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.

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.

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.

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.

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 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.

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.

Can acupuncture enhance therapeutic effectiveness of antidepressants and reduce adverse drug reactions in patients with depression? A systematic review and meta-analysis

Background: Some depressed patients receive acupuncture as an adjunct to their conventional medications.Objective: This review aims to provide evidence on whether acupuncture can enhance the therapeutic effectiveness of antidepressants for treating depression, and explore whether acupuncture can reduce the adverse reactions associated with antidepressants.Search strategy: English and Chinese databases were searched for randomized controlled trials(RCTs)published until December 1, 2021.Inclusion criteria: RCTs with a modified Jadad scale score ≥ 4 were included if they compared a group of participants with depression that received acupuncture combined with antidepressants with a control group that received antidepressants alone.Data extraction and analysis: Meta-analysis was performed, and statistical heterogeneity was assessed based on Cochran’s Q statistic and its related P-value. Primary outcomes were the reduction in the severity of depression and adverse reactions associated with antidepressants, while secondary outcomes included remission rate, treatment response, social functioning, and change in antidepressant dose.The Grading of Recommendations Assessment, Development and Evaluation(GRADE) framework was used to evaluate the overall quality of evidence in the included studies.Results: This review included 16 studies(with a total of 1958 participants). Most studies were at high risk of performance bias and at low or unclear risk of selection bias, detection bias, attrition bias, reporting bias, and other bias. Analysis of the 16 RCTs showed that, compared with antidepressants alone, acupuncture along with antidepressants reduced the Hamilton Depression Rating Scale-17(HAMD-17) scores(standard mean difference [SMD]-0.44, 95% confidence interval [CI]-0.55 to-0.33, P < 0.01;I^(2)= 14%), Self-rating Depression Scale(SDS) scores(SMD-0.53, 95% CI-0.84 to-0.23, P < 0.01;I^(2)= 79%), and the Side Effect Rating Scale(SERS) scores(SMD-1.11, 95% CI-1.56 to-0.66, P < 0.01;I^(2)= 89%). Compared with antidepressants alone, acupuncture along with antidepressants improved World Health Organization Quality of Life-BREF scores(SMD 0.31, 95% CI 0.18 to 0.44, P < 0.01;I^(2)= 15%), decreased the number of participants who increased their antidepressant dosages(relative risk[RR] 0.32, 95% CI 0.22 to 0.48, P < 0.01;I^(2)= 0%), and resulted in significantly higher remission rates(RR1.52, 95% CI 1.26 to 1.83, P < 0.01;I^(2)= 0%) and treatment responses(RR 1.35, 95% CI 1.24 to 1.47, P < 0.01;I^(2)= 19%) in terms of HAMD-17 scores. The HAMD-17, SDS and SERS scores were assessed as low quality by GRADE and the other indices as being of moderate quality.Conclusion: Acupuncture as an adjunct to antidepressants may enhance the therapeutic effectiveness and reduce the adverse drug reactions in patients receiving antidepressants. These findings must be interpreted with caution, as the evidence was of low or moderate quality and there was a lack of comparative data with a placebo control.Systematic review registration: INPLASY202150008.

Physicians’perspectives on adverse drug reactions in pediatric routine care:a survey

Background Children and adolescents are at particular risk for adverse drug reactions(ADRs).We investigated physicians’perceptions on ADRs in pediatric routine care.Methods In this exploratory study from April to November 2020,we invited physicians treating pediatric patients across Germany to complete an online questionnaire consisting mainly of closed questions.Results Completion rate was 98%(127/129).Of all participants,23%(29/127)stated they were not able to estimate how many of their pediatric patients experienced ADRs during drug therapy.The remaining physicians estimated that 7.5%(median;Q25/Q753%/20%)of their pediatric patients were afected by ADRs.Regarding counseling on ADRs,61%(77/127)stated they do not ask regularly the extent to which parents want to be informed.In total,26%(33/127)stated they avoid counseling on ADRs concerning commonly used approved therapies,whereas only 4%(5/127)did so concerning of-label use(P<0.001).Altogether,16%(20/127)stated they rather prescribe new medicines as they hope for better efectiveness;72%(91/127)said they are cautious about doing so owing to yet unknown ADRs.Of all respondents,46%(58/127)stated they do not report ADRs to the authorities.Concerning the black triangle symbol,a European pharmacovigilance measure,11%(14/127)stated they knew it and 6%(7/127)stated they reported any suspected ADR for drugs with that symbol.Conclusions Physicians’perspectives on ADRs were ambivalent:ADRs infuenced their parent counseling and drug prescribing;yet,they struggled to estimate the impact of ADRs on their patients and were not aware of specifc pharmacovigilance measures.

