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Abstract Background Automated recognition and redaction of personal identifiers in free text can enable organisations to share data while protecting privacy. This is important in the context of pharmacovigilance since relevant detailed information on the clinical course of events, differential diagnosis, and patient-reported reflections may often only be conveyed in narrative form. The aim of this study is to develop and evaluate a method for automated redaction of person names in English narrative text on adverse event reports. The target domain for this study was case narratives from the United Kingdom’s Yellow Card scheme, which collects and monitors information on suspected side effects to medicines and vaccines. Methods We finetuned BERT – a transformer-based neural network – for recognising names in case narratives. Training data consisted of newly annotated records from the Yellow Card data and of the i2b2 2014 deidentification challenge. Because the Yellow Card data contained few names, we used predictive models to select narratives for training. Performance was evaluated on a separate set of annotated narratives from the Yellow Card scheme. In-depth review determined whether (parts of) person names missed by the de-identification method could enable re-identification of the individual, and whether de-identification reduced the clinical utility of narratives by collaterally masking relevant information. Results Recall on held-out Yellow Card data was 87% (155/179) at a precision of 55% (155/282) and a false-positive rate of 0.05% (127/ 263,451). Considering tokens longer than three characters separately, recall was 94% (102/108) and precision 58% (102/175). For 13 of the 5,042 narratives in Yellow Card test data (71 with person names), the method failed to flag at least one name token. According to in-depth review, the leaked information could enable direct identification for one narrative and indirect identification for two narratives. Clinically relevant information was removed in less than 1% of the 5,042 processed narratives; 97% of the narratives were completely untouched. Conclusions Automated redaction of names in free-text narratives of adverse event reports can achieve sufficient recall including shorter tokens like patient initials. In-depth review shows that the rare leaks that occur tend not to compromise patient confidentiality. Precision and false positive rates are acceptable with almost all clinically relevant information retained.

Background: Esketamine is the only pharmacological agent with glutamatergic neuromodulator properties approved by the US Food and Drug Administration and European Medicines Agency to enhance the effects of serotonin selective or serotonin and norepinephrine reuptake inhibitors. Treatment-resistant depression (TRD) is a challenging and prevalent condition in the psychiatric field, in which patients often experience persistent and severe depressive symptoms, as well as a higher risk of suicidal thoughts and attempts. Esketamine has demonstrated its safety and effectiveness as a pharmacological therapy for TRD. Our report aims to present 2 cases of depressive symptom deterioration and suicide ideation in patients treated with esketamine. Case Reports: We present 2 cases of TRD that initially responded well to intranasal esketamine but later deteriorated rapidly, with a worsening of depressive symptoms and suicidal ideation. Upon discontinuing esketamine, both patients clinically improved and showed a reduction in suicide ideation. The evaluation of affective symptoms' response to esketamine and evolution was assessed using the Montgomery-Asberg Scale and Clinical Global Impression Severity and Improvement scales. Conclusions: The underlying cause for the paradoxical antidepressant reaction is not entirely clear, but we observed this phenomenon in 2 patients with TRD who were treated with esketamine. Identifications of paradoxical reactions could be difficult in TRD, with highly resistant responses to treatment and suicidal ideation. However, it is relevant to know the prevalence of this phenomenon and for clinicians to be aware of the complications of esketamine treatment. [ABSTRACT FROM AUTHOR]

Background: Automated recognition and redaction of personal identifiers in free text can enable organisations to share data while protecting privacy. This is important in the context of pharmacovigilance since relevant detailed information on the clinical course of events, differential diagnosis, and patient-reported reflections may often only be conveyed in narrative form. The aim of this study is to develop and evaluate a method for automated redaction of person names in English narrative text on adverse event reports. The target domain for this study was case narratives from the United Kingdom's Yellow Card scheme, which collects and monitors information on suspected side effects to medicines and vaccines. Methods: We finetuned BERT – a transformer-based neural network – for recognising names in case narratives. Training data consisted of newly annotated records from the Yellow Card data and of the i2b2 2014 deidentification challenge. Because the Yellow Card data contained few names, we used predictive models to select narratives for training. Performance was evaluated on a separate set of annotated narratives from the Yellow Card scheme. In-depth review determined whether (parts of) person names missed by the de-identification method could enable re-identification of the individual, and whether de-identification reduced the clinical utility of narratives by collaterally masking relevant information. Results: Recall on held-out Yellow Card data was 87% (155/179) at a precision of 55% (155/282) and a false-positive rate of 0.05% (127/ 263,451). Considering tokens longer than three characters separately, recall was 94% (102/108) and precision 58% (102/175). For 13 of the 5,042 narratives in Yellow Card test data (71 with person names), the method failed to flag at least one name token. According to in-depth review, the leaked information could enable direct identification for one narrative and indirect identification for two narratives. Clinically relevant information was removed in less than 1% of the 5,042 processed narratives; 97% of the narratives were completely untouched. Conclusions: Automated redaction of names in free-text narratives of adverse event reports can achieve sufficient recall including shorter tokens like patient initials. In-depth review shows that the rare leaks that occur tend not to compromise patient confidentiality. Precision and false positive rates are acceptable with almost all clinically relevant information retained. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used to treat obesity and diabetes but are linked to a variety of gastrointestinal (GI) adverse events (AEs). Real-world data on GLP-1 RA-related GI AEs and outcomes are limited. This study assessed GI AEs and adverse outcomes using the US FDA Adverse Event Reporting System (FAERS). Methods: This retrospective pharmacovigilance study used the US FDA FAERS database (2007–2023). We searched GLP-1 RA medications, AEs, and adverse outcomes. Demographic, treatment indication, and AE data were collected. Descriptive analysis involved frequencies and percentages, while reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and multivariate logistic regression were used to analyze GLP-1 RA-related GI AEs and outcomes. Results: From 2007 to 2023, a total of 187,757 AEs were reported with GLP-1 RAs, and 16,568 were GLP-1 RA-associated GI AEs in the US. Semaglutide was linked to higher odds of nausea (IC025: 0.151, βCoeff: 0.314), vomiting (IC025: 0.334, βCoeff: 0.495), and delayed gastric emptying (IC025: 0.342, βCoeff: 0.453). Exenatide was associated with pancreatitis (IC025: 0.601, βCoeff: 0.851) and death (ROR: 4.50, IC025: 1.101). Overall, semaglutide had a broader range of notable adverse effects; by comparison, dulaglutide and liraglutide use was associated with fewer significant GI AEs. Conclusions: Analysis of the FAERS data reveals that GLP-1 RAs, particularly semaglutide and exenatide, are significantly associated with specific GI AEs, such as nausea, vomiting, delayed gastric emptying, and pancreatitis. Clinicians should be aware of these potential risks to ensure optimal monitoring and patient safety. This study demonstrated the utility of pharmacovigilance data in identifying safety signals, which can inform future pharmacoepidemiological investigations to confirm causal relationships. Clinicians should be aware of these potential risks to ensure optimal monitoring and patient safety. [ABSTRACT FROM AUTHOR]

Reporting adverse events (adverse drug reactions) associated with medicines and vaccines assists with identifying previously unrecognised side effects and other safety concerns. Reporting adverse events to the Therapeutic Goods Administration is mandatory for sponsors (pharmaceutical companies), and strongly encouraged but voluntary for healthcare professionals and consumers. Adverse events should be reported even when causality is uncertain, as reports may contribute to identification of a safety signal for new or uncommon events. Suspected adverse events associated with new medicines and vaccines (registered in the last 5 years), and medicines included in the Black Triangle Scheme, should be prioritised for reporting. For other medicines, serious adverse events and unexpected adverse events should be prioritised. The Therapeutic Goods Administration analyses adverse event reporting data and uses signal detection methods to identify and evaluate emerging safety signals, which may lead to regulatory actions and communication to address safety issues. [ABSTRACT FROM AUTHOR]

Introduction: Systematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database. Methods: Individual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification. Results: In total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases). Conclusion: Spontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality. [ABSTRACT FROM AUTHOR]

Introduction: Systematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database. Methods: Individual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification. Results: In total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases). Conclusion: Spontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality. [ABSTRACT FROM AUTHOR]

Background: People with gender dysphoria are treated with hormone therapy for gender reassignment. The indication of this therapy was initially for the opposite sex, and information on potential adverse drug reaction (ADR) is lacking. Objective: To describe ADR associated with gender transition medication in transgender individuals reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: Data from the FAERS database up to June 2023 were examined, focusing on reports of gender transition medication use in the context of gender dysphoria. The ADRs were categorized using the Medical Dictionary for Regulatory Activities at both Preferred Term and System Organ Class (SOC) levels. Descriptive statistics summarized report counts, medication types, indications, and ADR severity. Results: For individuals assigned female at birth undergoing gender transition to male (transgender men), 82 reports (230 ADRs) were analyzed, with an average age of 29.5 years. Transgender hormonal therapy was cited in 72% of reports, predominantly from the United States (67.1%). A striking 88% were categorized as serious ADRs, primarily SOC injury, poisoning, and procedural complications (26.5%), followed by psychiatric disorders (14.8%) and nervous system disorders (12.2%). Among those assigned sex male at birth transitioning to female (transgender women) (81 reports, 237 ADRs), mean age was 33.3 years, with 58% indicating use for gender dysphoria. A significant proportion (53.6%) were serious ADRs, primarily SOC: injury, poisoning, and procedural complications (26.6%). Conclusions and Relevance: The FAERS data reveal significant ADRs in transgender individuals using hormone therapy, sometimes unintended for their recipient gender. Population-level studies are crucial to enhance transgender health care. Spontaneous surveillance databases like FAERS illuminate off-label ADRs, urging health care providers to approach hormone therapies with informed caution. [ABSTRACT FROM AUTHOR]

