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Cancer Medicine Aug 2023Non-inferiority of NEPA (fixed combination of NK receptor antagonist (RA), netupitant, and 5-HT RA, palonosetron) versus an aprepitant regimen was previously shown in a... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Non-inferiority of NEPA (fixed combination of NK receptor antagonist (RA), netupitant, and 5-HT RA, palonosetron) versus an aprepitant regimen was previously shown in a pragmatic study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). In the MEC group a numerically higher complete response (CR: no emesis, no rescue) rate was seen for NEPA during the overall 0-120 h phase (NEPA 76.1% vs. 63.1% aprepitant). As NEPA exhibits long-lasting efficacy, this study evaluated a prolonged period up to 144 h, beyond the traditional 120 h post-chemotherapy. In this post-hoc analysis we explore the comparative efficacy of NEPA versus the aprepitant regimen in the MEC group up to 144 h, while also assessing the impact of risk factors on CINV prevention.
METHODS
This was a pragmatic, multicenter, randomized, prospective study. Oral NEPA was administered as a single dose on day 1, while aprepitant was given on days 1-3 + ondansetron on day 1; all patients were to receive dexamethasone on days 1-4. Patients were chemotherapy-naïve and receiving MEC, with a subset evaluation of those with a risk factor for developing CINV (i.e., female, male <60 years, male ≥60 years who received carboplatin, or male ≥60 years with anxiety). CR rates were compared during the extended overall (0-144 h) phase.
RESULTS
The MEC group included 211 patients; of these 181 were in the risk factor subset. Significantly higher CR rates were seen for NEPA than aprepitant during the extended overall phase for the total MEC group (NEPA 77.1%, aprepitant 57.8%, p = 0.003) and also in the subset of patients with CINV risk factors (NEPA 73.9%, aprepitant 56.2%, p = 0.012).
CONCLUSION
A single dose of NEPA, administered on day 1 only, was more effective than a 3-day aprepitant regimen in preventing CINV for an extended duration in patients receiving MEC and in those with emetic risk factors.
Topics: Humans; Male; Female; Aprepitant; Antiemetics; Vomiting; Prospective Studies; Isoquinolines; Quinuclidines; Drug Combinations; Nausea; Cyclophosphamide; Anthracyclines; Antineoplastic Agents; Dexamethasone
PubMed: 37537943
DOI: 10.1002/cam4.6121 -
Journal of Medicinal Chemistry Aug 2023Growth differentiation factor 15 (GDF15) is a contributor to nausea, emesis, and anorexia following chemotherapy via binding to the GFRAL-RET receptor complex expressed...
Growth differentiation factor 15 (GDF15) is a contributor to nausea, emesis, and anorexia following chemotherapy via binding to the GFRAL-RET receptor complex expressed in hindbrain neurons. Therefore, GDF15-mediated GFRAL-RET signaling is a promising target for improving treatment outcomes for chemotherapy patients. We developed peptide-based antagonists of GFRAL that block GDF15-mediated RET recruitment. Our initial library screen led to five novel peptides. Surface plasmon resonance and flow cytometric analyses of the most efficacious of this group, termed GRASP, revealed its capacity to bind to GFRAL. studies in rats revealed that GRASP could attenuate GDF15-induced nausea and anorexia resulting from cisplatin. Combined with Ondansetron, GRASP led to an even greater attenuation of the anorectic effects of cisplatin compared to either agent alone. Our results highlight the beneficial effects of GRASP as an agent to combat chemotherapy-induced malaise. GRASP may also be effective in other conditions associated with elevated levels of GDF15.
Topics: Animals; Rats; Anorexia; Cell Membrane; Cisplatin; Growth Differentiation Factor 15
PubMed: 37506293
DOI: 10.1021/acs.jmedchem.3c00667 -
Farmacia Hospitalaria : Organo Oficial... 2023Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016... (Observational Study)
Observational Study
OBJECTIVE
Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016 incorporating anthracycline schemes as highly emetogenic chemotherapy (HEC), proposing triple antiemetic therapy to control nausea and vomiting. Likewise, they recommend triple therapy for carboplatin. The objectives of this study were to analyze the degree of concordance between guidelines and antiemetic prophylaxis used in the Chemotherapy Outpatient Unit in patients undergoing treatment with HEC and carboplatin, to evaluate its effectiveness and to determine the savings due to the use of netupitant/palonosetron (NEPA) oral (or) with intravenous (iv) dexamethasone (NEPAd) compared to iv Fosaprepitant with ondansetron and dexamethasone (FOD iv).
