Background: Routinely collected electronic healthcare data have created new opportunities for active, near real-time post-marketing drug safety surveillance. Sequential analysis offers a natural framework for periodic signal detection as data accrue and may facilitate earlier identification of emerging safety concerns. However, its application in drug safety surveillance has not been comprehensively characterized. Objective: To systematically identify and characterize empirical applications and methodological developments of sequential analysis for safety signal detection in post-marketing drug surveillance using electronic healthcare data and to summarize key methodological approaches and evidence gaps in the literature. Eligibility criteria: Eligible studies included empirical observational studies that applied sequential analyses to periodically monitor prespecified drug-outcome pairs, and methodological studies that proposed or evaluated sequential approaches for post-marketing surveillance. Sources of evidence: Six databases (PubMed, EMBASE, the Cochrane Library, CNKI, WanFang, and VIP) were searched from inception to 21 July 2025. Charting methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Two reviewers independently screened studies and extracted data using a standardized form. Findings were mapped to predefined analytical dimensions and synthesized narratively. Results: Forty-six studies were included, comprising 20 empirical observational studies and 26 methodological studies. All empirical studies were conducted in high-income countries, predominantly the United States, and 80% were pilot or feasibility assessments. Electronic health/medical records and administrative claims were the primary data sources. Considerable methodological heterogeneity was observed in study designs, analytical frequency, and sequential approaches. Two broad paradigms were identified: sequential testing and sequential risk estimation. Methodological studies were largely motivated by challenges inherent to observational settings, particularly confounding control. Conclusion: Despite growing interest and methodological development, the application of sequential analysis in post-marketing drug safety surveillance remains limited. Future work should prioritize stronger approaches to confounding, clearer implementation standards, and better integration of sequential monitoring into routine pharmacovigilance practice.

Baloxavir marboxil (baloxavir), a cap-dependent endonuclease inhibitor, has been proven safe and efficacious against influenza and approved for the treatment of influenza in children aged ≥ 5 years in China. There were limited data on baloxavir in Chinese pediatric patients aged 1 to < 5 years with influenza. This study aimed to evaluate the safety, clinical efficacy, and virologic outcomes of baloxavir for treating influenza in this younger age group. In this single-arm, multicenter trial, patients received a single oral dose of baloxavir (2 mg/kg for participants weighing < 20 kg, or 40 mg for participants weighing ≥ 20 kg to < 80 kg). The primary endpoint was safety. Efficacy, virology, and palatability endpoints were also assessed. All 100 enrolled children completed the study and received baloxavir. Adverse events were reported in 29 (29.0

Objective To analyze the serious medication errors (MEs) on dabigatran, and their related factors, in order to avoid or reduce the occurrence of adverse events. Methods Serious MEs related to dabigatran were extracted from the WHO global database of reported potential side effects of medicinal products (VigiBase) by using “Medication errors and other product use errors and issues” High Level Group Term (HLGT) of the international Medical Dictionary for Regulatory Activities (MedDRA). Well-documented reports, vigiGrade completeness score ≥ 0.80, or with an informative narrative were analyzed with a focus on the clinical features of the cases. The PCNE Classification for drug-related problems (DRP) was used to classify medication errors in our analysis of cases. Results Until January 26, 2020, there were 453 cases with serious MEs related to dabigatran in VigiBase, and 113 were well-documented. Among these, 69 patients (61%) were hospitalized or had prolonged hospitalization, 16 (14%) had life-threatening events, and 12 (11%) died. The MEs occurred in the prescription phase in 77 cases, in administration in 35, and at the dispensing stage in one case. The MEs in prescription were related to a drug selection error in 44 cases (24 concerning contraindications and 20 drug interactions) and to dose error in 33 cases (17 with excessive dose; eight with insufficient frequency; four had an incorrect time; in three, the dose was too low; and in one, too frequent). The MEs in administration were medical-staff-related errors in five cases (three with wrong administration route, one administration omission, and one overdose), patient-related errors in 28 (14 insufficient dose or no administration, seven improper drug storage, four wrong administration method, and three over prescribed dose), and other errors in two (without efficacy monitoring). The dispensing error of a wrong drug strength occurred in a pharmacy. The main adverse events in the 113 patients were haemorrhage in 57 cases (50%) and ischemia in 29 cases (26%). Conclusion Based on the analysis of reports in VigiBase, serious MEs related to dabigatran mainly occurred during prescription and administration. Although the incidence of MEs with clinical consequences in the use of dabigatran cannot be determined, attention should be paid to selection of the appropriate dose to a right patient in the prescription, and to patient compliance and storage in drug administration. The patient harm mainly manifested itself as bleeding or ischemia including fatal outcome in rare patients.

