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International Immunopharmacology Jul 2024Although immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) has become increasingly used for cancers, the impact of combination therapy on...
Immune-related adverse events of immune checkpoint inhibitors combined with angiogenesis inhibitors: A real-world pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database (2014-2022).
INTRODUCTION
Although immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) has become increasingly used for cancers, the impact of combination therapy on immune-related adverse events (irAEs) in real-world settings has not been well elucidated to date.
METHODS
The FDA Adverse Event Reporting System (FAERS) database from 2014 to 2022 was retrospectively queried to extract reports of irAEs referred as standardized MedDRA queries (SMQs), preferred terms (PTs) and system organ classes (SOCs). To perform disproportionality analysis, information component (IC) and reporting odds ratio (ROR) were calculated and lower limit of 95 % confidence interval (CI) for IC (IC) > 0 or ROR (ROR) > 1 with at least 3 reports was considered statistically significant.
RESULTS
Compared to ICIs alone, ICIs + AGIs demonstrated a lower IC/ROR for irAEs-SMQ (2.343/5.082 vs. 1.826/3.563). Regarding irAEs-PTs, there were fewer irAEs-PTs of significant value in ICIs + AGIs than ICIs alone (57 vs. 150 PTs) and lower signal value for most PTs (88 %) in ICIs + AGIs. Moreover, lower IC for most of irAEs-SOCs in ICIs + AGIs (11/13) compared with ICIs alone was observed. As for outcomes of irAEs, ICIs + AGIs showed a lower frequency of "fatal" for irAEs-SMQ than ICIs alone (4.88 % vs. 7.83 %), so as in cardiac disorder (SOC) (15.45 % vs. 26.37 %), and respiratory, thoracic and mediastinal disorders (SOC) (13.74 % vs. 20.06 %). Similarly, there were lower occurrence and fewer fatality of irAEs in ICIs + AGIs + chemotherapy (CT) than ICIs + CT.
CONCLUSION
ICIs combined with AGIs may reduce incidence and mortality for most of irAEs compared to ICIs alone whether or not with CT.
Topics: Humans; Immune Checkpoint Inhibitors; Pharmacovigilance; United States; Adverse Drug Reaction Reporting Systems; Male; United States Food and Drug Administration; Female; Angiogenesis Inhibitors; Retrospective Studies; Middle Aged; Databases, Factual; Aged; Neoplasms; Adult; Young Adult; Adolescent; Aged, 80 and over
PubMed: 38838553
DOI: 10.1016/j.intimp.2024.112301 -
PLoS Neglected Tropical Diseases Jun 2024Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such...
Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such as chloroquine, plus an 8-aminoquinoline. However, 8-aminoquinolines cause hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, requiring prior screening to exclude those at risk. Brazil is pioneering the implementation of tafenoquine, a single-dose 8-aminoquinoline indicated for P. vivax patients with >70% of normal G6PD activity. Tafenoquine implementation in Manaus and Porto Velho, two municipalities located in the western Brazilian Amazon, included comprehensive training of healthcare professionals (HCPs) on point-of-care quantitative G6PD testing and a new treatment algorithm for P. vivax radical cure incorporating tafenoquine. Training was initially provided to higher-level facilities (phase one) and later adapted for primary care units (phase two). This study analyzed HCP experiences during training and implementation and identified barriers and facilitators. In-depth interviews and focus discussion groups were conducted 30 days after each training for a purposive random sample of 115 HCPs. Thematic analysis was employed using MAXQDA software, analyzing data through inductive and deductive coding. Analysis showed that following the initial training for higher-level facilities, some HCPs did not feel confident performing quantitative G6PD testing and prescribing the tafenoquine regimen. Modifications to the training in phase two resulted in an improvement in understanding the implementation process of the G6PD test and tafenoquine, as well as in the knowledge acquired by HCPs. Additionally, knowledge gaps were addressed through in situ training, peer communication via a messaging app, and educational materials. Training supported effective deployment of the new tools in Manaus and Porto Velho and increased awareness of the need for pharmacovigilance. A training approach for nationwide implementation of these tools was devised. Implementing quantitative G6PD testing and tafenoquine represents a significant shift in P. vivax malaria case management. Consistent engagement with HCPs is needed to overcome challenges in fully integrating these tools within the Brazilian health system.
Topics: Humans; Brazil; Malaria, Vivax; Antimalarials; Aminoquinolines; Glucosephosphate Dehydrogenase Deficiency; Health Personnel; Female; Glucosephosphate Dehydrogenase; Male; Plasmodium vivax; Adult
PubMed: 38837977
DOI: 10.1371/journal.pntd.0012197 -
JGH Open : An Open Access Journal of... Jun 2024Alendronate is used to treat Paget's bone disease, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis because it suppresses osteoclast activity to stop...