Objective: to describe suspected adverse drug events (ADEs) involving antineoplastics reported in Brazil. Methods: descriptive study of reports to the VigiMed system between 01/01/2019 and 03/31/2023. Results: 29,656 reports involving antineoplastics were identified, most were spontaneous (85.5%) and came from health services (59.0%). Adults (48.1%) and females (63.0%) were more involved in the reports, with a large number of unreported data on age and sex. The most common antineoplastic medicines were paclitaxel (10.4%) and oxaliplatin (7.6%), with emphasis on parenteral presentations (45.1%). A reduced number of medication errors involving antineoplastics were identified (1.3%) and the Reporting Odds Ratio (0.22; 95% CI 0.21-0.23) demonstrated they were less frequent for this class than for other products. Conclusion: reports of ADE involving antineoplastics are frequent in Brazil, and it is important to improve safety barriers and monitor cancer patients, in addition to promoting education and engagement to improve notifications. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the current knowledge and experiences of consumers in Australia on adverse drug reaction (ADR) reporting and their reasons for reporting or not reporting ADRs, with a focus on the use of digital tools for ADR reporting. Methods: A cross-sectional online survey was conducted among adults who had taken medicine in Australia. A structured questionnaire with multiple choice or Likert scale responses with an option for participants to provide free-text responses and pretested for face validity was used. Consumer characteristics, knowledge, and ADR reporting practices were analyzed using descriptive statistics and the chi-square test or Fisher's exact test. Results: A total of 544 survey responses were included in the analysis. The majority of respondents were women (68%), and 22% were aged between 65 and 74 years. Fifty-eight percent (n = 317) of respondents knew that they could report ADRs to either the Therapeutic Goods Administration (TGA), state or territory government health department, or healthcare professionals. Three-quarters (n = 405) of respondents stated that they had experienced an ADR; of these, 36% reported an ADR to either the TGA, state or territory government health department, or healthcare professionals. Among those who reported ADRs, 58% were unaware that they could use digital tools to report ADRs. The main reason for not reporting was that they did not think the ADR was serious enough to report (39%). Conclusion: Over half of consumers knew that they could report ADR; however, improved consumer awareness about using digital tools for ADR reporting and increased ADR reporting is needed. [ABSTRACT FROM AUTHOR]

ObjectiveTo analyses real-world safety data of mRNA COVID-19 vaccines within the European Economic Area (EEA), using Individual Case Safety Reports (ICSR), and to evaluate the variability in safety profiles between different vaccine versions.MethodsWe utilized EudraVigilance data from 1 January 2020, to 31 December 2023, focusing on Moderna (Spikevax) and Pfizer/BioNTech (Comirnaty) vaccines against COVID-19. We performed descriptive statistics, co-occurrence analysis, and correspondence analysis to identify patterns and clusters of adverse events following immunization (AEFI).ResultsWe retrieved 993,199 ICSR (Moderna: 394,484; Pfizer: 605,794), with most reports related to women patients (69%) and non-healthcare professionals (65%). A total of 10,804 distinct AEFI terms were described across the retrieved ICSR, with a cumulative occurrence frequency of 3,558,219 (Moderna: 1,555,638; Pfizer: 2,031,828). The most prominent serious clusters included headache, fatigue, pyrexia, myalgia, arthralgia, malaise, nausea, and chills, which frequently co-occurred with vaccination failure. Specific AEFI like fever, chills, malaise, arthralgia, injection site pain, inflammation, and warmth were more often linked to Moderna, while Pfizer was more commonly associated with vaccination failure, menstrual disorders (heavy menstrual bleeding and dysmenorrhea), and hypoesthesia. In older adults, serious clusters included confusional states, cerebrovascular accidents, and myocardial infarctions, while myocarditis and pericarditis were noted in younger males. Although rare, serious systemic AEFI, like anaphylactic reactions, were identified but require further causality evaluation.ConclusionThe overall safety of mRNA COVID-19 vaccines for mass vaccination is supported, but continuous pharmacovigilance remains essential. Identified clusters of AEFI, particularly serious and systemic ones, although rare and potentially influenced by other underlying causes, underscore the need for continuous monitoring and further epidemiological investigations to explore potential causal relationships.

Several medications are associated with delirium; however, studies with adequate statistical power are limited, and it is difficult to determine the effects of the various concomitant medications used in clinical practice. Therefore, in this study, we aimed to comprehensively evaluate the safety signals of delirium-associated drugs using a spontaneous adverse event reporting system. The JAPIC AERS (Food and Drug Administration Adverse Event Reporting System pre-processed by the Japan Pharmaceutical Information Center) was used for the analysis in this pharmacovigilance study. The reporting odds ratio (ROR) for delirium was adjusted for using multivariate logistic regression analysis with sex, age, indication, and melatonin receptor agonist use, and 22 drug categories were targeted as covariates. After excluding patients with missing information, 7,527,568 patients were included in the study. Delirium signals were detected even after adjusting for covariates in 17 drug categories, including benzodiazepines (adjusted ROR, 1.76; 95% confidence interval [CI], 1.64–1.89), opioids (adjusted ROR, 4.42; 95% CI, 4.21–4.64), and tricyclic antidepressants (adjusted ROR, 2.44; 95% CI, 2.20–2.71). These findings suggest that many drug classes, such as benzodiazepines, are independent risk factors for delirium and strengthen the evidence of an association between delirium and medications. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to perform a nationwide analysis of medication errors (MEs) from hospitals using national reporting system data and to compare the ME patterns among different age groups. Methods: We analyzed medication‐related incidents in acute care hospitals reported to the Korean Patient Safety Reporting and Learning System (KOPS), which is a patient safety reporting system, from July 2016 to December 2020. The stages of the medication use process, type of errors, medication class involved in MEs, and degree of harm were analyzed. Results: Among a total of 5071 medication‐related incidents, 37.7% (1911 cases) were incidents that caused patient harm and 1.2% caused long‐term, permanent, and fatal harm. The proportion of medication‐related incidents that resulted in harm was the highest among the <1‐year‐old age group (67 cases, 51.5%), followed by the elderly (≥ 65 years) (828 cases, 40.9%). The cases leading to patient death were most frequently reported in patients aged ≥65 years. Medication‐related incidents occurred mainly in the administration stage (2954 cases, 58.3%), and wrong dose was the most frequently reported ME type. The most prevalent medication class occurring in the 20–64‐year age group (256 cases, 11.7%) was 'antibacterials for systemic use', whereas 'contrast media' (236 cases, 11.6%) and 'blood substitutes and perfusion solutions' (98 cases, 19.3%) were the most prevalent drug classes in the ≥65‐ and <20‐year‐old age groups, respectively. Conclusions: It is necessary to establish guidelines for the prevention of medication‐related incidents according to the medication use process and patient age group. [ABSTRACT FROM AUTHOR]

While multiple pharmacological drugs have been associated with myocarditis, temporal trends and overall mortality have not been reported. Here we report the spectrum and main features of 5108 reports of drug-induced myocarditis, in a worldwide pharmacovigilance analysis, comprising more than 21 million individual-case-safety reports from 1967 to 2020. Significant association between myocarditis and a suspected drug is assessed using disproportionality analyses, which use Bayesian information component estimates. Overall, we identify 62 drugs associated with myocarditis, 41 of which are categorized into 5 main pharmacological classes: antipsychotics (n = 3108 reports), salicylates (n = 340), antineoplastic-cytotoxics (n = 190), antineoplastic-immunotherapies (n = 538), and vaccines (n = 790). Thirty-eight (61.3%) drugs were not previously reported associated with myocarditis. Antipsychotic was the first (1979) and most reported class (n = 3018). In 2019, the two most reported classes were antipsychotics (54.7%) and immunotherapies (29.5%). Time-to-onset between treatment start and myocarditis is 15 [interquartile range: 10; 23] days. Subsequent mortality is 10.3% and differs between drug classes with immunotherapies the highest, 32.5% and salicylates the lowest, 2.6%. These elements highlight the diversity of presentations of myocarditis depending on drug class, and show the emerging role of antineoplastic drugs in the field of drug-induced myocarditis.

