Adverse Drug Reaction Database Research Articles

STUDY ABOUT KNOWLEDGE, ATTITUDE, AND PRACTICES OF MEDICAL STAFF ON REPORTING OF ADVERSE DRUG REACTIONS IN THE KINGDOM OF SAUDI ARABIA

Reporting adverse drug reactions (ADRs) are a significant action in any community, and it should be done by healthcare professionals. Although there is much research on this issue all over the world, especially the issues related to: the better reporting of adverse drug reaction, and the developed countries culture, reporting by healthcare professionals. Development of adverse drug reactions databases in most of countries worldwide has been determined in many previous studies, most of these studies have shown prevalence of this issues in developed countries, not in the developing countries. Also, most of these previous studies from different areas in the world, including the kingdom of Saudi Arabia, have focused on the perception and practice of ADR reporting among physicians only, while excluding other medical stuff of healthcare workers. However, in this study, we tried to evaluate the knowledge, attitude, and practice of ADRs monitoring and reporting among healthcare Professionals (physicians, nurses, and pharmacists) in medical field, including hospitals, and pharmacies, in the Kingdom of Saudi Arabia by using a simple survey, and collected from 52 qualified participants. The results were analyzed by the most convenient statistical tests. The study revealed many results, including: a positive attitude, and adequate knowledge and practice towards ADR reporting.

Abstract 4945: Computational modeling-based discovery of novel anticancer drug candidates targeting centromere-associated protein E

Abstract Purpose: Centromere-associated protein E (CENP-E), a mitotic motor protein, is crucial for cell division. Inhibition of CENP-E can lead to chromosome misalignment and aneuploidy. Our recent studies revealed that the CENP-E inhibitor (CENP-Ei), Compound A, induces aneuploid-mediated cGAS-STING pathway activation in cancer cell lines, which is expected to trigger innate immune response and induce immunological conversion of the tumor microenvironment from cold to hot. However, known CENP-Eis exhibited limited efficacy, and none have gone beyond phase I trials since 2012. The aim of this study is to develop a workflow integrating structure and artificial intelligence-based modeling approaches to accelerate the discovery of novel CENP-Eis with improved efficacy and overcome related challenges. Method: The inhibitor-bound CENP-E structure was modeled using chimeric homology modeling followed by induced fit docking with known CENP-Eis. Structure-based virtual screening (VS) was performed on large compound libraries in Enamine REAL, Synthetically Accessible Virtual Inventory, and MolPort databases. Consensus scoring methods were applied by averaging ranks of individual molecules obtained from VS against different CENP-E conformations. An active learning-enhanced VS pipeline was developed using ATOM Modeling PipeLine (AMPL) to find the best-ranked ligands more efficiently. CENP-E ligand candidates were further filtered based on their safety properties predicted by machine learning models trained with curated databases of adverse drug reactions using AMPL. The success of this study was measured by its ability to reveal novel chemotypes that could modulate CENP-E in kinesin ATPase assays. Result: Conformations of CENP-E’s ligand binding site were predicted for VS using the homology model. Structure-based VS was performed to select high-ranked compounds based on consensus scoring. The active learning-enhanced VS pipeline achieved 75% accuracy in ranking the top 20% of hit compounds. The graph convolutional network model with a ROCAUC, 0.76, was created using AMPL to filter ligand candidates based on their predicted safety properties. Seventy-three potential CENP-E ligands computationally prioritized from the Molport database were experimentally tested using kinesin ATPase assays from which 4 potential inhibitors and 8 potential activators were identified indicating overlapping binding sites of inhibitors and activators. Conclusion: Our integrated workflow is effective in discovering novel CENP-E modulators. The discovery of CENP-E activators provides an opportunity to identify novel therapeutics in hepatocellular carcinoma malignancies known to experience decreased CENP-E activity leading to aneuploidy. The predictions generated by computational models combined with experimental validations could further accelerate anticancer drug discovery. Citation Format: Pinyi Lu, Ryo Kamata, Michael R. Weil, Naomi Ohashi, Akihiro Ohashi, Eric A. Stahlberg. Computational modeling-based discovery of novel anticancer drug candidates targeting centromere-associated protein E [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4945.

