Cases Of Adverse Drug Reactions Research Articles

Assessment of severity and avoidability of adverse drug reactions in neonates: a reproducibility study of the Hartwig tool and LAAT.

Tools for classifying adverse drug reactions (ADRs) have not yet been validated in the context of the neonatal intensive care unit (NICU). The study aims to investigate the inter-rater reliability of the Hartwig tool and the Liverpool avoidability assessment tool (LAAT) in assessing the severity and avoidability of ADR cases in hospitalized neonates. An observational and prospective study was conducted in the NICU of a maternity hospital in Natal, Brazil. The Hartwig tool and LAAT were employed to assess the severity and avoidability of ADRs, respectively. Three experienced clinical pharmacists independently assessed all ADR cases. Inter-rater reliability was measured using Cohen's kappa coefficient (k) with corresponding 95% confidence intervals (CI). Among 79 ADR cases, the mean gestational age was 29.7 ± 4.4weeks, and the birth weight averaged 1446.0 ± 1179.3g. The assessment of ADR severity using the Hartwig tool revealed a significant overall correlation (overall k = 0.573; 95% CI 0.395 to 0.753) with exact agreement (EA) and extreme disagreement (ED) rates between evaluators of 86.5% and 2.5%, respectively. However, no statistically significant correlation was observed for determining avoidability using the LAAT (overall k = 0.017; 95% CI - 0.048 to 0.082), with an EA rate of 83.6% and ED rate of 10.1%. The Hartwig tool demonstrates good reproducibility among different evaluators in determining the severity of ADRs, unlike the LAAT for assessing avoidability.

Social Media as a Source of Information for the Detection of Adverse Drug Reactions in Post-Marketing Surveillance: A Review

INTRODUCTION. With the development of the Internet and the increasing availability of social networks and fora, patients have received an opportunity to share their medication experiences online. According to the guidelines on Good Pharmacovigilance Practices, social media can be considered an important additional source of patient-derived information in post-marketing surveillance, but the effectiveness of their use in detecting adverse drug reactions (ADRs) is still being investigated.AIM. This study aimed to analyse the results of relevant original studies and assess the potential of using social networks and online patient fora as a source of information on ADRs associated with the use of medicinal products.DISCUSSION. Published studies indicate that posts on social networks and patient fora describe both minor and serious ADRs, including new ADRs. The relevance of social media as a source of information about the safety of a medicinal product varies depending on several factors, including the medicinal product class and time on the market, as well as the platform demographics. Young users (18–44 years) are interested in online discussions about medicinal products for mental and reproductive system disorders. Users aged 45–64 years tend to discuss the use of medicinal products for chronic pain (including muscle pain), menopause, and gastritis. Discussions among users over 65 years old predominantly focus on medicinal products for diabetes, heart conditions, and muscle pain. People are much more likely to describe ADRs associated with the use of medicinal products for orphan diseases and cancer on fora for patients than on social networks in general, and vice versa for ADRs associated with the use of medicinal products for mental disorders. In addition, social media may be of interest as a source of information about cases of overdose, misuse and off-label use of medicinal products, and use of medicinal products during pregnancy and lactation.CONCLUSIONS. Social media can be a source of valuable information about the safety of medicinal products and the impact of ADRs on the quality of patients’ lives. Marketing authorisation holders can obtain new information about the safety of medicinal products by extending their safety monitoring strategies to include social media. Nevertheless, since the relevance of a particular social network or patient forum for the detection of ADR cases varies considerably, a preliminary assessment is necessary to ascertain the presence of information on the medicinal product of interest.

Assess Incidence and Presentation of Cutaneous Adverse Drug Reactions in Patients Presenting at Jeddah's Tertiary Care Facilities

Background: It is often necessary to differentiate cutaneous signs of adverse medication reactions from other similar appearances. Because patients frequently fail to recognize the connection between drug consumption and ensuing cutaneous manifestations, early detection of these responses is imperative. Purpose: Investigating the prevalence of Cutaneous Adverse Drug Reactions (CADRs) at a teaching hospital for tertiary care is the goal of this study. Methods: A self-reporting technique was used to select cases in a prospective, observational trial that lasted six months in Saudi German hospital in Jeddah . The following categories applied to Cutaneous Adverse Drug Reactions: definite, potential, and probable. Results: The most common cutaneous manifestation of ADRs (42.85%) was maculopapular rash, which was linked to antimicrobials (48.30%) and nonsteroidal anti-inflammatory drugs (21.90%) during the study period, which resulted in 91 cases of Cutaneous Adverse Drug Reactions. Conclusion: Since cutaneous adverse drug reactions are common, raising awareness of them is crucial to diagnosing and preventing them.

Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained use primarily due to their weight-reduction effects, although a regulatory review was undertaken for potential suicidality concern. To evaluate potential signals for suicidal and self-injurious adverse drug reactions (ADRs) associated with the GLP-1 RAs semaglutide and liraglutide. Disproportionality analysis through the case-control design using the World Health Organization (WHO) global database of suspected ADRs. Participants were clinical patients worldwide experiencing an ADR suspectedly attributable to semaglutide or liraglutide in the database from inception to August 30, 2023. Data were analyzed from September to December 2023. Treatment with semaglutide or liraglutide regardless of indication or treatment duration. Reporting odds ratio (ROR) and the bayesian information component (IC) with 95% CIs were calculated as measures of disproportionate reporting of suicidal and self-injurious ADRs associated with semaglutide and liraglutide compared with all other medications. Sensitivity analyses were conducted including patients with coreported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. A disproportionality signal was considered when the lower limits of the ROR and IC were above 1 and 0, respectively. A total of 107 (median [IQR] age 48 [40-56] years; 59 female patients [55%]) and 162 (median [IQR] age 47 [38-60] years; 100 female patients [61%]) cases of suicidal and/or self-injurious ADRs were reported between November 2000 and August 2023 with semaglutide and liraglutide, respectively. Significant disproportionality was detected only for semaglutide-associated suicidal ideation (ROR, 1.45; 95% CI, 1.18-1.77; IC, 0.53; 95% CI, 0.19-0.78), which remained significant in patients with coreported use of antidepressants (ROR, 4.45; 95% CI, 2.52-7.86; IC, 1.96; 95% CI, 0.98-2.63) and benzodiazepines (ROR, 4.07; 95% CI, 1.69-9.82; IC, 1.67; 95% CI, 0.11-2.65), when compared with dapagliflozin (ROR, 5.56; 95% CI, 3.23-9.60; IC, 0.70; 95% CI, 0.36-0.95), metformin (ROR, 3.86; 95% CI, 2.91-5.12; IC, 1.20; 95% CI, 0.94-1.53) and orlistat (ROR, 4.24; 95% CI, 2.69-6.69; IC, 0.70; 95% CI, 0.36-0.95). This study using the WHO database found a signal of semaglutide-associated suicidal ideation, which warrants urgent clarification.

Patterns, outcomes, and preventability of clinically manifest drug-drug interactions in older outpatients: a subgroup analysis from a 6-year-long observational study in North India.

Older adults are vulnerable to adverse drug reactions (ADRs) and drug-drug interactions (DDIs). Evidence on clinically manifest DDIs in older outpatients is scanty. The present study aims to report clinically manifest DDIs, their risk factors, and preventive measures. A subgroup analysis of a 6-year (2015-2021) long prospective study was conducted in a tertiary hospital in North India. Older outpatients with ADRs constituted the study participants. Among 933 ADRs reported in 10,400 patient registrations, clinically manifest DDIs were involved in 199 (21.3%). DDIs accounted for 29.9%, 26.5%, and 21.3% of drug-related metabolic, vascular, and nervous system disorders, respectively. Movement disorders (n = 18), hypotension (n = 16), and hypoglycemia (n = 15) were the most common manifestations. Eighty-six percent of DDIs were of the pharmacodynamic type, and 13.1% were immune-mediated. Around 35% of DDIs resulted in hospitalization, with hyponatremia, movement disorder, and renal impairment as the common reasons. Older adults with Parkinsonism, infection, coronary artery disease, neuropsychiatric disease, and diabetes mellitus, respectively, had 3.28, 2.85, 1.97, 1.76, and 1.80 times higher odds of DDIs. Those receiving ≥ 10 drugs had 5.31 times higher odds of DDIs compared to individuals receiving 1-4 drugs. "Avoiding the causative drug," "optimal monitoring of the patient," and "start-low and go-slow" policy together could prevent 85% of DDIs. In conclusion,every fifth case of ADRs and nearly one third of ADR-related hospitalizations in older adults are related to DDIs. Movement disorder, hypotension, and hypoglycemia are the common manifestations. A holistic approach with drug omission, optimal patient monitoring, and slow titration of therapy can prevent significant DDIs in older adults.

