochemical staining results of SSTR2 in patients′ biopsy tissues (Trial 3).　Results The 3 healthy volunteers included in Trial 1 were male, aged 28, 45, and 25 years respectively; the injection doses of 131I-labeled mepuzumab were 21.0, 25.9, and 17.6-mg, and the injection doses of radioactivity were 364, 420, and 304 MBq, respectively. Among the 6 healthy volunteers included in Trial 2, 3 were male and 3 were female, with an age of (46±11) years, ranging from 35 to 63 years. The dose of radioactivity injected was (80±7) MBq, ranging from 69 to 87 MBq. Among the 9 patients included in Trial 3, 5 were male and 4 were female, with an age of (54±10) years, ranging from 39 to 69 years. The dose of radioactivity injected was (777±74) MBq, ranging from 740 to 925 MBq. After intravenous infusion of 131I-labeled mepuzumab, the blood radioactivity concentration reached the peak 1.5-hours later. 131I-labeled mepuzumab mainly bound to blood cells, and its whole-blood clearance half-life was 420-hours. The urine radioactivity concentration reached the peak 16-24-hours after administration and then gradually decreased after 24-hours of administration. After intravenous injection of 68Ga-labeled Sgc8, the organs with strong to weak radioactive signals were bladder, kidney, heart, uterus, liver, spleen, gallbladder, large intestine and lung. Within 3 hours after drug administration, the clearance rate was fastest in heart, followed by uterus, kidney, and liver; the clearance rate was slower in spleen and gallbladder and were slowest in large intestine and lung. All of the 9 patients had abnormal radioactivity accumulation 4 hours after intravenous injection of 99mTc-labeled octreotide and the immunohistochemical staining results of biopsy tissues showed strong positive expression of SSTR2, indicating that 99mTc-labeled octreotide had good affinity and targeting to SSTR2. The safety evaluation showed that in Trail 1, one subject developed iodine-related hyperthyroidism one month after intravenously infusion of 131I-labeled mepuzumab, which returned to normal after 8 months of continuous monitoring without intervention. No adverse reactions occurred in other subjects.　Conclusions Radioisotope tracer tech- nology can noninvasively, dynamically, and visually evaluate the pharmacokinetics, biological distribution, and targeting of biological drugs in human body. It has good safety and great application value in the clinical evaluation of biological drugs.

Objective To explore the clinical features of tacrolimus-associated posterior rever- sible encephalopathy syndrome (PRES) in patients after kidney transplantation.　Methods Relevant databases at home and abroad were searched as of August 2020, and case reports of tacrolimus-associated PRES after kidney transplantation were collected. Clinical information including patient′s basic characteristics, tacrolimus application (such as route of administration, dose, blood concentration, drug combination regimen, etc.), and the occurrence time, clinical manifestation, imaging characteristics, intervention measures, and outcomes of PRES were extracted and analyzed by descriptive statistical method.　Results A total of 16 patients were enrolled in the study, including 7 males and 9 females, aged from 7 to 54 years with a median age of 26 years. Of them, 6 patients were <18 years old and 10 patients were ≥18 years old. Among the 16 patients, 8 received intravenous administration and 8 oral administration. Thirteen patients had records of drug combination regimen and 1, 2, and 3 immunosuppressants were combined in 3, 8, and 2 patients, respectively. PRES occurred from 3 days to 3 months after renal transplantation and 10 patients (62.5%) occurred within 1 month after operation. Eleven of 13 patients who underwent tacrolimus plasma concentrations testing did not exceed the upper limit of the treatment window when PRES occurred. The main symptoms of PRES included convulsions/seizures-like seizures (in 11 patients), visual abnormalities (in 7 patients), persistent headache (in 6 patients), and coma or disturbance of consciousness (in 6 patients). CT and/or magnetic resonance imaging were performed in all 16 patients. Imaging features of cerebral edema or vasogenic cerebral edema were found in 15 patients and the lesions located mainly in occipital lobe (13 patients), parietal lobe (12 patients), and the frontal lobe (8 patients). After discontinuation or reduction of the tacrolimus dose and/or giving symptomatic and supportive treatments for 2-44 days (the median time of 9 days), symptoms subsided in all 16 patients and imaging examination showed cerebral edema, vasogenic cerebral edema, and other lesions subsided in 15 patients.　Conclusions Tacrolimus-associated PRES mostly occurred within 3 months after renal transplantation, which was not related to the route of administration or blood concentration of tacrolimus. The clinical manifestations of tacrolimus-associated PRES were similar to those caused by other factors. After discontinuation of tacrolimus, reduction of drug dose and/or administration of symptomatic treatment, most of the symptoms disappeared quickly and the imaging changes returned to normal.

A 72-year-old male patient received anti-infectious treatments with piperacillin sodium and tazobactam sodium, moxifloxacin, and posaconazole, and expectorant treatment with acetylcysteine for pulmonary infection after lung transplantation; original antirejection therapy with tacrolimus and mycophenolate mofetil was continued. Before treatments, serum creatinine was 98-μmol/L and blood urea nitrogen was 3.4-μmol/L. On the 5th day of treatments, the trough blood concentration of tacrolimus increased to 22.9-μg/L, serum creatinine increased to 497-μmol/L, and blood urea nitrogen increased to 17.91-mmol/L. During the consultation, the clinical pharmacists learned that the patient used posaconazole and tacrolimus in combination. They also understood that posaconazole could inhibit the activity of liver cytochrome P450 (CYP) 3A4, while tacrolimus was mainly metabolized by CYP3A4 by searching the literature. Then it is considered that the acute kidney injury caused by tacrolimus occurred due to the increase of blood concentration following the simultaneous application of tacrolimus and posaconazole. Clinical pharmacists recommended that posaconazole was replaced by caspofungin and the dose of tacrolimus was reduced. The clinician adopted the above recommendations and the patient was given continuous venous-venous hemofiltration meantime. Eight days later, the patient′s serum creatinine level gradually decreased to 334-μmol/L, blood urea nitrogen was 7.6-mmol/L, and urine volume was 200-ml. Then hemodialysis was performed 3 times a week; 1 month later, the patient′s serum creatinine was 115-μmol/L, and blood urea nitrogen was 7.2-mmol/L.

Objective To explore the risk signals of edoxaban-related adverse reactions and provide reference for the clinical safety of edoxaban. Method The US FDA adverse Event Reporting System database was searched and the adverse event (AE) reports on edoxaban as the suspicious drug from the second quarter of 2011 to the first quarter of 2022 were collected. An AE with reports>3, 95% confidence interval (CI) lower limit of ROR>1, PRR>2, and χ2>4 was defined as a positive signal. AEs were counted and classified using the preferred term (PT) and system organ class of Medical Dictionary for Regulatory Activities 25.0. The PTs of top 50 in AE report amount and signal intensity were selected and analyzed.　Results A total of 4-113 AE reports on edoxaban as the suspicious drug were collected and 996 PTs were involved. After calculation using ROR and PRR methods, 158 positive risk signals were obtained, involving 1-898 AE reports. PTs of the top 50 in AE report amount and signal intensity were merged 89 PTs were selected after screening out duplicates, involving 1-468 AE reports. The top 5 PTs in report amount were dyspnea, anemia, atrial fibrillation, melena, and cardiac failure; the top 5 PTs in signal intensity were angiodysplasia, urogenital haemorrhage, cardiac amyloidosis, chorea, and ischaemic cerebral infarction/cardioac- tive drug level increased. Fourty-five PTs were not included in the drug labels. Of them, acute renal injury, renal impairment, and interstitial lung disease were with more AE reports and stronger signals.　Conclusions Bleeding-related events are still the key AEs that need to be monitored during the use of edoxaban. Edoxaban may also lead to renal injury and interstitial lung disease, which requires special attention.

The ocular adverse reactions of paclitaxels can involve the ocular surface, ocular appendages and intraocular tissue, with various clinical manifestations, such as dry eye, lacrimal duct obstruction, conjunctivitis, keratitis, macular edema, retinal injury, optic nerve injury, etc., which can lead to irreversible visual impairment. The mechanism of ocular adverse reactions is still unclear. In these adverse reactions, macular edema may be related to the dysfunction of retinal pigment epithelial cells and Müller cells caused by paclitaxel, and others may be related to the cytotoxicity of paclitaxels. Baseline eye examination should be performed prior to the use of paclitaxels, and new ocular symptoms should be closely monitored during the treatment. Ocular adverse reactions can be diagnosed definitively through routine ophthalmic examination. The main treatments are timely adjustment of drugs and symptomatic treatments.

A 3-day and 16-hour old male newborn was treated with IV infusion of meropenem 0.136 g once per 12-h combined with vancomycin 0.05 g once per 12-hours for severe infection. The platelet (PLT) was 116×109/L before treatment and reduced to 7×109/L after 11-h of treatment. Apheresis platelet by intravenous infusion was added, and PLT was 32×109/L 3 days later.Clinical pharmacists remind doctors to pay attention to adverse reactions of vancomycin when participating in ward rounds, and monitor the blood concentration of vancomycin in time. The physicians considered that the thrombocytopenia might be related to severe infection, and methylprednisolone, human immunoglobulin, cryoprecipitated antihemophilic factors, apheresis platelet products and etc. were added. The PLT increased to a transient level of 121×109/L and then continued to decrease. After 8 days of treatment, the platelet PLT decreased to 30×109/L and the trough concentration of vancomycin was 27.0-mg/L. Thrombocytopenia caused by vancomycin was considered.The pharmacist recommended temporary discontinuation of vancomycin. Vancomycin was stopped, PLT was 174×109/L 5 days later.

为了解非典型抗精神病药物引起锥体外系症状(EPS)的情况,利用Medline检索系统对已公开发表的临床随机对照试验与流行病学资料进行分析。非典型抗精神病药物间引起EPS的程度各有差异,有的与剂量相关,总体较经典的抗精神病药物发生率低,严重程度轻。但临床仍应重视锥体外系症状的预防与治疗问题。

太尼透皮贴剂是一种新型强效镇痛透皮缓释给药剂型,使用方法简便,不良反应较低,止痛效果好,广泛用于癌性疼痛(CP)和非癌性疼痛(NCP)的治疗。常见的不良反应有便秘、恶心、呕吐和嗜睡等。但如果使用不当或过量,可造成呼吸抑制甚至死亡。因此,使用芬太尼透皮贴剂时应正确选择适应证,掌握个体用药剂量,避免严重不良反应的发生。

A 78-year-old female patient was treated with orelabrutinib 100-mg once daily orally due to recurrence of lymphoma. On the 2nd day of treatment, the patient′s fecal occult blood was weakly positive. Three days later, fibrinogen was 0.61-g/L. After intravenous infusion of cryoprecipitated coagulation factor and frozen plasma, the fibrinogen level rose slightly. The patient did not follow the doctor′s advice and took orelabrutinib irregularly, and her fibrinogen level recovered to 1.71-g/L. After further regular treatment with orelabrutinib, her fibrinogen decreased to 0.74-g/L and irregular skin ecchymosis and bleeding spots appeared in the inner side skin of both lower limbs. The fibrinogen in the patient returned to 2.17-g/L after temporary suspension of orelabrutinib and receiving 2 times of intravenous infusion of cold precipitated coagulation factor 10 U, then decreased to 0.94 g/L after reuse of orelabrutinib, and finally recovered to 3.82-g/L after 3 times of intermittent infusion of cold precipitated coagulation factor. It is considered that the hypofibrinogenemia in the patient was caused by orelabrutinib.

There are risks of medication error in the whole process of drug use and management in the operating room. The types of medication errors in operating room include prescription issuing/doctor′s order giving error, prescription/doctor′s order delivery error, drug dispensing error, labeling error, preparation error, drug application technology error, drug monitoring error, drug storage error, essential drug setting error, etc. The risk factors of medication errors in the operation room mainly exist in the links of prescription issuing and delivery, drug dispensing and distribution, drug administration and monitoring, drug management, etc. The prevention strategies of medication errors in operating room include technical strategies (mandatory and constraint strategies, implementation of automation and computerization, development of standardized identifiers and processes, establishment of audit project lists) and management strategies (recommending the management mode of operation pharmacy, increasing the support of clinical pharmacy, storing drugs in different areas in operation room, allocating human resources reasonably, standardizing management of drug maintenance, advocating safe drug use culture, and strengthening professional skills training based on post competency). This guideline is applicable to all personnel involved in the use and management of drugs in the operating room.

Medication rationality index (MAI) scale sets up 10 items to evaluate the rationality of prescription medication, including indication, effectiveness, dosage, correct direction, practical direction, drug-drug interaction, drug-disease interaction, duplication, duration, and cost. MAI scale has good reliability, which can be used to evaluate the rationality of drug use and the non-essential drug use, the potential inappropriate medication in elderly patients, verify the reliability and effect of irrational drug use detection software, quantify clinical intervention measures, and predict adverse events and quality of life. Since MAI scale application involves subjective judgment, evaluators should be trained before use.

Objective To explore the effects of tenofovir alafenamide fumarate (TAF) and tenofovir disoproxil fumarate (TDF) on blood lipid.　Methods The relevant databases (up to August 31, 2021) were searched. The data of dyslipidemia in treatment of hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection with TAF (trial group) and TDF (control group) in randomized controlled trials (RCTs) were collected. Methodological quality was evaluated by bias risk assessment tool of Cochrane collaborative network, and the meta-analysis was conducted using RevMan 5.3-software. The effect value was the risk ratio (RR) and its 95% confidence interval (CI).　Results A total of 11 RCTs were enrolled in the analysis, including 4 on the treatment of hepatitis B (HBV subgroup) and 7 on the treatment of AIDS (HIV subgroup), and the methodological quality evaluation results showed low risk of bias for all. Eleven thousand eight hundred and eighty-eight patients were involved in the 11 RCTs, of which 6-273 were in the trial group and 5-615 in the control group. The results of meta-analysis showed that the incidences of increased low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) with the severity of ≥3 grade were higher in the trial group than those in the control group and the differences of incidences in LDL-C and TC increase were significant between the 2 groups ［LDL-C: 2.9% (157/5-347) vs. 0.8% (37/4-727), RR=3.39, 95%CI: 2.35-4.89, P=0.001; TC: 0.7% (36/4-880) vs. 0.1% (6/4-397), RR=4.25, 95%CI: 1.91-9.45, P<0.001; TG: 0.5%（16/3-157） vs. 0.3%（8/3-102），RR=1.83，95%CI：0.81-4.15, P=0.140］. The changes of blood lipid after treatment were compared and the results showed that the increase of LDL-C was higher in the trial group (14.00-mg/dl) than that in the control group (4.00-mg/dl), and the difference was statistically significant (P=0.004).　Conclusion TAF can significantly increase the levels of LDL-C and TC in patients.

A 69-year-old man was treated with adalimumab 80-mg subcutaneously for psoriasis for the first time. Two days later, the patient developed diffuse erythema with pruritus. Because the active stage of psoriasis was not excluded, adalimumab 40-mg subcutaneous injection was continued once a week for 4 times. The patient′s skin erythema and pruritus continued to worsen. After intravenous infusion of methylprednisolone sodium succinate 40-mg/d for 1 week, the systemic erythema and pruritus were slightly relieved, but the condition was repeated after stopping the drug. Urine routine and sediment analysis showed urinary occult blood (+++), 190 red blood cells/μl, urinary protein（+）, and serum creatinine 80-μmol/L. Renal biopsy and skin histopathology suggested IgA nephropathy and psoriasiform dermatitis, respectively. After consultation with dermatologists, erythroderma caused by deterioration of psoriasis was considered. Excluding other factors, it is considered that IgA nephropathy and erythroderma were probably induced by adalimumab. Methotrexate 10-mg per week was given orally and halometasone ointment was used externally. The skin damage in the patient was gradually improved. Hematuria and proteinuria were self-relieved slowly.At one-year of follow-up, the patient′s renal function and urine routine remained normal, and nephropathy and rash did not recur.

Objective:To investigate adverse effects associated with traditional Chinese medicines for clinical reference.Method:ADR reports of our hospital during1998-2001were analysed.Results:ADRs occured in several organs systems,mainly in skin and its appendages and cardiovascular system.Among more severe reactions were anaphylactic shock,laryngeal edema and dyspnea,probably caused by allergy.Conclusion:Traditional Chinese medicines should be used with more care owing to yearly increase of unwanted reactions.

Objective: To discuss the characteristics and related factors of ciprofloxacin-induced anaphylactic shock, and provide reference for clinical safe drug use. Methods: The literature between January 1979 and December 2005 was retrieved from "Chinese Journal Full-text Database", "Chinese Science and Technology Journal Full-text Database", and "Wanfang Medicine Data China info", Eighty-one cases with ciprofloxacin-induced anaphylactic shock of 73 papers were collected and analyzed. Results: Of the 81 cases, 42(52.5%) were male, 38(47.5%) were female, and one case' sex was unknown; 62(76.5%) were intravenous infusion, and 19(23.5%) were oral administration; 78(96.3%) were recovered, 3(3.7%) were dead. The time to onsef of anaphylactic shock varied from 10 seconds after intravenous infusion of ciprofloxacin to 60 minutes in fifth day after successive treatment of intravenous infusion of ciprofloxacin. Of the cases, 24 had allergic history, 25 had no allergic history. The investigation showed that ciprofloxacin-induced anaphylactic shock was not rare, and it was occurred in almost all areas of the whole country from 1975 to 2005. Conclusion: Careful attention should be paid to the serious reaction of ciprofloxacin-induced anaphylactic shock in clinical practice to ensure safemedication use.

Objective To understand the occurrence and the clinical characteristics of meropenem- related central nervous system (CNS) adverse reactions.　Methods Using the hospital information system, the electronic medical records of patients who were hospitalized in the Department of Respiratory， the 305 Hospital of the People′s Liberation Army from January 2016 to December 2021 and received meropenem were collected. Medical records of patients who developed CNS symptoms after meropenem administration were screened and analyzed retrospectively. The data extracted from the medical records mainly included gender, age, infectious diseases, underlying diseases, renal function at admission ［serum creatinine, endogenous creatinine clearance (Ccr)］ in the patient, the application of meropenem (dose, whether dose was adjusted according to Ccr), and the occurrence (occurrence time, main clinical manifestations, etc.), treatment, and outcome of meropenem-related CNS adverse reaction. The incidence of meropenem-related CNS adverse reactions was calculated, and their clinical characteristics was descriptively analyzed.　Results A total of 636 patients used meropenem during the set period and 17 of them developed meropenem-related CNS adverse reactions, with an incidence of 2.7%. Among 17 patients, 10 were male and 7 were female, aged from 74 to 94 years with a median age of 86 years. Thirteen patients had pulmonary infection (one with urinary system infection) and 4 had acute exacerbation of chronic obstructive pulmonary disease (2 with type Ⅱ respiratory failure); 14 patients had combined renal insufficiency (10 of them had a Ccr <50-ml/min) and 5 had sequelae of cerebral infarction. Ten patients were with Ccr <50-ml/min and 3 of them did not adjust the dose of meropenem according to Ccr, resulting in excessive dosage. The time to onset of CNS symptoms in 17 patients ranged from 1 to 7 days after starting meropenem, with a median time of 3 days. Twelve patients presented mainly with psychiatric disorders (including delirium, agitation, hyperarousal, hallucinations, confusion and sleep reversal, etc.), and 5 with limb or orolingual convulsions. Meropenem was discontinued in all 17 patients after the onset of CNS symptoms and 5 of them were given symptomatic treatments. Symptoms were relieved after 1-7 days in all the patients, with a median time of 3 days.　Conclusions Meropenem- related CNS adverse reactions are more common in elderly patients and patients with renal insufficiency, respiratory failure, and a history of CNS diseases. The main manifestations are mental disorders and convulsions, which mostly occur within one week of drug use. Stopping meropenem in time and receiving appropriate symptomatic treatments contribute a good prognosis in patients.

A 75-year-old male patient with pulmonary infection received an IV infusion of piperacillin sodium and tazobactam sodium 4.5 g twice daily. Fifteen minutes after the first medication, the patient developed patches on the skin of both upper limbs with pruritus, chest tightness and suffocation. Physical examination showed heart rate 110 beats/min, breathing rate 26 breaths/min, blood pressure 196/118-mmHg, and oxygen saturation 0.85. Immediate-type hypersensitivity related to piperacillin sodium and tazobactam sodium was considered. The drug was discontinued and symptomatic treatments including glucocorticoids and antiasthma were given. Two hours later, the skin itching was alleviated, the color of erythema became lighter, and the symptoms of chest tightness and suffocation were relieved. Physical examination showed that the heart rate was 100 beats/min, the blood pressure was 150/90-mmHg, and the blood oxygen saturation was 0.90.

A 16-year-old female patient with acute T-cell leukemia was going to undergo allogeneic hematopoietic stem cell transplantation. Pretreatment chemotherapy was required before operation. In order to reduce the degree of adverse reactions during the chemotherapy, the patient received treatments with ondansetron, dexamethasone, and fosaprepitant dimeglumine. After intravenous injections of ondansetron 4-mg and dexamethasone 5-mg, fosaprepitant dimeglumine 150-mg dissolved in 0.9% sodium chloride injec- tion 150-ml was intravenously pumped at a speed of 300-ml/h. Five minutes later, the patient developed sweating, foreign body sensation in pharynx, dyspnea, periumbilical pain, and vomiting. Anaphylactic reaction caused by fosaprepitant dimeglumine was considered. The drug was stopped immediately and intravenous injection of dexamethasone 5-mg and oxygen inhalation were given. Twenty minutes later, her symptoms of dyspnea and abdominal pain were relieved. Fifty minutes later, the allergic symptoms disappeared.

A 17-year-old male patient received rituximab due to nephrotic syndrome. No obvious discomfort occurred during the first treatment (500-mg by intravenous infusion). After half a year, when the second treatment (300-mg by intravenous infusion) was given, the patient developed symptoms such as fatigue of limbs and inability to lift both lower limbs. Laboratory test showed blood potassium 2.37-mmol/L. Before treatment, the serum potassium was 4.16-mmol/l, and other laboratory test indicators were basically normal. Acute hypokalemia caused by rituximab was considered. Oral potassium chloride was given. On the 2nd day, the symptoms in the patient were relieved, the feeling of powerlessness disappeared, and the blood potassium was 3.06-mmol/L. On the 3rd day, the blood potassium was 4.34-mmol/L. the potassium supplement was stopped after 3 days of medication. The next day, the blood potassium was 4.70-mmol/l, and the patient′s limb weakness and discomfort symptoms disappeared. After that, the patient did not use rituximab again, and no hypokalemia recurred.

A 26-year-old male patient with type 2 diabetes mellitus was given liraglutide (0.6-mg/d) on the basis of insulin combined with metformin because of the poor therapeutic effect. Four days later, the dose of liraglutide was doubled and empagliflozin (10-mg orally, once daily) was added. The next day, the patient developed nausea, vomiting, and abdominal pain accompanied by elevated serum amylase and lipase (peak levels were 1-048-U/L and 26-U/L, respectively). Acute pancreatitis was diagnosed, all hypoglycemic drugs were discontinued, and fasting, gastrointestinal decompression, intravenous fluid infusion, continuous infusion of low-dose insulin, and symptomatic treatments with lansoprazole and somatostatin were given. Three days later, the patient′s symptoms were relieved, and serum amylase and lipase levels returned to normal. Ten days later, the hypoglycemic drug was changed to subcutaneous injection of insulin aspart 30 injection (24 U in the morning and 16 U in the evening) before meals and oral metformin 0.5 g thrice daily. His blood glucose was controlled and no symptoms of pancreatitis recurred. Therefore, it was considered that the patients′ pancreatitis might be related to the combined use of liraglutide and empagliflozin.

氨基糖苷类抗生素具有抗菌谱广,对大多数革兰阴性(G-)杆菌引起的感染疗效确切等特点。但该类药物具有个体差异大、治疗指数窄等缺点,应用不当,可引起严重不良反应。本文参考近期文献从葡萄糖转运及其代谢、第二信使、微量元素和线粒体功能等方面就氨基糖苷类抗生素耳毒性的可能机制及临床处置作一综述。

Reactive metabolites is one of the main causes of drug-induced liver injury (DILI). After entering the body, some drugs can be metabolized by liver to generate drug reactive metabolites, which can deplete glutathione, and in turn bind to macromolecules such as proteins or nucleic acids in the body, alter biomacromolecule function, induce cellular oxidative stress and the body′s immune response, interfere with the body′s normal physiological function, and produce hepatotoxicity. Reactive metabolites mediated DILI may be not the action of one mechanism, but the combined effects of multiple mechanisms. This article reviews the production process of drug reactive metabolites, the mechanism of liver injury, and the means of prevention and treatment, providing an important reference for clinical safe drug use.

A 65-year-old man took 4 Lianhuaqingwen capsules thrice daily by himself for upper respiratory tract infection. The patient developed facial swelling and cervical lymphadenopathy after second treatment. Laboratory examination showed the following results: alanine aminotransferase (ALT) 219 U/L,  aspartate aminotransferase (AST) 106 U/L, gamma-glutamyl transpeptidase (γ-GT) 312 U/L, alkaline phosphatase (ALP) 223 U/L, total protein 65 g/L, albumin 33 g/L, albumin-globulin ratio (A/G) 1.02, total bilirubin (TBill) 14.4 μmol/L, direct bilirubin (DBil) 6.7 μmol/L, C-reactive protein (CRP) 110.4 mg/L. drug anaphylaxis and drug-induced liver injury were diagnosed. The patient was given IV infusions of polyene phosphatidylcholine 697.5 mg, reduced glutathione 2.4 g, magnesium isoglycyrrhizinate 150 mg, sodium thiosulfate 1.28 g and intramuscular injection of dexamethasone 5 mg once daily respectively. On day 6, the laboratory tests showed the following results: ALT 69 U/L, AST 19 U/L, γ-GT 275 U/L, ALP 191 U/L, total protein 56 g/L, albumin 24 g/L, A/G 0.76, TBil 16.6 μmol/L, DBil 8.5 μmol/L, CRP 148.2 mg/L。On day 16, the facial swelling disappeared. On day 21, the laboratory tests showed the following results: ALT 53 U/L, AST 36 U/L, γ-GT 155 U/L, ALP 149 U/L, total protein 76 g/L, albumin 32 g/L, A/G 0.71, TBil 6.1 μmol/L, DBil 3.1 μmol/L, CRP 89.5 mg/L.

Benifits outweigh the risks for patients with autoimmune disease (AID) in remission period to be vaccinated with coronavirus disease 2019 (COVID-19) vaccines. The mRNA vaccines, inactivated vaccines, and recombinant protein subunit vaccines are safe for AID patients, whereas the safety of recombinant adenovirus vector-based vaccines is still uncertain. Some drugs for the treatment of AID may reduce the immune response of the body to the COVID-19 vaccines and affect the immune efficacy of the vaccine, which may be related to the timing of vaccination. Based on several published relevant guidelines and recommendations for the COVID-19 vaccines in AID patients, this article elaborates on vaccination problems to be paid attention to in patients with AID treated with different drugs.

Objective To explore the international research hotpots and development trend of therapeutic drug monitoring (TDM).　Methods Web of Science database was searched as of February 16, 2022, with search term of "therapeutic drug monitoring" or "drug monitoring". The research articles on TDM were collected and analyzed for the annual publication amount, countries, authors, and institutions. Citation burst was detected using CiteSpace software, and keywords-cluster was carried out by VOSviewer to visually show the research hotpots.　Results A total of 2-318 articles were included, and the first one was published in 1975. The United States published the largest amount of related articles and had the closest cooperation with other countries. University of Queensland in Australia was the institution with the most publications, and Roberts JA was the author with the most publications. A total of 10 citation bursts were detected, and 6 keywords-clusters related to TDM were found by cluster analysis method. Recent international research hotspots included TDM of biologics in patients with inflammatory bowel disease, TDM of anti-infective drugs in critically ill patients, and TDM of anti-tumor drugs.　Conclusions Referring to the international research hotspots, TDM should be carried out for more drugs, such as infliximab, adalimumab, and imatinib, etc., to provide personalized and precise medication care for patients and improve the safety of drug therapy.

A 31-year-old male patient received moxifloxacin 400-mg orally once daily for pulmonary infection. After 9 days of treatment, the patient developed hemoptysis, hematochezia, and scattered petechia and ecchymosis on his body, with platelet count (PLT) 1×109/L. Thrombocytopenic purpura was diagnosed. Moxifloxacin were stopped and treatments such as hemostasis, recombinant human interleukin-11, and an IV infusion of concentrated platelets were given. Six days later, the patient′s petechia and ecchymosis disappeared and the PLT was 376×109/L. Bone marrow puncture result showed that it was immune thrombocytopenia.

Barcode technology is a kind of automatic recognition technology which is produced and developed in computer application and practice. Barcode technology has been widely used in drug purchase, management, dispensing, use and other aspects, and plays an important role in reducing human errors, improving work efficiency, and reducing medication errors in drug information check, information matching of drug and patient, and other important links. However, barcode technology can also lead to medication errors due to human operation, technical level, and other factors during application. In order to strengthen the prevention of medication errors related to the application of drug barcode technology in medical institutions, experts in pharmaceutical, nursing, informational, and management, who were organized by Medication Safety Panel in China Core Group of International Network for the Rational Use of Drugs, Chinese Pharmacological Society Professional Committee of Drug-induced Diseases, and Adverse Drug Reactions Journal Agency, formulate the guideline for prevention of medication errors in application of barcode technology in medical institutions after several argumentation based on the Expert Consensus on Medication Error Management in China. The medication errors related to drug barcode technology may occurred in links of drug storage and delivery, drug dispensing and distribution, intravenous drug admixture, inpatient drug administration, and etc. The risk factors include systematic factors (damaged barcode quality, poor barcode printing quality, scanning and printing equipment problems, packaging problems, system defects, and sharing difficulties of internal barcode information) and human factors (barcode information maintenance error, not timely information update, wrong pasted barcode, too little internal barcode information, operation error, and improper implementation). The prevention strategies for medication errors related to drug barcode application include technical strategies (including enforcement and constraint policies, automation and information, establishment of good checking system) and management strategies (including regulatory framework, environment and personnel). The guideline is formulated for all medical staff involved in the application and management of drug barcode technology in medical institutions.

Objective To explore the clinical characteristics of dabigatran etexilate-related serious adverse events(AE).　Methods Databases of CNKI, WanFang, PubMed, and Embase were searched as of October 31, 2020 and case reports on serious AE related to dabigatran etexilate were collected. Relevant information in patients (nationality, gender, age, weight, application of dabigatran etexilate, co-existing diseases and combined drugs, the occurrence, treatment and outcome of AE, etc.) was extracted and analyzed descriptively.　Results A total of 77 literature were included, involving 101 patients from 20 countries. There were 64 males (63.4%) and 37 females (36.6%), aged 56-94 years with the body weight of 38-193-kg. In terms of the reasons for medication, 87 were for prevention of stroke caused by atrial fibrillation, 12 were for the treatment of venous thromboembolism or for prevention of the possible venous thromboem- bolism, and the other 2 were not described. Co-existing diseases or past medical history were described in 88 patients, including hypertension, renal insufficiency, and type 2 diabetes mellitus, etc. Combined medication was described in 67 patients, of which drugs that might increase the risk of bleeding (non-steroidal anti-inflammatory drugs, clopidogrel, P-glycoprotein inhibitors, etc.) were used in 35 patients. Other combined drugs were antihypertensive drugs and hypoglycemic drugs, etc. Serious AE occurred from 2 minutes to 5 years after medication and 33 cases occurred within 1 month after the start of medication. Serious AE associated with dabigatran etexilate were bleeding in 81 patients (including gastrointestinal bleeding, intracerebral hemorrhage, coagulation disorder, etc.), kidney injury/renal failure in 8 patients, esophageal ulcer in 4 patients, liver injury in 2 patients, and thrombocytopenia, leukocyte fragmentation vasculitis, and severe cough with dyspnea in 1 patient respectively. The main measure taken after AE occurence was drug withdrawal. Those who were not improved after drug withdrawal were given symptomatic treatment, and hemodialysis were performed on those who fail to respond to the treatment. A total of 29 patients died and all of them had bleeding events. Among the 101 patients, 43-had medication errors, of which 33-had overdose, 6 had contraindications, and 4 had wrong administration methods.　Conclusions Serious AE related to dabigatran etexilate manifest mostly as bleeding in clinic and can occur from 2-minutes to 5 years after medication, which can lead to death in severe cases. Medication error is one of the important causes of serious AE related to dabigatran etexilate, so the label should be strictly followed when prescribing the drug and medi- cation guidance should be given to patients.

