No Incidence of Liver Cancer Was Observed in A Retrospective Study of Patients with Aristolochic Acid Nephropathy / 中国结合医学杂志

OBJECTIVE@#To assess the risk of aristolochic acid (AA)-associated cancer in patients with AA nephropathy (AAN).@*METHODS@#A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December 2014. Long-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of cancer. The primary endpoint was the incidence of liver cancer, and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to 2014.@*RESULTS@#A total of 337 patients diagnosed with AAN were included in this study. From the initiation of taking AA to the termination of follow-up, 39 patients were diagnosed with cancer. No cases of liver cancer were observed throughout the entire follow-up period, with urinary cancer being the predominant type (34/39, 87.17%). Logistic regression analysis showed that age, follow-up period, and diabetes were potential risk factors, however, the dosage of the drug was not significantly associated with urinary cancer.@*CONCLUSIONS@#No cases of liver cancer were observed at the end of follow-up. However, a high prevalence of urinary cancer was observed in AAN patients. Establishing a direct causality between AA and HCC is challenging.

Self-assumed Neurologic Related Condition Deviated Metoclopramide-Induced Acute Dystonic of Oculogyric Crisis in a Woman of Childbearing Age: A Case Report

A 26-year-old Malaysian woman (childbearing age) attended a private primary care clinic with a known case of gastroesophageal reflux disease (GERD) and complained of persistent nausea and a few episodes of vomiting. She had no known drug allergy, no surgical history, no hospitalization in the last two years, was a non-smoker, and no history of drug or alcohol abuse. The patient was prescribed Tab metoclopramide 10 mg TDS and Tab ranitidine 150 mg BD for five days. About 30 min after oral administration of both medicines, her eyes rolled involuntary upward, leading to lateral deviation of the eyes, and mouth jaws clenched as if “dislocated jaws.” The patient was immediately brought into an emergency department (ED) of a public tertiary care hospital. A drug challenge test was done which resulted in the withdrawal of metoclopramide. The accompanied sister later disclosed that the patient had taken metoclopramide and ranitidine from a private clinic earlier in the day. The patient self-assumed to have a sudden seizure, due to excessive hot weather and dehydration. A slow intravenous infusion of 50 mg/mL diphenhydramine hydrochloride in 0.9% w/v NaCl 100 mL was administered stat. Consequently, the symptoms vanished after approximately 30 min of the therapy, devoid of relapse. The patient was discharged from ED post 8 hours of monitoring with complete recovery. Physicians frequently prescribe metoclopramide to treat nausea and vomiting, which may cause adverse drug reaction of acute dystonic oculogyric crisis (OGC). Due to its unwanted and unpredictable extrapyramidal symptoms, metoclopramide should be prescribed and dispensed with caution. Thorough history taking at ED is imperative for correct early diagnosis and treatment, as metoclopramide-induced dystonic OGC has a high probability of confusion with other causes of dystonia such as conversion and seizures, encephalitis, tetanus, and hypercalcemic tetany.

Research Progress of Upadacitinib in the Treatment of Crohn’s Disease / 中山大学学报(医学科学版)

Crohn’s Disease （CD） is a destructive， relapsing and remitting chronic inflammatory bowel disease that usually progresses to irreversible intestinal structural and functional changes， such as intestinal lumen stenosis， fistula formation and perianal lesions， severely affecting the quality of life of patients. This review summarized the research progress on the mechanism， clinical application and safety of upadacitinib in the treatment of CD. Upadacitinib can increase the clinical remission and endoscopic response rates in patients with CD， improve the long-term outcome of CD patients and provide a new idea for the treatment of CD patients by using biological agents.