Association between HLA-B*46:01 and cutaneous adverse drug reactions in Han Chinese

The majority of patients who experience cutaneous adverse drug reactions(cADRs)concurrently receive multiple medications,meaning that the causative drug remains unidentified.We explored the association between human leukocyte antigen(HLA)alleles and cADRs,regardless of the allergenic drug,to investigate whether different drug-induced cADRs were associated with the same or similar risk alleles in a Han Chinese population.We genotyped a sample of 146 cADR patients and 230 population controls from the same hospital and systematically analyzed the association between HLA Class I genes and cADRs.The carrier frequency of HLAB∗46:01 in cADR patients was found to be significantly higher than that in population controls(P=.0021,odds ratio[OR]=2.18,95%confidence interval[CI]:1.33-2.58).Subgroup analysis showed that HLA-B∗46:01 was significantly associated with urticaria and erythema multiforme(P=.0077,OR=2.53,95%CI:1.30-4.91;and P=.0049,OR=2.77,95%CI:1.39-5.50,respectively).Furthermore,a significant association was also detected between HLA-A∗02:01 and erythema multiforme(P=.0038,OR=2.65,95%CI:1.31-5.33).This study is the first to demonstrate that HLA-B∗46:01 is a risk allele for cADRs in a Han Chinese population,indicating that screening for HLA-B∗46:01 prior to the administration of medication may predict the risk of developing cADRs.

Landscape of Hepatobiliary Adverse Drug Reactions Related to Preparations Containing Psoraleae Fructus and Its Application in Pharmacovigilance

Objective To analyze clinical feature and information of medication to explore the risk signals of preparations containing Psoraleae Fructus(BGZP)related with hepatobiliary adverse drug reactions(ADR),in order to reinforce pharmacovigilance.Methods A retrospective study was conducted based on hepatobiliary ADR related with BGZP from the China Adverse Drug Reaction Monitoring System in years from January 2012 to December 2016.Serious and general ADRs were analyzed and assessed.Results There were 355 cases of hepatobiliary ADR related to BGZP.Both the amount of cases and the proportion of serious ADR showed an increasing growth by years(P<0.05).It was found that 10.43%of 355 cases may be involved with irrational drug use,including overdose,repeated medication,and combination of multiple drugs.There were 190 cases which used BGZP(non-combination),and they were mainly for common in diseases caused by abnormal immune activation(accounting for 40.53%of the total cases).Especially at the age group with the most cases with age of 41–50 years,the cases associated with immunological diseases of female were obviously more than that of male(P<0.05).The latency of hepatobiliary ADR related to BGZP ranged from 1 to 386 days,and the median latency was 27.5 days,along with the range of cumulative dose(0.45–520.02 g)as well as the daily dose(0.09–2.64 g/d)after the conversion.Conclusions Cases of hepatobiliary ADR related to BGZP showed significant individual differences,and there was no correlation between drug usage duration and dosage and the occurrence of hepatobiliary ADR.It may be similar with idiosyncratic drug-induced liver injury,and recommended that BGZP should be used with more caution under monitoring liver function,especially in female patients with immunological diseases.

Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in nonalcoholic steatohepatitis patients

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and transporters.Non-alcoholic steatohepatitis(NASH)causes disease-specific alterations to the absorption,distribution,metabolism,and excretion(ADME)processes,including a decrease in protein expression of basolateral uptake transporters,an increase in efflux transporters,and modifications to enzyme activity.This can result in increased drug exposure and adverse drug reactions(ADRs).Our goal was to predict drugs that pose increased risks for ADRs in NASH patients.Bibliographic research identified 71 drugs with reported ADRs in patients with liver disease,mainly non-alcoholic fatty liver disease(NAFLD),54 of which are known substrates of transporters and/or metabolizing enzymes.Since NASH is the progressive form of NAFLD but is most frequently undiagnosed,we identified other drugs at risk based on NASH-specific alterations to ADME processes.Here,we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH,based on their transport and/or metabolism processes.It encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients,especially when eliminated through multiple pathways altered by the disease.Therefore,these results may inform clinicians regarding the selection of drugs for use in NASH patients.

Awareness and attitudes of healthcare professionals in Wuhan,China to the reporting of adverse drug reactions