A 45-year-old male patient underwent craniotomy and biopsy for intracranial lesions. In order to prevent epilepsy, sodium valproate 800-mg dissolved in 0.9% sodium chloride injection 8-ml was injected intravenously after operation, and then the sodium valproate solution of this concentration was continuously pumped at a speed of 0.6-ml/h. One hour after administration, the serum lactate level of the patient increased gradually, reaching the highest level of 14.7-mmol/L, accompanied by metabolic acidosis and compensatory respiratory alkalosis, and with the lowest pH of 7.09 and the lowest base excess of -26.3. The patient fell into a coma. The hyperlactatemia and metabolic acidosis were considered to be related to sodium valproate. Sodium valproate was stopped, intravenous infusion of 5% sodium bicarbonate injection and blood purification were given at the same time. After 3 days, the lactate level of the patient returned to normal, metabolic acidosis was basically corrected, and his mind was clear.

A 59-year-old male patient received SOX chemotherapy regimen (IV infusion of oxaliplatin injection 200-mg dissolved in 5% glucose injection 250-ml for 2 hours on the first day, oral tegafur, gimeracil and oteracil potassium 60-mg once daily on day 1-14, every 3 weeks was a cycle) for gastric cancer with multiple lymph nodes metastases. One week after the infusion of oxaliplatin during the third cycle, the patient suddenly developed deafness and blurred vision. The patient was diagnosed with sudden sensorineural deafness and acute optic neuritis after otorhinolaryngologist consultation. His sudden sensorineural deafness and acute optic neuritis were considered to be associated with oxaliplatin. Chemotherapy was discontinued and the patient was given neurotrophic and microcirculation-improving medications. One 1 week later, the patient′s vision gradually returned to normal, but the deafness persisted.

Enteral nutrition (EN) is defined as the administration of a nutrient solution orally or by means of a feeding tube with the purpose of contributing the supply of all or part of the body's nutrient requirements. EN preparations can be classified into three types: elemental type, non-elemental type, and module type. EN is usually given with feeding tube. Non-invasive tube includes nasogastric tube and nasointestinal tube, and invasive tube includes gastrostomy tube and enterostomy tube. Indications for EN include radical surgery in patients with upper alimentary tract or upper respiratory tract, tracheal intubation, esophageal stenosis, dysphagia, anorexia nervosa, largescale burning or trauma. Although considered safer than parenteral nutrition, enteral feeding is not of without complications. The common complications of EN were as follows: (1) mechanical complications such as obstructions of the feeding tube; (2) gastrointestinal complications are abdominal distension, nausea, vomiting, and diarrhea, and they can be reduced or avoided by using gastrointestinal pump or nasointestinal tube, reducing infusion speed, increasing nutrient solution temperature, and using gastrointestinal prokinetic drugs; (3) metabolic complications are mainly hyperglycaemia, and it can be treated with insulin; (4) infectious complications are mainly inhalation pneumonia caused by inhaling nutrient solution or regurgitation into the lungs presenting with sudden dyspnea, fever, increased heart rate. Attention should be paid to its gastric retention.

A 52-year-old male patient with primary bronchogenic carcinoma received an IV infusion of sintilimab 200-mg on the first day, oral anlotinib capsules 12-mg once daily on day 1-14, and 3 weeks were a cycle. At the 3rd cycle of treatments, the laboratory tests showed thyroid stimulating hormone (TSH) 0.08 mU/L, and no intervention was given. At the 5th cycle, his free thyroxine (FT4) was 11.45-pmol/L and TSH was 8.19 mU/L, indicating hypothyroidism. The patient received levothyroxine sodium tablets 50-μg orally once daily. Fifty-six days later, his thyroid function returned to normal. On the 3rd day of the 8th cycle of treatments, the patient developed dry mouth, polydipsia, polyuria, nausea, and vomiting, and laboratory tests showed blood pH 7.02, β-hydroxybutyric acid 6.740-mmol/L, and random blood glucose 66.0-mmol/L, indicating diabetes ketoacidosis. Sintilimab and anlotinib were stopped and fluid replacement and insulin hypoglycemic therapy were given. Eleven days later, his ketone body turned negative, and the fasting blood glucose was 5.8-mmol/L. About 2 weeks later, the laboratory tests showed that hemoglobin A1c was 7.8%, the serum C-peptide levels on an empty stomach and 2 hours after breakfast both were less than 0.01-nmol/L, and the islet cell antibody, insulin autoantibody, glutamic acid decarboxylase antibody, and protein tyrosine phosphatase autoantibody were negative, which was consistent with the characteristics of fulminant type 1 diabetes (T1DM). On the morning of the 32nd day of sintilimab and anlotinib withdrawal, laboratory tests showed cortisol 50.7-nmol/L and adrenocorticotropic hormone (ACTH) 2.73-pmol/L, indicating hypoadreno- corticism. Treatment with glucocorticoid was given. It was considered that the patient was with  autoimmune polyendocrinopthy syndrome (APS) type II (hypothyroidism,fulminant T1DM,hypoadrenocorticism) caused by sintilimab. After 9 months of glucocorticoid treatment, cortisol was 16.6, 79.4, and 17.2-nmol/L at 8:00,16:00, and 24:00, respectively, and ACTH was 1.12-pmol/L. The patient still needed maintenance treatment with alternative hormone.

Objective To compare the pharmacokinetics and safety of single intravenous injection of the generic bevacizumab injection WBP264 and the original bevacizumab injection Avastin- in healthy male volunteers.　Methods The study was designed as a randomized, double-blind, single dose, parallel, and controlled phase I clinical trial. Healthy male volunteers who were recruited publicly were randomized into the trial group (intravenous infusion of WBP264) and the control group (intravenous infusion of Avastin-), and the dose was 3-mg/kg. Peripheral venous blood was collected within 30-minutes before administration, 45-minutes after onset of the administration, immediately after finishing the administration, 2.5, 3.5, 5.5, 9.5, 13.5, 24, 48-hours and on the 5th, 8th, 15th, 22nd, 29th, 36th, 43rd, 57th, 71st, 85th, and 99th days after the administration. The plasma concentration was measured by enzyme-linked immunosorbent assay, the plasma concentration-time curve and its semilogarithmic plot were plotted, and the pharmacokinetic parameters such as the area under the plasma concentration-time curve [including AUC from time zero to the time of the last quantifiable concentration (AUC0-t) and AUC from time zero to infinity (AUC0-∞)], peak concentration (Cmax), time to peak (Tmax), plasma elimination half-life (t1/2), clearance rate (CL), and apparent volume of distribution (Vd) were calculated. When the 90% confidence intervals (CI) of the geometric mean ratio of AUC0-t, AUC0-∞, and Cmax between the trial group and the control group were between 0.80-1.25, it indicated that pharmacokinetics of WBP264 and Avastin- were similar. The physical examination, vital signs detection, electrocardiogram, and laboratory tests were performed on the subjects, the occurrence of adverse events (AEs) and the severity classification were recorded, and correlation between the AEs and the trial drug was evaluated. The anti-drug antibody and its neutralizing antibody were detected before administration and on the 8th, 15th, 29th, 43rd, 71st, and 99th days after administration to evaluate the immunogenicity of the drug.　Results A total of 78-subjects were recruited, 39 in the trial group and 39 in the control group. In the trial group, 2 cases withdrew from the trial (1 case did not take the drug and 1 case withdrew for personal reason after taking the drug). Seventy-seven cases were in the safety analysis set and 76 cases in the pharmacokinetic analysis set. The differences in age, height, weight, and body mass index between the 2 groups were not significant (all P>0.05). The plasma concentration-time curves of bevacizumab between the trial group and the control group were similar. The geometric mean ratios (90%CI) of AUC0-t, AUC0-∞, and Cmax were 1.04 (0.98-1.10), 1.03 (0.98-1.10), and 1.09 (1.03-1.14), respectively. The differences in the incidence of overall AEs ［89.5% (34/38) vs. 87.2% (34/39)］ and the incidence of AEs possibly related to the trial drug ［86.8% (33/38) vs. 79.5% (31/39)］ between the trial group and the control group were not significant (all P>0.05). Only one case of AE in the trial group was grade 3 in severity and was assessed as being not related to the drug, and the rest were grade 1-2, with grade 1 AEs accounting for the vast majority. The difference in the positive rate of anti-drug antibody between the trial group and the control group was not significant ［10.5% (4/38) vs. 10.3% (4/39), P>0.05］. The neutralizing antibody test was negative in the patients with positive anti-drug antibody.　Conclusion The pharmacokinetics and safety of WBP264 and Avastin- are similar.

To explore the risk signals of letrozole related adverse reactions and provide reference for the clinical safety of letrozole.　Methods The risk signals related to letrozole in the adverse events (AEs) reports from the first quarter of 2009 to the first quarter of 2019 in the US FDA adverse event reporting system (FAERS) were mined using the reporting odds ratio (ROR) method and the proportional reporting odds ratio (PRR) method. An AE with reports>3 and 95% confidence interval (CI) lower limit of ROR and PRR>1 was defined as a positive signal. AEs were counted and classified using the preferred system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities (MedDRA). The PTs of top 50 adverse event reports and signal strength were selected and analyzed.　Results From the first quarter of 2009 to the first quarter of 2019, a total of 31 743 AE reports with letrozole as the primary suspicious drug were reported in the FAERS database. Four hundred and eighty‑three AE risk signals with reports>3 and the 95%CI lower limit of ROR and PRR>1 were detected, involving 16 295 AE reports. After the second screening, PTs with the top 50 AE reports and those with the top 50 PTs ROR values were obtained. After screening out repeated PTs, 93 PTs were included in the analysis, involving 10 138 AE reports. The top 5 system organs in AE reports were neoplasms benign, malignant and unspecified (cysts and polyps) ［24.48%(2 482/10 138)］, musculoskeletal and connective tissue disorders ［21.78%(2 208/10 138)］, general disorders and administration site conditions ［17.04%(1 728/10 138)］, blood and lymphatic system disorders ［17.04%(1 728/10 138)］, and investigations ［5.47%(555/10138)］. There were 32 PTs not labelled in the drug instructions, and PTs with the top 5 signal strength were ovarian fibrosis［ROR=379.63, 95%CI lower limit: 120.87; PRR=278.66, 95%CI lower limit: 120.39］, ret gene mutation［ROR=379.63, 95%CI lower limit: 120.87; PRR=278.66, 95%CI lower limit: 120.39］, antisynthetase syndrome［ROR=208.84, 95%CI lower limit: 190.30）; PRR=174.20, 95%CI lower limit: 101.56］, hashimoto′s encephalopathy［ROR=164.85, 95%CI lower limit: 69.68; PRR=142.51, 95%CI lower limit: 67.74］, and bone marrow oedema syndrome ［ROR=122.82, 95%CI lower limit: 65.47; PRR=110.00, 95%CI lower limit: 64.34］.　Conclusions Through data mining, 32 adverse reaction risk signals were found, which were not labelled in the drug instructions. Of them, ovarian fibrosis, ret gene mutation, antisynthetase syndrome, Hashimoto′s encephalopathy, and bone marrow oedema syndrome had strong signals, which were worthy of clinical attention.

A 53-year-old male patient received intramuscular injection of diclofenac sodium and lidocaine injection 2-ml for abdominal pain. After one hour of medication, the patient developed upper abdominal discomfort, chest tightness, shortness of breath, sweating, and slight cyanosis of lips. Oxygen inhalation was given immediately. Electrocardiogram monitoring showed blood pressure 105/60-mmHg, heart rate 125 beats/min, and blood oxygen saturation 0.75. His peripheral blood glucose could not be detected. Glucose supplement and hormone therapy were given immediately. About 30-minutes later, the patient developed unconsciousness, no pulsation of the main artery, and cardiac and respiratory arrest. Cardiopulmonary resuscitation and other treatment measures were given immediately. However, the patient did not return to spontaneous heartbeat and breathing and was declared dead. It was considered that the patient′s severe hypoglycemia might be related to diclofenac sodium and lidocaine.

Drug-induced thrombocytopenia is defined as a platelet count lower than normal range(<100×10⁹/L) caused by a drug,resulting in bleeding and some related symptoms.Drug-induced thrombocytopenia includes at least three mechanisms such as marrow suppression,immunological and non-immunological thrombocytopenia.Drugs that have been more commonly reported to cause thrombocytopenia include cancer chemotherapy agents,heparin,quinidine,quinine,gold salts,valproic acid,and antibacterials.The incidence of thrombocytopenia induced by cancer chemotherapy agents is substantially higher than that caused by other types of drugs.Signs and symptoms associated with drug-induced thrombocytopenia are petechiae,ecchymosis,epistaxis,gingival bleeding.More significant bleeding such as gastrointestinal hemorrhage,hematauria,colporrhagia,and intracranial hemorrhage may occur.Treatment options for drug-induced thrombocytopenia include stopping the suspected causative agent;administering corticosteroids,immunog…更多lobulin or platelet transfusions;gold salt or arsenide-induced thrombocytopenia can be treated with IM dimercaprol to eliminate heavy metals.

A 73-year-old male patient with metastatic sarcomatoid carcinoma of lymph node received an IV infusion of tirelizumab 200-mg on day 1, and 3 weeks was 1 cycle. After 10 cycles of treatment, the patient developed dizziness, chest tightness, nausea, and vomiting. Laboratory tasts showed random blood glucose 99.1-mmol/L, serum creatinine (Scr) 260 μ mo/L, blood potassium 5.8-mmo/L, blood sodium 129-mmol/L, and blood osmotic pressure 368 mOsm/(kg·H2O). Blood gas analysis showed pH 7.1 and lactic acid 2.8-mmol/L. Ketoacidosis was considered and treatments such as rehydration, hypoglycemic with insulin, and electrolyte supplement were given. After 5 days of treatments, the patient′s symptoms were improved, and laboratory tests showed blood potassium 4.4-mmol/L, blood sodium 134-mmol/L, carbon dioxide binding capacity 17.0-mmol/L, and fasting C-peptide 0.02-nmol/L. Seven days later, laboratory tests showed fasting C-peptide 0 and 2 h post-prandial C-peptide 0. The patient was diagnosed with fulminant type 1 diabetes mellitus, which was considered to be related to tirelizumab. After 19 days of treatments, laboratory tests showed fasting blood glucose 5.8-mmol/L, blood glucose at 2 hours after meal 19-mmol/L, Scr 102-μmol/L, blood sodium 139-mmol/L, blood chlorine 108-mmol/L, and blood potassium 3.9-mmol/L.

A 49-year-old male patient with type 2 diabetes mellitus and diabetic nephropathy received long term use of retaglinide thrice daily orally, 1-mg in the morning, 2-mg in the afternoon and 1-mg in the evening. Because of the sudden acute cerebral infarction, clopidogrel was added, on the 4th day of the medication, the fasting blood glucose in the patient decreased to 2.6-mmol/L. It was considered that the interaction of clopidogrel and repaglinide caused the increase of repaglinide plasma concentration, which resulted in severe hypoglycemia in the patient. Clinical pharmacist suggested stopping repaglinide and using insulin. The physician reduced the dosage of repaglinide to twice daily, 1-mg in the morning and 0.5-mg in the afternoon, and after 3 days the patient′s fasting blood glucose fluctuated between 4.0 and 4.5-mmol/L. Since the patient had diabetes nephropathy and renal insufficiency, which might increase the risk of hypoglycemia, repaglinide was stopped, and insulin glutamine 3 U was injected subcutaneously before meals, at the same time blood glucose was closely monitored. Fasting blood glucose fluctuated between 4.9 and 5.4-mmol/L after insulin treatment.

本文根据近年文献报告,对5种质子泵抑制剂的作用特点、药代动力学、不良反应及相互作用进行综合比较,为临床安全合理用药提供依据。

Objective: To investigate and analyse the situation of digoxin used in our hospital and the factors affecting on serum-digoxin concentration. Methods: Eight hundred and sixty-one data of serum-digoxin concentration were collected in our hospital in 2005. The relationship between serum-digoxin concentration and the factors including age ,sex, serum-creatine concentra-tion was analysed by multivariate regression analysis. Results: The serum-digoxin concentration was affected by the four factors of age, sex, serum- creatine concentration, and the dose (P≤0.05). The relationship between them were con= -0.474+0.750×dose+0.154×Scr+0.128×sex+0.003×age by multivariate regression analysis. Conclusion: Serum-digoxin concentration varies with individuals and is affected by many factors. As regards most patients, the dose of digoxin should not be over 0.125 mg daily. If the serum-creatine concentration exceed the normal range, it is likely to be renal dysfunction to the patient. In such a case, the dose of digoxin should be reduced. As regards women, the dose of digoxin should be carefully adjusted to avoid digoxin toxicity.

Metoprolol and propafenone are commonly used drugs in cardiovascular diseases. Both drugs are metabolized by liver cytochrome P450 (CYP) 2D6. However, propafenone is not only a CYP2D6 substrate, but also a CYP2D6 inhibitor, which may interact with metoprolol and cause adverse reactions. This interaction also depends on CYP2D6 genotype. For patients with CYP2D6 phenotypes of poor metabolizer (PM) and intermediate metabolizer (IM), the combination with propafenone can increase plasma concentration of metoprolol due to the inhibition of propafenone on CYP2D6. Therefore, the combination of metoprolol and propafenone should be avoided as far as possible. For the patients who need the combined treatment with the 2 drugs, attention should be paid to the monitoring of blood pressure, heart rate, and electrocardiogram changes during medication. If possible, CYP2D6 genotype should be detected and the drug dose should be adjusted according to the test results.

鉴于20世纪末,我国出现俗称″冰毒(甲基苯丙胺)、摇头丸(亚甲二氧基甲基苯丙胺)和K粉(氯胺酮)″的毒品滥用问题。这些毒品被称为″新型毒品″,是相对鸦片、海洛因等传统毒品的一大类滥用毒品的称谓,同海洛因等传统阿片类毒品相比,此类毒品具有精神依赖性强,而身体依赖性相对弱的特点。现主要在娱乐场所被滥用,″新型毒品″滥用的群体广泛,不仅导致严重身心损害,也影响社会安定团结。本文主要介绍了全球范围滥用的几种″新型毒品″的药理学、毒理学作用特点和滥用导致的危害。

Objective: To investigate the adverse reactions of cephalosporins. Methods: 148 cases with allergic shock were collected and analysed mostly through Chinese literature retrieval of 1986 - 2000 in addition to a few patients of our hospital. Results: The shock appeared immediately after the drug administration in 66 cases with a severe nature and death followed if the first aid delayed. Conclusion: The treatment of shock and the skin test of drug were discussed. More attention should be attached to the shock associated with cephalosporins.

A 64-year-old male patient with comminuted intertrochanteric fracture of right femur received subcutaneous injection of 4-100 U nadroparin calcium once daily for anticoagulant treatment due to pulmonary embolism and thrombosis of both lower limbs before operation. His platelet count (PLT) was 166×109/L before the treatment. After 5 days of treatment, the dose of nadroparin calcium was increased to 4-100 U once per 12-h. On the 8th day after the dose increase, the patient′s PLT increased to 800×109/L. Thrombocytosis was diagnosed, which was considered to be related to nadroparin calcium. The drug was stopped and replaced by rivaroxaban 20-mg once daily orally. Five days later, the patient′s PLT decreased to 590×109/L; 34 days later, PLT was 297×109/L.

Objective: To study the pathogenesis , prevention and management of the liver damage caused by tra-dional Chinese medicines on analysis of cases with liver damage. Methods: This article summarized 427 cases of liver damage caused by traditional Chinese medicines in the last fifteen years and surveyed incidence of liver damage caused by traditional Chinese medicines, distribution of primary diseases, and clinical characteristics. Results: Liver damage cases induced by traditional Chinese medicines were on the increase year by year , amounted to 32.6% in all cases of the drug-induced liver damage. Those traditional Chinese medicines used to treat osteoarthropathy, kidney diseases and skin diseases induced liver damage more often. Zhuanggu Guanjie Wan , Tripterygium wilfordii Hook. f., and Dioscorea bulbifera L. were the most major medicines inducing liver damage. The clinical characteristics and the pathogenesis of liver damage caused by different medicine were varient. Conclusion: Ratio...更多nal use of traditional Chinese medicines and study of their hepatotoxicity should be strengthened further in clinical practice .

Objective To investigate the occurrence and clinical characteristics of extremely severe tirofiban-induced thrombocytopenia (TIT).　Methods Patients who used tirofiban during hospitali- zation in Linyi people′s Hospital from March 2015 to September 2021 was screened through the hospital information system. The medical records of patients with extremely severe TIT after medication were collected and analyzed retrospectively. The patient data extracted from the medical records included gender, age, medication indication, comorbidities, tirofiban application, combined drugs, platelet count (PLT) before and after tirofiban use, thrombocytopenia onset time from the application of tirofiban, the time to minimum value of PLT from medication, and the clinical manifestations, intervention, and prognosis of TIT, etc.　Results A total of 10-354 inpatients who used tirofiban during the set period were entered, of which 20 (0.19%) had extremely severe TIT. Among the 20 patients, 16 were male and 4 were female, aged 39-84 years with an average age of 66 years, 12 of which were ≥65 years. The medication indications of tirofiban were acute myocardial infarction in 8 patients, cerebral infarction in 5 patients, unstable angina pectoris in 4 patients, and post-operation of coronary artery bypass grafting, transient ischemic attacks, and post-operation of coronary- stent implantation in 1 patient respectively. The comorbidities included hypertension in 13 patients, diabetes mellitus in 4 patients, cerebral infarction in 3 patients, and New York Heart Association (NYHA) greater than or equal to class Ⅲ heart failure in 3 patients. Tirofiban was administered by continuous intravenous pumping for 1-48-hours. The combined drugs included aspirin enteric-coated tablets, clopidogrel tablets, ticagrelor tablets, heparin, low molecular weight heparin, alteplase, and plasmin. Five patients had symptoms of chills and shivers within 1-6 hours after treatment, 7 had oral mucosal bleeding, epistaxis, gingival bleeding, skin ecchymosis, ecchymosis on venipuncture sites, tarry stool, or bloody stool within 1-7 days after treatment, and 10-had no clinical symptoms. The median time from tirofiban application to the onset of PLT decrease and to the minimum value of PLT ［(1-18)×109/L］ were 12 (6, 20) and 18 (12, 22) hours, respectively, and the 2 kinds of time above were consistent in 13 patients. Tirofiban was discontinued in all patients after the diagnosis of extremely severe TIT, and treatments with glucocorticoids, human immunoglobulin, and platelet infusion were given. PLT recovered to (100-258)×109/L after 3-17 days (median time 4 days) of treatments in 18 patients. The other 2 patients developed tarry stool and bloody stool 2 and 1 days after the diagnosis of TIT, respectively, followed by respiratory and cardiac arrest, and died.　Conclusions Extremely severe TIT has low incidence but urgent onset, which can lead to fatal bleeding events, and some patients may have no clinical symptoms. The prognosis is generally good after tirofiban withdrawal and receiving glucocorticoids and symptomatic treatments. However, it should be alert to the adverse consequences caused by secondary bleeding events.

A 69-year-old male patient with depression was treated with amfebutamone and mirtazapine for a long time. Because of poor control of symptoms, the treatment plan was adjusted to oral duloxetine (60-mg in the morning) and mirtazapine (15-mg at night). After 13 days of treatments, the patient developed high fever (41.0-℃) with disturbance of consciousness, followed by muscle rigidity and dyspnea. His heart rate was 180 beats/min and blood oxygen saturation was 0.84. Laboratory tests showed serum creatinine (Scr) 609-μmol/L, creatine kinase (CK) 7-102-U/L, myoglobin (MYO)>3-000-μg/L, aspartate aminotransferase (AST) 88-U/L， and total bilirubin (TBil) 33.7-μmol/L. ECG monitoring showed rapid atrial fibrillation. The patient was diagnosed with malignant syndrome caused by duloxetine after excluding infection and other conditions. Duloxetine and mirtazapine were stopped immediately, and symptomatic and supportive treatments including endotracheal intubation, hemofiltration, improvement of water-electrolyte balance, and hepatoprotection were given. On the 6th day of drug withdrawal, the patient′s temperature was 38.2-℃, the blood oxygen saturation was 0.96, muscle tone was improved, and muscle tremor disappeared. On the 16th day of drug withdrawal, the patient′s condition was obviously improved, the consciousness was clear, the temperature was normal, the call could be answered, and no limb convulsion and muscle tremor occurred. Laboratory tests showed Scr 116-μmol/L, CK 250-U/L, MYO 148-μg/L, AST 38-U/L, and TBil 21.4-μmol/L.

Objective To explore the adverse reaction risk signals of perampanel-related psychia- tric disorders, and provide reference for the clinical safe application of perampanel.　Methods The US FDA Adverse Event Reporting System database was searched, and the adverse event (AE) reports on psy- chiatric disorders from the third quarter of 2012 to the third quarter of 2021, which judged perampanel as the primary suspect drug were collected. The expression of AE was standardized using the preferred term (PT) in the Medical Dictionary for Regulatory Activities. Data such as patient general condition and psychiatric AE outcomes was extracted from AE reports and was analyzed descriptively. Risk signal mining for psychiatric adverse reactions to perampanel was performed using the reporting odds ratio (ROR) method. The positive signal PT was set as that the number of AE reports was 3 and more and the lower limit of the 95% confidence interval (CI) of the ROR was greater than 1.　Results A total of 922 reports on psychiatric AE with perampanel as the primary suspect drug were collected. Of the 922 patients involved, 439 were male, 441 were female, and 42 were unknown in gender. Age were recorded in 676 patients, and the age was (38±19) years. AE outcomes were recorded in 807 patients, of which hospitalization/prolonged hospitalization, urgent treatment needs, life threatening, and death due to AE occurred respectively in 409 (44.4%), 316 (34.3%), 60 (6.5%) and 22 patients (2.4%). The 922 AEs involved 1-580 PTs, and 46 PTs were detected with positive signals by ROR method. The top 5 PTs mostly reported were aggression (286 AEs), irritability (128 AEs), suicidal ideation (110 AEs), suicide attempt (100 AEs), and anger (77 AEs). The top 5 PTs with strongest signal intensity (ROR value) were postictal psychosis (383.13), schizophreniform disorder (355.27), homicidal ideation (203.56), dissociative disorder (119.64) and delusional perception (108.34), among which dissociative disorder and postictal psychosis were AEs not recorded in the drug labels. In the 46 PTs with positive signal, 14 (30.4%) were not recorded in the drug labels, and the other 12 PTs were listed as sexually inappropriate behaviour (81.43), suspiciousness (65.20), disinhibition (32.72), impulsive behaviour (31.18), perso- nality change (22.56), abnormal behaviour (16.31), social avoidant behaviour (12.95), restlessness (6.15), bipolar disorder (5.23), affect lability (5.09), nightmare es (2.86), and fear (2.79).　Conclusion psychiatric adverse reaction is a common and serious adverse reaction of perampanel, which should be paid attention to clinically.

Objective To systematically evaluate cardiotoxicity of programmed cell death 1 receptor (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors.　Methods Clinical trials of PD-1/PD-L1 inhibitor alone or in combination with other treatments for tumors were collected by searching related databases at home and abroad (up to March 2, 2019). The methodological quality of studies was evaluated using the internationally accepted Cochrane collaboration′s risk of bias assessment tool. A meta-analysis was performed using RevMan 5.3 software to compare the incidences of cardiotoxicity between PD-1/PD-L1 inhibitors (trial group) and placebo or other antineoplastic agents(control group).　Results A total of 10 randomized controlled trials (RCTs) were enrolled, 9 of which were about PD-1 inhibitor alone or in combination with other antineoplastic agents, and 1 of which was about PD-L1 inhibitor monotherapy. There were a total of 5-291 patients, including 3-022 in the trial group and 2-269 in the control group. Evaluation of the methodological quality for studies showed that 4 RCTs were at high risk of bias and the other 6 were at low risk of bias. The meta-analysis showed that the incidence of cardiotoxicity in the trial group was significantly higher than that in the control group, and the difference was statistically significant［1.13% (34/3-022) vs. 0.22% (5/2-269), RR=2.38, 95%CI: 1.19-4.78, P=0.01］.　Conclusion PD-1/PD-L1 inhibitors have the risk of causing heart related adverse events, which should be paid attention to in clinical application.

A 49-year-old male patient received transcutaneous transcatheter arterial chemoembolization and an IV infusion of camrelizumab 200-mg (on day 1 and 14 days was a cycle) due to liver cancer with intrahepatic metastasis, liver cirrhosis, splenomegaly, and ascites. On day 12 after the third IV infusion of camrelizumab, the patient developed fever, cough, and chest tightness. On day 34 after the third IV infusion of camrelizumab,chest CT showed ground glass exudation shadow in bilateral lungs. Immune-related pneumonitis and infection caused by camrelizumab was considered. High-dose methylprednisolone was given to inhibit immune reaction and cefoperazone sodium and sulbactam sodium was given to resist infection, supplemented with symptomatic and supportive treatments such as oxygen inhalation and expectorant. Eighteen days later, the patient′s body temperature returned to normal, chest tightness disappeared, but he coughed occasionally. Chest CT showed that the ground glass exudation shadow of bilateral lungs was narrowed on the scope.

A 16-year-old female patient received ethinylestradiol and cyproterone acetate tablets (1 tablet once daily for 21 days) for artificial menstrual cycle treatment due to irregular menstruation. On the 7th day of medication, the patient developed swelling of the distal right lower extremity, accompanied by pain, and slight limitation of movement, which did not attract attention. The drug was stopped 21 days later. On the 2nd day after drug withdrawal, the patient had vaginal withdrawal bleeding and blood expectoration occurred once on the same day. After 16 days of drug withdrawal, the swelling and pain of the right lower limb was aggravated. Ultrasound showed deep vein thrombosis in the right lower limb, and CT angiography of the pulmonary artery showed embolism in the right lower pulmonary artery. Deep vein thrombosis complicated with subacute pulmonary embolism were diagnosed. Enoxaparin sodium for anticoagulation and symptomatic treatments were given, the symptoms were improved 17 days later. Laboratory tests showed that the platelet count was 90×109/L, the anticardiolipin antibody IgG was 209 GPL/ml, and the platelet-related antibody was positive. Antiphospholipid syndrome was diagnosed. It was considered that the thrombosis was related to ethinylestradiol and cyproterone acetate tablets.

An 81-year-old male patient with bipedal blue toe syndrome received IV pumping of dexmedetomidine 0.2-mg dissolved in 0.9% sodium chloride injection 48-ml at the rate of 4-ml/h once daily because of severe pain in his left toe. The patient developed irritability and delirium about 6 hours after the 3rd IV pumping. The next day, the pain was relieved and dexmedetomidine was stopped. After drug withdrawal, the patient occasionally had delirium. Due to difficulty in falling asleep, the same dose of dexmedetomidine was given again on the 3rd day of drug withdrawal. The same dose of dexmedetomidine was given twice the next day and obvious delirium and irritability occurred 2-3 hours after drug administration of each time. Delirium was suspected to be related to dexmedetomidine. Dexmedetomidine was stopped again and replaced by tramadol and midazolam. On the 6th day of drug withdrawal, the patient′s consciousness turned clear, and no delirium recured.

Selective serotonin reuptake inhibitors (SSRIs) are a widely used newer class of antidepressants, which can treat different types of depression. The commonly used SSRIs are fluoxatine, paroxetine, sertraline, fluvoxamine, and citalopram. The SSRIs can cause various types of adverse reactions. The main adverse reactions are gastrointestinal disorders, withdrawal reactions, sexual disturbances, and syndrome of inappropriate secretion of antidiuretic hormone (SIADH), etc. SSRIs may increase the risk of suicidal thinking and behaviour in children and adolescents, but the issue remained controversial. The recent studies have suggested that exposure to SSRIs early in pregnancy appeared to be no increase in the risk of congenital malformations; however, exposure to SSRIs late in pregnancy may incresae the risk of pulmonary hypertension and withdrawal reactions of the newborn. In general, breastfeeding with SSRIs is regarded as safe because the amount of drug is very low in breast milk. But the possibility of longterm effects on development in the infant is unknown. As for the elderly, SSRIs may increase the risk of fracture. Adverse reactions resulting from interations of SSRIs with some drugs are given below. MAOIs: serotonin syndrome; diuretics: severe hyponatremia; anticoagulants: increased risk of bleeding; NSAIDs: increased risk of upper gastrointestinal bleeding; tryptophan: serotonin syndrome; astemizole, terfenadine: ventricular arrhythmias and Q-T interval prolongation; haloperidol, maprotiline: severe extrapyramidal symptoms; lithium increase in plasma lithium concentration and lithium toxicity. Overall, SSRIs have fewer adverse effects than tricyclic antidepressants, but the SSRIs do have characteristic adverse reactions of their own. Therefore, doctors should exercise caution when prescribing SSRIs to patients in clinical practice.