Drug-induced dysphagia risk in elder people——A pharmacovigilance study of FDA Adverse Event Reporting System (FAERS) database / 中国临床药理学与治疗学

AIM: To evaluate the risk of drug-related dysphagia in elder people based on the FDA Adverse Event Reporting System (FAERS). METHODS: We collected the reports of dysphagia in elder people (Age≥65) from 2004 quarter 1 through 2022 quarter 2 of FAERS by Open Vigil 2.1 database. The reported odds ratio (ROR) and the proportional reported ratio (PRR) were calculated to detect the adverse reaction signal of drug-induced dysphagia in elder people. Signal generation standard of ROR: number of reports≥3 with the lower limit of 95% confidence interval (CI) of the ROR value>1, PRR≥2 and c

Emerging trends in organ-on-a-chip systems for drug screening

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

A multi-behavior recognition method for macaques based on improved SlowFast network / 生物医学工程学杂志

Macaque is a common animal model in drug safety assessment. Its behavior reflects its health condition before and after drug administration, which can effectively reveal the side effects of drugs. At present, researchers usually rely on artificial methods to observe the behavior of macaque, which cannot achieve uninterrupted 24-hour monitoring. Therefore, it is urgent to develop a system to realize 24-hour observation and recognition of macaque behavior. In order to solve this problem, this paper constructs a video dataset containing nine kinds of macaque behaviors (MBVD-9), and proposes a network called Transformer-augmented SlowFast for macaque behavior recognition (TAS-MBR) based on this dataset. Specifically, the TAS-MBR network converts the red, green and blue (RGB) color mode frame input by its fast branches into residual frames on the basis of SlowFast network and introduces the Transformer module after the convolution operation to obtain sports information more effectively. The results show that the average classification accuracy of TAS-MBR network for macaque behavior is 94.53%, which is significantly improved compared with the original SlowFast network, proving the effectiveness and superiority of the proposed method in macaque behavior recognition. This work provides a new idea for the continuous observation and recognition of the behavior of macaque, and lays the technical foundation for the calculation of monkey behaviors before and after medication in drug safety evaluation.

Utilidad estadística de los estudios de farmacovigilancia para evaluar reacciones adversas a medicamentos

Introducción: la detección oportuna y la evaluación de las reacciones adversas de los medicamentos es cada vez más importante. En Cuba existe la necesidad de profundizar y extender con alcance nacional los estudios de Farmacovigilancia, por tal motivo se expone como objetivo fundamentar sustentados en la estadística el uso de estudios de farmacovigilancia para la detección, registro, notificación y evaluación de las sospechas de las reacciones adversas de los medicamentos valorando su seguridad. Desarrollo: se brinda un resumen de tipos de estudios de farmacovigilancia con ejemplos de objetivos de investigaciones realizadas y publicadas en revistas científicas posibles a considerar y aplicar a las condiciones reales que tenga cada investigador, se presentan variables que ya han sido establecidas en otros estudios que se deben tener en cuenta para estudiar seguridad de los medicamentos y técnicas estadísticas teniendo en cuenta los tipos de variables a relacionar. Conclusiones: se concluye que resulta un logro científico conocer formas de profundizar y extender los estudios de Farmacovigilancia para tomar conocimiento de la seguridad de los fármacos y promover un uso racional, científico y adecuado de los mismos, en beneficio de la comunidad.

Introduction: timely detection and evaluation of adverse drug reactions is increasingly important. In Cuba there is a need to deepen and extend pharmacovigilance studies nationwide. That is why it is stated, based on statistics, the use of studies for the detection, registration, notification and evaluation of suspected adverse drug events, assessing their safety. Development: a summary of types of pharmacovigilance studies is provided with examples of objectives of research works already done and published in scientific magazines likely to consider and use in actual conditions each researcher has, and there are also presented variables that have already been established in other studies, which must be taken into account to study drug safety and statistical techniques considering the types of variables to be related. Conclusion: it is concluded that knowing ways to deepen and spread the Pharmacovigilance studies in order to be aware of drug safety and foster their rational, scientific and adequate use in the interests of the community is indeed a scientific accomplishment.

