Objective To analyze the occurrence and influencing factors of adverse reactions in patients with inflammatory bowel disease (IBD) during the long-term treatment with vedolizumab （VDZ）.　Methods The study was a retrospective observational design. The study subjects were selected from patients who long-termly used VDZ to treat moderate-to-severe active IBD in Tianjin Medical University General Hospital from February 1, 2021 to December 31, 2023. Clinical data of patients were collected through the hospital system of clinical pharmacy management, including general information, IBD condition, VDZ maintenance treatment plan, combination of drugs, laboratory test results, etc. The adverse reactions of VDZ were screened and their clinical manifestations, severity, intervention and outcomes were analyzed descriptively. The patients were divided into 2 groups according to whether VDZ adverse reactions occurred, and the differences in clinical data between them were compared; the influencing factors of adverse reactions were analyzed by multivariate logistic regression method.　Results A total of 142 patients were included in the study, including 81 males and 61 females, aged (37.6±6.4) years with a range from 18 to 57 years. There were 103 patients (72.5%) developed VDZ adverse reactions, which mainly involved skin (52 patients, account for 50.5%), digestive system (33 patients, account for 32.0%) and respiratory system (18 patients, account for 17.5%). All 103 patients did not stop VDZ treatment, and the adverse reaction symptoms disappeared or were relieved after symptomatic treatments. Compared with patients without VDZ adverse reactions, the age of patients with VDZ adverse reactions were higher [(39.5±5.4) years vs. (32.4±6.7) years], and the proportions of patients with chronic relapsing clinical type [65.0%(67/103） vs. 41.0%(16/39)], severe disease activity [60.2%(62/103） vs. 33.3%(13/39)], combined drug use [67.0%(69/103） vs. 46.2%(18/39)], and injecting VDZ once every 4 weeks during maintenance treatment [27.2%(28/103） vs. 10.3%(4/39)] in the group were larger, with statistical significance (all P<0.05). Multivariate logistic regression analysis showed that the chronic relapsing clinical type ［odds ratio (OR)=1.012, 95% confidence interval (CI): 1.001-1.028, P=0.002］, severe disease activity (OR=1.096, 95%CI: 1.010-1.158, P=0.040), combination drugs (OR=1.035, 95%CI: 1.003-1.122, P=0.041), VDZ maintenance therapy injection interval of 4 weeks (OR=1.014, 95%CI: 1.002-1.113, P=0.005) were the risk factors for VDZ adverse reactions.　Conclusions Among IBD patients receiving long-term treatment of VDZ, the incidence of adverse reactions of VDZ was 72.5%, mainly involving skin, digestive system and respiratory system. Symptomatic treatments could be given, and the prognosis was good. Patients with chronic relapsing clinical type, severe disease activity, com- bination therapy, and shorter VDZ maintenance injection interval were at higher risk of adverse reactions.

Objective To explore the clinical features of nivolumab-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN).　Methods Relevant databases at home and abroad (as of December 31, 2023) were searched to collect case reports of nivolumab-induced SJS/TEN, and the demographic characteristics, nivolumab application, combination drugs, clinical manifestations, intervention measures, and outcomes were extracted and analyzed descriptively and statistically.　Results A total of 27 case reports were included and 29 patients were enrolled in the study, including 18 males and 11 females. The age ranged from 45 to 86 years, with an average age of 67 years. The primary diseases were mainly melanoma, stomach cancer, and lung cancer. Twelve patients had records of nivolumab administration, and the dosage was within the recommended range in the labels; 13 patients had records of combination drugs, mainly other antineoplastic drugs, hypoglycemic drugs, antihypertensive drugs, lipid-regulating drugs, etc. The time from using nivolumab to the diagnosis of SJS/TEN was 7 d to 3 years, and 20 patients were <8 weeks. The clinical manifestations were mainly diffuse erythema, flaky skin peeling and erosion, mucosal involvement, etc. Sixteen patients had skin biopsy records, all of which met the histopathological characteristics of SJS/TEN. After the diagnosis of SJS/TEN, 17 patients discontinued nivolumab and received symptomatic treatments, of which 15 patients had improved skin symptoms, one patient had worsened skin symptoms, and one patient had no record of skin outcome; 12 patients had no record of whether or not discontinuing nivolumab, of which 8 patients had improved skin symptoms, 2 patients had worsened skin symptoms, one patient had no record of skin outcome, and one had no record of prognosis. One patient rechallenged nivolumab, severe SJS/TEN recurred. Thirteen of 29 patients died. Of them, 1 died due to cardiac arrest, 4 due to worsened skin rash, and 8 due to primary disease progression.　Conclusions SJS/TEN caused by nivolumab mostly occurs within 8 weeks of treatment, and the clinical manifestations were similar to those caused by other drugs. The mortality rate of nivolumab-induced SJS/TEN is high, and skin rash could be improved after withdrawal of nivolumab and symptomatic treatments.

Objective To mine the risk signals of adverse events (AEs) in mavacamten treatment for hypertrophic cardiomyopathy, and provide reference for safe use of the drug in clinic.　Methods AE reports on mavacamten from June 2022 to June 2024 were collected by searching US Food and Drug Adminis- tration Adverse Event Reporting System (FAERS) database. AEs were classified and standardized according to the system organ class (SOC) and preferred term (PT) of Medical Dictionary for Regulatory Activities version 26.1. Reporting odds ratio (ROR) method and comprehensive standard method of the UK Medicines and Healthcare Products Regulatory Agency (MHRA) were used to mine the AE risk signals. An AE that simultaneously met the criteria of ≥3 reports, lower limit of the 95% confidence interval (CI) of ROR >1, PRR ≥2, and χ2 ≥4 was defined as a risk signal. Descriptive statistical analysis on signals was performed.　Results A total of 1 041 AE reports were collected, involving 47 PTs and 12 SOCs. The top 10 risk signals based on the number of AE reports were dyspnea, dizziness, fatigue, atrial fibrillation, cardiac failure, palpitation, nasopharyngitis, chest pain, COVID-19, and weight increased. Except dizziness and heart failure, above AEs were not recorded in the label. The top 10 risks in signal intensity were acquired left ventricle outflow tract obstruction, transvalvular pressure gradient increased, cardiovascular symptom, echocardiogram abnormal, hypervolaemia, left ventricular failure, ejection fraction decreased, coronavirus infection, brain fog, and atrial fibrillation. Except cardiovascular symptom, left ventricular failure, and ejection fraction decreased, above AEs were not recorded in the label.　Conclusions The AE risk signals of mavacamten in the treatment for hypertrophic cardiomyopathy recorded in the label are mainly heart failure and ejection fraction decreased. Clinicians and pharmacists should also be vigilant against risk signals not recorded in the lakel, such as atrial fibrillation, fatigue, nasopharyngitis, coronavirus infection, and brain fog, etc.

Objective To analyze the risk factors of hypocalcemia in 3-5 stages of chronic kidney disease (CKD) patients with hyperkalemia and non-dialysis after potassium lowering therapy.　Methods Clinical data of 3-5 stages of CKD patients with hyperkalemia and non-dialysis treated in Linyi Central Hospital from January 2019 to November 2024 were collected through the electronic medical record system. According to whether the corrected calcium level after potassium lowering treatments was lower than 2.12 mmol/L, the patients were divided into hypocalcemia group and non-hypocalcemia group. The gender, age, body mass index, primary disease, disease duration, comorbidity, use of potassium lowering drugs, concomitant medication, and blood potassium, corrected calcium, carbon dioxide binding capacity, blood magnesium, blood phosphorus, estimated glomerular filtration rate, and total parathyroid hormone before potassium lowering treatments between the 2 groups were compared. Multiple logistic regression analysis was used to identify the risk factors for hypocalcemia in 3-5 stages of CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy.　Results A total of 260 patients were entered, including 58 with blood calcium lower than 2.12 mmol/L, and incidence of hypocalcemia was 22.3%. The differences in the baseline corrected calcium, blood phosphorus, carbon dioxide binding capacity, estimated glomerular filtration rate, and total parathyroid hormone between the hypocalcemia group and the non-hypocalcemia group were statistically significant (P<0.05). The factors with P<0.1, including primary disease, baseline corrected calcium, blood phosphorus, carbon dioxide binding capacity, estimated glomerular filtration rate, and total parathyroid hormone, were included in the multivariate logistic regression analysis. The results showed that the probability of hypocalcemia at baseline corrected calcium levels of 2.12-2.21, 2.22-2.31, and 2.32-2.41 mmol/L was 49.306 times, 13.651 times, and 13.342 times that of at ≥2.42 mmol/L, respectively. Low carbon dioxide binding capacity (odds ratio=0.909, 95% confidence interval: 0.836-0.987) was also a risk factor of hypocalcemia in 3-5 stages CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy.　Conclusions Three to five stages of CKD patients with hyperkalemia and non- dialysis are prone to hypocalcemia after potassium lowering therapy. The low levels of baseline corrected calcium and carbon dioxide binding may be closely related to the occurrence of hypocalcemia in 3-5 stages of CKD patients with hyperkalemia and non-dialysis after potassium lowering therapy.