Abstract Objective To evaluate the risk of myasthenia gravis (MG) associated with immune checkpoint inhibitors (ICI). Methods Adverse event (AE) reports related to MG, myasthenic syndrome, and MG crisis for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab in the US FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q3 2022 were collected. The proportional reporting odds ratio (PRR) method was used to evaluate the correlation between the six drugs and the three AEs. Statistical significance was defined as having reports ≥3, PRR ≥ 2, and chi‐square (χ2) ≥ 4. Results A total of 36, 78, 276, 380, 5, and 53 AE reports were collected for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For myasthenic syndrome, the PRR values reflecting the correlation with the drugs were 27.83 (χ2 = 102.66), 26.20 (χ2 = 235.67), 44.17 (χ2 = 1313.98), 32.09 (χ2 = 1229.54), 21.31 (χ2 = 151.15), and 0 for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG, the PRR values reflecting the correlation with the drugs were 24.21 (χ2 = 682.04), 18.34 (χ2 = 900.27), 39.32 (χ2 = 7945.15), 26.93 (χ2 = 6636.45), 14.73 (χ2 = 566.47), and 15.69 (χ2 = 54.77) for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG crisis, there were no data for durvalumab, atezolizumab, avelumab, and ipilimumab; the PRR values reflecting the correlation with the drugs were 16.54 (χ2 = 225.23) and 9.20 (χ2 = 119.14) for pembrolizumab and nivolumab, respectively. All six drugs were statistically correlated with their corresponding AEs. Conclusions ICI may lead to ICIs‐associated MG during therapy. Analysis of FAERS data identified signals for AEs of MG with ICI regimens. Practitioners should consider the factors that may increase the likelihood of MG. The findings support a continued surveillance and risk factor identification.

N/a.

AIMS: With the explosion of anticancer drugs, an emerging concern is the risk for drug-induced sudden death (SD) via ventricular arrhythmias (VA). METHODS AND RESULTS: We used the international pharmacovigilance database VigiBase (n = 18 441 659 reports) to compare drug-induced long QT (diLQT, n = 18 123) and VA (n = 29 193) including torsade de pointes (TdP, n = 8163) reporting for 663 anticancer drugs vs. all other drugs until 01/01/2019. The analysis used the 95% lower-end credibility interval of the information component (IC025), an indicator for disproportionate Bayesian reporting; significant when IC025 >0. There were 2301 reports (13.8% fatal) for 40 anticancer drugs significantly associated with diLQT (with 27 also associated with VA or SD) and 9 drugs associated with VA without diLQT. Half of these (46.9%, 23/49) were associated with SD. Most (41%, 20/49) were kinase inhibitors, 8% (4/49) were hormonal therapies, 6% (3/49) were immunotherapies, 24% (12/49) were cytotoxics, and 20% (10/49) were miscellaneous. In VigiBase, reports of diLQT, TdP, or VA increased from 580 in the period 1967-83 to 15 070 in 2014-18 with the proportion related to anticancer drugs increasing from 0.9% (5/580) to 14.0% (2115/15 070) (P

Antibiotic resistance is an emerging global public health threat. One of the main drivers of this threat is the inappropriate use of antibiotics. In Sri Lanka, antibiotic consumption is increasing, but little is known locally about how patients perceive antibiotics. We conducted a qualitative study to gain a better understanding of the knowledge, perceptions, and attitudes of patients regarding antibiotics and antibiotic resistance. Semi-structured interviews involving 18 patients with lower respiratory tract infection (LRTI) admitted to a large, public tertiary care hospital in southern Sri Lanka were conducted. Interviews were analyzed to identify themes regarding the patients' knowledge of LRTI etiology and treatment, perceptions and attitudes toward LRTI treatment, including antibiotics, and patient-physician communication. Most patients mentioned multiple care visits and the use of multiple pharmaceuticals prior to admission. Patients sought a quick resolution to their ailments and frequently visited several private physicians to obtain a satisfying answer. Self-medication was also common. Patients reused prescriptions for antibiotics, kept antibiotics for later use after prematurely stopping their course of treatment, and bought over-the-counter antibiotics. Patients' knowledge of disease etiology and antibiotics was poor. Only a few patients were aware of antibiotic resistance. Despite the desire to receive more information regarding disease and treatment, patient-provider communication was limited and mainly confined to prescription instructions. This qualitative study performed in Sri Lanka suggests that inappropriate use of antibiotics is a multifactorial problem. To improve antibiotic use, a multifactorial approach that includes educating the public, increasing awareness among physicians, and implementing systems-level changes to restrict access to antibiotics is urgently needed.

3,4-Methylenedioxymethamphetamine (MDMA) is currently being evaluated by the Food and Drug Administration (FDA) for the treatment of post-traumatic stress disorder (PTSD). If MDMA is FDA-approved it will be important to understand what medications may pose a risk of drug-drug interactions. The goal of this study was to evaluate the risks due to MDMA ingestion alone or in combination with other common medications and drugs of abuse using the FDA drug safety surveillance data. To date, nearly one thousand reports of MDMA use have been reported to the FDA. The majority of these reports include covariates such as co-ingested substances and demographic parameters. Univariate and multivariate logistic regression was employed to uncover the contributing factors to the reported risk of death among MDMA users. Several drug classes (MDMA metabolites or analogs, anesthetics, muscle relaxants, amphetamines and stimulants, benzodiazepines, ethanol, opioids), four antidepressants (bupropion, sertraline, venlafaxine and citalopram) and olanzapine demonstrated increased odds ratios for the reported risk of death. Future drug-drug interaction clinical trials should evaluate if any of the other drug-drug interactions described in our results actually pose a risk of morbidity or mortality in controlled medical settings.

Antibodies targeting the PD-1, PD-L1, and CTLA-4 immune checkpoint axis have been used in a variety of tumor types. They achieve anti-tumor activity through activating the patient's own immune system to target immune response evading cancer cells. However, this unique mechanism of action may cause immune-related adverse events, irAEs. One of these irAEs is myocarditis which is associated with an alarming mortality rate. In this study we presented clinical cases of myocarditis from safety trial datasets submitted to the U.S. Food and Drug Administration, FDA. Additionally, we analyzed over fourteen million FDA Adverse Event Reporting System, FAERS, submissions. The statistical analysis of the FAERS data provided evidence of significantly increased reporting of myocarditis in patients administered immune checkpoint inhibitors alone, in combination with another immune checkpoint inhibitor, the kinase inhibitor axitinib, or chemotherapy, for all cancer types, when compared to patients administered chemotherapy. All combination therapies led to further increased reporting odds ratios of myocarditis. We further analyzed the occurrence of myocarditis by stratifying the reports into sub-cohorts based on specific cancer types and treatment/control groups in major cancer immunotherapy efficacy trials and confirmed the observed trend for each cohort.

Chimeric antigen receptor (CAR) T-cell therapy presents a promising treatment for hematologic malignancies, displaying high efficacy but not being exempt from toxicity. In this observational study, we assessed adverse events (AEs) reported to the Food and Drug Adverse Event Reporting System (FAERS) including any of the six approved CAR T-cell therapies. A total of 5249 reports mentioning a CAR T-cell as a suspect product were retrieved from the FAERS database, containing a total of 24333 AEs, of which 3236 (13.3%) were cytopenias. The highest number of AEs mentioned by the report was observed for tisagenlecleucel (mean = 6.7), with the lowest for ciltacabtagene (mean = 1.3). Among all reports, hematopoietic leukopenia was the most frequently reported AEs (n = 1386, 5.7%), with hematopoietic erytropenia the least reported (n = 291, 1.2%). Tisagenlecleucel showed a high reporting odds ratio for hematopoietic erythropenia (27.28, 95%CI 14.04–53.00), leukopenia (4.04, 95%CI 3.52–4.64), and thrombocytopenia (4.01, 95%CI 3.19–5.03). Cytopenias represent one of the most frequently reported AEs in FAERS, a CAR T-cell therapy is indicated, with haematopoetic leukopenia being the most common. When comparing different CAR-T cell therapies, the cytopenias' reporting odds ratio was particularly high for tisagenlecleucel, especially in relation to hematopoietic erythropenia. [ABSTRACT FROM AUTHOR]