Introdução: a detecção e avaliação oportunas de reações adversas a medicamentos está se tornando cada vez mais importante. Em Cuba há uma necessida de de aprofundar e ampliar os estudos de farmacovigilância com âmbito nacional, por esta razão é declarado como um objetivo fundamentar com base em estatísticas o uso de estudos de farmacovigilância para a detecção, registro, notificação e avaliação de suspeitas de reações adversas de medicamentos que avaliam sua segurança. Desenvolvimento: um resumo dos tipos de estudos de farmacovigilância é fornecido com exemplos de objetivos de pesquisa realizados e publicados em possíveis revistas científicas a serem consideradas e aplicadas às condições reais que cada pesquisador possui, variáveis que já foram estabelecidas em outros estudos que devem ser levadas em conta para estudar a segurança de medicamentos e técnicas estatísticas levando em conta os tipos de variáveis a serem relacionadas. Conclusões: conclui-se que é uma conquista científica conhecer formas de aprofundar e ampliar os estudos de farmacovigilância para tomar conhecimento da segurança dos medicamentos e promover um uso racional, científico e adequado dos mesmos, em benefício da comunidade.

Antibiotic safety among neonates and paediatrics in a public hospital: KwaZulu-Natal

Background: The World Health Organization (WHO) guidelines recommend the empiric treatment of infections before definitive treatment begins. However, ethical concerns limit the availability of clinical trials in neonates and paediatrics to fully ascertain the safety profile of antibiotics in these populations. Aim: This study aimed to quantify the use of antibiotics among neonates and paediatrics and commented on the use, rationale and appropriateness of antibiotics prescribed. Setting: A secondary level public sector hospital located in Durban, KwaZulu-Natal. Methods: Demographic and treatment information of neonates and paediatrics were collected retrospectively from January 2022 to June 2022. Data were obtained from patient files and extracted for analysis using Microsoft Excel®. Analytical and descriptive statistics were used to analyse patient demographics and treatment variables. Results: A total of 568 antibiotics, issued to 389 patients, were reviewed. Penicillins (40.1%), aminoglycosides (24.3%) and combination penicillin-beta-lactam inhibitors (23.3%) were identified as the most frequently prescribed antibiotics for inpatients. Most antibiotics prescribed to inpatients were for complications associated with pre-term birth (66.9%). Combination penicillin-beta-lactam inhibitors (34.7%), penicillins (29.5%) and cephalosporins (29.5%) were the most frequently prescribed antibiotics to outpatients. A correlation was found between the route of administration and the duration of therapy; the intravenous route (63.6%) was preferred over the oral route (36.4%) for administration. Conclusion: Many broad-spectrum antibiotics were prescribed, thus increasing the risk of resistance. Antibiotics were being prescribed according to the guidelines; however, there is still a need for therapeutic drug monitoring to ensure the continuation of rational drug use. Contribution: There was evidence of rational use of antibiotics in the public hospital (KwaZulu-Natal), in keeping with economic and availability factors.

Conocimientos, actitudes y prácticas de farmacovigilancia en el contexto de la COVID-19 en profesionales de la salud del Seguro Social del Perú / Knowledge, attitudes and practices of pharmacovigilance in the context of COVID-19 in health professionals of the peruvian social insurance

RESUMEN El estudio tuvo como objetivo evaluar el conocimiento, las actitudes y prácticas de un grupo de profesionales de la salud sobre la farmacovigilancia en el contexto de la COVID-19 en el Seguro Social de Salud del Perú (EsSalud). Se realizó un análisis secundario descriptivo de una base de datos que incluía las respuestas de una encuesta en línea realizada por el Centro de Referencia Institucional de Farmacovigilancia y Tecnovigilancia de EsSalud. De 144 participantes, el 66% mostró alto nivel de conocimiento y el 81,2%, actitud positiva; sin embargo, el 71,5% tuvo un inadecuado nivel de práctica de farmacovigilancia. Si bien los profesionales de EsSalud demostraron tener alto conocimiento y actitud positiva para implementar farmacovigilancia, esto no se ve reflejado en la práctica de esta actividad en la época de pandemia por el SARS-CoV-2. Se deben emplear estrategias para integrar a la farmacovigilancia en las actividades asistenciales en beneficio de la seguridad del paciente.

