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Veterinary Journal (London, England :... Jun 2024In their letter to the editor, Farrell et al., (2024) presented questions related to canine joint health after treatment with the anti-Nerve Growth Factor (NGF)...
In their letter to the editor, Farrell et al., (2024) presented questions related to canine joint health after treatment with the anti-Nerve Growth Factor (NGF) monoclonal antibody (mAb) bedinvetmab, which was presented as a component of a non-clinical laboratory safety assessment published in Krautmann et al., (2021). Their questions appear to have stemmed from an anti-NGF mAb developed for the treatment of osteoarthritis in humans (tanezumab; FDA, 2021) which in 2021 failed to achieve marketing approval due to an unfavorable benefit: risk profile, primarily due to a syndrome called Rapidly Progressive Osteoarthritis (RPOA) which occurred more commonly in treatment groups when compared to controls. Farrell et. al. (2024) have posed questions on radiographic and histopathologic bone findings from studies included in Krautmann, et al., (2021) and communicated in the FDA's Freedom of Information summary for Librela (FDA, 2023). These findings have previously been determined to be incidental and not bedinvetmab-associated. To address the questions posed, it is important to briefly define RPOA and summarize the syndrome in humans, review why the bone/joint findings in bedinvetmab safety studies in dogs are not indicative of RPOA or an RPOA-like condition, provide an update on joint health after use of bedinvetmab since market approval (>3 years in some markets), and summarize why Zoetis, the manufacturer of Librela, has confidence in joint safety after use of bedinvetmab in dogs.
PubMed: 38885831
DOI: 10.1016/j.tvjl.2024.106175 -
Epigenomics Jun 2024Methylation of , and CpG sites was assessed in patients with familial hypercholesterolemia (FH). DNA methylation of was analyzed by pyrosequencing in 131 FH patients...
Methylation of , and CpG sites was assessed in patients with familial hypercholesterolemia (FH). DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects. , and methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. and methylation was higher in MD and non-MD groups than NL subjects ( < 0.05). , and methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients ( < 0.05). Differential methylation of , and is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.
PubMed: 38884343
DOI: 10.1080/17501911.2024.2351792 -
Journal of Research in Nursing : JRN May 2024
PubMed: 38883251
DOI: 10.1177/17449871241253603 -
Journal of Research in Nursing : JRN May 2024The national pharmacovigilance (PV) system has been established in many countries worldwide following the thalidomide tragedy. Nurses have an important role in...
BACKGROUND
The national pharmacovigilance (PV) system has been established in many countries worldwide following the thalidomide tragedy. Nurses have an important role in recognising and reporting any Adverse Drug Reaction (ADR); however, their role has not been widely explored, particularly in Southeast Asian countries.
AIMS
To assess the knowledge, attitudes and practice (KAP) about PV activities, along with barriers and facilitators that affect ADR reporting among hospital nurses in Malaysia. The present study also explores the relationship between demographic characteristics and predictors of KAP among hospital nurses in Malaysia.
METHODS
A multicentre, questionnaire-based, cross-sectional study was conducted in March-May 2021, among nurses working at tertiary care hospitals in Malaysia.
RESULTS
The mean KAP score of study participants was 57 ± 11. Overall participants had poor ADR knowledge (37.4%), and poor reporting practices (48.9%). Age >30 years (AOR = 2.7 (1.13-6.8), = 0.02), and working experience of greater than 10 years (AOR = 2.44 (1.08-5.52), 0.03), were significantly associated with good ADR knowledge and reporting practices among study participants.
CONCLUSIONS
In summary, study findings offer valuable insight for developing targeted interventions and formal training to improve nurses' ADR knowledge and reporting practices. Addressing gaps in these areas can enhance patient safety and overall healthcare quality.
PubMed: 38883248
DOI: 10.1177/17449871241232340 -
Therapeutic Advances in Drug Safety 2024Cefuroxime has played a crucial role in the prevention and treatment of bacterial infections. However, the differences in adverse events across formulations and routes...