A 66-year-old woman, ex-smoker, diagnosed with hypertension, hypercholesterolemia, asthma, anxiety and migraine, who presented pruritus and urticaria, was given Medication Review with Follow-Up Service (MRF). She was taking 5 medications. After the review of the pharmacotherapy and conducting an in-depth interview, the presence of pruritus and urticaria was determined as a Negative Outcomes Releated to Medicines (NOM) and a Drug Related Problem (DRP) derived from the use of Rosuvastatin/Ezetimibe, and a possible DRPs of probability of adverse effects and prescription error. It was proposed to the patient to suspend the treatment and a referral was made to the Primary Care Physician (PCP) by means of a referral report that was submitted by the patient at the medical appointment to assess a pharmacological alternative to treat hypercholesterolemia. The proposal was accepted by the PCP. A follow-up of the case was carried out, which allowed verifying the resolution of the DRPs and NOMs detected, achieving an improvement in the patient's health and favoring adherence to treatment. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the risk of myasthenia gravis (MG) associated with immune checkpoint inhibitors (ICI). Methods: Adverse event (AE) reports related to MG, myasthenic syndrome, and MG crisis for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab in the US FDA Adverse Event Reporting System (FAERS) from Q1 2004 to Q3 2022 were collected. The proportional reporting odds ratio (PRR) method was used to evaluate the correlation between the six drugs and the three AEs. Statistical significance was defined as having reports ≥3, PRR ≥ 2, and chi‐square (χ2) ≥ 4. Results: A total of 36, 78, 276, 380, 5, and 53 AE reports were collected for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For myasthenic syndrome, the PRR values reflecting the correlation with the drugs were 27.83 (χ2 = 102.66), 26.20 (χ2 = 235.67), 44.17 (χ2 = 1313.98), 32.09 (χ2 = 1229.54), 21.31 (χ2 = 151.15), and 0 for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG, the PRR values reflecting the correlation with the drugs were 24.21 (χ2 = 682.04), 18.34 (χ2 = 900.27), 39.32 (χ2 = 7945.15), 26.93 (χ2 = 6636.45), 14.73 (χ2 = 566.47), and 15.69 (χ2 = 54.77) for durvalumab, atezolizumab, pembrolizumab, nivolumab, avelumab, and ipilimumab, respectively. For MG crisis, there were no data for durvalumab, atezolizumab, avelumab, and ipilimumab; the PRR values reflecting the correlation with the drugs were 16.54 (χ2 = 225.23) and 9.20 (χ2 = 119.14) for pembrolizumab and nivolumab, respectively. All six drugs were statistically correlated with their corresponding AEs. Conclusions: ICI may lead to ICIs‐associated MG during therapy. Analysis of FAERS data identified signals for AEs of MG with ICI regimens. Practitioners should consider the factors that may increase the likelihood of MG. The findings support a continued surveillance and risk factor identification. [ABSTRACT FROM AUTHOR]

BackgroundWomen experience adverse drug reactions, ADRs, nearly twice as often as men, yet the role of sex as a biological factor in the generation of ADRs is poorly understood. Most drugs currently in use were approved based on clinical trials conducted on men, so women may be overmedicated. We determined whether sex differences in drug pharmacokinetics, PKs, predict sex differences in ADRs.MethodsSearches of the ISI Web of Science and PubMed databases were conducted with combinations of the terms: drugs, sex or gender, pharmacokinetics, pharmacodynamics, drug safety, drug dose, and adverse drug reaction, which yielded over 5000 articles with considerable overlap. We obtained information from each relevant article on significant sex differences in PK measures, predominantly area under the curve, peak/maximum concentrations, and clearance/elimination rates. ADRs were identified from every relevant article and recorded categorically as female-biased, male-biased, or not sex-biased.ResultsFor most of the FDA-approved drugs examined, elevated blood concentrations and longer elimination times were manifested by women, and these PKs were strongly linked to sex differences in ADRs. Of the 86 drugs evaluated, 76 had higher PK values in women; for 59 drugs with clinically identifiable ADRs, sex-biased PKs predicted the direction of sex-biased ADRs in 88% of cases. Ninety-six percent of drugs with female-biased PK values were associated with a higher incidence of ADRs in women than men, but only 29% of male-biased PKs predicted male-biased ADRs. Accessible PK information is available for only a small fraction of all drugs CONCLUSIONS: Sex differences in pharmacokinetics strongly predict sex-specific ADRs for women but not men. This sex difference was not explained by sex differences in body weight. The absence of sex-stratified PK information in public records for hundreds of drugs raises the concern that sex differences in PK values are widespread and of clinical significance. The common practice of prescribing equal drug doses to women and men neglects sex differences in pharmacokinetics and dimorphisms in body weight, risks overmedication of women, and contributes to female-biased adverse drug reactions. We recommend evidence-based dose reductions for women to counteract this sex bias.

Background: Medication errors can result in adverse drug events (ADEs) and cause considerable patient harm. Limited data are available from Saudi Arabia and the Middle East regarding the prevalence of preventable adverse drug events (pADEs) in primary care settings. Objectives: To estimate the period prevalence of pADEs and assess the medication error severity in primary care setting in Saudi Arabia. Methods: This retrospective study is a continuation of a previous study where 117 of 2000 adult patients managed at the Family Medicine clinics of King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, were identified to have had least one medication error in the past 15 months. The electronic health records of these 117 patients were analyzed for a 3-month post-medication error period to explore the presence of pADE. Medication errors were categorized according to the National Coordinating Council for Medication Error Reporting and Prevention index (NCC MERP) and the occurrence of pADE was assessed using the NCC MERP scheme. Results: Of the included 117 patients, 9 (7.7% [95% confidence interval (CI): 2.79–12.59]) experienced pADE (Category E), while 108 (92.3% [95% CI: 87.97–98.35]) did not (Category C). All patients who experienced pADE were using over-the-counter medications and were on polypharmacy. Outcomes 2a and 2b (asthma and β-blocker) accounted for two and four cases, respectively, while Outcomes 6 (warfarin and international normalized ratio), 7 (lithium and lithium level), 16 (new oral anti-coagulant or warfarin and antiplatelet), and 17 (acetylsalicylic acid [aspirin] and antiplatelet) each accounted for one case. Conclusions: This study provides the period prevalence of patients with pADEs from Family Medicine clinics at a major tertiary hospital of Saudi Arabia, and highlights the need for a multicenter study of clinically important medication errors at the prescribing and monitoring stages for the development of quality improvement programs.

Purpose: Studies on the detection of COVID‐19 vaccine signals in South Korea are insufficient. Therefore, to investigate adverse events (AEs) that might be associated with COVID‐19 vaccines, signals were detected using spontaneous reports from South Korea. We compared the signals with the vaccine insert lists of the regulators in the four countries. Methods: Spontaneous reports from 62 sites were collected by the National Medical Center between January 2013 and May 2022. A descriptive analysis of AEs associated with COVID‐19 vaccines (Pfizer, Moderna, AstraZeneca, and Janssen) was performed, and the proportional reporting ratio, reporting odds ratio, and information component were calculated. We performed five analyses, with five cases and one control group. Results: During the study period, 68 355 cases were reported, of which 12 485 were COVID‐19 vaccine AEs. Injection site pain (2198 cases, 17.6%), myalgia (1552 cases, 12.4%), headache (1145 cases, 9.2%), pyrexia (1003 cases, 8.0%), and fatigue (735 cases, 5.9%) were frequently reported. When comparing all COVID‐19 vaccines with other viral vaccines, 20 signals were detected, of which cachexia, dyspepsia, abdominal discomfort, and mood swings were not listed on the vaccine inserts in all four countries. Overall, 20, 17, 29, and 9 signals were detected in vaccines developed by Pfizer, Moderna, AstraZeneca, and Janssen, respectively. Conclusions: Based on a disproportionate analysis of COVID‐19 vaccine AEs using spontaneous reports from South Korea, different signals were detected for each vaccine manufacturer. [ABSTRACT FROM AUTHOR]

This study aimed to determine the type of drugs reported as suspected of causing severe supraventricular arrhythmias from the Spanish Human Pharmacovigilance System database. A total of 1053 reports were analysed, of which 526 (50%) were on men and 516 (49%) were on women. The most affected age group was the over-65s, with 593 reports (56%). Of the 1613 drugs, those belonging to the cardiovascular system (ATC Group C) were the most numerous (414 reports, 26%), with digoxin being the most frequent drug (49 reports, 12%). Other common groups were antiinfectives for systemic use (ATC Group J; 306 reports, 19%), antineoplastic and immunomodulating agents (ATC Group L; 198 reports, 12%), and nervous system drugs (ATC Group N; 185 reports, 11%). The most common supraventricular arrhythmia was atrial fibrillation (561 reports, 51%). Regarding outcomes, 730 (66%) patients recovered, 76 (7%) did not recover, 25 (3%) recovered but with sequelae, and 23 (2%) resulted in death. This study revealed that certain drugs have reported to be associated more frequently to supraventricular arrhythmias as serious adverse reactions, especially in the older population. Proper clinical management and effective strategies to ensure medication appropriateness should always be considered to improve patient safety when prescribing drugs. [ABSTRACT FROM AUTHOR]

Introduction: Post-marketing identification and report of unknown adverse drug reactions (ADRs) are crucial for patient safety. However, complete information on unknown ADRs seldom is available at the time of spontaneous ADR reports and this can hamper their contribution to the pharmacovigilance system. Methods: In order to characterize the seriousness and outcome of unknown ADRs at the time of report and at follow-up, and analyze their contribution to generate pharmacovigilance regulatory actions, a retrospective observational study of those identified in the spontaneous ADR reports of patients assisted at a hospital (January, 2016-December, 2021) was carried out. Information on demographic, clinical and complementary tests was retrieved from patients' hospital medical records. To evaluate the contribution to pharmacovigilance system we reviewed the European Union SmPCs, the list of the pharmacovigilance signals discussed by the Pharmacovigilance Risk Assessment Committee, and its recommendations reports on safety signals. Results: A total of 15.2% of the spontaneous reported cases during the study contained at least one unknown drug-ADR pair. After exclusions, 295 unknown drug-ADR pairs were included, within them the most frequently affected organs or systems were: skin and subcutaneous tissue (34, 11.5%), hepatobiliary disorders (28, 9.5%), cardiac disorders (28, 9.5%) and central nervous system disorders (27, 9.2%). The most frequent ADRs were pemphigus (7, 2.4%), and cytolytic hepatitis, sudden death, cutaneous vasculitis and fetal growth restriction with 6 (2%) each. Vaccines such as covid-19 and pneumococcus (68, 21.3%), antineoplastics such as paclitaxel, trastuzumab and vincristine (39, 12.2%) and immunosuppressants such as methotrexate and tocilizumab (35, 11%) were the most frequent drug subgroups involved. Sudden death due to hydroxychloroquine alone or in combination (4, 1.4%) and hypertransaminasemia by vincristine (n = 3, 1%) were the most frequent unknown drug-ADR pairs. A total of 269 (91.2%) of them were serious. Complementary tests were performed in 82.7% of unknown-ADR pairs and helped to reinforce their association in 18.3% of them. A total of 18 (6.1%) unknown drug-ADR pairs were evaluated by the EMA, in 8 (2.7%) the information was added to the drug's SmPC and in 1 case the risk prevention material was updated. Conclusion: Identification and follow-up of unknown ADRs can be of great relevance for patient safety and for the enrichment of the pharmacovigilance system. [ABSTRACT FROM AUTHOR]

