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BioMed Research International 2024[This retracts the article DOI: 10.1155/2022/1662194.].
[This retracts the article DOI: 10.1155/2022/1662194.].
PubMed: 38230163
DOI: 10.1155/2024/9841865 -
BioMed Research International 2024[This retracts the article DOI: 10.1155/2022/2467574.].
[This retracts the article DOI: 10.1155/2022/2467574.].
PubMed: 38230014
DOI: 10.1155/2024/9802835 -
Frontiers in Pharmacology 2023Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive...
Drug-induced QT prolongation and (or) Torsade de Pointes (TdP) is a well-known serious adverse reaction (ADR) for some drugs, but the widely recognized comprehensive landscape of culprit-drug of QT prolongation and TdP is currently lacking. To identify the top drugs reported in association with QT prolongation and TdP and provide information for clinical practice. We reviewed the reports related to QT prolongation and TdP in the FDA Adverse Event Reporting System (FAERS) database from January 1, 2004 to December 31, 2022, and summarized a potential causative drug list accordingly. Based on this drug list, the most frequently reported causative drugs and drug classes of QT prolongation and TdP were counted, and the disproportionality analysis for all the drugs was conducted to in detect ADR signal. Furthermore, according to the positive-negative distribution of ADR signal, we integrated the risk characteristic of QT prolongation and TdP in different drugs and drug class. A total of 42,713 reports in FAERS database were considered to be associated with QT prolongation and TdP from 2004 to 2022, in which 1,088 drugs were reported as potential culprit-drugs, and the largest number of drugs belonged to antineoplastics. On the whole, furosemide was the most frequently reported drugs followed by acetylsalicylic acid, quetiapine, citalopram, metoprolol. In terms of drug classes, psycholeptics was the most frequently reported drug classes followed by psychoanaleptics, analgesics, beta blocking agents, drugs for acid related disorders. In disproportionality analysis, 612 drugs showed at least one positive ADR signals, while citalopram, ondansetron, escitalopram, loperamide, and promethazine were the drug with the maximum number of positive ADR signals. However, the positive-negative distribution of ADR signals between different drug classes showed great differences, representing the overall risk difference of different drug classes. Our study provided a real-world overview of QT prolongation and TdP to drugs, and the presentation of the potential culprit-drug list, the proportion of reports, the detection results of ADR signals, and the distribution characteristics of ADR signals may help understand the safety profile of drugs and optimize clinical practice.
PubMed: 38186652
DOI: 10.3389/fphar.2023.1259611 -
Frontiers in Cellular and Infection... 2023Sepsis is a life-threatening disease with high morbidity and mortality, characterized by an inadequate systemic immune response to an initial stimulus. Whether the use...
BACKGROUND
Sepsis is a life-threatening disease with high morbidity and mortality, characterized by an inadequate systemic immune response to an initial stimulus. Whether the use of ondansetron (OND) during intensive care unit (ICU) stay is associated with the prognosis of sepsis patients remains unclear.
METHODS
Critically ill patients with sepsis were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Multivariate logistic regression and Cox regression analyses were used to explore the association between OND use and clinical outcomes after adjusting for confounders. Kaplan-Meier survival curve was used for survival analysis. Propensity score matching (PSM) and subgroup analysis were performed to further confirm the results.
RESULTS
The OND-medication group showed reduced in-hospital mortality, 28-day and 90-day mortalities. The OR for in-hospital mortality was 0.80 (0.64-0.99) and HRs for 28-day mortality and 90-day mortality were 0.77 (0.64-0.92) and 0.83 (0.70-0.98), respectively. After PSM, the clinical outcomes remained consistent. In-hospital mortality was lower in the OND-medication group (28.1% . 35.8%, P= 0.044), as well as 28-day mortality (23.4% . 32.1%, P=0.022) and 90-day mortality (27.4% . 35.8%, P=0.035). The protective effect of OND in sepsis patients was relatively robust, independent of age, septic shock, vasopressin and mechanical ventilation. Additionally, the OND users had longer lengths of stay in ICU (6.9(3.1-13.2) . 5.1(2.5-11.0), P = 0.026) while no statistical differences were found in lengths of stay in hospital (P = 0.333).
CONCLUSION
OND exposure might be associated with lower in-hospital, 28-day, and 90-day mortality rates in critically ill patients with sepsis. This study indicated that OND might help improve the prognosis of patients with sepsis.