Iron deficiency is the most common cause of anemia. Intravenous iron is a common therapeutic drug for iron deficiency and iron deficiency anemia, which is commonly used in the treatment of anemia patients with chronic kidney disease, heart failure, inflammatory bowel disease, and cancer, as well as anemia patients in perioperative period and during pregnancy and lactation. In order to strengthen the rational use of intravenous iron and improve the pharmaceutical care level, the Chinese Pharmacological Society Professional Committee of Drug-induced Diseases and the Guangdong Pharmaceutical Association organized experts majoring in medicine, pharmacy, nursing, hospital mana- gement and other specialties to develop this consensus through discussing, retrieving domestic and foreign literature, and collecting evidence-based medical evidence. The differences among intravenous iron agents, clinical situations of applica- tion, and the safety issues are considered in the consensus, in order to provide the basis for the rational application and pharmaceutical care in clinic.

Sodium-glucose transporter 2 inhibitors (SGLT2i) are currently widely used as a class of hypoglycemic drugs. Due to their unique hypoglycemic mechanism and significant cardio-renal protective effect, SGLT2i have become one of the core drugs in the treatment of type 2 diabetes mellitus. However, in recent years, it has been found that SGLT2i can lead to increased serum creatinine and urea nitrogen in some patients, and the risk of kidney injury has gradually attracted clinical attention. How to effectively prevent and supervise the potential renal injury risk while giving full play to its therapeutic advantages has become an important topic in current clinical practice and drug safety management. Multi-dimensional prevention and supervision strategies should be adopted in clinical practice such as identifying high-risk populations based on the latest evidence, strictly screening patients, dynamically monitoring renal function, optimizing combination medication regimens, and achieving risk warning using biomarkers and artificial intelligence tools.

Objective To analyze the characteristics of Fournier gangrene (FG) induced by sodium-glucose cotransporter 2 inhibitors (SGLT2i), and provide reference for clinical safe drug use.　Methods CNKI, Wanfang Med Online, VIP, PubMed, Web of Science and other databases (up to January 2024) were retrieved and clinical data on patients with FG associated with the 5 kinds of SGLT2i currently used in clinical practice in China were collected and descriptively analyzed, including gender, age, comorbidities, concomitant medications, onset time and clinical manifestations of SGLT2i-related FG, laboratory and imaging examination results, treatment and outcomes, etc.　Results A total of 15 documents were included in the analysis, involving 15 patients, with 12 males and 3 females. The age of these patients ranged from 34 to 72 years, with 11 cases being over 50 years. Dapagliflozin was used in 7 cases, empagliflozin in 6 cases, canagliflozin in 2 cases, and no related reports on ertugliflozin and henagliflozin were collected. The main clinical manifestations of the 15 patients were redness, swelling, pain, abscess or purulent discharge in perineum, scrotum and perianal, etc. The time from application of SGLT2i to onset of FG ranged from 1 month to 6 years. Wound secretion bacterial culture was performed in 10 patients, and the results were all positive, including 9 cases of bacterial infection and 1 case of mixed infection of bacteria and fungi. All 13 patients who underwent imaging examinations had imaging manifestations related to FG. SGLT2i were discontinued in all patients. After treatments with broad-spectrum antibiotics and surgery, 14 cases were improved and 1 case was cured.　Conclusions SGLT2i has the risk of causing FG, which is more common in males. The clinical use of SGLT2i should be monitored closely. Secretion culture and imaging examination are helpful for the diagnosis of FG. The patient′s prognosis is good after discontinuation of medication, symptomatic treatment, and surgery.

Objective To mine the adverse event (AE) risk signals of semaglutide and liraglutide in weight management populations, and provide references for the safe use of these drugs in relevant patients.　Methods The reporting odds ratio (ROR) method, proportional reporting ratio (PRR) method, Bayesian confidence propagation neural network (BCPNN) method, and empirical Bayesian geometric mean (EBGM) method were used to mine the AE risk signals of semaglutide and liraglutide in weight management populations from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1st quarter of 2010 to the 4th quarter of 2023. Adverse events that met the criteria of all 4 mining methods were considered as risk signals. The adverse events were classified and statistically analyzed using the system organ class (SOC) and preferred term (PT) of the 26.1 version of the Medical Dictionary for Regulatory Activities 26.1 version, and the identified risk signals were analyzed.　Results During the set period, 2 292 AE reports for semaglutide for weight management (excluding diabetes) and 2 973 for liraglutide were retrieved. The semaglutide-related AE reports involved 83 PTs, among which 57 were already recorded in the instructions and 26 were not. Among the 26 PTs not recorded in the labels, the top 5 PTs in terms of AE report numbers were increased appetite, hunger, panic attack, binge eating, and feeling cold; the top 5 PTs in terms of ROR values were lack of satiety, hunger-induced ketoacidosis, myoglobinuria, binge eating, and bulimia. The liraglutide-related AE reports involved 74 PTs, among which 60 were already recorded in the instructions and 14 were not. Among the 14 PTs not recorded in the labels, the top 5 PTs in terms of AE report numbers were weight gain, increased appetite, binge eating, weight fluctuation, and pancreatic cyst; the top 5 PTs in terms of ROR values were lack of satiety, binge eating, hepatic adenoma, increased appetite, and pancreatic cyst. Three PTs of severe AEs that were not recorded in the labels for semaglutide were identified, namely, olfactory abnormality, ketoacidosis, and panic attack. One PT of severe AE that was not recorded in the labels for liraglutide was identified, namely, metastatic pancreatic cancer.　Conclusion The AE risk signals of semaglutide and liraglutide in weight management include AEs not recorded in the labels, and some are even serious AEs, which need to be identified and prevented in clinical practice.

Objective To understand the influencing factors for cardio-cerebrovascular complications in patients with T2DM and construct a nomogram risk prediction.　Methods The study design was a prospective observational study, and the subjects were selected from hospitalized patients with T2DM admitted to Huangshan City People′s Hospital from May 2022 to April 2023. Data on patients' gender, age, body mass index, alcohol consumption, smoking status, family history of cardio-cerebrovascular diseases, insulin use, duration of diabetes, blood pressure, and routine laboratory test results were collected using the hospital electronic medical record system. At discharge, patients were assessed using the T2DM-Specific Medication Belief Scale (total score range: 10-50), Medication Literacy Assessment Scale (total score range: 0-7), and Morisky Medication Adherence Scale (total score range: 0-8). Patients were followed up by telephone for 6 months after discharge and divided into 2 groups based on the occurrence of cardio-cerebrovascular complications. Logistic regression analysis was performed using SPSS 26.0 software to identify influencing factors for cardio-cerebrovascular complications in T2DM patients. A nomogram prediction model was constructed using R 4.1.0 software, and internal validation of the model was conducted using the Bootstrap method.　Results A total of 294 T2DM patients were included in the analysis. The medication belief score was (32.6±5.6) score, the medication literacy score was (4.2±0.5) score, and the medication adherence score was (6.1±0.8) score. During the 6 month follow-up, a total of 43 patients (14.6%) experienced cardio- cerebrovascular complications, including of coronary heart disease (23 cases), heart failure (12 cases), and stroke (8 cases). Compared to patients without cardio-cerebrovascular complications, patients with complications had higher body mass index, glycosylated hemoglobin A1c (HbA1c), D-dimer, and uric acid levels, as well as lower medi- cation belief scores, medication literacy scores, and medication adherence scores (all P<0.05). Binary logistic regression analysis showed that HbA1c, D-dimer, uric acid, medication belief, medication literacy, and medication adherence were influencing factors for cardio-cerebrovascular complications in T2DM patients. Accordingly, a nomogram prediction model was established. Internal validation results of the model showed that the concordance index was 0.958, the area under the receiver operating characteristic curve was 0.824, and the calibration curve was close to the ideal curve.　Conclusions The current status of medication belief, medication literacy, and medication adherence in T2DM patients was not ideal. High levels of HbA1c, D-dimer, and uric acid, as well as poor medication belief, medication literacy, and medication adherence were risk factors for cardio-cerebrovascular complications in T2DM patients. The nomogram model, which integrated multiple influencing factors, had high value in predicting the risks.