A 51-year-old male patient received an operation treatment for paranasal sinusitis induced by radiotherapy and chemotherapy of nasopharyngeal carcinoma. One oxycodone and acetaminophen tablet (each tablet contains oxycodone hydrochloride 5-mg and acetaminophen 325-mg) was given orally thrice daily before and after the operation. Pregabalin 75-mg twice daily was added because of the poor analgesic effectiveness. During the treatment, oral oxycodone hydrochloride 10-mg was given once daily by his family members for 2 days. Two days after the addition of pregabalin, the patient developed mental disorders, such as delirium, irritability, involuntary convulsions of limbs, cognitive impairment, and disorientation. All above-mentioned analgesics were discontinued and dexmedetomidine was given for pain relief and sedation. Three days later, the mental state of the patient was improved, there was no obvious delirium, the discrimination and orientation returned to normal, and dexmetomidine was discontinued. There was an obvious time correlation between the occurrence and disappearance of mental disorders and the combination of analgesic drugs. Referring to the previous literature, it was considered that the mental disorders of the patient were caused by the interaction between oxycodone and pregabalin.

Objective To compare the occurrence and clinical characteristics of hypersensitivity reactions induced by 3 non-ionic iodine contrast media (NICMs) during percutaneous coronary intervention (PCI). Methods The patients who developed hypersensitivity reactions in iopromide, iohexol, and iodixanol application during PCI were screened out from adverse drug reaction reports of Beijing Anzhen Hospital from January 1, 2013 to December 31, 2018 and the total number of patients who underwent the PCI during that period and received the above NICMs was obtained by searching the hospital information system. The overall incidences of hypersensitivity reactions and severe hypersensitivity reactions and incidences of those induced by each of the 3 NICMs were calculated and their clinical characteristics were analyzed.　Results The overall incidences of hypersensitivity reactions and severe hypersensitivity reactions induced by the 3 NICMs were 0.603% (422/69-955) and 0.024% (17/69-955). The incidences of hypersensitivity reactions induced by iohexol, iopromide, and iodixanol were 0.418% (109/26-097), 0.364% (83/22-787), and 1.092% (230/21-071), respectively; the incidences of severe hypersensitivity reactions were 0.023% (6/26-097), 0.039% (9/22-787), and 0.009% (2/21-071), respectively. Iodixanol had a higher incidence of hypersensitivity reactions than iopromide and iohexol (both P<0.001) but the lowest incidence of severe hypersensitivity reactions, which was significantly different from that of iopromide (P=0.047). Of the 422 patients who developed hypersensitivity reactions, 327 were male and 95 were female with an average age of 59 years (range: 27-101 years). The time of hypersensitivity reactions occurrence was recorded in 373 patients and time from NICMs injection to hypersensitivity reactions occurrence were 30-minutes to 90-hours with the median time of 5 hours; hypersensitivity reactions were immediate type (latency ≤1 hour) in 127 patients (34.0%) and delayed type (latency>1 hour) in 246 patients (66.0%). The hypersensitivity reactions induced by iopromide were mainly immediate type (79.5%, 62/78), while those induced by ioxamol were mainly delayed type (87.7%, 193/220). The proportion of patients with a previous history of allergy in the immediate type patients was significantly higher than that in the delayed type patients ［15.0% (15/100) vs. 7.1% (14/197), P=0.030］. The most common clinical manifestation of hypersensitivity reactions was rash ［78.0% (329/422)］. Among 17 cases of severe hypersensitivity reactions, 15 (88.2%) were anaphylactic shock, 1 was laryngeal edema, and 1 was dyspnea, all of which were immediate type. Hypersensitivity reactions were all improved after treatments, but PCI failed to be fully performed in 6 patients due to severe hypersensitivity reactions.　Conclusions The safety of 3 NICMs for PCI was good and the incidence of hypersensitivity reactions was low; the incidence of severe hypersensitivity reactions due to iopromide was the highest. Severe hypersensitivity reactions such as anaphylactic shock might affect the performance of PCI and caution should be given.

A 37-year-old female patient with psoriasis received subcutaneous injection of secukinumab 300-mg once a week. Four weeks later, it was changed to subcutaneous injection of 300-mg once every 4 weeks. Seventy-five days later, the patient developed abdominal pain, diarrhea, and fever. The patient had no previous intestinal disease and family history of inflammatory bowel disease. Ulcerative colitis (initial, whole colon, and severe type) was diagnosed by enteroscopy, which was considered to be related to secukinumab. After 2 days of anti-inflammatory treatment with glucocorticoid, the patient′s body tempera- ture returned to normal and the abdominal pain was alleviated； after 9 days, the patient only had a dull abdo- minal pain at night and no other discomfort occurred.

An 89-year-old female patient received escitalopram 10-mg once daily for depression. Three months later, the patient was admitted to hospital for sudden dizziness and a fall. Escitalopram was continued after the admission. On the 6th day of admission, the patient developed syncope again, transient ventricular tachycardia was found by electrocardiogram (ECG) monitoring, and the ECG showed the rate-corrected QT interval (QTc) 612-ms. Escitalopram was discontinued. However, the next day the patient developed ventricular tachycardia again, and the ECG showed Torsades de Pointes and QTc 727-ms. The serum potassium level was 2.84-mmol/L and the patient was given intravenous and oral potassium supplementation. On the 9th day of admission, the patient′s serum potassium level and ECG returned to normal, and the QTc was 487-ms. Escitalopram (with the same dose as before) was given again. The next 5 days, her QTc gradually extended to 506-ms, but serum potassium was normal. Escitalopram was discontinued again and the QTc shortened to 495-ms 2 days later. After 27 days of drug withdrawal, the ECG showed the QTc was 467-ms.

Smoking is one of major causes leading to death and more than five million people die from smoking each year worldwide. It has become a serious public health problem. Studies have been identified that there are more than 4000 compounds in tobacco and tobacco smoke. Among them at least 43 compounds are carcinogens. Regular smoking can cause a number of diseases like cancer, emphysema, heart disease, organ damage as well as dependence (addiction). The dependence is mainly caused by nicotine containing in tobacco. Most regular smoking are addicted to nicotine. So regular smokers stopping smoking may induce nicotine withdrawal symptoms including irritability, restlessness, dizziness, headache, difficulty sleeping, and inability to concentration. Most smokers who fail to succeed in quitting smoking is mainly related to the nicotine addiction. In view of this fact, a nicotine replacement therapy (NRT) was advanced. NRT is a way of getting nicotine slowly into the body without smoking. This help people not only to stop or reduce the symptoms of nicotine withdrawal, but also avoid the hazards from smoking. The results from the various studied have showed that NRT increase the rate of success in quitting smoking, and the risk for dependence to NRT product is small. NRT medicines are available as gums, patches, inhalers, sprays, and so on. All dosage forms of NRT medicines have adverse reactions. The severity of adverse reactions are generally mild, but their types differ across NRTs. The common adverse reactions are dizziness, headache, nausea, vomiting, and gastrointestinal discomfort. NRT can safely used for pationts with cardiovascular disease. NRT is not recommended for pregnant women, nursing mothers, and adolescents. In a word, nicotine replacement therapy is safe and effective in helping smokers stop using cigarettes. NRT products have been used in many countries worldwide as OTC. It is worthy of recommendation.

Iodinated contrast encephalopathy is a rare complication after angiography or interventional therapy with iodinated contrast medium (ICM), with an incidence of 0.13%-2.92%. Iodinated contrast encephalopathy usually occurs minutes to hours after the use of ICM. Its clinical manifestations are diverse, and transient cortical blindness is the most common. Most patients have a good prognosis and generally recover completely within 48-72-hours, while a few may have irreversible neurological damage. The pathogenesis of iodinated contrast encephalopathy is not clear, which may be related to high-dose exposure of ICM due to the damage of blood-brain barrier and the direct cytotoxicity of ICM. Previous history of chronic kidney disease and stroke are risk factors for iodinated contrast encephalopathy, and types of ICM and body parts of angiography or intervention may have different influence on it. After angiography or interventional treatment using ICM, whether patients have symptoms such as mental disorder, visual field defect, and epilepsy should be observed. Once suspicious symptoms appear, CT or magnetic resonance imaging should be completed in time to avoid delaying treatment.

A 79-year-old male patient was given an IV infusion of piperacillin sodium and tazobactam sodium 4.5 g once every 8 hours for head injury complicated by Escherichia coli pneumonia. Before the treatment, his white blood cell count (WBC) was 10.20×109/L, red blood cell count (RBC) was 3.58×1012/L, hemoglobin (HB) was 101-g/L, and platelet count (PLT) was 202×109/L. On day 2 of medication, his blood cell count began to decrease, with the lowest values of WBC 2.96×109/L, RBC 2.40×1012/L, Hb 66-g/L, and PLT 128×109/L, respectively. It was misdiagnosed as gastrointestinal bleeding because of positive occult blood in gastric juice of the patient at the same time. However, the patient had no obvious melena, his gastric fluid occult blood did not match the development of anemia, and there was no evidence of hemolysis or hemorrhage at other sites. The relationship between the blood cell count decrease and piperacillin sodium and tazobactam sodium was considered. The drug was discontinued and the patient′s blood cell count returned to levels before treatment 3 days later.

目的 对利巴韦林和干扰素α的不良事件（AE）进行数据挖掘，为鉴别应用这两种药物治疗新型冠状病毒肺炎（新冠肺炎）过程中出现的临床症状/体征和实验室检查异常是药物引起还是疾病本身所致提供依据。　方法 根据文献及《新型冠状病毒肺炎诊疗方案（试行第五版）》中提到的新冠肺炎症状/体征及实验室检查异常结果选出本研究关注的AE。收集2004年1月1日至2019年12月31日美国FDA不良事件报告系统（FAERS）相关数据，采用报告比值比（ROR）法对利巴韦林和干扰素α进行数据挖掘。　结果 设定时段内FAERS数据库共收到7-582-463份药物相关的有效AE报告，其中利巴韦林31-775份，干扰素α 2-345份。分析结果显示，在呼吸系统、胸及纵隔疾病中可能与利巴韦林具有相关性的AE有鼻充血、咳嗽、喉疼痛、咽部水肿、咳痰和呼吸困难，可能与干扰素α具有相关性的AE有喉疼痛和咯血；在其他系统器官分类中可能与利巴韦林和干扰素α均具有相关性的AE包括发热、寒冷感、疲乏、恶心、呕吐、腹泻、头痛、关节痛、肌痛和皮疹。在实验室检查异常AE中，与利巴韦林相关的有白细胞计数降低、血小板计数降低、天冬氨酸转氨酶升高和丙氨酸转氨酶升高；与干扰素α相关的有白细胞计数降低、淋巴细胞计数降低、血小板计数降低、天冬氨酸转氨酶升高和丙氨酸转氨酶升高。　结论 利巴韦林和干扰素α相关AE中一部分与新冠肺炎的临床表现和实验室检查异常结果相似，临床实践中应当注意鉴别。

In 2019, a total of 15 056 cases of medication error (ME) from 234 hospitals in 24 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 32.20% compared with that in 2018 (177 hospitals), and the number of reported cases increased by 28.02% compared with that in 2018 (11 761 cases). In 15 056 cases of ME reports, 52 (0.35%) were classified as grade A, 11 175 (74.22%) as grade B, 3 351 (22.26%) as grade C, 350 (2.32%) as grade D, 79 (0.52%) as grade E, 44 (0.29%) as grade F, 0 as grade G, 4 (0.03%) as grade H, and 1 (0.01%) as grade I. Among the 15 004 patients involved in ME of grade B‑I, 8 801 (58.66%)were male and 6 203 (41.34%) were female; the age of these patients ranged from 1 day to 103 years, 2 027 patients (13.51%) were <18 years old, 7 377 patients (49.17%) were ≥18 to <60 years old, and 5 600 patients (37.32%) were ≥60 years old. Serious MEs (grade E‑I) involved 128 patients, of whom 65 (50.78%) were aged over 60 years. The top 3 drugs involved in serious MEs were insulin glargine, methotrexate tablets, and warfarin tablets. The 52 cases of grade A MEs did not involve person who triggered the MEs and places where MEs occurred. In the 15 004 cases of grade B‑I MEs, 9 821 (65.46%) were triggered by physicians, 3 561 (23.73%) by pharmacists, 634 (4.23%) by nurses, 306 (2.04%) by patients and their family members, and 2.04% (4.54%) by other persons; the proportion of MEs triggered by physicians and patients and their family members were higher than those in 2018 (60.89% and 1.06%), respectively; 5 662 (37.74%) occurred in the clinics, 4 001 (26.67%) in hospital wards, 3 721 (24.80%) in the pharmacies, 1 084 (7.22%) in pharmacy intravenous admixture services, 224 (1.49%) in the nurse stations, 133 (0.89%) in patients′ houses, 4 (0.03%) in the community health service stations, and 175 (1.17%) in other places; the proportion of MEs in pharmacy intravenous admixture services and patients′ houses were higher than those in 2018 (5.52% and 0.41%), respectively. The top 3 contents of MEs were wrong drug class, wrong usage, and wrong single dose. The top 3 persons who discovered the MEs were pharmacists, nurses, and physicians. The top 3 factors cau- sing MEs were lack of related pharmacologic knowledge, tiredness, and insufficient training of medical workers.

A 34-year-old female patient received an intramuscular injection of compound amionpyrine antipyrine barbitone injection for acute upper respiratory infection and fever. Eight hours after medication, the patient developed deep yellow urine followed by fatigue, anorexia, and yellowish skin. Laboratory tests showed alanine aminotransferase (ALT) 764-U/L, aspartate aminotransferase (AST) 211-U/L, alkaline phosphatase (ALP） 280-U/L, gamma-glutamyltransferase (γ-GT) 861-U/L, total bilirubin (TBil） 72.0-μmol/L, direct bilirubin (DBil） 61.3-μmol/L, and indirect bilirubin (IBil)10.7-μmol/L. The patient was diagnosed as having drug-induced liver injury, which might be related to compound amionpyrine antipyrine barbitone injection. Therapy with liver-protective drugs was given immediately. Sixteen days later, her jaundice subsided. The laboratory tests showed ALT 58-U/L, AST 34-U/L, ALP 237-U/L, γ-GT 345 U/L, TBil 26.0-μmol/L, and DBil 13.1-μmol/L.

Objective To explore the clinical characteristics of immune checkpoint inhibitor- related pneumonitis (CIP) caused by pembrolizumab.　Methods We reported a case of CIP caused by pembro- lizumab admitted in Peking Union Medical College Hospital and searched case reports on CIP caused by pembrolizumab in PubMed, Embase, ScienceDirect, CNKI, VIP, and Wanfang databases (as of October 1, 2019). The main clinical data (gender, age, primary diseases, use of pembrolizumab, combination drugs, time to onset of CIP, symptoms, imaging results, CIP grade, and treatment and outcome) in all reported cases were collected and analyzed.　Results A total of 33 patients were enrolled, including 23 males and 10 females, aged from 44 to 91 years with a median age of 64 years. The primary diseases in 11 cases were melanoma, in 9 cases were lung adenocarcinoma, in 4 cases were lymphoma, in 3 cases were colon cancer, and in 6 patients were esophageal cancer, breast cancer, nasopharyngeal cancer, pulmonary pleomorphic carcinoma, pulmonary large-cell neuroendocrine carcinoma, and lung squamous cell cancer, respectively. Thirty patients received pembrolizumab as monotherapy, 1 patient received combination therapy of pembrolizumab with carboplatin and pemetrexed, and 2 patients received pembrolizumab combined with radiation therapy. Time to onset of CIP in the 33 patients was 1 day at the shortest and 2 years at the longest with a median time of 12(4, 16) weeks. The symptoms of CIP mainly were dyspnea in 19 cases, cough and expectoration in 15 cases, and fever in 9 cases. The common radiological features were ground glass opacities in 17 cases, consolidations in 11 cases, and grid-like high-density shadow in 8 cases. After the diagnosis of CIP, all patients stopped using pembrolizumab. Twenty-nine patients were treated with glucocorticoids, 19 patients received antibacterial therapy, 2 patients received human immunoglobulin, 1 patient received infliximab, and 2 patients did not receive any intervention. Of the 30 patients with known clinical outcomes, 24 patients were improved and 6 died. Among the improved patients, 6 patients underwent rechallenge with pembrolizumab and 1 of them developed CIP again.　Conclusions The clinical symptoms and radiologic features of CIP caused by pembrolizumab are lack of specificity. Constant vigilance for the presences of fever and respiratory symptoms within 12 weeks after pembrolizumab treatment is required. The CIP in most patients can be improved after drug withdrawal and additional use of glucocorticoids, but the potential fatal risk of CIP is still need to be alert to.

Objective To explore the effect of evolocumab on the risk of early intracranial hemor- rhage in patients with acute anterior circulation ischemic cerebral infarction.　Methods The medical records of patients with acute anterior circulation ischemic cerebral infarction who were admitted to Tianjin Huanhu Hospital within 48-hours of onset from January 2019 to September 2020 were collected and analyzed retrospectively. On the day of admission, all patients were given statin lipid-lowering therapy and the patients with fasting low density lipoprotein cholesterol (LDL-c) >3.37-mmol/L received combination therapy with statin and evolocumab. The patients who used statins alone were enrolled in the statins group and those with combined application of evolocumab were enrolled in the combination group. The situation of blood lipid level up to standard (LDL-c <1.70-mmol/L) and the occurrence of intracranial hemorrhage in the second week after admission were compared between the 2 groups. The patients were divided into bleeding group and non-bleeding group according to the occurrence of intracranial hemorrhage. The basic information, combined diseases, etiological classification of cerebral infarction, lipid-lowering program, National Institute of Health Stroke Scale (NIHSS) score on admission, blood pressure, blood lipid level, and blood lipid level in the second week of lipid-lowering treatment between the 2 groups were compared. The factors with P<0.05 were enrolled in the multivariate logistic regression analysis, odds ratio (OR) and its 95% confidence interval (CI) were calculated, and the risk factors of intracranial hemorrhage were analyzed.　Results A total of 437 patients were enrolled in the analysis, including 358 (81.9%) in the statins group and 79 (18.1%) in the combination group. The differences in basic information, combined diseases, etiological classification of cerebral infarction, lipid-lowering program, NIHSS score on admission, blood pressure, and other clinical features between the 2 groups were not statistically significant (all P>0.05). The baseline levels of total cholesterol (TC), triglyceride (TG), LDL-c, and high-density lipoprotein cholesterol (HDL-c) in the statins group were lower than those in the combination group (TC: P<0.001, TG: P<0.001, LDL-c: P=0.004, HDL-c: P=0.024). At the 2nd week of lipid-lowering treatment, the levels of LDL-c and TC in the statins group and the combination group were lower than those before treatment, but the differences of LDL-c and TC levels before and after treatment in the statins group were significantly lower than those in the combination group ［LDL-c: (0.66±0.91) mmol/L vs. (2.58±0.38) mmol/L, P<0.001; TC: (0.37±0.18) mmol/L vs. (1.94±0.44) mmol/L, P<0.001］. The rate of lipid level up to standard in the combination group was significantly higher than that in the statins group ［87.3% (69/79) vs. 9.7% (37/358), P<0.001］. The incidences of intracranial hemorrhage were 12.0% (43/358) in the statins group and 13.9% (11/79) in the combination group within 2 weeks after admission respectively. Multivariate logistic regression analysis showed that complication with atrial fibrillation (OR=3.054, 95%CI: 1.402-6.651, P=0.005), higher NIHSS score on admission (OR=3.431, 95%CI: 1.554-7.573, P=0.001), and etiological classificantion as cardiac embolism (OR=1.544, 95%CI: 1.047- 2.278, P=0.028) were independent risk factors for early intracranial hemorrhage. Conclusions The combination of statins and elouzumab has better lipid-lowering effect in patients with acute anterior circulation cerebral infarction. No correlation is found between evolocumab and early intracranial hemorrhage.

A 31-year-old pregnant woman was treated with progesterone soft capsule 0.2 g vaginally twice daily and nadroparin calcium injection 4 100 U subcutaneously once daily due to threatened abortion at 23+1 weeks of menopause. On the 16th day of treatments, laboratory tests showed alanine aminotransferase (ALT) 766-U/L, aspartate aminotransferase (AST) 411-U/L, γ-glutamyl transferase (γ-GT) 98-U/L, alkaline phosphatase (ALP) 180-U/L, and total bile acid (TBA) 40.1-μmol/L. Liver injury caused by nadroparin calcium was considered. The drug was stopped and liver protective treatments were given. On the 21st day of nadroparin calcium withdrawal, the patient had inevitable abortion and delivered a dead baby through vagina. Laboratory tests showed ALT 83 U/l, AST 103 U/l, γ-GT 37-U/L, ALP 157-U/L, and TBA 42.0-μmol/L. Liver protective treatments were continued After 35 days of nadroparin calcium withdrawal, laboratory tests showed ALT 18-U/L, AST 15-U/L, γ-GT 33-U/L, ALP 156-U/L, and TBA 6.2-μmol/L.

Objective To systematically evaluate the occurrence of interstitial lung disease (ILD) in patients with non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI).　Methods PubMed, Embase, The Cochrane Library, CNKI, WanFang, and VIP databases were searched up to April 30, 2022. Randomized controlled trials (RCT) about NSCLC treated with EGFR-TKI (8 kinds listed in China, including gefitinib, erlotinib, icotinib, afatinib, dacomitinib, osimertinib, almonertinib, and furmonertinib) compared with chemotherapy were collected. Patients was treated with EGFR-TKI monotherapy in the trial group and chemotherapy in the control group. The outcomes included the occurrence of ILD. RevMan 5.4-software was used for meta-analysis, and the effect sizes were odds ratio (OR) and the 95% confidence interval (CI).　Results A total of 15 RCT were entered in the analysis, including 6 about gefitinib, 5 about erlotinib, 2 about icotinib, and 2 about afatinib， involving 2-318 patients in the trial group and 1-975 in the control group. Meta-analysis showed that the overall incidence of ILD in the trial group were higher than that in the control group ［1.47% (34/2-318) vs. 0.51% (10/1-975), OR=2.44, P=0.004］; difference in incidences of ILD-related death between the 2 groups was not significant ［0.35% (8/2-318) vs. 0.05% (1/1-975), OR=3.29, P=0.07］. The severity of ILD was graded in 14 RCT, and the meta-analysis showed that the incidence of more than grade 3 ILD in the trial group was higher than that in the control group ［0.62%(13/2-089) vs. 0.11% (2/1-864), OR=2.60, P=0.04］. The overall incidences of ILD and the incidences of more than grade 3 ILD in the gefitinib group were higher than those in the corresponding control groups ［2.31%(27/1-167) vs. 0.71% (8/1-123), OR=2.88, P=0.004; 0.86% (7/1-167) vs. 0.09% (1/1-123), OR=3.98, P=0.03］. There was no significant difference in ILD occurrence between the trial group and the control group for afatinib and erlotinib (all P>0.05). No ILD occurred in the trail group or in the control group in RCT about icotinib.　Conclusions Compared with chemotherapy, NSCLC patients receiving EGFR-TKI, especially gefitinib, have higher risks of ILD and serious ILD. Therefore, clinical vigilance and monitoring should be strengthened.

Objective To mine risk signals related to tafamidis, which was a rare disease drug and newly included in the medical insurance list.　Methods The drug-related adverse event (AE) reports from the 1st quarter of 2013 to the 2nd quarter of 2022 were searched based on the US FDA Adverse Event Reporting System and AE reports with tafamidis as the primary suspect drug were extracted. The report odds ratio (ROR) method and Bayesian confidence propagation neural network (BCPNN) method were used to detect the AE risk signals of tafamidis. A target AE with reports ≥3 and 95% confidence interval (CI) lower limit of ROR>1 was defined as a positive signal for ROR method and the larger the ROR and its lower limit of 95%CI, the stronger the signal strength. The information component (IC)-2SD>0 (SD is the standard deviation) was defined as a positive signal for BCPNN method, and the larger the IC-2SD value, the stronger the signal. According to the preferred system organ class (SOC) and preferred term (PT) from terminology of adverse drug reactions in Medical Dictionary for Regulatory Activities, AEs were counted and classified. The risk signal with positive detection results from both ROR and BCPNN methods was determined as the AE risk signal of tafamidis and analyzed. Results A total of 3-999 cases with tafamidis as the primary suspect drug were collected, including 2-942 males (73.6%), 688 females (17.2%), and 369 unknown cases (9.2%); 3-148 cases (78.7%) aged >65 years, 192 cases (4.8%) aged 18-65 years, 52 cases (1.3%) aged <18 years, and 607 cases (15.2%) were unknown; 1-064 patients were with cardiac amyloidosis, 872 patients with cardiac amyloidosis, 148 patients with peripheral nerve amyloidosis, and 176 with other diseases; 1-403 cases (35.1%) died. A total of 110 positive signals were screened with both ROR and BCPNN methods, involving 20 SOCs. The top 5 PTs of AE reports were dyspnea (338 cases), fatigue (301 cases), edema (167 cases), dizziness (111 cases), and fall (110 cases). The SOC involved were systemic lesions, neurological diseases, respiratory/thoracic and mediastinal diseases, examination, metabolic and nutritional diseases. The top 5 PTs (ROR and the 95%CI lower limit) were early feeling of fullness （28.07，11.64), lumbar spinal stenosis （26.73，15.15), aortectasia （24.36，9.11), hypoxia （22.64，10.15), and cervical radiculopathy （22.13，7.11). Four of the top 20 PTs in the AE reports were not recorded in the drug label, including dizziness, height loss, chest pain, and renal failure; 16 of the top 20 PTs in signal strength (ROR method) were not recorded in the drug label, including lumbar spinal stenosis, aortic dilatation, physical decline, cervical radiculopathy, height reduction, carotid artery disease, hyperlipidemia, orthopnea, peripheral vein disease, benign prostatic hyperplasia, carpal tunnel syndrome, emaciation, foreign body sensation in the throat, immune thrombocytopenia, positional dizziness, and aortic atherosclerosis.　Conclusion Through data mining, it is found that early feeling of fullness, lumbar spinal stenosis, aortic dilatation, physical decline, and cervical radiculopathy may be the common adverse events of tafamidis, some risk signals are not recorded in the drug label, which should be paid attention to during the clinical use.

Vaccines have made great contributions to the prevention of infectious diseases, but vaccine hesitancy is widespread in the world. The reasons for vaccine hesitancy are complex, but the main reasons are the lack of public awareness of vaccine-preventable diseases and the lack of confidence in vaccine effectiveness and safety. In the context of the continuous spread of the coronavirus disease 2019 (COVID-19) epidemic, boosting public confidence and ensuring the orderly development of the vaccination work of COVID-19 vaccines and conventional vaccines are necessary to curb the resurgence of the COVID-19 epidemic and prevent the outbreak of various infectious diseases in China. Under the current situation, the main measures to deal with vaccine hesitancy are to play the role of health care institutions, improve public health literacy, normalize the public opinion orientation of the media platform, strengthen the supervision of vaccine clinical research and production, and do a good job in surveillance and compensation for adverse events following immunization.

A 67-year-old male patient with small cell lung cancer was given chemotherapy combined with immunotherapy (irinotecan+nedaplatin+tislelizumab), 21 days as a cycle. The patient′s cough was significantly improved without blood in sputum. After 2 cycles of treatment, chemotherapy and immunotherapy were suspended because of grade Ⅳ bone marrow suppression, and radiation therapy was changed. After the 29th radiotherapy, the patient developed paroxysmal cough and sputum with bloody, accompanied by shortness of breath and no fever. Blood gas analysis showed type Ⅰ respiratory failure. Chest computed tomography (CT) showed new pleural reticular vague shadows in both lungs, especially in the right lung. Radiotherapy was stopped and chemotherapy was restarted. The patient's cough and expectoration were improved, but the shortness of breath gradually aggravated. The interstitial pneumonia lesions involved both lungs rather than being localized, by which radiation pneumonitis were ruled out. Virus and atypical pathogen infection were excluded by etiology and imaging examination. Immune-related pneumoniatis complicated with infection caused by tislelizumab was considered. High-dose methylpre- dnisolone combined with gamma globulin and infliximab were given to inhibit immune response, mero- penem, moxifloxacin, voriconazole were given successively to prevent infection, and oxygen inhalation was given. The patient′s cough, expectoration, and shortness of breath disappeared, oxygenation index was improved, and chest CT showed that the range of interstitial changes in both lungs gradually reduced.

A female infant aged 7 months and 29 days received an IV infusion of ceftriaxone sodium for injection (ceftriaxone sodium) 0.5 g dissolved in 0.9% sodium chloride injection 100-ml once daily because of acute diarrhea, moderate dehydration, and myocardial injury. Symptomatic treatments such as maintaining water and electrolyte balance and nourishing myocardium were given at the same time. Her platelet count (PLT) was 269×109/L before treatment. On day 4 of treatments, the laboratory test showed that her PLT was 893×109/L. Infection-induced thrombocytosis was considered and ceftriaxone sodium was continued at the original dose. On day 6 of treatments, her PLT was 931×109/L; on day 8 of treatments, her PLT increased to 1-018×109/L. It was considered that the increase of PLT might be related to ceftriaxone sodium. Ceftriaxone sodium was stopped and anticoagulant therapy was given. Six days later, her PLT decreased to 359×109/L; 19 days later, the PLT decreased to 224×109/L.

A 47-year-old female patient received compound polyethylene glycol electrolytes powder (III) 4 bags (73.59 g/bag) dissolved in 4 L warm water in 16 divided doses to prepare for colonoscopy the next day. The patient took medicated warm water 2 L within 2 hours. She had loose stool and watery stool for more than 10 times within 1 hour after medication. The patient did not continue to take drugs because of the severe diarrhea. Fourteen hours after medication, the patient developed apathy, no response to voice stimuli, and involuntary movement of both upper limbs. Sixteen hours after medication, the patient developed unconsciousness and tetanic convulsion of limbs. Laboratory tests showed that serum sodium was 120-mmol/L and plasma osmolality was 258.22 mOsm. She was diagnosed with hyponatremia encephalopathy. Except polyethylene glycol electrolytes powder (III), the patient did not take any other drug. It was considered that hyponatremia encephalopathy was related to polyethylene glycol electrolytes powder (III). Symptomatic treatments such as sodium supplement and dehydration were given immediately. After 1 hour of treatment, the patient′s consciousness recovered; 8 hours later, her serum sodium was 142-mmol/L.

A 49-year-old male patient was treated with first-line and second-line chemotherapy regimens successively for 7 months because of Hodgkin′s lymphoma. However, the tumor failed to be well controlled. His treatment was changed to intravenous infusion of sintilimab 200-mg once every 21 days. His liver function was normal before treatment. After the second administration of sintilimab (on day 42 after the first medication), the patient developed chest distress, abdominal distension, poor appetite, and etc. Reexa- mination of liver function showed alanine aminotransferase (ALT) 1-590-U/L, aspartate aminotransferase (AST) 3-678-U/L, alkaline phosphatase (ALP) 468-U/L, gamma-glutamyl transferase (γ-GT) 399-U/L, total bilirubin (TBil) 50.1-μmol/L, and direct bilirubin (DBil) 26.8-μmol/L. Sintilimab was discontinued, but the patient′s jaundice was deteriorated. Intravenous infusion of methylprednisolone 150-mg once daily was given for 3 days, but the bilirubin reached the peak (TBil 152.6-μmol/L，DBil 109.2-μmol/L). Oral mycophenolate mofetil 0.5 g twice daily was added, the patient′s symptoms were gradually improved, and his liver function gradually recovered. After 6 days of combination use of methylprednisolone and mycophenolate mofetil, the laboratory tests showed ALT 63-U/L, AST 78-U/L, TBil 25.2-μmol/L, and DBil 12.9-μmol/L. Twenty-two dags later, his liver function returned to normal.

 A 26-year-old female patient took oral methimazole 20-mg twice daily due to hyperthyroidism. More than a month later, she developed spastic pain of limb muscles. Laboratory tests showed alanine aminotransferase (ALT) 45-U/L, aspartate aminotransferase (AST) 121-U/L, creatine kinase (CK) 6-090-U/L, and serum potassium 4.1-mmol/L. The dose of methimazole was reduced to 10-mg once daily, but the patient′s myalgia was not improved after 3 days. Adverse reactions due to methimazole were considered and therefore the drug was discontinued. Four days after drug withdrawal, the patient′s myalgia was obviously relieved, and laboratory tests showed ALT 36-U/L, AST 50-U/L, and CK 1-954-U/L. After 18 days of drug withdrawal, her myalgia disappeared, and the ALT, AST, and CK returned to normal.

