Efficacy and safety of a novel polytetrafluoroethylene-coated self-expandable metal stent for distal malignant biliary obstruction.

Background: Stent migration and sludge formation remain significant problems associated with covered self-expandable metal stents (CSEMSs). The EGIS biliary stent fully covered flare type (EGIS biliary stent), a new type of polytetrafluoroethylene-coated self-expandable metal stent with low axial force and an anti-migration system, was developed to overcome these disadvantages. We conducted this study to evaluate the efficacy and safety of this stent in comparison with conventional CSEMS (c-CSEMS). Methods: We retrospectively analyzed consecutive patients with unresectable pancreatic cancer who received initial CSEMS for distal malignant biliary obstruction. The primary outcome was time to recurrent biliary obstruction (RBO). Secondary outcomes included technical success rate, functional success rate, stent-related adverse events, causes of RBO, and re-intervention. Results: A total of 40 patients were included (EGIS group: 20; c-CSEMS group: 20). The technical and functional success rates were similar between the two groups. Stent-related adverse event rates (20% vs. 15%, p > 0.99) and overall RBO rates (56% vs. 50%, p > 0.99) were not significantly different between the two groups. Stent migration was the most common cause of RBO in the EGIS group, while stent occlusion was in the c-CSEMS group. The median time to RBO (102 vs. 434 days, p = 0.10) was not significantly different between the two groups. Endoscopic transpapillary re-intervention was successful in most patients in both groups. Conclusions: The EGIS biliary stent was not associated with a longer time to RBO compared to c-CSEMS. Further improvements, especially against stent migration, are needed to improve its efficacy.

Bilateral exudative retinal detachment with subretinal light-chain protein in a patient with multiple myeloma -case report.

BACKGROUND: Exudative retinal detachment in patients with multiple myeloma is exceedingly rare. Only two Cases are known to us. We successfully identified light-chain proteins in subretinal fluid, allowing for a more precise understanding of the pathogenesis of this complication. CASE PRESENTATION: A 68-year-old patient presented with bilateral exudative retinal detachment. The visual impairment was reported one day after stem cell mobilization by granulocyte-colony stimulating factor (G-CSF) and the additional administration of Plerixafor. The symptoms began during stem cell apheresis. The patient underwent surgical treatment for both eyes through vitrectomy and silicone oil tamponade. Light-chain proteins were detected in the collected subretinal fluid through electrophoresis in one eye. CONCLUSIONS: We successfully identified light-chain proteins in subretinal fluid, allowing for a more precise understanding of the pathogenesis of this complication. The pathomechanism likely involves damage to the outer blood-retina barrier due to the deposition of light-chain proteins. Whether mobilization of bone marrow cells with Plerixafor led to a breakdown of the outer blood-retina barrier in these patients is a topic for discussion and has to be considered in the use of Plerixafor.

Prevalence and Predictors of Adverse Events Associated With Dipeptidyl Peptidase-4 (DPP-4) Inhibitors in Type 2 Diabetic Patients: A Cross-sectional Study.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral hypoglycemic agents widely prescribed in India despite safety concerns. However, studies focused on their safety profile are scarce, especially in South India. Objective: To evaluate the prevalence and predictors of adverse events (AEs) with DPP-4 inhibitors in patients with type 2 diabetes mellitus (T2DM). Research design and methods: This retrospective cross-sectional study analyzed data from medical records of T2DM patients prescribed DPP-4 inhibitors admitted to the medicine department from 2019 to 2021 at a South Indian tertiary care hospital. The causality of AEs was assessed using the WHO-Uppsala Monitoring Centre (WHO-UMC) criteria and the Naranjo scale, and severity using the Modified Hartwig and Seigel scale. We applied a Generalized model with a binary response and logit-link function to understand the factors that best explain the AE. The best-fit models were chosen based on least Akaike's information criterion and highest PseudoR 2 and presented the odds ratio (OR) with a 95% confidence interval. The analyses were performed in R software version 4.2.1. Results: Among the 796 patients included in the study, 26% experienced AEs. A total of 212 AEs were observed, and Saxagliptin-associated AEs were the most prevalent (66.6%). Hepatic AEs were predominant (37.7%), followed by gastrointestinal events (16.5%) and electrolyte imbalances (12.3%). Most AEs were possible based on WHO-UMC criteria (78.7%) and the Naranjo scale (86.7%), with 58% being of moderate severity and 42% mild. In the multivariate analysis, aspartate transaminase [OR: 1.013 (0.006-1.020)], alkaline phosphatase [OR: 1.004 (1.001-1.007)] and patients already on DPP-4 inhibitors [OR 1.191(1.012-1.366)] were significant predictors for AEs with DPP-4 inhibitors. Conclusion: The study highlighted a high prevalence of AEs with DPP-4 inhibitors and identified significant predictors of these AEs. These findings underscore the necessity of vigilant monitoring and risk assessment while prescribing DPP-4 inhibitors to the Indian population.

