The antiemetic actions of GIP receptor agonism.

Nausea and vomiting are primitive aspects of mammalian physiology and behavior that ensure survival. Unfortunately, both are ubiquitously present side effects of drug treatments for many chronic diseases with negative consequences on pharmacotherapy tolerance, quality of life, and prognosis. One of the most critical clinical examples is the profound emesis and nausea that occur in patients undergoing chemotherapy, which continue to be among the most distressing side effects, even with the use of modern antiemetic medications. Similarly, antiobesity/diabetes medications that target the glucagon-like peptide-1 system, despite their remarkable metabolic success, also cause nausea and vomiting in a significant number of patients. These side effects hinder the ability to administer higher dosages for optimal glycemic and weight management and represent the major reasons for treatment discontinuation. Our inability to effectively control these side effects highlights the need to anatomically, molecularly, and functionally characterize novel neural substrates that drive and inhibit nausea and emesis. Here, we discuss clinical and preclinical evidence that highlights the glucose-dependent insulinotropic peptide receptor system as a novel therapeutic central target for the management of nausea and emesis.

2020 ASCO, 2023 NCCN, 2023 MASCC/ESMO, and 2019 CCO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with various malignancies ranging from early to end stages. In light of frequent changes to the guidelines for optimal management of CINV, we undertook this narrative review to compare the most recent guidelines published by ASCO (2020), NCCN (2023), MASCC/ESMO (2023), and CCO (2019). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, MASCC/ESMO, and CCO guidelines for the treatment and prevention of CINV share many fundamental similarities, the literature surrounding low and minimal emetic risk regimens is lacking. Current data regarding adherence to these guidelines is poor and warrants further investigation to improve care.

MASCC 2023 Patient-Centered Antiemetic Guidelines and Education Statements: an evidence-based and consensus resource for patients.

PURPOSE: The Multinational Association of Supportive Care in Cancer (MASCC)/European Society of Medical Oncology (ESMO) Patient Antiemetic Guideline Committee aimed to (1) adapt the updated evidence-based, clinical guidelines to patient-centered antiemetic guidelines and (2) develop patient education materials and statements. METHODS: The MASCC 2023 Patient Antiemetic Guidelines were created and reviewed by antiemetic experts and patient advocates by incorporating the 2023 MASCC/ESMO antiemetic guidelines into patient-friendly language. Patient Education Statements were developed based on current literature and by utilizing an expert modified Delphi consensus (≥ 75% agreement). Patient advocate/focus group input and patient survey results were further integrated into Patient-Centered Antiemetic Guidelines and Education Statements. RESULTS: Patient-Centered Antiemetic Guidelines were created using patient-friendly language and visual slides. Patient-friendly language was also utilized to communicate the Educational Statements. Key content categories identified for the Educational Statements included the following: nausea/vomiting definitions, causes, risk factors, categories, complications, accompanying symptoms, prophylactic antiemetic treatment, general management, when to call/what to ask the healthcare team, what caregivers can do, and available resources. All identified content met the ≥ 75% expert agreement threshold. Fifteen (15) items demonstrated 100% agreement, 11 items achieved ≥ 90% agreement, and three content items demonstrated 80 ~ 82% agreement. CONCLUSIONS: The inaugural MASCC 2023 Patient Antiemetic Guidelines can help patients and caregivers understand the prevention of nausea and vomiting related to their cancer treatment. Educational Statements provide further patient information. Educating patients on how to utilize guideline antiemetics and the education statements can contribute improvements in the control of anticancer treatment-related nausea and vomiting.

Outcome of antiemetic prophylaxis among pediatric cancer patients receiving moderate to highly emetogenic chemotherapy at pediatric hemato-oncology ward of Tikur Anbessa specialized hospital: A prospective observational study.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a major issue for chemotherapy pediatric patients, especially in developing countries due to limited access to essential antiemetics. This study aimed to assess antiemetic prophylaxis outcomes in pediatric cancer patients at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. METHODS: A longitudinal prospective observational study design was conducted among 201 pediatric cancer patients followed up to 120 h post-chemotherapy. RESULTS: The majority of patients (75.1%) received combination prophylactic antiemetics in the acute phase. Complete response (CR) was the highest in the acute phase (71.1%). Emesis episodes occurred most frequently on the first day of treatment (28.4%) and gradually decreased over time. History of motion sickness, platinum-based chemotherapy, and prior chemotherapy-induced vomiting (CIV) were associated with emesis during the acute phase whereas multiple-day chemotherapy, prior CIV, receipt of antiemetics, and a history of motion sickness in the delayed phase. However, the odds of CIV were reduced with steroid presence in the chemotherapy regimen. CONCLUSIONS: A considerable number of participants could not achieve a CR. It is important for clinicians to be cognizant of risk factors that influence the outcome of antiemetic prophylaxis to achieve better control of CINV among pediatric cancer patients.

