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Kidney International Reports Sep 2023In the management of anemia in chronic kidney disease, hemoglobin levels often fall below or exceed target ranges. Past retrospective cohort studies of patients...
INTRODUCTION
In the management of anemia in chronic kidney disease, hemoglobin levels often fall below or exceed target ranges. Past retrospective cohort studies of patients undergoing hemodialysis with conventional erythropoiesis stimulating agents (ESAs) found that hemoglobin level fluctuations predicted mortality and cardiovascular adverse events; long-acting agents were thereafter widely available. An updated validation by a prospective cohort study was needed.
METHODS
Using Cox regression models, we evaluated associations between hemoglobin variability and all-cause death, hospitalization, and cardiovascular, thrombotic, or infectious adverse event outcomes in 3063 hemodialysis patients' data from the Japanese Dialysis Outcomes and Practice Patterns Study (J-DOPPS) from 2012 to 2018.
RESULTS
During a median follow-up time of 2.5 years, all-cause mortality was lowest in the first quartile and tended to be higher in groups with greater hemoglobin variability (hazard ratio [HR]: 95% confidence interval for the fourth quartile of an absolute value of hemoglobin variability: 1.44 [0.99-2.08], for trend = 0.056). Infectious event incidence in these patients was also lower in the first quartile than for the other quartiles ( for trend < 0.01). The association was more pronounced in patients with lower serum ferritin levels or iron supplementation. Cardiovascular and thrombotic event incidence was not associated with hemoglobin variability.
CONCLUSIONS
Maintenance hemodialysis patients on ESA treatment with higher hemoglobin variability are at higher risk for all-cause mortality and particularly infectious events.
PubMed: 37705913
DOI: 10.1016/j.ekir.2023.06.004 -
Frontiers in Pharmacology 2023Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment...
Testosterone is an essential sex hormone in maintaining masculine characteristics, which is prescribed for male hypogonadism as testosterone replacement treatment (TRT). Herein, we investigated long-standing controversies about the association between TRT and major adverse cardiovascular events (MACEs), based on real world adverse event (AE) reports, registered in the Food and Drug Administration Adverse Event Reporting System (FAERS). Publicly available FAERS data from 1 January 2004 to 31 December 2022 were retrieved from the Food and Drug Administration (FDA) website. The data mining protocol including the reporting odds ratio (ROR) and the Bayesian confidence propagation neural network (BCPNN) was applied to analyze overreporting caused by risk factors and MACEs, including TRT, morbidities, and ages. The ROR and the BCPNN were also applied to investigate the annually developing trend of pharmacovigilance (PV) signals in the real world, retrospectively. A total of 3,057 cases referring to MACEs, with a median age of 57 years old (yo), were identified from 28,921 cases of testosterone users. MACEs related to PV signals have emerged since 2014, including cardiac death, non-fatal myocardial infarction, and non-fatal stroke. Myocardial infarction (MI) (ROR: 9.46; IC: 3.08), acute myocardial infarction (AMI) (ROR: 16.20; IC: 3.72), ischemic cardiomyopathy (ROR: 11.63; IC: 2.20), and cardiomyopathy (ROR: 5.98; IC: 1.96) were the most significant signals generated, and weaker signals included cardiac failure acute (ROR: 4.01; IC: 0.71), cardiac arrest (ROR: 1.88; IC: 0.56), and ventricular fibrillation (VF) (ROR: 2.38; IC: 0.38). The time-to-onset (TTO) of MACEs was calculated with a median of 246 days for AMI. For myocardial infarction and cardiomyopathy, TRT statistically tended to increase the risk of MACEs, while for cardiac arrhythmia, cardiac failure, and stroke, TRT demonstrated beneficial effects among the population with morbidities, such as testosterone deficiency (TD), diabetes mellitus (DM), and hypertension. MACEs were rare but led to serious outcomes including significant increase in death and disability. Since 2018, and before 2014, reports referring to TRT associated with MACEs were relatively scarce, which indicated that there might be a considerable number of cases that went unrecorded, due to neglection. Health workers and testosterone users might pay more attention to testosterone-induced MACEs.
PubMed: 37502210
DOI: 10.3389/fphar.2023.1182113 -
Current Oncology (Toronto, Ont.) Nov 2023Patients with incurable cancers have an increasing number of comorbidities, which can lead to polypharmacy and its associated adverse events (drug-to-drug interaction,... (Review)
Review
Patients with incurable cancers have an increasing number of comorbidities, which can lead to polypharmacy and its associated adverse events (drug-to-drug interaction, prescription of a potentially inappropriate medication, adverse drug event). Deprescribing is a patient-centered process aimed at optimizing patient outcomes by discontinuing medication(s) deemed no longer necessary or potentially inappropriate. Improved patient quality of life, risk reduction of side effects or worse clinical outcomes, and a decrease in healthcare costs are well-documented benefits of deprescribing. Deprescribing and advance care planning both require consideration of patients' values, preferences, and care goals. Here, we provide an overview of comorbidities and associated polypharmacy risks in cancer patients, as well as useful tools and resources for deprescribing in daily practice, and we shed light on how deprescribing can facilitate advance care planning discussions with patients who have advanced cancer or a limited life expectancy.
