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.

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.

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.

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.

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.

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.

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.

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.

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.

Analysis of Data on Adverse Drug Events Reported to the Food and Drugs Administration of the United States of America

Background: The Spontaneous Reporting System (SRS) of the Food and Drugs Administration (FDA) of the United States of America (US), known as the FDA Adverse Event Reporting System (FAERS), is a mechanism for collecting information on safety concerns associated with the use of drugs for redress, as they are used on large scale. The data which is the subject of this paper came from the FAERS database. This paper reports on the analysis of data covering 2013 to 2018 period, but compares the observed trends in the variables during this period with that of the 2007 to 2012 period to ascertain whether the trends change over time;as this paper is, in a sense, a sequel to an earlier one with a similar title as this but covering the period 2007 to 2012. Objectives: The objectives of the study reported in this paper were to: i) explore the trends in the variables involved with the adverse events problem in the 2013 to 2018 period and compare these trends with that found in the study covering the 2007 to 2012 period;ii) determine whether or not the level of missing variable values in the 2013 to 2018 period is lower than, the same or higher than it was in the 2007 to 2012 period;iii) find out how the first twenty principal suspect drugs most cited to be involved in adverse events occurring during drug use in the 2013 to 2018 period compare with that of the 2007 to 2012 period. Methods: The Food and Drugs Administration (FDA) makes extracts from the FAERS database freely available to the public on quarterly basis. Fourteen (14) out of over fifty (50) variables contained in these extracts were reckoned to be connected with the objectives of the study and were examined using the tools of frequencies, proportions and averages, on account of the nature of the data. Results: For the period 2013 to 2018, adverse events reports submitted to the FDA (US) more than doubled (2.1 times), accounting for an annual average growth rate of 15.8 %, which is considerably lower than the annual average growth rate of 22.1% for the 2007 to 2012 period. However, the reported number of cases for 2015 was 53.8% more than that of 2014. Consistent with the results for 2007 to 2012 period, the 2013 to 2018 period saw Female subjects accounting for over 60% of the annual and the overall number of reports. Overall, non-health professionals appear to have a slight edge over health professionals in reporting adverse drug events in the 2013 to 2018 period, with an indication that reports from non-health professionals are on the decline and that from health professionals is on the rise. Non-health professionals and health professionals were almost equally likely to report adverse events in the 2007 to 2012 period. Also, the findings for the 2013 to 2018 period suggest that the older one gets the more vulnerable one becomes to adverse events associated with drug use, which is consistent with the findings for the 2007 to 2012 period. Conclusion: The dangers that come with the use of drugs is an evolving one and therefore there is the need to examine SRS data from time to time so that emerging drug safety concerns can be dealt with timeously.

Active surveillance of adverse drug reactions in children in five Italian paediatric wards

Adverse drug reactions (ADRs) are an important clinical problem and contribute significantly to mortality and morbidity. Scant data on the safety of drug use in children are usually available at the time of marketing authorization, due to the limited number of trials performed in the paediatric population. Few studies monitored the incidence of ADRs in Italian hospitalized children, that cannot be compared for methodological reasons. A 6-month prospective observational study was, therefore, conducted on the paediatric wards of five hospitals in the Campania Region, Italy. Data were collected on all patients admitted to the wards during the study period through a structured questionnaire administered to the mothers and through a hospital chart review. Of the 752 patients enrolled, 86.2% were exposed to one or more drugs during hospitalization. The therapeutic class most prescribed was systemic antibacterial agents (47%). Six ADRs occurred during hospitalization (incidence 0.9%;95% CI 0.2% - 1.7%). In addition, one child was admitted to a hospital for an ADR. Five out of seven ADRs occurred in girls. The skin was the most affected organ. The medications implicated were amoxicillin, acyclovir, ibuprofen, ceftriaxone, paracetamol, and ranitidine. According to the Naranjo probability criteria, six ADRs were probably, and one possibly, related to the suspected drug. In conclusion, this study reveals that ADRs may be under-reported in children hospitalized in the Campania Region. Consequently, healthcare personnel should be alert to the possibility of ADRs. More accurate reporting of ADRs in children would result in safer use of drugs in such patients.

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.

Interim Outcomes and Adverse Events among Drug-Resistant Tuberculosis Patients Treated with Bedaquiline in the Philippines

Objectives: This study aimed to assess the interim outcomes for drug-resistant tuberculosis (DR-TB) patients treated with bedaquiline regimen under the operational research conditions compared to DR-TB patients treated without bedaquiline in their regimen, and to describe the adverse events that occurred among patients treated with bedaquiline in the Philippines. Design: Patients who were treated with a bedaquiline-containing regimen from June 2016 to May 2017 were included in this study as the intervention group, while patients who were treated without bedaquiline regimen from January 2013 to May 2016 were included as the comparison group. The interim treatment outcomes were compared using Chi-square test. The analysis of time to culture conversion within 6 months of treatment was conducted. A Cox proportional hazard model was constructed to identify the variables associated with a favorable interim treatment outcome. The R program was used for statistical analysis. Results: On the 6th month of treatment, the culture conversion for patients treated with a bedaquiline-containing regimen was significantly higher than with the comparison group [63/75 (84.0%) vs 84/117 (71.8%), p = 0.012)]. Nearly 15% of the patients treated with bedaquiline were lost to follow-up. Frequent adverse events included vomiting, dizziness, nausea, joint pain, and abdominal pain. Conclusion: The patients who were treated with bedaquiline-containing regimen have better interim treatment outcomes than those treated without bedaquiline, but the proportion of patients who were lost to follow-up remains substantial.