A 64-year-old male patient with colon cancer received one cycle chemotherapy of oxaliplatin+capecitabine and 7 cycles of oxaliplatin+raltitrexed chemotherapy. There were no interstitial changes in chest CT before operation. After 8 cycles of chemotherapy, the patient deve- loped chest tightness and shortness of breath. Chest CT showed interstitial changes in bilateral lungs, which were considered to be related to oxaliplatin. After 31 days of treatments with drugs such as broad-spectrum antibiotics, glucocorticoids, acetylcysteine, and reduced glutathione, as well as noninvasive ventilator assisted ventilation, oxygen inhalation, and other symptomatic treatments, his symptoms of chest tightness and shortness of breath were relieved, and chest CT showed that interstitial lesions in the bilateral lungs were obviously relieved.

Objective To understand and analyze the occurrence of medication error (ME) on insulin preparations and its influencing factors and provide reference for the standard use of insulin preparations.　Methods The ME reports on insulin preparation-related MEs in the National Monitoring Network for Clinical Safe Medication (monitoring network) from May 6, 2015 to June 30, 2022, were collected and information of MEs including drugs involved, grading, error content, the persons who caused and found the errors, and the factors that triggered the errors were analyzed.　Results During the set period, a total of 2-215 ME reports from 193-hospitals in 26 provinces and municipalities in China were collected in the monitoring network. A total of 2-215 patients were involved, including 1-345 males (60.72%) and 870 females (39.28%), aged from 1 to 95 years, with an average age of (52±4） years. Two thousand one hundred and eighty-two MEs (98.51%) were mild and 33 (1.49%) were severe. The 2-215 ME reports involved 8 classes and 29 kinds of insulin, and a total of 2-263 times of ME content. The top 3 ME contents of insulin preparations were variety errors (40.70%, 921), interaction/compatibility errors (18.29%, 414), and dosage errors (9.06%, 205). Among the 2-215 MEs, 58.24% (1-290 MEs) were triggered by physicians, 28.26% (626 MEs) by pharmacists, 6.5% (144 MEs) by patients and their families, 5.6% (124 MEs) by nurses, and 1.40% (31 MEs) by others; 1-741 MEs (78.60%) were detected and intercepted in time, of which 75.70% (1-318) were found by pharmacists, 14.01% (244) by patients/family members, 7.76% (135) by nurses, and 2.53% (44) by physicians. The main factors that caused MEs were lack of knowledge (23.28%, 701), similar drug names (19.36%, 583), fatigue (14.51%, 437), etc.　Conclusions The contents of insulin preparations-related MEs mainly include variety error, interaction/compatibility error, and dosage error. MEs are mainly caused by physicians and mostly discovered and intercepted by pharmacists. Lack of knowledge, similar drug names, and fatigue are the major factors causing MEs.

Objective To evaluate the efficacy, safety, and economy of meropenem in the treatment of infectious diseases by means of rapid health technology assessment.　Methods The relevant databases (up to October 6, 2021) were searched to collect the meta-analyses and economic studies on the comparison of efficacy, safety, and economy in the treatment of infectious diseases with meropenem and other antibiotics. The quality of meta-analysis and economic research were evaluated by the Quality Assessment Scale for Systematic Review and Health Economics Evaluation Reporting Standard, respectively. The outcome indicators of meta-analysis were efficacy (clinical cure rate, bacterial clearance rate) and incidence of adverse drug reaction (ADR), the effect indicators were relative risk (RR), odds ratio (OR), or risk difference (RD), and the 95% confidence interval (CI). The economic research indicators were incremental cost- effectiveness ratio and minimum cost. Qualitative description of the results enrolled in this study was conducted.　Results A total of 6 meta-analyses and 5 economic studies were enrolled in this study, all of which were of high quality. Efficacy: the clinical cure rate of meropenem in the treatment of febrile neutropenia were higher than those of β-lactam antibiotics alone and β-lactam antibiotics combined with aminoglycoside antibiotics, the differences were statistically significant ［55.6% (956/1-720) vs. 49.3% (888/1-798), OR=1.36, 95%CI: 1.18-1.56, P<0.01； 58.3% (429/735) vs. 54.1% (415/767), OR=1.24, 95%CI: 1.01-1.53, P=0.04］. The clinical cure rate of meropenem in the treatment of abdominal infection was higher than those of ceftazidime- avibactam combined with metronidazole, ceftolozane-tazobactam combined with metronidazole, and imipenem, and the differences were all statistically significant ［86.6% (581/671) vs. 82.6% (571/691), RD=-0.04, 95%CI: -0.08-0, P=0.03; 87.8% (388/442) vs. 83.1% (374/450), RD=-0.05, 95%CI: -0.10-0, P=0.04; 90.8% (1-791/1-972) vs. 87.6% (1-884/2-151), OR=1.52, 95%CI: 1. 23-1. 86, P<0.05］. The bacterial clearance rate of meropenem in the treatment of abdominal infection was higher than those of ceftazidime-avibactam combined with metronidazole, and imipenem, and the differences were all statistically significant ［89.8% (491/547） vs. 85.5% (430/503), RD=-0.04, 95%CI: -0.08-0, P=0.04; 87.0% (1-109/1-274) vs. 82.3% (1-054/1-278), OR=1.45, 95%CI: 1.15-1.80, P<0.05］. The differences of bacterial clearance rate in treatment of abdominal infection among meropenem, ceftolozane-tazobactam combined with metronidazole, and β-lactam antibiotics were not statistically significant (all P>0.05). Safety: the differences of incidence of ADR in treatments of febrile neutropenia and pneumonia among meropenem, β-lactam antibiotics alone, β-lactam anti- biotics combined with aminoglycoside antibiotics, and non-carbapenem antibiotics were not statistically significant (all P>0.05). Economy: ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem had better cost- effectiveness advantages than meropenem in the treatment of abdominal infection, pneumonia, and febrile neutropenia.　Conclusions Meropenem has good efficacy in the treatment of febrile neutropenia and abdominal infection. There is no significant difference in safety between meropenem and other anti-biotics, but meropenem has no economic advantage.

A 48-year-old female patient received compound Congrong Yizhi capsules 1.2 g (4 capsules) orally thrice daily for memory decline. About 20 days later, the patient developed nausea, anorexia, yellow urine, and yellow staining of skin and sclera. Compound Congrong Yizhi capsules were discontinued. Seven days after drug withdrawal, laboratory tests showed that alanine aminotransferase (ALT) was 1-349-U/L, aspartate aminotransferase (AST) was 827-U/L, alkaline phosphatase (ALP) was 156-U/L, and total bilirubin (TBil) was 213.7-μmol/L. Liver injury induced by compound Congrong Yizhi capsules was considered. Reduced glutathione, compound glycyrrhizin, ademetionine 1,4-butanedisulfonate, and dexa- methasone were given. The patient′s appetite was gradually improved and jaundice gradually subsided. After 36 days of treatments, ALT was 26-U/L， AST was 30-U/L， ALP was 86-U/L， and TBil was 27.2-μmol/L. The liver injury of the patient was considered to be related to Radix Polygoni Multiflori Preparata (prepared fleeceflower root) in compound Congrong Yizhi capsules.

Objective To report the clinical features of pulmonary hypertension diagnosed by echocardiography in 5 patients with novel coronavirus pneumonia (COVID-19) in order to understand the special clinical manifestations of COVID-19 and explore the possible mechanism.　Methods The echocardiographic data and clinical characteristics of COVID-19 patients complicated with pulmonary hypertension diagnosed by echocardiography in Beijing Ditan Hospital, Capital Medical University were analyzed descriptively from February 5 to March 31, 2020.　Results A total of 15 patients with severe and critical COVID-19 patients underwent echocardiography. Of them, 7 patients were diagnosed with pulmonary hypertension, 5 of which were confirmed as complications of COVID-19. Among the 5 patients, 4 were female and 1 was male, aged 62-78 years; 4 were with hypertension, 3 were with diabetes, and 1 was with coronary atherosclerotic heart disease. All 5 critically ill patients with COVID-19 were given ventilator-assisted breathing, 2 of which were given extracorporeal membrane oxygenation at the same time. According to echocardiography, the systolic pressure of pulmonary artery in 5 patients was 43-65-mmHg, with an average of 54-mmHg. The severity of pulmonary hypertension was graded as mild in 1 patient and moderate in 4 patients. During the follow-up, pulmonary artery systolic pressure gradually decreased to normal in 4 patients, and then ventilator and ECMO were withdrawn; 1 patient died due to respiratory failure and persistent pulmonary hypertension.　Conclusions Patients with COVID-19 may be complicated by pulmonary hypertension, which is often found in the critical patients. Echocardiography is an important imaging diagnostic method for pulmonary hypertension in patients with COVID-19.

Objective To explore the risk factors and the predicting value of early urinary tract infection in patients treated with tacrolimus (TAC)-containing immunosuppressive regimen after kidney transplantation.　Methods The medical records of patients who underwent allogeneic kidney transplantation in the Provincial Hospital Affiliated to Shandong First Medical University from January 1, 2015 to October 30, 2021 and received triple immunosuppressive regimen with TAC+mycophenolate mofetil+methylprednisolone were collected and analyzed retrospectively. Relevant clinical data of patients were extracted from the hospital information system. Patients were divided into infection group and non-infection group according to whether urinary tract infection occurred within 1 month after taking TAC and the clinical characteristics in patients between the 2 groups were compared. The risk factors of urinary tract infection were analyzed by binary logistic regression method, and the odds ratio (OR) and its 95% confidence interval (CI) were calculated. The receiver operating characteristic (ROC) curve was used to analyze the predicting value of risk factors on the risk of urinary tract infection.　Results A total of 256 patients were entered in the analysis, including 208 males and 48 females, aged 34 (29, 42) years with an range from 18 to 66 years, and the body mass index of these patients was 22.9 (20.4, 25.4) kg/m2, ranging from 13.9 to 34.4-kg/m2. There were 163 living donors from relatives and 93 cardiac dead organ donors (DCD). Among the 256 patients, 56-had urinary tract infection (asymptomatic bacteriuria in 32 patients and symptomatic urinary tract infection in 24 patients) after kidney transplantation with an incidence of 21.9%. The differences in gender, age, body weight, body mass index, primary disease, comorbidity disease, donor source, length of hospital stay after surgery, time of indwelling urinary tube and ureteral stent, postoperative complications, complicated infection in other parts of the body after surgery, laboratory test results and so on in patients between the 2 groups were not significant (all P>0.05). The trough plasma concentrations of TAC on the 7th, 14th, and 21st days after taking TAC in the infection group was higher than those in the non-infection group ［9.7 (8.4, 13.5) μg/L vs. 8.0 (6.3, 9.8) μg/L, P<0.001; 9.4 (7.6, 11.0) μg/L vs. 8.0 (6.3, 9.8) μg/L, P=0.002; 9.2 (7.6, 11.1) μg/L vs. 8.2 (6.3, 9.8) μg/L, P=0.002］. The binary logistic regression analysis showed that the high trough plasma concentrations of TAC on the 7th day after taking TAC (OR=1.815, 95%CI: 1.332-2.474, P<0.001) was an independent risk factor for urinary tract infection in the early stage after kidney transplantation. The ROC curve analysis results showed that the area under the ROC curve of TAC trough plasma concentration on the 7th day was 0.704 (95%CI: 0.626-0.782), with the cutoff value 8.35-μg/L, the sensitivity 76.8%, and the specificity 53.5%. The patients were divided into >8.35-μg/L group and ≤8.35-μg/L group according to this cutoff value, the incidences of urinary tract infection in the 2 groups were 31.4% (43/137) and 20.6% (13/119) respectively and the difference was statistically significant (χ2=15.603, P<0.001).　Conclusion High trough plasma concentration of TAC on the 7th day after taking TAC is an independent risk factor for urinary tract infection after kidney transplantation and the predicting value is 8.35-μg/L, which has certain predicting value for early urinary tract infection after kidney transplantation.

A 69-year-old male patient was treated with nivolumab combined with tegafur-gimeraci- loteracil potassium due to gastric adenocarcinoma with liver, pancreas, and abdominal lymph node metastasis after completing 4 cycles of chemotherapy with oxaliplatin and raltitrexed. Ten days later, the patient developed severe rashes all over the body, which was considered to be adverse skin reactions caused by nivolumab and tegafur-gimeracil-oteracil potassium. Then the 2 drugs were stopped and treatments with methylprednisolone and antiallergic drugs were given. The rashes were gradually improved, the dose of glucocorticoid was reduced gradually, and it was stopped at last. However, on the day of glucocorticoid withdrawal, the patient developed fever, chills, and severe respiratory failure. In combination with clinical treatment, laboratory test results, and imaging changes in the patient, it was considered to be immune-related pneumonitis caused by nivolumab. Methylprednisolone, anti-infection, and high-flow nasal cannula oxygen therapy were given. Four days later, the asthma symptoms in the patient were obviously improved, and 28 days later, the pulmonary CT showed the pneumonitis was markedly improved than before.

近年来抗菌药物与乙醇相互作用致双硫仑样反应的发生呈明显增加,本文就此反应发生机制及相关抗菌药物予以分析探讨。其中主要涉及头孢菌素类、硝基咪唑类,以期引起临床医务人员和患者的共同关注,保证用药安全。

秋水仙碱为抗痛风药,可有效控制关节局部的红肿热痛等炎症反应。但其治疗剂量与中毒剂量接近,在体内可被代谢为具有极强毒性的二秋水仙碱,对消化道有刺激作用,可抑制骨髓造血功能,并对神经、平滑肌有麻痹作用,甚至可引起呼吸中枢麻痹而死亡。故不宜长期或大剂量应用。出现严重不良反应须立即停药,并对症救治。

Objective To explore the occurrence and clinical characteristics of thyroid dysfunction caused by camrelizumab.　Methods The subjects were selected from all malignant tumor patients who were treated with camrelizumab during hospitalization in Heping Hospital Affiliated to Changzhi Medical College from June 2020 to September 2021. The electronic medical records of patients who met the inclusion criteria were collected, and the general conditions, camrelizumab application, combined medication, and the thyroid function test results before and after the application of camrelizumab were collected. The causality between drugs and injuries in patients who developed thyroid dysfunction was assessed using Naranjo′s causality assessment scale. The clinical characteristics of thyroid dysfunction were analyzed based on the medical records that had evaluation results of "certainly" or "probably".　Results A total of 71 patients were included in the analysis, and 22 patients (31.0%) developed camrelizumab-related thyroid dysfunction (causality assessment results were all "probably"). When thyroid dysfunction was found for the first time, hypothyroidism and hyperthyroidism were diagnosed in 11 patients, respectively, and 3 patients with hyperthyroidism developed into hypothyroidism later. The incidences of hypothyroidism and hyperthyroidism were 19.7% and 11.3% respectively. Among the 22 patients, 15 were male and 7 were female, aged 47-78 years; 10 patients were with lung cancer, 4 with gastric cancer, 3 with esophageal cancer, 2 with liver cancer, 2 with breast cancer, and 1 with peritoneal omental mesothelioma; 3 patients were treated with camrelizumab monotherapy, and 19 were treated with camrelizumab combined with chemotherapy and/or targeted drug therapy. Thyroid dysfunction all occurred in the first to sixth cycles of camrelizumab treatment, of which 15 (68.2%) in the first to third cycles. Of the 11 patients with initial diagnose of hypothyroidism, 6 had no obvious symptoms, 5 had fatigue (1 was complicated with apathy), and 4 were subclinical hypothyroidism; the severity was grade 1 in 4 cases and grade 2 in 7 cases. None of the 11 patients with initial diagnose of hyperthyroidism had significant symptoms, and 5 of them had subclinical hyperthyroid. All of the 11 cases were grade 1 in severity, 3 developed into hypothyroidism after 3, 6, and 7 cycles of camrelizumab treatment, which was grade 2 in severity. None of the 22 patients discontinued camrelizumab. No intervention was given to the patients with grade 1 hypothyroidism and hyperthyroidism, of which 3 patients with hyperthyroidism returned to normal on their own and the remaining showed no obvious changes in their thyroid function. Ten patients with grade 2 hypothyroidism received thyroid hormone replacement therapy; thyroid function was normal in 2 patients, improved in 5 patients, and without obvious changes in 3 patients.　Conclusions Thyroid dysfunction is a very common adverse reaction of camrelizumab, which can present as both hypothyroidism and hyperthyroidism, and initial hyperthyroidism can evolve to hypothyroidism. Thyroid dysfunction was mostly grade 1-2 in severity and the drug does not need to be discontinued generally. Patients with grade 2 hypothyroidism should be given thyroid hormone replacement therapy.

A 63-year-old male patient with hepatocellular carcinoma received sintilimab (200-mg by IV infusion on day 1, 21 days as one cycle) after surgery. After 3 cycles of treatment, the patient developed unclear speech, mental fatigue, drowsiness, and weight loss. Laboratory tests showed triiodothyronine (T3) 0.54-nmol/L, thyroxine (T4) 13.0-nmol/L, thyroid-stimulating hormone (TSH) 98.62 mU/L, free triiodothyronine (FT3) 0.43-pmol/ml, free thyroxine (FT4) 0.25-pmol/L, cortisol (Cor) (8:00) 6.1-nmol/L, adrenocorticotropic hormone (ACTH) (8:00) 0.22-pmol/L/L. He was diagnosed as having immune-related hypothyroidism and adrenal cortex hypofunction, which was caused by sintilimab. After 4 days of treatments with glucocorticoid, the above symptoms in the patient were improved, and levothyroxine was given. The dosage of glucocorticoids given to patients was gradually reduced.After 11 days of treatments with levothyroxine, the laboratory tests showed that the thyroid function returned to normal, and levothyroxine was stopped. Adrenal cortex function was still lower than normal ［Cor (8:00) 51.6-nmol/L，ACTH (8:00) 0.22-pmol/L］. Then prednisone acetate tablets 5-mg once daily orally were given continuously. At 8 months of follow-up, the adrenal cortex function in the patient remained low, and sintilimab was stopped forever.

A 60-year-old male patient was hospitalized due to acute attack of bronchial asthma and pneumonia and antitussive, antiasthmatic, and anti-inflammatory treatments was given. Then his symptoms were improved. Discharge medication included budesonide and formoterol fumarate powder for inhalation and montelukast sodium. On the 4th day of medication after discharge, the patient developed bilateral metatarsophalangeal joint pain with redness and swelling, abdominal distension, fatigue, and dark urine. Laboratory tests showed serum creatinine (Scr) 112-μmol/L, serum uric acid 228-μmoL/L, urine protein (+), and urine occult blood (++). Gout, rheumatoid arthritis, and other autoimmune diseases were excluded and the possibility of acute kidney injury and metatarsophalangeal joint pain related to montelukast sodium was considered. Montelukast sodium was discontinued, budesonide and formoterol fumarate powder for inhalation was continued, and symptomatic treatment was given at the same time. Seven days later, the pain of metatarsophalangeal joint was improved and the urine color returned to normal. Two weeks later, his Scr level returned to normal (75-μmol/L).

Objective To understand the current status of perioperative analgesics use and management in China.　Methods A questionnaire was self-designed with the content consisting of 4 dimensions (the basic information of the respondents, perioperative analgesics management, medical behaviors in perioperative analgesia, and understanding of analgesics-related knowledge) and 55 questions (8, 10, 22, and 15 questions under 4 dimensions, respectively). The questionnaire was sent through Wechat by the members of Chinese Pharmacological Society Professional Committee of Drug-induced Diseases and Anesthesiology Branch of the Chinese Medical Association. Anesthesiologists, surgeons/nurses and clinical pharmacists volunteered to participate in the survey and submitted in anonymous form directly. The investigation period was from August 1 to 31, 2020.　Results A total of 204 effective questionnaires were received from 45-hospitals in 19 provinces and cities, including 43 tertiary hospitals (95.6%) and 2 secondary hospitals (4.4%). Among the 204 respondents, 46 were surgeons (22.5%), 80 were anesthesiologists (39.2%), 32 were clinical pharmacists (15.7%), and 46 were surgical nurses (22.5%). Of the 45-hospitals where the respondents work, 35 (77.8%) had established regular communication mechanisms for perioperative pain management, and 22 (48.9%) arranged clinical pharmacist to assist the work of the physician in the clinical division. Among the 204 respondents, 76.5% (156 respondents) received knowledge training on analgesics once or twice a year; 60.3% (123 respondents) had found irrational use of perioperative analgesics in their daily work, and the top 3 problems were about drug selection ［74.0% (91/123)］, usage and dosage ［69.1% (85/123)］, and drug interactions ［46.3% (57/123)］; 37.3% (76 respondents) had found the problem of irrational use of the analgesia pump, and the top 3 problems were about the usage and dosage ［69.7% (53/76)］, drug selection ［67.1% (51/76)］, and contraindications ［36.8% (28/76)］. Only 13.7% (28/204) of the respondents had a score of ≥120 points (full score of 150 points) in the survey for understanding of knowledge about analgesics. There was 53.9% (110/204) of the respondents with a score of <90 points, including 50.0% (23/46) of the surgeons, 43.8% (35/80) of the anesthesiologists, 46.9% (15/32) of the clinical pharmacists, and 80.4% (37/46) of the surgical nurses. Only 4 of the 15 questions had a correct answer fill rate of >50%.　Conclusion Most of the hospitals surveyed have established relevant mechanisms for perioperative pain management, but there are still problems of irrational use of perioperative analgesics and analgesia pumps. About half of the surgeons, anesthesiologists, clinical pharmacists, and most of the surgical nurses have little understanding of knowledge about analgesics.

对乙酰氨基酚被认为具有较好的安全性而广泛用于感冒引起的发热、头痛以及各种疼痛的治疗。但其不良反应时有发生,并且大剂量使用易引起肝损害。因此,对乙酰氨基酚的安全性与合理使用问题有必要加以讨论。

A 68-year-old male patient with type 2 diabetes mellitus received saxagliptin, metformin, and voglibose for 10 months, voglibose was switched to acarbose due to poor blood glucose control firstly and then to empagliflozin (oral 10-mg thrice daily) 2 days later. Next day，compound tropicamide eye drops was used to mydriasis and 3 hours later (2 hours after the second administration of empagliflozin), the patient developed scattered red wheal like rash with pruritus on the chest and abdomen, followed by eyelid edema. Considering allergy to compound tropicamide eye drops, loratadine and cetirizine were given, the rash gradually subsided, but the skin pruritus increased. Diffuse red macules and papules, which faded from pressure, gradually appeared on his trunk and upper limbs. Allergic dermatitis caused by empagliflozin was considered after consulting the dermatologist, empagliflozin was discontinued, fexofenadine and calamine lotion were added, and the rash subsided. Due to the patient′s condition, empagliflozin was readministered 3 days later, and the patient experienced a skin allergic reaction again 9 days after the treatment. Empagliflozin was stopped again and the rash did not recur after anti-allergic treatment. It was considered that the patient′s skin allergic reaction was possibly related to empagliflozin.

A 55-year-old male patient with hepatic complex alveolar echinococcosis, who had a history of gout for more than 4 years, developed swelling and high skin temperature of feet when he waited for the result of remote consultation and prepared for optional right hemihepatectomy in the hospital. Laboratory tests showed that uric acid was 530-μmol/L and rheumatic factor was negative. Acute gout attack was considered. He was treated with oral colchicine 0.5-mg thrice daily. About 10-hours after the first administration, the patient developed urinary incontinence. According to the consultation results, it was considered that the urinary incontinence might be related to colchicine. Colchicine was stopped immediately. The symptoms of urinary incontinence disappeared 24-hours after drug withdrawal. The symptoms of urinary incontinence recurred after the patient took the drug again by himself. Urinary incontinence did not recur after the colchicine withdrawal again.

A 32-year-old female patient received long-term use of paroxetine 40-mg/d orally for depression. Because of uncontrolled behavior, the patient took paroxetine about 1-000-mg at one time. About 24-hours after taking the medicine, the patient developed cough and expectoration, followed by dyspnea, and 2 days later, the patient became unconscious. The partial pressure of oxygen was 38-mmHg, and the partial pressure of carbon dioxide was 43-mmHg. Chest CT showed ground glass opacities in bilateral lungs, indicating interstitial pulmonary edema. Acute lung injury and respiratory failure were diagnosed. Then mechanical ventilation via a tracheal cannula, continuous intravenous pumping of methylprednisolone 160-mg/d, and symptomatic treatments such as anti-infection, fluid infusion, correction of acid-base imbalance were given. Her respiratory condition was gradually improved, and the partial pressure of oxygen gradually returned to normal; 5 days later, the ventilator was stopped and the tracheal tube was removed.

A 69-year-old female patient with diabetes mellitus was scheduled to undergo angiography of head because of acute cerebral infarction. When iopromide injection-370 was injected intravenously with a high-pressure syringe before operation, the contrast medium extravasated at the injection site of her right hand, resulting in severe subcutaneous hematoma, tissue necrosis, and infection. The maximum area of extravasation wound extended to 6.0-cm × 7.0-cm. Therapies such as local wet compress with cold 50% magnesium sulfate and dexamethasone, daily debridement and dressing change, and external application of hydrogel, silver containing hydrophilic foam, and hydrocolloid were given. On day 14 after extravasation, the necrotic tissue of the wound gradually fell off and the wound began to heal. Then the wound healed on day 35 after extravasation.

Objective To understand the problems of data mining in adverse drug reaction (ADR)/adverse event (AE) signal detection study in China.　Methods The literature on ADR/AE signal detection study in SinoMed, CNKI, WanFang Data and VIP databases were retrieved (up to May 30, 2022). The relevant content of the data mining in the literature was investiagted and evaluated from the following 4 dimensions and 9 items: (1) background data, including 1 item; (2) data preprocessing, including 4 items such as drug mapping, AE mapping, missing value processing, and data deduplication; (3) data mining algorithm (DMA), including 3 items such as DMA selection, DMA formula interpretation, and signal threshold; (4) interpretation of the results, including 1 item. According to the relevant specifications and technical requirements of data mining, the reporting/reporting error-free rate of the 4 dimensions and 9 items in the literature was taken as the overall quality evaluation index. Reporting/reporting error-free rate ≥60% was considered to be an excellent level of overall quality.　Results A total of 165 articles were included. On the background data dimension, the reporting/reporting error-free rate of using all the other drug data of the entire database in the literature was 35.2% (58/165), which did not reach an excellent level. On the data preprocessing dimension, the reporting/reporting error-free rates of drug mapping, AE mapping, missing value processing, and data deduplication in the literature were 22.4% (37/165), 73.9% (122/165), 10.3% (17/165), and 55.2% (91/165), respectively. The reporting/reporting error-free rate on this dimension was 40.5% (267/660), which did not reach the excellent level, only the rate of AE mapping reached the excellent level. On the DMA dimension, the reporting/reporting error-free rates of ≥2 DMA, DMA formula interpretation, and signal threshold in the literature were 63.6% (105/165), 78.2% (129/165), and 87.9% (145/165), respectively. The reporting/reporting error-free rate on this dimension was 76.6% (379/495), which reached an excellent level. The reporting/reporting error-free rate was 87.4% (144/165), reaching an excellent level. The signals were interpreted as "positive" or "negative" signals in 7 articles, and the meaning of signals were interpreted as causality in 14 articles. The overall reporting/reporting error-free rate in the 165 literature, analyzed from 9 items on 4 dimensions, was 57.1% (848/1-485), which did not reach the excellent level.　Conclusion The main problems in the domestic literature of ADR/AE signal detection study are the incomplete selection of background data and the lack of data preprocessing, suggesting that the further relevant studies in China should be improved on above 2 dimensions for better quality of ADR/AE signal detection research.

Methamphetamine(MA), commonly called as ice, is a stimulant of the family of phenethylamines, which is one of widely abused illicit drugs in the world. Methamphetamine increases the release and blocks the reuptake of the monoamine neurontransmitter, such as dopamine, norepinephrine, and serotonin, leading to high level of the chemicals in the synaptic cleft and inducing psychological and physical effects. Methamphetamine users may develop euphoria, increased physical activity and hypersexuality. Sudden withdrawal of methamphetamine in methamphetaminedependent subjects may result in abstinence reactions including sleep disturbance, depressed mood, anxiety, agnosia, and decreased physical activity. A methamphetamine abstinence reaction can be categoried into two phases: the acute phase (lasting 7～10 days), and the subacute phase (lasting a further 2 weeks). The relapse rates to the methamphetaminedependent subjects is rather high. Preventing the occurrence of relapse is of very important practical siginifance.

他汀类药物(Statins),即3-羟-3甲-戊二酰-辅酶A(HMG-CoA)还原酶抑制剂(HMG-CoA reduc—tase inhibitors),是一种新型降血脂药物,通过竞争性抑制HMG-CoA还原酶,阻断甲羟戊酸代谢的中间产物及最终产物——胆固醇的合成,降低血浆总胆固醇和LDL胆固醇,并影响机体的免疫及炎症反应、血管内皮功能、血栓形成等病理生理过程。他汀类药物有降脂和非降脂两种效应,对于延缓动脉粥样硬化进展及恶化、减少急性冠脉事件和心血管病死率,发挥着重要的作用。此类药物大多在肠道吸收,肝脏代谢,少数可直接经肾脏排泄。临床试验表明,他汀类药物安全、有效,毒副作用少。随着他汀类药物在心血管病一、二级预防中的广泛应用,有必要系统地了解本类药物的临床药理作用和常见毒副作用,为此本文特作介绍。

Objective To explore the adverse event (AE) risk signals of romiplostim, and provide reference for the safe use of the drug in clinic.　Methods The adverse event reports on romiplostim included in the US FDA Adverse Event Reporting System from the first quarter of 2008 to the second quarter of 2022 were collected. AEs were standardized using preferred term (PT) in the Medical Dictionary for Regulatory Activities. The general situation of patients and the outcome of AEs were extracted from the AE reports and analyzed descriptively and statistically. The AE risk signals of romiplostim was explored using the reporting odds ratio (ROR) method and the proportional reporting odds ratio (PRR) method. The positive signal PT was set as that the number of AE reports was 3 and more and the lower limit of the 95% confidence interval (CI) of the ROR and PRR were greater than 1.　Results A total of 12-222 AE reports with romiplostim as the primary suspected drug were collected. Among the 12-222 patients involved, 10-295-had gender records, including 4-818 males and 5-477 females; 3-789 patients with age records, ranging from 0 to 98 years, with an average age of 58 years; 5-919 patients with AE outcome records, the patient number of hospitalizations, death, life-threatening, disabling, and congenital malformation due to AEs were 3-092, 2-305, 363, 152, and 7, respectively. Twelve thousand two hundred and twenty-two AE reports involved 2-090 PTs，which occurred 20-639 times. Signal mining was performed on the top 100 PTs in the number of reports and 42 positive signals were detected. The top 5 PTs in the number of AE reports were decreased platelet count (PLT) (1-510 patients), lack of efficacy (1-488 patients), decreased efficacy (921 patients), abnormal PLT (857 patients), and death (853 patients). The PTs with signal intensity ranking in the top 5 were bone marrow reticulin fibrosis (ROR=631.43, PRR=341.43), abnormal bone marrow biopsy (ROR=202.73, PRR=159.36), abnormal platelet count (ROR=200.90, PRR=159.49), splenectomy (ROR=118.82, PRR=102.55) and thrombocytosis (ROR=84.66, PRR=76.14). There were 10 PTs not recorded in the drug instruction, whose signal intensity from high to low in the order were splenectomy, chronic lymphocytic leukemia, hemolysis, hospitalization, pleural effusion, sepsis, bone pain, off-label drug use, hemoglobin reduction, and migraine.　Conclusions Bone marrow reticulin fibrosis and abnormal platelet count, as well as the resulting bleeding and thrombotic complications, are the AEs that need to be monitored during the use of romiplostim. Among the 10 PTs not recorded in the drug instruction, pleural effusion and sepsis need to be noticed.

Dexamethasidine (DEX) is an alpha-2 adrenoreceptor (α2-AR) agonist, which is not only used in the perioperative period, but also in outpatient examination or treatment. The characteristics and advantages of sedation and hypnosis with DEX are that patients can enter a state similar to natural sleep, which is not only beneficial to improve the sedation effect, but also easy to wake up, and there is little jaw relaxation and no obvious respiratory inhibition. The additional advantages of DEX lie in its function of anti-stress response and potential organ protection and its little influence on cognitive function. The main adverse reactions of DEX were temporary hypertension, hypotension, bradycardia, and so on. Another characteristic of DEX is the relatively slow disappearance of drug effect. Patients may have drowsiness and postural hypotension after operation. It must be noted that DEX cannot be used as an independent anesthetic in general anesthesia to act as the main analgesic and sedative, but only to play an auxiliary role, which depends on the reasonable use and dosage and is not "all" or "none". And the vital signs of patients must be closely monitored during the process of DEX application.