Intravitreal injection (IVI) is an administration technique that uses a syringe to deliver drugs into the vitreous cavity. Currently, multiple IVI drugs have been successively approved for the treatment of various fundus diseases, including antivascular endothelial growth factor drugs, intravitreal sustained- release glucocorticoid drugs, and so on. Meanwhile, there are many injection drugs off label used by IVI. At present, there is a lack of pharmaceutical care guidance documents for the clinical application of IVI drugs. To promote the development of pharmaceutical care for IVI drugs, Ophthalmic Pharmacy Professional Committee of Peking Safety Medicine Foundation, Medicine Therapy Management Working Committee of Chinese Pharmacists Association, and Clinical Pharmacy Branch of China International Exchange and Promotive Association for Medical and Health Care organized experts to formulate this consensus based on clinical practice experience and with reference to relevant domestic and foreign research data, guidelines, and literature. This consensus combs the characteristics of clinical application of IVI drugs, relevant pharmaceutical services before, during and after injection, and forms 26 recommendations for 5 clinical issues, which can be used by medical institutions at all levels to carry out pharmaceutical services of IVI drugs. The users are medical staff in medical institutions at all levels (including pharmacists, physicians, nurses, and other relevant staff), and the target population for application is mainly patients using IVI drugs.

Drug-induced neurological disorders (DINDs) refer to the central or peripheral nervous system disease caused by drugs. DINDs account for a large proportion of adverse drug reactions/events in China, and its onset is complex to some extent. Common DINDs include epilepsy, movement disorders, stroke, peripheral neuropathy, spinal cord injury, cognitive impairment and so on. Usually, DINDs have characters of gradual development and late-onset reactions, and it is difficult to associate their clinical manifestations with drugs, leading to misdiagnosis and poor prognosis in clinic. To reduce the neurotoxicity of drugs, multidisciplinary cooperation should be strengthened, and individualized treatment plans for high-risk people and closer monitoring should be implemented for timely identification and diagnose. At the same time, relevant researches on DINDs should be strengthened in the clinic to cope with the complexity and long-term prognosis challenges of the diseases.

Objective Based on the adverse drug event active surveillance and assessment system-Ⅱ (ADE-ASAS-Ⅱ) and the information of inpatients in the hospital information system (HIS), the automatic monitoring module of movement disorders was constructed and its application effect in the real- world study of drug-induced movement disorders (DIMDs) was explored.　Methods Literature reviews, case reports, spontaneous reports and medical records were collected, the keyword set was screened based on ADE-ASAS-Ⅱ system and text classification technology, and an automatic monitoring module was constructed. The information of hospitalized patients in Chinese PLA General Hospital （our hospital） was selected from October 10 to 16, 2022. The results of manual evaluation and the system alarm by the automatic monitoring module were compared, and the performance of the automatic monitoring module was evaluated and optimized through repeated machine learning. The medical record information of hospitalized patients who used sodium valproate throughout the year in our hospital in 2022 were collected, and the occurrence of movement disorders related to sodium valproate was analyzed using the automatic monitoring module.　Results A total of 4 918 hospitalized patients (146 with movement disorders) were collected, and the final setting conditions of the automatic monitoring module were determined, including inclusion criteria (43 text keywords, 3 diagnosis) and exclusion criteria (11 text and 20 document titles were omitted). Among the 1 138 hospitalized patients using sodium valproate in 2022, the incidence of DIMDs with tic and tremor as main clinical manifestations detected by automatic monitoring module was 1.67% (19/1 138).　Conclusion The automatic monitoring module of druginduced movement disorders based on machine learning and manual evaluation can be applied to explore the occurrence characteristics of DIMDs in the real world, and provide information for pharmacovigilance in clinic.

Objective To understand the clinical characteristics of myelopathy induced by intrathecal chemotherapy of methotrexate (MTX) and/or cytarabine (Ara-C).　Methods Relevant databases at home and abroad (up to February 18, 2024) were searched and case reports of myelopathy induced by intrathecal chemotherapy of MTX and/or Ara-C were collected. The patients′ general situation (gender, age, primary disease, etc.), use of MTX and/or Ara-C, previous radiotherapy, and occurrence time, clinical manifestations, spinal magnetic resonance imaging (MRI) results, cerebrospinal fluid test results, treatments and outcomes of myelopathy were extracted and analyzed descriptively and statistically.　Results A total of 75 articles were enrolled, involving 104 patients, with 62 males, 35 females, and 7 unknown genders. Their ages ranged from 1 to 74 years, with a median age of 26 years. The primary diseases included hematological malignancy in 101 cases, and other solid tumors in 3 cases. Before the occurrence of myelopathy, 42 cases had central nervous system tumor infiltration. Seventy-three patients received intrathecal injection of MTX combined with Ara-C, 21 patients received single MTX therapy, 10 patients received single Ara-C therapy. The number of intrathecal injections ranged from 1 to 62, with a median of 5 injections. Twenty-nine patients had received radiotherapy before. When myelopathy occurred, the cumulative dose of MTX was 7.5-480.0 mg, with a median cumulative dose of 60.0 mg; the cumulative dose of Ara-C was 15 1 599 mg, with a median cumulative dose of 280 mg. The onset time of myelopathy was from immediately to 365 days after the last intrathecal injection, with a median time of 2 days. The main clinical manifestations were weakness of both lower limbs, urinary and fecal incontinence or retention, paresthesia, and paraplegia, etc. Fifty-three patients had spinal abnormality in MRI examination, 32 had abnormal cerebrospinal fluid protein quantity, intrathecal basic protein, or homocysteine. After the diagnosis of myelopathy, 86 patients were treated with drugs, radiotherapy, plasma exchange, and cerebrospinal fluid exchange, and 18 patients had no record of treatment situation. Therapeutic agents included glucocorticoids, B vitamins, folic acid, immunoglobulin, leucovorin, S-adenosylmethionine, and dextromethorphan. Of the 104 patients, 20 achieved complete remission, with a median remission time of 30 hours; 25 experienced partial remission, with a median duration of 120 days; 32 showed no significant improvement; 26 died; one patient′s prognosis and outcome were unknown.　Conclusions The median occurrence time of myelopathy induced by intrathecal injection of MTX and/or Ara-C is 2 days. The main clinical manifestations are bilateral lower extremity weakness, urinary and bowel incontinence or retention, paresthesia, and paraplegia, etc. Abnormal spinal in MRI examination, quantitative cerebrospinal fluid protein, intrathecal basic protein occurred in some patients. Intrathecal injection should be stopped immediately after diagnosis of myelopathy, and the treatments such as drug and cerebrospinal fluid replacement should be given. The clinical outcome of myelopathy induced by intrathecal MTX and/or Ara-C was poor.

Objective To understand the clinical characteristics of hypophysitis due to nivolumab and provide reference for the safe use of nivolumab in clinic.　Methods Relevant databases at home and abroad (up to May 31, 2024) were searched and case reports of hypophysitis caused by nivolumab were collected. Relevant information of patients (gender, age, primary disease), single and combined use of nivo- lumab, occurrence of hypophysitis, causality evaluation, intervention measures and outcomes were extracted and analyzed descriptively and statistically.　Results A total of 56 case reports, 53 in English and 3 in Chinese, were enrolled in the analysis, involving 59 patients, with 40 males and 19 females. Their ages ranged from 26 to 84 years, with an average age of 61 years. The primary diseases were malignant melanoma in 20 cases, renal cell carcinoma in 19 cases, lung cancer in 11 cases, glossopharyngeal cancer in 4 cases, esophageal cancer in 2 cases, and gastric cancer, colon cancer and pleural mesothelioma in 1 case each. Among the 59 patients, 33 were treated with nivolumab monotherapy, 24 with nivolumab and ipilimumab, 1 with nivolumab and anlotinib and 1 with nivolumab and platinum. The average time of hypophysitis caused by nivolumab alone was 25.6 weeks after treatment, and that caused by the combination therapy was 9.9 weeks after treatment. The main clinical manifestations of hypophysitis caused by nivolumab were fatigue, anorexia, headache, and nausea. Among the 59 patients, 56 patients discontinued nivolumab and received glucocorticoid, 20 of whom resumed nivolumab treatment after improvement of clinical symptoms; 3 patients′ situation was not described clearly. The outcomes of the 59 patients were as follows. Four were recovered, 46 were relieved, 2 patients′ pituitary function was not recovered, 4 died, 1 developed secondary autoimmune vasculitis, 1 developed secondary autoimmune hepatitis, and it was unknown in one patient.　Conclusions The average occurrence time of hypophysitis caused by nivolumab monotherapy is longer than that caused by combination therapy. The main clinical manifestations are fatigue, anorexia, headache, etc. After timely discontinuation of medication and symptomatic treatments with glucocorticoid, most patients have a good prognosis, but it can lead to death in severe cases.