Detecção de Reações Adversas a Medicamentos em pacientes hospitalizados: uma abordagem de análise em rede

Objective: We aimed to investigate whether network analysis can be used to estimate patterns of Adverse Drug Reactions and drugs involved. Methods: Patients admitted from 18 years of age or older, hospitalized for more than 24 hours, and using at least one drug during hospitalization were included. Results: 8060 patients were observed, and 358 cases of Adverse Drug Reactions were identified (4.43%). The network graph shows that the occurrence of hypotension induced by furosemide, spironolactone and enalapril is related to serum changes in potassium and the occurrence of renal failure. Centered around nausea and vomiting node, there is a great variety of drugs from different classes involved with this Adverse Drug Reaction and without other connections. Conclusion: Network analysis is a promising strategy for identifying patterns that correlate adverse reactions to drugs administered during hospitalization.

КОМПЛЕКСНЫЙ АНАЛИЗ ПРИЧИН РАЗВИТИЯ НЕЖЕЛАТЕЛЬНЫХ РЕАКЦИЙ НА ОМАЛИЗУМАБ

Currently, there are no comprehensive studies to assess the causes of adverse reactions in terms of the use of omalizumab. The aim of the study was to conduct a comprehensive analysis of the causes of adverse reactions to omalizumab. Materials and methods. Based on these criteria, experts of medical organizations conducted a retrospective assessment of 300 cases of omalizumab use with registration of existing defects based on the data of primary medical documentation (inpatient records, outpatient records). By the method of a sociological survey of 100 doctors, the level of their awareness of the procedure for reporting adverse reactions of drugs and, in particular, omalizumab was studied. The data were processed using applied computer programs. Outcomes. The incidence of medical-organizational defects in safety monitoring of omalizumab was 591 per 100 cases overall. The highest frequency was observed in such defects as: "lack of analysis of identified adverse reactions and cases of ineffectiveness"; "lack of a plan for corrective and preventive measures in connection with the detection of cases of adverse drug reactions"; "violation of the deadlines for the transfer of notices". In the structure of defects in reporting and filling out notifications of adverse reactions of omalizumab by doctors of medical organizations, the leading positions are occupied by: the absence of indications of the presence of bad habits (drug addiction, alcohol abuse, smoking) in the patient; absence of indications of the patient's reaction to the drug; lack of information about the period of time that has elapsed from the administration of the drug to the onset of symptoms of an adverse reaction. The weakest points of professional awareness of doctors about the procedure for reporting adverse reactions of omalizumab are: awareness of the need and content of the analysis of the identified adverse reactions; on regulatory documents on the quality, efficacy and safety of medicines; on the notification scheme of the person responsible for monitoring the safety of the medicinal product.

Analysis of cases of adverse drug reactions in pediatrics

Analysis of cases of adverse drug reactions in pediatrics

Prospective,multi-center,and large-scale hospital centralized monitoring of clinical safety of Reduning Injection in 100249 children cases