目的 分析中国儿科人群干细胞临床研究现状,为国内研究者提供儿科人群干细胞临床研究参考.方法 通过检索美国临床试验数据库网站进行我国儿科人群干细胞临床研究登记信息的采集,对临床研究每年新增项目数、临床阶段、适应症、应用干细胞类型、申报者、资金来源、研究设计等方面进行统计分析.结果 截至2021-11-30,网站共登记包含儿科人群的干细胞临床研究共89项;我国儿科人群干细胞临床研究在2013年和2019年开展项目数最多,可能与我国近些年陆续出台政策相关;我国儿科人群干细胞临床研究多处于早期探索阶段,以间充质干细胞临床研究为主,研究疾病类型涉及广泛,以血液系统疾病为主;临床研究多由医疗机构发起,以科研探索为主;临床研究类型主要是干预性研究,少数研究设盲,涉及预计样本量例数较少.结论 我国儿科人群干细胞临床研究近年来发展平稳,技术仍处于早期发展水平,临床应用前景十分广阔.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

目的:挖掘儿童使用喹诺酮类代表性药物(环丙沙星、左氧氟沙星与莫西沙星)的不良反应(adverse drug reaction,ADR)信号,为临床安全用药提供参考.方法:利用OpenVigil2.1工具从美国FAERS数据库中提取2004年第1季度至2022年第2季度18岁以下儿童数据,采用报告优势比(reporting odds ratio,ROR)与比例报告比(proportional reporting ratio,PRR)对三种喹诺酮类药进行ADR信号挖掘,重点分析肌肉骨骼系统ADR.结果:FAERS数据库共检索到18岁以下儿童的报告323 032份,其中环丙沙星相关报告1 163份、左氧氟沙星相关报告617份、莫西沙星相关报告256份.经ROR法和PRR法共挖掘得到ADR信号387个,其中环丙沙星222个,左氧氟沙星117个,莫西沙星48个;ADR信号累及的系统器官广泛(24个),主要包括胃肠系统、肌肉骨骼系统与神经系统等.对于肌肉骨骼系统,环丙沙星检出信号26个,左氧氟沙星14个,莫西沙星并未检出信号;关节痛报告频数最多,而信号强度最高的是肌腱类疾病,包括肌腱疼痛、肌腱炎、肌腱病变等均出现了显著信号.结论:儿童使用喹诺酮类抗菌药物需严格监测ADR,特别警惕于肌肉骨骼系统损伤,保障患者的治疗安全.