ABSTRACT The study aimed to evaluate a group of health professionals' knowledge, attitudes, and practices on pharmacovigilance in the context of COVID-19 in the Peruvian Social Health Insurance (EsSalud). A descriptive secondary analysis was carried out on a database that included responses from an online survey conducted by the Institutional Referral Center for Pharmacovigilance and Technovigilance of EsSalud. Of 144 participants, 66% showed a high level of knowledge and 81.2% had a positive attitude; however, 71.5% had an inadequate level of pharmacovigilance practice. Although EsSalud professionals demonstrated a high level of knowledge and positive attitude to implement pharmacovigilance, this is not reflected in the practice of this activity during the SARS-CoV-2 pandemic. Strategies should be implemented to integrate pharmacovigilance into healthcare activities to benefit patient safety.

Evaluation of efficiency of drug safety supervision in China based on DEA model and Malmquist index / 中国药房

OBJECTIVE To evaluate the efficiency of drug safet y supervision in China after issuing a series of new policies in 2018，and to provide the suggestions for optimizing the construction of drug safety supervision system in China and narrowing regional differences. METHODS The panel data of input-output indexes of 18 provinces in 7 administrative regions were collected from the official website of provincial drug regulatory departments ，the open platform of budget and final accounts and the official website of National Bureau of Statistics. Data envelopment analysis （DEA）model and Malmquist index were adopted to conduct an empirical analysis on the efficiency of drug safety supervision in China during 2019-2020. RESULTS & CONCLUSIONS DEA analysis showed that during 2019-2020，the overall technical efficiency （TE）of drug safety supervision in China was lower than 1.000，which didn ’t meet effective DEA. Only Liaoning ，Guangdong and Guangxi had TE of 1.000，indicating significant differences in efficiency of drug safety supervision in different regions. The results of Malmquist index analysis showed that the overall efficiency of drug safety regulation in China was declining ，among which insufficient regulatory capacity supported by technology and large loss of professional personnel were the main factors ，and the improvement of drug regulatory departments ’ management and supervision level could ensure the improvement of overall regulatory efficiency. The current scale of drug supervision in nearly half of provinces （8/18）was close to the optimal state. It is necessary to strengthen the infrastructure construction and pay attention to the training of professional talents to optimize the drug regulatory team ；strengthen the innovation of supervision technology and improve the construction of technological support system ；rationally allocate regulatory resources and balance regional regulation according to local conditions to improve the construction of drug safety supervision system in China.

CHINA PH ARMACY Volume 33，Number 3，February 15，2022 Semimonthly Table of Contents Study on the action framework and key problem of drug safety governance in China / 中国药房

OBJECTIVE To provide reference for clarifying the action and development direction of China ’s drug safety governance. METHODS Based on governance theory ，an analysis framework of “Motivation-Sharing-Performance and Feedback ” was established to explain the mechanism of cross-sector collaboration governance of drug safety. By constructing the action framework of national drug safety governance of “3 stages+1 incubation period ”，the connotation of each stage and possible challenges were analyzed ，and improvement suggestions were put forward. RESULTS & CONCUSIONS The obstacles that restricted the effectiveness of drug safety governance in China were mainly due to insufficient information ，resource mobilization and power sharing. Therefore ，the“basic collaboration stage ”should expand the scope of information sharing and involve non-governmental entities ；the“legislative coordination stage ”should focuse on the provision of formal legal systems so that non-governmental forces can play a necessary role in governance activities ；the“deepening of the coordination stage ”should promote the formal integration of social forces into governance system ，and truly realize the transition from “passive participation ” to self-management. It is recommended to continuously improve the construction of drug safety governance system in China in terms of governance norms ，communication mechanisms ，capacity development based on a holistic perspective.

