Why Don’t We Adequately Identify and Manage Adverse Drug Reactions despite Having the Needed Information?

Importance/Objective: Adverse Drug Reactions (ADRs) are unavoidable, but recognizing and addressing ADRs early can improve wellness and prevent permanent injury. We suggest that available medical information and digital/electronic methods could be used to manage this major healthcare problem for individual patients in real time. Methods: We searched the available digital applications and three literature databases using the medical subject heading terms, adverse drug reaction reporting systems or management, filtered by clinical trial or systemic reviews, to detect publications with data about ADR identification and management approaches. We reviewed the reports that had abstract or summary data or proposed or implemented methods or systems with potential to identify or manage ADRs in clinical settings. Results: The vast majority of the 481 reports used retrospectively collected data for groups of patients or were limited to surveying one population group or class of medication. The reports showed potential and definite associations of ADRs for specific drugs and problems, mostly, but not exclusively, for patients in hospitals and nursing homes. No reports described complete methods to collect comprehensive data on ADRs for individual patients in a healthcare system. The digital applications have ADR information, but all are too cumbersome or incomplete for use in active clinical settings. Several studies suggested that providing information about potential ADRs to clinicians can reduce these problems. Conclusion and Relevance: Although investigators and government agencies agree with the need, there is no comprehensive ADR management program in current use. Informing the patient’s healthcare practitioners of potential ADRs at the point of service has the potential for reduction of these complications, which should improve healthcare and reduce unneeded costs.

Prevalence and Risk Factors Associated with Adverse Drug Reactions among Previously Treated Tuberculosis Patients in China

We assessed the incidence of adverse drug reactions （ADRs） with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen （2HREZS/6HRE） as recommended by the national guidelines.

阿帕替尼上市后的ADR文献分析

目的探讨阿帕替尼所致药物不良反应(ADR)的特点及规律,为其临床安全用药提供参考。方法检索自阿帕替尼2014年上市以来,中国知网、万方医学网、维普及PubMed等中英文数据库中关于其ADR及安全性评估的个案和群体报道,经筛选后对文献资料进行提取及分析。结果共纳入病例101例,涉及ADR 221例次。发生ADR的患者中,男女比例为1.24∶1,年龄以51~70岁最多,给药剂量以500 mg及以上者居多,但其中给予小剂量阿帕替尼并联合使用了其他抗肿瘤药物的患者也较易发生ADR。ADR的种类以1~2种居多,而种类最多者可高达6种。该药的ADR多发生在用药后30 d内,累及器官/系统以心血管系统损害、皮肤及其附件损害、胃肠系统损害和泌尿系统损害为主,主要临床表现为高血压/加重、手足综合征、腹痛腹泻和蛋白尿等,其严重ADR以高血压/加重、手足综合征和骨髓抑制多见。多数ADR均可通过停药、减量及对症处理实现好转/痊愈。4例死亡患者均存在基础病,且美国东部肿瘤协作组评分均≥2分。特殊ADR(如可逆性后部脑病综合征、精神异常和认知障碍等)多由阿帕替尼自身引起,亦存在阿帕替尼与原发疾病或基础疾病共同引起的可能。结论高龄、剂量较大、联合用药、存在基础病及体力状态不佳是使用阿帕替尼患者发生ADR的高危因素。建议对所有使用该药患者的血压、尿蛋白及手足皮肤进行日常监测,并注意特殊ADR的发生,以便及时发现并给予有效干预,从而避免ADR加重及继发其他ADR。

A Personalized Adverse Drug Reaction Early Warning Method Based on Contextual Ontology and Rules Learning

Background: The fatality of adverse drug reactions (ADR) has become one of the major causes of the non-natural disease deaths globally, with the issue of drug safety emerging as a common topic of concern. Objective: The personalized ADR early warning method, based on contextual ontology and rule learning, proposed in this study aims to provide a reference method for personalized health and medical information services. Methods: First, the patient data is formalized, and the user contextual ontology is constructed, reflecting the characteristics of the patient population. The concept of ontology rule learning is then proposed, which is to mine the rules contained in the data set through machine learning to improve the efficiency and scientificity of ontology rule generation. Based on the contextual ontology of ADR, the high-level context information is identified and predicted by means of reasoning, so the occurrence of the specific adverse reaction in patients from different populations is extracted. Results: Finally, using diabetes drugs as an example, contextual information is identified and predicted through reasoning, to mine the occurrence of specific adverse reactions in different patient populations, and realize personalized medication decision-making and early warning of ADR.