This study utilized a prospective, large-sample, multi-center, and registered key specialty approach of hospitals to monitor the application of Reduning Injection. A total of 100 249 adolescent patients aged 14 years and below who received Reduning Injection were monitored, resulting in 83 cases of adverse events, with 76 of them being classified as adverse drug reaction(ADR). The calculated incidence rate of ADR for Reduning Injection was 0.076%, indicating a very rare ADR. The main symptoms of ADR were pruritus, diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsion, and chills. All ADR cases were reported for the first time, including three new ADR cases and 73 known ADR cases. The categories of ADR was general ADR. All ADR was mild in severity. There were more males than females in ADR patients. One patient had a history of ADR, and the drug causing ADR was buprofen. The largest number of ADR cases occurred when the dosage of Reduning injection was 5-10 mL. The dropping speed was 30 drops or less per min, and the solvent type was 5% glucose injection. The most common manifestation of ADR patients was pruritus, followed by diarrhea, abdominal pain, vomiting, high fever, dyspnea, convulsions, and chills. 72 patients(94.74% of ADR patients) discontinued the drug, and three patients(3.95% of ADR patients) were given oxygen inhalation. 47 cases(61.84% of ADR patients) were treated with medication, of which dexamethasone was the most used(24 cases, 46.15% of ADR patients). 76 ADR patients were cured or improved. ADRs are more likely to occur when diagnosed with acute bronchitis by western medicine and cough by traditional Chinese medicine(TCM), TCM syndrome type is wind heat syndrome, and the combination medicine is ambroxol hydrochloride and bromhexine hydrochloride injection, ascorbic acid/vitamin C injection. This result provides an evidence-based safety basis for active pharmacovigilance of Reduning Injection in adolescents aged 14 years and below.

ADVERSE DRUG REACTIONS OF BACLOFEN, NALTREXONE, AND ACAMPROSATE IN PATIENTS HAVING ALCOHOL DEPENDENCE: A CROSS-SECTIONAL PHARMACOVIGILANCE STUDY

Objectives: The research aims to investigate the prevalence and patterns of adverse drug reactions (ADRs), gauge the severity of these reactions, establish causality in ADR cases, and assess the preventability of such adverse reactions. Methods: ADR information was gathered through personal interviews with patients or their relatives. Causality was assessed using the Naranjo algorithm, and a modified Hartwig and Siegel Severity Assessment Scale was used for estimating the severity of ADR. ADRs were grouped into various preventability categories based on the modified Schumock and Thornton criteria. Results: The total number of patients evaluated in the baclofen, naltrexone, and acamprosate groups was 65, 28, and 42, respectively. The most commonly reported adverse events with baclofen were nausea (31.25%), followed by fatigue (18.75%) and headache (12.50%). The majority of patients receiving acamprosate reported nausea (57.14%), followed by diarrhea (28.57%). Patients receiving naltrexone most commonly reported nausea (35.71%), followed by abdominal pain (21.43%) and headache (14.28%). Conclusion: This study shed light on the prevalence, severity, causality, and preventability of ADRs associated with anti-craving agents used to treat patients with alcohol withdrawal syndrome, providing valuable insights into the safety profiles of these medications.

Adverse drug reaction after application of Amapachana upanaha (~poultice application): An observation

It is the most common belief in Indians that herbal drugs are completely safe and do not produce any adverse effects. However, this belief is not always true. A case of Adverse Drug Reaction (ADR) after the application of an Ayurveda formulation is presented in this case report. An 82-year-old male patient, a resident of Belagavi, with a history of hypertension, presented to Ayurveda hospital with complaints of pain in bilateral knee joints for the last two months that aggravated since last week. As per Ayurveda parameters, he was diagnosed with a case of Sandhigata vata (~vitiated Vata dosha in joints; National Ayurveda Morbidity Code: AAE-16) comparable to osteoarthritis. He was admitted to the inpatient department on March 28, 2022, and after taking consent, Ayurveda treatment was started. Amapachana upanaha (~poultice application) over the bilateral knee joints was one among the treatment procedures followed in the case. On the second day of treatment (March 30, 2022), he suddenly developed reddish discoloration and the appearance of boils over the bilateral knee joint after the administration of Amapachana upanaha. The patient was managed with external application of Shatadhouta ghrita (~processed ghee) over the affected part along with internal administration of tablet Laghusootashekara vati (1600 mg) twice a day for three days for the suspected ADR. After three days of therapeutic intervention, blisters and discoloration were reduced and the patient was discharged on April 4, 2022, with internal follow-up medications for the next 15 days. This case report highlights the importance of preassessment and awareness toward the careful use of Ayurveda medicines like that of contemporary medications to address such ADRs.