目的 调研硝酸甘油开封后的贮藏现状,分析硝酸甘油贮藏环节中的风险点并提出防范措施.方法 2021年6月1日药师对我院硝酸甘油基数药进行现场调研;2021年8月1日至31日对门诊处方硝酸甘油患者进行电话问卷调查和2021年6月23日至9月30日对全国医务人员问卷星问卷调查,了解硝酸甘油开封后贮藏现状.结果 我院备有硝酸甘油基数药的病区有32个,其中存储不规范的有:4个病区使用口服分包塑料袋贮藏,29个病区效期标注为36个月(同说明书未拆封效期).患者调查问卷67份,男性43人,女性24人;平均年龄65(37～90)岁,60岁及以上51人;非第1次使用硝酸甘油61人;硝酸甘油开封后效期>3个月占97.01％;外出贴身(裤子或上衣口袋)携带人数占75.76％;未接受硝酸甘油用药教育占88.06％.医务人员调查问卷4365份:来自全国31个省份931家医院及机构,822家公立、87家私立和22机构(疾控中心和药品生产企业),其中心血管医院75家;护士、药师、医生、其他医技人员和行政人员分别为1580、1232、1005、413、135人,病房、药房、家中及外出3种情景下硝酸甘油开封后效期超过3个月人数分别占65.41％、49.59％和59.89％,外出贴身携带(裤子或上衣口袋)人数占34.30％.结论 医务人员和患者对硝酸甘油开封后贮藏知识欠缺,硝酸甘油患者教育不足,建议针对硝酸甘油开封后贮藏容器、效期、携带方式及患者教育进行改善,从而保障患者硝酸甘油使用安全有效.

Background Medication nonadherence is a significant public health problem as it contributes to poor clinical outcomes and increased healthcare costs. Older patients with multimorbidity and polypharmacy often have low medication adherence. These patients also have a high prevalence of potentially inappropriate medication (PIM) use. Aim To explore risk factors related to medication nonadherence in older patients with multimorbidity and polypharmacy and examine the association between medication nonadherence and PIM use. Method A multicenter cross-sectional study was conducted from May to December 2019 in 16 tertiary hospitals from 12 provinces and cities in China. Data were collected from outpatients 65 years or older with multimorbidity and polypharmacy. The PIMs were evaluated using the 2019 Beers Criteria. Self-reported medication adherence was assessed using the Visual Analog Scale (VAS). Results A total of 773 outpatients were recruited. The prevalence of medication nonadherence was 31.8%. In the univariate analysis, nonadherence was significantly associated with sex, cognitive impairment, stroke, visiting the same physicians, self-administration of medication, the percentage of drug costs ≥ 10% of the medical expenses, and PIMs for the alimentary tract and metabolism. In the multivariate analysis, the results almost paralleled those of the univariate associations. Notably, the use of PIM was significantly associated with medication adherence. Conclusion Several factors that influence medication adherence were identified. Targeted interventions can be implemented to improve medication adherence, such as encouraging self-administering medications and reducing medication expenses.

Objective:To help clinical pharmacists clearly position themselves, seize the opportunity, and actively participate in pediatric clinical research projects.Methods:Through SWOT analysis, this study analyzed the advantages and disadvantages of clinical pharmacists of Beijing Children's Hospital participating in drug clinical research from four aspects: superiority (S), weak (W), opportunity (O), and threat (T), so as to form development suggestions for pediatric clinical pharmacists in drug clinical research.Results:Pediatric clinical pharmacists could take advantage of external opportunities to initiate drug clinical studies and participate in drug clinical trials as the principal investigator, and participate in the formulation of clinical research protocols and drug safety incident management as a research team member. Relying on internal advantages, pediatric clinical pharmacists could strengthen popular science education, reduce irrational drug use, and promote clinical research. Seizing the external opportunities, they could improve their professional quality, play a role in drug management for clinical research and drug clinical research quality control to increase clinical research practice experience. Overcoming internal disadvantages, they could play a role in protecting subjects' rights and interests and provide consulting services to improve subjects' compliance.Conclusion:Pediatric clinical pharmacists should clearly position themselves, seize the opportunity of children's drug research and development, participate in drug clinical research, and provide better pharmaceutical services for children.