Topics: Humans; Deprescriptions; Drug-Related Side Effects and Adverse Reactions; Neoplasms; Polypharmacy; Quality of Life
PubMed: 37999124
DOI: 10.3390/curroncol30110704 -
Frontiers in Pharmacology 2023To investigate adverse events (AEs) associated with denosumab (Dmab) and zoledronic acid (ZA), compare their association strengths, and explore potential applications...
To investigate adverse events (AEs) associated with denosumab (Dmab) and zoledronic acid (ZA), compare their association strengths, and explore potential applications to provide clinical reference. We collected data from FAERS from January 2004 to November 2022 and mined AE signals for Dmab and ZA using ROR values. We compared signal intensity for same AEs and investigated off-label use. We also examined their AEs in adjuvant therapy for breast and prostate cancer. 154,735 reports of primary suspect drugs were analyzed in the FAERS database (Dmab: 117,857; ZA: 36,878). Dmab and ZA had 333 and 1,379 AE signals, with 189 overlaps. The AEs of Dmab included death (ROR:3.478), osteonecrosis of jaw (ROR:53.025), back pain (ROR:2.432), tooth disorder (ROR:16.18), bone pain (ROR:6.523). For ZA, the AEs included osteonecrosis (ROR:104.866), death (ROR: 3.645), pain (ROR:3.963), osteonecrosis of jaw (ROR: 91.744), tooth extraction (ROR: 142.143). Among overlap signals, Dmab showed higher strength in exostosis of the jaw (ROR: 182.66 vs. 5.769), atypical fractures (ROR: 55.589 vs. 9.123), and atypical femur fractures (ROR:49.824 vs. 4.968). And ZA exhibited stronger associations in abscess jaw (ROR: 84.119 vs. 11.12), gingival ulceration (ROR: 74.125 vs. 4.827), increased bone formation (ROR: 69.344 vs. 3.218). Additionally, we identified 528 off-label uses for Dmab and 206 for ZA, with Dmab mainly used in prostate cancer (1.04%), breast cancer (1.03%), and arthritis (0.42%), while ZA in breast cancer (3.21%), prostate cancer (2.48%), and neoplasm malignant (0.52%). For Dmab in breast cancer treatment, AEs included death (11.6%), disease progression (3.3%), and neutropenia (2.7%), while for ZA included death (19.8%), emotional disorder (12.9%), osteomyelitis (11.7%). For prostate cancer treatment, Dmab`s AEs were death (8.9%), prostate cancer metastatic (1.6%), renal impairment (1.7%), while ZA`s included death (34.4%), general physical health deterioration (19.9%), and hemoglobin decreased (18.9%). Our analysis of FAERS database provided postmarketing surveillance data and revealed different strengths of reported AE signals between Dmab and ZA in some of their common AEs. It's also worth noting that both drugs have potential off-label applications, which could introduce new AEs. This highlights the necessity for safety monitoring when using Dmab and ZA off-label.
PubMed: 38027014
DOI: 10.3389/fphar.2023.1225919 -
JAMA Network Open Jul 2023Selective serotonin reuptake inhibitors (SSRIs) are a commonly prescribed medication class to treat a variety of mental disorders. However, adherence to SSRIs is low,...
IMPORTANCE
Selective serotonin reuptake inhibitors (SSRIs) are a commonly prescribed medication class to treat a variety of mental disorders. However, adherence to SSRIs is low, and uncovering the reasons for discontinuation among SSRI users is an important first step to improving medication persistence.
OBJECTIVE
To identify the reasons SSRIs are discontinued or changed, as reported by patients and caregivers in online drug reviews.
DESIGN, SETTING, AND PARTICIPANTS
This qualitative study used natural language processing and machine learning to extract mentions of changes in SSRI intake from 667 drug reviews posted on the online health forum WebMD from September 1, 2007, to August 31, 2021. The type of medication change, including discontinuation, switch to another medication, or dose change and the reason for the change were manually annotated. In each instance in which an adverse event was reported, the event was categorized using Medical Dictionary for Regulatory Activities primary system organ class (SOC) codes, and its relative frequency was compared with that in spontaneous reporting systems maintained by the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency.
MAIN OUTCOMES AND MEASURES
Reasons for SSRI medication change as assessed using SOC codes.