Topics: Humans; Cohort Studies; Ondansetron; Critical Illness; Retrospective Studies; Intensive Care Units; Sepsis
PubMed: 38179420
DOI: 10.3389/fcimb.2023.1256382 -
Integrative Cancer Therapies 2023evaluate the efficacy of Zingiber Officinale in the management of nausea and vomiting induced by treatment with cisplatin associated with radiotherapy in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
evaluate the efficacy of Zingiber Officinale in the management of nausea and vomiting induced by treatment with cisplatin associated with radiotherapy in patients with uterine cervical neoplasms.
METHODS
a triple-blind, randomized, placebo-controlled trial. Interventions: Comparing the effects of ginger with institutional antiemetic therapy (ondansetron with dexamethasone). Patients with cervical cancer who started treatment with cisplatin with an indication of 40 mg/m² associated with radiotherapy, aged over 18 years, and with the ability to tolerate swallowing a capsule were recruited and equally allocated (1:1:1) into 3 groups of 16 patients each (the ginger capsules 250 mg group, ginger capsules 500 mg group, and placebo group). Nausea and vomiting were measured on baseline, 7 days after the first dose of medication and every seven consecutive days during a treatment break.
RESULTS
The 250 mg ginger group had an 8.0% greater chance of experiencing nausea within 24 h after the chemotherapy infusion than the placebo group, although there is no statistical significance ( = .92986). The 500 mg ginger group showed a 63.9% reduction in nausea under the same conditions ( = .40460). No change was detected in the occurrence of nausea episodes during the 6 weeks ( = .8664) or between the groups ( = .2817). No change was detected in acute or late vomiting during the 6 weeks ( = .3510) or between the groups ( = .8500 and = .5389, respectively).
CONCLUSION
Ginger supplementation does not reduce the intensity of acute and late nausea and vomiting. REBEC (RBR-47yx6p9).
Topics: Female; Humans; Adult; Middle Aged; Cisplatin; Zingiber officinale; Double-Blind Method; Vomiting; Nausea; Uterine Cervical Neoplasms
PubMed: 38140826
DOI: 10.1177/15347354231220608 -
Plants (Basel, Switzerland) Dec 2023Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the...
Quercetin (QUA), a flavonoid compound, is ubiquitously found in plants and has demonstrated a diverse range of biological activities. The primary objective of the current study is to assess the potential antiemetic properties of QUA using an in vivo and in silico approach. In this experiment, 4-day-old chicks were purchased to induce emesis by orally administering copper sulfate pentahydrate (CuSO·5HO) at a dose of 50 mg/kg (orally). Domperidone (DOM) (6 mg/kg), Hyoscine (HYS) (21 mg/kg), and Ondansetron (OND) (5 mg/kg) were treated as positive controls (PCs), and distilled water and a trace amount of Tween 80 mixture was employed as a negative control (NC). QUA was given orally at two distinct doses (25 and 50 mg/kg). Additionally, QUA (50 mg/kg) and PCs were administered separately or in combination to assess their antagonistic or synergistic effects on the chicks. The binding affinity of QUA and referral ligands towards the serotonin receptor (5HT3), dopamine receptors (D2 and D3), and muscarinic acetylcholine receptors (M1-M5) were estimated, and ligand-receptor interactions were visualized through various computational tools. In vivo findings indicate that QUA (25 and 50 mg/kg) has a significant effect on reducing the number of retches (16.50 ± 4.65 and 10.00 ± 4.19 times) and increasing the chick latency period (59.25 ± 4.75 and 94.25 ± 4.01 s), respectively. Additionally, QUA (50 mg/kg) in combination with Domperidone and Ondansetron exhibited superior antiemetic effects, reducing the number of retches and increasing the onset of emesis-inducing time. Furthermore, it is worth noting that QUA exhibited the strongest binding affinity against the D2 receptor with a value of -9.7 kcal/mol through the formation of hydrogen and hydrophobic bonds. In summary, the study found that QUA exhibited antiemetic activity in chicks, potentially by interacting with the D2 receptor pathway.
PubMed: 38140516
DOI: 10.3390/plants12244189 -
Pharmaceuticals (Basel, Switzerland) Dec 2023Ondansetron is a drug that is routinely prescribed for the management of nausea and vomiting associated with cancer, radiation therapy, and surgical operations. It is...
INTRODUCTION
Ondansetron is a drug that is routinely prescribed for the management of nausea and vomiting associated with cancer, radiation therapy, and surgical operations. It is mainly metabolized in the liver, and it might accumulate in patients with hepatic impairment and lead to unwanted adverse events.