With the aging of the population and the increasing number of patients with throm- boembolic diseases, oral anticoagulants are more and more widely used. Anticoagulant-related nephropathy (ARN) is a significant adverse reaction in the treatment with oral anticoagulants, generally considered to be a form of acute kidney injury caused by excessive anticoagulation. The mechanisms involved may include glomerular hemorrhage, obstruction of renal tubules by red cell casts, and damage to tubular epithelial cells. Abnormalities in coagulation function and renal function are the main risk factors for ARN; older age, diabetes mellitus, and cardiovascular diseases such as hypertension and heart failure also increase the  risk of ARN occurrence. ARN should be managed based on individual patient characteristics. Benefits and risks of treatment should be carefully considered when choosing oral anticoagulants; renal function should be closely monitored during treatments to detect potential risks early. In case of ARN, it is advised to promptly adjust the anticoagulant therapy and provide symptomatic supportive treatments. In severe cases, treatments with methylprednisolone combined with hemodialysis can be employed.

Objective To explore the effect of concomitant amiodarone on the bleeding risk in atrial fibrillation patients treated with dabigatran etexilate.　Methods This study was a retrospective cohort study. The clinical data of hospitalized patients with atrial fibrillation who took dabigatran etexilate in Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology from July 1, 2022 to June 30, 2023 were collected. Patients were divided into concomitant amiodarone group and non concomitant amiodarone group according to whether they were treated with oral amiodarone. Propensity score matching (PSM) was performed at a 1∶1 ratio in patients between the 2 groups according to patient's gender, age, main basic diseases and the number of basic diseases, baseline liver and kidney function, dosage of dabigatran etexilate, etc. The incidence of bleeding events was compared between the 2 groups.　Results A total of 878 patients were included in the study, including 568 males (64.7%) and 310 females (35.3%), with a age of 67 (59, 74) years. There were 252 patients (28.7%) in the concomitant amiodarone group and 626 patients (71.3%) in the non concomitant amiodarone group. Within 3 months of follow-up, the incidence of bleeding events in patients of concomitant and non concomitant amiodarone groups were 19.0% (48/252) and 21.2% (133/626), respectively, which were 19.0% (48/252) and 16.7% (40/239) after PSM, respectively, with no significant difference (all P>0.05). The main type of bleeding in patients of both groups was mild bleeding events ［62.5% (30/48) vs. 67.5% (27/40)］, and bleeding was more common in the gums, skin, and nose. There was no statistically significant difference in incidence of the bleeding types and bleeding sites of patients between the 2 groups (all P>0.05).　Conclusions Compared with patients with atrial fibrillation when treated with dabigatran etexilate and without concomitant amiodarone, the bleeding risk of patients with amiodarone did not significantly increased in the short term. The bleeding events during treatment of dabigatran etexilate were mainly mild bleeding, but clinical vigilance was still necessary.

Objective To mine the risk signal of acute kidney injury (AKI) induced by different oral anticoagulant drugs (OACs) in various populations and provide a reference for clinical use of OACs.　　Methods Reports of AKI induced by OACs and non-OACs in the US Food and Drug Administration Adverse Event Reporting System database from the 1st quarter of 2004 to the 3rd quarter of 2023 were collected. The relationship between the drugs mentioned above and the AKI in patients were analyzed by methods of reporting odds ratio (ROR) and Bayesian confidence propagation neural network (BCPNN). When the number of reports of the target adverse event (AE) for the target drug was ≥3, and the lower limit of the 95% confidence interval (CI) of ROR was >1 or the lower limit of the 95%CI of the information component (IC025) was >0, it indicated a statistically significant association between the target drug and the target AE.　Results A total of 12 402 AKI reports related to OACs were collected, including 1 313 for warfarin, 3 086 for dabigatran, 4 730 for rivaroxaban, 2 918 for apixaban, and 365 for edoxaban; 454 378 AKI reports were related to non-OACs. The overall analysis of OACs showed an ROR (lower limit of 95%CI) of 1.791 (1.759) and an IC (IC025) of 0.813 (0.787) for AKI caused by OACs. Analysis of individual OACs showed that warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban all posed risks for AKI, with ROR (lower limit of 95%CI) of 1.220（1.156）, 2.386（2.302）, 2.044（1.986）, 1.375（1.326）, 3.003（2.706）, respectively, and IC (IC025) of 0.284（0.204）, 1.231（1.178）, 1.010（0.968）, 0.452（0.399）, 1.560（1.407）, respectively. Edoxaban had the highest ROR and IC values, while warfarin had the lowest. Subgroup analysis showed that in the <18 years subgroup, neither warfarin nor rivaroxaban showed a risk of AKI; the ROR method did not show dabigatran to have a risk of AKI, but the BCPNN method did. In the 18-45 years subgroup, both methods showed that apixaban did not have a risk of AKI, while all other OACs did. In the 45-64 years subgroup, all OACs showed a risk of AKI. In the ≥65 years subgroup, warfarin and apixaban posed risks for AKI. Gender subgroup analysis showed that both methods indicated a risk of AKI with warfarin in males; all OACs showed a risk of AKI in females.　Conclusions OAC has a statistically significant risk of AKI, among which edoxaban has the highest risk intensity and warfarin has the lowest. Different OACs have different risks of AKI in patients with different ages.

Objective To explore the risk factors of severe medication errors (ME) of tranexamic acid injection (TXAI), and put forward prevention suggestions.　Methods TXAI-related ME reports in the National Monitoring Network for Clinical Safe Medication (Monitoring Network) and medical literature databases at home and abroad were searched, and case reports of TXAI-related ME were collected; China Judgements Online and PKULAW database were searched, and TXAI-related judicial cases judged to be responsible by the hospital were collected. The retrieval time of all data was up to May 1, 2024. The severity grade, occurrence link and place, and the trigger person of TXAI-related ME reported in the Monitoring Network were retrospectively analyzed. The year of report, country of occurrence, clinical application, error content, and occurrence place of the collected severe ME cases, and the clinical characteristics of patient injury, patient outcome and the ME grading were retrospectively analyzed.　Results From September 22, 2012 to May 1, 2024, the Monitoring Network received a total of 138 TXAI-related ME reports, and there was an increasing trend in the number of reports year by year. Among 138 cases of ME, 79 (57.3%) occurred in the drug dispensing and distribution link; 58 (42.0%) occurred in the prescription/doctor′s order prescribing and delivery link and mainly involved easily mixed drugs and drug overdose, of which 1 (1.7%) was a severe ME (grade E); 1 (0.7%) occurred in the drug administration link, and iodohexol was mistakenly injected as TXAI into the patient′s joint cavity. A total of 29 severe ME reports related to TXAI were collected. Of them, 24 (82.8%) were due to incorrect administration routes (22 were confused with anesthetics and 2 were confused with injection catheters, all resulting in incorrect intrathecal injections) and 5 (17.2%) were due to prescription errors (3 were overdosed, 1 was used for high-risk thrombosis patient, and 1 was treated with combination use of hemocoagulase for high-risk thrombosis patient); 23 (79.3%) occurred in the operating rooms, and 6 (20.7%) occurred in the wards. The 24 patients involved in incorrect intrathecal injections of TXAI mainly developed severe pain, neurotoxicity (status epilepticus) and/or cardiotoxicity (arrhythmia and ventricular fibrillation), of which 11 (45.8%) died and 2 (8.3%) had sequelae of limb muscle weakness. Among the 5 patients with prescription errors, 4 developed severe thrombotic disease, resulting in 2 deaths and 2 cerebrovascular-related sequelae, and the other one developed palpitation, shortness of breath, nausea and vomiting. Among the 29-severe ME cases, 2 (6.9%) were grade E, 3 (10.3%) were grade F, 4 (13.8%) were grade G, 7 (24.2%) were grade H, and 13 (44.8%) were grade I.　Conclusions TXAI-related ME mainly involved easily mixed drugs and prescription errors. The severe ME main occurred in the operating room and mainly due to incorrect intrathecal injection, leading to fatal neurological and cardiac toxicity in patients.