基于帕累托图的荧光素钠注射液致ADR报告分析及影响因素评估

目的 分析临床使用荧光素钠注射液发生药品不良反应(ADR)的临床特点,为用药安全提供参考依据。方法 收集2012年1月至2022年12月该院上报至国家ADR监测系统的荧光素钠注射液致ADR 146例患者报告,采用帕累托图分析ADR累及的系统/器官,并对患者性别、年龄及荧光素钠注射液生产厂家等进行统计分析。结果 146例患者发生194例次ADR,消化系统最为多见(127例次,65.46%),其次为呼吸系统(40例次,20.62%)和皮肤及其附件(21例次,10.82%)。年龄(≥60岁)是荧光素钠注射液致ADR的危险因素(P<0.05)。结论 消化系统反应是荧光素钠注射液致ADR的主要表现,患者年龄是ADR的主要影响因素,对该类患者进行眼底血管荧光造影时要做好用药指导,确保临床用药安全。

Analysis and Enlightenment of Big Data Platform for Adverse Drug Reaction Supervision in China and the United States

Objective To introduce the relevant big data platforms of FDA regulatory sciences and to provide reference for the construction of big data platform for China’s regulatory science under the“14th five-year plan”to deepen the reform of medical and health system.Methods A comparative analysis was made on China’s big data for regulatory science after studying the development process,operation mode,practical significance and characteristics of the big data platform for FDA regulatory science,which would help China to establish a perfect big database.Results and Conclusion The construction of big data platform for China’s regulatory science is not comprehensive compared with that in the United States.It is necessary to build data platforms in line with China’s national conditions through efforts in law,talents,standards,and other aspects.

Analysis of Adverse Reactions in the Treatment of COVID-19 with Three Chinese Patent Medicines and Three Herbal Formulas

Objective To explore the rules and characteristics of the adverse drug reactions(ADRs)of three Chinese patent medicines and three herbal formulas for the treatment of COVID-19,and to provide a reference for clinical safe medication.Methods The cases and ADR reports of the three Chinese patent medicines and three herbal formulas in PubMed,Web of Science,Springer Link,CNKI,Wanfang and VIP database were retrieved from December 2019 to May 2021.Then we extracted and analyzed the effective information included in the literature.Results and Conclusion According to the pre-developed retrieval plan,a total of 136 documents were obtained,and a total of 6 documents met the inclusion criteria finally.553 patients used three Chinese patent medicines and three herbal formulas,and there were 133 cases of adverse reactions.The adverse reactions of patients taking the three Chinese patent medicines and three herbal formulas can all be explained under the theory of traditional Chinese medicine,and the adverse reactions can be eliminated by adding or subtracting the flavor of the medicine or stopping the medicine.

Epidemiology and prevention of adverse drug reactions in the elderly

Many studies have demonstrated a correlation between increasing age and adverse drug reactions. This increased risk is related to aged-related changes in pharmacokinetics and pharmacodynamics. In addition, chronic illnesses such as congestive heart failure, coronary artery disease and hypertension are more prevalent in the elderly who also have an increased risk of diabetes, arthritis and cancer. Consequently elderly patients are often treated with multiple medications, which may cause drug interactions and adverse drug reactions. Adequate undergraduate training in clinical pharmacology and continued professional development in evidence-based therapeutics will undoubtedly reduce inappropriate prescribing and improve the quality of medications. Good communications between physicians and patients are also critically important in avoidance or prevention of adverse drug reactions in the elderly.

Analysis of Adverse Drug Reactions Caused by Chinese Patent Medicine Treatment Based on Kidney Damp-heat Syndrome and Damp-turbidity Syndrome

[Objectives]To determine relationship of the adverse drug reaction(ADR)occurrence of the single use and combined use of Huangkui Capsule and Haikun Shenxi Capsule.[Methods]To determine relationship of the ADR occurrence of the single use and combined use of Huangkui Capsule and Haikun Shenxi Capsule.[Results]The main adverse drug reactions of the single use of Huangkui Capsule or Haikun Shenxi Capsule was severe diarrhea(n=7,n=9),however the combined use of the two resulted in more occurrence of adverse drug reactions(n=23)with significant difference in contrast to the single use group(P=0.0015,P=0.0069).[Conclusions]When traditional Chinese patent medicines are used in combination to treat kidney damp-heat syndrome and damp-turbid syndrome,it is necessary to pay close attention to the occurrence of adverse drug reactions,especially the digestive system.

Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

AIM:To analyze sex differences in adverse drug reactions(ADR) to the immune suppressive medication in inflammatory bowel disease(IBD) patients.METHODS:All IBD patients attending the IBD outpatient clinic of a referral hospital were identified through the electronic diagnosis registration system.The electronic medical records of IBD patients were reviewed and the files of those patients who have used immune suppressive therapy for IBD,i.e.,thiopurines,methotrexate,cyclosporine,tacrolimus and anti-tumor necrosis factor agents(anti-TNF);infliximab(IFX),adalimumab(ADA) and/or certolizumab,were further analyzed.The reported ADR to immune suppressive drugs were noted.The general definition of ADR used in clinical practice comprised the occurrence of the ADR in the temporal relationship with its disappearance upon discontinuation of the medication.Patients for whom the required information on drug use and ADR was not available in the electronic medical record and patients with only one registered contact and no further followup at the outpatient clinic were excluded.The difference in the incidence and type of ADR between male and female IBD patients were analyzed statistically by χ 2 test.RESULTS:In total,1009 IBD patients were identified in the electronic diagnosis registration system.Out of these 1009 patients,843 patients were eligible for further analysis.There were 386 males(46%),mean age 42 years(range:16-87 years) with a mean duration of the disease of 14 years(range:0-54 years);578 patients with Crohn's disease,244 with ulcerative colitis and 21 with unclassified colitis.Seventy percent(586 pts) of patients used any kind of immune suppressive agents at a certain point of the disease course,the majority of the patients(546 pts,65%) used thiopurines,176 pts(21%) methotrexate,46 pts(5%) cyclosporine and one patient tacrolimus.One third(240 pts,28%) of patients were treated with anti-TNF,the majority of patients(227 pts,27%) used IFX,99(12%) used ADA and five patients certolizumab.There were no differences between male and female patients in the use of immune suppressive agents.With regards to ADR,no differences between males and females were observed in the incidence of ADR to thiopurines,methotrexate and cyclosporine.Among 77 pts who developed ADR to one or more anti-TNF agents,significantly more females(54 pts,39% of all anti-TNF treated women) than males(23 pts,23% of all antiTNF treated men) experienced ADR to an anti-TNF agent [P = 0.011;odds ratio(OR) 2.2,95%CI 1.2-3.8].The most frequent ADR to both anti-TNF agents,IFX and ADA,were allergic reactions(15% of all IFX users and 7% of all patients treated with ADA) and for both agents a significantly higher rate of allergic reactions in females compared with males was observed.As a result of ADR,36 patients(15% of all patients using anti-TNF) stopped the treatment,with significantly higher stopping rate among females(27 females,19% vs 9 males,9%,P = 0.024).CONCLUSION:Treatment with anti-TNF antibodies is accompanied by sexual dimorphic profile of ADR with female patients being more at risk for allergic reactions and subsequent discontinuation of the treatment.

Ophthalmic adverse drug reactions:A nationwide detection using hospital databases

AIM: To detect ophthalmic adverse drug reactions(ADRs), that occurred in Portugal from 2000 to 2009, through the utilization of administrative hospital databases. We also intended to compare the results of this methodology with spontaneous reporting.METHODS: We conducted a retrospective nationwide study using hospital administrative databases, which included all inpatients and outpatients in all public hospitals in Portugal, from 2000 to 2009. We used International Classification of Diseases- 9th Revision- Clinical Modification(ICD-9-CM) coding data that allowed the detection of ADRs. We used WHO's definition for ADR. We searched all of ICD-9-CM terms in Ophthalmology for codes that included "drug-induced", "iatrogenic", "toxic" and all other that could signal an ADR, such as "362.55- toxic maculopathy" or "365.03- steroid responders", and also "E" codes(codes from E930 to E949.9, that exclude intoxications and errors).RESULTS: From 11944725 hospitalizations or ambulatory episodes within that period of time, we identified 1524 probable ophthalmic ADRs(corresponding to a frequency of 1.28 per 10000 episodes) and an additional 100 possible ophthalmic ADRs. We used only 4 person-hours in the application of this methodology. A total of 113 spontaneous reports arose from ophthalmic ADRs from 2000 to 2009 in Portugal(frequency of 0.095 per 10000 episodes).To our knowledge, this was the first estimate of the frequency of ophthalmic ADRs through the use of databases, and the first nationwide estimate of ophthalmic ADRs, in Portugal. We identified 1524 probable ADRs and 100 possible ADRs. CONCLUSION: This database methodology adapted for Ophthalmology may represent a new approach for the detection of ophthalmic ADRs, since these codes exist in the ICD-9-CM classification. Its performance was clearly superior to spontaneous reporting.