RESULTS
In total, 667 reviews posted by 659 patients or caregivers (516 [78%] of patients were female; 410 [62%] 25-54 years of age) were identified that indicated a medication change: 335 posts indicated SSRI discontinuation, 188 posts indicated dose change, and 179 posts indicated switched medications. Most authors 625 (95%) were patients. The most common reason for medication discontinuation or switching was adverse events experienced, and the most common reason for dose change was titration. Both uptitration and downtitration were initiated by either a health care professional or patient. The most common adverse events were classified by SOC codes as psychiatric disorders, including insomnia, loss of libido, and anxiety. Compared with those in regulatory data, psychiatric adverse events, adverse events recorded by investigations (mostly weight gain) and adverse events associated with the reproductive system (mostly erectile dysfunction) were reported disproportionately more often.
CONCLUSIONS AND RELEVANCE
This qualitative study of online drug reviews found that useful information was provided directly by patients or their caregivers regarding their medication behavior, specifically, information regarding SSRI treatment changes that may inform interventions to improve adherence. These findings suggest that these reported adverse events may be associated with SSRI persistence and that people may feel more inclined to report such events on social media than to clinicians or regulatory agencies.
Topics: United States; Male; Humans; Female; Selective Serotonin Reuptake Inhibitors; Pharmaceutical Preparations; Mental Disorders; Anxiety
PubMed: 37459097
DOI: 10.1001/jamanetworkopen.2023.23746 -
Cureus Dec 2023Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and mortality. The optimal approach to managing AF, specifically rate control... (Review)
Review
Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and mortality. The optimal approach to managing AF, specifically rate control versus rhythm control, remains a topic of debate in clinical practice. This systematic review aims to compare the rate control and rhythm control strategies based on their clinical outcomes, quality of life, and adverse events associated with them. A comprehensive search was conducted using PubMed, Google Scholar, Science Direct, Research Gate, MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, and Embase (Excerpta Medica dataBASE) databases. A total of 1657 research papers were identified through the search strategy, and after applying the eligibility criteria, 28 studies were selected for the analysis. The studies encompassed a range of methodologies, including randomized controlled trials, observational studies, and meta-analyses. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for study selection, data extraction, and analysis. The outcomes of interest included all: cause mortality, stroke, bleeding events, cardiovascular hospitalizations, quality of life, and adverse effects of treatment. Data were synthesized and presented in tables, charts, and forest plots for meta-analysis where appropriate. The results indicate that both rate control and rhythm control strategies have their own merits and limitations, with the outcomes varying based on patient characteristics and comorbidities. While rhythm control strategies may lead to better symptom control and improved quality of life, rate control strategies may be associated with lower risks of adverse events and complications. This systematic review provides a comprehensive overview of the current evidence regarding rate and rhythm control strategies in AF management, offering insights for clinical decision-making and highlighting the need for individualized treatment approaches.
PubMed: 38169694
DOI: 10.7759/cureus.49869 -
International Journal of Clinical... Apr 2024Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients...
Psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide: a pharmacovigilance analysis of individual case safety reports submitted to the EudraVigilance database.
BACKGROUND
Semaglutide, liraglutide and tirzepatide are glucagon-like peptide-1 (GLP-1) receptor agonists that are effective for weight reduction. Recent reports of patients experiencing suicidal thoughts and other psychiatric adverse events while using GLP-1 agonists have raised concerns about the potential risk of self-harm and led the European Medicines Agency to investigate these medications.
AIM
To identify and analyse the psychiatric adverse events associated with semaglutide, liraglutide and tirzepatide.
METHOD
All individual case safety reports for semaglutide, liraglutide, and tirzepatide reported to the EudraVigilance database from 01/01/2021 to 30/05/2023 were analysed. Descriptive statistics were used to explore study population characteristics.
RESULTS
During the study period, 31,444 adverse event reports were identified: semaglutide (n = 13,956; 44.4%), liraglutide (n = 16,748; 53.2%), and tirzepatide (n = 740; 2.3%). There were 372 reports with psychiatric adverse event reports (n = 372; 1.18%) with a total of 481 adverse events. Women accounted for 65% (n = 242) of these reports. Depression was the most commonly reported adverse event (n = 187; 50.3%), followed by anxiety (n = 144; 38.7%) and suicidal ideation (n = 73; 19.6%). Nine deaths (8 with liraglutide and 1 with semaglutide) and 11 life-threatening outcomes (4 associated with liraglutide and 7 with semaglutide) were reported. The fatal outcomes occurred primarily among men (8 out of 9) resulting from completed suicidal attempts and depression.
CONCLUSION
Psychiatric adverse events comprised only 1.2% of the total reports for semaglutide, liraglutide, and tirzepatide. However, the severity and fatal outcomes of some of these reports warrant further investigation.