Introduction: DPP-4 inhibitors are a class of drugs used to manage type 2 diabetes mellitus. These drugs are commonly prescribed regardless of their safety issues in the Indian population. The studies focusing on the side effects or adverse events associated with these drugs and the contributing factors are limited in India. Understanding how common these adverse events are is vital to providing better patient care and management. Aim: To assess the frequency of adverse events with DPP-4 inhibitors and the contributory factors to these events. Method: A retrospective study analyzing the medical records of diabetic patients on DPP-4 inhibitors admitted to a major hospital in South India between 2019 and 2021 was conducted. The frequency, severity and potential causes of adverse events were identified through descriptive analysis. Result: A total of 796 diabetic patients on DPP-4 inhibitors were included in the study, out of which 26% (212 adverse events) experienced adverse events. Most common adverse events were related to liver (37.7%) followed by gastrointestinal (16.5%) and electrolyte imbalance (12.3%). The severity of the events was moderate (58%) and mild (42%). Elevated liver enzymes aspartate transaminase and alkaline phosphatase, and patients already on DPP-4 inhibitors were at high odds of developing adverse events. Conclusion: The study identifies DPP-4 inhibitor-associated adverse events and contributory factors that should be addressed when prescribing these drugs to diabetic patients.

Frequency and factors associated with DPP-4 inhibitor-induced adverse events in diabetic patients.

Delayed-Onset Immune-Related Colitis Following Pancreaticoduodenectomy in Patients With Gastric Cancer and Pancreatic Invasion Treated With Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have been approved for treating various advanced malignancies. Immune-related adverse events (irAEs) can manifest diversely and at varying times. However, postoperative diarrhea is a common complication in pancreaticoduodenectomy (PD). This case report presents a unique instance of delayed-onset irAE colitis occurring one year after PD in a patient with gastric cancer who received neoadjuvant nivolumab, a monoclonal antibody targeting human programmed death 1. A 54-year-old male developed severe diarrhea and weight loss, ultimately diagnosed with irAE colitis, which responded to steroid therapy. This report underscores the importance of extended monitoring, recognizing the potential for late-onset toxicities associated with ICIs, and differentiating from PD-related diarrhea.

EASIX-guided risk stratification for complications and outcome after CAR T-cell therapy with ide-cel in relapsed/refractory multiple myeloma.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated significant benefits in the treatment of relapsed/refractory multiple myeloma (RRMM). However, these outcomes can be compromised by severe complications, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome (ICANS) and immune effector cell-associated hematotoxicity (ICAHT), predisposing for life-threatening infections. METHODS: This retrospective observational study examined a total of 129 patients with RRMM who had received idecabtagene vicleucel (ide-cel) at two major myeloma centers in Germany and one center in the USA to assess the Endothelial Activation and Stress Index (EASIX) as a risk marker for an unfavorable clinical course and outcome after CAR T-cell therapy. EASIX is calculated by lactate dehydrogenase (U/L) × creatinine (mg/dL) / platelets (109 cells/L) and was determined before lymphodepletion (baseline) and at the day of CAR T-cell infusion (day 0). The analysis was extended to EASIX derivatives and the CAR-HEMATOTOX score. RESULTS: An elevated baseline EASIX (>median) was identified as a risk marker for severe late ICAHT, manifesting with an impaired hematopoietic reconstitution and pronounced cytopenias during the late post-CAR-T period. Patients with high EASIX levels (>upper quartile) were particularly at risk, as evidenced by an increased rate of an aplastic phenotype of neutrophil recovery, severe late-onset infections and ICANS. Finally, we found associations between baseline EASIX and an inferior progression-free and overall survival. Moreover, the EASIX at day 0 also demonstrated potential to serve as a risk marker for post-CAR-T complications and adverse outcomes. CONCLUSIONS: In conclusion, EASIX aids in risk stratification at clinically relevant time points prior to CAR T-cell therapy with ide-cel. Increased EASIX levels might help clinicians to identify vulnerable patients to adapt peri-CAR-T management at an early stage.