目的 关注阿司匹林对甲状腺的影响.方法 通过分析1例阿司匹林引起出血性甲状腺肿大的病例,从用药与不良反应的相关性、阿司匹林致出血性甲状腺肿大的药学分析和药学建议等方面进行讨论.结果 患者服用阿司匹林前甲状腺超声提示多发结节、甲状腺功能正常,服药24 d后患者发现颈部肿大且越来越明显,甲状腺超声提示有血流信号,4个月后就诊医药联合门诊,药师和医生建议停用阿司匹林并复查甲状腺功能正常,停药10 d后自觉颈部肿大逐渐缩小,1个多月后颈部肿大完全消退、复查甲状腺超声未见血流信号.结论 服用阿司匹林的患者甲状腺肿大可能是阿司匹林出血导致,应引起医生和药师的关注,建议服用阿司匹林的患者若出现甲状腺肿大应行甲状腺功能和甲状腺超声检查,尤其是既往有甲状腺疾病的患者.

Objective:To analyze the status quo of clinical trials of rare disease drugs in China and abroad, to provide reference for further promoting the development of clinical research of rare disease drugs in China.Methods:By extracting the data of clinical trials of rare disease drugs in China's "drug clinical trial registration and information publicity platform", weanalyzedthe characteristics of clinical trials of rare disease drugs in China from the aspects of project registration, test type and stage, involved diseases, and scheme design, and comparedthem with the registration data of foreign clinical trials of rare disease drugs.Results:As of March 31, 2022, there were a total of 337 clinical trials of rare disease drugs in China's "drug clinical trial registration and information publicity platform", involving 37 diseases and 125 experimental drugs. Among them, there were 127 bioequivalence tests, accountingfor 37.6%; 278 domestic projects, accountingfor 82.4%; and 103 projects involving children, accountingfor about 37.0%.Compared with those in other countries, clinical trials of rare disease drugs in China had the following characteristics: (1) the number of clinical trialsshowedan obviously increasing trend; (2) there were few clinical trials of innovative drugs but many bioequivalence tests of generic drugs; and (3) the proportion of trials involving children was high.Conclusion:The clinical research on innovative drugs for rare diseases is still a weak link in China, and we need to improve legislation, increase financial support, enhance personnel training, and improve innovative research paths and methods.

The aim of this study was to analyze the clinical characteristics of fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline the importance of the rational use of drugs. The WHO global database of reported potential side effects of medicinal products (VigiBase) was searched for fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical characteristics of those cases with sufficient information (vigiGrade completeness score ≥ 0.80) were analyzed. By January 19, 2020, 2309 fatal adverse event reports of rivaroxaban combined with aspirin from 21 countries were entered in VigiBase. One hundred and twenty cases contained further information, of which 42 were female (35%) and 78 were male (65%). The median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly patients (≥ 65 years). The AEs listed in the fatal case reports included bleeding in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 and 46 respectively, accounting for 88%) and ischemic events in six cases (ischemic stroke in three, acute myocardial infarction in two, myocardial infarction combined with acute liver failure in one). Among the patients with bleeding events, 108 (95%) had existing risk factors for bleeding or for interacting with aspirin or rivaroxaban. These may be divided into the following: diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). There were 45 cases with two or more of these risk factors in addition to rivaroxaban and aspirin. Patients with ischemic events are often in very high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or self-discontinuation of treated drugs. Medication errors occurred in 24 patients (20%): excessive treatment in 17 cases, contraindication in three, frequency error in two, excessive treatment combined with contraindication in one, and self-discontinuation in one. Fatal AEs related to rivaroxaban combined with aspirin, including bleeding and ischemic events, have been reported mostly in the elderly, and sometimes involved medication errors. The fatal AEs mainly manifested as serious bleeding, and most of them occurred in patients with concurrent multiple risk factors. Monitoring coagulation during rivaroxaban treatment is recommended in very high-risk ASCVD populations, and attention should be paid to prevention of medication errors.