Comparison of WHO-UMC and Naranjo Scales for Causality Assessment of Reported Adverse Drug Reactions.

The 2 most commonly used scales worldwide are the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) and the Naranjo scales. The present study was planned to assess the degree of agreement between the 2 scales when the same adverse drug reactions (ADR) were assessed by 5 raters independently. One hundred individual case safety reports were selected randomly from the ADR database of our institute and the details were emailed to 5 different experts (raters), who were DM Clinical Pharmacology residents from different institutes in India. An independent causality assessment of these ADRs was performed independently by these raters using both the WHO-UMC and Naranjo causality assessment scales. The agreement between the 2 scales was assessed for each rater using Cohen κ, and the overall interrater agreement was assessed using Fleiss κ. The Cohen κ level of agreement between the 2 scales for the 5 raters were substantial, fair, substantial, moderate, and substantial, respectively. The most common causality assessment category as per WHO-UMC scale was "possible" but varied among the raters on the Naranjo scale. No ADR was categorized as "certain" by any rater on the Naranjo scale. The Fleiss κ value for agreement among the 5 raters was found to be 0.2 (slight) for the WHO-UMC scale and 0.297 (fair) for the Naranjo scale. A moderate level of agreement was observed in this study between the WHO-UMC and Naranjo scales. The level of agreement among these 5 raters was found to be similar for the WHO-UMC and the Naranjo scales, indicating a similar degree of subjectivity for the 2 scales. Hence, more robust and less subjective scales are required for causality assessment.

A Bayesian generating function approach to adverse drug reaction screening.

Determining causality of an adverse drug reaction (ADR) requires a multifactor assessment. The classic Naranjo algorithm is still the dominant assessment tool used to determine causality. But, in spite of its effectiveness, the Naranjo algorithm is manually intensive and impractical for assessing very many ADRs and drug combinations. Thus, over the years, many "automated" algorithms have been developed in an attempt to determine causality. By-and-large, these algorithms are either regression-based or Bayesian. In general, the automatic algorithms have several major drawbacks that preclude fully automated causality assessment. Therefore, signal detection (or causality screening) plays a role in a "first pass" of large ADR databases to limit the number of ADR/drug combinations a skilled human further assesses. In this work a Bayesian signal detector based on analytic combinatorics is developed from a point of view commonly adopted by engineers in the field of radar and sonar signal processing. The algorithm developed herein addresses the commonly encountered issues of misreported data and unreported data. In the framework of signal processing, misreported ADRs are identified as "clutter" (unwanted data) and unreported ADRs are identified as "missed detections". Including the aforementioned parameters provides a more complete probabilistic description of ADR data.

Retrospective Analysis of Spontaneous Reports of Fatal Adverse Reactions Associated with Lidocaine

SCIENTIFIC RELEVANCE. Pain and pain relief are among the most important problems that arise during medical procedures. Lidocaine is used not only as an anaesthetic during interventions but also as a diluent for other medicinal products. Analysis of adverse drug reactions (ADRs) associated with lidocaine contributes to studying lidocaine toxicity and, as a result, developing measures to reduce side effects.AIM. The authors aimed to conduct a retrospective analysis of spontaneous reports of fatal ADRs associated with lidocaine.MATERIALS AND METHODS. This study analysed spontaneous ADR reports of fatal outcomes associated with lidocaine submitted to the federal ADR database in the Automated Information System of the Federal Service for Surveillance in Healthcare of the Russian Federation (Pharmacovigilance, versions 1.0 and 2.0) from 1 January 2008 to 31 December 2020.RESULTS. The ADR reports included 102 fatal outcomes associated with lidocaine. Most often, lidocaine was prescribed as a local anaesthetic or as a diluent for antibacterials. Studying the administered lidocaine doses, the authors identified several overdose cases. Most life-threatening conditions were due to hypersensitivity reactions of anaphylactic shock (54 cases, 52.9%). Lidocaine administration was accompanied by loss of consciousness, respiratory failure, and cardiac arrest in 10 cases (9.8%). Convulsions were a significant clinical sign in 9 cases (8.8%).CONCLUSIONS. Awareness of the risks of systemic toxic effects of local anaesthetics, including lidocaine, necessitates the practical implementation of certain safety measures, such as allergy skin tests before administration and mandatory monitoring of doses and patients’ well-being after administration.