Cutaneous Adverse Drug Reactions on application of Nagaradi Lepa - A Retrospective analysis

Introduction: Cutaneous adverse drug reactions are among the most common types of drug hypersensitivity reactions. Although considered natural and safe, Ayurveda medicines can cause adverse reactions. This article highlights the cases of cutaneous adverse drug reactions possibly due to external application of Nagaradi lepa. Materials and Methods: This is an observational, retrospective and record based study conducted by analyzing the spontaneous reported ADR forms, caused by the external application of Nagaradi lepa, collected over a period of 12 months (April 2022 to March 2023) at Peripheral Pharmacovigilance Centre, VPSV Ayurveda College Kottakkal, Kerala. Results: During the period of one year, 3 cutaneous ADRs were reported due to external application of Nagaradi lepa. All the 3 cases fall under the category of Probable according to Naranjo’s ADR Probability scale. 2 cases were mild and 1 case was moderate in severity. All the 3 cases were recovered from ADR. Conclusion: Though under reporting, we may have to consider the possibility of Ayurvedic drugs to cause adverse drug reactions. Pharmacovigilance is an ongoing and continuous process. Reporting of ADR to Pharmacovigilance centers help to generate information on ADR related Ayurvedic formulations and also to prevent its recurrence.

Streamlining Considerations for Safety Measures: A Predictive Model for Addition of Clinically Significant Adverse Reactions to Japanese Drug Package Inserts.

The addition of clinically significant adverse reactions (CSARs) to Japanese package inserts (PIs) is an important safety measure that can be used to inform medical personnel of potential health risks; however, determining the necessity of their addition can be lengthy and complex. Therefore, we aimed to construct a machine learning-based model that can predict the addition of CSARs at an early stage due to the accumulation of both Japanese and overseas adverse drug reaction (ADR) cases. The target comprised CSARs added to PIs from August 2011 to March 2022. The control group consisted of drugs without the same CSARs in their PIs by March 2022. Features were generated using ADR case accumulation data obtained from the Japanese Adverse Drug Event Report and the U.S. Food and Drug Administration Adverse Event Reporting System databases. The model was constructed using DataRobot, and its performance evaluated using the Matthews correlation coefficient. The target for the addition of CSARs included 414 cases, comprising 302 due to domestic case accumulation, 22 due to both domestic and overseas case accumulation, 12 due to overseas case accumulation, and 78 due to revisions of the company core data sheet. The best model was a generalized linear model with informative features, achieving a cross-validation of 0.8754 and a holdout of 0.8995. In conclusion, the proposed model effectively predicted CSAR additions to PIs resulting from the accumulation of ADR cases using data from both Japan and the United States.

Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.

Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database. We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV. Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

Safety profiles of vancomycin in pediatrics based on China hospital pharmacovigilance system: A retrospective cohort study

The safety of vancomycin in children requires special attention. The evidence from active pharmacovigilance systems about vancomycin-related adverse drug reactions (ADRs) was rare. We aimed to investigate the association between doses of vancomycin and ADRs among children. This retrospective cohort study included a total of 643 inpatient children. Children who received vancomycin were regarded as exposed groups and classified into low-dose, normal-dose, and high-dose groups. Those who did not receive vancomycin and had similar severity of infection were classified into the unexposed group. ADR signal detection was performed by the China Hospital Pharmacovigilance System. Logistic regression analyses were conducted to explore the effect of intravenous vancomycin on ADRs. This study included 156 patients (178 ADR cases) in the exposed group and 487 patients (364 ADR cases) in the unexposed group. The top three reported ADRs were eosinophilia ( n = 75, 48.1%), hemoglobin decreased ( n = 72, 46.2%), and blood bilirubin increased ( n = 13, 8.3%) in the exposed group. Patients in the low-dose, normal-dose, and high-dose groups showed a higher risk of hemoglobin decreased when compared with those in the unexposed group, with the fully adjusted ORs (95% CIs) of 6.91 (3.61, 13.20), 7.80 (3.87, 15.76), and 8.80 (4.08, 19.01), respectively. Besides, compared with patients in the unexposed group, those in the normal-dose and high-dose groups show a significantly higher risk of eosinophilia and blood bilirubin increased, respectively. It is important to monitor eosinophilia, hemoglobin decreased, and blood bilirubin increased in pediatrics receiving vancomycin, especially those receiving normal-dose and high-dose vancomycin.