A Time to Event Analysis of Adverse Drug Reactions Due to Tenofovir, Zidovudine and Stavudine in a Cohort of Patients Receiving Antiretroviral Treatment at an Outpatient Clinic in Zimbabwe

Background: Achieving the long terms goals of antiretroviral treatment (ART) requires a careful approach during treatment initiation that takes into account patient’s psychosocial state, availability and accessibility of treatment combinations, and adherence support. Adverse drug reactions that occur during the initial phases have a bearing on treatment outcomes and thus need to be monitored and treated. Objective: This study was done to assess length of time (survival time) it took for clinically significant adverse drug reactions to occur in patients taking Nucleoside Reverse Transcriptase Inhibitors (N(t)RTI) available for treatment of Human Immunodeficiency Virus (HIV) infection in Zimbabwe. Methods: A retrospective cohort of patient data collected from January 2009 to December 2012 was extracted from an Electronic Health Record database. Data from patients who were initiated on antiretroviral (ARV) drug regimens containing N(t)RTI drugs were analysed for survival time. A sample of 205 patient files was extracted for the time period for survival analysis using adverse drug reactions due to N(t)RTI drugs. Results: After data extraction, a total of 205 patient records were used in determining the time to event analysis of ADR’s in the cohort. The age range for the patients included in the study was 9 - 76 with a mean of 41 years (s.d = 14.8). Patients initiated on stavudine had a lower survival time before a clinically significant ADR compared to tenofovir (-365 days, p-value < 0.0005). Patients on zidovudine also had a less time before a significant reaction compared to those on tenofovir (-230 days;p-value = 0.008). Patients on zidovudine fared better compared to those on stavudine (-134 days;p-value < 0.0005). The mean survival time was highest for tenofovir (618 days), followed by zidovudine (388 days), and then stavudine (254 days).Conclusion: Patients on tenofovir have a longer survival time before a clinically significant adverse reaction. Treatment programmes need to continue commencing patients on tenofovir containing regimens as patients can be maintained for longer periods on this regimen.

Analysis and Management of Adverse Drug Reactions after Injection of Amphotericin B in AIDS Patients with Fungal Infection

Objective: To understand the condition of adverse drug reactions and the treatment procedures of amphotericin B for injection in patients with AIDS complicated with fungal infection. Methods: For the research object, a retrospective analysis of adverse reactions of amphotericin B injection in 121 patients of AIDS complicated with fungal infection was reported in our hospital from October 2017 to June 2021 to observe the adverse drug reactions of patients after treatment with amphotericin B for injection, 87 cases with general degree (regarded as the general group) and 34 cases with serious degree (regarded as the serious group), and analyze the general data, medication and course of disease of the two groups for symptomatic treatment. Results: Adverse reactions such as hypokalemia, abnormal liver function, renal impairment, leucopenia and drug fever were more common in the two groups, and there were also many adverse reactions such as bone marrow suppression, rash, anemia, thrombocytopenia, nausea, vomiting, fatigue, dizziness, pruritus, angina pectoris, vertigo, abdominal pain and diarrhea. The rates of leukopenia and drug fever in general group were significantly lower than those in severe group (P < 0.05);in the dose of amphotericin B used, the rate of using 25 mg and more than 25 mg in the general group was significantly lower than that in the severe group (P < 0.05). After symptomatic treat-ment, most patients have improved, and a few are unknown or have not improved. Con-clusion: Amphotericin B for injection has great side effects and will cause different degrees of adverse drug reactions. The dose of amphotericin B for clinical treatment should be ad-justed and disposed according to the adverse reactions to avoid serious consequences.