A 53-year-old female patient received IV infusion of meropenem for injection 1.0 g once every 8 hours for urinary tract infection. Her platelet count (PLT) was 151×109/L before using meropenem. On the 9th day of meropenem treatment, the laboratory test showed PLT 577×109/L and on the 12th day, the patient′s infection was controlled but PLT increased to 829×109/L. The thrombocytosis related to meropenem was considered. Meropenem was stopped and replaced by IV infusion of piperacillin sodium and sulbactam sodium for injection 5 g dissolved in 100-ml of 0.9% sodium chloride injection once 8 hours. Three days later, the patient′s PLT decreased to 782×109/L; 23 days later, PLT was 272×109/L.

 2020年3月3日，国家卫生健康委员会发布《新型冠状病毒肺炎诊疗方案（试行第七版）》，提出抗病毒药物治疗方案、中医中药治疗方案及免疫治疗等。临床一线专业人员如何依据患者的病理、生理状况和药物的药理特性选择药物以及治疗中需要监测的指标，亟需明确和权威的学术支持。为此，中国药师协会治疗药物监测药师分会等11个学术团体联合编写了“新型冠状病毒肺炎及常见合并症药物治疗与药学监护指引”，期望为一线医师、药师和护士提供参考。

A 62-year-old female patient received oral aspirin enteric-coated tablets 100-mg once daily, clopidogrel hydrogen sulphate tables 75-mg once daily, metoprolol tartrate tablets 18.75-mg twice daily, and rosuvastatin calcium tablets 10-mg once daily after coronary artery stent implantation regularly according to the doctor′s instructions. Several days later, the patient developed edema of hands and feet from the distal end to the proximal end of the extremities, and he developed facial edema with rash and pruritus at the edema site. After 3 days of antiallergic treatment, there was no obvious regression of edema and new rash. After careful inquiry, the patient said that he always developed edema and increased rash symptoms about 2 hours after taking metoprolol tartrate tablets. After discontinuation of metoprolol tartrate tablets for 1 day, and other drugs were continued to be used, the patient′s edema and rash were relieved on the next day, and the above symptoms reappeared when the drug was used again according to the doctor′s instructions on the same day. When the drug was stopped again, the edema and rash were obviously improved the next day.After 2 days of discontinuation, the patient took metoprolol succinate sustained-release tablets at their own discretion, and still developed edema and rash. After discontinuation of metoprolol succinate sustained-release tablets, the edema and rash disappeared completely 10 days later.

静脉输液是最常用的药物治疗方法,但易发生不同程度的静脉炎。输液静脉炎诱发因素主要有输液的pH值及可滴定酸度、输液的渗透压、药物的化学毒性、机械性刺激等。本文对静脉炎的诱发因素及其防治进行概述,旨在对各诱发因素采取相应的预防措施,尽量减少静脉炎的发生。

A 73-year-old female patient received monotherapy with pembrolizumab (IV infusion of 200-mg once every 3 weeks) for lung cancer with bone metastases. On day 12 after the 6th treatment with pembrolizumab, the patient developed severe nausea and vomiting. Laboratory tests showed random blood glucose 53.6-mmol/L and serum potassium 6.8-mmol/L. Blood gas analysis showed pH 7.3, partial pressure of carbon dioxide 19.5-mmHg, partial pressure of oxygen 15.6-mmHg, base excess -8.9-mmol/L, bicarbonate 9.5-mmol/L, lactic acid 2.5-mmol/L, and anionic gap 23.5-mmol/L. Blood ketone body test was positive. The patient had no previous history of diabetes mellitus， fulminant type 1 diabetes mellitus and ketoacidosis due to pembrolizumab were considered. Pembrolizumab were stopped and rehydration, hypoglycemia, acidosis correction, and other symptomatic treatments were given. Seven days later, her symptoms were improved partly. Laboratory tests showed fasting blood glucose 12.9-mmol/L and serum potassium 4.5-mmol/L. Blood gas analysis showed pH 7.5, bicarbonate 28.3-mmol/L, and base excess +5.7-mmol/L. Blood ketone body test was negative.

A 63-year-old female patient was treated with 30 Mugua pills and Zhuifeng Tougu pills 6 g twice daily for tenosynovitis. After taking the medicine for 10 days, the patient developed nausea and vomiting, which were aggravated gradually; after taking the medicine for 22 days, the patient had fever, nausea, retching, slight pain in the upper abdomen, systemic edema, skin pruritus, and poor spirit, appetite, and sleep. Laboratory tests showed alanine aminotransferase (ALT) 454-U/L, aspartate aminotransferase (AST) 946-U/L, alkaline phosphatase (ALP) 133-U/L, gamma glutamyltransferase (γ-GT) 170-U/L, direct bilirubin (DBil) 12.8-μmol/L, and glutamate dehydrogenase 17.3-U/L. Viral hepatitis and biliary obstruction were excluded by laboratory tests and imaging examination. Drug-induced liver injury was diagnosed, Mugua pills and Zhuifeng Tougu pills were stopped, and diisopropylamine dichloroacetate injection and compound glycyrrhizin tablets were given. Liver function was gradually improved in the patient and laboratory tests showed ALT 62-U/L, AST 49-U/L, γ-GT 38-U/L, and DBil 7.2-μmol/L 12 days later. The medication was adjusted to 3 compound glycyrrhizin tablets thrice daily for 2 weeks. After 4 weeks, laboratory tests showed ALT 31-U/L, AST 26-U/L, γ-GT 30-U/L, and DBil 5.0-μmol/L.

A 41-year-old female patient received Rupixiao capsules 1.6 g thrice daily for hyperplasia of mammary glands. About 30 days later, the patient developed nausea, dark urine, and yellowish skin and sclera. After 20 days of continued treatment, her symptoms worsened, so she stopped using Rupixiao capsules by herself. After 10 days of drug withdrawal, her symptoms were not improved. The laboratory tests showed alanine aminotransferase (ALT) 1-234-U/L, aspartate aminotransferase (AST) 778-U/L, gamma-glutamyltransferase (γ-GT) 174-U/L, alkaline phosphatase (ALP) 156-U/L, total bilirubin (TBil) 78.7-μmol/L, and total bile acid (TBA) 45.4-μmol/L. After excluding liver injury caused by other reasons through laboratory and auxiliary examination, drug-induced liver injury was diagnosed, which was considered to be related to Rupixiao capsules. Drugs such as reduced glutathione, polyene phosphatidylcholine, compound glycyrrhizin, ademetionine 1,4-butanedisulfonate, and bicyclol were given. The patient′s symptoms of nausea, yellow urine, and jaundice gradually subsided. After 35 days of treatments, laboratory tests showed ALT 39-U/L, AST 43-U/L, γ-GT 57-U/L, ALP 85-U/L, TBil 17.3-μmol/L, and TBA 14.3-μmol/L.

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 72-year-old female patient received intravenous injection of furosemide injection and oral metoprolol succinate sustained-release tablets, furosemide tablets, spironolactone tablets, digoxin tablets, and isosorbide mononitrate sustained release tablets for heart failure. Continuous intravenous pumping of levosimendan 12.5-mg dissolved in 0.9% sodium chloride 45-ml at a speed of 1.5-ml/h was additionally given because of her unimproved symptoms of heart failure. After 20-hours of intravenous pumping, the patient developed unconsciousness, no response to voice stimuli, and bilateral mydriasis suddenly. The electrocardiogram monitoring showed heart rate 200 beats per minute, prolonged QT interval, and QTc period 520-ms. The laboratory tests showed serum potassium 3.02-mmol/L. She was diagnosis as Torsades de Pointes and Aspen syndrome, which were considered to be related with levosimendan. Levosimendan was stopped immediately. The treatments such as closed-chest cardiac massage, electric defibrillation, and potassium supplementation were given. Four days later, the reexamining results showed her serum potassium 4.60 mmol/L, heart rate 80 beats per minute, and QTc period 450-ms.

A 26-year-old woman received laser decolorization therapy for facial freckles. After the operation, compound arbutin cream 1 g once per night was applied on the face. She developed redness, swelling, and water blisters with desquamation on her face about 12-hours after the first application of the drug. She was diagnosed as having contact dermatitis, which was considered to be related to compound arbutin cream. Then the cream was withdrawn. She received prednisone acetate 20-mg orally once daily, levocetirizine 5-mg orally once per night, and local hydropathic compress with 3% boric acid lotion. Three days later, her facial redness, swelling, and desquamation were obviously improved, and most of the water blisters disappeared. At a one-week telephone follow-up, the patient′s water blisters disappeared.

A 47-year-old male patient received irbesartan 225-mg orally once daily due to nephrotic syndrome. Three days later, the dose was changed to 300-mg once daily according to the doctor′s advice. His hemoglobin (Hb) was 153-g/L before irbesartan treatment. After 6 days of medication, the patient developed fatigue and weakness. Laboratory test showed that his Hb was 89-g/L. No laboratory test abnormality was found in serum creatinine, stool routine, and bone marrow puncture. After 13 days of medication, his Hb was 87-g/L. Moderate anemia related to irbesartan was diagnosed. Irbesartan was discontinued and IV infusion of methylprednisolone sodium succinate for injection 60-mg once daily and subcutaneous injection of erythropoietin 3-000 U thrice a week were given. Seven days later, the symptoms of fatigue and weakness were improved and laboratory test showed Hb 102-g/L. Twenty-seven days later, his Hb returned to 131-g/L.

Objective To establish the Chinese version of Medication Appropriateness Index (MAI) and evaluate the appropriateness of medication in elderly inpatients on trial.　Methods According to Brislin′s translation model for cross-cultural research, the MAI was translated into Chinese through 4 steps: translation, back translation, cultural adaptation, and pre-survey. Using convenient sampling method, 300 elderly inpatients in the Department of Geriatrics, Nanjing Drum Tower Hospital from July to December 2019 were selected as the research subjects, and the Chinese version of MAI was used to evaluate the appropriateness of medication. Reliability of the Chinese version of MAI was evaluated using Cronbach′s α coefficient and intraclass correlation coefficient (ICC); the content validity and structural validity of the Chinese version of MAI were evaluated using 4-level scoring method and exploratory factor analysis, respectively. The appropriateness of medication in 300 elderly inpatients was evaluated by analyzing the MAI scores and the distribution of irrational items.　Results The Chinese version of MAI contained 10 items. The evaluation results of 300 elderly inpatients were statistically analyzed. The Cronbach′s α coefficient of the scale was 0.892 and the ICC of the scale was 0.876 when 20 patients were selected for re-testing 14 days later. The item-level content validity index (I-CVI) of the Chinese version of MAI was 0.86 to 1.00 and the scale-level content validity index/average (S-CVI/Ave) was 0.96. A total of 4 common factors were extracted by explo- ratory factor analysis, the cumulative variance contribution rate was 58.132%, and the factor loading of 8 items was more than 0.4. The evaluation results of appropriateness of medication showed that the average MAI score in 300 patients was 2.6, of which 198 patients did not score 0; inappropriate medication counted 66.00% and the average MAI score of each drug was 0.2. The top 3 items with more inappropriate medication were drug-disease/abnormal condition interaction (88 cases, 29.3%), duplication (69 cases, 23.0%), and incorrect dosage (67 cases, 22.3%).　Conclusions The Chinese version of MAI had good reliability and validity. The items with more inappropriate medication in elderly inpatients in the Department of Geriatrics, Nanjing Drum Tower Hospital were mainly drug-disease/abnormal condition interaction, duplication, and incorrect dose.

A 23-year-old male patient received moxifloxacin, recombinant human interferon α-2b for injection, and lopinavir and ritonavir for 7 days for novel coronavirus pneumonia. There was no abnor-malityof serum potassium. Moxifloxacin was stopped, Qingfei Paidu decoction(清肺排毒汤) was given, and then the patient′s serum potassium began to rise. On day 10 after taking the decoction, laboratory tests showed serum potassium 5.7-mmol/L and the patient was diagnosed with hyperkalemia. Insulin injection 4 U diluted to 5% glucose injection 250-ml was given once by IV infusion, and then the serum potassium decreased to 5.0-mmol/L 6 hours later and 4.6-mmol/L 2 days later. After 5 days, the serum potassium rose again and finally to 5.4-mmol/L on day 17 after taking the decoction. Insulin was given once that day and 2 days later once daily according to the previous method. Then the serum potassium decreased and did not rise again. The patient recovered from novel coronavirus pneumonia and was discharged on day 28 after hospitalization.

ObjectiveCompare criteria of eight countries such as United States for potentially inappropriate medications (PIM) in elderly, to provide a reference for formulating China′s PIM criteria. MethodsUsing the database and network, the authors collect the PIM criteria in elderly that has been released from the inception to December 2012. Eight countries PIM criteria were selected and their development method, expert panel′s composition and contents were compared.ResultsPIM criteria from a total of eight countries including the United States, Canada, Japan, France, Norway, Germany, South Korea and Austria were selected for the analysis. Except the United States PIM criteria has been updated to version 4 (2012), the other countries have just published their first edition. The applicable age of respective country about PIM criteria is slightly different (≥ 65 ~ ≥ 75 years). Seven countries except Japan were using the Delphi method as a research methodology. The composition of the expert panel has pharmacist, geriatrician, psychiatrist, general and family practitioner, and so on. Eight countries′ PIM criteria were not completely consistent in the content and the form, but mainly contain three parts: independent risk factors, drug-disease interactions, and drug-drug interactions. Drugs were included in PIM criteria with the following features: the elderly are proneto poisoning and adverse reactions; the benefits of treatment outweigh its potential risks for the elderly; poor efficacy or uncertain efficacy for the elderly; drugs can be replaced with similar products. ConclusionReference and learning from foreign method and experience of PIM criteria in elderly can help us to formulate a PIM criteria for China′s situation as early as possible and promote rational use of drugs.

A 46 year old female patient with primary biliary cholangitis received Lanqin oral solution (蓝芩口服液) 10 ml orally thrice daily because of pharyngeal pain due to cold. About 20 minutes after taking the first dose of the drug, the patient suddenly felt general discomfort and numbness of mouth and tongue, followed by vomiting, sweating, pale complexion, dyspnea (27 times per minute), and hypotension (104/56 mmHg). Anaphylaxis induced by Lanqin oral solution was considered, the drug was discontinued and the liquid supplement to expand the blood volume and chlorphenamine maleate for anti allergy were given. One hour later, the patient′s symptoms disappeared and the blood pressure returned to 124/76 mmHg. The next day, the patient did not follow the doctor′s advice and took Lanqin oral liquid 10 ml again by herself. A few minutes later, she developed nausea and abdominal pain. The fluid infusion and symptomatic treatment were given immediately, and the symptoms disappeared 20 minutes later.

Migraine is one of the most common disorders in neurological clinic.New advances in pathogenesis and drug therapy for migraine have been obtained in recent years.This paper presents the drug therapy for migraine including treatment of acute attacks and preventive therapy.The common drugs used to treat acute migraine attacks are nonsteroidal non-inflammatory drugs,triptans,ergot alkaloids,etc.And the drugs used for preventive therapy are tricycle antidepressants,anticonvulsants,β-blockers,calcium channel blockers,etc.This article reviews the therapeutic actions and potential adverse reactions of these drugs in order to benefit the safe and rational drug use in clinical practice.

A 38-year-old female patient with thyroid nodule received Xingqi Sanjie cream 30 g orally twice daily for 4 treatment courses in total. Each treatment course was 1 month and the interval between the 2 courses was 14 days. On the 29th day of the 4th treatment course, the patient developed poor appetite, yellowish skin and sclera, and dark urine. Laboratory tests showed alanine aminotransferase (ALT) 3-201-U/L, aspartate aminotransferase (AST) 2-262-U/L, total bilirubin (TBil) 257.2-μmol/L, direct bilirubin (DBil) 186.9-μmol/L, and alkaline phosphatase (ALP) 159-U/L. Drug-induced liver injury (severe) was diagnosed, which was considered to be related to Xingqi Sanjie cream. The drug was stopped, and symptomatic and supportive treatments including hepatoprotection and rehydration were given. Twenty-two days later, the above symptoms in the patient were improved. Laboratory tests showed ALT 209-U/L, AST 117-U/L, TBil 92.7-μmol/L, DBil 63.2-μmol/L, and ALP 82-U/L. Fifty-one days later, the yellowish skin and sclera in the patient subsided, and the urine color returned to normal. Laboratory tests showed ALT 37-U/L, AST 22-U/L, TBil 30.3-μmol/L， DBil 14.7 μ mol/L, and ALP 58-U/L.

Ricin derived from castor beans is a potent toxin, the main machanism of its toxic effects to cells is to inhibit protein synthesis in cells and result in their death. People can be poisoned via different routes of exposure to ricin. The clinical presentations of ricin poisoning depend on the route of exposure and the dose received. The patients with severe ricin poisoning may develop multi-organ failure and death. So for no specific antidote exists for ricin. The toxin vaccine of ricin is being tried out on laboratory animal. Treatment for ricin poisoning is primarily supportive medical care to minimize the effects of the poisoning.

Objective To investigate the risk factors of acute kidney injury (AKI) in patients with severe drug eruption.　Methods Clinical data including basic information (gender, age, body mass index), type of severe drug eruption, allergenic drugs, co-existing diseases, first laboratory findings after admission, renal function during hospitalization, etc. in patients with severe drug eruption admitted to Department of Dermatology, Guangdong Provincial People′s Hospital from January 2014 to December 2020 were collected and analyzed retrospectively. Patients were divided into AKI group and non-AKI group and the clinical data were compared between the 2 groups. The risk factors of AKI in patients with severe drug eruption were analyzed by a binary logistic regression model and the odds ratio (OR) and its 95% confidence interval (CI) were calculated.　Results A total of 91 patients were enrolled in the study, including 50 males and 41 females, aged 54 (40, 65) years with a range of 9-85 years. The drugs that induced severe drug eruptions were allopurinol in 48 patients, antiepileptic drugs in 23 patients, antibacterial drugs in 6 patients, and other drugs in 14 patients. There were 21 patients (AKI incidence: 23.1%) in the AKI group and 70 patients in the non-AKI group. The proportion of patients sensitized to antiepileptic drugs, baseline estimated glomerular filtration rate, levels of serum albumin and hemoglobin in the AKI group were lower than those in the non-AKI group ［0（0/21） vs. 32.9% (23/70), (70±12) ml/(min·1.73 m2) vs. (103±6) ml/(min·1.73 m2), 26(23, 30) g/L vs. 36(34, 38) g/L, (116±17) g/L vs. (129±15) g/L］, the proportions of patients sensitized to allopurinol, with diabetes mellitus, and with chronic kidney diseases, baseline serum urea nitrogen level, serum creatinine level, and proportion of urinary albumin positive patients were all higher than those in the non-AKI group ［81.0%(17/21) vs. 44.3%(31/70), 28.6%(6/21) vs. 7.1%(5/70), 28.6%(6/21) vs. 5.7%(4/70), 7.2（4.6, 12.2） mmol/L vs. 5.0（3.8，6.4）mmol/L, 103（63, 134）μmol/L vs. 67（56, 79）μmol/L, 47.6%(10/21) vs. 17.1%(12/70)］, and the differences were statistically significant (all P<0.05). Binary logistic regression analysis showed that allopurinol sensitization (OR=6.588, 95%CI: 1.006-43.123, P=0.049) was the independent risk factor for AKI in patients with severe drug eruption and serum albumin (OR=0.595, 95%CI: 0.471-0.752, P<0.001) was a protective factor.　Conclusions Allopurinol sensitization was the independent risk factor for AKI in patients with severe drug eruption. Patients with low serum albumin were more likely to develop AKI.

Objective To analyze and evaluate the enhancement of anticoagulant effect of warfarin by herbal and dietary supplements (HDS) based on case report literature.　Methods The case reports on enhancement of anticoagulant effect of warfarin by HDS were selected by searching the relevant databases at home and abroad (up to October 10, 2021). The degree of enhancement of anticoagulant effect of warfarin by HDS was evaluated according to the increase of International Standardized Ratio and the occurrence of bleeding events in patients in the case reports. The reliability scoring standard of HDS-warfarin interaction was established according to the causatity evaluation results between HDS and enhancement of anticoagulant effect of warfarin, the number of case reports, and the other evidences (warnings issued by relevant national institutions, clinical studies, pharmacokinetic/pharmacodynamic studies, experimental animal studies, etc.) and the reliability of enhancement of anticoagulation effects of warfarin by HDS was evaluated. The reliability was evaluated as highly, relatively, possible, and suspicious reliable if the total score was ≥9, 6-8, 3-5, and
≤2 points, respectively.　Results A total of 41 case reports were enrolled in the analysis, involving 56 patients and 26 kinds of HDS. Five kinds of HDS increased the anticoagulant effect of warfarin slightly, including Chinese angelica (Radix Angelicae Sinensis), melilotus extract tablets, pumpkin seed, fish oil, and milk thistle; 6 kinds of HDS increased the anticoagulant effect of warfarin moderately, including ginger (Rhizoma Zingiberis Recens), mango, bee pollen, scarponon grape, Persian walnut, and grifola frondosa; and 15 kinds of HDS increased the anticoagulant effect of warfarin severely, including cranberry, danshen (Salvia miltiorrhiza), glycyrrhiza (Radix Glycyrrhizae), safflower (Flos Carthami), dandelion (Herba Taraxaci), Lyciumbar barum L., grapefruit, matricaria chamomilla, pomegranate juice, astaxanthin, Artemisia absinthiu, royal jelly, bilberry(Vaccinium vitis-idaea), red dates, and St. John′s wort (Hypericum perforatum L.). The reliability of enhancement of anticoagulant effect of warfarin was evaluated as highly reliable in 1 kind of HDS, namely cranberry (11 points), relatively reliable in 8 kinds of HDS, including danshen, glycyrrhiza, safflower, dandelion, Lycium barbarum L., grapefruit, matricaria chamomilla, and pomegranate juice (8, 7, 7, 7, 6, 6, and 6 points, respectively), possibly reliable in 12 kinds of HDS, including Chinese angelica, ginger, melilotus extract tablets, mango, astaxanthin capsules, bee pollen, Artemisia absinthium, royal jelly, scarponon grape, Persian walnut, bilberry, and grifola frondosa (5, 5, 5, 5, 4, 4, 4, 3, 3, 3, 3, and 3 points, respectively), and suspicious reliable in 5 kinds of HDS, including pumpkin seed, red dates, fish oil, milk thistle, and St. John′s wort (2, 2, 2, 0, and -1 points, respectively).　Conclusions The degree and reliability of enhancement of anticoagulant effect of warfarin by cranberry, danshen, glycyrrhiza, safflower, dandelion, Lycium barbarum L, grapefruit, matricaria chamomilla, and pomegranate juice are higher, which should be avoided during warfarin therapy.

A 62-year-old female patient with stomach cancer received an IV infusion of oxaliplatin and mannitol injection on day 1 and oral tegafur， gimeracil, and oteracil potassium on days 1-14 in a 21-day cycle after radical mastectomy. Pretreatment with dexamethasone and other drugs was given 3 hours before the infusion to alleviate possible adverse reactions. During the 1st cycle of chemotherapy, the patient had no other adverse reaction except nausea and fatigue, and no intervention was given. About 2 hours after oxaliplatin and mannitol injection in the 2nd cycle, the patient′s limbs were swollen and flushed, and red patches appeared on the skin. Then the erythema increased and merged into patches and her skin on the feet was desquamated. The above symptoms were improved after anti-allergic treatments. About 3 hours after oxaliplatin and mannitol injection in the 3rd cycle, the patient developed dyspnea, and systemic skin flushing and swelling accompanied by scratches. Then visible blisters on part of the skin appeared, which cracked at the flexion of the joints with exudate impregnation. The patient was given anti-allergic therapy such as prednisolone. Four days later, her skin on the whole body showed scaly desquamation, her hands and feet showed gloved desquamation, and she was diagnosed as having exfoliative dermatitis; 9 days later, her skin color became lighter and there was no new rash. Considering that exfoliative dermatitis was caused by oxaliplatin and mannitol injection, the chemotherapy regimen was switched to docetaxel (day 1) and tegafur, gimeracil, and oteracil potassium (days 1-14). The skin allergic reactions did not recur.

Objective To explore the adverse reactions to sintilimab in patients with non-small cell lung cancer (NSCLC) and Hodgkin lymphoma (HL).　Methods The clinical data of all NSCLC and HL patients who were treated with sintilimab during hospitalization in the Fifth Medical Center of the PLA General Hospital from January 2019 to August 2020 were collected by searching Hospital Information System. The clinical data including patients′ basic information (gender, age, diagnosis), medication (initial treatment or retreatment with sintilimab, single and cumulative dose, combined medication), and occurrence of adverse reactions (involved organs or systems, clinical manifestations, occurrence time, intervention and outcome) were recorded and analyzed retrospectively. The correlation between sintilimab and adverse reactions and the grade of adverse reactions were evaluated according to Hand Book of Adverse Drug Reaction Reporting and Monitoring in China and the International Adverse Reaction Evaluation System of Cancer Chemotherapy Drugs.　Results A total of 90 patients were enrolled in the analysis, including 75 NSCLC patients and 15 HL patients, aged from 16 to 81 years with the median age of 63 years; 81 patients were initially treated with sintilimab and 9 were retreated. Eighty-eight patients received sintilimab 200-mg per cycle and 2 patient received 100-mg per cycle. The cumulative dose was 200, >200-1-000, and >1-000-mg in 39, 35, and 16 cases, respectively; 32 patients were treated with sintilimab alone and 58 were treated with sintilimab combined with other regimens. Fifty-three (58.9%) patients had adverse reactions, among which, 41 (45.6%) and 12 cases (13.3%) had grade 1-2 and ≥ grade 3 adverse reactions, respectively. The occurrence time was 1-242 days after treatment. Among the 53 patients, 37 were male and 16 were female, aged 28-80 years; 48 were with NSCLC and 5 with HL. The incidence of adverse reactions in NSCLC patients was significantly higher than that in HL patients ［64.0% (48/75) vs. 33.3% (5/15), χ2=4.856, P=0.028］. Forty- eight patients were initially treated and 5 were retreated. Fifty-two patients received sintilimab 200-mg per cycle and 1 patient received 100-mg per cycle. The cumulative dose was 200, >200-1 000, and >1000-mg in 16, 26, and 11 cases, respectively. The difference in the incidences of adverse reactions among patients with different cumulative doses was significant (χ2=9.21, P=0.01). Fourteen patients were treated with sintilimab alone and 39 patients were treated with sintilimab combined with other therapeutic regimens; the incidence of adverse reactions in patients with sintilimab combined with other therapeutic regimens was higher than that in patients with sintilimab monotherapy, and the difference was statistically significant ［66.1% (39/58) vs. 43.8% (14/32), χ2=4.701, P=0.03］. A total of 101 times of adverse reactions to sintilimab occurred in 53 patients (1, 2, 3, 4 and 5 kinds of adverse reactions occurred in 24, 16, 9, 2, and 2 patients, respectively), 52 times of them were recorded in the medical records, and 49 times were found by rechecking the results of laboratory and auxiliary tests; 1, 3, and 97 times of adverse reactions were evaluated as “certainly”,“probably”, and “possibly”, respectively. Eighty-nine times (88.1%) of adverse reactions were grade 1-2 and 12 times (11.9%) were equal to or greater than grade 3. Multiple systems or organs were involved in the adverse reactions including blood, hepatobiliary, gastrointestinal, endocrine, respiratory, skin and appendix, heart, skeletal muscle and connective tissue, urinary, and nervous systems, and those with the top 5 incidence rates were blood, hepatobiliary, gastrointestinal, endocrine, and respiratory system adverse reactions［24.4% (22/90), 15.6% (14/90), 14.4% (13/90), 12.2% (11/90), and 11.1% (10/90)］. Twelve patients stopped sintilimab due to adverse reactions, 4 were only closely monitored without special treatment, and 49 received one day to seven months of symptomatic treatments. Among the 53 patients, 8 were cured, 29 were improved, 6 were not improved, 9 were unknown, and 1 died.　Conclusions　Sintilimab could lead to adverse reactions in multiple systems or organs in patients with NSCLC and HL, such as blood, hepatobiliary, gastrointestinal, endocrine, respiratory, and skin and appendages. The incidence and grade of adverse reactions were lower than those documented in the drug label, and no new adverse reactions were detected.

In 2020, a total of 15-849 cases of medication error (ME) from 255-hospitals in 24 provincial administrative regions were collected in the National Monitoring Network for Clinical Safe Medication. The number of hospitals reporting ME increased by 8.97% compared with that in 2019 (234-hospitals), and the number of reported ME cases increased by 5.27% compared with that in 2018 (15-056 cases). In 15-849 cases of ME reports, 54 (0.34%) were classified as grade A, 12-297 (77.59%) as grade B, 3-010 (18.99%) as grade C, 358 (2.26%) as grade D, 72 (0.45%) as grade E, 52 (0.33%) as grade F, 0 as grade G, 5 (0.03%) as grade H, and 1 (0.01%) as grade I. Among the 15-795 patients with ME of grade B to I, 9-347 (59.18%) were male and 6-448 (40.82%) were female, aged from 1 day to 101 years; 1-714 (10.85%) were children (<18 years old), 8-355 (52.90%) were middle aged patients (≥18 to <60 years old), and 5-726 (36.25%) were elderly patients (≥60 years old). Among the 130 patients with serious ME (grade E-I) that caused injury, 77 (59.23%) were male and 53 (40.77%) were female, aged from 4 months and 14 days to 94 years; 16(12.31%) were children, 46（35.38%） were middle aged patients, 68(52.31%) were elderly patients. Among the 9 patients with serious ME caused by mistaken use of drugs, 7 were children, accounting for 43.75% (7/16) of all children with serious ME. The 54 grade A MEs did not involve person who triggered the MEs and place where MEs occurred. Among the 15-795 grade B-I MEs, 10-748 (68.05%) were triggered by physicians, 3-797 (24.04%) by pharmacists, 578 (3.66%) by nurses, 329 (2.08%) by patients and their family members, and 343 (2.17%) by other persons; the proportion of MEs triggered by patients and their family members increased year by year for 3 consecutive years (1.06% and 2.04% in 2018 and 2019, respectively), and 49.23% (64/130) of severe ME were triggered by patients and their family members; 6-830 (43.24%) occurred in clinics, 3-808 (24.11%) in hospital wards, 3-776 (23.91%) in pharmacies, 985 (6.24%) in pharmacy intravenous admixture services, 220 (1.39%) in the nurse stations, 161 (1.02%) in patients′ houses, 2 (0.01%) in the community health service stations, and 13 (0.08%) in other places; the proportion of MEs occurred in clinics and patients′ houses increased year by year for 3 consecutive years (37.32% and 0.41% in 2018, 37.74% and 0.89% in 2019, respectively). The top 3 contents of MEs were wrong drug class, wrong usage, and wrong quantity. The top 3 persons who discovered the MEs were pharmacists, physicians, and nurses. The top 3 factors causing MEs were lack of related pharmacologic knowledge, tiredness, and insufficient training of medical workers.

A 61-year-old female patient underwent intestinal preparation before electronic colonoscopy. She took polyethylene glycol electrolytes powder (Ⅳ) in 6 times (dissolved content A 24 bags and B 24 bags in warm water 3-000-ml and then took 500-ml orally per 30-minutes). During the intestinal preparation, the patient′s urine output was about 4-500-ml, diarrhea occurred 8 times, and she vomited 2 times within 5.5-hours. The patient fell into a coma at 14:00 on the day, accompanied by limb convulsion and trismus. Laboratory tests showed that the serum sodium and potassium decreased from 140-mmol/L and 4.0-mmol/L to 120-mmol/L and 2.7-mmol/L before and after treatment, respectively. In addition, his chloride was 87.2-mmol/L and bicarbonate was 11.5-mmol/L. Blood gas analysis showed pH 7.29-mmHg, partial pressure of carbon dioxide 31-mmHg, partial pressure of oxygen 105-mmHg, and base excess -10.4-mmol/L. Metabolic acidosis was diagnosed. Head CT and MRI showed no abnormalities. Electrolyte disorder, metabolic acidosis, and hyponatremia encephalopathy due to hyponatremia caused by polyethylene glycol electrolytes powder (Ⅳ) was considered. Oxygen inhalation, continuous ECG monitoring, correction of electrolyte disorders, correction of acidosis, rehydration, and other symptomatic and supportive treatments were given immediately. After 4 hours of treatments, the vital signs of the patient were gradually stable but she was still in a coma. On the third day of treatments, the patient was conscious, her serum electrolytes returned to normal, and no seizures occurred.

Objective: To analyze the causes of the adverse reactions induced by Qingkailtng injection and research the ways of prevention and treatment. Methods: This article summarized 136 cases of the adverse reactions caused by Qingkailing injection in recent years, analysed the category, the clinical characteristics and causes of the adverse reactions induced by Qingkailing injection. Results: The major adverse effects of Qingkailing injection were allergic reaction type I , and were related to the allergic history and CNS diseases of the patient, diluted concentration of the drug, and other drugs combined with Qingkailing injection. Conclusion: The components and formula of Qingkailing injection should be studied in order to reduce the adverse reactions.