Comparative Analysis of Information Provided in German Adverse Drug Reaction Reports Sent by Physicians, Pharmacists and Consumers.

Adverse drug reactions (ADRs) can be reported by Health Care Professionals (HCPs; e.g., physicians, pharmacists) and non-Health Care Professionals (non-HCPs; e.g., consumers). Previous studies investigating differences between reports from HCPs and non-HCPs rarely considered the completeness of information provided. In addition, they mostly did not distinguish between physicians and pharmacists or were performed years ago. The aim of our study was to analyse and compare the completeness of information provided in reports from physicians, pharmacists and consumers from Germany in a more recent dataset. We analysed all spontaneous reports from Germany received between 2018 and 2021 in the ADR database EudraVigilance exclusively reported by physicians (n = 69,976), pharmacists (n = 42,396) or consumers (n = 121,144). Demographical parameters of the patients were analysed descriptively. Completeness of reports was evaluated applying an established score (vigiGrade). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression analysis in order to identify report, patient, drug or ADR-specific information provided more often in reports from physicians, pharmacists or consumers. Within the study period the number of reports per year by physicians and pharmacists decreased steadily, while an opposite trend was observed for consumer reports. The proportion of female patients was higher in reports from pharmacists (64.4%) and consumers (64.8%) compared to those from physicians (55.3%). On average, patients in reports from pharmacists (58.7) were older compared to those from physicians (53.5) and consumers (52.6). As an example for the presence of specific information, the time to onset of the ADR could be calculated more often in consumer compared to physician (OR 1.9 [1.8-1.9]) and pharmacist reports (OR 1.7 [1.6-1.7]). In contrast, pharmacist (OR 0.5 [0.4-0.5]) and consumer (OR 0.5 [0.5-0.5]) reports included the indication of the suspected drug less often than physician reports. Physician reports on average (mean = 0.5) were slightly more complete according to the vigiGrade score compared to reports from consumers (mean = 0.4) and pharmacists (mean = 0.4). The ADR reports from consumers were comparable with regard to the completeness score with those from physicians and pharmacists underlining their value. Differences in completeness of specific information between the reporter types were found, suggesting that a common reporting of interactions between the three reporters may further improve the completeness of ADR reports. Furthermore, stratified analysis of ADR reports per reporter type may be helpful for certain objectives in scientific research.

Root cause analysis of medication errors of the most frequently involved active substances in paediatric patients

Use of medicinal products in paediatric patients is identified as a risk factor for the occurrence of medication errors. To describe and identify root causes of medication errors in children and adolescents spontaneously reported to Agency for Medicinal Products and Medical Devices of Croatia (Agency). Agency's adverse drug reaction database was searched by using the Standardised MedDRA Query: medication errors (Broad) with data lock point set at 30th June 2022. Cases in which medication errors occurred in patients up to 18 years of age were analysed according to the patients' age group and gender, reporter's qualification, seriousness, reported preferred terms and active substances. For the first 30 most frequently reported active substances, an in-depth analysis was performed to identify the root cause of medication errors. Altogether, 6254 reports were spontaneously reported to the Agency, out of which 1947 (31%) contained at least one preferred term belonging to Standardised MedDRA Query medication errors. More than half of patients experiencing medication errors belonged to the age group 2-11 years (66%) and male gender (53%). The most frequently reported ME PTs included accidental exposure to product by a child (64%) and accidental overdose (17%). Medication error root causes for the first 30 most frequently involved active substances included misinterpretation of prescribed dosage due to a very small volume resulting in salbutamol overdose; replacing millilitre and milligram units resulting in paracetamol solution overdose; interchange between medicinal products due to primary package similarities resulting in cholecalciferol overdose and interchange between oral solution and syrup resulting in valproate overdose. Healthcare professionals should counsel caregivers about the importance of keeping medicinal products out of children's reach and provide detailed instructions on how to appropriately use medicinal products.