Duration of Chemotherapy-Induced Nausea and Vomiting (CINV) as a Predictor of Recurrent CINV in Later Cycles.

BACKGROUND: The relationship between CINV duration and recurrence in subsequent cycles is largely unstudied. Our objective was to determine if patients experiencing CINV in their first cycle of chemotherapy (C1) would face increased risk of CINV in later cycles and whether the duration of the CINV would predict increased risk of recurrence. PATIENTS AND METHODS: Using data from a previously reported phase III trial, we assessed patients' recurrence of breakthrough CINV after antiemetic prophylaxis for anthracycline+cyclophosphamide (AC) for breast cancer, comparing C1 short CINV vs. extended CINV as a secondary analysis. Complete response (CR) and CINV duration were primary and secondary endpoints, respectively. CR was considered prophylaxis success; lack of CR was considered treatment failure (TF). RESULTS: Among 402 female patients, 99 (24.6%) had TF in C1 (TF1). The remaining 303 patients (CR1) had ≥93% CR rates in each subsequent cycle, while the 99 patients with TF1 had TF rates of 49.8% for cycles 2-4 (P < .001). The 51 patients with extended TF (≥3 days) in C1 had recurrent TF in 73/105 later cycles (69.5%, P < .001), while the 48 patients with short TF (1-2 days) in C1 had recurrent TF in 33/108 later cycles (30.6%). The relative risk of recurrence after C1 extended TF was 2.28 (CI 1.67-3.11; P < .001) compared to short TF. CONCLUSIONS: Prophylaxis success in C1 led to >90% repeat success across cycles of AC-based chemotherapy. For patients with breakthrough CINV, extended duration strongly predicted recurrent CINV. The duration of CINV should be closely monitored, and augmenting antiemetic prophylaxis considered for future cycles when extended CINV occurs.

Serotonin type-3 receptor antagonists selectively kill melanoma cells through classical apoptosis, microtubule depolymerisation, ERK activation, and NF-κB downregulation.

Malignant melanoma is a highly metastatic tumour, resistant to treatment. Serotonin type-3 (5-HT3) receptor antagonists, such as tropisetron and ondansetron, are well-tolerated antiemetic drugs commonly used to prevent nausea caused by chemotherapy or radiotherapy. We investigated the anticancer effects of these drugs on melanoma cancer cell lines WM-266-4 and B16F10 with or without paclitaxel. We constructed IC50 curves and performed Chou-Talalay analysis, using data obtained with the MTT assay. Flow cytometry and fluorescent microscopy were used to examine characteristics of the cell cycle, cell death and cytoskeleton changes. Protein levels and activation were analysed by western blotting and molecular docking studies carried out. Data were analysed by one way ANOVA and post hoc testing. Ondansetron and tropisetron showed selective concentration-dependent cytotoxicity in melanoma cell lines WM-266-4 and B16F10. The effect in combination with paclitaxel was synergistic. The drugs did not cause cell cycle arrest but did promote characteristics of classical apoptosis, including accumulation of subG1 DNA, cleaved caspase-3, mitochondrial membrane permeability and phosphatidylserine exposure. As well, the cytosolic calcium level in the melanoma cells was enhanced, phosphorylated ERK1/2 induced and NF-κB inhibited. Finally, the formation of microtubules was shown to be impaired in melanoma cells treated with ondansetron or tropisetron. Docking studies were used to predict that these drugs could bind to the colchicine binding site on the tubulin molecule. Antiemetic drugs, already given in combination with chemotherapy, may enhance the cytotoxic effect of chemotherapy, following successful delivery to the tumour site.

Postoperative nausea and vomiting: is the big little problem becoming a smaller little problem?