BACKGROUND
Alendronate is used to treat Paget's bone disease, glucocorticoid-induced osteoporosis, and postmenopausal osteoporosis because it suppresses osteoclast activity to stop bone resorption.
CASE REPORT
We present an exceptional case of esophagitis caused by alendronate. Blood tests and other data were normal when the patient was taken to the hospital, but an endoscopic examination revealed significant esophageal redness, erosion, and ulceration, along with pseudomembrane. The patient was given medicine after receiving a diagnosis of alendronate pill-induced esophagitis based on the pathological findings.
CONCLUSION
This case report is a timely reminder of the importance of thorough pharmacovigilance, patient education, and smart therapeutic decision-making in the context of alendronate use. To properly treat and prevent problems with the esophagus caused by alendronate, additional research is required.
PubMed: 38832136
DOI: 10.1002/jgh3.13080 -
Gaceta Sanitaria May 2024To investigate the gender of the authors who publish articles of health economic evaluations in medicine and healthcare journals.
OBJECTIVE
To investigate the gender of the authors who publish articles of health economic evaluations in medicine and healthcare journals.
METHOD
We evaluated a random sample of economic evaluations indexed in MEDLINE during 2019. Gender of the first, last and corresponding author was determined by review of the author's first name. Data were summarized as frequency and percentage for categorical items and median and interquartile range (IQR) for continuous items. We also calculated the index of authors per paper.
RESULTS
We included 200 studies with 1365 authors (median of 6 authors per paper; IQR: 4-9). Gender identification was possible for all authors in the study sample: 802 (59%) were men and 563 (41%) were women. The number of female first, last, and corresponding authors respectively were 78 (39%), 68 (34%), and 80 (40%) for health economic evaluations.
DISCUSSION
Female scientists were underrepresented as co-authors and in prominent authorship positions in health economic evaluations. This study serves as a call to action for the scientific community to actively work towards equity and inclusion.
PubMed: 38820982
DOI: 10.1016/j.gaceta.2024.102402 -
Annales de Dermatologie Et de... Jun 2024
Topics: Stevens-Johnson Syndrome; Humans; France; Adult; Clinical Protocols
PubMed: 38810539
DOI: 10.1016/j.annder.2024.103282 -
JMIR Formative Research May 2024Nonmedical use of prescription drugs can cause overdose; this represents a serious public health crisis globally. In this digital era, social networking services serve...
BACKGROUND
Nonmedical use of prescription drugs can cause overdose; this represents a serious public health crisis globally. In this digital era, social networking services serve as viable platforms for illegal acquisition of excessive amounts of medications, including prescription medications. In Japan, such illegal drug transactions have been conducted through popular flea market applications, social media, and auction websites, with most of the trades being over-the-counter (OTC) medications. Recently, an emerging unique black market, where individuals trade prescription medications-predominantly nervous system drugs-using a specific keyword ("Okusuri Mogu Mogu"), has emerged on X (formerly Twitter). Hence, these dynamic methods of illicit trading should routinely be monitored to encourage the appropriate use of medications.
OBJECTIVE
This study aimed to specify the characteristics of medications traded on X using the search term "Okusuri Mogu Mogu" and analyze individual behaviors associated with X posts, including the types of medications traded and hashtag usage.
METHODS
We conducted a cross-sectional study with publicly available posts on X between September 18 and October 1, 2022. Posts that included the term "Okusuri Mogu Mogu" during this period were scrutinized. Posts were categorized on the basis of their contents: buying, selling, self-administration, heads-up, and others. Among posts categorized as buying, selling, and self-administration, medication names were systematically enumerated and categorized using the Anatomical Therapeutic Chemical (ATC) classification. Additionally, hashtags in all the analyzed posts were counted and classified into 6 categories: medication name, mental disorder, self-harm, buying and selling, community formation, and others.
RESULTS
Out of 961 identified posts, 549 were included for analysis. Of these posts, 119 (21.7%) referenced self-administration, and 237 (43.2%; buying: n=67, 12.2%; selling: n=170, 31.0%) referenced transactions. Among these 237 posts, 1041 medication names were mentioned, exhibiting a >5-fold increase from the study in March 2021. Categorization based on the ATC classification predominantly revealed nervous system drugs, representing 82.1% (n=855) of the mentioned medications, consistent with the previous survey. Of note, the diversity of medications has expanded to include medications that have not been approved by the Japanese government. Interestingly, OTC medications were frequently mentioned in self-administration posts (odds ratio 23.6, 95% CI 6.93-80.15). Analysis of hashtags (n=866) revealed efforts to foster community connections among users.