Purpose: Fluoropyrimidines are anticancer drugs and can cause hyperammonemia both intravenously and orally. Renal dysfunction may interact with fluoropyrimidine to cause hyperammonemia. We performed quantitative analyses of hyperammonemia using a spontaneous report database to examine the frequency of intravenously and orally administered fluoropyrimidine, the reported frequency of fluoropyrimidine-related regimens, and fluoropyrimidine's interactions with chronic kidney disease (CKD). Methods: This study used data collected between April 2004 and March 2020 from the Japanese Adverse Drug Event Report database. The reporting odds ratio (ROR) of hyperammonemia was calculated for each fluoropyrimidine drug and was adjusted for age and sex. Heatmaps depicting the use of anticancer agents in patients with hyperammonemia were drawn. The interactions between CKD and the fluoropyrimidines were also calculated. These analyses were performed using multiple logistic regression. Results: Hyperammonemia was observed in 861 of the 641,736 adverse events reports. Fluorouracil was the most frequent drug associated with hyperammonemia (389 cases). The ROR of hyperammonemia was 32.5 (95% CI 28.3–37.2) for intravenously administered fluorouracil, 4.7 (95% CI 3.3–6.6) for orally administered capecitabine, 1.9 (95% CI 0.87–4.3) for tegafur/uracil, and 2.2 (95% CI 1.5–3.2) for orally administered tegafur/gimeracil/oteracil. Calcium levofolinate, oxaliplatin, bevacizumab, and irinotecan were the most frequently reported agents in cases of hyperammonemia with intravenously administered fluorouracil. The coefficient of the interaction term between CKD and fluoropyrimidines was 1.12 (95% CI 1.09–1.16). Conclusion: Hyperammonemia cases were more likely to be reported with intravenous fluorouracil than orally administered fluoropyrimidines. Fluoropyrimidines might interact with CKD in hyperammonemia cases. [ABSTRACT FROM AUTHOR]

ObjectiveTo evaluate reporting of surgical complications and other adverse events in clinical research articles describing soft tissue and oncologic surgery in dogs and cats.Study designSystematic literature review.SampleEnglish-language articles describing soft tissue and oncologic surgeries in client-owned dogs and cats published in peer-reviewed journals from 2013 to 2016.MethodsCAB, AGRICOLA, and MEDLINE databases were searched for eligible articles. Article characteristics relevant to complications were abstracted and summarized, including reported events, definitions, criteria used to classify events according to severity and time frame, and relevant citations.ResultsOne hundred fifty-one articles involving 10 522 animals were included. Canine retrospective case series of dogs predominated. Ninety-two percent of articles mentioned complications in study results, but only 7.3% defined the term complication. Articles commonly described complications according to time frame and severity, but terminology and classification criteria were highly variable, conflicting between studies, or not provided. Most (58%) reported complications could have been graded with a published veterinary adverse event classification scheme, although common intraoperative complications were notable exceptions.ConclusionDefinitions and criteria used to classify and report soft tissue and oncologic surgical complications are often absent, incomplete, or contradictory among studies.Clinical significanceLack of consistent terminology contributes to inadequate communication of important information about surgical complications. Standardization of terminology and consistency in severity scoring will improve comparative evaluation of clinical research results.

Proton-pump inhibitors, PPIs, are considered effective therapy for stomach acid suppression due to their irreversible inhibition of the hydrogen/potassium pump in the gastric parietal cells. They are widely prescribed and are considered safe for over-the-counter use. Recent studies have shown an association between PPI use and Alzheimer dementia, while others have disputed that connection. We analyzed over ten million United States Food and Drug Administration Adverse Event Reporting System reports, including over forty thousand reports containing PPIs, and provided evidence of increased propensity for memory impairment among PPI reports when compared to histamine-2 receptor antagonist control group. Furthermore, we found significant associations of PPI use with a wide range of neurological adverse reactions including, migraine, several peripheral neuropathies, and visual and auditory neurosensory abnormalities.

Immune checkpoint inhibitors have improved outcomes for patients with numerous hematological and solid cancers. Hematologic toxicities have been described, but the spectrum, timing, and clinical presentation of these complications are not well understood. We used the World Health Organizations pharmacovigilance database of individual-case-safety-reports (ICSRs) of adverse drug reactions, VigiBase, to identify cases of hematologic toxicities complicating immune checkpoint inhibitor therapy. We identified 168 ICSRs of immune thrombocytopenic purpura (ITP), hemolytic anemia (HA), hemophagocytic lymphohistiocytosis, aplastic anemia, and pure red cell aplasia in 164 ICSRs. ITP (n = 68) and HA (n = 57) were the most common of these toxicities and occurred concomitantly in four patients. These events occurred early on treatment (median 40 days) and were associated with fatal outcome in 12% of cases. Ipilimumab-based therapy (monotherapy or combination with anti-programmed death-1 [PD-1]) was associated with earlier onset (median 23 vs. 47.5 days, p = .006) than anti-PD-1/programmed death ligand-1 monotherapy. Reporting of hematologic toxicities has increased over the past 2 years (98 cases between January 2017 and March 2018 vs. 70 cases before 2017), possibly because of increased use of checkpoint inhibitors and improved recognition of toxicities. Future studies should evaluate incidence of hematologic toxicities, elucidate risk factors, and determine the most effective treatment algorithms. KEY POINTS: Immune-mediated hematologic toxicities are a potential side effect of immune checkpoint inhibitors (ICIs).Providers should monitor complete blood counts during treatment with ICIs.Corticosteroids are the mainstay of treatment for immune-mediated hematologic toxicities.Further research is needed to define patient-specific risk factors and optimal management strategies for hematologic toxicities.

Introduction: Post-marketing identification and report of unknown adverse drug reactions (ADRs) are crucial for patient safety. However, complete information on unknown ADRs seldom is available at the time of spontaneous ADR reports and this can hamper their contribution to the pharmacovigilance system.Methods: In order to characterize the seriousness and outcome of unknown ADRs at the time of report and at follow-up, and analyze their contribution to generate pharmacovigilance regulatory actions, a retrospective observational study of those identified in the spontaneous ADR reports of patients assisted at a hospital (January, 2016-December, 2021) was carried out. Information on demographic, clinical and complementary tests was retrieved from patients’ hospital medical records. To evaluate the contribution to pharmacovigilance system we reviewed the European Union SmPCs, the list of the pharmacovigilance signals discussed by the Pharmacovigilance Risk Assessment Committee, and its recommendations reports on safety signals.Results: A total of 15.2% of the spontaneous reported cases during the study contained at least one unknown drug-ADR pair. After exclusions, 295 unknown drug-ADR pairs were included, within them the most frequently affected organs or systems were: skin and subcutaneous tissue (34, 11.5%), hepatobiliary disorders (28, 9.5%), cardiac disorders (28, 9.5%) and central nervous system disorders (27, 9.2%). The most frequent ADRs were pemphigus (7, 2.4%), and cytolytic hepatitis, sudden death, cutaneous vasculitis and fetal growth restriction with 6 (2%) each. Vaccines such as covid-19 and pneumococcus (68, 21.3%), antineoplastics such as paclitaxel, trastuzumab and vincristine (39, 12.2%) and immunosuppressants such as methotrexate and tocilizumab (35, 11%) were the most frequent drug subgroups involved. Sudden death due to hydroxychloroquine alone or in combination (4, 1.4%) and hypertransaminasemia by vincristine (n = 3, 1%) were the most frequent unknown drug-ADR pairs. A total of 269 (91.2%) of them were serious. Complementary tests were performed in 82.7% of unknown-ADR pairs and helped to reinforce their association in 18.3% of them. A total of 18 (6.1%) unknown drug-ADR pairs were evaluated by the EMA, in 8 (2.7%) the information was added to the drug’s SmPC and in 1 case the risk prevention material was updated.Conclusion: Identification and follow-up of unknown ADRs can be of great relevance for patient safety and for the enrichment of the pharmacovigilance system.