With the rapid progress of cancer treatment, the treatment of chronic kidney disease (CKD) in cancer survivors has become more and more important in clinical practice. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, in which the epidemiology, influencing factors, and treatment options of CKD in cancer survivors was comprehensively discussed. The above guideline emphasizes the complexity of managing CKD in cancer survivors from the perspective of clinical practice, and puts forward personalized treatment recommendations for this special population. This article interprets this chapter in the guideline in order to provide reference for clinicians.

Intravenous infusion has played an important role in emergency treatments in China, but there is also the phenomenon that emergency infusion is overused. The high burden of emergency infusion may cause more medication safety problems, such as adverse drug reactions, medication errors, drug interactions, and so on. The risks in emergency infusion should be paid high attention to. We should actively construct a comprehensive management model for the prevention and control of emergency infusion safety risks by strengthening multidisciplinary cooperation, avoid unnecessary intravenous infusion, and develop diagnostic criteria and treatment guidelines for adverse events in intravenous infusion, so as to better ensure the medication safety in emergency patients treated with intravenous infusion.

Objective To investigate the clinical characteristics and interventions associated with drug-induced anaphylaxis in the emergency infusion room.　Methods Bases on the adverse drug reaction database from the emergency medicine center of the First Affiliated Hospital of Nanjing Medical University, clinical data of patients who experienced drug-induced anaphylaxis in the emergency infusion room between November 2019 and November 2023 were collected, including gender, age, history of previous adverse drug reactions, allergy history, Charlson comorbidity index, medication details, information related to drug-induced anaphylaxis (onset time, clinical manifestations), interventions, outcomes, and follow-up. The clinical characteristics and interventions in these patients were analyzed.　Results During the study period, a total of 398 772 patients in the emergency infusion room in our hospital received intravenous infusion of drugs. Of them, 625 cases developed adverse drug reactions (ADRs) and 75 cases developed drug- induced anaphylaxis, accounting for 0.02% (75/398 772) of the total infusion patients and 12.0% (75/625) of all ADR cases. Of the 75 patients with anaphylaxis, 30 cases (40%) were classified as grade Ⅱ, and 45 cases (60%) as grade Ⅲ, with no grade Ⅳ cases. The most common drugs involved in 75 cases of anaphylaxis were anti-infective drugs (41 cases, 54.7%). Drug-induced anaphylaxis exhibited diverse clinical manifestations, with cardiovascular symptoms being the most common, primarily varying degrees of transient hypotension (67 cases, 89.3%), followed by systemic and neurological symptoms, including profuse sweating (31 cases, 41.3%) and dizziness (28 cases, 37.3%). All 75 patients with anaphylaxis were treated with measures such as discontinuation of medication, replacement of infusion sets, rapid assessment of circulation and respiration, and monitoring of vital signs, of which 65 (86.7%) received rapid intravenous infusion for volume expansion, 6 (8.0%) received intravenous injection of glucocorticoids, 3 (4.0%) received intramuscular injection of 0.5 mg epinephrine, and 2 (2.7%) received antihistamines. All 75 patients showed improvement in symptoms, and no sequelae or deaths were found.　Conclusions In the emergency infusion room, the severity of anaphylaxis is mainly grade Ⅱ and Ⅲ with a good prognosis after timely intervention. The treatment measures mainly focus on rapid intravenous infusion for volume expansion, and the use of epinephrine is relatively low.

Objective To explore the occurrence and clinical characteristics of infusion-related reactions (IRRs) caused by lecanemab in Chinese patients with Alzheimer disease, and summarize the nursing management experience of IRRs.　Methods This study was a single center retrospective study and the subjects were Alzheimer′s disease patients who received lecanemab (10 mg/kg, once every 2 weeks) in the Department of Neurology, Xuanwu Hospital, Capital Medical University from June 26 to August 18, 2024. The occurrence, clinical characteristics, severity, and outcome of IRRs that occurred during the treatment of lecanemab in these patients were descriptively analyzed.　Results A total of 45 patients were included in the study, including 15 males (33.3%) and 30 females (66.7%); the age ranged from 52 to 82 years, with a median age of 62 years. Among the 45 patients, 15 (33.3%) developed IRRs, including 6 males and 9 females, and 2 of them had a previous history of allergy. In the 15 patients, there were 3, 8, 1 and 3 patients with 1, 2, 3 and 4 treatment cycles, respectively; 13 patients were pretreated with diphenhyd-ramine 30 minutes before lecanemab treatment; 14 patients had IRRs in the first cycle of lecanemab treatment, and 1 in the second cycle; IRRs occurred within 5 hours after finishing the intravenous infusion of lecanemab in 13 patients and on the second day after the administration in 2 patients. The main manifestations of IRRs were fever and chills; some patients had headache, nausea, and vomiting symptoms, and only 1 patient developed rash and itching. After symptomatic treatments, these symptoms in the 13 patients were relieved soon, and IRRs did not recur after the continued treatment of lecanemab according to the regime. The severity of IRRs was grade 1, 2, and 3 in 5, 9, and 1 patient, respectively. The incidence of severe IRRs was 2.2% (1/45).　Conclusions IRRs are common adverse reactions of lecanemab, mainly characterized by fever and chills, with mild severity. Generally, lecanemab-related IRRs occurs after the first administration, and may not occur again in the continued treatments. Vital signs should be routinely monitored in lecanemab treatment. Once IRRs occur, timely treatments should be given according to the severity, and the prognosis is usually good.

Anticancer drugs are important causes of kidney injury in cancer patients. Once kidney injury occurs, it will affect anticancer therapy and patient prognosis. Thus, the Japanese Society of Nephro- logy, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated the Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022 and made a particular discussion on the prevention and management of anticancer drug-induced kidney injury. This article focuses on interpreting the management of kidney injury related to cytotoxic anticancer drugs, targeted therapies, and immune checkpoint inhibi-tors to more effectively guide clinical practice.

The safety of traditional Chinese Medicine (TCM) has garnered widespread attention and has become a major obstacle to its further development and internationalization. The complexity of TCM and the unpredictability of its interactions with the human body pose significant challenges to safety research. The causes of TCM safety issues are multifaceted, including intrinsic and extrinsic toxicity, confusion of herbal sources and misuse in clinical practice, inadequate patient awareness of safe medication use, and insufficient regulatory oversight of TCM quality and safety. To strengthen the risk managements, it is essential to employ scientific technologies to investigate the fundamental nature of TCM safety, leverage artificial intelligence for big data analysis and early risk warning, promote the scientific concept of safe TCM use, and establish a comprehensive lifecycle pharmacovigilance system for TCM. These will facilitate TCM safety research in China, ensure patient medication safety, and promote the healthy and sustainable development of the TCM industry and its internationalization.