Regional diversity in drug-induced lung diseases among the USA, European Union, and Japan.

Background: Drug-induced lung disease (DILD) is a considerable and potentially fatal adverse event with poorly understood risk factors. Large-scale, data-driven analyses investigating regional discrepancies in DILD incidence are lacking. The aim of this study was to investigate the potential association among DILD prevalence, regional differences and other factors based on large-scale data base. Methods: This retrospective observational study analyzed spontaneous adverse event reports from the FDA Adverse Event Reporting System (FAERS) database between January 2010 and December 2020. Regional disparities in DILD incidence were assessed among reports from the United States of America (USA), the European Union (EU), and Japan (JP). Using multivariate logistic regression accounting for age, sex, and reporting years, we calculated the reporting odds ratios (RORs) with 95% confidence intervals. Subgroup analyses were performed for different types of anticancer agents, including tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), antibody-drug conjugates (ADCs), and cytotoxic agents. Results: Regional differences in RORs were observed for anticancer drugs in reports from JP and the EU compared with those from the USA (JP, ROR 4.432; EU, ROR 1.291) and for non-anticancer drugs (JP, ROR 3.481; EU, ROR 1.086). Significantly higher RORs were observed for all anticancer drug regimens reported in JP than in the USA (TKIs, ROR 3.274; ICIs, ROR 2.170; ADCs, ROR 2.335; cytotoxic agents, ROR 3.989). The EU reports exhibited higher RORs for TKIs and cytotoxic agents than the USA reports, with no significant differences in ICIs or ADCs (TKIs, ROR 1.679; ICIs, ROR 1.041; ADCs, ROR 1.046; cytotoxic agents, ROR 1.418). Conclusion: The prevalence of DILD in JP, the EU, and the USA differed. These findings have important implications in evaluating the safety profiles of drugs and patient safety in drug development and clinical practice. This study is the first to identify regional differences in DILDs using a large global database.

Consensus Statements on Assessments and Vaccinations Prior to Commencement of Advanced Therapies for the Treatment of Inflammatory Bowel Diseases.

BACKGROUND: Given the introduction of new advanced therapies for inflammatory bowel diseases (IBDs), expanded risk mitigation strategies are essential. AIMS: To create a comprehensive set of statements on assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) modulators for IBD. METHODS: We examined literature, guidelines and drug product information regarding vaccination and assessment recommendations for initiating advanced IBD therapies. Using a modified Delphi approach, delegates voted anonymously on the acceptability of these statements prior to and following consensus discussion. RESULTS: We developed eight statements on the domains of infectious diseases screening, vaccinations and assessments prior to commencing JAK inhibitors and S1P modulators. Six statements received agreement. Pre-advanced therapy screening for infectious diseases was established, and the vaccination protocol was revised. Malignancy, cardiovascular and thromboembolic risk assessments are necessary before initiating JAK inhibitors. Those starting S1P modulators need cardiac and ophthalmic assessments. CONCLUSIONS: These consensus statements combine vaccination and assessments on the currently available advanced therapies for IBD as a single comprehensive document that may reduce IBD complications associated with use of advanced therapies. Knowledge gaps identified during the consensus process will provide further research opportunities.

Severe thrombocytopaenia caused by trastuzumab emtansine in a patient with breast cancer: A case report.

We present the case of a 48-year-old woman with human epidermal growth factor receptor 2- and hormone receptor-positive left early breast cancer who developed severe thrombocytopaenia and moderate liver dysfunction after administration of trastuzumab emtansine as an adjuvant therapy. Briefly, she experienced grade 2 subcutaneous bleeding, decreased platelet count (18,000/µL), and elevated aspartate aminotransferase/alanine aminotransferase levels (254/193 IU), resulting in admission to the emergency room. Although thrombocytopaenia is a well-known adverse event associated with trastuzumab emtansine, we observed it immediately after trastuzumab emtansine administration in our patient. Based on the literature survey, we hypothesised that trastuzumab emtansine may have affected mature platelets in our patient. In addition, moderate hepatotoxicity may be partially explained based on the pharmacological mechanisms of trastuzumab emtansine action involving microtubule disorganisation in hepatocytes via cytoskeleton-associated protein 5 on the cell surface by emtansine. We discuss the mechanism of the development of thrombocytopaenia and liver dysfunction.