Postoperative nausea and vomiting (PONV) has been identified as a big (very frequently encountered) little (not linked to life-threatening outcomes) problem. Traditional drugs (dexamethasone, droperidol or similar drugs, serotonin receptor antagonists) each have significant but limited effect, leading to an increasing use of combination therapies. High-risk patients, often identified through use of risk scoring systems, remain with a significant residual risk despite combining up to three traditional drugs. A recent correspondence in this Journal proposes the use of up to five anti-emetic drugs to further minimise the risk. This disruptive strategy was supported by favourable initial results, absence of side-effects and lower acquisition costs of the added new drugs (aprepitant and palonosetron) because of their recent loss of patent protection. These results are provocative and hypothesis generating, but need confirmation and do not warrant immediate changes in clinical practice. The next steps will also necessitate wider implementation of protocols protecting patients from PONV and a search for additional drugs and techniques aimed at treating established PONV.

Work loss and activity impairment due to extended nausea and vomiting in patients with breast cancer receiving CINV prophylaxis.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV)'s impact on work loss remains poorly described. We evaluated associations between the duration of CINV episodes, CINV-related work loss (CINV-WL), and CINV-related activity impairment (CINV-AI) in patients with breast cancer receiving highly emetogenic chemotherapy. METHODS: We analyzed data from a prospective CINV prophylaxis trial of netupitant/palonestron and dexamethasone for patients receiving an anthracycline and cyclophosphamide (AC) for breast cancer (NCT0340371). Over the observed CINV duration (0-5 days), we analyzed patient-reported CINV-WL and CINV-AI for the first two chemotherapy cycles. We categorized patients as having either extended (≥ 3 days) or short (1-2 days) CINV duration and quantified its impact on work using the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS: Overall, we captured data for 792 cycles in 402 women, including 136 (33.8%) employed patients with 35.3% reporting CINV. Of those with CINV, patients reported CINV-WL in 26 cycles and CINV-AI in 142 cycles. Of those with CINV, 55.3% of extended CINV cycles experienced CINV-WL compared to 16.7% of short CINV cycles (p < 0.001). The relative risk of CINV-WL between extended and short CINV was 3.32 (p < 0.01) for employed patients. The mean difference in CINV-AI scores (higher = worse) between extended and short duration CINV was 5.0 vs. 3.0 (p < 0.001). CONCLUSION: Extended (≥ 3 days) CINV was associated with more than triple the risk of CINV-WL and higher CINV-AI compared with short CINV.

2023 Updated MASCC/ESMO Consensus Recommendations: prevention of radiotherapy- and chemoradiotherapy-induced nausea and vomiting.

PURPOSE: Radiotherapy and chemoradiotherapy-induced nausea and vomiting (RINV and C-RINV) are common and distressing, and there is a need for guidance for clinicians to provide up to date optimal antiemetic prophylaxis and treatment. Through a comprehensive review of the literature concerning RINV and C-RINV, this manuscript aims to update the evidence for antiemetic prophylaxis and rescue therapy and provide a new edition of recommendations for the MASCC/ESMO antiemetic guidelines for RINV and C-RINV. METHODS: A systematic review of the literature including data published from May 1, 2015, to January 31, 2023, was performed. All authors assessed the literature. RESULTS: The searches yielded 343 references; 37 met criteria for full article review, and 20 were ultimately retained. Only one randomized study in chemoradiation had the impact to provide new recommendations for the antiemetic guideline. Based on expert consensus, it was decided to change the recommendation for the "low emetic risk" category from "prophylaxis or rescue" to "rescue" only, while the drugs of choice remain unchanged. CONCLUSION: As for the previous guideline, the serotonin receptor antagonists are still the cornerstone in antiemetic prophylaxis of nausea and vomiting induced by high and moderate emetic risk radiotherapy. The guideline update provides new recommendation for the management of C-RINV for radiotherapy and concomitant weekly cisplatin. To avoid overtreatment, antiemetic prophylaxis is no longer recommended for the "low emetic risk" category.

Efficacy and safety of 5HT3RA, DEX, and NK1RA for the prevention of FOLFIRINOX-induced nausea and vomiting in patients with pancreatic cancer: a retrospective cohort study.