Effects of bevacizumab injection on immune function and drug safety in patients with non-small cell lung cancer / 中国医师进修杂志

Objective:To investigate the effects of bevacizumab injection on immune function and drug safety in patients with non-small-cell lung cancer (NSCLC).Methods:A total of 80 NSCLC patients admitted to Liaocheng Second People′s Hospital from August 2018 to August 2020 were selected as study subjects. They were divided into the observation group and the control group by random number table method, each group with 40 cases. The control group received routine chemotherapy and the observation group received bevacizumab injection as adjuvant therapy on the bases of control group. Short-term efficacy, serum T lymphocyte subsets, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF) levels and the incidence of adverse reactions were compared between the two groups.Results:The total effective rate and disease control rate in the observation group were significantly higher than those in the control group: 77.5%(31/40) vs. 55.0%(22/40), 92.5%(37/40) vs. 75.0%(30/40), χ2 = 4.53, 4.50, P<0.05. After the treatment, the levels of CD 3+, CD 4+, CD 8+ and CD 4+/CD 8+ in the observation group were increased ( P<0.05), while those in the control group were decreased ( P<0.05), the levels of CD 3+, CD 4+, CD 8+ and CD 4+/CD 8+ in the observation group after treatment were higher than those in the control group ( P<0.05). After the treatment, the levels of serum VEGF and b-FGF in both groups were decreased ( P<0.05), and the above indicators in the observation group were significantly lower than those in the control group ( P<0.05). The rate of adverse reactions in two groups had no significant differences ( P>0.05). Conclusions:Bevacizumab injection is safe and effective in the treatment of NSCLC, which can significantly improve the immune function of patients and reduce their serum VEGF and b-FGF levels.

Risk factors for herb-induced liver injury / 临床肝胆病杂志

Drug-induced liver injury (DILI) is one of the common adverse drug reactions and is the main cause of withdrawal of drugs after marketing, which has attracted more and more attention of the public, and herb-induced liver injury (HILI) is a special type of DILI. In recent years, the frequent occurrence of HILI not only seriously endangers the health of patients, but also causes the controversy over the safety of traditional Chinese medicine. Therefore, this article reviews the potential risk factors for HILI from the three aspects of "patient", "drug", and "use", so as to provide a basis for the objective identification, prevention, and control of HILI and a reference for the construction of traditional Chinese medicine pharmacovigilance system represented by liver injury.

Which Is Safer, Chinese Medicine or Western Medicine? Comparative Analysis Based on Chinese Spontaneous Reporting Database / 中国结合医学杂志

OBJECTIVE@#To compare the safety differences between Chinese medicine (CM) and Western medicine (WM) based on Chinese Spontaneous Reporting Database (CSRD).@*METHODS@#Reports of adverse events (AEs) caused by CM and WM in the CSRD between 2010 and 2011 were selected. The following assessment indicators were constructed: the proportion of serious AEs (PSE), the average number of AEs (ANA), and the coverage rate of AEs (CRA). Further comparisons were also conducted, including the drugs with the most reported serious AEs, the AEs with the biggest report number, and the 5 serious AEs of interest (including death, anaphylactic shock, coma, dyspnea and abnormal liver function).@*RESULTS@#The PSE, ANA and CRA of WM were 1.09, 8.23 and 2.35 times higher than those of CM, respectively. The top 10 drugs with the most serious AEs were mainly injections for CM and antibiotics for WM. The AEs with the most reports were rash, pruritus, nausea, dizziness and vomiting for both CM and WM. The proportions of CM and WM in anaphylactic shock and coma were similar. For abnormal liver function and death, the proportions of WM were 5.47 and 3.00 times higher than those of CM, respectively.@*CONCLUSION@#Based on CSRD, CM was safer than WM at the average level from the perspective of adverse drug reactions.

Retrospective investigation and analysis of off-label drug use for tic disorder in a tertiary women’s and children’s hospital / 药学实践杂志

Objective To analyze the current situation of off-label drug use for tic disorder in a tertiary maternity and child hospital, so as to promote clinical safe and rational drug use. Methods Through the hospital information system, the pediatric outpatient prescriptions diagnosed with tic disorder from July 2019 to August 2020 were selected, and the prescriptions of off-label use was evaluated according to the 2020 off-label drug management regulations. Results A total 1251 pediatric prescriptions diagnosed with tic disorder were collected. The incidence of off-label drug use was 29.58%. The main types of off-label were over-indications and over-age. The main varieties of off-label drug use were risperidone tablets (47.84%) and aripiprazole tablets (43.74%). Conclusion The off-label use of drug for tic disorder in pediatric outpatient department of our hospital is relatively common，and it is necessary to standardize the management of off-label drug use to ensure rational drug use.