BACKGROUND
Cefuroxime has played a crucial role in the prevention and treatment of bacterial infections. However, the differences in adverse events across formulations and routes remain unclear.
OBJECTIVES
This study aimed to investigate the post-marketing safety of cefuroxime, particularly concerning formulations and routes.
DESIGN
A retrospective pharmacovigilance study of cefuroxime was conducted using the data from Food and Drug Administration Adverse Event Reporting System database.
METHODS
The clinical characteristics and concomitant drugs reported with cefuroxime were investigated. Adverse event signals of cefuroxime were identified based on four disproportionality algorithms. The signal differences of cefuroxime across formulations and routes were further examined.
RESULTS
A total of 1810 adverse event reports associated with cefuroxime were identified, and 181 cefuroxime-associated signals were detected. Compared with tablets, injections were more likely to cause preferred terms 'blood pressure decreased' and 'anaphylactic shock'. In addition, system organ class 'eye disorders' significantly increased when cefuroxime was administered intraocularly, underscoring the importance of exercising caution regarding ocular toxicity.
CONCLUSION
The adverse events associated with cefuroxime were significantly different across formulations and routes, which deserve special attention in clinical use.
PubMed: 38881538
DOI: 10.1177/20420986241258049 -
The Journal of the Association of... Apr 2024Calcium channel blockers (CCBs) are widely used antihypertensive agents due to their effectiveness in reducing blood pressure (BP), along with their good tolerability... (Review)
Review
Calcium channel blockers (CCBs) are widely used antihypertensive agents due to their effectiveness in reducing blood pressure (BP), along with their good tolerability and evidence of reducing hypertension (HTN)-related cardiovascular and renal diseases. Cilnidipine, a unique dihydropyridine calcium antagonist, exhibits potent inhibitory action on both N-type and L-type voltage-dependent calcium channels. With excellent oral absorption and a prolonged duration of action, it demonstrates a significant antihypertensive effect. It effectively reduces BP both systolic and diastolic while providing renal, neurological, and cardiovascular protection. Unlike L-type CCBs, cilnidipine does not increase pulse rates (PRs) and is associated with reduced occurrence of pedal edema. Cilnidipine is an effective treatment choice for individuals with mild to moderate essential HTN, whether it is administered alone or in conjunction with other treatment modalities.
Topics: Dihydropyridines; Humans; Calcium Channel Blockers; Hypertension; Antihypertensive Agents; Calcium Channels, N-Type; Blood Pressure; Calcium Channels, L-Type
PubMed: 38881084
DOI: 10.59556/japi.72.0516 -
Journal of Clinical Anesthesia Jun 2024Sugammadex, a selective steroidal neuromuscular blocking agent reversal agent, is increasingly employed for the rapid restoration of neuromuscular function. This study...
BACKGROUND
Sugammadex, a selective steroidal neuromuscular blocking agent reversal agent, is increasingly employed for the rapid restoration of neuromuscular function. This study aimed to conduct a comprehensive evaluation of sugammadex's safety profile.
METHODS
Adverse events (AEs) related to sugammadex reported in the FDA Adverse Event Reporting System (FAERS) database from January 2009 to September 2023 were extracted. Disproportionality analysis with four measures: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) were employed to detect significant AEs. We also inspected for unexpected AEs absent from the sugammadex FDA approval documentation and categorized AEs based on the latest version (26.1) of 'Important Medical Event Terms List (IME list)' developed by the EudraVigilance Expert Working Group.
RESULTS
A total of 1452 reports were linked to sugammadex. At the preferred terms (PTs) levels, 98 sugammadex-related AEs were identified, including "anaphylactic reaction", "bradycardia", "bronchospasm" and "cardiac arrest". Among them, 37 representing unexpected events were absent from official FDA labeling, and 50 AEs were recognized as IME warranting observation. Notably, 19 PTs denoted serious AEs were absent from labeling yet needing IME surveillance, including: "Kounis syndrome", "angioedema", "pulseless electrical activity" and "laryngeal edema".