CONCLUSIONS
This study highlighted the escalating complexity of trading of illegal prescription medication facilitated by X posts. Regulatory measures to enhance public awareness should be considered to prevent illegal transactions, which may ultimately lead to misuse or abuse such as overdose. Along with such pharmacovigilance measures, social approaches that could direct individuals to appropriate medical or psychiatric resources would also be beneficial as our hashtag analysis shed light on the formation of a cohesive or closed community among users.
PubMed: 38805262
DOI: 10.2196/54023 -
Frontiers in Cardiovascular Medicine 2024To identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT...
PURPOSE
To identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT interval prolongation.
METHODS
We employed the preferred term (PT) "electrocardiogram QT prolonged" from the Medical Dictionary for Regulatory Activities (MedDRA) 26.0 to identify adverse drug events (ADEs) of QT interval prolongation in the FAERS database from the period 2004-2022. Reporting odds ratio (ROR) was performed to quantify the signals of ADEs.
RESULTS
We listed the top 40 drugs that caused QT interval prolongation. Among them, the 3 drugs with the highest number of cases were quetiapine (1,151 cases, ROR = 7.62), olanzapine (754 cases, ROR = 7.92), and citalopram (720 cases, ROR = 13.63). The two most frequently reported first-level Anatomical Therapeutic Chemical (ATC) groups were the drugs for the nervous system ( = 19, 47.50%) and antiinfectives for systemic use ( = 7, 17.50%). Patients with missing gender ( = 3,482, 23.68%) aside, there were more females (7,536, 51.24%) than males (5,158, 35.07%) were involved. 3,720 patients (25.29%) suffered serious clinical outcomes resulting in deaths or life-threatening conditions. Overall, most drugs that caused QT interval prolongation had early failure types according to the assessment of the Weibull's shape parameter (WSP) analysis.
CONCLUSIONS
Our study offered a list of drugs that frequently caused QT interval prolongation based on the FAERS system, along with a description of some risk profiles for QT interval prolongation brought on by these drugs. When prescribing these drugs in clinical practice, we should closely monitor the occurrence of ADE for QT interval prolongation.
PubMed: 38803662
DOI: 10.3389/fcvm.2024.1363382 -
Frontiers in Pharmacology 2024Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of...
Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application. We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA's Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0. 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the "primary suspected" drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia-all documented on bendamustine's label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug's label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0-59 days, predominantly occurring on the first day post-initiation. The β of bendamustine-related AEs suggested risk reduction over time. Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.
PubMed: 38803441
DOI: 10.3389/fphar.2024.1372401 -
Journal of Medical Economics 2024
Topics: Humans; Transcatheter Aortic Valve Replacement; Japan; Aortic Valve Stenosis; Aged; Risk Assessment; East Asian People
PubMed: 38794992
DOI: 10.1080/13696998.2024.2360835 -
Pharmaceuticals (Basel, Switzerland) Apr 2024Conventional therapy is commonly used for the treatment of inflammatory skin conditions, but undesirable effects, such as erythema, dryness, skin thinning, and... (Review)
Review
Conventional therapy is commonly used for the treatment of inflammatory skin conditions, but undesirable effects, such as erythema, dryness, skin thinning, and resistance to treatment, may cause poor patient compliance. Therefore, patients may seek complementary treatment with herbal plant products including essential oils (EOs). This scoping review aims to generate a broad overview of the EOs used to treat inflammatory skin conditions, namely, acne vulgaris, dermatitis and eczema, psoriasis, and rosacea, in a clinical setting. The quality, efficacy, and safety of various EOs, as well as the way in which they are prepared, are reviewed, and the potential, as well as the limitations, of EOs for the treatment of inflammatory skin conditions are discussed. Twenty-nine eligible studies (case studies, uncontrolled clinical studies, and randomized clinical studies) on the applications of EOs for inflammatory skin conditions were retrieved from scientific electronic databases (PubMed, Embase, Scopus, and the Cochrane Library). As an initial result, tea tree () oil emerged as the most studied EO. The clinical studies with tea tree oil gel for acne treatment showed an efficacy with fewer adverse reactions compared to conventional treatments. The uncontrolled studies indicated the potential efficacy of ajwain () oil, eucalyptus () oil, and cedarwood () oil in the treatment of acne, but further research is required to reach conclusive evidence. The placebo-controlled studies revealed the positive effects of kānuka () oil and frankincense ( spp.) oil in the treatment of psoriasis and eczema. The quality verification of the EO products was inconsistent, with some studies lacking analyses and transparency. The quality limitations of some studies included a small sample size, a short duration, and the absence of a control group. This present review underscores the need for extended, well-designed clinical studies to further assess the efficacy and safety of EOs for treating inflammatory skin conditions with products of assured quality and to further elucidate the mechanisms of action involved.
PubMed: 38794141
DOI: 10.3390/ph17050571