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.

Analysis of Innovations in Monitoring Adverse Drug Reaction and Application

Objective To systematically study foreign adverse drug reaction monitoring technologies and applications to extract valuable experience,and provide reference for promoting its application in China.Methods Literature research,comparative research and other methods were used to investigate foreign adverse drug reaction(ADR)monitoring technologies and applications such as passive reporting systems,active monitoring systems,electronic health records and real-world data,and analyze the problems in the application of the above technologies in China.Results and Conclusion At present,China is relatively mature in the application of ADR passive reporting system,but there are some problems in the application of ADR active monitoring system,electronic health records and real-world data.In the future,we should improve the application of adverse drug reaction active monitoring system,establish close cooperation with universities,research institutes and other institutions to improve the evaluation of adverse drug reactions.Besides,we should promote the construction of the Chinese medical language processing system and strengthen the understanding of real-world data.This will improve the level of monitoring adverse drug reactions in China and promote rational drug use.

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.

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.

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:

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.

Clinical observation of Shenmai injection in the treatment for adverse reactions of chemotherapy on advanced non-small cell lung cancer

Objective: To observe the efficacy of Shenmai injection in the treatment for adverse reactions of chemotherapy on advanced non-small cell lung cancer (NSCLC). Methods: 45 NSCLC patients with stages IIIb-IV were randomly divided into two groups: the treatment group (treated by chemotherapy combined with Shenmai injection) and the control group (treated by chemotherapy only). The efficacy of the two groups was evaluated after 3 cycles of treatment. Results: There was no significant difference between the two groups in the recent curative effects (P > 0.05), while there were significant differences between them in Karnofsky score and weight (P < 0.05). The treatment group was better than the control group in preventing leucopenia and decreased hemoglobin, and significant differences were found between them (P < 0.05). The incidence of thrombocytopenia, nausea and vomiting, hepatic and renal dysfunction in the treatment group was lower than that in the control group, but no significant differences were found between them (P > 0.05). Conclusion: Shenmai injection would not influence the efficacy of chemotherapy on advanced NSCLC patients, while it could improve the quality of life, increase the body weight of patients, alleviate adverse reactions of chemotherapy as myelosuppression so as to improve the tolerance of organism to chemotherapy.

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%.

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.

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.

Incidence of adverse reactions to COVID-19 vaccination:A meta-analysis of randomized controlled trials

Objective:To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019(COVID-19)vaccination.Methods:We systematically searched PubMed,Embase,The Cochrane Library,Web of Science,CNKI,WanFang Data,and VIP Database from the inception of each database to August 31,2021.Randomized controlled clinical trials(RCTs)on the safety of different types of COVID-19 vaccines were retrieved and analyzed.A random or fixed-effects model was used with an odds ratio as the effect size.The quality of each reference was evaluated.The incidence of the adverse reactions of the placebo group and the vaccination group was compared.Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses.Results:A total of 13 articles were included,with 81287 subjects.Compared with the placebo group,the vaccination group showed a higher combined risk ratio(RR)of total adverse reactions(RR=1.67,95%CI:1.46-1.91,P<0.01),local adverse reactions(RR=2.86,95%CI:2.11-3.87,P<0.01),systemic adverse reactions(RR=1.25,95%CI:0.92-1.72,P=0.16),pain(RR=2.55,95%CI:1.75-3.70,P<0.01),swelling(RR=4.16,95%CI:1.71-10.17,P=0.002),fever(RR=2.34,95%CI:1.84-2.97,P<0.01),fatigue(RR=1.36,95%CI:1.32-1.41,P<0.01)and headache(RR=1.22,95%CI:1.18-1.26,P<0.01).The subgroup analysis showed the incidence of adverse reactions of the vaccination group after injection of the three COVID-19 vaccines(inactivated viral vaccines,mRNA vaccines and adenovirus vector vaccines)was higher than that of the placebo group,and the difference between the placebo group and the vaccination group in the mRNA vaccine subgroup and the adenovirus vector vaccine subgroup was statistically significant(P<0.01).The incidence of adverse reactions after injection of COVID-19 vaccine in subgroups of different ages was significantly higher than that in the placebo group(P<0.01).Conclusions:COVID-19 vaccines have a good safety,among which adenovirus vector vaccine has the highest incidence of adverse reactions.Both adolescents and adults vaccinated with novel coronavirus vaccine have a certain proportion of adverse reactions,but the symptoms are mild and can be relieved by themselves.Our meta-analysis can help boost global awareness of vaccine safety,promote mass vaccination,help build regional and global immune barriers and effectively curb the recurrency of COVID-19.

Safely Using TCM Herbs: Adverse Reaction and Precautions (Continued)

Chan su (Venenum Bufonis,蟾酥)Its main active and toxic constituent is bufotoxin, which has a function similar to digitalis glycosides.Adverse reactions and toxicity: Chan su, althoughit is used in patent preparations, is traditionally known for its toxicity and is seldom used in decoctions. Toxicity is often due to over dosage of the patents, such as Liushenwan (六神丸) and Houzhengwan (喉症丸). After administration

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.

