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.

Prevention and Nursing of Adverse Reactions of Novel Coronavirus Inactivated Vaccine (Vero Cells)

Objective:To discuss and analyze the causes of adverse reactions caused by the inactivated novel coronavirus vaccine(Vero cells),and to propose methods of prevention and care.Methods:A questionnaire was used to randomly select 229 adults who were vaccinated with the inactivated novel coronavirus vaccine(Vero cells)at Xi’an People’s Hospital(Xi’an Fourth Hospital).The adverse reactions were statistically analyzed.Results:Among the 229 adults vaccinated with the inactivated novel coronavirus vaccine(Vero cells),30 experienced vaccination reactions.The main reaction was local induration at the inoculation site,and dizziness was the primary systemic symptom.Conclusion:To reduce the incidence of adverse reactions to the inactivated novel coronavirus vaccine(Vero cells),it is necessary to effectively evaluate the health status of adults before vaccination,select the correct vaccination site,and strictly implement the rules of 3-inspections,7-checks,and 1-verification.Standardizing the operation process and providing thorough health education after vaccination can effectively reduce the occurrence of adverse reactions.

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.

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.

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.

Safely Using TCM Herbs： Adverse Reactions and Precautions

Although most people believe that herbal remedies are relatively safe to use, some are toxic or possess adverse reactions, especially when used incorrectly.Commonly used TCM herbs with known adverse reactions, as well as the most toxic herbs in the Pharmacopoeia of People’s Republic of China are listed as follows:

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.

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.

Patterns of Antiplatelet and Anticoagulant Agents Use in Urological Inpatients and Their Perception of Adverse Reactions

Purpose: To evaluate the rate of any type of anticoagulant drug use in urological inpatients and patients awareness of their effect on coagulation. Material and methods: This observational study was conducted prospectively in a cohort of 193 consecutive urological inpatients who were asked to state the medications they were taking and following that, were specifically asked whether they were taking aspirin or other antiplatelet/anticoagulant agents. In case they did so, they were further asked why they were taking them, whether they knew their effect on coagulation and who had informed them on the matter. Results: Forty-seven patients received some kind of antithrombotic treatment. Twenty-nine per cent of aspirin users had to be specifically prompted in order to state its use, in comparison to 35.7% and 25% of other antiplatelets and warfarin users, respectively. Half of patients receiving warfarin were not aware of its effect on coagulation in comparison to 32.3% and 21.4% of those taking aspirin and other antiplatelets, respectively. Conclusion: Urologists should be aware of the high use of such agents by their patients and that not all patients are aware of their effect on coagulation, while some, even fail to report their use and have to be specifically prompted.

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.

Protective Effect of Oral Steroid Premedication: Adverse Reactions to Nonionic Iodine Contrast Media for Computed Tomography

This study aimed to investigate the protective effect of oral steroid premedication in terms of adverse reactions to non-ionic contrast media. We investigated the incidence of adverse reactions among patients who underwent contrast-enhanced computed tomography. Patients in the premedication group took 30 mg of prednisolone orally the night before and on the morning of the scheduled computed tomography. Sixty-five patients received the same contrast media. Among them, 56 took prednisolone orally prior to the procedure (premedication without change of contrast media group) and nine without premedication (no premedication and no change of contrast media group). In total, 379 patients received different contrast media. Among them, 340 took prednisolone orally (premedication with change of contrast media group), while 39 did not take the premedication (no premedication with change of contrast media group). The adverse reaction rates in the premedication with change of contrast media and no premedication with change of contrast media groups were 1.8% (6/340 cases) and 2.6% (1/39 cases) (P = 0.54), respectively. The incidence of adverse reaction after the administration of non-ionic iodinated contrast media did not differ significantly based on whether an oral steroid was administered prior to compute tomography. Our evaluation is limited due to the small sample size of the contrast media-changed group. However, even if premedication with steroids is effective, it may only result in an adverse reaction reduction rate of ≤3%.