Objective: To introduce renal failure by Mutong and the way of its prevention and treatment. Methods: 17 cases of the renal failure by Mutong in our hospital were collected to analyze the clinical characteristics and causes of the adverse reactions. Results: Mutong and the compound Mutong preparations probably caused renal failure after long-term administration and overdosage. Conclusion: Great care could be required of appropriate dosage, treatment course and correct indications in order to assure the efficacy and safe use of the drug.

Vaccine development and vaccination are the most effective means to prevent and control coronavirus disease 2019 (COVID-19). At present, there are 4 types of COVID-19 vaccines approved for emergency use by the World Health Organization and approved conditionally for marketing and emergency use by State Drug Administration of China, including inactivated vaccine, recombinant protein subunit vaccine, messenger RNA vaccine, and adenovirus vector-based vaccine. Pre-marketing clinical studies show that the vaccines above-mentioned can effectively stimulate the body′s immune system to produce antibodies against COVID-19, the overall safety is good. Most of the adverse events after vaccination are mild or moderate. However, COVID-19 vaccination involves a large number and wide range of people, and its safety problems can not be ignored. The medical workers and researchers should be on high alert and conduct long-term monitoring to ensure vaccine safety.

本共识分别从新型冠状病毒肺炎疫情防控期间居家隔离药物治疗的必要性和意义、居家消毒剂的选择和合理应用、医院处方药的相关规定、长期居家药物治疗的管理等多个维度，为大众居家期间的合理用药提供指导和帮助。

A 69-year-old male patient with peripheral T-cell lymphoma received chemotherapy with intravenous doxorubicin liposome. In the first chemotherapy cycle, no obvious adverse reactions appeared. In the second chemotherapy cycle, the patient developed transient muscle soreness during the IV infusion of doxorubicin liposome. In the third chemotherapy cycle, dexamethasone and chlorphenamine were given to prevent anaphylaxis before doxorubicin liposome treatment and the infusion rate was controlled in a standardized way. However, at about 20-minutes of infusion, the patient developed nausea and vomiting. The infusion of doxorubicin was stopped immediately and replaced by IV infusion of 0.9% sodium chloride injection 250-ml. Then the patient developed facial numbness, laryngeal pain, neck discomfort, and multiple parts of skin rash with pruritus. The electrocardiogram monitoring showed heart rate 130 times/min, blood pressure 80/50-mmHg, and oxygen saturation 0.98. The patient was given oxygen inhalation and in half-lying position following the doctor′s advice, but the patient developed dyspnea, hoarseness, and slurred speech 20-minutes later. Physical examination showed the patient′s tongue was hypertrophic, his neck was swollen and thickened. Acute laryngeal edema induced by doxorubicin liposome was considered. Intravenous injection of dexamethasone 10-mg, IV infusion of 10% calcium gluconate, and aerosol inhalation of budesonide inhalation aerosol were given immediately and about 3 hours later, the symptoms gradually improved. Two days later, the allergic symptoms disappeared.

Rituximab is a human-mouse chimeric monoclonal antibody synthesized using genetic engineering technology and exert pharmacological effects by specifically binding to the transmembrane protein CD20 on the surface of B cells. The clinical therapeutic effect of rituximab is significant, but its pharmacological mechanism is complex, the pharmacokinetics/pharmacodynamics (PK/PD) presents as nonlinear models and is highly variable, which brings great variability and uncertainty to the effectiveness and safety of rituximab in clinic, so individualized therapy needs to be implemented to improve the rationality of medication. At present, rituximab has the basic conditions for therapeutic drug monitoring (TDM), such as detection technology of blood drug concentration, tumor biomarkers, and related genetic polymorphisms. Using these technologies, combined with comprehensive analysis of factors such as disease diagnosis, population specificity, route of administration, and drug interactions, the PK/PD model of rituximab can be constructed to predict the efficacy, toxicity, and drug resistance. It is of great significance for pharmacists to participate in the individualized rituximab treatment and carry out TDM, which can provide safer and more effective individualized treatment for patients.

A 41-year-old female patient received long-term treatment with metformin, glimepiride, sitagliptin, and acarbose for type 2 diabetes mellitus. Due to elevated blood-glucose, the hypoglycemic regimen was adjusted to metformin, acarbose, and dulaglutide (1.5-mg, subcutaneously injected once a week). After each injection of dulaglutide, the patient had severe anorexia but no intervention was given because that the patient could tolerate. Empagliflozin 10-mg orally once daily were added 3 days after the first injection and then the dose was adjusted to 10-mg next day. The day after the fourth injection, the patient developed dizziness, nausea, vomiting, general fatigue, etc. Laboratory tests showed blood glucose 20-mmol/L, arterial blood pH 7.22, partial pressure of carbon dioxide 22.1-mmHg, bicarbonate concentration 8.8-mmol/L, standard bicarbonate 12-mmol/L, total carbon dioxide content 10-mmol/L, ketone body in urine (+++), and urine sugar (++++). Diabetic ketoacidosis was diagnosed. Considering that severe anorexia after the application of dulaglutide caused serious insufficient carbohydrate intake and then empagliflozin- induced diabetic ketoacidosis was stimulated, the 2 drugs were discontinued and symptomatic and supportive treatments were given. Five days later, laboratory tests showed post-lunch blood glucose 10.1-mmol/L, ketone body in urine (+), negative urine sugar, and urine pH 5.5. Empagliflozin 5-mg once daily was added and laboratory tests showed carbon dioxide binding capacity of the blood 23.2-mmol/L, urine ketones (+++), urine sugar (++++), and uric acidity 5.0 four days later. The patient insisted on leaving the hospital. After discharge, she was treated with recombinant insulin glargine, acarbose, and empagliflozin. At 1 month of follow-up, symptoms of diabetic ketoacidosis did not recur.

Objective To explore the clinical characteristics of syndrome of inappropriate antidiu- retic hormone secretion (SIADH) induced by duloxetine.　Methods The diagnosis and treatment of a patient with duloxetine-related SIADH who was admitted to Nanjing Drum Tower Hospital Affiliated to Medical College of Nanjing University was reported, and the main clinical data (gender, age, prevalent diseases, use of duloxetine, combined medication, occurrence of SIADH, and intervention and outcome) of the case and related cases collected from the PubMed and Embase databases (up to December 31, 2021) were analyzed by descriptive statistics.　Results A total of 27 patients were included in the analysis, including 6 males and 21 females, aged from 38 to 92 years with a median age of 74 years. duloxetine with daily dose of 20, 30, 40, 60-mg and unknown dose were in 5, 9, 1, 10 and 2 patients, respectively, and one patient with daily dose of 30-mg developed SIADH after a single overdose of 450-mg. Sixteen patients were treated with drugs that may cause hyponatremia or interact with duloxetine. Among them, 6, 2, 6, and 2 patients were treated with 1, 2, 3, and 4 drugs, respectively. The time from the beginning of duloxetine administration to the occurrence of SIADH, was 2 days to 36 months in 26 patients, with a median time of 3 days, except that one patient of overdose was 1 hour after administration, among which 21 patients occurred within 7 days. The main clinical manifestations of SIADH included nervous system symptoms (headache, dizziness, drowsiness, etc. in 20 patients), digestive system symptoms (nausea, vomiting, anorexia, etc. in 15 patients), and systemic symptoms (fatigue, limb weakness, etc. in 6 patients). When SIADH was diagnosed, the serum sodium level of the 27 patients was 98 to 132-mmol/L, with a median level of 117-mmol/L. The severity of SIADH with grade 1, 3, and 4 was in 1 (3.7%), 7 (25.9%), and 19 (70.4%) patients, respectively. After the diagnosis or suspicion of duloxetine-related SIADH, duloxetine was discontinued in all patients, fluid intake was restricted and sodium supplement was administered. Furosemide was given in 5 patients, and the serum sodium levels returned to normal within 2 to 15 days, with a median recovery time of 5 days.　Conclusions Duloxetine- related SIADH mostly occurs within 7 days after the start of medication, and the degree is more serious. After stopping duloxetine, restricting the fluid intake, giving sodium supplement, and giving diuretics depending on the condition, the patient has a good prognosis.

Carbapenems are a class of βlactam antibiotics with a broad spectum of antibacterial activity. The commonly used carbapenems are imipenem, meropenem, ertapenem, faropenem, panipenem, doripenem, and so on. Carbapenem antibiotics could induce neurotoxicity and the incidence is about 0.01%-0.3%. The main clinical manifestations of neurotoxicity are headache, convulsions, seizures, myoclonus, and disorder of consciousness. The mechanism of neurotoxicity induced by carbapenem antibiotics is thought to be related to inhibition of the γ-aminobutyric acid (γ-GABA) binding to the receptors and interruption neural inhibitory effect of γ-GABA eventally resulting in seizures and other neurological disorders. The risk factors for neurotoxic reactions include decreased renal function, pathologic changes in CNS, and combination therapy. The prevention and treatment of neurotoxicity induced by carbapenems are as follows: it is essential to consider appropriate choice of carbapenem antibiotics according to the relationship between seizures and the different types of the antibiotics; dosage should be carefully adjusted in patients with renal failure; concomitant use with other drugs such as highdose theophylline, NSAIDs, probenecid, and so on should be avoided; the children and elderly patients should be monitored during treatment; if carbapeneminduced seizures occur, the agent should be stopped and diazepam or sodium valproate may be given if necessary; hemodialysis could be used for patients with uncontrolled seizures induced by the antibiotics.

A 31-year-old female patient took mesalazine 1 g thrice daily orally for colitis gravis. Her serum creatinine (Scr) was 78-μmol/L before medication. Five months later, her blood urea (BUN) was 8.3-mmol/L, Scr was 185-μmol/L, and estimated glomerular filtration rate (eGFR) was 31-ml/(min·1.73m²).  Pathological examination of renal biopsy showed acute tubulointerstitial nephritis and glomerulosclerosis. Kidney injury related to mesalazine was considered. Then the drug was stopped. After 26 days of mesalazine withdrawal, laboratory tests showed BUN 4.0-mmol/L, Scr 130-μmol/L, and eGFR 47-ml/(min·1.73 m²). Prednisone acetate 30-mg daily was given and the dose was decreased to 15-mg daily 2 months later. Then laboratory tests showed BUN 5.5-mmol/L, Scr 93-μmol/L, and eGFR 71-ml/(min·1.73 m²).

Three antiviral drugs, including interferon α (aerosol inhalation), lopinavir/ritonavir (oral medication), and ribavirin (intravenous infusion), are recommended by Diagnosis and Treatment of Novel Coronavirus Pneumonia (revised version, the 5th ed), which was issued by the National Health Commission of People′s Republic of China and National Administration of traditional Chinese Medicine. In addition, clinical trials on a new antiviral drug ---remdesivir which is not yet on the market has also been launched in China. Medication safety related data on treatment for infections of severe acute respiratory syndrome coronavirus, middle respiratory syndrome coronavirus, human immunodeficiency virus, lopinavir/ritonavir, and ribavirin, safety data of remdesivir in animal experiment, phase I clinical trials and clinical trials of treating Ebola virus infection, and preliminary reports of treatment in novel coronavirus pneumonia were briefly reviewed, aiming to provide evidence for clinical safety medication.

Objective To explore the occurrence and clinical characteristics of hyperprogression of metastatic malignant melanoma caused by toripalimab (JS001).　Methods The medical records of patients with metastatic malignant melanoma treated with JS001 alone or in combination with other antineoplastic agents between February 2018 and September 2019 in Department of Kidney Cancer and Melanoma of Beijng Cancer Hospital were collected. Patients displaying hyperprogression were screened into the case group, who were matched with those without hyperprogression evidence (the control group) in a 1/4 ratio according to baseline age, gender, Eastern Cooperative Oncology Group score, location of the primary lesion, and elevated level of lactate dehydrogenase (LDH). The clinical characteristics and prognosis of patients between the 2 groups were compared and the hyperprogression in the case group was analyzed descriptively.　Results A total of 130 patients with metastatic malignant melanoma who received JS001 alone or in combination with other antineoplastic agents were collected. Hyperprogression occurred in 8 patients (the case group), including 5 males and 3 females, aged (52.5±8.5) years. The incidence of hyperprogression was 6.15%. Thirty-two patients without displaying hyperprogression were matched as the control group according to the baseline characteristics of patients in the case group. Patients with metastatic lesions in more than 2 organs at baseline in the case group were significantly more than those in the control group (6/8 vs. 7/32, P=0.014); the LDH level of patients in the case group significantly increased after treatment than before ［(965±710) U/L vs. (264±64) U/L, P=0.025］; the progression-free survival and overall survival in patients were significantly lower than those of patients in the control group ［1.7 (95%CI: 1.4-2.0) months vs. 3.1 (95%CI: 2.7-3.5) months, P<0.001; 4.8 (95%CI: 0-11.2) months vs. 10.7 (95%CI: 10.4-10.9) months, P=0.031］.　Conclusions Patients with melanoma may experience hyperprogression in early stages of JS001 treatment. Patients with metastatic lesions in more than 2 organs before treatment are more likely to develop hyperprogression, and patients displaying hyperprogression have a poor prognosis. Serum LDH level monitoring can help detect tumor hyperprogression as early as possible.

A 6-year-old girl received sinupret oral drops and mometasone furoate aqueous nasal spray for allergic rhinitis for more than 1 month, but her symptoms were not improved. Additional use of oral montelukast sodium chewable tablets 4-mg every night was given due to adenoid hypertrophy. After 7 days of montelukast sodium administration, the girl developed somnambulism once per week, which manifested as sitting up suddenly in the dream and lying down to sleep after 1-minute. Two months later, all drugs were stopped because the nasal symptoms were relieved and no sleepwalking occurred 1 week after drug withdrawal. More than a year later, the above 3 drugs were given by her parents due to the recurrence of rhinitis and the girl developed somnambulism again with worse symptoms 5 days later. After 2 weeks of continued medication, somnambulism continued to worsen. Montelukast sodium was stopped, symptoms of somnambulism were relieved 2 days later and disappeared 1 month later. Considering that somnambulism in the girl was an adverse reaction to montelukast sodium, it was replaced by oral loratadine 5-mg every night. At 3 months of telephone follow-up, the somnambulism did not occur in the girl.

A 76-year-old male patient with small cell lung cancer received EC (etoposide and carboplatin) chemotherapy combined with camrelizumab. On the 22th day of medication, the patient deve- loped chest tightness, shortness of breath, dyspnea, limb weakness, walking difficulty, etc. Laboratory tests revealed creatine kinase (CK) 1-210-U/L and CK-MB 63 U/L. The chemotherapy and immunotherapy were stopped, but the patient′s symptoms continued to worsen. Laboratory tests showed troponin T (TnT) 336-ng/L, CK 1-025-U/L, CK-MB 74-U/L, and N-terminal pro brain natriuretic peptide (NT-proBNP) 648-ng/L. The muscle magnetic resonance imaging (MRI) and electromyogram showed muscle injury and cardiac MRI showed left ventricular fibrosis. Then immune-related skeletal muscle and myocardial injury caused by camrelizumab was considered. The patient received an IV infusion of methylprednisolone sodium succinate for injection 100-mg once daily for 13 days. Then the patient′s fatigue symptoms were improved, the levels of CK and NT-proBNP decreased to the reference range, but the levels of TnT and CK-MB were 491-ng/L and 113-U/L, respectively. Therefore, an intravenous infusion of immunoglobulin 20 g once daily was given. Five days later, his dyspnea was improved, and TNT and CK-MB decreased to 201-ng/L and 59-U/L, respectively.

A 56-year-old male patient purchased Shiduqing capsules by himself and took the drug orally 1.5 g thrice daily for pruritus and rash. After 7 days of administration, the patient developed yellow urine, abdominal distension, and yellowish skin. Laboratory tests showed alanine aminotransferase (ALT) 1-871-U/L, aspartate aminotransferase (AST) 1-502-U/L, alkaline phosphatase (ALP) 222-U/L, total bilirubin (TBil) 260.6-μmol/L, and direct bilirubin (DBil) 187.7-μmol/L. Viral hepatitis, autoimmune liver disease, and intra and extrahepatic space-occupying lesions were excluded by virological detection of hepatitis, autoantibody examination, and imaging examination. Liver injury caused by Shiduqing capsules was considered. Then Shiduqing capsules were discontinued and magnesium isoglycyrrhizinate injection and Shuganning injection(舒肝宁注射液) were given by intravenous infusion. Twenty-eight days later, the patient′s symptoms were improved significantly, and laboratory tests showed ALT 56-U/L, AST 65-U/L, TBil 68.9-μmol/L, and DBil 51.5-μmol/L. It was considered that the liver injury was related to the component of densefruit pittany root-bark (Cortex Dictamni) in Shiduqing capsules.

Objective To explore the occurrence and influencing factors of serum uric acid elevation in patients with coronavirus disease 2019 (COVID-19) treated with favipiravir.　Methods Medical records of patients with COVID-19 who were hospitalized in Beijing Ditan Hospital between June 1, 2020 and June 30, 2021 and treated with the 5- or 10-day regimen of favipiravir were collected and retrospectively analyzed. After favipiravir withdrawal, if the elevation in serum uric acid was ≥30% of baseline level, it was defined as serum uric acid elevation. Then patients were divided into serum uric acid elevation group and non-serum uric acid elevation group. The clinical characteristics such as gender, age, body mass index, comorbidities, smoking and drinking behavior, COVID-19 grade, favipiravir regimen, and serum uric acid level and renal function before treatment in patients between the 2 groups were compared. Influencing factors of favipiravir-associated serum uric acid elevation was analyzed using multivariate logistic regression method.　Results A total of 179 patients were included in the analysis, including 104 (58.1%) males and 75 (41.9%) females, aged from 19 to 70 years with a median age of 43 years. The level of serum uric acid in 179 patients after favipiravir treatment was significantly higher than before ［(451±119) μmol/L vs. (332±94) μmol/L， P<0.001］. The change rate of serum uric acid from baseline level ranged from -57.1% to 157.8% with the median of 38.6%. The elevation in serum uric acid of ≥ 30% of baseline level occurred in 108 (60.3%) patients. The incidences of serum uric acid elevation in patients treated with 5-day and 10-day regimens of favipiravir were 46.8% (36/77) and 70.6% (72/102), respectively, and the difference between them was significant (P=0.001). Multivariate logistic regression analysis showed that body mass index 24.0 to <28.0-kg/m2 (OR=3.109, 95%CI: 1.209-7.994, P=0.019) and 10-day regimen of favipiravir (OR=3.017, 95%CI: 1.526-5.964, P=0.001) were independent risk factors for favipiravir-associated serum uric acid elevation.　Conclusions More than half of COVID-19 patients treated with favipiravir can develop serum uric acid elevation. Overweight and 10-day regimen of favipiravir are independent risk factors for serum uric acid elevation in patients.

A 68-year-old male patient with advanced lung squamous cell carcinoma received intravenous infusion of pembrolizumab 200-mg once every 3 weeks. One week after the 4th IV infusion of pembrolizumab, the patient developed nausea and vomiting. Laboratory tests showed blood potassium 7.39-mmol/L, fasting blood glucose 28.1-mmol/L, β-hydroxybutyric acid 3.23-mmol/L, arterial blood pH 7.16, and bicarbonate 7.5-mmol/L. The patient was diagnosed as diabetic ketoacidosis, which was considered to be associated with pembrolizumab. After 8 days of treatments such as lowering blood sugar and correcting electrolyte disorder, his nausea and vomiting disappeared. Laboratory tests showed blood potassium 3.65-mmol/L, fasting blood glucose 7.5-mmol/L, β-hydroxybutyric acid 0.38-mmol/L, and bicarbonate 25.2-mmol/L.

本文对已在临床应用的抗肿瘤药物所出现的不良反应结合文献进行复习,分常见的和少见的不良反应,并提出相应的预防及处理方法,供临床医务人员参考。

Vincristine is an antineoplastic agent for intravenous use only;inadvertent intrathecal administration of vincristine may cause severe neurologic damage,and often is fatal.The first fatal case of inadvertent intrathecal vincristine administration was reported by Schacht et al.in 1968.Since then,at least 20 deaths from inadvertent vincristine intrathecal administration are known to have occurred in the United States,Canada,the United Kingdom,Germany,Saudi Arabia,Singapore,Korea,and China.In published case reports,the patients developed rapid sensory and motor dysfunction followed by encephalopathy,coma,and death after inadvertent intvathecal administration of Vincristine.Early signs and symptoms were tremors,disorientation,nausea,and vomiting.The patients became unresponsive within one week.Ascending paralysis occurred in some patients.The time to death ranged from 7 to 83 days.If vincrrstine is mistakenly given by the intrathecal route,the following treatment should be initiated immedi…更多ately:removal of spinal fluid,flushing with sodium lactated Ringer' s injection and fresh frozen plasma diluted in sodium lactated Ringer' s injectiom,administration of glutamic acid,folic acid,vitamin B6 and so on.Reasons for inadvertent intrathecal vincristine administration can be the end-results of either a sigle medication error or a series of medication errors.Suggestions for preventing inadvertent intrathecal vincristine administration include vincristine should be labelled warning label on the syringe and outer wrap,stating "for intravenous use only—fatal if given intrathecally",vincristine should be prepared in a minibag for intraveous infusion rather than a syringe,the storage and delivery of vincristine should be separated from all medicines intended for intrathecal administration,and only specifically trained and designated oncology staff should prepare and administer vincristine.

A 23-year-old healthy male received subcutaneous injection of recombinant human granulocyte colony-stimulating factor injection (rhG-GSF) 600-μg once daily for 6 days before allogeneic hematopoietic stem cell transplantation as a donor. Before medication, there were no abnormalities in the patient′s coagulation markers, blood routine and biochemical tests, as well as electrocardiographic examination. Seven days after discontinuation of the drug, the patient developed sudden chest pain, sweating, and vomiting. Laboratory tests showed high sensitivity cardiac troponin T 3 144-ng/L, creatine kinase MB>300 μ G/L, myoglobin 505.6-μg/L, N-terminal pro-brain natriuretic peptido 1-138-ng/L, white blood cell count 17.7×109/L, platelet count 160×109/L. The electrocardiogram showed ST segment elevation myocardial infarction. A dual antiplatelet therapy of aspirin and ticagrelor was administered in conjunction with percutaneous transluminal coronary angioplasty. After surgery, anticoagulation, antiplatelet, and lipid-lowering treatments were given. On the 3rd day after surgery, the patient developed toe pain, fever, and a platelet count of 382×109/L, symptoms were gradually relieved after symptomatic treatment, but platelet count increased to 566×109/L. After consultation with hematologists and rheumatologists, combined with relevant laboratory test indicators, autoimmune and hematological system-related diseases were excluded. It was considered that coronary artery thrombosis and thrombocytosis may be related to the use of rhG-CSF, and platelet count gradually decreased to 275×109/L without special treatment. During the follow-up of 7 months, his platelet count was 235×109/L .

Warfarin is an oral anticoagulant used in the treatment and prophylaxis of thromboembolic disorders.Many factors affect warfarin's anticoagulant effect(enhancement or diminishment).These factors include genetics,diseases,drugs,herbal medicines,food,etc.Several polymorphisms of CYP2C9(mainly CYP2C9^*2 and CYP2C9^*3),liver function insufficiency,hyperthyroidism,heart failure,and interactions of warfarin with aspirin,clopidogrel,miconazole,angelica,fennel,celery,pineapple,onion,and garlic enhance the anticoagulant effect of warfarin.Gene mutation of VKORC1 and interactions of warfarin with rifampicin,carbamazepine,ginseng,green tea,and plenty vitamin K-containing preparations or diets diminish the anticoagulant effect of warfarin.Further more,some drugs such as phenytoin sodium can increase as well as decrease warfarin's anticoagulant effect.Understanding of these factors affecting the anticoagulant effect of warfarin,regular monitoring of INR,and individualizing medication are beneficial to safe and effective use of warfarin.

Strychni semen is the dried ripe seed of Strychnos nuxvomica L. The crude drug contains alkaloids, of which the main alkaloids are strychnine and brucine. Strychnine is the main toxic component of strychni semen. Generally, the oral intoxicating dose of strychnine in adults is 5～10 mg, and the oral lethal dose is 30 mg. Strychnine can cause excitation of all parts of the central nervous system. Early signs of intoxication are headache, dizziness, nausea, vomiting, anxiety, restlessness, and slight twitching. Generalized convulsion, increasing sensitivity of sense organs, trismus, risus sardonicus, opisthotonus, dysphagia, and dyspnea follow. The patients often die from respiratory arrest. The principle of therapy in strychni semen poisoning is the prevention or control of convulsions and asphyxia. Management includes gastric lavage, the administration of activated charcoal, sedation with diazepam or phenobarbital, respiration support, and symptomatic treatment. The following precautions should be taken for safe use of strychni semen: crude drug should not be used, and the dosage should conform to the dosage limit in Chinese Pharmacopoeia; strychni semen should not combine with some drugs such as spirit, poppy capsule, musk, and so on; strychni semen is contraindicated in pregnant women; strychni semen should be used with caution in patients with liver and renal function insufficiency, neurological disorders, hypertension, and heart disease; overuse and prolonged use of strychni semen should be avoided, otherwise careful monitoring should be performed; the dosage should be adjusted when using strychni semen from different producing area.

随着现代医药的发展及治疗的需要,使绝大多数患者几乎都存在多药并用状况,从而药物相互作用所致的不良反应也日趋严重,已成为处方医师和服药患者必须认真考虑的一个重要而又现实的问题。其中,以前知之甚少的药物代谢性相互作用更是人们关注的热点。本文旨在对此问题的研究进展作一概要介绍,以期引起有关方面和医务人员的重视,及早采取措施,将药物因代谢性相互作用引致的不良反应减少到最低限度。

Traditional Chinese medicine (TCM) is widely used in medical institutions in China. Because TCM is often regarded as "natural and non-toxic", the irrational use of TCM is more common, such as repeated medication, incompatibility, long-term prescription, inappropriate usage and dosage, and inapprop- riate drug combination. The development and application of TCM prescription pre-audit system is of great significance to the safety management of TCM, but the existing TCM decoction prescription audit system still has some defects and needs to be further improved. The safety of TCM can be further improved by setting up TCM clinical pharmacist post, and strengthening the monitoring of adverse reactions and the study of the interaction between TCM and western medicines. In medical institutions, the management measures of TCM safety should be constantly explored and the pharmaceutical service level of TCM should be improved to ensure the patient safety.

环境污染的加剧,导致过敏反应相应地增加,由此引伸对第2代组胺H1受体阻断药开发的日趋重视,新药不断上市,其作用强而持久,对中枢和植物神经系统的不良反应甚微,但部分药物对心脏的毒性却日益突出,过量或同时并用肝酶P450抑制剂偶可出现严重的心律失常(尖端扭转型室性心动过速)。为此,对其产生心脏毒性原因及合理应用问题进行探讨,以寻求应用时的防范措施。

重组人血管内皮抑素(YH-16,商品名:恩度,ENDOSTAR),是一种多靶点的血管内皮抑制剂。具有抑制内皮细胞迁移,诱导其凋亡,发挥其抗肿瘤血管生成作用,是用于非小细胞肺癌临床治疗的靶向药物之一,可以明显提高非小细胞肺癌的治疗有效率。但YH-16的不良反应也不应忽视,尤其是对心血管系统具有一定程度的毒副反应。临床使用中应加强患者心血管系统生理状况的评价,进行心电图监测,避免与蒽环类等具有心肌毒性的化疗药物联合使用,以减少不良反应的发生。

Hepatic injury may induced by long-term use of total parenteral nutrition.The clinical presentations were elevated values of liver enzyme and bilirubin,cholestasis,fatty degeneration,and cirrhosis.The exact mechanism of TPN-induced hepatic injury is presently unknown;it may associated with the long-term fasting,imbalance of administered nutrients,and intestinal bacterial translocation.Balance of administered nutrients,use of cyclic infusion,early enteral feeding,and supplementation of some nutrients(such as choline and L-glutamine)may be beneficial to prevention and treatment of TPN-induced hepatic injury

Objective To explore the causes of medical disputes related to drug-induced liver injury (DILI).　Methods The Excel data sheet of drug-related medical disputes provided by the Beijing Municipal People′s Mediation Committee for Medical Disputes were searched and data on solved cases of DILI-related medical disputes from 2013 to 2019 were collected. The distribution characteristics, related drugs, and causes of disputes in these cases were analyzed retrospectively.　Results A total of 30 cases of DILI-related medical disputes were entered. Among the 30 patients, 23 (76.7%) were female and 7 (23.3%) were male, the age ranged from 3 months to 66 years, and the median age was 37 years; 25 (83.3%) were outpatients and 5 (16.7%) were inpatients. The drugs causing liver injury were traditional Chinese medicine (decoction and/or Chinese patent drugs) in 20 patients (66.7%), western medicine in 6 patients (20.0%), traditional Chinese medicine combined with western medicine in 4 patients (13.3%). Among the hospitals involved, tertiary hospitals accounted for 80.0% (24/30) and specialized hospitals of traditional Chinese medicine accounted for 60.0% (18/30). Of the 30 cases, 19 (63.3%) were judged to be the responsibility of the hospitals and the causes of liver injury were medication defects/errors, in which 17 cases (89.5%) were the responsibility of doctors and 2 cases (10.5%) were of nurses. The main problems were lack of inquiry before medication, lack of monitoring during treatment, illegal prescription, and overdosage due to negligence.　Conclusion DILI-related medical disputes often occur in outpatient department, most of the drugs involved were traditional Chinese medicine, which may be related to the lack of understanding of hepatotoxi- city of traditional Chinese medicine in physicians (especially physicians in specialized hospitals of traditional Chinese medicine) and the neglect of management for Chinese medicine prescriptions.

 A 35-year-old female patient received metronidazole sustained release tablets 0.75 g once daily and cefuroxime axetil 0.25 g twice daily after hysteroscopy curettage for infection. Because of postoperative fever and cough, she took ibuprofen granules 0.2 g each time orally by herself. After 3 days of treatments with metronidazole sustained release tablets and cefuroxime axetil and 4 times of ibuprofen granules, the patient developed right upper abdominal pain and dark urine. On the next day, the patient′s right upper abdominal pain was aggravated progressively, she developed soy sauce-like urine and yellowish skin and sclera. Laboratory tests showed alanine aminotransferase (ALT) 403-U/L, aspartate aminotransferase (AST) 248-U/L, gamma glutamyl transpeptidase (γ-GT) 327-U/L, alkaline phosphatase (ALP) 58-U/L, total bilirubin (TBil) 72.5-μmol/L, and direct bilirubin (DBil) 41.5-μmol/L. Liver injury induced by concomitant use of metronidazole and ibuprofen was considered. Metronidazole and ibuprofen were stopped and liver-protective and symptomatic treatments were given. Cefuroxime axetil was continued. Three days later, the patient′s abdominal pain disappeared gradually, her urine color became lighter, the yellow staining of skin and sclera was alleviated, and the respiratory symptoms were improved. Nine days later, the reexamination of liver function showed ALT 88-U/L, AST 35-U/L, γ-GT 185-U/L, ALP 52-U/L, TBil 19.6-μmol/L, and DBil 9.7-μmol/L.

Objective: To analyse the causative drugs, clinical manifestations and precautions of liver damage. Methods: 111 reports of drug-induced liver damage were presented by clinical departments in the hospital from January 2000 to December 2003 and retrospectively reviewed. Results: In 111 cases there were 58 males and 53 females,with a mean age of 46.96 years(range 8-82). 77drugs were involved,mainly antibacterials (18/111 cases,accounting for 16.22%),hormones and other related substances(17/111,15.32%), drugs acting on the CNS ,traditional Chinese medicines and antineoplastics (12/111,10.81%). Classification of drug-induced liver damage was made: hepatocellular damage(40 cases,36.04%),cholestatic damage (43cases, 38.74%)and mixed type damage(28cases, 25.22%). Conclusion: Routine liver function test, early diagnosis, immediate discontinuance of the causative drug and timely treatment are the key to management of drug-induced liver damage.