Cardiovascular adverse events associated with targeted therapies for multiple myeloma: a pharmacovigilance study.

Introduction: Multiple myeloma (MM) is a leading cause of hematopoietic cancer-related mortality, accounting for 20% of deaths. MM-targeted therapies have demonstrated efficacy, and since 2015, the United States Food and Drug Administration (FDA) has approved five targeted drugs. However, their cardiovascular safety has not been comprehensively evaluated. Objective: This study aimed to investigate the association between MM-targeted therapy and cardiovascular adverse events (AEs). Methods: Disproportionality analysis was conducted on reports from the FDA AE Reporting System database from 2014 to the second quarter of 2023. Cardiovascular AEs were grouped into nine narrow categories using the Standardized Medical Dictionary for Regulatory Activities Queries (SMQs). Results: A total of 3,228 cardiovascular AE cases involving MM-targeted therapy were extracted and analyzed. Significant disproportionality was identified for daratumumab, elotuzumab, and isatuximab. Among the nine narrow SMQ categories, the three most reported cardiovascular AEs were cardiomyopathy, cardiac arrhythmias, and embolic and thrombotic events. Noninfectious myocarditis/pericarditis, cardiac arrhythmias, and embolic and thrombotic events exhibited the strongest signal strengths. The cardiovascular AE risk was higher within the first month and gradually decreased thereafter; however, it increased rapidly again after 1 year. This trend was observed for all cardiovascular AEs. The Kaplan-Meier curve and the log-rank test revealed that isatuximab and elotuzumab exhibited a significantly lower probability of cardiovascular AEs than daratumumab (p < 0.001). Conclusions: MM-targeted therapy is significantly associated with an increased risk of previously unknown cardiovascular AE profiles, with the range and onset differing among various drugs, thereby warranting specific monitoring and appropriate management.

Post-marketing safety profile of solriamfetol: A real-world disproportionality analysis using FDA adverse event reporting system (FAERS) database.

Solriamfetol is a selective dopamine and noradrenalin reuptake inhibitor applied in adult patients with excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA). However, the post-marketing safety profile of solriamfetol in large number of people was unrevealed. The purpose of our study is to unravel solriamfetol's adverse events (AEs) in real-world to refine medication safety using Food and Drug Administration Adverse Event Reporting System (FAERS) database. We derived the data associated with solriamfetol from FAERS between 2019 and 2023, and removed the duplicated entries. We evaluated the disproportionality of solriamfetol's AEs by reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS). Among 8,846,085 AE reports, 1659 recorded solriamfetol as the 'primary suspected (PS)'. 74 significant disproportionality preferred terms (PTs) were retained across 27 organ systems. Moreover, 16 unexpected AEs not mentioned in the FDA label of solriamfetol were identified. Our findings provided the post-marketing safety profile of solriamfetol, highlighting potential solriamfetol's AEs. Further researches are significant to define the causality between solriamfetol and newly identified AEs.

Combined nephrotoxicity of Polymyxins and Vancomycin: a study on adverse event reporting for monotherapy versus combinations using the FDA adverse event reporting system (FAERS).

BACKGROUND: Multidrug-resistant (MDR) infections pose a global public health crisis with significant mortality and economic burdens. Combination of polymyxins and vancomycin has shown effectiveness against MDR infections. However, their combined nephrotoxicity complicates clinical use. Given these concerns, we conducted a pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) to assess the nephrotoxicity of combinations of polymyxins and vancomycin compared to monotherapy. RESEARCH DESIGN AND METHODS: In this retrospective study, data from FAERS reports (2012 Q4 to 2023 Q2) were deduplicated and analyzed for adverse events (AEs) related to vancomycin, polymyxin B, and colistin. Disproportionality analyses were performed to evaluate the association between drugs and nephrotoxicity. RESULTS: A total of 9,796,784 adverse event reports, including 73,009 reports associated with nephrotoxicity, were included. All three drugs showed significant associations with nephrotoxicity. In combination therapy, polymyxin B-vancomycin exhibited a stronger association with nephrotoxicity compared to monotherapy, whereas colistin-vancomycin demonstrated a lower association with nephrotoxicity than colistin monotherapy. CONCLUSIONS: This study found that combining vancomycin with colistin alleviated colistin-induced nephrotoxicity, while combining vancomycin with polymyxin B worsened polymyxin B-induced nephrotoxicity.