Objective To explore the status and problems of safety recommendations in clinical practice guidelines and expert consensuses (guidelines/consensuses) on Chinese patent medicine (CPM) in China.　Methods Wanfang Med Online, CNKI, VIP, China Biology Medicine Database, Chinese Medical Journal Full Text Database, and the websites of Medlive, and China Association of Chinese Medicine were searched, and the guidelines/consensuses related to CPM were collected. The basic information, types, subject areas, evidence rating methods, safety reporting items, safety recommendation levels, and evidence sources of these guidelines/consensuses were extracted and analyzed by descriptive statistics.　Results A total of 138 guidelines/consensuses were included in the analysis, including 19 guidelines and 119 consensuses. The first guideline/consensus on CPM was published in 2004. Five, 3, 9, 15, 29, 32, 29, and 11 guidelines/consensuses were published respectively from 2016 to 2023. From 2020 to 2023, 101 guidelines/consensuses were published, which was 2.73 times the total number of those published in the past 16 years.(101/37). Among the 138 guidelines/consensuses, 59 (42.75%) were "disease?based" and 79 (57.25%) were "drug?based". The top 5 institutions in terms of the number of publications were National Administration of Traditional Chinese Medicine, China Association of Chinese Medicine, Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences, Chinese Association of Integrative Medicine, and Chinese Medical Association, of which National Administration of Traditional Chinese Medicine issued 19 guidelines. However, the issuing units of 26 guidelines/consensuses were medical colleges/medical institutions and the issuing units of 8 guildlines/consensuses were not clearly stated. Among the 138 guidelines/consensuses, 18 (13.04%) did not describe the safety of drugs and 120 (86.96%) described. Among the 120 guidelines/consensuses, none of the safety recommendations were graded according to The Grading of Recommendations Assessment, Development and Evaluation, and only 32.50% (39/120) of the evidence sources contained randomized controlled trials. A proportion of 50.72% (70/138) in 138 guidelines/consensuses did not report the funding situation, and 37.68% (52/138) did not disclose the conflict of interest.　Conclusions In recent years, the number of guidelines/consensuses on CPM has increased significantly in China, but the issuing agencies of some of them had poor authority. Most of the guidelines/consensuses are "drug-based", the descriptions of safety are insufficient, the evidence level is low, and there may be some bias.

Objective To explore the characteristics and mechanism of Chinese herbs with fertility toxicity.　Methods Chinese herbs with reproductive toxicity, developmental toxicity and genetic toxicity were retrieved from Traditional Chinese Medicine System Toxicology Database. The property, taste, meridian tropism, toxicity classification and performance, and the toxic component and action target of each medicinal material were collected and descriptive statistical analysis was performed.　Results A total of 55 kinds of Chinese herbs with fertility toxicity were screened out. They were mostly warm ［20 (36.4%)］ or cold ［15 (27.3%)］ in property, and mostly bitter and pungent in taste ［bitter-pungent, bitter, and pungent accounted for 30.9% (17/55), 23.6% (13/55) and 18.2% (10/55)］. The channel tropisms were mainly liver, lung, spleen, and kidney ［58.2% (32/55), 38.2% (21/55), 38.2% (21/55) and 34.5% (19/55)］, and the main manifestations of its reproductive toxicity were reproductive function damage in males and females, abnormal embryonic growth and development and genetic/cytotoxicity, which might lead to reduced pregnancy rate, miscarriage, abnormal fetal growth and development, etc. There were 29 kinds of Chinese herbs with 35 known fertility toxic components. Among them, 30 toxic components had 11 known toxic targets. The more common toxic targets included thyroid hormone receptor beta, cytochrome P450 1A1, sex hormone-binding globulin and interleukin-1 beta.　Conclusions Chinese herbs with fertility toxicity are mostly warm or cold in property, and bitter and pungent in taste; their channel tropisms are mainly liver, lung, spleen and kidney; they mainly affect fertility and embryonic development by changing the body′s endocrine and interfering with sex hormone metabolism.

Pre-marketing clinical trials may fail to detect rare or delayed adverse drug reactions (ADRs) due to insufficient sample size and short follow-up periods. Therefore, continuous post-marketing safety evaluation is necessary. Evidence generation relies on discovering ADR signals and conducting studies to verify specific risks. Integrating evidence from multiple sources through methods like meta-analysis can further enhance the comprehensiveness and reliability of drug safety evaluations. Additionally, risk management in clinical practice should be emphasized by developing standardized clinical guidelines and establishing decision support systems to facilitate the dissemination and application of evidence, ensuring its practical use. Constructing an evidence ecosystem not only helps identify and understand potential medication safety issues, but also enhance the scientific and practical aspects of risk management, ultimately reducing patient harm from ADRs.

Objective To summarize the evidence related to the prevention and nursing of iatrogenic botulism.　Methods The relevant literature on prevention, nursing and management of iatrogenic botulinum in relevant websites and medical literature databases at home and abroad were systematically searched (up to December 30, 2023). Evidence-based methods were used to evaluate the quality of literature and conduct extraction and summarization of the evidence.　Results A total of 14 literature was included, including 1 guideline, 6 expert consensus, 4 systematic reviews and 3 clinical decisions, all of which were of high overall quality. After summary and analysis of the evidence, a total of 7 evidence topics and 41 evidence-based evidences for the prevention and nursing of iatrogenic botulism were sorted out, including prevention and management, health education, early warning and evaluation, drug treatment management, supportive nursing, functional exercise, and psychological nursing.　Conclusion The evidence of prevention and nursing of iatrogenic botulinum summarized by evidence-based method has a high overall quality, and the recommendations have high reference value in clinical nursing.

Objective To summarize the relevant evidence for the prevention of contrast-associated acute kidney injury (CA-AKI) after enhanced CT examination in patients with nephropathy.　Methods The literature on prevention of CA-AKI in patients with nephropathy who underwent enhanced CT examination in relevant websites and medical literature databases at home and abroad were systematically searched, the quality of the literature was evaluated, and the relevant evidence was extracted and summarized. The retrieval period was from January 1, 2013 to December 1, 2023.　Results A total of 17 literature was included, including 6 guidelines, 5 expert consensuses, 2 clinical decisions, 2 cohort studies, 1 evidence summary and 1 systematic review. Evidence was extracted from these literature. After summary and analysis of these evidence, 10 evidence topics were sorted out, including threshold of estimated glomerular filtration rate and high-risk population, screening, hydration prevention, drug prevention, use of nephrotoxic drugs, use of metformin, precautions for dialysis patients, alternative imaging strategies, choice of iodine contrast agents, and points for attention after enhanced CT examination, forming 47 pieces of evidence.　Conclusion The relevant evidence for the prevention of CA-AKI can provide a more systematic evidence- based basis for medical staffs in screening high-risk population and preventing and managing CA-AKI in patients with chronic kidney disease before enhanced CT examination.

Objective To systematically evaluate the relationship between thiazide diuretics and the risk of hip fracture in the elderly patients.　Methods The relevant databases at home and abroad were searched up to December 31, 2023 and case-control studies and cohort studies on the relationship between thiazide diuretics and the risk of hip fractures in the elderly patients were collected. Quality of the enrolled studies was evaluated by bias risk assessment tool of Newcastle-Ottawa Scale (NOS). RevMan 5.4 software was used for meta-analysis on related outcome indicators, and the effect sizes were odds ratio (OR) and the 95% confidence interval (CI). Funnel plots, Egger′s method and Begg′s method were performed using Stata 15.1 software to analyze the inclusion literature for publication bias.　Results A total of 18 studies were enrolled in the study, including 7 case-control studies and 11 cohort studies and involving 175 200 patients in the trial group (thiazide diuretics) and 1 574 989 in the control group (placebo or other medications). All 18 studies scored ≥5 on the NOS (15 articles of high quality and 3 articles of medium quality). The meta-analysis results indicated that the risk of hip fractures in the trial group was lower than that in the control group (OR=0.82, 95%CI: 0.75-0.89, P<0.001). Subgroup analyses by study type and gender both revealed that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR in case-control studies was 0.78, 95%CI: 0.72-0.84, P<0.001; adjusted OR in cohort studies was 0.83, 95%CI: 0.74-0.93, P=0.002; adjusted OR in female was 0.78, 95%CI: 0.72-0.85, P<0.001; adjusted OR in male was 0.73, 95%CI: 0.68-0.80, P<0.001). The subgroup analysis of 11 large-sample studies (≥2 000 cases) indicated that thiazide diuretics were associated with a reduced risk of hip fractures in the elderly (adjusted OR=0.79, 95%CI: 0.72-0.87, P<0.001). However, 6 small-sample studies did not find the similar correlation. A combined analysis of studies that rigorously controlled for confounding factors revealed that thiazide diuretics were associated with a lower risk of hip fractures in the elderly (OR=0.79, 95%CI: 0.74-0.84, P<0.001), and the combined results showed no heterogeneity (P=0.72, I2=0%).　Conclusions Thiazide diuretics were associated with a reduced risk of hip fractures in the elderly patients. Based on a comprehensive assessment of the risks and benefits of medication for elderly patients, clinicians may prioritize thiazide diuretics as a component of combination therapy for eligible patients, which may be beneficial in reducing their risk of hip fractures.