METHODS
A physiologically based pharmacokinetic (PBPK) model was developed to predict the exposure of ondansetron in healthy and liver cirrhosis populations. The population-based PBPK simulator PK-Sim was utilized for simulating ondansetron exposure in healthy and liver cirrhosis populations.
RESULTS
The developed model successfully described the pharmacokinetics of ondansetron in healthy and liver cirrhosis populations. The predicted area under the curve, maximum systemic concentration, and clearance were within the allowed twofold range. The exposure of ondansetron in the population of Child-Pugh class C has doubled in comparison to Child-Pugh class A. The dose has to be adjusted for liver cirrhosis patients to ensure comparable exposure to a healthy population.
CONCLUSION
In this study, the developed PBPK model has described the pharmacokinetics of ondansetron successfully. The PBPK model has been successfully evaluated to be used as a tool for dose adjustments in liver cirrhosis patients.
PubMed: 38139819
DOI: 10.3390/ph16121693 -
The Korean Journal of Pain Jan 2024Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of...
BACKGROUND
Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity.
METHODS
Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K pathway in the antinociceptive effect of sitagliptin (5 mg/kg).
RESULTS
Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly ( < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect.
CONCLUSIONS
NO/cGMP/K, 5HT and D pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.
PubMed: 38123184
DOI: 10.3344/kjp.23262 -
JAMIA Open Dec 2023Pediatric emergence delirium is an undesirable outcome that is understudied. Development of a predictive model is an initial step toward reducing its occurrence. This...
OBJECTIVES
Pediatric emergence delirium is an undesirable outcome that is understudied. Development of a predictive model is an initial step toward reducing its occurrence. This study aimed to apply machine learning (ML) methods to a large clinical dataset to develop a predictive model for pediatric emergence delirium.
MATERIALS AND METHODS
We performed a single-center retrospective cohort study using electronic health record data from February 2015 to December 2019. We built and evaluated 4 commonly used ML models for predicting emergence delirium: least absolute shrinkage and selection operator, ridge regression, random forest, and extreme gradient boosting. The primary outcome was the occurrence of emergence delirium, defined as a Watcha score of 3 or 4 recorded at any time during recovery.
RESULTS
The dataset included 54 776 encounters across 43 830 patients. The 4 ML models performed similarly with performance assessed by the area under the receiver operating characteristic curves ranging from 0.74 to 0.75. Notable variables associated with increased risk included adenoidectomy with or without tonsillectomy, decreasing age, midazolam premedication, and ondansetron administration, while intravenous induction and ketorolac were associated with reduced risk of emergence delirium.
CONCLUSIONS
Four different ML models demonstrated similar performance in predicting postoperative emergence delirium using a large pediatric dataset. The prediction performance of the models draws attention to our incomplete understanding of this phenomenon based on the studied variables. The results from our modeling could serve as a first step in designing a predictive clinical decision support system, but further optimization and validation are needed.
CLINICAL TRIAL NUMBER AND REGISTRY URL
Not applicable.
PubMed: 38098478
DOI: 10.1093/jamiaopen/ooad106 -
Frontiers in Pharmacology 2023The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during...
The medicines information service, SafeMotherMedicine, regularly receives inquiries from breastfeeding women asking about antiemetics for nausea and vomiting during pregnancy (NVP) or hyperemesis gravidarum (HG). However, treatment guidelines for NVP or HG do not address the use of antiemetics in women who are breastfeeding while becoming pregnant again. Our objective was to characterize inquiries to describe the need for lactation risk information among women with NVP or HG and also to raise awareness of this topic. We conducted a review of inquiries to the Norwegian web-based medicines information service, SafeMotherMedicine. In total, 97 inquiries addressing the use of antiemetics for NVP or HG during breastfeeding were identified. The following medications were addressed in the inquiries ( = 97): meclizine (51%), metoclopramide (33%), promethazine (16%), ondansetron (9%), and others (6%). The breastfed child was older than 6 months and 1 year in 96% and 71% of the inquiries, respectively. There was a preponderance of general inquiries (unclear motivation/double checking) (64%); however, one-third of the inquiries were generated by restrictive information from sources such as product information. Based on our small review of spontaneous inquiries, there seems to be an information need about the use of antiemetics during lactation among women breastfeeding an older infant whilst suffering from NVP or HG. Addressing such use in guidelines for NVP and HG and/or other easily available information sources may be considered in order to balance out the restrictive information provided by the manufacturers. This could avoid potential unnecessary weaning of breastfeeding in an otherwise challenging situation.
PubMed: 38094894
DOI: 10.3389/fphar.2023.1238875