Evaluation of adverse drug reactions to off-label use of drugs in children from spontaneously reported cases at a tertiary care hospital

Background: Off-label use of drugs (OLUDs) is relatively common in pediatric and this may be associated with adverse drug reactions (ADRs). The studies about the safety of drugs used in children cannot be applied to safety of drugs during OLUDs as drug is used in way that is different from that described in regulatory body. Hence, it is worthwhile to evaluate the off-label status of the suspected drugs causing ADRs. Aims and Objectives: The aim of the study was to analyze the pattern of ADRs occurring during OLUDs in pediatric patients from the spontaneously reported ADRs cases at the pharmacovigilance unit of a tertiary care hospital. Materials and Methods: Single center, retrospective, observational study was conducted in the department of pharmacology. ADRs spontaneously reported from January 2016 to December 2017, which occurred during OLUDs in children, where causality is certain, probable and possible. Results: A total of 46 ADRs occurred during OLUDs in 44 patients, these patients received 174 medicines among which 66 were off-labeled drugs. Off-label drugs mainly belonged to anti-infectives for systemic use (70.31%) and it is associated with 30 ADRs (68.18%). The most commonly affected organ system is skin and subcutaneous tissue (43.18%). Conclusion: OLUDs is associated with ADR, so caution should be taken while prescribing a drug in off-label manner in children.

Time series analysis of using the PDCA method combined with the Teach-back method to improve spontaneous reports of adverse drug reactions in a grade IIIA hospital in China.

Spontaneous reporting of adverse drug reactions (ADRs) is essential for the post-marketing safety evaluation of drugs. Therefore, good monitoring of ADRs is vital for strengthening drug supervision, management, and guiding rational drug use. Chinese medical institutions are the primary source of ADR case reports, but the proportion of the reports in grade IIIA hospitals is still low due to serious under-reporting. The 3rd Affiliated Hospital of Chengdu Medical College, Chengdu Pidu District People's Hospital, also has such a problem. To improve the quantity and quality of ADR reports and enhance the level of pharmacovigilance in hospitals, the Third Affiliated Hospital of Chengdu Medical College, People's Hospital of Chengdu Pidu District experienced 10years to gradually establish a management model to improve the medical staff's reporting rate of spontaneous reporting of ADRs. The management model is led by clinical pharmacists and combines the PDCA with Teach-back methods. The purpose of this paper is to introduce the management model and discuss its advantages and shortcomings of this model. This study was conducted at the Third Affiliated Hospital of Chengdu Medical College-Chengdu Pidu District People's Hospital. From 2016, the daily management of reporting, auditing, and data improvement of adverse drug reactions in the hospital was carried out by clinical pharmacists, who used the PDCA method combined with the Teach-back method to continuously improve the reporting program of ADRs in the hospital during 2016-2021. Then, the proportion of spontaneous reports of total, new, and serious ADRs was compared before and after the intervention. Also, we performed a time series analysis using an autoregressive moving average model to assess changes in the total number of spontaneous ADR reports before the intervention (2013-2015), the first intervention (2016-2018), and the second intervention (2019-2021). After the combined PDCA and Teach-back method intervention, the median number of reported ADRs per year increased from 50 (range 37-55) in the pre-intervention period to 88 (range 83-162) in the first intervention period and to 374 in the second (range 312-566). Breakpoint regression analysis of the spontaneous reporting rate of ADRs showed that the instantaneous increase after the first intervention was not statistically significant (P = 0.526). However, the reporting rate of ADRs increased at a month-by-month growth rate during the second intervention compared to the first intervention. Its spontaneous reporting rate improved 1.034 times (P = 0.002). After the second intervention, the spontaneous reporting rate of ADRs transiently increased 6.111-fold (P < 0.001), and the month-to-month growth rate increased 1.024-fold (P < 0.001) again. The management model that combines the PDCA and the Teach-back method significantly improves the reporting rate of adverse drug reactions.