我们对近年来中药不良反应文献进行调研,将收集的文献信息进行分类总结,阐述中药不良反应产生的机制及原因,望能引起广大临床医务工作者重视中药不良反应产生的严重后果;减少中药不良反应的发生,促进我国中医药事业的发展。

我国《新型冠状病毒肺炎诊疗方案（试行第六版）》在中医治疗中推荐了6个品种的口服中成药，包括藿香正气方（胶囊、丸、水、口服液）、金花清感颗粒、连花清瘟方（胶囊、颗粒）、疏风解毒方（胶囊、颗粒）、苏合香丸和安宫牛黄丸。其中藿香正气方、金花清感颗粒、连花清瘟方和疏风解毒方仅推荐在医学观察期使用，但也有用于新型冠状病毒肺炎轻型和普通型患者的报道；而苏合香丸和安宫牛黄丸则仅用于新型冠状病毒肺炎危重症患者。这6种口服中成药的安全性较好，很少有不良反应发生，但临床应用时应注意中医辨证、禁忌证、配伍禁忌，避免主治证型相似的药物叠加使用，加强不良反应的监测。

Objective: To investigate the clinical characteristics of antibacterials-induced neuropsychiatric symptoms in patients with chronic renal failure. Methods: Patients with chronic renal failure treated with antibacterials, during January 1999 and December 2001,were retrospectively analysed. Results: 12 patients with chronic renal failure developed antibacterials- induced neuropsychiatric symptoms, 6 males and 6 femals, with a mean age of 64.3±9.7 years. After receiving intravenous injection daily for 1-6 days, patients presented with progressive neuropsychiatric symptoms, including extra-pyramidal system symptoms, disorientation, depressed consciousness, even coma, or apathy, agitation, hallucination, and personality changes. The very common drug involved was cephalosporins, the others were penicillins, carbopenems, quinolones and isoniazid. After withdrawal of evil agents, the neuropsychiatric symptoms disappeared within a few days. Conclusion: Antibacterial agents can cause neuropsychiatric symptoms in patients with chronic renal failure. Physicians should be aware of these potentially dangerous neurotoxicity during performing anti-infection therapy and withdrawal of the drugs whenever the adverse effects occur.

A 56-year-old male patient with tuberculosis complicated by infection did not get better after treatment with moxifloxacin combined with rifampicin, isoniazid, ethambutol, and pyrazinamide. The invasive pulmonary aspergillosis was diagnosed by bronchoalveolar lavage fluid culture and detection of 1,3-beta-D-glucan, galactomannan antigen, and Aspergillus antibody. Moxifloxacin and anti-tuberculosis drugs were discontinued and an IV infusion of voriconazole (the dose was 300-mg once per 12-hours on the first day, the maintenance dose was 150-mg once per 12-hours) was given. On the 5th day of medication, the plasma concentration of voriconazole was zero. The consultation pharmacist considered that the voriconazole plasma concentration was related to rifampicin. The next day, the dose of voriconazole was adjusted to 200-mg once per 12-hours. Two days later, the plasma concentration of voriconazole was 1.3-mg/L. The patient′s cough and expectoration were relieved, but he still repeatedly developed high fever. On the 9th day of increase of voriconazole dose, intravenous infusion of methylprednisolone 40-mg once daily was given because connective tissue disease could not be excluded by consulting rheumatologists. The patient′s temperature returned to normal the next day and the plasma concentration of voriconazole was 3.0-mg/L. Clinical pharmacists and physicians reviewed the literature and reached a consensus: the induction effect of rifampicin on drug metabolizing enzymes in the body can last for 7-10 days or even longer after discontinuation of the drug, the monitoring of plasma concentration of voriconazole should be strengthened in patients treated with rifampicin sequential voriconazole, and the dose of voriconazole should be adjusted according to the plasma concentration until the induction effect of rifampicin on drug metabolizing enzymes completely disappears and the plasma concentration of voriconazole reaches a steady state.

ObjectiveTo develop primary standard of potentially inappropriate medication (PIM) in Chinese aged people under morbid state and provide the basis and guide for clinical rational drug use in aged people.MethodsStandards of PIM in aged people under morbid state of the United States, Canada, Thailand, South Korea, and the Taiwan area of China were collected and, after summarizing, removing duplication, and integrating, the first round questionnaire was designed according to Delphi method to ask for the experts′ opinions. The experts′ feedback and suggestions were organized and the second round questionnaire was designed to ask for opinions again. Authoritative coefficient, positive coefficient, coordinate coefficient, mean score, and full mark rate were calculated. The selected drugs were respectively divided into grade A (frequency ≥ 3 000) and B (frequency < 3 000) standard according to medication frequency.ResultsThirty nine and 38 experts respectively took part in the 2 rounds of Delphi method investigations, who were selected from 23 grade Ⅲa hospitals in 11 provinces and 3 municipalities directly under the central government. These experts′ specialties involved 11 clinical medical specialties including neurology, psychiatry, cardiology, gastroenterology, endocrinology, urogenital epidemiology, gerontology, general medicine, pain medicine, dermatology, and respiratory medicine and 3 pharmacy specialties including clinical pharmacy, clinical pharmacology, and hospital pharmacy. After the 2 rounds of investigations, all of the authoritative coefficients of the experts were above 0.7, all of positive coefficients were 100%, and the first coordination coefficient were 0.17 and 0.21, respectively. Meanwhile, the mean scores were 3.65 and 3.94 and the means of full mark rates were 0.15 and 0.32, respectively. The first round investigation contained 188 points of drug-induced risks of 89 species (categories) of drugs under 31 kinds of morbid states and the second round investigation contained 74 points of drug-induced risks of 44 species (categories) of drugs kinds of morbid states. These indexes listed in the second round investigation were all enrolled the primary standard of PIM in Chinese aged people under morbid state. Grade A standard contained 62 points of drug-induced risks of 35 species (categories) of drugs under 25 kinds of morbid states, and grade B standard contained 12 points of drug-induced risks of 9 species (categories) of drugs under 9 kinds of morbid states.ConclusionsThe development of primary standard of PIM in Chinese aged people under morbid state has completed preliminarily. However, the standard still needs to be improved by clinical application to be used as a powerful tool for promoting rational drug use and lowering drug-induced risks of aged people.

ObjectiveTo investigate the feasibility of detecting adverse drug event (ADE) using Global Trigger Tool (GTT) in Chinese medical institutions.MethodsDischarged patients′ records of the Xuanwu Hospital of Capital Medical University from January 1st to December 31st 2013 were collected. After sorting by discharged date, 30 cases were selected in a half month period by a random sampling tool of Microsoft Excel 2007 software. Unqualified cases were eliminated according to the inclusion criteria (patients aged 18 and over, one time admission in 2013, and hospitalization for more than 1 day) and exclusion criteria (patients in the Department of Obstetrics, Family Planning, Rehabilitation, Oncology, Pediatrics, and day-care ward). The 20 cases were reviewed every half a month in sequence of random sampling using 35 triggers, including laboratory indexes, antidotes, clinical symptoms, and treatment measures, that were identified by GTT recommendation, relevant foreign researches, and self-experience of Xuanwu Hospital of Capital Medical University. All cases were enrolled if the number of cases which met the inclusion criteria was less than 20. The cases in whom triggers could be detected were marked as the cases with positive triggers. The cases with positive triggers-related situations were further reviewed in order to identify or exclude ADE and then the identified ADEs were classified. The positive triggers and ADEs were analyzed by Microsoft Excel 2007 software and the positive predictive values of positive triggers were calculated.ResultsTotally 465 cases were reviewed. Of them, 256 were male and 209 female with the mean age of 57 (19~92) years. The time of hospital stay was 2 to 37 days with the mean hospital stay of 10 days. Of the 465 patients, in 208 patients(44.7%)positive triggers could be detected. Of all the 35 triggers, 22 triggers (62.9%) were positive referring to 342 times. There were 18 ADEs identified involving 16 patients and the detectable rate was 3.4% (16/465). Of the 18 ADEs, 13 ADEs had their corresponding triggers containing 8 triggers. The overall positive predictive value of 22 positive triggers was 3.8%. The 18 ADEs included pneumonia (2 ADEs), liver injury (2 ADEs), chill (2 ADEs), skin rash (2 ADEs), antibiotic-associated diarrhea (1 ADE), headache (1 ADE), dizziness (1 ADE), nausea and vomiting (1 ADE), hypoglycemia (1 ADE), over-sedation (1 ADE), delirium (1 ADE), bleeding (1 ADE), leucopenia (1 ADE), and excitation (1 ADE). There were 14 ADEs of class E and 4 ADEs of class F in the 18 ADEs which referred to 21 drugs including 5 kinds of antibacterial agents, 3 kinds of blood system drugs, 3 kinds of psychotherapeutic agents, 2 kinds of cardiovascular drugs, 2 kinds of hormone drugs, 2 kinds of Chinese patent medicines, 1 kind of lipid drug, 1 kind of drug acting bone metabolism, 1 kind of antipyretic analgesic, and 1 kind of anesthetic.ConclusionsGTT could help to early detect the signals of ADEs and provide the reference evidence of preventing drug risk. It is valuable that GTT is popularized and used in Chinese medical institutions.

A 47-year-old male patient with bipolar disorder was given olanzapine tablets 10-mg orally once daily combined with lithium carbonate sustained-release tablets 0.3 g orally once daily due to manic episode. On the 6th day of medication, the patient received irbesartan and hydrochlorothiazide (containing irbesartan 150-mg and hydrochlorothiazide 12.5-mg in each tablet) 1 tablet orally once daily due to elevated blood pressure. Due to the aggravation of the patient′s manic symptoms, the dose of lithium carbonate was increased to 0.9 g/d from the 11th day of medication. After 13 days of combination therapy, the patient′s body temperature rised (up to 39.0-℃) and headache and tremor of both hands appeared. Laboratory test showed that his lithium concentration was 1.58-mmol/L (target plasma concentration was 0.80-1.20-mmol/L) and lithium poisoning was diagnosed. Lithium carbonate sustained-release tablets and other oral drugs were stopped immediately and symptomatic and supportive treatments such as rehydration, cooling, and diuresis were given. Meanwhile, vital signs were monitored. On the 2nd day of drug withdrawal, the plasma lithium concentration decreased to 1.14-mmol/L, the body temperature returned to normal, and the tremor of hands was relieved. On the 8th day after drug withdrawal, the plasma lithium concentration decreased to 0.45-mmol/L, and the symptoms and abnormal signs disappeared.

Object iv e:To investigate kidney damage caused by low-dose of enteric-coated aspirin t ablets.Method:The outcomes of600patients tak ing aspirin(50～75mg dai ly)were retrospectively analysed from January1995to August2003in our h ospital.Results:Kid ney damage occurred in16of600cases.Its frequen cy wa s related to age of patients,dosage and treatment duration of aspirin.And imp aired renal function was returned to normal gradually when aspirin was withdrawn in them.Conclusion:Prolonged oral admi nist ration of aspirin in low-dose can cause kidney damage and ordinary exam ination of urine and renal function is suggested,especially for the elderly.

Objective To compare the efficacy and safety between the generic sertraline tablets, which was selected in the national centralized volume-based procurement of drugs (trade name: Weitating), and the original sertraline tablets (trade name: Levofloxacin) in the treatment for depressive disorder, and to provide a basis for promoting the rational use of the generic drugs.　Methods Real world study using retrospective mirror-image comparison was adopted. The outpatient data of patients who were prescribed sertraline tablets one year after the implementation of the national centralized volume-based  procurement policy in Beijing Anding Hospital, Capital Medical University were collected. The patients were divided into the generic drug group and the original drug group. After the propensity score matching, the daily dose of prescription, blood concentration of sertraline, and incidence of abnormal laboratory test items (prolactin, liver and kidney function, blood lipids, etc.) of patients in the 2 groups were analyzed.　Results A total of 13-659 patients with depression, generalized anxiety disorder, and obsessive-compulsive disorder were enrolled in the study, including 5-973 (43.73%) patients in the generic drug group and 7-686 (56.27%) patients in the original drug group. Among the 5-973 patients in the generic drug group, 2-167 (36.28%) were male and 3-806 (63.72%) were female, aged (34±18) years, ranging from 6 to 94 years. Among the 7-686 (56.27%) patients in the original drug group, 2-709 (35.24%) were male and 4-977 (64.75%) were female, aged (35±19) years, ranging from 6 to 95 years. The difference between the daily dose of sertraline in prescription in the generic drug group and the original drug group was statistically significant ［(161.00±46.58) mg vs. (166.34±43.67) mg, t=6.614, P<0.001］. The difference of blood concentration of sertraline in patients between the generic drug group and the original drug group was statistically significant ［(50.41±39.49) μg/L vs. (53.80±39.62) μg/L, t=2.616, P=0.009］. The differences in incidence of prolactin elevation and liver and kidney dysfunction between the 2 groups were not statistically significant (all P>0.05). The difference in the proportion of patients with high-density lipoprotein cholesterol lower than limit of the reference value between the generic drug group and the original drug group was statistically significant ［41.75% (734/1-758) vs. 38.28% (673/1-758), χ2=4.409, P=0.039］. The difference in the proportion of patients with low-density lipoprotein cholesterol higher than the upper limit of the reference value between the 2 groups was statistically significant ［41.75% (734/1-758) vs. 45.39% (798/1-758), χ2=4.738, P=0.032］.　Conclusion In this study, no clinically significant differences in efficacy and safety of the generic and original sertraline tablets were found.

Objective:To observe the effect of ribavirin on hemoglobin(Hb )of SARS patients.Method:Hb changes were detected in57SARS patients around the period of ribavirin administration.Results:Estimation of Hb levels showed signifi-cant difference between before and after the start of treating(P<0.05).Hb drop was associated with daily dosage of ribavirin(P<0.05),not with its cumulative action and teatment duration.Con clusion:Ribavirin of lower dose daily is recommended in clinical practice of anti-SARS so as to avoid its adverse effects on Hb.

华法林为香豆素类口服抗凝剂，临床上应用越来越广泛，但他与许多药物和食物同时服用均会发生相互作用，从而影响抗凝效果。本文对华法林与西药、中草药和食物的不良相互作用进行概述，一起能为临床安全用药提供参考依据。

Oxaliplatin (OXA) is the third‑generation platinum antineoplastic agents, mainly used in the treatment of metastatic colorectal cancer. Sinusoidal obstruction syndrome (SOS) is a common and serious adverse reaction of OXA. The main clinical manifestations are splenomegaly, thrombocytopenia, abnormal liver function, and portal hypertension. The mechanism is closely related to OXA‑induced oxidative stress and inflammatory reactionsin the liver, which lead to injury of hepatic sinusoidal endothelial cells, and then lead to platelet aggregation and vascular obstruction in hepatic sinusoids. The occurrence of SOS is related to the accumulated dose and the treatment cycle of OXA. Splenomegaly is an independent predictor of OXA‑related SOS. Thrombocytopenia, elevated serum hyaluronic acid and aspartate aminotrans- ferase‑to‑platelet ratio index can also predict the occurrence of SOS. OXA should be used with caution in patients with chronic liver disease, especially in those with portal hypertension. Special attention should be paid to the occurrence of SOS during OXA treatment. For patients with symptoms of suspicious SOS, imaging examination should be performed in time. Early diagnosis and timely withdrawal of drugs are bene- ficial for the reversal of liver fibrosis, and the prognosis of patients with severe fibrosis is poor.

A 66-year-old male urothelial carcinoma patient with liver and lymph node metastasis received an IV infusion of paclitaxel for injection (albumin bound) 400-mg on day 1 and tegafur, gimeracil and oteracil potassium capsules 50-mg orally twice daily on day 1 to day 14, the interval was 1 week, and each cycle was 21 days. A total of 9 cycles of chemotherapy were performed. The patient complained of priapism occurring about 15-hours (about 1: 00 of the next morning) after intravenous infusion of paclitaxel (albumin bound) in the cycles 1-5 and 7-9, which could disappear about 2 hours later. No special treatment was given. After that, paclitaxel for injection (albumin bound) was not used, and the patient did not have the above symptoms again after changing to immunotherapy as disease progresses. It was considered that the patient′s priapism might be related to paclitaxel for injection (albumin bound).

In the past, clinical pharmacists were less involved in the perioperative pharmaceutical management for surgical patients, mainly related to the analgesic management of postoperative pain. In recent 2 years, clinical pharmacists have found that the perioperative patients often suffer from other underlying diseases and need long-term medication. The lack of perioperative pharmaceutical management and evaluation may increase the risk of intraoperative accidents or postoperative complications in some patients. In May 2020, a female patient with rheumatoid arthritis in Nanjing Drum Tower Hospital Affiliated to Medical College of Nanjing University failed to fully evaluate the risk of difficult airway caused by long-term use of prednisolone tablets before operation developed difficulty with facemask ventilation and tracheal intubation after anesthesia, and the operation was forced to be terminated. This incident attracted great attention from pharmacists, so they began to implement comprehensive pharmaceutical management for perioperative patients, including formulating a number of management specifications for common perioperative drugs, opening a perioperative pharmaceutical care clinic for daytime surgical patients, and implementing comprehensive perioperative pharmaceutical management for surgical inpatients. Half a year after clinical pharmacists strengthened the perioperative pharmaceutical management, the satisfaction of surgeons, nurses, and patients with their works were 98.2%, 99.1%, and 93.9%, respectively.

Exposure to antineoplastics is a potential health threat. If improperly disposed, it will also cause environmental pollution, which is a medical safety issue worthy of attention. In order to improve the protection awareness of healthcare professionals exposed to antineoplastic drugs (medical personnels, drug transportation staffs, patients and their caregivers, etc.), standardize exposure protection operations, and reduce the risk and harm of occupational exposure, the Division of Therapeutic Drug Monitoring of Chinese Pharmacological Society, the Hospital Pharmacy Professional Committee of Chinese Pharmaceutical Association, the Oncology Society of Chinese Medical Association, the Nursing Branch of China International Exchange and Promotive Association for Medical and Healthcare, and Chinese Pharmacological Society Professional Committee of Drug-induced Diseases formulated the Management guidelines for preventing exposure to antineoplastics, which was published in the 1st issue of Chinese Journal of Cancer Research in 2023. The guideline was developed referring to the World Health Organization handbook for guideline develo- pment and other international methodologies and focused on the full-process management of antineoplastics in hospitals. Using the Delphi method, clinical questions and 14 recommendations were formulated. This paper interprets 14 recommendations, hoping to help promote the implementation of the guideline.

治疗心血管病常用药物在医治躯体疾病的同时,可能影响病人的性生活质量,其中用于冠心病二级预防的药物尤为明显。本文综述了近年来治疗心血管病常用药物对性功能的影响、作用机制及防治方法。

Drug safety is always the primary concern in both the stage of new drug development and the post-marketing clinical application stage, and it is also the main reason for drug development failure and even post-marketing drug withdrawal. The physiologically-based pharmacokinetic (PBPK) model can not only routinely predict the human plasma pharmacokinetics, but also predict the concentration distribution of drugs in different tissues, which has become an important tool for predicting the adverse reactions of new drugs and has gradually attracted the attention of drug regulatory authorities. In this article, the latest progress and application of the PBPK model for predicting drug-induced nephrotoxicity, cardiotoxicity, and neurotoxicity are briefly reviewed to provide references for early prediction of adverse drug reactions in new drug development and rational clinical use of drugs.

A 52-year-old male patient was given escitalopram 5-mg/d (gradually increased to 15-mg/d), trazodone 100-mg/d, and lorazepam 1-mg/d for depression. Increased salivary secretion occurred 3 days after taking the medicine. After 13 days of taking the medicine, she only took escitalopram and lorazepam due to lack of trazodone. After stopping trazodone for 3 days, the symptoms of increased salivary secretion disappeared. Trazodone 100-mg/d was added again later due to poor sleep and increased salivary secretion relapsed after 2 days of trazodone administration. Considering that the above symptoms were related to trazodone, the doctor ordered him to stop the drug and take escitalopram and lorazepam only. Three days later, the patient′s increased salivary secretion disappeared again. The patient′s depressive symptoms were relieved and increased salivary secretion did not recur at a 2-week follow-up.

根据近年有关研究和报道对含马兜铃酸中药的毒性成分、马兜铃酸的代谢、马兜铃酸肾病的发病机制、临床特征及其诊断方法进行综述,旨在对马兜铃酸的毒理学及马兜铃酸肾病的诊治加深认识。

A 76-year-old female patient took soaking water of Tetrastigma hemsleyanum 15 g daily by herself after lung cancer resection and chemotherapy. After 3 months of medication, the patient developed fatigue and dry mouth. After 4 months of medication, decrease of white blood cells and hemoglobin and increase of fasting blood glucose and glycosylated hemoglobin appeared and were gradually aggravated. After 6 months of medication, the white blood cell count was 2.8×109/L, hemoglobin was 88-g/L, red blood cell count was 3.05×1012/L, fasting blood glucose was 10.01-mmol/L, and glycosylated hemoglobin was 6.93%. Diabetes mellitus, leukopenia, and anemia were diagnosed, which were considered to be related to Tetrastigma hemsleyanum. The patient was asked to stop drinking the soaking water of Tetrastigma hemsleyanum and the traditional Chinese medicine decoction was given. Two months later, the patient′s blood cells returned to normal, fasting blood glucose was 6.08-mmol/L, and glycosylated hemoglobin was 6.10%. The prescribed daily dose of Tetrastigma hemsleyanum in Chinese Medicine Record is 3-9 g. Diabetes mellitus and hemocytopenia in the patient might be related to overdose and long-time use of the drug.

Objective To understand the usage status of high-alert medicines (HAM) for children in outpatient and emergency prescriptions and inpatient medication orders at department of pediatric.　Methods All outpatient and emergency prescriptions and inpatient medication orders in patients with an age of <18 years between July 1, 2016 and June 30, 2018 in Huairou Maternal and Child Health Hospital Affiliated to Beijing Obstetrics and Gynecology Hospital, Capital Medical University were collected. According to the List of High-Alert Medications for the Chinese Children, the use of HAM for children in prescriptions and medication orders was analyzed retrospectively.　Results A total of 297-968 prescriptions and medication orders were collected in the study, including 270-024 outpatient and emergency prescriptions (90.62%) and 27-944 inpatient medication orders (9.38%). There were 162-521 prescriptions (54.54%) involving male children and 135-447 (45.46%) involving female children with an age of (4±3) years, ranged 0-17 years. The number of drugs included in each prescription was (2±1), ranged 1-9. Of the 297-968 prescriptions and medication orders, 23-476 (7.88%) involved HAM for children. The proportion of prescriptions containing HAM for children in outpatient and emergency prescriptions was significantly higher than that in inpatient medication orders ［7.92% (21-381/270-024) vs. 7.50% (2-095/27-944), P=0.013］; the proportion of prescriptions and medication orders containing HAM for children in Surgery Department ［32.84% (1-220/3-715)］ was significantly higher than that in Medicine Department ［8.17% (22-043/269-777)］ and other departments ［0.87% (213/24-476)］, and the difference was statistically significant (all P<0.001). The 23-476 prescriptions involved 13 categories and 42 kinds of HAM for children and the total frequency of HAM for children was 26-084. The top 3 drug categories that most frequently used were traditional Chinese medicine injections (8-694, 33.33%), antipyretic analgesic and anti-inflammatory drugs (7-505, 28.77%), and anti-infective drugs (4-011, 15.38%); the top 10 HAM for children that most frequently used were paracetamol, Yanhuning injection (炎琥宁注射液), Xiyanping injection (喜炎平注射液), vitamin K1, vidarabine, tetanus antitoxin, penicillins, phenobarbital, promethazine injections, and heparin. Adverse events occurred in 9 children due to medication errors of HAM for children, which were all grade E, and the drugs involved were Xiyanping injection, paracetamol, and vitamin K1 injection.　Conclusions HAM for children was commonly used, among which the traditional Chinese medicine injection-related HAM was used more, and the proportion of prescriptions containing HAM for children was higher in departments of outpatient, emergency, and surgery. Medication errors related to HAM for children may lead to serious adverse events, so the management of HAM for children should be strengthened.

Objective: To analyse the cases with allergic shock induced by traditional Chinese medicines for rational use of the drugs. Methods: Reports of 131 cases with allergic shock published at home during 1989-1999 were collected and the way of drug administration, dosage forms and some other aspects were sorted out and investigated. Results: Injection came first in order of the cause of allergic shock (72.52%) followed by per os (16.03 % ) , preparation for external use only (2.29% ) and others (9.16% ) . Conclusion: The rational use of the drugs with a close attention during its continuation was recommended.

Drug-induced liver injury (DILI) is caused by the direct toxicity of drugs and/or their metabolites or the body-specific heterogeneous response to drugs. Since 2019, the European Association for the Study of the Liver, the American College of Gastroenterology, and the Asia Pacific Association of Study of Liver have successively updated previously published guidelines on DILI. Based on the above 3 updated guidelines and in combination with Chinese Diagnosis and Treatment Guideline on Drug-Induced Liver Injury, the Guideline for Primary Care of Drug-Induced Liver Injury (2019), and the relevant literature at home and abroad in recent years, we review the progress on the diagnosis and treatment of DILI in this paper, aiming to help the diagnosis and treatment of DILI in clinic.

With the continuous deepening of the research on tumor pathogenesis, more and more innovative oncology drugs have been approved on the market, mainly including targeted antitumor drugs and immune checkpoint inhibitors. These new antitumor drugs have the advantages of high specificity, precise targeting, good efficacy, and low toxicity to greatly improve the patient quality of life and prognosis. However, because of the different types and monitoring methods of their adverse drug reactions from those of the traditional chemotherapy ones, the research on these drugs from aspects of prediction of adverse drug reactions, the relationship between adverse drug reactions and gene polymorphisms, and the therapeutic drug monito- ring are still necessary to be further researched.

Minocycline is a semi-synthetic tetracycline antibiotic. In recent years, minocycline has been used in the treatment of chronic infections caused by multi-drug resistant bacteria and chronic diseases such as pemphigus and rheumatoid arthritis due to its lower incidence of bacterial resistance and good antibacterial effect. Long term use of oral minocycline can cause skin hyperpigmentation. According to the location, clinical features, and histopathological changes, minocycline-induced skin hyperpigmentation (MISH) is divided into 4 subtypes, but the definition of subtype 4 remains controversial. The incidence of MISH varies greatly in different studies, which may be closely related to factors such as patients′ underlying pathophysiological status, comorbid diseases, dose, and duration of treatment. For those patients who need to take minocycline for a long time, skin color should be observed. Once skin color changes were found, relevant examinations (e.g. skin biopsy) should be carried out in time to make a definite diagnosis as soon as possible. Patients with MISH should pay attention to sun protection. Reducing the dose or stopping minocycline is an effective strategy to improve MISH. Q-switched laser or picosecond laser is recommended to treat pigmentation which can not be recovered after drug withdrawal.

Hyperprolactinemia is a common adverse effect of antipsychotic drugs. The clinical presentations of hyperprolactinemia are gynecomastia in men, and breast distending pain, galactorrhea, menstrual disturbance, sexual dysfunction, osteoporosis, and metabolic disturbance in women. The incidence of hyperprolactinemia is 25%-89%. The factors related to antipsychotic-induced hyperprolactinemia are gender, age, the type of antipsychotic drugs and dosage. The mechanism of antipsychotic-induced hyperprolactinemia may be related to blockade of dopamine D2 receptors on the anterior pituitary by antipsychotic drugs and reduction of dopamine inhibitory effect on prolactin secretion of prolactin cells, leading to prolactin elevation. Antipsychotic-induced hyperprolactinemia should be distinguished from hyperprolactinemia due to severe stress, depressive state, pregnancy, hypothyroidism, renal failure, pituitary tumor and ovarian disease. The treatment of antipsychotic-induced hyperprolactinemia includes discontinuing antipsychotic drugs, reducing antipsychotic drugs dosage, switching to a prolactin-sparing agent, prescribing a dopamine receptor agonist or Chinese herbal medicines, and using low-frequency repetitive transcranial magnetic stimulation.

Drug-induced liver injury(DILI) is one of the common adverse drug reactions. Over 1100 drugs and related substances are associated with DILI. However, there is no specific diagnostic marker to DILI so far. This paper introduces and discusses some main diagnostic criterias in order to be helpful for diagnosis of DILI in clinical practice.

Objective To explore the occurrence and clinical characteristics of leukopenia induced by amoxicillin sodium and clavulanate potassium for injection in patients with acute pyelonephritis.　Methods The subjects were patients with acute pyelonephritis who used amoxicillin sodium clavulanate potassium for injection during hospitalization in the Department of Nephrology, the University of Hong Kong-Shenzhen Hospital from January to December 2019 and had a white blood cell count (WBC) ≥4.0×109/L before amoxicillin sodium clavulanate potassium for injection administration. Cases of leucopenia caused by amoxicillin sodium clavulanate potassium for injection were collected and the patients′ basic information, duration of treatment with amoxicillin sodium clavulanate potassium for injection, concomitant medications, blood cell count before and after administration, leukopenia occurrence, and interventions and outcomes of leukopenia were extracted from electronic medical records. The incidence of leucopenia was calculated and the clinical characteristics of the adverse reaction were analyzed. Leukopenia was defined as WBC <4.0×109/L (lower limit of WBC reference value in our hospital).　Results A total of 134 patients were included in the analysis. Of them, 12 developed leukopenia, the incidence was 9.0%. Among the 12 patients, 1 (8.3%) was male and 11 (91.7%) were female with an age of (35±12) years. The time from drug administration to the onset of leukopenia ranged from 2 to 6 days and it was 3 days in 6 patients (50.0%). The WBC, neutrophil count, and neutrophil proportion were (4.7~17.5)×109/L, (3.1~15.4)×109/L, and (0.60~0.90) before drug administration, and then decreased to (2.3~3.9)×109/L, (0.8~2.4)×109/L, and (0.35~0.65) after drug adminis- tration, respectively. Fifty percent (6/12) of the patients had hemoglobin decrease >20-g/L and (or) erythrocyte count decrease >0.5×1012/L. None of the 12 patients had obvious clinical symptoms, and no other interventions were given after discontinuation of the drug. WBC returned to normal in 11 patients and was unknown in the other 1 patient because the patient was lost to follow-up on day 2 of drug discontinuation after discharge.　Conclusions Amoxicillin sodium clavulanate potassium for injection can cause leukopenia in patients with acute pyelonephritis, which mostly occurs within 6 days of medication. It is generally asymptomatic and can recover after drug discontinuation. The prognosis is good.

Objective To compare the clinical efficacy and safety of cefdinir dispersible tablets selected in the national centralized volume-based procurement (VBP) and the original drug cefdinir capsules.　Methods Clinical data of single-use cefdinir in outpatient of Xuanwu Hospital, Capital Medical University between January 1, 2020 and December 31, 2021 were collected through the hospital information system. The clinical data included gender, age, type of medical insurance, type of infection, application of cefdinir, whether to combine other antibacterial drugs, laboratory test results such as blood routine, C-reactive protein, liver and kidney function before and after cefdinir treatment, and adverse reaction report of cefdinir. After propensity score matching (PSM) of the age, sex, type of medical insurance, type of infection and whether to combine with other antibacterial drugs in the cefdinir dispersible tablets group selected in the VBP (VBP group) and the original cefdinir group (original group), the clinical application in patients in the 2 groups was compared to indirectly evaluate the efficacy of the 2 drugs. The white blood cell count, neutrophils percentage, and C-reactive protein levels before and after the use of cefdinir was compared to evaluate the efficacy. Adverse drug reaction report of cefdinir and liver and kidney function before and after the use of cefdinir were compared to evaluate the safety.　Results A total of 9-514 patients treated with cefdinir were entered, including 7-037 patients in the VBP group and 2-477 patients in the original group. After PSM, each group comprised 1-268 patients, the differences in gender, age, type of infection, and combination with other antibacterial drugs were not statistically significant (all P>0.05). The daily dose, course, and use density of cefdinir in the VBP group were lower than those in the original group［(0.30±0.04) g vs. (0.35±0.12) g, P<0.001; 8(4, 8) d vs. 10(8, 10) d, P<0.001; (3.96±1.70) g vs. (5.22±2.03) g, P<0.001］. The white blood cell count, neutrophils percentage, and C-reactive protein levels after the cefdinir application in patients in the VBP group were lower than those before the use of the cefdinir ［11.2(8.7, 13.8)×109 vs. 7.2(5.5, 9.9)×109, P<0.001; 80(74, 87)% vs. 66(56, 73)%, P<0.001; 23(10, 64) mg/L vs. 13(6, 44) mg/L, P=0.032］. No adverse drug reactions related to cefdinir were reported in the 2 groups. The differences in alanine aminotransferase, aspartate aminotransferase, blood creatinine, and urea nitrogen levels in patients between the 2 groups before and after use of cefdinir were not statistically significant (all P>0.05). The difference in aspartate aminotransferase before and after use of the cefdinir in the original group was statistically significant ［21(18, 23) U/L vs. 23(20, 29) U/L, P=0.040］, and the differences in alanine aminotransferase, blood creatinine, and urea nitrogen levels were not statistically significant (all P>0.05). The detection values of liver and kidney function in the 2 groups before and after use of the cefdinir were within the reference range.　Conclusion No significant differences were found in the clinical efficacy and safety between the VBP cefdinir dispersible tablets and the original cefdinir capsules.