Utilizing social media data in post-market safety surveillance / 北京大学学报(医学版)

Post-marketing surveillance is the principal means to ensure drug use safety. The spontaneous report is the essential method of post-marketing surveillance for drug safety. Often, most spontaneous reports come from medical staff and sometimes come from patients who use the drug. The posts published by individuals on social media platforms that contain drugs and related adverse reaction content have gradually been seen as a new data source similar to spontaneous reports from drug users in recent years. Those user-generated posts potentially provide researchers and regulators with new opportunities to conduct post-marketing surveillance for drug safety from patients' perspectives mostly rather than medical professionals and can afford the possibility theoretically to discover drug-related safety issues earlier than traditional methods. Social media data as a new data source for safety signal detection and signal reinforcement have the unique advantages, such as population coverage, type of drugs, type of adverse reactions, data timeliness and quantity. Most of the social media data used in post-marketing surveillance research for drug safety are still text data in English, and even multiple languages are used by different people worldwide on several social media platforms. Unfortunately, there is still a controversy in the academic circles whether social media data can be used as reliable data sources for routine post-marketing surveillance for drug safety. A couple of obstacles of data, methods and ethics must be overcome before leveraging social media data for post-marketing surveillance. The number of Chinese social media users is large, and the social media data in the Chinese language is rapidly snowballing, which can be employed as the potential data source for post-marketing surveillance for drug safety. However, due to the Chinese language's specific characteristics, the text's diversity is different from the English text, and there is not enough accepted corpus in medical scenarios. Besides, the lack of domestic laws and regulations on privacy and security protection of social media data poses more challenges for applying Chinese social media data for post-market surveillance. The significance of social media data to post-marketing surveillance for drug safety is undoubtedly significant. It will be an essential development direction for future research to overcome the challenges of using social media data by developing new technologies and establishing new mechanisms.

Construction and exploration of pregnancy registries for medicine based on pharmaceutical service / 中华医院管理杂志

The pregnancy registry for medicine is a common method for risk evaluation for drug safety evaluation during pregnancy. The authors introduced the exploration and practice of the pregnancy drug registry mode based on pharmacy service in Women′s Hospital School of Medicine Zhejiang University. The registry of pregnancy medication with the drug consultation clinic as the fulcrum was managed by the pharmacist team in a homogenization way, and implemented according to the information process of consultation, pharmacy guidance and regular follow-up. In the consultation and follow-up work, the pharmacists established the consultation drug history through three data sources: independent report of the consultant, inquiry of pharmaceutical personnel and case sampling. The pharmacists designed and constructed information screening system, classified the consultation medicine history according to the pregnancy exposure of specific drugs. The prospective research method was designed to meet the characteristics of pregnancy medication. The study was carried out on the relationship between pregnancy exposure and birth defects of offspring. Relying on the improvement of standardization, refinement and information management level of pharmaceutical services, multi center cooperation will be strengthened in the future to carry out continuous research on pregnancy drug exposure registry and follow-up system.

How to improve CHMs quality: Enlighten from CHMs ecological cultivation / 中草药·英文版

Chinese herbal medicines (CHMs) are one of the important bioresources of medicine, which works by unlocking nature's ability to prevent diseases and recover from illnesses. Recently, it has ascended to the world stage and become a global icon. Nowadays, a considerable of researches have focused on the quality evaluation of CHMs. However, it is difficult to meet the reasonable needs of human beings for safe drug use to evaluate the quality of a huge number of inferior goods for the CHMs contaminated by pesticides and heavy metals. Hence to explore an eligible medicinal plant cultivation pattern, which can provide high quality CHMs sustainably, is most promising. This review analyzed the situation and characteristics of medicinal plant resources in different periods, including wild-harvested and cultivated resources during different stages, putting forward that ecological cultivation must be the way to develop medicinal plant cultivation and to obtain high quality CHMs.