Interstitial lung disease associated with ALK inhibitors and risk factors: an updated comparative pharmacovigilance analysis.

Background: Inhibitors of the anaplastic lymphoma kinase (ALK) gene mutation are first-line treatments in patients with ALK-positive lung cancer. The FDA label warns of the risk of interstitial lung disease (ILD) in patients receiving ALK TKIs. However, ILD associated with ALK TKIs is not fully understood. The aim of this study was to characterize the features of ALK TKI-related ILD and to explore risk factors for ALK TKI-related ILD. Methods: FDA's Adverse Event Reporting System (FAERS) reports from 2011 Q1 to 2023 Q2 were extracted and combined. Standardized MedDRA queries (SMQs) were used to search for AEs at the preferred term (PT) level. Four algorithms were employed to quantify the signals of ILD associated with ALK TKIs. The risk of ILD was further analyzed using logistic regression. Results: A total of 20,064 reports of ALK TKIs and 640 (3.2%) reports of ILD AEs were extracted. Significant disproportionality was detected in all five ALK TKIs. Interstitial lung disease and pneumonitis were the most common lung toxicities induced by ALK TKIs. Results of further analyses revealed a different spectrum of lung toxicity among the various TKIs. The median time to onset of ILD related to ALK TKIs was 53 days (Q1:12, Q3:209), and more than 70% of AEs occurred within the first 2 months. Logistic regression analysis and risk prediction model both showed that different ALK TKIs and their combination with PPIs, amlodipine, and magnesium oxide were independent risk factors for ILD (p<0.05). Conclusion: ALK TKIs have different safety profiles regarding lung toxicity, which normally occurs within the first 2 months. Administration in combination with PPIs, amlodipine, and magnesium oxide significantly increases the risk of ILD. These results provide risk prediction for ILD related to ALK TKIs and support pharmacovigilance to promote safe prescribing in oncology.

A real-world pharmacovigilance study of tafasitamab: data mining of the US food and drug administration adverse event reporting system.

BACKGROUND: Tafasitamab is the first anti-CD19 monoclonal antibody approved for relapsed/refractory diffuse large B-cell lymphoma patients ineligible for autologous stem cell transplantation. The study was designed to evaluate tafasitamab-associated adverse events (AEs) by data mining the United States Food and Drug Administration Adverse Event Reporting System (FAERS). RESEARCH DESIGN AND METHODS: A disproportionality analysis was performed to assess the safety profile of tafasitamab based on the reports from the FAERS database between 2020Q3 and 2023Q3. Proportional reporting ratio (PRR) and empirical Bayesian geometric mean (EBGM) were used to identify the signals of AEs in patients receiving tafasitamab. RESULTS: A total of 529 reports with tafasitamab as the primary suspect drug were collected, including 1,262 AEs. Of these, 28 repeated AEs were identified using two algorithms. After excluding events unrelated to drug therapy, the top five repeated AEs by intensity ranking were cytopenia, immunosuppression, neutropenic sepsis, blood lactate dehydrogenase increased, and hematotoxicity. Unexpected significant AEs included polyneuropathy, splenomegaly, hemophagocytic lymphohistiocytosis, hypercalcemia, and ascites. CONCLUSIONS: This study provides additional evidence for risk identification of tafasitamab in the real world, which could help clinicians and pharmacists increase vigilance and improve the safety of tafasitamab in clinical practice.

Safety study on adverse events of zanubrutinib based on WHO-VigiAccess and FAERS databases.