With the spread of hemodialysis therapy and the continuous breakthrough of kidney transplantation technology, the survival period of patients with end stage renal disease is prolonged, and malignant tumor has become one of the main causes for hospitalization and death of patients on hemodialysis and undergoing kidney transplantation. Due to the particularity of pharmacokinetics in patients on dialysis and the long term maintenance immunosuppressive therapy in kidney transplant patients, many aspects need to be considered and balanced in these patients when they need anti tumor drug treatments. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, and systematically answers many clinical questions about anticancer drug therapy in patients on hemodialysis and underwent kidney transplantation in the second chapter. This article interprets this part to provide references for the anti-tumor drug treatments of patients on dialysis and after kidney transplantation in China.

Drugs or their metabolites may accumulate in the body due to the decline of renal excretion function in cancer patients with renal insufficiency. Therefore, adjusting the treatment scheme and drug dose according to the patient′s renal function is an important part of anticancer treatment for these patients. The Japanese Society of Nephrology, Japan Society of Clinical Oncology, Japanese Society of Medical Oncology, and Japanese Society of Nephrology and Pharmacotherapy have jointly formulated Clinical Practice Guidelines for Management of Kidney Injury During Anticancer Drug Therapy 2022, and specifically discusses the dose adjustment of anticancer drug treatment for patients with renal injury in the second chapter.
This article focuses on the interpretation of the application and dose adjustment of antifolate agents, BCRABL1 tyrosine kinase inhibitors, epithelial growth factor receptor tyrosine kinase inhibitors, antibody molecularly targeted agents and tumor adjuvant therapy drugs such as bone‑modifying agents in patients with renal injury in this chapter. 

Unsafe medication and medication errors are the main causes of avoidable harm in the health system. In order to reduce drug?related harm, it is necessary to pay special attention to medication safety in high?risk situations, medication safety during polypharmacy, and medication safety during the transitions of medical care. The main factors leading to high?risk situations include drugs (high?alert drugs), human (drug provider and patient), and environment (drug management, treatment environment and human resources, etc.). Strengthening management for polypharmacy can promote the rational use of drugs and minimize drug?related harm. Reducing medication errors and/or adverse drug events in transitions of care requires collaboration from multiple parties, including interdisciplinary care teams such as physicians, pharmacists, and nurses, as well as active participation from patients and their families. Compared with developed countries, there is still a significant gap in the 3 areas in China, and physicians, pharmacists, and nurses need to take active actions and make joint efforts to ensure the medication safety of patients.

To explore the effects of maternal exposure to Morinda officinalis oligosaccharides (MOO) during lactation on the Sprague?Dawley (SD) maternal rats and their offspring′s growth and development. Methods Seventy?two female rats with a surviving litter size of ≥ 6 were divided into the excipients control group, MOO low?dose group (50?mg/kg), MOO medium?dose group (160?mg/kg), and MOO high?dose group (500?mg/kg) using a snake-shaped grouping based on body weight, with 18 rats per group. The rats were gavage fed once daily until 20 days of delivery. The response of maternal rats after MOO exposure during lactation, as well as the appearance, response, gross anatomical abnormalities of their F1 and F2 offspring were observed. The body weight and food intake of maternal rats during lactation and those of their offspring before and after weaning were measured. The behavior (central nervous system function) of the F1 and F2 offspring was evaluated using functional observation battery (FOB). The learning and memory function of the F1 offspring was evaluated using Y?maze test. The male and female F1 offspring in the same dose group were mated when they were raised to 10?12 weeks in order to observe the reproductive function of F1 female rats.　Results Compared with the excipients control group, no abnormality was found in the clinical observation of maternal rats in the 3 MOO exposure groups during lactation, and there was no significant differences in their body weight and daily food intake during lactation (all P>0.05). No significant effects were found on the appearance, clinical symptoms, gross anatomy, body weight, and food intake of the F1 and F2 offspring after maternal rats receiving MOO exposure during lactation. In the FOB of the F1 and F2 offspring and the Y?maze test of F1 offspring, few differences in MOO exposure groups were observed and lack of significant dose?response relationship. After pregnancy, there were no statistically significant differences in the number of corpus luteum, implantation number, birth index, delivery index, survival index, and weaning index in F1 female offspring of maternal rats exposed to MOO at different doses during lactation compared with those of the excipients control group (all P>0.05).　Conclusions There were no obvious toxic reactions in maternal rats after exposure to different doses of MOO during lactation, nor in the growth and development, nervous system, learning and memory, and reproductive function of their offspring.

Objective To establish a prescription pre⁃audit system based on the structureprocess⁃outcome (SPO) model in the the Affiliated Hospital of Qingdao University and explore its application effect. Methods Based on the structural dimension of SPO model, the organizational structure, pharmaceutical team, management system of pharmaceutical prescription audit, and audit environment of the prescription pre⁃audit system were established. Based on the process dimension of SPO model, the preaudit process, medication knowledge base, and audit rule base were established, quality monitoring and control were implemented, and relevant personnel training were conducted. Based on the outcome dimension of SPO model, the review rate, manual review rate, clinician acceptance rate of prescription review, reasonable rate of outpatient and emergency prescription comments, and intervention rate of inpatient medical order were verified after the prescription pre⁃audit system application. Results The prescription preaudit system was first launched in the main hospital area of the Affiliated Hospital of Qingdao University in March 2021, and achieved full coverage in all five hospital areas by May 2023. The review rates of outpatient and emergency prescriptions and inpatient medical orders had been increasing year by year from 2021 to 2023, and all reached more than 99% of the expected rates in 2023. Compared with 2021, the proportions of outpatient and emergency prescriptions and inpatient medical orders submitted to manual review decreased in 2023
[1.2% (112 206/9 509 430) vs. 2.9% (16 214/549 672), 2.9% (206 258/7 152 620) vs. 3.9% (147 679/3 814 929), the proportions of prescriptions that failed to be reviewed in time decreased [0.7% (62 382/9 509 430) vs. 1.4% (7 429/549 672), 0.3% (22 816/7 152 620) vs. 2.2% (83 303/3 814 929)], and the acceptance rates of outpatient and emergency prescription review and inpatient medical orders review by clinicians increased [76.1% (2 421/3 180) vs. 57.0% (339/595), 94.3% (1 000/1 060) vs. 70.7% (797/1 128)],
with statistically significant differences (all P<0.001). But there were still some prescriptions and orders that needed manual review but were not reviewed in time and finally missed review. Compared with 2021, the reasonable rates of outpatient and emergency prescription comments increased in 2023 [96.7% (924 558/956 252) vs. 92.2% (983 827/1 067 357), 98.7% (518 307/525 227) vs. 98.0% (181 296/185 069)], and the intervention rate of inpatient medical orders decreased [0.7% (196 522/26 751 992) vs. 0.9% (195 660/22 631 289)], with statistically significant differences (all P<0.001). Conclusions Applying the SPO model can improve the organization and management of the prescription pre⁃audit system, and ensure the smooth launch and safe operation of the system. After verification, the operating speed of the prescription pre⁃audit system and prescription review speed of pharmacists could basically meet the clinical needs, the indicators of rational drug use in the hospitals were improved, and the professional and technical ability of pharmacists were enhanced.

Objective To investigate the reasons for contraindication of chemical drugs and biological products that were marked as contraindication for children in drug labels in China.　Methods The drugs labeled as contraindication for children in drug labels of chemicals and biological products covered by the China Pharmacopoeia 2020 and the 2023 China′s Basic Medical Insurance, Work?related Injury Insurance and Childbirth Insurance (western medicine) were searched. The reasons of contraindication for children were collected through searching the drug labels, Clinical Medication Instructions of the China Pharmacopoeia 2020, the website of the National Medical Products Administration, and drug labels from the Unite States, and analyzed descriptively.　Results There were 222 drugs were labeled as contraindication for children in the drug labels, involving 20 categories and mainly antibiotics and digestive system drugs. Among 222 drugs, 137(61.7%) had the reasons for contraindication in pediatric patients, and the main reasons were adverse drug reactions (65.7%, 90/137) and lack of effectiveness and safety information yet in children (30.7%, 42/137), followed by the unsafe auxiliary materials (1.5%, 2/137), unsuitable pres- cription design or ingredients for children (1.5%, 2/137) and unsuitable dosage form for children (0.7%, 1/137). The above reasons were collected from domestic drug instructions (100 drugs), U.S. drug labels (17 drugs), NMPA website instructions revision announcements and popular science knowledge (15 drugs), and Clinical Medication Instructions of the China Pharmacopoeia 2020 (5 drugs).　Conclusions It is relatively common in China to label drugs that are contraindicated for children without specifying the reasons for contraindication or with non?standard explanations in the instructions. Therefore, it is necessary to further standardize the contraindication information for children and apply continuous updates and improvement in order to provide timely and up?to?date drug use information for clinical practice.