PURPOSE: Modified FOLFIRINOX (mFFX), a standard chemotherapy regimen for advanced pancreatic cancer (APC), is expected to be associated with a higher risk of chemotherapy-induced nausea and vomiting (CINV). Herein, we conducted a retrospective cohort study to evaluate the efficacy and safety of a three-drug combination of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA), dexamethasone (DEX), and neurokinin 1 receptor antagonists (NK1RA) for the prevention of CINV during mFFX therapy. METHODS: This study enrolled patients with APC who received mFFX as initial therapy with a combination of 5HT3RA, DEX, and NK1RA as antiemetic prophylaxis. The primary endpoint was the complete response (CR) rate during cycle 1, which was defined as no emetic episodes and no rescue medication use during the overall period (0-120 h). Safety was also evaluated with a focus on hyperglycemia, which is a concern in patients with APC. RESULTS: Seventy patients were eligible for this retrospective analysis. The CR rate during the overall period was 51.4%. Significant nausea, defined as grade 2 or higher, peaked to 77.1% on days 4-5, but remained above 65% until day 7. Hyperglycemia occurred in 37.1% of patients, and 34.3% were grade 3 hyperglycemia. CONCLUSIONS: CINV induced by mFFX was poorly controlled even with prophylactic antiemetic therapy using 5HT3RA, DEX, and NK1RA, and was found to persist beyond 5 days. Enhanced antiemetic measures for mFFX are desirable. However, in patients with diabetes mellitus complications, sparing of steroids and glycemic control should be considered.

ST36 acupoint injection with anisodamine for postoperative nausea and vomiting in female patients after bariatric surgery: a prospective, randomized controlled trial.

BACKGROUND: The use of multimodal pharmacological prophylactic regimes has decreased postoperative nausea and vomiting (PONV) in general but it still occurs in over 60% of female patients after bariatric surgery. This study aimed to evaluate the efficacy of ST36 acupoint injection with anisodamine in prevention of PONV among female patients after bariatric surgery. METHODS: Ninety patients undergoing laparoscopic sleeve gastrectomy were randomly allocated to anisodamine or control group at the ratio of 2:1. Anisodamine or normal saline was injected into Zusanli (ST36) bilaterally after induction of general anesthesia. The incidence and severity of PONV were assessed during the first 3 postoperative days and at 3 months. The quality of early recovery of anesthesia, gastrointestinal function, sleep quality, anxiety, depression, and complications were also evaluated. RESULTS: Baseline and perioperative characteristics were comparable between two groups. In the anisodamine group, 25 patients (42.4%) experienced vomiting within postoperative 24 h compared with 21 (72.4%) in the control group (relative risk 0.59; 95% confidence interval 0.40-0.85). Time to first rescue antiemetic was 6.5 h in anisodamine group, and 1.7 h in the control group (P = 0.011). Less rescue antiemetic was required during the first 24 h in the anisodamine group (P = 0.024). There were no differences in either postoperative nausea or other recovery characteristics. CONCLUSIONS: The addition of ST36 acupoint injection with anisodamine significantly reduced postoperative vomiting without affecting nausea in female patients with obesity undergoing laparoscopic sleeve gastrectomy.

Multi-institutional survey of antiemetic therapy in lung cancer patients treated with carboplatin in Hokushin region.

OBJECTIVE: Appropriate monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with prophylactic antiemetics is important for cancer patients. This study was performed to validate the clinical practice of antiemetic use with carboplatin-based chemotherapy in lung cancer patients in the Hokushin region (Toyama, Ishikawa, Fukui, and Nagano prefectures), Japan. METHODS: We surveyed retrospective data of newly diagnosed and registered lung cancer patients initially treated with carboplatin-based chemotherapy in 21 principal hospitals in the Hokushin region linked with health insurance claims data between 2016 and 2017. RESULTS: A total of 1082 lung cancer patients (861 [79.6%] men, 221 [20.4%] women; median age 69.4 years [range, 33-89 years]). All patients received antiemetic therapy, with 613 (56.7%) and 469 patients (43.3%) receiving 5-hydroxytryptamine-3 receptor antagonist/dexamethasone double regimen and 5-hydroxytryptamine-3 receptor antagonist/dexamethasone/neurokinin-1 receptor antagonist triple regimen, respectively. However, the rates of double regimen and use of palonosetron were higher in Toyama and Fukui prefectures. Thirty-nine patients (3.6%) changed from double to triple regimen, while 41 patients (3.8%) changed from triple to double regimen after the second cycle, but six of these returned to triple antiemetics in subsequent cycles. CONCLUSION: Adherence to antiemetic guidelines in clinical practice was high in Hokushin region. However, rates of double and triple antiemetic regimens differed between the four prefectures. Simultaneous analysis of nationwide registry and insurance data was valuable for evaluating and comparing the differences in the status of antiemesis and management.

Droperidol Use in the Emergency Department: A Clinical Review.