OBJECTIVE: The study endeavors to elucidate AE signals associated with zanubrutinib data from the WHO-VigiAccess and FAERS databases. The aim is to furnish robust scientific evidence to inform clinical practice and regulatory decisions. METHODS: We meticulously extracted all AE breports tied to zanubrutinib from the both databases, encompassing the period from the drug's market introduction until 30 April 2024. Retrospective quantitative analysis employing ROR, PRR, and BCPNN methodologies were utilized to analysis. RESULTS: The investigation unveiled 1,304 reports from WHO-VigiAccess and 1,141 reports from FAERS related to zanubrutinib. Among the top 30 reported PTs in both databases, those not recorded in the drug label included pyrexia, dizziness, and death. In the FAERS database, signals for zanubrutinib were detected across 19 SOCs. Systems not covered in the drug label included reproductive system and breast disorders, metabolism and nutrition disorders, ear and labyrinth disorders, among others. Unmentioned signals included intestinal perforation, onychoclasis, night sweats, etc. CONCLUSION: This study confirms common AEs of zanubrutinib and identifies new ones, highlighting the need for careful monitoring and personalized treatment. It also emphasizes the importance of ongoing drug safety surveillance and patient management to maximize therapeutic benefits and minimize risks.

Participant-reported neurological events following immunization in the Canadian National Vaccine Safety Network-COVID-19 vaccine (CANVAS-COVID) study.

INTRODUCTION: The Canadian National Vaccine Safety Network (CANVAS) conducted active participant-based surveillance for adverse events following immunization during the COVID-19 vaccine campaign. This study evaluated the association between COVID-19 vaccination and neurological adverse events. METHODS: Participants were invited to complete online surveys to report health events that prevented daily activities and/or required medical attention within 7 days after COVID-19 vaccination or 7 days prior to the survey (unvaccinated controls); follow-up surveys were sent 7 months later. Neurological events were health events where the most severe symptom reported was ≥1 of: numbness/tingling, loss of taste or smell, vision loss, facial weakness/paralysis, seizure, weakness/paralysis of arms or legs, confusion, change in personality or behavior, or difficulty with urination or defecation. Data were extracted from the CANVAS-COVID database for analysis. RESULTS: Completed survey responses were received from 15,273 unvaccinated controls, 758,619 dose 1 recipients, 406,884 dose 2 recipients, and 126,586 dose 3 recipients. Rates of neurological events ranged from 15.9 (95 % CI 13.6-18.4) per 10,000 dose 1 ChAdOx1 recipients to 8.4 (6.5-10.8) and 7.9 (5.7-11.0) per 10,000 dose 3 mRNA-1273 and BNT162b2 recipients, respectively. Multivariable regression adjusted for age, sex, previous SARS-CoV-2 infection, and baseline health status showed an increased risk of neurological event among ChAdOx1 dose 1 recipients versus controls (adjusted OR 2.3, 95 % CI 1.2-4.3), but not among mRNA vaccine recipients after any dose. Risk of anaesthesia/paresthesia were increased following ChAdOx1 dose 1 (aOR 4.7, 1.7-13.1), and consistently but not statistically significantly higher following any dose of either mRNA vaccine. Risk of loss of smell/taste was decreased among recipients of any dose of either mRNA vaccine versus controls. CONCLUSIONS: The results support the safety of COVID-19 vaccines while confirming reported associations between ChAdOx1 dose 1 and neurological events. Participant-based AEFI surveillance is a useful component of post-market surveillance programs.

Novel Treatment for Pre-XDR Tuberculosis Linked to a Lethal Case of Acute Myocarditis.

The management of resistant tuberculosis (tb) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensively drug-resistant (XDR) tb who received a treatment regimen including pretomanid, bedaquiline, linezolid, cycloserine, and amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG), and laboratory examinations, were typical for acute myocarditis; however, the patient was considered unstable, and further investigations, including magnetic resonance imaging (MRI), pericardiocentesis, and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which raised a high suspicion of drug induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant tb should be aware of this newly reported, potentially lethal, adverse event.

Predictors of measles-rubella vaccination status in the Savannah Region, Ghana: A cross-sectional study among caregivers of children aged 18-59 months.