METHODS
Prospective observational study recording demographic variables, chemotherapy protocol, tumor location, patient emetogenic risk, antiemetic regimen prescribed, concordance with the MASCC/ESMO guideline, and effectiveness, evaluated by MASCC survey, use of rescue medication and visits to the Emergency Department or hospitalization due to emesis. A cost minimization pharmacoeconomic study was carried out.
RESULTS
61 patients were included; 70% women; median age 60.5. Platinum schemes were more frequent in period 1, being 87.5% compared to 67.6% in period 2. Anthracycline schemes were 21.6% and 10% respectively in each period. A 21.1% of the antiemetic regimens did not coincide with the MASCC/ESMO recommendations, being entirely in period 1. The score of the effectiveness questionnaires was total protection in 90.9% in acute nausea, from 100% in acute vomiting and delayed nausea, and 72.7% in delayed vomiting. The frequency of use of rescue medication was 18.7% in period 1 and was not necessary in period 2. No visits to the emergency room or admissions were detected in any of the periods.
CONCLUSIONS
Use of NEPAd led to a 28% reduction in costs with respect to the use of FOD. A high level of concordance was obtained in both periods between the latest published guideline and healthcare practice in our field. Surveys carried out on patients seem to suggest that both antiemetic therapies have similar effectiveness in clinical practice. The inclusion of NEPAd has led to a reduction in costs, positioning itself as an efficient option.
Topics: Humans; Female; Middle Aged; Male; Antiemetics; Carboplatin; Anthracyclines; Nausea; Vomiting; Antibiotics, Antineoplastic; Dexamethasone; Antineoplastic Agents
PubMed: 37500396
DOI: 10.1016/j.farma.2023.06.007 -
The efficacy of aprepitant for the prevention of postoperative nausea and vomiting: A meta-analysis.Medicine Jul 2023Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs suggest that aprepitant has the strongest antiemetic effect of any single drug. This meta-analysis aimed to explore the efficacy of aprepitant for preventing PONV based on the existing literature.
METHODS
To identify RCTs investigating the use of aprepitant for PONV prevention, we searched PubMed, Embase, and Cochrane Library databases for articles published prior to March 20, 2022. Seventeen RCTs were identified, with 3299 patients, meeting the inclusion criteria. PONV incidence, complete response, 80 mg aprepitant combined with dexamethasone and ondansetron, vomiting, nausea, and analgesic dose-response were the main outcomes measured.
RESULTS
Compared with the control group, PONV incidence was significantly reduced among those receiving aprepitant (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.26, 0.44; P < .0001), with a more complete response (OR: 1.35; 95% CI: 1.14, 1.59; P = .0004). Supplementation of 80 mg aprepitant in combination with dexamethasone and ondansetron substantially improved the effects of PONV (OR: 0.36; 95% CI: 0.16, 0.82; P = .01). Further, administration of 80 mg aprepitant was better at preventing vomiting than nausea (OR: 8.6; 95% CI: 3.84, 19. 29; P < .00001). No statistically significant difference between the dose-response of analgesics was identified (mean difference: -1.09; 95% CI: -6.48, 4.30; P = .69). The risk of bias was assessed independently by paired evaluators.
CONCLUSION
Aprepitant effectively reduces the incidence of PONV; however, the effects of postoperative analgesia require further exploration.