目的:探讨儿科医疗机构研究型病房的运行和管理模式.方法:通过查阅文献资料和实地考察,对北京市第一批示范性研究型病房建设单位不同的病房运行模式和管理模式进行分析比较,并结合儿科医疗机构自身特点,提出一种研究型病房新型运行和管理模式.结果:参考成人综合医院和专科医院两种不同的研究型病房运行模式和管理模式,分析儿科机构自身特点,结合研究型病房建设目标及功能定位,探索出一套具有儿科特色的研究型病房高效高质量运行的管理模式——"平急结合"模式,并提出进一步改进和完善建议.结论:儿科临床研究有其特殊性,不能照搬成人医疗机构研究型病房已有的运行和管理模式,需结合儿科临床研究现状和医院自身需求,建立适合自身的发展模式,并在临床研究管理体系、支撑平台、信息化系统以及人才梯队等方面加强建设.

椎动脉型颈椎病(CSA)是颈椎病中常见类型,由于椎节不稳所导致.颈部疼痛、颈部活动受限、视力异常、头晕、头痛等是CSA常见的临床症状,眩晕的发作通常与颈部体位改变密切相关,部分患者甚至出现猝倒,对日常生活造成严重影响[1].

目的 探讨北京市老年住院慢性疾病(简称慢病)患者多重用药的发生情况及其影响因素.方法 抽取北京市5家三级甲等医院4个科室(神经内科、老年科、心内科、内分泌科)中年龄不小于65岁,至少患高血压、高脂血症、冠状动脉粥样硬化性心脏病(简称冠心病)、脑梗死、2型糖尿病中的1种,并于2017年3月、6月、9月、12月首周出院患者的临床基本信息.统计住院期间使用5种及以上药物患者的临床基本信息,计算多重用药发生率,并分析其影响因素.结果 共纳入912例患者,其中男455例,女457例;中位年龄74岁;中位用药品种数为9种.多重用药发生率为93.42％.单因素分析结果表明,年龄、出院诊断疾病数、查尔森合并症指数(CCI)评分、高血压、2型糖尿病、冠心病、高脂血症是多重用药的影响因素;多因素Logistic回归分析结果表明,出院诊断疾病数、2型糖尿病、冠心病是多重用药的独立影响因素.结论 多病共存、患有2型糖尿病或冠心病的老年慢病住院患者更易发生多重用药,临床应重点关注相关人群,减少过度治疗,提高用药的合理性.

The Fuyou (Fy) formula is an in-hospital preparation consisting of traditional Chinese medicine (TCM) that has been used for treating precocious puberty (PP) for more than 20 years. In this study, we aimed to clarify the effect of the Fy formula and its major components on PP. To confirm the effect of the Fy formula on the release of hypothalamic gonadotropin-releasing hormone (GnRH), GT1-7 cells were treated with estrogen to build the model group and subsequently treated with the Fy formula and its major components to explore their effects on the secretion of GnRH. The level of GnRH in GT1-7 cells was determined using enzyme-linked immunosorbent assay. The results illustrated that, compared to the model group, the Fy formula inhibited the release of GnRH. In addition, the expression levels of proteins related to GnRH secretion, including GnRH, gonadotropin-releasing hormone receptor (GnRHR), Kiss-1 metastasis-suppressor (Kiss1), G-protein coupled receptor 54 (GPR54), estrogen receptor α (ERα), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor-1 receptor (IGF-1R), were detected by real-time polymerase chain reaction (RT-qPCR). The results demonstrated that the Fy formula significantly reduced the level of GnRH secretion in the GT1-7 cell lines compared with the model group. Moreover, it significantly downregulated the expression of GnRH, GnRHR, Kiss1, GPR54, ERα, IGF-1, and IGF-1R. In summary, our results indicate that the Fy formula and its major components may inhibit the effects of estrogen, which alleviates PP through transcriptional regulation of target genes.