Background A voluntary procedure for reporting adverse drug reactions (ADRs) was formally put in place in 1989. However,only a small proportion of ADR reports are actually forwarded to the national monitoring center. To identify the reasons for underreporting,the authors investigated the awareness and attitudes of healthcare professionals (doctors,nurses,and administrators) toward the ADR system in China. In addition,the authors sought to formulate approaches to improve the current ADR reporting system.Methods Structured interviews were carried out in 16 hospitals selected from 27 municipal hospitals in Wuhan,Hubei Province,China. A questionnaire survey of a stratified random sample of approximately 15% of healthcare professionals in each selected hospital was conducted during February to March 2003.Results The response rate of this survey was 85%. One thousand six hundred and fifty-three questionnaires were used in the final analysis. Only 2.7% of the healthcare professionals had a correct understanding to the definition of ADR. Eighty-nine point two percent of the healthcare professionals had encountered ADRs. Ninety-four percent of them were aware of the need to report these to the ADR monitoring center. However,only 28.5% of doctors,22.8% of nurses,and 29.7% of administrators actually submitted a report. For the most part,they reported ADRs to the hospital pharmacy (66.0%),to other departments in the hospital (72.5%),and to the pharmaceutical industry (23.0%),rather than to the national monitoring center (2.9%) or regional monitoring center (9.5%). Severe or rare ADRs and ADRs to new products were generally perceived to be significant enough to report. Sixty-two point one percent of the healthcare professionals had encountered ADRs,yet not reported them to anybody. The major reasons for not reporting included no knowledge of the reporting procedure (71.4%),unavailability of the reporting center mailing address (67.9%),unavailability of the ADR report form (60.4%),lack of knowledge of the existence of a national ADR reporting system (52.2%),and belief that the ADR in question was already well known (44.1%). Conclusions Healthcare professionals in Wuhan,China have little basic knowledge of ADR and of the voluntary reporting system. The main reasons for underreporting were lack of basic knowledge about ADRs and the voluntary reporting procedure. Education and training of healthcare professionals is needed to improve the current ADR reporting system.

Analysis of spontaneous adverse drug reactions to echinacea, valerian,black cohosh and ginkgo in Australia from 2000 to 2015

Objective: Assessing adverse drug reactions(ADRs) is a proven method to estimate the safety of medicines. The ADRs to herbal medicines in Australia(and by inference, the safety of herbal medicines in Australia) remain unknown. This study examines spontaneous ADR cases to four of the most popular herbs in Australia from 2000 to 2015: echinacea(Echinacea purpurea), valerian(Valeriana officinalis), black cohosh(Actaea racemosa) and ginkgo(Ginkgo biloba).Methods: ADRs of echinacea, valerian, black cohosh and ginkgo reported to the Australian Therapeutic Goods Administration(TGA) between 2000 and 2015 were obtained from the TGA database. Data were collated and analysed according to age, sex, severity, type of ADR and body system affected. Statistics were calculated using Graph Pad Prism software.Results: Most ADRs were mild or moderate. However, every herbal medicine was associated with lifethreatening ADRs. In each life-threatening case, the herbal medicine was taken concomitantly with prescription medications. Black cohosh was associated with a significant number of severe ADRs(30.3% of the total), with 39.4% of these ADRs being associated with abnormal hepatic function, hepatitis or hepatotoxicity.Conclusion: This study highlights the lack of public awareness with regard to herb–drug interactions,since most of the severe ADRs involved a herb–drug interaction.

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.

Systematic review on the adverse reactions of oral administration of Indigo Naturalis and its preparations

Objective:This article systematically analyses the effects of adverse drug events/adverse drug reactions(ADEs/ADRs)of oral Indigo Naturalis(Qingdai)preparations in order to provide references for its rational clinical application.Methods:All clinical studies reporting ADE/ADR related to the oral administration of Qingdai preparations were searched through electronic databases,including PubMed,the Cochrane Library,Embase,China National Knowledge Infrastructure(CNKI),China Biology Medicine disc(CBM),VIP Information Chinese Journal Service Platform(VIP),and Wanfang database,from inception to September 27,2020.Information were extracted from these literatures,including primary disease,type of adverse reactions,dose,treatment,outcomes and so on.Incidence of ADE/ADR was estimated,as well as distribution of primary diseases and victim organs and systems were analyzed.Results:A total of 682 articles were included,with 651 clinical population studies and 31 case reports.Among them,604 detailed ADR/AE involving 33459 patients using oral Qingdai preparations,and a total of 5061 cases were found to present adverse events,including 2827 cases of digestive system(abdominal pain,diarrhea,etc.),469 cases of blood system damage(thrombocytopenia,leukopenia,anemia,etc.),313 cases of liver damage(abnormal liver function,liver toxicity,elevated liver enzymes,etc.),327 cases of nervous system reactions(headache,dizziness,poor sleep,etc.)and 1186 cases of other systems and organs.Severe adverse events(SAEs)mainly were liver damage,and could be relived after symptomatic treatment.Conclusion:From the systematic information retrieval and analysis,it is found that oral Qingdai preparations application may clinically cause ADEs/ADRs in terms of gastrointestinal tract and liver damage.Therefore,when using oral Qingdai preparations,liver and stomach protection should be done.At the same time,pay close attention to various biochemical indicators and the patient's drug response during the treatment process,and,if necessary,deal with it in time so as not to deteriorate the condition.Moreover,active surveillance system should be conducted to monitor ADE/ADR,so as to establish a clearer causal relationship between the drug and the adverse event.