Topics: Humans; Aprepitant; Postoperative Nausea and Vomiting; Ondansetron; Morpholines; Antiemetics; Vomiting; Dexamethasone
PubMed: 37478247
DOI: 10.1097/MD.0000000000034385 -
Cureus Jun 2023In a generation where advancements in research and understanding have led to remarkable achievements in medicine, it is still unfathomable that, after more than a... (Review)
Review
In a generation where advancements in research and understanding have led to remarkable achievements in medicine, it is still unfathomable that, after more than a century, the cause of schizophrenia is still a mystery. While antipsychotics, without a doubt, have brought on an exemplary revolution in the way psychiatric disorders are now treated, there are still imperative deficits that need to be addressed to ultimately enable individuals with schizophrenia to function normally in society. However, without a definite cause of schizophrenia, even though speculation has been made on its inflammatory and neurodegenerative nature, it has provided an unnecessary hindrance to finding further potential treatment modalities for these patients. Nevertheless, some trials are investigating potential adjunctive treatment regimens to antipsychotics, which can help achieve complete remission. Exploring these drugs will have significant implications for managing schizophrenia in future clinical practices. This systematic review was conducted between January 2012 to July 2022 according to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines to evaluate the safety and efficacy of ondansetron and simvastatin as adjunctive treatment to antipsychotics in adult patients with schizophrenia. This review included nine randomized controlled trials. Overall, both simvastatin and ondansetron, when used as adjunctive treatment in schizophrenia, appear to be safe. Ondansetron showed promising results, with all studies on this drug showing positive overall results on schizophrenia symptoms. On the other hand, simvastatin demonstrated mixed results, which can be attributed to the limited participants in the studies and the shorter duration of the trials. However, more extensive trials with uniform assessment tools are needed to demonstrate concrete evidence of the effectiveness of these drugs, whether alone or in combination with each other or perhaps another drug such as aspirin in schizophrenia.
PubMed: 37456496
DOI: 10.7759/cureus.40474 -
Turkish Journal of Anaesthesiology and... Jun 2023We evaluated whether systemic ondansetron was also useful in the attenuation of propofol injection pain similar to ondansetron pretreatment.
OBJECTIVE
We evaluated whether systemic ondansetron was also useful in the attenuation of propofol injection pain similar to ondansetron pretreatment.
METHODS
Eighty patients were enrolled. Patients in group S received ondansetron 4 mg in saline in the right hand followed 30 min later by 5 mL saline in the left hand along with venous occlusion. Group L patients received 4 mL of saline in the right hand followed by 5 mL 4 mg ondansetron in the left hand after 30 min. Two minutes later the occlusion was released. Patients received one-fourth of the calculated total dose of propofol, and their level of pain was graded on a scale of 0 to 3, with 0 denoting no discomfort. Mean blood pressure and heart rates were also recorded. Continuous variables were checked for normality using Shapiro-Wilks test. Normal continuous variables were expressed as mean standard deviation and non-normal continuous variables were expressed as median interquartile range. T-test for the difference in the mean and paired test were used for normally distributed continuous variable whereas Mann-Whitney U test-Wilcoxon test and sign test were used for non-normally distributed variables. Repeated measure analysis of variance was used for a variable measured over different periods of time to control for the baseline effect on subsequent measures.
RESULTS
Our results demonstrated that both systemic administration 30 min before and local venous pretreatment with ondansetron were equally beneficial in reducing pain during propofol injection.
CONCLUSION
A systemic administration of ondansetron may play a role in the attenuation of propofol injection pain.
PubMed: 37455522
DOI: 10.4274/TJAR.2023.221112 -
Turkish Journal of Anaesthesiology and... Jun 2023In the literature, there are confusing data about educational tools and device use. Therefore, it is not clear which method is superior to the other. The aim of this...
OBJECTIVE
In the literature, there are confusing data about educational tools and device use. Therefore, it is not clear which method is superior to the other. The aim of this study was to evaluate the effects of educational tools on patient-controlled analgesia (PCA) usage in patients undergoing hysterectomy.
METHODS
Ninety-six patients undergoing hysterectomy were enrolled in the study. Patients were randomly assigned to a group (verbal, brochure, or video) consisting of 32 patients each using the closed envelope method. After operations, all patients were sent to the ward and evaluated with numerical rating scale score for pain at 15 min., 2, 4, 6, 12, 18, 2, 4, 6, 12, 18, 24 hours. Given dose, the number of button presses, presence of nausea and vomiting, and static and dynamic pain scores were recorded. During visits, patients who had a pain score ≥4 were administered paracetamol 1 g IV. Ondansetron 8 mg IV was injected into patients who had nausea and vomiting.