Guía internacional para una dosificación más segura de la clozapina en adultos mediante el uso de 6 titulaciones personalizadas de dosis basados en la etnicidad, la proteína C reactiva y los niveles de clozapina

This is the Spanish translation of an international guideline which proposes improving clozapine package inserts worldwide by using ancestry-based: 1) dosing and 2) titration. Adverse drug reaction (ADR) databases suggest clozapine: 1) is the third most toxic drug in the United States (US), and 2) produces worldwide pneumonia mortality four times greater than that of agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers require the lowest dose and male smokers the highest dose). Poor metabolizer (PM) status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity or inflammation with C-reactive protein (CRP) elevations. People with ancestry from Asia (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/ml. Daily doses of 300-600 mg/day are recommended in the US. Slow personalized titration may prevent early ADRs (including syncope, myocarditis and pneumonia). The core of this guideline consists of six personalized titration schedules for inpatients: 1) Asian/Amerindian ancestry with lower metabolism (in cases of obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) Asian/Amerindian ancestry with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (in cases of obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US of non-Asian/Amerindian ancestry with lower clozapine metabolism (in cases of obesity or valproate) needing 150-300 mg/day, and 6) in the US of non-Asian/Amerindian ancestry with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least 4 weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

Fluoroquinolones: a look at the hidden risks of a popular antibiotic

British Journal of Community NursingVol. 28, No. 6 TreatmentsFluoroquinolones: a look at the hidden risks of a popular antibioticAysha MendesAysha MendesE-mail Address: [email protected]Freelance Journalist, specialising in Healthcare and PsychologySearch for more papers by this authorAysha MendesPublished Online:1 Jun 2023https://doi.org/10.12968/bjcn.2023.28.6.272AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Food and Drug Administration. FDA updates warnings for fluoroquinolone antibiotics on risks of mental health and low blood sugar adverse reactions. 2018. https://tinyurl.com/y932zyey (accessed 15 May 2023) Google ScholarMedicines and Healthcare products Regulatory Agency. Drug Safety Update. 2019. https://tinyurl.com/3d9wcfey (accessed 15 May 2023) Google ScholarNational Institute of Health and Care Excellence. 2020 Scenario: acute management of a patient at risk of self harm. 2020. https://tinyurl.com/2x5mxjjy (accessed 15 May 2023) Google ScholarSamyde J, Petit P, Hillaire-Buys D et al.. Quinolone antibiotics and suicidal behavior: analysis of the World Health Organization's adverse drug reactions database and discussion of potential mechanisms. Psychopharmacology. 2016;233:2503–2511. https://doi.org/10.1007/s00213-016-4300-3 Crossref, Medline, Google ScholarWang J, Gagne JJ, Kattinakere-Sreedhara S, Fischer MA, Bykov K. Association between initiation of fluoroquinolones and hospital admission or emergency department visit for suicidality: population based cohort study. Br Med J. 2022;379:e069931. https://doi.org/10.1136/bmj-2021-069931 Medline, Google Scholar FiguresReferencesRelatedDetails 2 June 2023Volume 28Issue 6ISSN (print): 1462-4753ISSN (online): 2052-2215 Metrics History Published online 1 June 2023 Published in print 2 June 2023 Information© MA Healthcare LimitedPDF download

Monitoring of adverse drug reactions in individuals with type 2 diabetes mellitus receiving oral hypoglycemic agents