CONCLUSION
The study identified unexpected and potentially life-threatening AEs associated with sugammadex, a valuable agent for rapidly reversing neuromuscular blockade. Clinicians are advised to be mindful of these potential risks, particularly in patients with allergies or existing cardiovascular or respiratory conditions.
PubMed: 38880003
DOI: 10.1016/j.jclinane.2024.111509 -
Archives of Toxicology Jun 2024Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an...
Valproic acid (VPA) is a primary medication for epilepsy, yet its hepatotoxicity consistently raises concerns among individuals. This study aims to establish an automated machine learning (autoML) model for forecasting the risk of abnormal increase of transaminase levels while undergoing VPA therapy for 1995 epilepsy patients. The study employed the two-tailed T test, Chi-square test, and binary logistic regression analysis, selecting six clinical parameters, including age, stature, leukocyte count, Total Bilirubin, oral dosage of VPA, and VPA concentration. These variables were used to build a risk prediction model using "H2O" autoML platform, achieving the best performance (AUC training = 0.855, AUC test = 0.789) in the training and testing data set. The model also exhibited robust accuracy (AUC valid = 0.742) in an external validation set, underscoring its credibility in anticipating VPA-induced transaminase abnormalities. The significance of the six variables was elucidated through importance ranking, partial dependence, and the TreeSHAP algorithm. This novel model offers enhanced versatility and explicability, rendering it suitable for clinicians seeking to refine parameter adjustments and address imbalanced data sets, thereby bolstering classification precision. To summarize, the personalized prediction model for VPA-treated epilepsy, established with an autoML model, displayed commendable predictive capability, furnishing clinicians with valuable insights for fostering pharmacovigilance.
PubMed: 38879852
DOI: 10.1007/s00204-024-03803-5 -
Computers in Biology and Medicine Jun 2024Artificial intelligence (AI) has emerged as a powerful tool to revolutionize the healthcare sector, including drug delivery and development. This review explores the... (Review)
Review
Artificial intelligence (AI) has emerged as a powerful tool to revolutionize the healthcare sector, including drug delivery and development. This review explores the current and future applications of AI in the pharmaceutical industry, focusing on drug delivery and development. It covers various aspects such as smart drug delivery networks, sensors, drug repurposing, statistical modeling, and simulation of biotechnological and biological systems. The integration of AI with nanotechnologies and nanomedicines is also examined. AI offers significant advancements in drug discovery by efficiently identifying compounds, validating drug targets, streamlining drug structures, and prioritizing response templates. Techniques like data mining, multitask learning, and high-throughput screening contribute to better drug discovery and development innovations. The review discusses AI applications in drug formulation and delivery, clinical trials, drug safety, and pharmacovigilance. It addresses regulatory considerations and challenges associated with AI in pharmaceuticals, including privacy, data security, and interpretability of AI models. The review concludes with future perspectives, highlighting emerging trends, addressing limitations and biases in AI models, and emphasizing the importance of collaboration and knowledge sharing. It provides a comprehensive overview of AI's potential to transform the pharmaceutical industry and improve patient care while identifying further research and development areas.
PubMed: 38878397
DOI: 10.1016/j.compbiomed.2024.108702 -
The Journal of Clinical Endocrinology... Jun 2024Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth...
PURPOSE
Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth factor-1 receptor. This study aimed to identify potential safety signals of teprotumumab by analyzing post-marketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023.
METHODS
The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered three or more.
RESULTS
Total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), deafness permanent (ROR [95% CI] = 1552.35 [789.07-3053.98]), deafness bilateral (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycaemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]) and amenorrhoea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals of teprotumumab.
CONCLUSIONS
This study identified ear and labyrinth disorders, reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.
PubMed: 38878281
DOI: 10.1210/clinem/dgae417