Objective To understand the occurrence of drug?drug interaction (DDI) in medical orders and the relevant common medications of hospitalized patients treated with voriconazole.　Methods The treatment information of hospitalized patients treated with voriconazole and had blood trough concentration (Cmin) results in Quanzhou First Hospital, Fujian Province from May 2018 to August 2023 was collected through the hospital information system. Descriptive statistical analysis was conducted on the incidence of DDI medical orders, the drugs involved in DDI, the types and risk levels of DDI, the departments where DDI occurred, and the Cmin changes of voriconazole in patients with 1 or 2 type of voriconazole?related DDI medical orders (including drugs not recommended in combination with voriconazole or voriconazole dose needs to be adjusted when combined) during voriconazole treatment.　Results A total of 752 patients were included, of which 592 (78.7%) had 1?344 medical orders with voriconazole?related DDI, involving 28 drugs. Among them, 67.7% (401/592) of patients used 2 or more DDI drugs. Glucocorticoids ［91.6% (542/592)］, followed by proton pump inhibitors ［87.8% (520/592)］, were most frequently involved in the medical orders of DDI with voriconazole. Among the 28 voriconazole?related DDI drugs, 5 were involved in type 1 or 2 DDI, including rifampicin, nirmatrelvir/ritonavir, phenobarbital, phenytoin sodium, and rifabutin. The 5 drugs involved 33 patients, of whom 51.5% (17 patients) had voriconazole Cmin<1.0?mg/L; rifampicin involved the most patients (17 patients), followed by nirmatrelvir/ritonavir (10 patients). When voriconazole was combined with rifampicin, rifabutin, phenobarbital and phenytoin sodium, its Cmin in most patients decreased significantly. The incidence of medical orders with voriconazole?related DDI was highest in the Intensive Care Unit, followed by the Department of Respiratory and Critical Care Medicine.　Conclusions Medical orders with DDI are very common in the clinical application of voricona- zole, and most patients have used two or more DDI drugs, in which glucocorticoids and proton pump inhibitors appeared more common. It is necessary to be alert to the occurrence of DDI between voriconazole and rifampicin, rifabutin, phenobarbital and phenytoin  sodium in clinic.

Objective To investigate the clinical features, management, and prognosis of amphotericin B (AmB)?associated nephrogenic diabetes insipidus (NDI).　Methods The diagnosis and treatment process of a patient with AmB?related NDI who was admitted to the General Hospital of Tianjin Medical University was reported, and the main clinical data of the patient and related cases such as gender, age, primary disease, medication, NDI occurrence, treatment and outcome collected from CNKI, Wanfang Medical, and VIP databases, PubMed, Web of Science, and ScienceDirect (up to August 22, 2023) were analyzed descriptively.　Results A total of 11 patients were included in the analysis, including 7 males and 4 females, with an average age of 41 years, ranging from 12 to 66 years. The correlation between AmB and NDI was probable in 7 cases and possible in 4 cases. The time from the beginning of medication to the occurrence of NDI was 3 days to 3 weeks, and the urine volume was 3.8-10.8 L/d. Among the 11 patients, 6 patients had hypokalemia and 5 patients had elevated serum creatinine; 9 patients did not stop using AmB due to their conditions, the intervention plans were described in details in 4 patients and AmB treatments were completed after symptomatic treatments, 7 patients were cured or improved, and 2 patients died. Among the 2 patients who stopped taking the medication, 1 patient showed significant improvement in symptoms and resumed using AmB without recurrence; the other case was improved after stopping the medication, but relapsed after resuming use without stopping the medication, and the patient died from the primary disease.　Conclusions During the use of AmB, close attention should be paid to the occurrence of NDI. After occurrence of NDI, most patients can continue taking the AmB and have a good prognosis after symptomatic treatments.

Objective To mine the risk signals of hypoxia?inducible factor prolyl hydrocylase inhibitor (HIF?PHI)?related adverse events (AEs) and provide reference for the safe use of the drugs in clinic practice.　Methods AE reports of HIF-PHI drugs were collected from the US FDA Adverse Event Repor- ting System (FAERS) database during January 1, 2004 to September 30, 2023. AEs were classified and standardized according to the system organ class (SOC) and the preferred term (PT) in Medical Dictionary for Regulatory Activities 25.0. The AE risk signals of above mentioned 3 drugs were mined using reporting odds ratio (ROR) method. An AE with reports ≥3 and the lower limit of the 95% confidence interval (CI) of ROR >1 was defined as a risk signal. Descriptive analysis on the signals was performed.　Results Only AE report data for roxadustat, daprodustat, and vacladustat were collected. A total of 78 AE reports related to roxadustat were collected, involving 12 PTs and 8 SOCs. The top 5 PTs in signal intensity were shunt occlusion, central hypothyroidism, gastrointestinal perforation, colon cancer, and hepatic function abnormal. Except for central hypothyroidism, the other 4 were not recorded in the labels. A total of 459 AE reports related to daprodustat were collected, involving 29 PTs and 13 SOCs. The top 5 PTs in signal intensity were gastrointestinal erosion, retinal haemorrhage, haemorrhoidal haemorrhage, abnormal feces and colon cancer. Retinal haemorrhage, abnormal feces and colon cancer were new adverse events not recorded in the labels. A total of 26 AE reports related to vadadustat were collected, involving 6 PTs and 4 SOCs. The top 5 PTs in signal intensity were drug eruption, face oedema, colon cancer, gastrointestinal haemorrhage, and dehydration, all of which were new adverse event not recorded in the labels.　Conclusions The risk signals of roxadustat, daprodustat and vadadustat are mostly adverse events not recorded in the labels, such as shunt obstruction, gastrointestinal perforation, colon cancer, etc. When using the 3 drugs, clinicians should not only pay attention to the adverse reactions recorded in the labels, but also be alert to the adverse events not recorded in the labels.

Objective To understand the clinical characteristics of hemophagocytic lymphohistiocytosis (HLH) induced by immune checkpoint inhibitors (ICIs).　Methods Relevant databases at home and abroad (up to February 15, 2024) were searched and case reports of HLH induced by ICIs were collected. Relevant information of patients (gender, age, primary disease), usage and dosage of ICI, combined drugs, occurrence time, clinical manifestations, management, and outcomes of HLH were extracted and analyzed descriptively and statistically.　Results A total of 37 case reports were enrolled in the analysis, involving 44 patients. Of them, 26 patients were male and 18 were female. The age ranged from 2 to 86 years, with a median age of 67 years. The primary diseases included melanoma in 14 patients, lung cancer in 12 patients, kidney cancer in 4 patients, oral squamous cell carcinoma and acute myeloid leukemia in 2 patients each, and other 10 malignant tumors in one patient each. A total of 8 ICIs were used, including pembrolizumab in 17 patients, nivolumab in 10 patients, nivolumab combined with ipilimumab in 8 patients, atezolizumab, camrelizumab, and ipilimumab in 2 patients each, and toripalimab, tislelizumab, and avelumab in 1 patient each. Among them, 33 patients received single ICI immunotherapy, 6 patients received immunotherapy combined with targeted therapy, and 5 patients received immunotherapy combined with chemotherapy. Twenty-two patients had medication dosage records, and the administration method was all intravenous infusion. The shortest time for HLH occurrence was 1 day after medication, the longest was 8 months, and the median time was 5 days. The clinical manifestations included recurrent fever, fatigue, loss of appetite, etc. Laboratory and auxiliary examinations showed decreased blood cells, elevated ferritin, increased hemophagocytic cells, and spleen enlargement. After the diagnosis of HLH, 40 cases discontinued the drug, 1 did not stop, and 3 were unknown. Forty?two patients received symptomatic treatments, of which 18 patients returned to normal, 17 patients were improved, 1 patient was unknown, and 6 patients died. Two patients who did not receive intervention died.　Conclusions The main clinical symptoms of ICI?related HLH are fever, fatigue, weakness, loss of appetite, and hemophagocytosis. Withdrawal and symptomatic treatments can effectively improve the symptoms of patients, but HLH has a higher risk of death.