Background: This study intends to ascertain the prevalence and overall burden of various adverse drug reactions (ADRs) driven by oral antidiabetics for treating type II diabetes mellitus (T2DM) in India. Methods: Patients with T2DM taking oral antidiabetic medications participated in prospective observational research. Data collection used the pretested format by the Indian pharmacovigilance program to record the history of drugs suspected to be responsible for ADRs. The causality evaluation is according to the guidelines of the Uppsala Monitoring Center and the World Health Organization. Results: This study included 424 patients with established diabetes. Female patients showed a non-significant higher percentage of ADRs (p = 0.059). Naranjo’s assessment recorded 51 suspected ADRs with significant (p = 0.042) categorical differences in casualty. According to ADR severity, there was a significant (p = 0.048) difference between moderate 8.25% (n = 35) and mild 3.80% (n = 16); however, none of the ADRs showed severity. Metformin caused abdominal discomfort, itching, and rashes, accounting for 4.95% (n = 21) of all reported adverse reactions. Gliclazide and glimepiride induced hypoglycemia, itch, and rashes, 1.65% (n = 7), abdominal pain, 1.18% (n = 5), flatulence caused by acarbose, abdominal discomfort caused by pioglitazone, and pedal edema caused by pioglitazone 1.18% (n = 5). Conclusion: ADRs due to oral antidiabetic agents are a frequent problem. Therefore, active pharmacovigilance is essential for risk identification, management, and establishing a robust antidiabetic drug ADR database.

Selective serotonin reuptake inhibitors and suicidality in children and young adults: analyses of pharmacovigilance databases

BackgroundSince the warnings by the United States (US) and European regulatory authorities in 2004 and 2005 it had been discussed whether there is some link between selective serotonin reuptake inhibitors (SSRIs) and suicidality in the pediatric population. The aim of our study was to describe trends and patterns in spontaneous reporting data referring to suicidality in children, adolescents and young adults treated with SSRI after the warnings.MethodsDescriptive analyses of reports for 0–24 year olds referring to suicide/suicidal ideations, self-harms and overdoses with SSRIs reported as suspected submitted to the US (FAERS) and the European (EudraVigilance) adverse drug reaction databases until 2019 were performed. The causal relationship was assessed in accordance with the WHO criteria for the European reports. For Germany, prescription data for SSRIs were provided and reporting rates (number of reports/number of prescriptions) were calculated for the reports with possible causal relationship (so called “confirmed reports”).ResultsSince 2004, the number of reports referring to suicide/suicidal ideations, self-harm and overdoses increased steadily in the US and EU. However, only a slight increase was seen for the confirmed EU reports. After 2008, the proportion of reports informing about suicidal ideations increased, while the proportion of fatal suicide attempts decreased. Reporting rates were higher for females and adolescents (12-18 years).ConclusionsOur results demonstrate the importance of further monitoring suicidality in 0–24 year olds treated with SSRI in order to recognize suicidality early avoiding fatal suicide attempts. The higher reporting rates for females and adolescents should be further investigated.

Signal Management: Updated Requirements of the EAEU Good Pharmacovigilance Practice

The Rules of Good Pharmacovigilance Practice of the Eurasian Economic Union (EAEU GVP Guideline) came into force in the EAEU Member States in 2017. Over the next 5 years, marketing authorisation holders and competent authorities managed to build effective pharmacovigilance systems. The current version of the EAEU GVP Guideline was published in May 2022 and enacted on 6 December 2022. Amongst the critical pharmacovigilance processes, a special place is reserved to the process of signal management. The aim of the study was to analyse the new content of the EAEU GVP Guideline related to signal management. The authors reviewed the amendments introduced to the module of the EAEU GVP Guideline on signal management. This article is the first scholarly publication in the Russian language on the updated signal management process. The key changes include a detailed consideration of terminology issues, signal validation and prioritisation processes, notifying competent authorities of signal evaluation results, managing emerging safety issues, and functions of new automated systems: an integrated database of adverse drug reactions and a system for tracking safety issues.

Is PEGylation of Drugs Associated with Hypersensitivity Reactions? An Analysis of the Italian National Spontaneous Adverse Drug Reaction Reporting System.