Jinlong capsule decreases adverse reactions after transcatheter arterial chemoembolization(TACE) in patients with hepatocellular carcinoma

Objective The aim of this study was to analyze whether Jinlong capsule could decrease adverse reactions after transcatheter arterial chemoembolization(TACE) in patients with hepatocellular carcinoma. Methods Eighty-two patients with hepatocellular carcinoma were randomly divided into the control group and experimental group. On the first day after TACE, the experimental group started receiving four Jinlong capsules orally three times daily, whereas the control group did not receive the treatment.Results The incidences of erythropenia and thrombocytopenia in the experimental group was lower than those in the control group(P = 0.040 and 0.033, respectively). The differences in serum levels of aminotransferase, albumin, potassium, and sodium between the two groups were significant(P = 0.034, 0.034, 0.013, and 0.044, respectively). The mean durations of stomachache and abdominal distension in the experimental group was significantly shorter than those in the control group(P = 0.004 and 0.021, respectively). However, there were no significant differences in the incidences of nausea, fever, and vomiting between the two groups(P = 0.490, 0.495, and 0.585, respectively). Conclusion The reduction in the incidence rate and duration of partial adverse reactions after TACE was observed in hepatocellular carcinoma patients treated with Jinlong capsule compared to untreated patients, suggesting possible beneficial effects exerted by Jinlong capsule on the reduction of TACE-induced liver damage, thereby improving liver function and, consequently, the quality of life.

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.

Analysis of 8611 Cases of Adverse Reaction Reports of Breviscapine for Injection

[Objectives]To analyze the occurrence rules and factors influencing adverse reactions of breviscapine for injection,explore potential drug risks,and guide the clinical rational medication.[Methods]The retrospective analysis method was used to analyze the case reports of adverse reactions of breviscapine for injection,and analyze the gender and age distribution of the cases,the patient's medication status,the adverse reactions involving organ/system damage and clinical manifestations,the occurrence time,duration,and outcome of the adverse reactions.[Results]Adverse reactions of breviscapine for injection were mainly concentrated in middle-aged and elderly patients aged 45 and above,accounting for 85.35%;in the gender distribution,females were higher than males;adverse reactions involved multiple organ/system damages.Among them,75.86%of patients had adverse reactions after the first medication,and 11.77%of reported patients had concomitant medications.[Conclusions]The adverse reactions caused by breviscapine for injection may be related to the patient's age,gender and irrational medication.

Analysis of the adverse reactions of atezolizumab: A real-world study based on FAERS database

Objective In this study,we aimed to determine the incidence of adverse drug reactions(ADRs)of atezolizumab,identify ADR signals that are significantly related to atezolizumab,and provide a reference for the rational use of atezolizumab in the clinic through the statistical analysis of its adverse drug events(ADEs)reported in the American Food and Drug Administration(FDA)Adverse Event Reporting System(FAERS)database.Methods In total,4796 cases of atezolizumab ADEs reported in the American FAERS database from 2017 to 2019 were retrospectively analyzed.Results The top three ADEs were febrile neutropenia(3.7%),anemia(2.9%),and acute renal failure(2.3%).In addition,the incidence rates of some ADEs were significantly different according to sex and age.The systematic organ classification of atezolizumab ADEs involved 32 systems,among which the top three were blood and lymphatic system disorders(585 cases,12.2%),gastrointestinal disorders(433 cases,9.0%),and infections and infestations(401 cases,8.4%).The reporting odds ratio(ROR)method was used to detect the ADR signals of atezolizumab.The ROR(95%confidence interval)of the top ADE,febrile neutropenia,was 39.236(33.757–45.604).In addition,we found 121 cases of complications associated with immune-related ADEs.Conclusion The ADRs of atezolizumab reported in the FAERS database were consistent with those mentioned in the instructions for atezolizumab use,suggesting that atezolizumab has an acceptable and controllable drug effect.

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.

Clinical Efficacy and Adverse Reactions of Photodynamic Therapy in the Treatment of Malignant Skin Tumors and Precancerous Skin Diseases

The purpose of the study was to investigate the efficacy and safety of photodynamic therapy in the treatment of malignant skin tumors and precancerous skin diseases.First of all,100 patients with malignant skin tumor and pre-cancer skin disease admitted to our hospital from January 20,2018 to September 18,2018 were selected,and all of them adopted photodynamic therapy.The 100 patients included 40 cases of basal cell carcinoma,14 cases of squamous cell carcinoma,7 cases of proliferative erythema,9 cases of Bowen’s disease and 39 cases of solar keratosis.Among the 100 patients,77 cases had excellent curative effect,18 cases had good effect and 5 cases had poor effect,and the overall effective rate was 95%(95/100).After 6 months of follow-up,5 cases of basal cell carcinoma,2 cases of squamous cell carcinoma,0 cases of proliferative erythra,1 case of Bowen’s disease and 3 cases of solar keratosis recurred,with an overall recurrence rate of 14%(14/100).The adverse reactions of pruritus were 90%(90/100),81%(81/100),90%(90/100)and 3%(3/100).Therefore,the application of photodynamic therapy in the treatment of malignant skin tumors and precancerous skin diseases is not only effective,but also safe and not easy to relapse.