Predicting the Addition of Information Regarding Clinically Significant Adverse Drug Reactions to Japanese Drug Package Inserts Using a Machine-Learning Model

PurposeTo develop a machine learning (ML)-based model for predicting the addition of clinically significant adverse reaction (CSAR)-associated information to drug package inserts (PIs) based on information of adverse drug reaction (ADR) cases during the post-marketing stage in Japan.MethodsWe collected data on CSARs added to PIs from August 2011 to March 2020. ADR cases that led to CSARs resulting in PI revisions were considered as a positive case, and ML was used to construct a binary classification model to predict the PI revisions. We selected 34 features based on the ADR aggregate data collected 6 months before PI revisions. Prediction performance was evaluated using the Matthews correlation coefficient (MCC).ResultsWe found CSAR information added to PIs in 617 cases, 334 of which were due to the accumulation of domestic cases, and used only domestic case data for the prediction model. Among prediction models developed using several kinds of algorithms, the support vector machine with the radial basis function kernel with feature selection showed the highest predictive performance, having an MCC of 0.938 for the cross-validation and 0.922 for the test dataset. The feature with the highest importance in the model was the “average number of patients reported per quarter.”ConclusionOur model accurately predicted PI revisions using information on ADR cases that occurred 6 months before. This is the first ML model that can predict the necessary safety measures and is an efficient method for guiding the decision to adopt additional safety measures early.

Drug-related deaths in a university hospital: Comparison to previous decades.

The incidence of fatal adverse drug reactions (ADRs) in hospitals varies widely, and ADRs are often underreported. The impact of medical safety processes is not easily evaluated, and although medical practice changes constantly, little is known about ADR trends. This study concentrated on the current incidence and properties of fatal ADRs occurring in a university hospital and compared the results with two previous studies performed in the same hospital. We investigated retrospectively all 1236 deaths that occurred during 2019 in the Helsinki University Hospital. All the cases were evaluated by a team of experts, and the causality was assessed using the categories by World Health Organization and Uppsala monitoring centre. Suicides were excluded. Among death cases, we identified 65 certain or probable ADR cases (5.3%), representing 0.011% of all hospital admissions. Cytostatics and antithrombotics remained the largest drug classes, with neutropenia or sepsis and bleedings as the most common fatal ADRs. Compared with our earlier studies, warfarin caused less, and direct oral anticoagulants caused more fatal bleedings, reflecting the drug usage among the population. In contrast to earlier studies, contrast media and insulin did not cause any fatal ADRs, which may reflect an improvement in pharmacovigilance awareness among healthcare workers.

Drug-induced immune hemolytic anemia: detection of new signals and risk assessment in a nationwide cohort study

AbstractMore than 130 drugs have been suspected to induce immune hemolytic anemia. Comparative studies measuring the risk of drug-induced immune hemolytic anemia (DIIHA) are lacking. We aimed (1) to detect new signals of DIIHA, excluding vaccines, and (2) to assess the association between all suspected drugs and the occurrence of immune hemolytic anemia in a nationwide comparative study. The new signals were identified using a disproportionality study (case/noncase design) in the World Pharmacovigilance Database, Vigibase, among the cases of adverse drug reactions reported up to February 2020 (>20 million). We then conducted a comparative study in the French National health database that links sociodemographic, out-of-hospital, and hospital data for the entire population (67 million individuals). Associations between exposure to drugs (those already reported as DIIHA, plus new signals identified in Vigibase) and incident cases of immune hemolytic anemia (D59.0 and D59.1 diagnosis codes of the International Classification of Diseases, version 10) from 2012 to 2018 were assessed with case-control and case-crossover designs. In Vigibase, 3371 cases of DIIHA were recorded. Fifty-nine new signals were identified resulting in a final list of 112 drugs marketed in France and measurable in the nationwide cohort (n = 4746 patients with incident immune hemolytic anemia included in the case-control analysis matched with 22 447 controls from the general population). We identified an association between immune hemolytic anemia occurrence and some antibiotics, antifungal drugs, ibuprofen, acetaminophen, furosemide, azathioprine, and iomeprol.