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.

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.

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.

Research on the Opening of Adverse Drug Reaction Data in the EU

Systematically analyze the composition of post-marketing adverse drug reaction data and the open mode in the EU, and summarize its characteristics. EU post-marketing ADR data is open to six categories of stakeholders: EMA, EC, medicines regulatory authorities in EEA member states, healthcare professionals and the public, Marketing Authorization Holders, academia, WHO and medicines regulatory authorities in third countries. The EU has implemented hierarchical opening for ADRs, with different levels containing different data and facing different stakeholders. Openness is divided into active and passive openness. In opening up data, the EU complies with relevant personal data protection laws to protect the privacy of individuals. The EU’s post-marketing adverse drug reaction data openness is characterized by a combination of data openness and privacy protection, active and passive openness, and a hierarchy of data openness. It is hoped that this can provide a reference for the opening up of post-marketing adverse drug reaction data in China.

Patterns of adverse drug reaction reporting in Ethiopia:A database analysis of spontaneous reports from 2013 to 2018

Objective:To examine the frequency and profile of spontaneous reports of adverse drug reactions(ADRs)sent to Ethiopia's pharmacovigilance(PV)database system.Methods:The descriptive and retrospective study analysed spontaneous ADR complaints reported to the PV database by healthcare professionals between 2013 and 2018.Spontaneous ADR reports that reached the PV center and met the minimum reporting criteria were identified and assessed in terms of reporting rate,patient characteristics,type of ADRs,suspected drugs,report sources,and reporters’profession.Results:A total of 657 spontaneous ADR reports were filed to the PV center between 2013 and 2018.During the study period,the reporting pattern of ADRs changed dramatically.The number of reports increased from 2013(n=12)and peaked in 2015(n=205),and then declined from 2016 to 2018(n=144,142 and 65 in 2016,2017 and 2018,respectively).Females had a higher percentage of reported cases(56.3%)than males(43.7%).The highest number of ADRs was reported in the age categories of 15-64 years(475,72.3%),followed by 0-14 years(154,23.4%),and 65 years and above(21,3.2%).Pharmacists reported the majority of ADRs(81.7%),followed by health officers(7.2%),nurses(5.8%),and physicians(5.2%).Skin and subcutaneous tissue abnormalities were the most commonly reported ADRs.The anatomical therapeutic chemicals code class"anti-infective for systemic use"was the most usually suspected medication.Trimethoprim with sulfamethoxazole as a combination ADRs was the most commonly reported drug that cause ADRs(14.2%).Conclusions:The number of ADRs reported in Ethiopia was small and unpredictable compared to developed countries,indicating the performance of PV system and level of awareness of health care professionals towards ADR reporting was not satisfactory.In order to increase the frequency of spontaneous reports,more efficient PV methods and public policies must be implemented.

Onset Time Profiles for Syncope Associated with <i>α</i>₁-Adrenoceptor Blockers in Males: Analysis of a Spontaneous Adverse Drug Event Database

Background: α1-Adrenoceptor blockers (α1Bs) are used for the treatment of benign prostatic hyperplasia and hypertension, but they are known to cause hypotension-related adverse events. The objective of the present study was to evaluate the onset time profiles for syncope associated with the use of α1Bs. Methods: We analyzed the data obtained from?the Japanese Adverse Drug Event Report (JADER) database for a period from April 2004 until November 2016 and calculated reporting odds ratios (RORs) for eight α1Bs available on the Japanese market, using disproportionality analysis. Moreover, time information recorded in the JADER database was analyzed to evaluate the onset times of adverse events. Results: In total, 186,724 reports for males older than 20 years were analyzed. Significant RORs for syncope, with 95% confidence intervals, were obtained for naftopidil (2.53, 1.81 - 3.53), silodosin (4.24, 2.37 - 5.20), and tamsulosin (2.22, 1.75 - 2.81). The median onset times of syncope for naftopidil, silodosin, and tamsulosin were 37, 26, and 108 days, respectively. The shape parameters obtained by fitting the data for the three α1Bs to the Weibull distribution were all less than 1.0, indicating that all these drugs could be classified as the early failure type. The cumulative incidence rates showed that the onset times of syncope tended to be similar among the three α1Bs. Conclusions: Patients treated with selective α1Bs should be closely monitored for 100 days, especially in the first 20 to 40 days after initiation of silodosin or naftopidil. This information may be useful for patients and healthcare professionals in preventing syncope due to the use of selective α1Bs.