Evidence highlights the allergenic potential of PEGylated drugs because of the production of anti-polyethylene glycol immunoglobulins. We investigated the risk of hypersensitivity reactions of PEGylated drugs using the Italian spontaneous adverse drug reaction reporting system database. We selected adverse drug reaction reports attributed to medicinal products containing PEGylated active substances and/or PEGylated liposomes from the Italian Spontaneous Reporting System in the period between its inception and March 2021. As comparators, we extracted adverse drug reaction reports of medicinal products containing the same non-PEGylated active substances and/or non-PEGylated liposomes (or compounds belonging to the same mechanistic class). A descriptive analysis of reports of hypersensitivity reactions was performed. Reporting rates and time to onset of hypersensitivity reactions were also calculated in the period between January 2009 and March 2021. As a measure of disproportionality, we calculated the reporting odds ratio. Overall, 3865 adverse drug reaction reports were related to PEGylated medicinal products and 11,961 to their non-PEGylated comparators. Around two-thirds of patients were female and reports mostly concerned patients aged between 46 and 64 years. The frequency of hypersensitivity reactions reporting was higher among PEGylated versus non-PEGylated medicinal products (11.7% vs 9.4%, p < 0.0001). The hypersensitivity reaction reporting rates were higher for PEGylated medicinal products versus non-PEGylated medicinal products, with reporting rate ratios that ranged from 1.4 (95% confidence interval 0.8-2.5) for pegfilgrastim versus filgrastim to 20.0 (95% confidence interval 2.8-143.5) for peginterferon alpha-2a versus interferon alpha-2a. The median time to onset of hypersensitivity reactions was 10 days (interquartile range: 0-61) for PEGylated medicinal products, and 36 days (interquartile range: 3-216) for non-PEGylated comparators. Statistically significant reporting odds ratios were observed when comparing the reporting of hypersensitivity reactions for PEGylated versus non-PEGylated medicinal products (reporting odds ratio: 1.3; 95% confidence interval 1.1-1.4). However, when using all other drugs as comparators, the disproportionality analysis showed no association with hypersensitivity reactions for PEGylated nor non-PEGylated medicinal products, thus suggesting that many other triggers of drug-induced hypersensitivity reactions play a major role. The findings of this analysis of the Italian spontaneous adverse drug reaction database suggest a potential involvement for PEGylation in triggering drug-related hypersensitivity reactions, especially clinically relevant reactions. However, when comparing both PEGylated and non-PEGylated drugs under study to all other drugs no disproportionate reporting of hypersensitivity reactions was observed, probably due to a masking effect owing to the presence in the same database of other medicinal products increasing the threshold required to highlight a safety signal when the entire database is used as a reference.

Assessment of knowledge, attitude, and practice towards adverse drug reaction reporting among healthcare students of Namakkal District, Tamil Nadu

Background: Adverse drug reactions (ADRs) are recognised causes of increased mortality, morbidity, and high healthcare costs. The contribution of healthcare students to ADR databases is essential and has enabled continued drug detection to such an extent that it has led to identifying unsuspected and rare ADR signals. Objectives: The study aims to evaluate healthcare students’ knowledge, attitude, and practice (KAP) toward ADR reporting. Methods: This descriptive, cross-sectional study was conducted among 265 healthcare students of Namakkal district, Tamil Nadu, from various departments. A three-section questionnaire was developed in English and distributed online from July to October 2020. Each participant received a score for each KAP section. Results: Of the 265 healthcare students included in the study, 56.98% were female. The majority were pharmacy students 132 (49.81%), followed by medical 74 (27.92%) and nursing 59 (22.26%) students. There was a significant difference in ADR reporting among healthcare students. KAP of ADR reporting was higher among pharmacy students (88.68%) compared to the medical (19.25%) and nursing students (29.63%), with a p-value of 0.05. Conclusion: This study showed that pharmacy students had more awareness of ADR reporting than other healthcare students due to pharmacovigilance courses in their curriculum and adequate training during clerkships and internships. Hence, it is necessary to include pharmacovigilance and ADR reporting in other healthcare curriculum to reduce ADR underreporting in the future. Periodic educational interventions can improve these parameters of pharmacovigilance.

Identifying adverse drug reactions from patient reviews on social media using natural language processing.