Mining potential adverse drug reactions of Houttuynia cordata Thunb from "real world" cases

Objective: Search the "real world" case reports of Houttuynia cordata Thunb (HCT)-associated adverse drug reactions (ADRs) to systematically mine potential ADRs of HCT and further investigate whether HCT contained preparations could cause aristolochic acid nephropathy or cancer. Methods: PubMed, EMBASE, Science Direct, Scopus, Web of Science, and CNKI, Wanfang, VIP, Sinomed databases were searched from databases setup to 1st January 2019. All case reports using HCT contained preparations were pooled according to inclusion and exclusion criteria. 15 items in case reportes including basic informations of studies/patients, characters/treaments of ADRs were extracted and analyzed. Results: A total of 346 case reports (441 patients) on the use of different preparations of HCT were finally pooled, among which 89 articles (117 patients) just presented efficacy reports without ADRs and 257 articles (324 patients) on the HCT-related ADRs were further analyzed.① HCT in vivo injections were recorded in 265 articles (338 patients) including 249 ADR reports (315 patients) and 16 efficacy reports (23 patients). As for the ADRs reports, allergic reaction was the major ADRs with different symptoms and onset time. The worst consequences were anaphylactic shock (116/315) and death (11/315), followed by dyspnea (228/315), change of complexion (181/315), heart of abnormality (180/315), chest tightness (147/315), cyanosis (142/315) and so on. The fast onset time was 10 seconds and the most ADRs happened in 30 minutes. Dexamethasone was the mainly medication to treat ADRs.② Oral HCT agents were descripted in 75 articles (94 patients) including 8 ADR reports (9 patients) and 67 efficacy reports (85 patients). Among the 8 ADR reports, 8 patients used Chinese patent medications contained HCT and only 1 patient used HCT decoction. The ADRs almost manifested as skin symptoms, including rubella, macula, rash and urticaria.③ HCT external preparations reported in 6 articles (9 patients), none of those presented any ADRs symptoms.④ No case was found to develop cancer, aristolochic acid nephropathy, interstitial nephritis, renal interstitial fibrosis or renal failure due to HCT preparations. Conclusion: The HCT-related ADRs were mostly caused by its processed preparations, including HCT injections and patent preparation. The oral HCT agents as docoction rearly caused ADRs. There were no reports of aristolochic acid nephropathy or cancer cases caused by HCT.

Research and Enlightenment of Text Mining Applications in ADR from Social Media

Objective To discuss how to use social media data for post-marketing drug safety monitoring in China as soon as possible by systematically combing the text mining applications,and to provide new ideas and methods for pharmacovigilance.Methods Relevant domestic and foreign literature was used to explore text classification based on machine learning,text mining based on deep learning(neural networks)and adverse drug reaction(ADR)terminology.Results and Conclusion Text classification based on traditional machine learning mainly include support vector machine(SVM)algorithm,naive Bayesian(NB)classifier,decision tree,hidden Markov model(HMM)and bidirectional en-coder representations from transformers(BERT).The main neural network text mining based on deep learning are convolution neural network(CNN),recurrent neural network(RNN)and long short-term memory(LSTM).ADR terminology standardization tools mainly include“Medical Dictionary for Regulatory Activities”(MedDRA),“WHODrug”and“Systematized Nomenclature of Medicine-Clinical Terms”(SNOMED CT).

Random Forest Analysis the Influencing Factors on Adverse Drug Reactions of Qingkailing Injection

Objective:To investigate the influencing factors of adverse drug reaction(ADR)in Qingkailing injection.Methods:Based on the hospitals centralized monitoring data of multicenter and prospective,the patients who used Qingkailing injection from January 2013 to March 2016 were monitored in 48 medical institutions in China.The nesting case-control study was used and the random forest was used for analysis.The main contents of the analysis are as follows:past history,past allergy history and ADR history,clinical diagnosis,dosage,interval drug,solvent type,combined drug use,etc.Results:A total of 30842 cases with Qingkailing injection were included,with 92 cases of adverse reactions and the incidence of adverse reactions was 3‰.According to the nested case-control study design,the influencing factors of 92 patients with ADR and 276 non-drug-related adverse reactions were displayed on the basis of statistical description(significance level P≤0.2 and clinical information)using Random forest analysis shows that the factors affecting the ADR of the Qingkailing injection according to the MeandecaseGini are from high to low in the first 15 positions:Vitamin supplements,tumors,gastrointestinal diseases,traditional Chinese medicine,previous allergic history,cerebral insufficiency,rash,urinary tract infection,vascular and lymphovascular diseases,pioglitazone,metabolic and endocrine system drugs,past ADR history,respiratory and mediastinal diseases,dioxpromazide,pneumonia.Conclusion:The incidence of adverse reactions in Qingkailing injection hospital is 3%.The factors closely related to the occurrence of ADR are previous tumors,gastrointestinal diseases,history of adverse reactions of rash,urinary tract infection,insufficient cerebral blood supply,respiratory system and other diseases,pioglitazone and other combined drugs.