The serotonin syndrome is a potentially life-threatening adverse reactions that results from therapeutic drug use. The mechanisms are attributed to the increase on activity of serotonergic system because 5-hydroxytryptamine (5-HT) accumulates in nervous system and 5-HT postsynaptic receptors are overactivated. The clinical feature is described as a clinical triad of mental-status changes, autonomic hyperactivity, and neuromuscular abnormalities. The syndrome often occurs in coadminstration among antidepressants or combination with other drugs. The diagnosis of the serotonin syndrome is mainly based on the clinical manifestation. Management of the serotonin syndrome involves the cessation of precipitating drugs, improvement of monitoring, control of agitation, administration of 5-HT antagonists, symptomatic treatment, the control of complication, etc. The prevention of the syndrome is more important than the treatment.

A 69-year-old female patient received immunotherapy with intravenous infusion of sintilimab 200-mg once per 21 days because of recurrence of left lung adenocarcinoma after operation. The patient had no history of diabetes mellitus and blood sugar level was normal before treatment. Three days after the first intravenous infusion of sintilimab, the patient felt dry mouth and fatigue, 10 days later her symptoms were worsened, accompanied by nausea. Laboratory examination showed random blood glucose 27.0-mmol/L and hypoglycemic treatment was given. On the 29th day of intravenous infusion of sintilimab, oral glucose tolerance test showed that fasting, 1, 2 and 3 hours postprandial blood glucose levels were higher than those of the upper reference value, C-peptide and insulin were lower than those of the lower reference value, urine routine showed ketone bodies (±) and glucose (++++). Autoimmune diabetes mellitus caused by sintilimab was considered. After several adjustments, the hypoglycemic regimen was finally determined as recombinant human insulin injection 12 units subcutaneously before morning and evening meals, 14 units before lunch; albumin biosynthesis human insulin injection 12 units subcutaneously at bedtime. Five days later, the patient′s symptoms such as dry mouth, fatigue, and nausea disappeared, with fasting glucose 4.8-5.8-mmol/L and postprandial glucose 7.8-8.7-mmol/L. Urine routine examination showed negative ketone body and glucose.

矿物类中药中可含有铅、汞、砷等重金属成分,过量应用会导致药源性铅、汞和砷等重金属中毒。临床上对重金属中毒的误诊率较高,应引起高度重视。通过仔细采集病史,拓宽临床思维,认识矿物类中药重金属中毒的临床表现,结合毒物化学成分的检测结果,可正确诊断药源性重金属中毒,并及时采取特效解毒剂驱排治疗。

Objective: To investigate the the allergic shock induced by cephalosporins. Methods: Literature was retrieved from domestic medical journals 1990-2003,and 244 cases with allergic shock in 210 papers were collected and analysed. Results: Twelve cephalosporins were involved in 244 cases and 93.8% of them were caused by six cephalosporins, namely, cefazolin, cefotaxime, cephalexin, cefoperazone, ceftriaxone and cefradine. The patients with and without allergic history accounted for 24.6% and 30.3% respectively and the others were unknown in this respect. 78.7% of the cases occurred during first administration and 86.1% did within 20 minutes of drug start. The mortality rate was about 8.2%. Conclusion: Cephalosporins could result in allergic shock and much attention should be especially paid to the patients with allergic history.

Hepatitis C virus protease inhibitors (PIs) are one of the major categories that constitute directly acting antivirals (DAA) regimen in the treatment for hepatitis C. These drugs are mainly metabolized by liver cytochrome P450 and have potential hepatotoxicity. Population pharmacokinetic study data showed that the metabolism of PIs was slower in Asians than that in White/Caucasian subjects, and the results of clinical trials and real-world studies in Asians showed that these drugs had the risk of causing liver enzyme abnormalities and bilirubin elevations. Medical workers in our country should pay full attention to the potential risks of PIs in liver safety, and should not rely too much on safety data in Europe and America. The baseline liver disease severity should be accurately assessed before selecting the DAA regimen containing PIs and the risk of disease progression should be considered. PIs are contraindicated in patients with decompensated liver disease. For patients without cirrhosis or with compensated cirrhosis, the liver function should be closely monitored during the administration of PIs and the management of liver-related adverse events should be paid attention to.

Objective To systematically evaluate the efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia (COVID-19).　Methods Randomized controlled trials (RCTs), cohort studies, and case-control studies on the efficacy and safety of arbidol for COVID-19, influenza, and other respiratory virus infections were collected by searching related database at home and abroad and network platform for preprint of Health Science Papers (medRxiv) (up to April 25, 2020). Quality of the enrolled studies was evaluated by bias risk assessment tool of Cochrane collaboration network and Newcastle- Ottawa Scale (NOS). Meta-analysis and descriptive analysis of relevant outcome indicators were performed using RevMan 5.3-software.　Results A total of 15-studies were enrolled in the study, including 7 cohort studies with high-quality and 8 RCTs, 6 of which were with low bias risk and the other 2 of which were with medium bias risk. Among these studies, 8 were on arbidol treatment for COVID-19, including 5 retrospective cohort studies, 2 prospective cohort studies, and 1 RCT, and involving 809 patients (479 patients in the arbidol group and 330 in the control group); 7 were RCTs on arbidol treatment for influenza or other respiratory virus infections, involving 1-471 patients (745 patients in the arbidol group and 726 in the control group).In these studies, patients were treated with arbidol (0.15-1.2 g daily for 5-21 d) in the arbidol group while with the other antiviral agents or without any antiviral drug in the control group. Meta analysis on the efficacy and safety of arbidol in treatment for COVID-19-showed that the novel coronavirus (2019-nCoV) nucleic acid negative conversion rate in the arbidol group was significantly higher than that in the control group ［71.7% (109/152) vs. 58.8% (94/160), relative risk (RR)=1.30, 95% confidence interval (CI): 1.01-1.67, P=0.04］; the difference of time taken for 2019-nCoV nucleic acid negative conversion between the 2 groups was not statistically significant (standardized mean difference=-0.17, 95%CI: -0.72-0.38, P=0.55); the difference of disease improvement rate shown by chest CT on day 7 after treatment between the 2 groups was not statistically significant ［46.2% (30/65) vs. 50.7% (36/71)， RR=0.88， 95%CI: 0.39-1.98， P=0.76］; and the difference of incidence of adverse reactions between the 2 groups was not statistically significant ［16.9% (39/231) vs. 19.2% (47/245), risk difference (RD)=-0.03, 95%CI: -0.10-0.04， P=0.44］. Meta analysis on the safety of arbidol in treatment for influenza and other respiratory virus infections showed that the incidence of adverse reactions in the arbidol group was significantly lower than that in the control group ［5.9% (44/745) vs. 11.3% (82/726), RR=0.52, 95%CI: 0.37-0.74, P<0.01］.　Conclusion Arbidol could effectively increase the 2019-nCoV nucleic acid negative conversion rate and it might be safe to treat COVID-19 using arbidol.

本文综述了有关甘草酸类药物引起不良反应的报道,其不良反应主要是对内分泌系统的影响:如水、钠潴留,低钾血症,高血压,假性醛固酮增多症等。过敏反应较少,罕见的不良反应有胆汁性肝硬化、上消化道或牙龈出血、腹泻和精神症状。甘草酸类药物不良反应发生的主要机制与该药的肾上腺皮质激素样作用有关。α异构体甘草酸类药物甘利欣的安全性优于β异构体甘草酸类药物。

A 55-year-old male patient with severe mitral valve insufficiency received long-time warfarin anticoagulation therapy after mechanical mitral valve replacement and the international standard ratio (INR) was 2.00-3.00. Because of oral ulcers, he took the water soaked with dandelion (Taraxacum mongolicum Hand-Mass.), which was self-purchased and sun-dried, for daily drinking. Fifteen days later, the patient developed chest tightness, shortness of breath, palpitation, and fatigue, followed by nausea, vomiting, mild edema of the lower limbs, orthopnea at night, ecchymosis on the right lower limb, and black stool successively. Laboratory tests showed hemoglobin 52-g/L, red blood cell count 2.05×1012/L. Gastrointestinal bleeding was considered, which might be related to the water soaked with dandelion drunk during warfarin therapy. Warfarin and water soaked with dandelion were stopped. The patient received symptomatic treatments including IV infusions of leukocyte-depleted red blood cell suspension 2 units (2 times in total) and esomeprazole 80-mg (twice daily), an intramuscular injection of vitamin K1-10-mg, and oral vitamin K1-20-mg. Two days later, the patient′s INR was 1.58, hemoglobin was 84-g/L, and red blood cell count was 2.33×1012/L. Five days later, his INR was 1.63, hemoglobin was 104-g/L, and red blood cell count was 3.92×1012/L.

本文根据近年国内外文献资料,对临床常用氟喹诺酮类药物的不良反应进行了分析,并概述其不良反应的机制与化学结构的关系。其中N₁、C₅、C₇、C₈取代基与不良反应的程度相关;C₂的H、C₆的F均不可取代,与抗菌药效关系密切,与不良反应无关;C₃、C₄与DNA螺旋酶结合,也与药物间相互作用有关。经验表明,临床医师在新药应用与研究开发中了解药物不良反应的监测资料是十分重要的。

Polymyxin B is mainly used in the treatment of severe drug-resistant gram-negative bacterial infection. In recent years, more and more cases of skin pigmentation caused by polymyxin B have been reported. The incidence of polymyxin B-related skin pigmentation in infants was higher than that in adults. The mechanism of polymyxin B-induced hyperpigmentation is not clear, which may be related to histamine release, skin inflammation, and the stimulation of melanin synthesis induced by polymyxin B. Although skin pigmentation has no significant effect on the treatment and prognosis in patients, it may cause psychological burden and affect the life quality, which should be paid more attention to and further studied.

A 68-year-old male patient with severe active ulcerative colitis developed sleep disorder after using hormone pulse therapy. He received dexzopiclone 3-mg orally once a night to improve sleep. On the next day of medication, the patient developed ataxia symptoms such as dizziness, head drooping, and body skewing when walking, etc. The patient had a history of Parkinson′s syndrome and treatment effect of levodopa and benserazide hydrochloride was good. Dyskinesia caused by levodopa and benserazide hydrochloride were suspected. Then the drug was stopped and symptomatic treatments were given for 3 days, but his symptoms were not improved. After consultation with the neurologist, the patient was diagnosed as having ataxia, which was suspected to be related to dextrzopiclone. Four days after dextrzopiclone withdrawal, the patient′s symptoms were improved obviously. The patient resumed to use levodopa and benserazide hydrochloride before discharge and the ataxia symptoms above mentioned did not recur.

Objective To evaluate the cardiovascular safety of febuxostat and allopurinol in patients with gout/hyperuricemia, and to explore the difference in cardiovascular safety between Asian and non-Asian patients.　Methods Randomized controlled trials (RCTs) and cohort studies of comparision of cardiovascular safety between febuxostat (the trial group) and allopurinol (the control group) in the treatment of gout/hyperuricemia were collected by searching related databases at home and abroad (up to October, 2021). The outcome indicators were the incidences of acute decompensated heart failure (ADHF), stroke, acute coronary syndrome (ACS), coronary revascularization, death from cardiovascular causes, and all-cause death. The Cochrane collaboration risk of bias risk tool and Newcastle Ottawa Scale were used to evaluate the quality of the RCTs and the cohort studies, respectively. RevMan 5.4-software was used for meta-analysis, and the effect sizes were relative risk (RR) and its 95% confidence interval (CI).　Results A total of 9 RCTs and 7 cohort studies were enrolled in the analysis and 385-700 patients were involved, including 123-565 in the trial group and 262-135 in the control group. The results of quality evaluation showed that there were 4 and 5 RCTs with low and uncertain bias risk in 9 RCTs, respectively; among the 7 cohort studies, 2 and 5 were of high and medium quality, respectively. The result of meta-analysis of RCTs showed that the incidence of ADHF in the trial group was significantly lower than that in the control group ［1.37% (77/5-620) vs. 2.21% (102/4-607), RR=0.74, 95%CI: 0.55-0.99, P=0.04］. The result of meta-analysis of cohort studies showed that the incidence of stroke in Asian patients in the trial group was lower than that in the control group ［0.87% (519/59-559) vs. 0.90% (810/89-836), RR=0.94, 95%CI: 0.75-1.17, P=0.58］; the incidence of stroke in non-Asian patients in the trial group was lower than that in the control group, and the difference was statistically significant ［1.49% (377/25-306) vs. 1.70% (1-305/76-864), RR=0.88, 95%CI: 0.78-0.98, P=0.02］; the incidence of cardiovascular death in Asian patients in the trial group was higher than that in the control group ［0.96% (473/49-373) vs. 0.68% (335/49-368), RR=1.41, 95%CI: 1.23-1.62, P<0.01］.　Conclusions The risk of ADHF caused by febuxostat is lower than that caused by allopurinol; the risk of stroke caused by febuxostat is lower than that caused by allopurinol in non-Asian patients; the risk of cardiovascular death caused by febuxostat is higher than that caused by allopurinol in Asian patients.

Objective: To analyze allergic reactions caused by traditional Chinese medicines statistically. Method: 187 ADRs were collected from national medical journals of 1999-2001 in consideration of gender, age, time, route and clinical manifastations. Results: ADR of traditional Chinese medicines was in no relation with gender and age of patients. But it was connected with route of administration. Drugs for injection ranked first on the ADR list, accounting for 109 cases. The time of ADR occurrence ranged from three minutes to seven days when drugs being taken, mostly in the period of treatment. Main manifestations of ADR were as follows: dermoreaction (122 cases), allergic shock (26), allergic rhinitis (7), allergic asthma (6), anaphylactoid purpura (5) and drug fever (17). Conclusion: Allergic reaction is the most common ADR and should be given close attention and prevented timely.

A 24-year-old female patient took about 150 carbamazepine tablets (15 g). About 17-hours later, she was found unconscious and frequent convulsions by her family and was immediately sent to the hospital. Laboratory tests showed that the serum concentration of carbamazepine was 58.7-mg/L, creatine kinase was 411-U/L, C-reactive protein was 23.7-mg/L, and blood oxygen saturation was 0.78. Toxic encephalopathy and status epilepticus induced by carbamazepine were diagnosed. Oxygen inhalation, ECG monitoring, intravascular fluid supplement, diuresis, bedside blood filtration, and symptomatic and suppor- tive treatments were given immediately. On the 2nd day, the number of epileptic seizures decreased and the serum concentration of carbamazepine decreased to 32.9-mg/L. On the 3rd day, the patient′s consciousness recovered and seizures occurred occasionally; on the 4th day, the serum concentration of carbamazepine decreased to 12.3-mg/L, and her convulsion disappeared. After 3 days of continued treatments, the patient recovered and discharged.

ObjectiveTo understand the characteristics of medication errors (ME) of traditional Chinese medicine in elderly patientsMethodsME reports of traditional Chinese medicine in elderly patients which were collected from International Network for the Rational Use of Drugs (INRUD) from January 1st, 2013 to November 31st, 2014 were selected and analyzed. The major types of ME, persons who triggered the ME, triggering factor, category, and persons who detected the ME were analyzed descriptively.ResultsA total of 520 ME reports were collected from 23 hospitals. The number of ME on medication usage and dosage in ME types ranked first and accounted for 48.5% (252/520), the number of deployment errors ranked second and accounted for 19.8% (103/520). In terms of the persons  triggering the ME, the percentage of physicians and pharmacists were 70.0% (333/476) and 29.4% (140/476), respectively. Triggering factors of ME were lack of knowledge of traditional Chinese medicine ［30.0% (114/380)］ and similar names of different drugs ［16.3% (62/380)］. Intermediate and primary titles of pharmacists in persons who detected ME accounted for 53.2% (271/509) and 37.5% (191/509), respectively. The ME belonging to category A, B, and C accounted for 16.0% (83/520), 68.5% (356/520), and 13.8% (72/520)］, respectively and all these errors did not do harm to patients. The errors belonging to category D and E accounted for 1.5% (8/520) and 0.2% (1/520), respectively. ConclusionsIn elderly patients, the errors in usage and dosage of traditional Chinese medicine were main types of errors and most of the ME were mild and did not do harm to patients. The triggering factor of the ME were lack of knowledge of traditional Chinese medicines in physicians and pharmacists.

A 27-year-old couple with suppurative tonsillitis received IV azithromycin 0.2 g．The next day，both of them presented with gross hematuria in the whole process of urination．Urinalysis revealed their presence of RBC(+)and(+++)respectively，and protein(+++)．Their liver function，renal function，and ASO were normal． A B-ultrasonic examination found no abnormality in their urinary svstem． Azithromycin was ceased immediately．After treatment with etamsylate，vitamin C，and fluid replacement，their urine became clear gradually．During 1 month of follow-up，their urine routine maintained normalization．

Objective: To investigate the characteristics and causative factors of tiopronin-induced anaphylatic shock for its rational use in clinic. Methods: Domestic medicine periodicals were searched between January 2000 and June 2005, and 38 cases with tiopronin-induced anaphylatic shock were analysed. Results: Routine dosages of tiopronin were administered by intravenous infusion in all cases. 86.84% of the cases developed anaphylactic shock within 30 minutes after administration, more male than female(P<0.01). Clinical symptoms of anaphylactic shock were mainly repid decrease in blood pressure, chest distress, dyspnea and chill. Allergic reactions of skin were uncommon. 97.37% of the cases(37/38) were recovered after treatment, and most cases(81.85%, 31/38)improved within one hour. Conclusion: Physicians should attach importantce to the rational use of tiopronin in clinical practice.

Fluoxetine is one of the selective serotonin reuptake inhibitors, which is often used for treating depression and obsessivecompulsive disorder. Fluoxetine cardiotoxicity includes arrhythmia, torsades de pointes ventricular tachycardia, QT internal prolongation syndrome, serious cardiac damage, and death. The mechanism of cardiac adverse reactions caused by fluoxetine remains uncertain presently. Fluoxetine can cause interactions with some drugs that are metabolized by CYP2D6 leading to cardiac adverse reactions. Clinicians should exercise caution when prescribing fluoxetine to patient with cardiovascular disease, female patients, and elderly patients. ECG monitoring might be performed, if necessary.

A 76-year-old male patient with unstable angina pectoris switched to an IV infusion of imipenem and cilastatin sodium 1.0 g once every 8 hours because of the ineffective treatment of pneumonia with amoxicillin and clavulanate potassium combined with levofloxacin. The platelet count (PLT) was 109×109/L before treatment. After 9 days of medication, the patient′s symptoms of cough and dyspnea were improved, his body temperature returned to normal, but he developed skin petechiae, accompanied by a small amount of epistaxis and hematuria. At the same time, his PLT was 0. Imipenem and cilastatin sodium was immediately discontinued, recombinant human thrombopoietin combined with methylpredniso- lone and human immunoglobulin were given, the patient′s PLT gradually increased and the bleeding symptoms disappeared. Ten days later, his PLT was 173×109/L. It is suggested that high-dose imipenem and cilastatin sodium should be used cautiously in elderly patients and the monitoring should be strengthened during the treatment.

A 48-year-old female patient received chemotherapy with etoposide and carboplatin combined with whole brain radiotherapy for small cell lung cancer located in the right lung with brain metastasis. An IV infusion of toripalimab 240-mg once per 21 days in the 4th cycle of chemotherapy was combined due to tumor progression, and no radiotherapy was given again. After 7 courses of chemotherapy, the patient received monotherapy with toripalimab. On the 2nd day after the 5th administration of toripalimab, the patient developed obvious fatigue, nausea, vomiting, and repeated fever. Laboratory tests showed decreased corticotropin and cortisol (1.5-μg/L, 3.9-μg/L), increased prolactin (127.6-μg/L), and normal thyroid function. Excluding tumor occupation by pituitary magnetic resonance imaging, it was considered as hypophysitis caused by toripalimab. Symptoms disappeared after hydrocortisone replacement therapy was given. After the 9th administration of toripalimab, the patient developed polyuria, thirst, and nocturia. Laboratory tests showed decreased urine specific gravity and urine osmolality (1.010, 132-mmol/L). Diabetes insipidus as the manifestation of hypophysitis caused by toripalimab was considered. The above symptoms were improved after discontinuation of toripalimab and administration of desmopressin. After more than 3 months of the treatment, symptoms of diabetes insipidus disappeared. Then desmopressin was discontinued and diabetes insipidus did not recur.

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.

抗生素滥用现象已引起国内外的严重关注,本文综述了抗生素滥用的根源及促进抗生素合理使用的策略。抗生素滥用根源包括治疗从经验出发、对医生及患者缺乏有效的宣传教育、患者对抗生素不切实际的期望、经济因素等;促进抗生素合理使用的策略包括对医生处方进行干预、实施抗生素控制政策、采用计算机决策支持系统、对医护人员及患者进行抗生素合理使用的宣传教育、引入临床治疗指南、对医疗过程进行审核与反馈以及对特定人群进行疫苗接种等。抗生素的合理使用需要医生、药师、患者的通力协作,避免抗生素的滥用,减少耐药性产生的机会,最终提高抗生素使用的有效性。

Objective To explore the risk signals of brigatinib-related adverse events (AEs) and provide reference for the safe use in clinical practice.　Methods The US FDA Adverse Event Reporting System database was searched and AE reports on brigatinib as the primary suspect drug from April 1, 2017 to March 31, 2022 were collected. AEs were standardized and classified according to the preferred terms (PT) and system organ class (SOC) of Medical Dictionary for Regulatory Activities 24.0. Reported odds ratio (ROR) and proportional reporting odds ratio (PRR) methods were used to mine the AE risk signals of brigatinib. An AE with reports ≥3, ROR≥2, 95% confidence interval (CI) lower limit of ROR>1, or reports ≥3, PRR≥2, and χ2>4 was defined as a positive signal. Positive PT signals were analyzed using descriptive method.　Results A total of 1-564 AE reports were included in the analysis, involving 672 PTs. After analysis using ROR and PRR methods, 52 PTs with positive risk signals were obtained, involving 16 SOCs. The top 10 PTs in report amount were fatigue, diarrhea, nausea, cough, abnormal serum creatine phosphokinase, dyspnea, headache, rash, vomiting, and hypertension, all of which were common AEs in the instructions. The top 10 PTs in signal intensity were pituitary infarction, radiation necrosis, elevated amylase, esophageal varices, early saturation, elevated lipase, abnormal serum creatine phosphokinase, pulmonary toxicity, prolonged activated partial thromboplastin time, and photosensitivity. Among them, the PTs ranked 1st, 2nd, 4th, 5th, 8th, and 10th were not recorded in the label. Pneumonia and interstitial lung disease (ILD) were serious AEs, with 31 and 8 reports, respectively. In the 52 PTs, 28 were not included in the drug label, involving 12 SOCs.　Conclusions The main adverse reactions of brigatinib were diarrhea, nausea, cough, and abnormal serum creatine phosphokinase and serious adverse reactions such as pneumonia and ILD were both reported, which were consistent with the common AE recorded in the drug label. In addition, brigatinib might cause pituitary infarction, radiation necrosis, pulmonary toxicity, photosensitivity, etc., which should be vigilant in clinical practice.

Rituximab is a human/mouse chimeric anti-CD20 monoclonal antibody mainly used in the treatment of non-Hodgkin’s lymphomas. The most common rituximab-caused adverse reaction is acute infusion-related reactions and serious adverse reactions are rare. This article reviews the rituximabinduced rare adverse reactions，such as acute respiratory distress syndrome, diffuse alveolar hemorrhage, cardiac arrhythmia, sudden cardiac death, chronic heart failure, progressive multifocal leukoencephalopathy, tumor lysis syndrome, and cytokine release syndrome, as well as the possible pathogenesis，clinical features, and the management in order to provide references for safe rituximab use in clinical practice.

Pharmaceutical excipients refer to any substances other than the active principal in the pharmaceutical preparation. Their functions are to protect, support or enhance the stability and bioavailability of the active ingredient besides formulating a dosage form. It is reckoned that 40 kinds and more of pharmaceutical excipients including over one thousand different materials are now used in the manufacturing of pharmaceutical products, such as solvents, absorbents, preservations,colouring agents, flavouring agents, thickening agents, antioxidants, and so on. In addition，new classes of excipients have been available in recent years. Pharmaceutical excipients are considered to be inert in contrast to active drug. However, adverse reactions to a wide range of excipients are now documented, such as hemolysis to propylene glycol, gasping syndrome to benzyl alcohol, etc. The safety of pharmaceutical excipients involves their toxicity, quality, and improper use. The clinicians should be aware of the adverse reactions associated with pharmaceutical excipients, and drug regulatory authority should strengthen the management of the safety of pharmaceutical excipients in order to safeguard the patient safety.

Objective To understand the occurrence of intraoperative memory (dream, halluci- nation, and intraoperative awareness) following anesthesia with propofol and sufentanil and analyze its influen- cing factors in patients undergoing painless curettage of the uterine cavity.　Methods The modified Brice questionnaire survey results in patients who underwent painless curettage of the uterine cavity under propofol and sufentanil anesthesia in Shuangqiao Hospital from January 2017 to September 2018 were retrospectively analyzed. The memory of patients from anesthesia induction to consciousness recovery after anesthesia was evaluated, and the incidences of dream, hallucination (including sexual hallucination), and intraoperative awareness were calculated. The possible influencing factors (including age, weight, operation time, initial and total dose of propofol, and total dose of sufentanil) of intraoperative memory after anesthesia with propofol and sufentanil were analyzed using logistic regression method.　Results A total of 2-142 patients were enrolled, aged (28.3±7.4) years and weighing (61.8±10.2) kg, with gestational age of (7.8±1.3) weeks and a median operation time of 5 (3-28) min; the initial dose of propofol was (94.1±20.9) mg, with a total dose of (110.0±39.8) mg; the total dose of sufentanil was (9.9±0.4) μg. Among the 2-142 patients, 1-038 (48.5%) had memory from anesthesia induction to consciousness recovery after anesthesia, 1-019 (98.2%) of which were defined as dreams, 19 (1.8%) as hallucinations, and no one had intraoperative awareness. Eleven of 1-038 patients were defined as having sexual hallucinations and the incidence was 0.5%. There was no significant correlation between the occurrence of intraoperative memory and age, weight, operation time, initial dose and total dose of propofol, and total dose of sufentanil (P>0.05 for all).　Conclusion The anesthesia of propofol combined with sufentanil may lead to dreams and hallucinations in patients undergoing painless curettage of the uterine cavity, and occurrence of sexual hallucinations should be more paid attention to.

本文简述抗精神失常药物所致撤药综合征的基本特征,并对抗精神病药、抗抑郁药所致撤药综合征的临床表现、发生机制与防治以及抗焦虑药引起戒断反应的高危因素、临床表现与防治作一概述。

Selective cyclooxygenase-2 (COX-2) inhibitors are a new type of non-steroidal anti-inflammatory drugs (NSAIDs), which are used in treatment of rheumatoid arthritis and osteoarthritis. Selective COX-2 inhibitors are divided into relatively selective COX-2 inhibitors ( meloxicam, nimesulide and diclofenac acid, and others) and highly selective COX-2 inhibitors( celecoxib, rofecoxib, valdecoxib, etoricoxib，and other). The inhibitory effect of the former against COX-2 is significantly stronger than that against COX-1, but also partially inhibits COX-1 at the same time, while the latter only has strong inhibitory effect on COX-2 inhibitor. The main adverse reactions of selective COX-2 inhibitors are gastrointestinal ulcers, perforation or bleeding, damage to renal function, coagulation disorders and thrombosis. The factors associated with the mechanisms are as follows: the COX-2 inhibitors inhibit both COX-1 and COX-2 at the same time and weaken the protective effects on the gastrointestinal mucosa; the COX-2 inhibitors decrease glomerular filtration rate and increase retention of sodium and potassium; the COX-2 inhibitors inhibit CYP2C9’s activity and decrease warfarin’s metabolic rate; the COX-2 inhibitors affect the balance between thromboxane A2 (TxA2) and prostaglandin I2 (PGI2). Proton pump inhibitors should be taken with the selective COX-2 inhibitors in order to decrease the incidence of gastrointestinal adverse reactions. For the patients with hypertension or sodium retention tendencies, plasma concentration and renal function should be monitored regularly, dose of antihypertensive drugs should be adjusted and coadministration of multiple NSAIDs at the same time should be avoided. Selective COX-2 inhibitors in combination with low-dose aspirin may prevent and cure cardiovascular adverse reactions. If adverse reactions induced by selective COX-2 inhibitors are confirmed, the drug should be discontinued and the symptomatic treatment should be given.

Objective To explore the clinical characteristics of granulomatous mastitis （GM）induced by antipsychotics.　Methods Antipsychotic-related GM cases were collected in Chengdu Women′s and Children′s Central Hospital. Meanwhile, antipsychotic-related GM literature cases in PubMed, Embase, ScienceDirect, Wanfang, VIP, and CNKI databases up to November 2019 were searched. The age, fertility status, primary mental disease, causative agents, duration of medication, diagnosis and characteristics of breast lumps, serum prolactin level, intervention measures, and prognosis of these patients were collected and analyzed retrospectively.　Results A total of 7 clinical patients and 9 literature cases with antipsychotic drug-related GM were collected, and all of them were female, aged 21-55 years, of which 10 patients were never giving birth. They took antipsychotics for 0.5-17.0 years. The causative drugs included risperidone in 8 of the 16 patients. Other antipsychotics included olanzapine, clozapine, sulpiride, aripiprazole, perphenazine, quetiapine, amisulpride, flupentixol and melitracen, and etc. Serum prolactin levels elevated in 12 patients (25.45-84.50-μg/L), were normal in 3 patients, and were not mentioned in 1 patient. Surgical resection was performed in 9 patients. GM were improved significantly in the remaining 7 patients with or without adjusting antipsychotics after receiving oral administration of bromocriptine and/or methylprednisolone. And GM recurred in 1 patient during the followed-up.　Conclusion Antipsychotic-related GM may occur in women of any age, regardless of whether they have giving birth. Risperidone is the main antipsychotic drug causing GM.

A 70-year-old female patient received oral rivaroxaban (10-mg once daily), amiodarone hydrochloride (200-mg thrice daily at the beginning and 200-mg twice daily 8 days later), and isosorbide mononitrate sustained release tablets (30-mg once daily) after radiofrequency ablation of atrial fibrillation. After 5 days of treatments, the patient developed weakness of both legs, which was gradually aggravated. Fifteen days later, the patient presented with weakness of the limbs, limited lifting of arms, inability to hold objects with hands, and inability to stand on legs for a long time. Electromyogram showed peripheral nerve damage. Peripheral neuropathy caused by tumor, metabolism, immunity, and inflammation were excluded by auxiliary examination, and the peripheral neuropathy caused by amiodarone was considered. Amiodarone was discontinued and oral vitamin B1, vitamin B6, and mecobalamin, and an IV infusion of thioctic acid were given. Ten days later, the patient′s symptoms were improved obviously.

A 64-year-old male patient with type 2 diabetes mellitus received metformin 0.5 g thrice daily, acarbose 100-mg thrice daily, and saxagliptin 5-mg once daily orally. The patient developed itching and erythema symptoms during the treatments. The patient learned that metformin could cause adverse reactions such as pruritus and rash by reading the drug label. Then the metformin was stopped by himself and his skin symptoms were relieved within a few days. Due to elevated blood glucose, the patient took metformin again and developed erythema and papules 2 days later, but he didn′t stop the drug. After that, swelling of both lower limbs, accompanied by skin erosion and exudation appeared gradually. Laboratory tests showed that eosinophil count was 0.66×109/L. Drug eruptions caused by metformin was considered. All oral hypoglycemic drugs were stopped and symptomatic treatments such as antihistamine and glucocorticoid were given. Five days later, his erythema and papules gradually subsided, and erosive surface of both lower limbs crusted without exudation. Laboratory tests showed eosinophil count 0.06×109/L. Dermatitis did not recur after the patient switched to insulin to control blood glucose.

Thrombocytopenia is a severe adverse reaction of vancomycin, which can cause hemorrhagic death. The pathogenesis of vancomycin induced thrombocytopenia (VIT) is not clear, and most studies suggest that VIT is related to vancomycin-dependent antiplatelet antibodies IgG and IgM. In vitro studies, it was found that vancomycin induced a series of changes in human platelets, resulting in activation, apoptosis, and reduction of platelets. Clinical manifestations of VIT are various degrees of bleeding. If patient was diagnosed with VIT after ruling out the influencing factors of other diseases or drugs, drug treatment should be promptly withdrawn or changed, and in severe cases, platelets transfusion, corticosteroids, immunoglobulins, rituximab, and hemodialysis should be considered.