Topics: Male; Humans; Female; Liraglutide; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Pharmacovigilance; Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide-2 Receptor; Glucagon-Like Peptides; Gastric Inhibitory Polypeptide
PubMed: 38265519
DOI: 10.1007/s11096-023-01694-7 -
Heliyon Mar 2024Alpelisib was approved for treatment of breast cancer. We assessed the safety signals associated with alpelisib by data mining the FDA pharmacovigilance database.
BACKGROUND
Alpelisib was approved for treatment of breast cancer. We assessed the safety signals associated with alpelisib by data mining the FDA pharmacovigilance database.
METHODS
Data from the second quarter of 2019 to the fourth quarter of 2022 had been retrieved from the FAERS database. Disproportionality analysis by reporting odds ratio were used to evaluate the potential association between adverse events (AEs) and alpelisib.
RESULTS
A total of 5,980,090 reports were extracted, 18,149 of them were chosen with alpelisib as the suspected drug. After combining the same PRIMARYID, 5647 patients remained. We observed 10 system organ classes (SOCs) with a reported number >50 and associated with alpelisib as gastrointestinal disorders, general disorders and administration site conditions, metabolism and nutrition disorders, skin and subcutaneous tissue disorders, investigations and neoplasms benign, malignant and unspecified (incl cysts and polyps), immune system disorders, nervous system disorders, psychiatric disorders, eye disorders. The median time to AEs in these patients was 13 days, with an IQR (Interquartile Range) of 7-70 days. 61.12% AEs happened within the initial month of alpelisib usage.
CONCLUSION
Our study provided a more in-depth and extensive understanding of AEs that may be associated with alpelisib, which will help to reduce the risk of AEs in the clinical treatment of alpelisib. AEs with novel preferred term (PTs) were constipation, dysphagia, diabetic ketoacidosis, feeding disorder, urticaria, eye disorders and vision blurred. 61.12% of cases developed AEs within 30 days after taking alpelisib.
PubMed: 38510044
DOI: 10.1016/j.heliyon.2024.e27599 -
Journal of Atherosclerosis and... Apr 2024Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial,...
Association of Antipsychotic Drugs with Venous Thromboembolism: Data Mining of Food and Drug Administration Adverse Event Reporting System and Mendelian Randomization Analysis.
AIMS
Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms.
METHODS
We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes.
RESULTS
In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action.
CONCLUSIONS
Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.
Topics: United States; Humans; Venous Thromboembolism; Antipsychotic Agents; Mendelian Randomization Analysis; United States Food and Drug Administration; Pulmonary Embolism; Data Mining
PubMed: 38030236
DOI: 10.5551/jat.64461 -
Frontiers in Pharmacology 2023Cholangiocarcinoma (CCA) is a highly lethal and aggressive epithelial tumor of the hepatobiliary system. A poor prognosis, propensity for relapse, low chance of cure...
Cholangiocarcinoma (CCA) is a highly lethal and aggressive epithelial tumor of the hepatobiliary system. A poor prognosis, propensity for relapse, low chance of cure and survival are some of its hallmarks. Pemigatinib, the first targeted treatment for CCA in the United States, has been demonstrated to have a significant response rate and encouraging survival data in early-phase trials. The adverse events (AEs) of pemigatinib must also be determined. To understand more deeply the safety of pemigatinib in the real world through data-mining of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Disproportionality analysis was employed in a retrospective pharmacovigilance investigation to identify the AEs linked to pemigatinib use as signals. Data were collected between 1 January 2020 to 30 June 2022. Four data-mining methods (proportional reporting odds ratio; proportional reporting ratio; Bayesian confidence propagation neural networks of information components; empirical Bayes geometric means) were used to calculate disproportionality. A total of 203 cases using pemigatinib as the prime-suspect medication were found in our search, which involved 99 preferred terms (PTs). Thirteen signals of pemigatinib-induced AEs in seven System Organ Classes were detected after confirming the four algorithms simultaneously. Nephrolithiasis was an unexpected significant AE not listed on the drug label found in our data-mining. Comparison of the differences between pemigatinib and platinum drugs in terms of 33 PTs revealed that 13 PTs also met the criteria of the four algorithms. Ten of these PTs were identical to those compared with all other drugs, in which (excluding a reduction in phosphorus in blood) other PT signal values were higher than those of all other drugs tested. However, comparison of the differences between pemigatinib and infigratinib in terms of the 33 PTs revealed no significant signals in each algorithm method. Some significant signals were detected between pemigatinib use and AEs. PTs with apparently strong signals and PTs not mentioned in the label should be taken seriously.
PubMed: 37554985
DOI: 10.3389/fphar.2023.1194545