A quantitative descriptive study based on Brazilian Active Pharmacovigilance of Dolutegravir (DTG) Project was performed to describe the adverse drug reactions (ADRs) to DTG reported and to evaluate the noncompleteness of data from DTG active pharmacovigilance in Brazil. ADRs and clinical and individual data were obtained from information from the Pharmacovigilance Questionnaire from April 2017 to August 2019. The reported ADRs were classified using the Medical Dictionary for Regulatory Activities (MedDRA). In the evaluated period, 249,066 individuals using DTG participated in the active pharmacovigilance of DTG, with 3472 (1.39%) reporting ADRs at least once. A total of 6312 ADRs were reported, of which 57.56% were persistent and 81.46% were not serious according to the individuals' reports. Most of the reported ADRs were gastrointestinal, neurological and psychiatric. ADRs related to neural tube defects and serious neuropsychiatric ADRs have been reported. Completion of more than half of the fields in the Pharmacovigilance Questionnaire was excellent. The frequency of ADR was low in relation to the number of people living with HIV (PLHIV) using DTG in Brazil, which suggests good tolerability and safety of DTG. The DTG active pharmacovigilance database in Brazil showed good data completeness. [ABSTRACT FROM AUTHOR]

The close contact between patients and community pharmacists, along with the extensive geographical distribution of pharmacies in Portugal, offer exceptional conditions to detect and report adverse drug reactions (ADR). This study aimed to evaluate the motivation and knowledge of spontaneous reporting of ADR by community pharmacists of Porto, Portugal. Secondly, we aimed to generate real-world evidence on the main factors determining ADR report and at raising potential alternatives to the current reporting procedure in community pharmacy. We performed a descriptive, cross-sectional, observational, anonymous web survey-based study. Between April and July 2021, a web survey was implemented, targeting community pharmacists in the Porto district, Portugal. We validated 217 surveys from pharmacists. Regular notifiers seem to be more familiarised than non-regular notifiers with the Portuguese Pharmacovigilance System (PPS), with the Portal RAM for reporting suspected ADR, and with the update of the concept of ADR. Moreover, regular notifiers seem to be more proactive with their care in questioning patients about ADR and have more self-knowledge to identify suspected ADR. Conversely, non-regular notifiers, seem to be more reluctant to be judged by their ADR reporting activities. Respondents suggested to simplify and optimise the reporting process (31% of the suggestions), or to integrate a reporting platform into the pharmacy's software (27%). This study identified opportunities to promote the ADR reporting process by community pharmacists, namely receiving feedback from the PPS on the reported case and its regulatory implications, implementing training programs in pharmacovigilance, and creating solutions to simplify the reporting process. [ABSTRACT FROM AUTHOR]

Abstract Background Pharmacovigilance may be defined as the continuous monitoring of the reaction between a drug agent or combination of drugs a patient took and steps taken to prevent any associated risk. Clinical trials conducted before drug approval cannot uncover every aspect of the health hazards of approved drugs. People with carefully selected characteristics are monitored for the safety and efficacy of the drug; hence, common adverse drug reactions (ADRs) following proper use of the medication can be detected. This calls for continuous monitoring of drugs to report any undocumented ADRs during the clinical trial. The study aimed to assess the knowledge, practice, and barriers to pharmacovigilance among nurses at a teaching hospital. Methods The study was a descriptive cross-sectional study, and a stratified sampling technique was used to select 125 nurses within the three units: medical, surgical, and pediatric wards. A structured questionnaire was developed and used for data collection based on the study's objectives and reviewed literature. Results The majority (67.2%) of the respondents were females, and 32.8% were males. Most (71.2%) of the nurses had low knowledge of ADR reporting procedures. Also, 84.8% of the nurses knew the purpose of reporting ADRs. The purpose of ADR reporting, as perceived by respondents, was to identify safe drugs (80.8%) and calculate the incidence of ADR (75.2%). Additionally, among the nurses who reported having nursed a patient with ADRs, 52.54% stated they reported the case, while 47.46% did not report it. The most cited reason for not reporting ADRs was that nurses considered the reaction normal and commonly associated with that medicine (35.7%). In comparison, 28.5% of the nurses said they did not know they were supposed to report the adverse drug reaction. There was no statistically significant difference between ranks of nurses, ward, attending in-service training, and pharmacovigilance practice. Conclusion In conclusion, nurses in this study had inadequate knowledge of pharmacovigilance and its reporting procedure. The study found that most nurses fear that reporting ADRs may be wrong because most of the nurses in the study did not have any form of pharmacovigilance training.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved clinical outcomes in multiple cancer types and are increasingly being used in early disease settings and in combinations of different immunotherapies. However, ICIs can also cause severe or fatal immune-related adverse-events (irAEs). We aimed to identify and characterise cardiovascular irAEs that are significantly associated with ICIs. METHODS: In this observational, retrospective, pharmacovigilance study, we used VigiBase, WHOs global database of individual case safety reports, to compare cardiovascular adverse event reporting in patients who received ICIs (ICI subgroup) with this reporting in the full database. This study included all cardiovascular irAEs classified by group queries according to the Medical Dictionary for Regulatory Activities, between inception on Nov 14, 1967, and Jan 2, 2018. We evaluated the association between ICIs and cardiovascular adverse events using the reporting odds ratio (ROR) and the information component (IC). IC is an indicator value for disproportionate Bayesian reporting that compares observed and expected values to find associations between drugs and adverse events. IC025 is the lower end of the IC 95% credibility interval, and an IC025 value of more than zero is deemed significant. This study is registered with ClinicalTrials.gov, number NCT03387540. FINDINGS: We identified 31 321 adverse events reported in patients who received ICIs and 16 343 451 adverse events reported in patients treated with any drugs (full database) in VigiBase. Compared with the full database, ICI treatment was associated with higher reporting of myocarditis (5515 reports for the full database vs 122 for ICIs, ROR 11·21 [95% CI 9·36-13·43]; IC025 3·20), pericardial diseases (12 800 vs 95, 3·80 [3·08-4·62]; IC025 1·63), and vasculitis (33 289 vs 82, 1·56 [1·25-1·94]; IC025 0·03), including temporal arteritis (696 vs 18, 12·99 [8·12-20·77]; IC025 2·59) and polymyalgia rheumatica (1709 vs 16, 5·13 [3·13-8·40]; IC025 1·33). Pericardial diseases were reported more often in patients with lung cancer (49 [56%] of 87 patients), whereas myocarditis (42 [41%] of 103 patients) and vasculitis (42 [60%] of 70 patients) were more commonly reported in patients with melanoma (χ2 test for overall subgroup comparison, p80%), with death occurring in 61 (50%) of 122 myocarditis cases, 20 (21%) of 95 pericardial disease cases, and five (6%) of 82 vasculitis cases (χ2 test for overall comparison between pericardial diseases, myocarditis, and vasculitis, p

OBJECTIVE: A prolonged QTc (LQT) is a surrogate for the risk of torsade de pointes (TdP). QTc interval duration is influenced by sex hormones: oestradiol prolongs and testosterone shortens QTc. Drugs used in the treatment of breast cancer have divergent effects on hormonal status. METHODS: We performed a disproportionality analysis using the European database of suspected adverse drug reaction (ADR) reports to evaluate the reporting OR (ROR χ2) of LQT, TdP and ventricular arrhythmias associated with selective oestrogen receptor modulators (SERMs: tamoxifen and toremifene) as opposed to aromatase inhibitors (AIs: anastrozole, exemestane and letrozole). When the proportion of an ADR is greater in patients exposed to a drug (SERMs) compared with patients exposed to control drug (AIs), this suggests an association between the specific drug and the reaction and is a potential signal for safety. Clinical and demographic characterisation of patients with SERMs-induced LQT and ventricular arrhythmias was performed. RESULTS: SERMs were associated with higher proportion of LQT reports versus AIs (26/8318 vs 11/14851, ROR: 4.2 (2.11-8.55), p

Introduction: Because patients and patient organizations want to strengthen their role in the care pathway and drug evaluation and in order to improve pharmacovigilance activities, European competent authorities implemented regulations to allow direct reporting of adverse drug reactions related to medicinal products by patients in 2012. Objectives: To describe evolution and analyze determinants of patient reporting activity in France in order to assess patient involvement in pharmacovigilance. Method: Using the French national pharmacovigilance database, univariate and multivariate analyses were performed to compare the characteristics of adverse drug reaction (ADR) reports from patients and healthcare professionals (HCP) between 2011 and 2020. The relationship between regional patient ADR report activity and regional care provision and socio-professional characteristics was analyzed using the principal component analysis. Results: A significant and higher increase in ADR reports over time from patients (r = 0.89, p < 0.001) compared to HCP (r = 0.27, p = 0.002) has been observed. Patient ADR report activities compared to HCP concerned more women (80% vs. 55%, p < 0.001), younger age classes (p < 0.001), reporting through web portal (83% vs. 17%, p < 0.001), and less serious events (26% vs. 63%, p < 0.001). In the principal component analysis, regional patient reporting activity was related to socio-professional categories, age classes, and densities of hospital beds and physicians. Conclusion: Our results confirm an increasing involvement of patients in ADR report activities. The determinants of patient reporting activities are not only related to drug and medical factors but also to social factors. Digital tools may also play a role in health democracy in pharmacovigilance. [ABSTRACT FROM AUTHOR]