小儿常用药ADR的发生规律、特点及给予用药指导的作用分析

目的分析小儿常用药不良反应的发生规律、特点,为临床用药提供参考指导。方法收集2019年1月至2020年10月河南省儿童医院150例小儿常用药不良反应(ADR)报告,分析ADR发生特点及规律。结果150例ADR报告中,轻度占45.33%,中度占40.67%,重度占14.0%。对原患疾病影响:无明显影响占54.0%,延长治疗时间占41.33%,疾病加重占4.67%。治疗情况:治愈占49.33%,好转占46.0%,出现后遗症占4.67%。男占52.0%,女占48.0%。年龄分布:1~3岁占35.33%,>3~6岁占27.33%,>6~9岁占23.33%,>9岁占14.0%。抗生素类药物占50.0%,中药制剂占27.33%,维生素类占12.0%,呼吸系统用药占4.0%,循环系统用药占4.0%,解热镇痛药物占2.67%。给药剂型:注射剂占85.33%,颗粒占8.0%,片剂占5.33%,滴剂占1.33%。给药途径:静脉滴注占83.33%,肌肉注射占2.0%,口服占6.67%。皮肤及其附件占59.33%;全身性损害占12.0%;五官系统占8.67%;消化系统占6.67%;神经系统占5.33%;呼吸系统占4.0%;循环系统占2.67%;肌肉及骨骼系统占0.67%,泌尿系统占0.67%。结论小儿常用药不良反应较多,加强用药监测,可为临床合理、安全用药提供参考。

Clinical features of adverse reactions associated with telbivudine

AIM: To analyze the clinical features and risk factors of adverse reactions associated with telbivudine. METHODS: Clinical data were collected from cases that presented with serious adverse reactions to telbivudine. We analyzed general information and medicine status, clinical features, results of examination, and misdiagnosis. RESULTS: Out of 105 patients who were treated with telbivudine for hepatitis B in an outpatient department from January, 2007 to January, 2008, five presented with serious adverse drug reactions. Most of these five patients had used other nucleoside analogues in the past. Four were treated with a combination of telbivudine and interferon or another nucleoside analogue, while the other received an increased dose of telbivudine. The main adverse reactions were myalgia and general weakness. This was accompanied by cardiac arrhythmia in one patient, and nervous symptoms in three. Serum creatine kinase was elevated. The rate of misdiagnosis was high. CONCLUSION: The adverse reactions were related to telbivudine, but the biological mechanism of the reactions is not yet clear. Combination therapy with interferon or another nucleoside analogue and a high dose may increase the risk of adverse reactions.

Induced pluripotent stem cells for therapy personalization in pediatric patients:Focus on drug-induced adverse events

Adverse drug reactions(ADRs)are major clinical problems,particularly in special populations such as pediatric patients.Indeed,ADRs may be caused by a plethora of different drugs leading,in some cases,to hospitalization,disability or even death.In addition,pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs,leading,in some cases,to more severe consequences.To improve the comprehension,and thus the prevention,of ADRs,the set-up of sensitive and personalized assays is urgently needed.Important progress is represented by the possibility of setting up groundbreaking patient-specific assays.This goal has been powerfully achieved using induced pluripotent stem cells(iPSCs).Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body,this model may be accurate in predicting drug toxicity,especially when this toxicity is related to individual genetic differences.This review is an up-to-date summary of the employment of iPSCs as a model to study ADRs,with particular attention to drugs used in the pediatric field.We especially focused on the intestinal,hepatic,pancreatic,renal,cardiac,and neuronal levels,also discussing progress in organoids creation.The latter are three-dimensional in vitro culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine,liver,pancreas,kidney,heart,and brain.Based on the existing knowledge,these models are powerful and promising tools in multiple clinical applications including toxicity screening,disease modeling,personalized and regenerative medicine.

Adverse reactions of Amiodarone

Adverse drug reaction is defined by the World Health Organization as any response to a drug that is noxious and unintended and occurs at a dose normally used in man.Older people are at elevated risk of adverse drug reactions—because of changes in pharmacodynamics,concurrent use of multiple medications and the related drug interactions.However,adverse drug reactions are significantly underestimated in the elderly population that is also exposed to inappropriate drugs.Amiodarone is an antiarrhythmic drug used commonly for the treatment of atrial fibrillation and is increasingly prescribed in older people.While amiodarone is an efficient drug for rhythm control,it’s a carrier of different adverse reactions,and pro and cons must be carefully evaluated before its use especially in older people.