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.

A 66-year-old male patient with esophageal cancer progressed after concurrent radiotherapy and chemoradiotherapy, and received immunotherapy combined with chemotherapy (intravenous infusion of sintilimab 200 mg on day 1, tegafur gimeracil oteracil potassium 50 mg orally twice daily from day 1 to 14), with 21 days as a cycle. After 13 days of treatments, diarrhea appeared, and gradually worsened with abdominal pain and a small amount of mucous bloody stools. Colonoscopy showed diffuse swelling and punctiform hemorrhagic erosion of the mucosa of the colon and rectum. Histopathological examination of the ascending colon and sigmoid colon showed regular arrangement of glands, infiltration of lymphocytes, neutrophils and eosinophils in the interstitium, and formation of crypt abscesses, which were considered to be immune-associated colitis caused by sintilimab. After discontinuing the use of sintilimab and administering low-dose methylprednisolone (24 mg orally twice daily) for 3 days, the patient′s symptoms were completely relieved. The dose of methylprednisolone was reduced gradually and discontinued within 4 weeks. The patient did not rechallenge immune checkpoint inhibitors and continued maintenance therapy with tegafur gimeracil oteracil potassium, and no diarrhea recurred

With the aging of the population and the increasing number of patients with thromboembolic 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 mine the risk signals of adverse events (AE) of satralizumab for treatment of neuromyelitis optica spectrum disorder (NMOSD) and provide reference for safe use of the drug in clinic.Methods:AE reports on satralizumab from the 1st quarter of 2020 to the 4th quarter of 2023 were collected by searching US Food and Drug Administration Adverse Event Reporting System (FAERS) database. AEs were classified and standardized according to the preferred term (PT) and system organ class (SOC) of Medical Dictionary for Regulatory Activities version 26.1. Reporting odds radio (ROR) method and Bayesian confidence progressive neural network (BCPNN) method were used to mine the AE risk signals. An AE with ≥3 reports, lower limit of the 95% confidence interval ( CI) of ROR >1, and the information component ( IC) of BCPNN method minus 2 times of standard deviation ( IC-2 SD) >0 were defined as a risk signal. Descriptive analysis on the signals was performed. Results:A total of 526 AE reports were collected, 39 risk signals (PT) were mined by ROR and BCPNN methods, involving 13 SOCs. Among the 39 PTs, 11 were adverse reactions recorded in the label, including blood triglycerides increased, hepatic function abnormal, cellulitis, and etc. Twenty-eight PTs were not recorded in the label, 11 of which involved infections and infestations. The top 5 PTs in signal intensity were atypical mycobacterium infection, pyelonephritis, compression fracture, spinal compression fractures, and lymphocyte count decreased. The top 5 PTs in number of reports were urinary tract infection, pneumonia, corona virus disease 2019, sepsis, and herpes zoster.Conclusion:In addition to the blood triglycerides increased, hepatic function abnormal, cellulitis, and other AEs recorded in the label, NMOSD treatment with satralizumab may also cause atypical mycobacterial infection, pyelonephritis, compression fracture and other AEs not recorded in the label, which clinical physicians should be vigilant.

In order to promote rational drug use in perioperative period, a perioperative clinical medication pathway system was constructed in the Affiliated Hospital of Qingdao University using the project management method of work breakdown structure (WBS). To establish this system, the following 7 tasks should be completed: requirement investigation of the pathway, formulation of drug usage standards, formulation of clinical medicine pathways, clinical communication and training, effect evaluation and supervision, informazation of medication supervision, and therapeutic drug monitoring, which were implemented by pharmacists of different specialties, respectively. After 4 years of effort, 6 general clinical medicine pathways were completed for antibiotics, analgesics, drugs in venous thromboembolism prophylaxis, nutritional support agents, airway management drugs, and proton pump inhibitors, respectively. These pathways had positive effects in improving the rational use of antibiotics, optimizing the postoperative pain management, and strengthening the risk assessment of thrombosis for patients in the surgical department. The personalized pathway constructed for the Cardiac Surgery Department and the multidimensional pharmaceutical intervention in the Anesthesiology Department also had remarkable effects. In conclusion, the construction of perioperative medication pathway system through WBS was helpful to refine the division of work tasks, reflect the value of pharmacists, and improve the quality of perioperative pharmaceutical services.

Antiretroviral therapy (ART) significantly improves the survival rate and quality of life of patients with human immunodeficiency virus (HIV) infection. However, with the extension of patients′ survival time, drug-induced new health problems such as blood glucose increase, dyslipidemia, and weight gain are becoming prominent. Different antiretroviral agents have different effects on blood glucose, blood lipid and adipose tissue. This paper reviews the research progress on effects of nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors on blood glucose, lipid metabolism and body weight in HIV-infected people in recent years, and puts forward corresponding control suggestions.

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.

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.