Purpose: A cornerstone of treatment for many cancers is the administration of platinum-based chemotherapies and/or ionizing radiation, which can be ototoxic. An accurate ototoxicity risk assessment would be useful for counseling, treatment planning, and survivorship follow-up in patients with cancer. Methods: This systematic review evaluated the literature on predictive models for estimating a patient's risk for chemotherapy-related auditory injury to accelerate development of computational approaches for the clinical management of ototoxicity in cancer patients. Of the 1195 articles identified in a PubMed search from 2010 forward, 15 studies met inclusion for the review. Conclusions: All but 1 study used an abstraction of the audiogram as a modeled outcome; however, specific outcome measures varied. Consistently used predictors were age, baseline hearing, cumulative cisplatin dose, and radiation dose to the cochlea. Just 5 studies were judged to have an overall low risk of bias. Future studies should attempt to minimize bias by following statistical best practices including not selecting multivariate predictors based on univariate analysis, validation in independent cohorts, and clearly reporting the management of missing and censored data. Future modeling efforts should adopt a transdisciplinary approach to define a unified set of clinical, treatment, and/or genetic risk factors. Creating a flexible model that uses a common set of predictors to forecast the full post-treatment audiogram may accelerate work in this area. Such a model could be adapted for use in counseling, treatment planning, and follow-up by audiologists and oncologists and could be incorporated into ototoxicity genetic association studies as well as clinical trials investigating otoprotective agents. Implications for Cancer Survivors: Improvements in the ability to model post-treatment hearing loss can help to improve patient quality of life following cancer care. The improvements advocated for in this review should allow for the acceleration of advancements in modeling the auditory impact of these treatments to support treatment planning and patient counseling during and after care. [ABSTRACT FROM AUTHOR]

Background: Medication errors can result in adverse drug events (ADEs) and cause considerable patient harm. Limited data are available from Saudi Arabia and the Middle East regarding the prevalence of preventable adverse drug events (pADEs) in primary care settings. Objectives: To estimate the period prevalence of pADEs and assess the medication error severity in primary care setting in Saudi Arabia. Methods: This retrospective study is a continuation of a previous study where 117 of 2000 adult patients managed at the Family Medicine clinics of King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, were identified to have had least one medication error in the past 15 months. The electronic health records of these 117 patients were analyzed for a 3-month post-medication error period to explore the presence of pADE. Medication errors were categorized according to the National Coordinating Council for Medication Error Reporting and Prevention index (NCC MERP) and the occurrence of pADE was assessed using the NCC MERP scheme. Results: Of the included 117 patients, 9 (7.7% [95% confidence interval (CI): 2.79–12.59]) experienced pADE (Category E), while 108 (92.3% [95% CI: 87.97–98.35]) did not (Category C). All patients who experienced pADE were using over-the-counter medications and were on polypharmacy. Outcomes 2a and 2b (asthma and β-blocker) accounted for two and four cases, respectively, while Outcomes 6 (warfarin and international normalized ratio), 7 (lithium and lithium level), 16 (new oral anti-coagulant or warfarin and antiplatelet), and 17 (acetylsalicylic acid [aspirin] and antiplatelet) each accounted for one case. Conclusions: This study provides the period prevalence of patients with pADEs from Family Medicine clinics at a major tertiary hospital of Saudi Arabia, and highlights the need for a multicenter study of clinically important medication errors at the prescribing and monitoring stages for the development of quality improvement programs. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic accelerated new vaccine development. Limited safety data necessitated robust global safety surveillance to accurately identify and promptly communicate potential safety issues. The African Union Smart Safety Surveillance (AU-3S) program established the Joint Signal Management (JSM) group to support identification of potential vaccine safety concerns in five pilot countries (Ethiopia, Ghana, Kenya, Nigeria, South Africa), accounting for approximately 35% of the African population., Objective: Our objective was to provide an overview of the JSM group's role in supporting signal management activities for the AU-3S program during the COVID-19 pandemic., Methods: Spontaneous, electronically reported COVID-19 vaccine adverse events following immunization (AEFI) from each country's safety data were integrated into the interim Data Integration and Signal Detection system. Statistical disproportionality methods were used to identify and review vaccine-event combinations (VECs) for potential safety concerns. The JSM group-which comprised pharmacovigilance and subject matter experts from National Medicine Regulatory Authorities, Expanded Programs on Immunization, and vaccine safety committees-conducted signal detection activities on cross-country safety data and provided recommendations., Results: From April 2021 to December 2023, a total of 48,294 spontaneously reported AEFI were analyzed for six COVID-19 vaccines (NRVV Ad [ChAdOx1 nCoV-19]; Ad26.COV2.S; Elasomeran; Tozinameran; Covid-19 vaccine [Vero Cell], Inactivated; NRVV Ad26 [Gam-Covid-Vac]) administered in Ethiopia (34.6%), Nigeria (30.3%), South Africa (16.9%), Ghana (13.5%), and Kenya (4.7%). Overall, 2,742 VECs were validated. A causal association between the COVID-19 vaccines and the reported AEFI cannot be inferred, as data were reported spontaneously. JSM group recommendations included monitoring for further evidence, no immediate action required, engaging marketing authorization holder(s) for additional information, or sensitizing healthcare providers and/or the public about events. Although no new safety signals were identified, nine safety-related recommendations were issued, including patient and healthcare provider education., Conclusions: The JSM group established a scalable and replicable model for future signal management of other priority health products in low- and middle-income countries, fostering ongoing collaboration and capacity building. Knowledge and experience gained from this pilot initiative will guide stakeholders in future safety surveillance initiatives within the African continent., Competing Interests: Declarations. Funding: Open access funding provided by Sefako Makgatho Health Sciences University. The implementation of the AU-3S program in the pilot countries, which resulted in the work presented in this paper, were funded by the Bill & Melinda Gates Foundation, Seattle, WA, USA (grant number: INV-045215 [OPP1213055]). Open access for this paper was enabled through an agreement between Sefako Makgatho Health Sciences University and Springer Nature. Conflict of interest: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Availability of data and material: N/A. Ethics approval: N/A. Consent to participate: N/A. Consent for publication: All authors have read the manuscript and consent to its publication. Code availability: N/A. Author contributions: JSM group involved in the implementation of the work presented in this paper: VPD, HMG, MBA, NYB, MB, GTS, JOG, EMG, TA, WA, HJL, MCL, AM, KAA, MM, UGE, HM, AKN, MS, MK, KM, YlT, AA, KMY, OE, LS, KD, KO, MCA, DMD, HG, BS, FS, AA, and JCM. Data acquisition and analysis: VPN, MBA, NYB, and HM. First draft of the manuscript: VPN and JCM. Revision for important intellectual content: VPD, HMG, MBA, NYB, MB, GTS, JOG, EMG, TA, WA, HJL, MCL, AM, KAA, MM, UGE, HM, AKN, MS, MK, KM, YlT, AA, KMY, OE, LS, KD, KO, MCA, DMD, HG, BS, FS, AA, and JCM. All authors have read and approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to accuracy or integrity of any part of the work are appropriately investigated and resolved., (© 2025. The Author(s).)