Drugs have the potential of causing adverse reactions or side effects and prior knowledge of these reactions can help prevent hospitalizations and premature deaths. Public databases of common adverse drug reactions (ADRs) depend on individual reports from drug manufacturers and health professionals. However, this passive approach to ADR surveillance has been shown to suffer from severe under-reporting. Social media, such as online health forums where patients across the globe willingly share their drug intake experience, is a viable and rich source for detecting unreported ADRs. In this paper, we design an ADR Detection Framework (ADF) using Natural Language Processing techniques to identify ADRs in drug reviews mined from social media. We demonstrate the applicability of ADF in the domain of Diabetes by identifying ADRs associated with diabetes drugs using data extracted from three online patient-based health forums: askapatient.com, webmd.com, and iodine.com. Next, we analyze and visualize the ADRs identified and present valuable insights including prevalent and less prevalent ADRs, age and gender differences in ADRs detected, as well as the previously unknown ADRs detected by our framework. Our work could promote active (real-time) ADR surveillance and also advance pharmacovigilance research.

Trends in tolvaptan prescription and the association between hypernatremia and aging in tolvaptan-treated patients in Japan: Real-world data mining using Japanese databases.

To identify the trends in tolvaptan prescription and the association between aging and tolvaptan-induced hypernatremia. A health insurance claims database and a spontaneous adverse drug reaction database were used. Of all patients who had been prescribed tolvaptan, the proportion of patients aged 60 - 79 years and ≥ 80 years was consistent at ~ 40%. Moreover, the prescription frequency of tolvaptan increased over time for patients in the same age groups. The adjusted reporting odds ratio of tolvaptan-induced hypernatremia was 5.54 (95% confidence interval, 3.31 - 9.25) in patients aged ≥ 60 years from among all patients and 2.09 (95% confidence interval, 1.59 - 2.75) in those aged ≥ 80 years from among those aged ≥ 60 years. It may be necessary to be aware of hypernatremia in elderly patients who are expected to have increased prescriptions of tolvaptan.

Results of Surveying Cardiologists and Clinical Pharmacologists on the Selection and the Efficacy and Safety Evaluation of Pharmacotherapy for Cardiovascular Diseases

The state policy for the safety of medicinal products involves analysis of specialists' competence in identifying adverse drug reactions (ADRs) during the use of medicinal products. It is of particular importance for the group of essential medicines, including those used in cardiology.The aim of the study was to assess ADR-reporting skills of doctors managing cardiology patients, with anti-arrhythmics as a case study.Materials and methods: from October 2019 to June 2021, the authors surveyed a sample of 223 practitioners that treated cardiology patients in Moscow and the Moscow region (36 of the respondents took the survey in person, and 187 participated on-line). The questionnaire inquired about selection criteria for the medicinal products, their assessment in terms of efficacy and safety in real-life clinical practice, and the competence and active involvement of the doctors in reporting identified ADRs.Results: most of the survey participants were high-level professionals (60.99% had 10 and more years of experience). Most of the doctors (90.13%) admitted having encountered ADRs in their practice, placing substandard quality of cardiovascular medicinal products among the causes. Moreover, 1.79% of the respondents faced such quality problems on a regular basis. Only 52.91% were familiar with the current documents regulating pharmacovigilance. A total of 61.88% applied information from Russian and foreign ADR databases in their practice. In 2021, 80.72% of the surveyed did not report data on the identified ADRs. According to the respondents, the main reasons for low reporting activity were high workload and lack of evidence for causality between a product and an ADR.Conclusion: the study demonstrated the need to intensify the work with practitioners on the safety of medicinal products and ADR identification, particularly, to train them in pharmacovigilance. According to the study results, it is feasible to develop and implement simple and user-friendly risk-oriented information systems for analysis and systematisation of ADR case reports.

Analyses of Basal and Squamous Cell Carcinoma Reported as an Adverse Drug Reaction and Comparison with Cases from the Cancer Registry from Germany.

