Ondansetron use is associated with lower COVID-19 mortality in a Real-World Data network-based analysis

Objective: The COVID-19 pandemic generated a massive amount of clinical data, which potentially holds yet undiscovered answers related to COVID-19 morbidity, mortality, long term effects, and therapeutic solutions. The objective of this study was to generate insights on COVID-19 mortality-associated factors and identify potential new therapeutic options for COVID-19 patients by employing artificial intelligence analytics on real-world data. Materials and Methods: A Bayesian statistics-based artificial intelligence data analytics tool (bAIcis®) within Interrogative Biology® platform was used for network learning, inference causality and hypothesis generation to analyze 16,277 PCR positive patients from a database of 279,281 inpatients and outpatients tested for SARS-CoV-2 infection by antigen, antibody, or PCR methods during the first pandemic year in Central Florida. This approach generated causal networks that enabled unbiased identification of significant predictors of mortality for specific COVID-19 patient populations. These findings were validated by logistic regression, regression by least absolute shrinkage and selection operator, and bootstrapping. Results: We found that in the SARS-CoV-2 PCR positive patient cohort, early use of the antiemetic agent ondansetron was associated with increased survival in mechanically ventilated patients. Conclusions: The results demonstrate how real world COVID-19 focused data analysis using artificial intelligence can generate valid insights that could possibly support clinical decision-making and minimize the future loss of lives and resources.

Fast-dissolving Sublingual Nanofibers of Ondansetron Hydrochloride: Formulation, Physicochemical Characterization, and Clinical Evaluation on Post-cataract Surgery Patients

Objective: Ondansetron hydrochloride (OND) is an antiemetic agent belongs to the 5-HT3 receptor antagonist class administrated widely in relieving nausea and vomiting which is the most common complication occurred after surgery. This study aimed to design and evaluate the physicochemical along with clinical effects of fast-dissolving nanofiber (FDN) of OND administrated sublingually to enhance the bioavailability, effectiveness, and patient compliance compared to orally disintegrating tablets (ODT). Methods: Nanofibers were prepared by the electrospinning method, using polyvinyl alcohol and alpha-cyclodextrin as polymers and sodium saccharin as the sweetener. Physicochemical and mechanical characteristics of nanofibers were examined then the clinical evaluation was performed. Eighty patients volunteering for cataract surgery were randomly divided into two groups, one received FDN, and the other treated with ODT of OND after recovery and in case of relieving nausea. The severity of nausea was assessed using a visual analogue scale in the 6 and 24 h intervals after drug administration. The SPSS 25.0 statistical software and statistical tests were used to analyze the obtained data. Results: Nanofibers possessed a mean diameter of 159 ± 30 nm beside suitable physicochemical and mechanical characteristics. Statistical evaluations showed that both FDN and ODT formulations had an equal anti-emetic effect (P>0.05) on reducing the severity of nausea but the FDN formulation caused significantly higher levels of patients’ satisfaction (P<0.05) compared to the ODT. Conclusions: Although both formulations had an almost equal anti-emetic effect, due to the benefits of this novel formulation including rapid disintegration, the ODT can be replaced by FDN.

A clinical survey on the electrocardiogram after intravenous granisetron hydrochloride administration in clinically normal dogs

Cardiac side effect of 5-hydroxytryptamine-3 receptor antagonists has been a concern for clinicians. There is a substantial need for greater clarity about the safety of granisetron hydrochloride, an antiemetic agent of this class used in oncological and parvoviral gastroenteritis with acute vomiting in dogs. This study aimed to assess the electrocardiographic effects of a single dose of intravenous granisetron. We randomly assigned 16 adult crossbreed female healthy dogs into two groups of intervention and control and injected them intravenously with granisetron and normal saline, respectively, at a dose of 0.5 ml/kg over one minute. Standard electrocardiography (ECG) was recorded at the baseline, as well as 5, 15, 30, 60, 120, 360, and 720 minutes after the intervention. Heart rate and ECG parameters (PR intervals, QRS duration, ST-segment, T-wave amplitudes, QT, JT, QTc and JTc intervals) were evaluated in lead II.No significant difference was observed between the intervention and the control groups in any of the measured variables at any of the time-points. Mean values of measured parameters showed no significant difference compared with baseline values in the control group, while the granisetron group saw statistically significant but clinically asymptomatic changes in heart rate, PR, QRS, QT, JT, and QTc at different time-points, compared to the baseline values (P<0.05). In conclusion, Granisetron administration was not associated with clinically significant adverse effects on ECG variables or heart rate. Thus, it can be regarded as a relatively safe drug.

Safety of metoclopramide in traumatic brain injury patients

Background: One in every three related-injury deaths in United State are linked directly to traumatic brain injury (TBI), for which it is considered as a leading cause of death. Traumatic brain injury took place due to severe head assault to a hard object, with headache and vomiting being amongst the most common presenting symptoms. Metoclopramide is an old antiemetic agent that has been used widely for nausea and vomiting in TBI patients. Aim: A systematic review of the literature to investigate the safety of metoclopramide in treating traumatic brain injury patients. Methods: A literature review was conducted in 6 databases, we determine the pertinence of a study to the inclusion criteria by assessing the title, keywords, and abstracts. Five studies were found to be relevant. Data were extracted using multiple variables that were formulated incongruent with the study aim and then further analyzed. Results: The collective sample size was 93 patients with an average of age 38.5 years. 51.6 % were male and 48.6% were females. Most patients received 10 mg metoclopramide IV with a percentage of 77.4%. While only 22.5% received 20 mg IV metoclopramide. Seventy-one patients received metoclopramide alone and 22 received combination therapy. Headache was the most common reported side effect (46.2 %), followed by anxiety and drowsiness with (39.7%) and (27.9 %); respectively. Fatigue reported in (24.7%), while dystonia was the least common and developed only in 5.3%. Conclusion: Metoclopramide is a common medication used to treat TBI patients in the emergency department. However, the review demonstrated that the central nervous system (CNS) side effect is excepted. Alternative options with lower CNS side effects may be better tried.