目的 探讨达比加群酯和利伐沙班用药错误(ME)的发生情况及影响因素,为制定针对性的防范措施提供依据.方法 收集全国临床安全用药监测网2016年1月1日至2020年12月31日期间达比加群酯和利伐沙班的ME报告,对ME的分级、错误内容、引发错误人员、发现错误人员和引发因素进行分析.结果 达比加群酯和利伐沙班ME报告共计100例,占总ME报告(59949例)的0.17％,严重ME报告5例,占总严重ME报告(508例)的0.98％.经逐例审阅最终符合要求的是98例,男65例、女33例,平均年龄62.45(29～92)岁;B级错误最多,76例(77.55％);严重ME 4例(4.08％),表现为出血及出血倾向,错误因素为药物相互作用和围术期用药.医师引发错误(45例,45.92％)中错误内容前3位为适应证、用量和数量/频次;药师引发错误(43例,43.88％)中错误内容前3位为数量、规格和品种;发现错误的人员主要是药师(77例,78.57％);引发错误的因素前3位分别为知识欠缺/培训不足、疲劳和药名相似/外观相似.结论 达比加群酯/利伐沙班严重ME占比大于总ME占比;重点需要关注处方和调配环节,同时需要加强医务人员合理用药培训和调整工作强度,减少和避免知识欠缺/疲劳,可以根据条件引进临床决策支持系统(如处方/医嘱前置审核)及自动化整盒发药机辅助减少ME.

Research ward construction is one of the important carriers to promote the transformation from traditional hospital to research hospital. Since the launch of the research ward construction project in Beijing in 2020, 30 medical institutions have been incorporated into the construction system in three batches, including grade-A general hospitals and specialty hospitals. Pediatric clinical research has its particularity, which determines that the construction of research ward in pediatric medical institutions cannot copy the construction idea of general hospitals. Referring to the experience of research hospital and research ward construction both at home and abroad, Beijing Children's Hospital explored and practiced a way of operation and management of research wards with pediatric characteristics based on the current situation of domestic pediatric medical institutions. In this paper, we put forward some suggestions and measures for further improvement of such construction, such as strengthening the service capacity of clinical research support departments and the comprehensive capacity construction of research team, in order to standardize the management of clinical research, improve the quality of clinical research, and promote the hospital to develop into a research-oriented innovative hospital.

目的 回顾性调查与分析我国儿童常用药品说明书中儿童药物代谢动力学(简称药动学)标注现状,以期为规范和完善我国儿童药品说明书信息提供参考.方法 总结和比较美国食品药品管理局、欧洲药品管理局及国家药品监督管理局发布的药品说明书相关指导原则对药动学标注内容和数据结构的要求,收集我国8家儿童医院常用药品说明书,从疾病种类、药动学数据来源、药动学参数标注情况等维度分析药品说明书儿童药动学标注情况.结果 共收集有效药品说明书1719份,说明书信息中标注有成人药动学信息的品种数有914种,标注率53.17％;标注有儿童药动学信息的品种数150种,标注率8.73％,来源于儿童临床试验的数据占70.67％.药动学参数中半衰期标注率88.00％,达峰时间标注率76.00％,达峰浓度标注率47.30％,蛋白结合率、表观分布容积、清除率、生物利用度以及血药浓度曲线下面积标注较少,标注率不超过33.30％.结论 药品说明书中儿童药动学信息缺乏现象普遍存在,标注格式不规范、内容不完整、质量不高,建议通过建立药动学数据库及儿童药动学研究方法优化体系等为完善儿童药品说明书儿童药动学信息提供方向.

新技术在儿童疾病的临床诊断、治疗和预防中发挥着重要作用,为解决儿童健康问题提供了更多的选择.是否在儿童群体开展新技术,开展研究和应用过程中如何保证儿童的最大利益是临床医生和研究者面临的重要问题.分别对基因技术、人类干细胞技术和人体器官移植三种现代技术在儿童群体研究或应用的特殊伦理问题进行探讨,为临床医生和研究者提供参考建议和应对策略,以期保障儿童权益.