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 qualitative study on the adverse reactions of mass treatment for lymphatic filariasis in Orissa,India

Objective:To describe the perceptions of community members and programme partners regarding severity,management and impact of adverse reactions on mass drug administration (MDA) compliance.Methods:Based on various qualitative data collected from five districts of Orissa,India,where MDA had been implemented during 2002 and 2004.The qualitative surveys included focus group discussions with community members and health workers,and semi-structured interviews with key informants in the community,medical officers at primary health centres,district level health officers and private practitioners.Results:It showed that many people suffered from adverse reactions,though the reactions were not serious.The paper reported different ways of management of adverse reactions at the community level.The impact of adverse reactions on MDA compliance was serious,as many people did not consume the drug due to fear of adverse reactions.The rumours of adverse reactions and news in media deterred people from consuming the tablets.Conclusion:All categories of respondents indicates the need of more information to address the problem of adverse reactions during MDA.The present paper warrants incorporating the messages on adverse reactions during health communication and social mobilization campaigns of MDA.

Risk factors for adverse reactions of fundus fluorescein angiography

Background:To explore the difference between the outcomes of correlations between a series of variables and adverse reactions(ARs)to fluorescein from univariate and multivariate analysis and to evaluate the nausea effects in different age groups.Methods:A retrospective study of patients undergoing consecutive fluorescein angiography between March2010 and February 2012 was conducted.No patients were excluded on the ground of age,presence of atopy,allergy history,previous procedures without severe allergic ARs,asymptomatic hypertension and kidney failure with serum creatinine levels lower than 250μmol/L or with renal dialysis.Results:A total of 829 patients were enrolled and 22.2%of them had ARs.The majority of reactions were nausea(12.1%)which occurred less when age became old(P<0.0001).When the correlations between a series of variables and ARs were assessed separately,age(P<0.0001),prior reactions(P<0.0001)and motion sickness(P=0.0062)were highly and cardio/cerebrovascular disease(P=0.0015),diabetes(P=0.0001)and renal disease(P=0.0219)were lowly related to ARs.However,when the correlations were assessed simultaneously,only age[odd ratio(OR)0.974;95%confidence interval(CI),0.962–0.986],prior reactions(OR 5.596;95%CI,2.083–15.029)and motion sickness(OR 4.849;95%CI,1.583–14.856)were statistically correlated with ARs.Conclusions:Fluorescein angiography is a safe procedure for patients who are relatively healthy but with a history of any systemic disease.Young age,prior reactions and motion sickness which are highly related to emetic events should be considered in the evaluation of ARs to fluorescein.

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.

Attention and Intervention of Oncologists on Oxaliplatin-induced Adverse Reactions in China' Mainland:A Cross-sectional Internet-based Survey

Objective This cross-sectional study aimed to investigate the current attention and intervention of oncologists on oxaliplatin(OXA)-induced adverse reactions(ADRs).Methods In 31 provinces or administrative regions across China,401 oncologists were surveyed through a self-designed questionnaire.The survey queried the basic information of respondents,clinical use of OXA,OXA-induced ADRs,and relative interventions.Chi-square tests and multiple logistic regression were used to explore the sociodemographic factors influencing the safety perception of OXA and the relevant interventions.Results The survey showed that the age of respondents was mainly distributed between 30 and 40 years and the working period for most oncologists was no more than 5 years.Oncologists with long working years were more willing to conduct patient education and inquire about ADRs than those with short working years.The rate of ADRs reported by oncologists with intermediate professional titles was significantly higher than that reported by oncologists with junior and senior professional titles.Conclusion Our findings indicate that oncologists in China's Mainland are concerned about OXA-induced ADRs,but the reporting of ADRs still needs to be strengthened.Therefore,training and educational programs are urgently needed to improve the risk management of OXA-induced ADRs among oncologists.

A Case of Adverse Reaction to Booster Dose of COVID-19 Vaccination: Could D-Dimer Elevation Suggest Increased Clotting Risk?

We report the clinical case of a 40-year-old Italian woman, who soon after her booster vaccination with mRNA-1273 after the two previous vaccinations with BNT162b2, developed severe headache, high fever, and Musculo-skeletal pain. She went to the emergency department, where computerized tomography (CT) scans of chest and brain were performed, resulting in both negative for pathologic findings. On the contrary, white blood count was strongly lowered and D-dimer severely elevated. She improved after treatment with enoxaparin and the blood analyses returned in the normal range after ten days. This case supports the hypothesis that COVID-19 vaccines could increase blood clotting in some predisposed subjects. Therefore, we believe that robust and well-designed clinical trials, considering the evaluation of D-dimer levels, should be performed to eliminate any doubts on this issue.

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.

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.