Safety of Metoclopramide in Traumatic Brain Injury (TBI) Patients

Introduction Traumatic brain injuries (TBIs) occur due to severe head assault to a hard object, with headache and vomiting being amongst the most common presenting symptoms. Metoclopramide is an old antiemetic agent that has been used widely for nausea and vomiting in TBI patients. Aim A systematic review of the literature to investigate the safety of metoclopramide in treating TBI patients. Methods A literature review was conducted in six databases, where we determined the pertinence of a study to the inclusion criteria by assessing the title, keywords, and abstracts. Five studies were found to be relevant. Data were extracted using multiple variables that were formulated incongruent with the study aim and then further analyzed. Results The collective sample size was 93 patients with an average of age 38.5 years. As much as 51.6% were male and 48.6% were females. Most patients received 10 mg metoclopramide IV with a percentage of 77.4%, while only 22.5% received 20 mg IV metoclopramide. Seventy-one patients received metoclopramide alone and 22 received combination therapy. Headache was the most common reported side effect (46.2%), followed by anxiety and drowsiness with (39.7%) and (27.9%), respectively. Fatigue was reported in 24.7%, while dystonia was the least common and developed in only 5.3% of patients. Conclusion Metoclopramide is a common medication used to treat TBI patients in the emergency department. However, the review demonstrated that the central nervous system (CNS) side effect is excepted. Treatments with lower CNS side effects may be better options.

Unscheduled hydrations: redefining complete response in chemotherapy-induced nausea and vomiting studies

Breakthrough chemotherapy-induced nausea and vomiting (CINV) is nausea and/or vomiting occurring within 5 days of chemotherapy administration despite using guideline-directed prophylactic antiemetic agents. It is highly prevalent (30–40%), usually requiring immediate treatment or “rescue” medication. If breakthrough CINV occurs, antiemetic guidelines recommend using an antiemetic agent from a different class not used in prophylaxis, along with intravenous hydration and/or dexamethasone. Data supporting these guideline recommendations are limited. Importantly, costs associated with breakthrough CINV can be substantial (i.e., unscheduled hydrations). Two retrospective analyses evaluating guideline-adherent CINV prophylaxis suggest that the initial antiemetic selection may decrease breakthrough CINV. Here we review optimal CINV prophylactic strategies and introduce unscheduled hydration as a potential important surrogate for breakthrough CINV aligning with cost-effective cancer care.

Optimal Management of Chemotherapy-related Adverse Events

This review article deals with the optimal management of chemotherapy-related adverse events which are the nausea, vomiting, diarrhea, neutropenia, peripheral polyneuropathy. Recent literatures are reviewed and pathogenetic mechanism and management of each of adverse events are summarized. It is not simple but complexed and wide. Most patients could be expected how much they feel the nausea before the chemotherapy. We could prescribe several types of antiemetic agent efficiently. When the patients suffered from the neutropenia after previous chemotherapy, we should closely monitor their blood cell count. And we could help them after giving the granulocyte colony stimulating factor. Diarrhea is one of big troublesome issue related with chemotherapy. We could control the diarrhea by reducing the dose of the chemotherapy and prescribing optimally loperamide. Cisplatin and oxaliplatin could make the patients feel paresthesia and numbness but it’s hard to reverse or prevent even though we use anticonvulsants (carbamazepine, oxcarbazepine), antidepressants (amitriptyline, venlafaxine), amifostine, nimodipine, vitamins and minerals.

Comparison Ability of Polymers Acrycoat S100 And HPMC K4M to Entrapment Efficiency Domperidone in Microspheres

Domperidone is a prokinetic and antiemetic agent which has low bioavaibility. To increase the bioavaibility of drug, it can be modified into microsphere that can hold drug more longer in gastric to improve the bioavaibility. The microsphere preparation requires a polymer that can make matrix system to protect and deliver the drugs. Acrycoat S100 and HPMC K4M are the usual polymers that used for encapsulation and have biodegradable characteristic. The aim of this research is to know the comparison ability of two different polymers to entrapment the drug in microsphere. Microsphere domperidone made by solvent evaporation method in 6 formula. F1, F2 and F3 using 50 mg, 100 mg and 150 mg Acrycoat S100 polymer, while F4, F5 and F6 using 50 mg, 100 mg and 150 mg HPMC K4m polymer. The tests were conducted by the determination of the percentage of entrapment efficiency using UV spectrophotometer and evaluation of organoleptic, particle measurement and surface microsphere morphology. The results showed that F3 with Acrycoat S100 polymer has a greater entrapment efficiency of 78,712% ± 4,260% compared to the highest percentage efficiency of HPMC K4M polymer of 4,734±0,390.Key words: Acrycoat S100, domperidone, entrapment efficiency, HPMC K4M, microsphere