Background and Objective: Adverse drug reactions (ADRs) pose a serious threat to patient health, potentially resulting in severe consequences, including mortality. Accurate prediction of ADRs before drug market release is crucial for early prevention. Traditional ADR detection, relying on clinical trials and voluntary reporting, has inherent limitations. Clinical trials face challenges in capturing rare and long-term reactions due to scale and time constraints, while voluntary reporting tends to neglect mild and common reactions. Consequently, drugs on the market may carry unknown risks, leading to an increasing demand for more accurate predictions of ADRs before their commercial release. This study aims to develop a more accurate prediction model for ADRs prior to drug market release., Methods: We frame the ADR prediction task as a sequence-to-sequence problem and propose the Bio-K-Transformer, which integrates the transformer model with pre-trained models (i.e., Bio&#95;ClinicalBERT and K-bert), to forecast potential ADRs. We enhance the attention mechanism of the Transformer encoder structure and adjust embedding layers to model diverse relationships between drug adverse reactions. Additionally, we employ a masking technique to handle target data. Experimental findings demonstrate a notable improvement in predicting potential adverse reactions, achieving a predictive accuracy of 90.08%. It significantly exceeds current state-of-the-art baseline models and even the fine-tuned Llama-3.1-8B and Llama3-Aloe-8B-Alpha model, while being cost-effective. The results highlight the model's efficacy in identifying potential adverse reactions with high precision, sensitivity, and specificity., Conclusion: The Bio-K-Transformer significantly enhances the prediction of ADRs, offering a cost-effective method with strong potential for improving pre-market safety evaluations of pharmaceuticals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Romiplostim, eltrombopag, and avatrombopag, as new-generation thrombopoietin receptor agonists (TPO-RAs), have been widely used in the treatment of immune thrombocytopenia (ITP). Given their similar efficacy, a comprehensive evaluation of their safety is crucial for optimizing treatment choices. This study aims to explore the potential safety issues of three major drugs for treating ITP: romiplostim, eltrombopag, and avatrombopag, thereby providing references and research directions for subsequent high-quality clinical studies., Methods: We retrieved data from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2018 to the second quarter of 2023. Using reporting odds ratio (ROR), proportional reporting ratio (PRR), bayesian confidence propagation neural network (BCPNN), and multiple gamma poisson shrinkage (MGPS), we mined and analyzed adverse events (AEs) associated with romiplostim, eltrombopag, and avatrombopag. The Designated Medical Event (DME) list from the European Medicines Agency (EMA) was used to screen out the DME of three drugs. Venn analysis was used to screen the specific AEs of each drug., Results: The study included 2,851 cases of romiplostim, 10,297 cases of eltrombopag, and 973 cases of avatrombopag. Venn analysis revealed nine common AEs across the three drugs. The number of significant specific AEs associated with romiplostim, eltrombopag, and avatrombopag were 58, 98, and 15 respectively. DMEs for romiplostim included autoimmune haemolytic anaemia (ROR = 6.1, n = 3), haemolytic anaemia (ROR = 8.13, n = 7), sudden hearing loss (ROR = 5.24, n = 3), haemolysis (ROR = 3.89, n = 3). DMEs for eltrombopag included hepatic infection (ROR = 9.56, n = 6), granulocytopenia (ROR = 2.91, n = 4), autoimmune haemolytic anaemia (ROR = 3.03, n = 5), haemolytic anaemia (ROR = 3.46, n = 10), haemolysis (ROR = 4.65, n = 12), hepatic failure (ROR = 2.51, n = 23). Not a single DME was found for avatrombopag., Conclusion: This study indicates that eltrombopag manifests significant safety signals within the hepatic system. This implies that monitoring liver function during treatment is advisable. Avatrombopag shows relatively lower hepatotoxicity signals; however, further large-scale studies are needed to validate these observations. Moreover, both romiplostim and eltrombopag therapies may be linked to a risk of sudden hearing loss or deafness, which merits clinical attention. These findings offer crucial safety references for clinical drug use. Nevertheless, the causal relationship between the drugs and AEs necessitates further in-depth investigation., Competing Interests: Declarations. Ethical approval: The present pharmacovigilance study was conducted using a public database of spontaneous reports. Given the use of deidentified data, ethical approval was not considered necessary. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Developing Countries Vaccine Manufacturers Network (DCVMN) is an alliance of vaccine developers, manufacturers, and marketing authorization holders (MAHs) from low- and middle-income countries (LMICs) that plays a vital role in ensuring equitable, inclusive, accountable, and timely access to affordable, high-quality vaccines in these countries. Besides research and development, this network promotes manufacturing and global supply chains for effective strengthening of regulatory and pharmacovigilance activities. Traditionally, vaccine safety surveillance systems in LMICs rely on spontaneous reporting. However, especially in resource-limited settings, robust passive surveillance is lacking, and active vaccine safety surveillance (AVSS) can complement passive surveillance by actively collecting adverse events at sentinel sites or via formally designed observational (non-interventional) studies. The rapid introduction of novel vaccines during the COVID-19 pandemic with rather limited safety information at deployment accelerated the need for comprehensive AVSS in LMICs to detect potential safety concerns that may not have been identified in pre-licensure trials. In this context, national regulatory agencies (NRAs) and the World Health Organization (WHO) prequalification team requested risk management plans (RMPs) in line with Pharmacovigilance Planning guideline. The submitted RMPs contained the companies' commitments to pharmacovigilance activities encompassing both post-approval routine surveillance (passive) and additional active surveillance activities. These AVSS activities were either committed voluntarily by the manufacturers/MAHs or imposed by the NRA/WHO prequalification in case of important identified or potential risks, or important missing information. Unlike passive surveillance, AVSS relies on various epidemiological methodologies that require resources and expertise. DCVMN initiated a "learn-by-doing" project to support manufacturers/MAHs in performing AVSS. This project focused on improving the understanding of AVSS and its tools, investigated the support needs, opportunities, challenges, and barriers to performing AVSS activities in LMICs, and proposed solutions that could be used to mitigate the main challenges in performing AVSS activities in these countries., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KH is an independent vaccine safety expert consulting for DCVMN and CEPI. Patricia Mouta Nunes de Oliveira reports article publishing charges and writing assistance were provided by DCVMN International. Patricia Mouta Nunes de Oliveira reports a relationship with Immunobiological Technology Institute that includes: employment. PMNO is an employee of Bio-Manguinhos, a public vaccine producer in Brazil If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Objects: The olanzapine/samidorphan (OLZ/SAM) combination is being regarded as a new strategy to combat weight gain induced by olanzapine (OLZ), and its safety is of significant concern. Specifically, as samidorphan is an opioid receptor-related drug, issues related to its potential for dependence and withdrawal symptoms deserve attention. This study aims to provide a comprehensive analysis of adverse events (AEs) associated with the OLZ/SAM., Methods: This study is a pharmacovigilance study based on the analysis of reports from the FDA Adverse Event Reporting System (FAERS) utilizing the Openvigil online analysis platform for the period from January 1, 2023, to June 30, 2024. Signal results were reported as Reporting Odds Ratios (ROR) along with 95% confidence intervals. A binary logistic regression model was used to analyze the association between the OLZ/SAM and specific AEs., Results: This study included 86 reports of AEs associated with the OLZ/SAM and 4,678 reports related to OLZ. In terms of frequency of OLZ/SAM-related AEs, off-label use (N = 12) and drug withdrawal syndrome (N = 11) were reported most frequently. Among various system organ classes, the highest frequency of AEs was observed in neurological disorders (SOC) (N = 23). We identified 15 signals associated with the OLZ/SAM. The results of the stepwise regression analysis indicated that in all models, the OLZ/SAM was significantly associated with drug withdrawal syndrome when compared to OLZ (p < 0.01)., Conclusion: The long-term safety of the OLZ/SAM warrants attention, particularly concerning drug withdrawal syndrome., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Financial disclosure: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Hepatitis B vaccines (HBVs) are widely used duo to their high clinical use and mild effects. However, as post-marketing data accumulate, several serious adverse events (SAEs) following HBV have been reported. Currently, quantitative studies based on real-world data are lacking, and information on their adverse events is limited. Adverse reaction signals of the HBV were mined and analyzed using the U.S. Vaccine Adverse Event Reporting System (VAERS) to provide a reference for the safe clinical use of this vaccine. Multiple statistical methods, including the reporting odds ratio (ROR) method, the Medicines and Healthcare Products Regulatory Agency (MHRA) method, and the Bayesian Confidence Propagation Neural Network (BCPNN) method, were utilized to identify signals of HBV-associated adverse reactions, and positive signals consistent with designated medical events (DMEs) were singled out for focused comparison and discussion. Analysis of 54,136 HBV-related adverse events (AEs) identified 254 positive signals across 22 System Organ Classifications (SOCs), with General disorders and administration site conditions being the most common. Three potential positive new signals consistent with Preferred Terms (PTs) were identified in DME: Aplastic anaemia, Dermatitis exfoliative, and Haemolytic anaemia. This study suggests that HBV has a potential risk in terms of causing Aplastic anaemia, Dermatitis exfoliative, and Haemolytic anaemia. Some subtypes of Aplastic anaemia, Dermatitis exfoliative, Haemolytic anaemia are autoimmune diseases, and immunization may stimulate potential autoimmune genetic predisposition, people with autoimmune diseases or a family history of hereditary immune diseases should be monitored after receiving HBV. Health professionals should be contacted to take measures to help if anaemia, palpitations, and high fever occur., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: Anonymized data were collected from a publicly available database and do not require ethics committee approval., (© 2025. The Author(s).)

Raynaud's phenomenon is a vascular condition characterized by episodic vasoconstriction, and recent reports suggest a potential link between calcitonin gene-related peptide (CGRP) inhibitors, used for migraine treatment, and the onset of this condition. This study evaluated the association between CGRP inhibitors and Raynaud's phenomenon using data from the FDA Adverse Event Reporting System (FAERS). A retrospective analysis of adverse events from the approval year of each drug through August 2023 was conducted. Disproportionality was assessed using Reporting Odds Ratios (ROR) and Information Components (IC), with significant signals of disproportionate reporting (SDR) identified by a lower 95% confidence interval (CI) for ROR > 1.0 and IC > 0. Intra-class and inter-class analyses were conducted to compare SDRs among CGRP inhibitors and other migraine therapies, including triptans, beta-blockers, and anticonvulsants. CGRP inhibitors demonstrated significant SDRs for Raynaud's phenomenon (ROR 19.12; 95% CI 15.44-23.69), with rimegepant, ubrogepant, and atogepant showing particularly strong signals. Intra-class analysis revealed a significant SDR only for galcanezumab (ROR 2.01; 95% CI 1.28-3.17). Inter-class analysis indicated significant SDRs for CGRP inhibitors compared to beta-blockers, anticonvulsants, and celecoxib, but not triptans. These findings underscore the importance of ongoing pharmacovigilance and further research to validate these associations and ensure patient safety., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)