Introduction: Savannah Region witnessed a decline in measles-rubella (MR) vaccination coverage prior to the measles outbreak in 2022. This study aimed to assess contributory factors of the low routine MR vaccination coverage and proffer recommendations to improve vaccination uptake. Methods: A cross-sectional study was conducted in two districts (Bole and Central Gonja) of Savannah Region from December 2022 to June 2023. Caregivers of children 18-59 months were randomly selected and interviewed using a structured questionnaire. Bivariate and multivariate logistic regression were performed to assess predictors of MR vaccination status. Results: Children of caregivers with inadequate knowledge of MR vaccination (AOR = 0.58, 95 %CI: 0.47-0.72), travelled more than five km to access health services (AOR = 0.48, 95 %CI: 0.39-0.59), described health workers attitude as poor (AOR = 0.44, 95 %CI: 0.26-0.74), and those who sought treatment for adverse events following immunization (AEFI) from the pharmacy (AOR = 0.65, 95 %CI: 0.51-0.84) were less likely to complete MR vaccination. On the contrary, children of female sex (AOR = 1.27, 95 %CI: 1.05-1.53), aged 24-59 month (AOR = 2.56, 95 %CI: 1.05-1.53), caregivers with primary or secondary education (AOR = 1.43, 95 %CI: 1.11-1.84; and AOR = 2.23, 95 %CI: 1.64-3.03 respectively), and those who did not experience rescheduling of vaccination sessions (AOR = 1.61, 95 % CI: 1.25-2.01) were more likely to complete routine MR vaccination schedule. Conclusion: Inadequate caregiver knowledge, poor geographical access to health services, poor healthcare worker attitude, and non-institutional management of AEFI significantly contributed to the low MR vaccination uptake in the Savannah Region. Adopting tailored approaches to addressing these factors could improve vaccination coverage.

A Real-World Study on Adverse Reactions of Belimumab Based on the FDA Adverse Event Reporting System Database.

BACKGROUND AND OBJECTIVES: This investigation leverages data derived from the United States Food and Drug Administration Adverse Event Reporting (FAERS) to real-world adverse reactions associated with Belimumab, with the intention of providing guidance for safe clinical pharmacotherapy. METHODS: Data encompassing adverse drug event (ADE) reports relating to Belimumab from Q1 2011 to Q4 2023 within the FAERS were extracted and analyzed using methodologies such as the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). RESULTS: The study identified a total of 19 825 ADE reports where Belimumab was the primary suspect medication, with the United States constituting the majority of reporting countries (16 312 cases, or 82.28%). Patients aged 18 to 64.9 years accounted for the largest demographic (36.29%), while the proportion of female patients (77.91%) significantly surpassed that of male patients (5.03%). The analysis uncovered 184 unique Preferred Terms (PTs) across 21 System Organ Classes (SOCs). Following selection through ROR, the SOC signal strength was prioritized as follows: Systemic disorders and administration site conditions, infections and infestations, a variety of musculoskeletal and connective tissue disorders, and conditions related to pregnancy, puerperium, and the perinatal period. The top five PTs for ADE reports not included in the product's labeling were hypersensitivity reactions, immunosuppression, non-vascular diseases, herpes virus infections, and Sjögren's syndrome. The top five PTs for ADE signal strength not included in the labeling were disseminated cutaneous herpes zoster, herpes zoster meningitis, onycholysis, cyclothymic disorder, and mixed connective tissue disease. DISCUSSION: Based on pharmacovigilance research utilizing the FAERS database, it is recommended that clinical monitoring of Bevacizumab should be intensified to support effective pharmaceutical care and ensure rational clinical medication use.

Association between statin use and immune-related adverse events in patients treated with immune checkpoint inhibitors: analysis of the FAERS database.

Background: Understanding the risk relationship between statin use and immune-related adverse events (irAEs) in patients undergoing immune checkpoint inhibitors (ICIs) therapy is crucial for optimizing oncological management. Objective: This study aimed to investigate whether the use of statins increases the risk of irAEs in patients receiving ICI therapy. Methods: This study primarily utilized data from FAERS database. Multivariable logistic regression was the principal method of analysis, and the Benjamini-Hochberg procedure was employed to adjust for multiple hypothesis testing. Results: In a group of 145,214 patients undergoing ICI therapy, 9,339 reported using statin medications. Multivariable analysis indicated an increased risk of irAEs among statin users (OR 1.199, 95% CI: 1.141-1.261; FDR p < 0.001) in comparison to those not using statins. Notably, increased risks were observed particularly in patients diagnosed with lung, pancreatic, and renal cancers. The link between statin usage and increased irAEs risk remained consistent across various ICIs treatments. Conclusions: Statin medication usage is linked to an elevated probability of experiencing irAEs in patients enrolled in ICI therapy. In cancer patients receiving immune checkpoint inhibitors, careful consideration of statin use is essential to avoid potentially increased irAEs risk. These findings provide critical guidance for clinicians in developing treatment strategies that balance therapeutic efficacy and safety in oncological management.