In Germany, incidence rates of basal cell (BCC) and squamous cell carcinoma (SCC) rose significantly from 1998 to 2010. Ultraviolet (UV) light exposure, immunosuppressants and drugs with photosensitising potential are known to increase the risk to develop BCC and SCC. The aim of our study was to analyse the adverse drug reaction (ADR) reports from Germany referring to BCC and SCC and to compare them to BCC and SCC occurring in the general population. We analysed all validated spontaneous ADR reports referring to BCC (n = 191) and SCC (n = 75) from Germany contained in the European ADR database EudraVigilance prior to 6 March 2019. These reports were compared to 1,267,210 BCC and 476,903 SCC cases from the German Centre for Cancer Registry Data recorded from 2006 to 2018. The number of BCC and SCC reports as well as the BCC and SCC incidences in the registry increased in the analysed time period. Patients with drug-associated BCC (60 years) and SCC (64 years) were younger than patients with BCC (72 years) and SCC (76 years) in the registry. In 57.1 and 60.0% of BCC and SCC reports immunosuppressants were reported as suspected. The reported suspected drug was assumed to possess a photosensitising potential in 41.9 and 44.0% of BCC and SCC reports. In Germany, drug-associated BCC and SCC occurred at a younger age than in the general population. The results underline the necessity for skin cancer screening of patients treated with immunosuppressants or with drugs with photosensitising potential.

Approaches to Assessing the Safety of Medicines during the COVID-19 Pandemic Using the Example of Azithromycin

Most of the medicines used to treat the novel coronavirus infection (COVID-19) are either approved under an accelerated procedure or not approved for the indication. Consequently, their safety requires special attention.The aim of the studywas to review methodological approaches to collecting data on the safety of medicines, using COVID-19 treatment regimens involving azithromycin as a case study.Materials and methods:PubMed® (MEDLINE), Scopus, eLIBRARY, and Cyberleninka databases were searched for publications on azithromycin as part of combination therapy for COVID-19 in 2020–2021. Search queries included names of the medicinal product or its pharmacotherapeutic group and words describing adverse drug reactions (ADRs) during treatment.Results:the analysis included 7 publications presenting the results of studies covering the use of azithromycin as part of COVID-19 combination therapy in more than 4000 patients. Most commonly, the patients receiving COVID-19 therapy including azithromycin developed cardiovascular ADRs (up to 30% of azithromycin prescription cases). In 3 of the analysed publications, safety information was collected through spontaneous reporting and active identification based on the findings of laboratory and instrumental investigations performed during the clinical studies; in other 3, only spontaneous reports were used; and in the last one, ADR database information was studied.Conclusion:currently, information on ADRs associated with the use of medicines is mainly gathered via spontaneous reporting. Direct sourcing of information on personal experiences with a certain product from patients, among other means through social media analysis, opens a promising direction towards the improvement of existing approaches to collecting safety data.

Twenty-First Century Global ADR Management: A Need for Clarification, Redesign, and Coordinated Action.

Adverse drug reactions (ADRs) are estimated to be between the fourth and sixth most common cause of death worldwide, taking their place among other prevalent causes of mortality such as heart disease, cancer, and stroke. ADRs impact a broad range of populations across a wide variety of global geography and demographics, with significant mortality and morbidity burden in vulnerable groups such as older people, pediatric populations, and individuals in low-income settings. Too large a share of medicines risk management remains limited to signal detection in big ADR databases (USFDA, EMA, WHO, etc.) This resource allocation is antiquated and applied statistical signal detection methodologies have reached their limits of usefulness. In addition, existing databases are designed for short-term reactions, closely related to medication use and, thus, can only partially assess important broader consequences across geography, time, and clinical relevance. There is an urgent need change the dynamic. We need to identify (earlier and more regularly) many of the important but often overlooked or missed ADRs. Rather than assigning blame, we need to identify the root causes of the problem so they can be clearly addressed and fixed. The public health implications are profound—particularly as we recognize the importance of predicting and mitigating the next pandemic. Consequently, medicines risk management must be integrated within a broader global public health vision. To accomplish this, we need to develop the new tools and methodologies critical to assessing these public health imperatives.