RESULTS
No significant differences were determined in resting and dynamic pain scores, number of button presses, and given doses between groups at 15 min., 2, 4, 6, 12, 18, 24h hours.
CONCLUSION
In this study, education type did not affect PCA device use. We believe that whatever method the infrastructure of hospitals is suitable for, should be used for PCA device education.
PubMed: 37455521
DOI: 10.4274/TJAR.2022.22988 -
Turkish Journal of Anaesthesiology and... Jun 2023Postoperative shivering (POS) is considered one of the most common complications that is encountered by the anaesthetists worldwide. Despite using several treatment...
Paracetamol Versus Ondansetron for Prevention of Postoperative Shivering in Liposuction Surgeries Under Combined General Epidural Anaesthesia: A Randomized Controlled Trial.
OBJECTIVE
Postoperative shivering (POS) is considered one of the most common complications that is encountered by the anaesthetists worldwide. Despite using several treatment options, there has not been a clear consensus regarding this issue. This trial was conducted to investigate the efficacy and safety of paracetamol and ondansetron in preventing POS in patients undergoing liposuction procedures under combined general epidural anaesthesia.
METHODS
One hundred twenty patients scheduled for liposuction were randomly allocated to one of three groups: group P (paracetamol group) which received 1 g paracetamol intravenously, group O (ondansetron group) which received 8 mg of ondansetron intravenously, and group S (saline group), which received 100 mL normal saline intravenously; all medications were given postoperatively. The primary outcome was the incidence of POS, and the secondary outcomes included shivering score, tympanic temperature, and the occurrence of side effects.
RESULTS
The incidence of occurrence of POS was found to be lower in groups P and O compared to group S with values of 25% and 37.50% vs. 77.50%, respectively, with a value <0.001. Additionally, the severity of POS was found to be lower in groups P and O compared to group S ( <0.001). Tympanic temperature and complications were comparable between the groups with no significant differences.
CONCLUSION
Prophylactic use of paracetamol or ondansetron at the end of the procedure was shown to be of great value in reducing the incidence and severity of POS, with no statistically significant difference between the paracetamol and ondansetron groups. Moreover, no significant drawbacks were reported as a result of using these medications.
PubMed: 37455437
DOI: 10.4274/TJAR.2022.22927 -
The Lancet. Healthy Longevity Aug 2023
Topics: Diplomacy; International Cooperation; Brain; Head; Global Health
PubMed: 37419135
DOI: 10.1016/S2666-7568(23)00109-5 -
Cureus May 2023Chronic respiratory insufficiency can result from respiratory infections like pneumonia, which can permanently harm the lungs and respiratory system. A 21-year-old...
Chronic respiratory insufficiency can result from respiratory infections like pneumonia, which can permanently harm the lungs and respiratory system. A 21-year-old female patient arrived at our emergency medicine department (ED) complaining of acute lower-limb pain that worsened when she walked. She also reported feeling weak and having an acute, undiagnosed fever that was resolved by taking medicine two days after the day of admission. She was found to have a body temperature of 99.4°F, decreased air entry on the left side of the chest, and diminished bilateral plantar responsiveness. With the exception of a low calcium level and an increased liver function test, her biochemical indicators were normal. The left lung's basal region had fibrosis, and the right lung's hyperplasia served as a compensatory mechanism, according to the chest radiograph and CT scan of the thorax. The patient underwent treatment with intravenous pantoprazole, ondansetron, ceftriaxone, multivitamin supplementation, gabapentin, and tablets of amitriptyline. On Day 7, her lower limb pain had significantly recovered. After an eight-day hospital stay, she was discharged with instructions to follow up with the pulmonary medicine outpatient department (OPD) and the neurology OPD. A well-known occurrence known as compensatory hyperinflation of the lung happens when one lung is severely injured or rendered inoperable, leading the other lung to enlarge to make up for the loss of respiratory function. This case demonstrates the ability of the respiratory system to compensate for significant damage to one of the lungs.
PubMed: 37398719
DOI: 10.7759/cureus.39771