Effect of CYP2C19 gene polymorphism on clopidogrel concentration, platelet inhibition rate and safety in patients after PCI / 药学实践杂志

Objective To explore the effect of CYP2C19 gene polymorphism on clopidogrel plasma concentration, rate of platelet inhibition and safety. Methods We screen the patients who took clopidogrel after PCI in our hospital, according to the inclusion and exclusion criteria. Blood samples were collected on the 6th day after clopidogrel administration. Clopidogrel blood concentration was determine by RP-HPLC. The CYP2C19 genotype was detected by non-amplified immune hybridization. The rate of platelet inhibition was evaluated by the thromboelastogram. The results were analyzed by SPSS 20.0 software. Results A total of 87 patients were recruited, including 46 males and 41 females. Among them, 34 cases were fast metabolism. 38 cases were medium metabolism. 15 cases were slow metabolism. The result showed that there was no significant difference in drug concentration between fast and intermediate metabolism(P=0.667). There was a significant difference in drug concentration between slow metabolism and fast metabolism or medium metabolism(P<0.05). Analysis of variance and chi-square test showed that CYP2C19 gene polymorphism has a significant effect on clopidogrel platelet inhibition rate and safety (P<0.05). Conclusion Guiding clopidogrel clinical medication based on CYP2C19 genotype alone does not necessarily achieve better therapeutic effects. CYP2C19 genotype detection and blood concentration monitoring can be combined to guide the clinical individualized administration of clopidogrel

Mining and Evaluation of Post-marketing Safe Alert Signals of Pegaspargase and L-asparaginase Based on BCPNN Method / 中国药房

OBJECTIVE： To mine and evaluate the post-marketing safety alert signals of pegaspargase （PEG-ASP） and L-asparaginase （L-ASP），and compare the safety differences between them ，so as to provide reference for clinical safe and rational drug use. METHODS ： The adverse drug event （ADE） reports of PEG-ASP and L-ASP issued by FDA adverse event reporting system from Jan. 1st，2004-Jun. 30th，2020 were retrieved. BCPNN method was used to mine the safety signals of these two drugs under the condition that the lower limit of information component （IC－2SD）＞0 and the number of events ≥3. The medium and strong signals of two drugs with IC －2SD≥1.5 were evaluated and compared in 8 system organ class，such as gastrointestinal system ，hepatobiliary system ，blood and lymphatic system ，blood vessels and lymphatic vessels ， nervous system ，immune system ，metabolism and nutrition ，various examinations. IC value of specific ADE signal and its 95％ confidence interval were analyzed by time scanning spectrum. RESULTS & CONCLUSIONS ：The reports of PEG-ASP and L-ASP as suspected drugs were 2 324 and 3 824；67 and 68 medium and strong signals were included ，respectively. In gastrointestinal system，the common strong signal of PEG-ASP and L-ASP was necrotic pancreatitis. In hepatobiliary system ，both of them showed strong signal in venoocclusive liver disease ，and this ADE was not included in the drug instruction. In blood and lymphatic system ， common strong signals of the two drugs were febrile neutropenia ，coagulation disorder ，neutropenia and febrile bone marrow regeneration disorder ；in blood vessels and lymphatic vessels ，in addition to haemodynamic instability ，IC values of other signals of L-ASP were higher than those of PEG-ASP. In nervous system ，IC values of other signals of L-ASP were higher than those of PEG-ASP except for intracranial haemorrhage. In immune system ，anaphylactic reaction was a medium signal for L-ASP but was a strong signal for PEG-ASP. In metabolism and nutritional diseases ，except for tumor lysis syndrome ，IC values of other signals of L-ASP were higher than those of PEG-ASP. The results of time scanning spectrum showed that the signals of necrotic pancreatitis and coagulation disorder of PEG-ASP were stable ，while the signals of veno occlusive liver disease and hypersensitivity were unstable and needed to be observed ；above four signals of L-ASP were stable signals. When using PEG-ASP or L-ASP clinically ， close attention should be paid to the safety problems such as hypersensitivity ，coagulation disorder ，thrombosis，necrotic pancreatitis，venoocclusive liver disease and hypoproteinemia.