BACKGROUND: Droperidol is a butyrophenone, with antiemetic, sedative, anxiolytic, and analgesic properties. Although droperidol was once widely used in both emergency and perioperative settings, use of the medication declined rapidly after a 2001 U.S. Food and Drug Administration (FDA) boxed warning called the medication's safety into question. OBJECTIVE: The purpose of this clinical review was to provide evidence-based answers to questions about droperidol's safety and to examine its efficacy in its various clinical indications. DISCUSSION: Droperidol is an effective sedative, anxiolytic, analgesic, and antiemetic medication. As a sedative, when compared with haloperidol, droperidol has faster onset, as well as greater efficacy, in patients experiencing acute psychosis, with no increase in adverse events. As an antiemetic, droperidol has been found to have equal or greater efficacy in reducing nausea and vomiting than ondansetron and metoclopramide, with similar adverse effects and the added effect of reducing the need for rescue analgesia in these patients. As an analgesic, droperidol is effective for migraines and has opioid-sparing effects when used to treat abdominal pain. Droperidol is a particularly useful adjunct in patients who are opioid-tolerant, whose pain is often difficulty to manage adequately. CONCLUSIONS: Droperidol seems to be effective and safe, despite the boxed warning issued by the FDA. Droperidol is a powerful antiemetic, sedative, anxiolytic, antimigraine, and adjuvant to opioid analgesia and does not require routine screening with electrocardiography when used in low doses in otherwise healthy patients before administration in the emergency department.

Pharmacokinetics of intramuscular maropitant in pigs (Sus scrofa domesticus).

Pigs are at risk of vomiting from medical conditions as well as the emetic side effects of drugs administered for peri-operative manipulations, but there is a lack of pharmacokinetic data for potential anti-emetic therapies, such as maropitant, in this species. The main objective of this study was to estimate plasma pharmacokinetic parameters for maropitant in pigs after a single intramuscular (IM) administration dosed at 1.0 mg/kg. A secondary objective was to estimate pilot pharmacokinetic parameters in pigs after oral (PO) administration at 2.0 mg/kg. Maropitant was administered to six commercial pigs at a dose of 1.0 mg/kg IM. Plasma samples were collected over 72 h. After a 7-day washout period, two pigs were administered maropitant at a dose of 2.0 mg/kg PO. Maropitant concentrations were measured via liquid chromatography/mass spectrometry (LC-MS/MS). A non-compartmental analysis was used to derive pharmacokinetics parameters. No adverse events were noted in any of the study pigs after administration. Following single IM administration, maximum plasma concentration was estimated at 412.7 ± 132.0 ng/mL and time to maximum concentration ranged from 0.083 to 1.0 h. Elimination half-life was estimated at 6.7 ± 1.28 h, and mean residence time was 6.1 ± 1.2 h. Volume of distribution after IM administration was 15.9 L/kg. Area under the curve was 1336 ± 132.0 h*ng/mL. The relative bioavailability of PO administration was noted to be 15.5% and 27.2% in the two pilot pigs. The maximum systemic concentration observed in the study pigs after IM administration was higher than what was observed after subcutaneous administration in dogs, cats, or rabbits. The achieved maximum concentration exceeded the concentrations for anti-emetic purposes in dogs and cats; however, a specific anti-emetic concentration is currently not known for pigs. Further research is needed into the pharmacodynamics of maropitant in pigs to determine specific therapeutic strategies for this drug.

Droperidol lowers the shivering threshold in rabbits.

PURPOSE: Perioperative shivering is common and can occur as a result of hypothermia or changes in the threshold of thermoregulation. Droperidol usage for anesthesia is currently limited to its sedative and antiemetic effects. We investigated the effects of high and low doses of droperidol on the shivering threshold in rabbits. METHODS: Forty-two male Japanese white rabbits were anesthetized with isoflurane and randomly assigned to the control, high-dose, or low-dose group. Rabbits in the high-dose group received a 5 mg/kg droperidol bolus followed by continuous infusion at 5 mg/kg/h, those in the low-dose group received a 0.5 mg/kg droperidol bolus, and those in the control group received the same volume of saline as the high-dose group. Body temperature was reduced at a rate of 2-3 °C/h, and the shivering threshold was defined as the subject's core temperature (°C) at the onset of shivering. RESULTS: The shivering thresholds in the control, high-dose, and low-dose groups were 38.1 °C ± 1.1 °C, 36.7 °C ± 1.2 °C, and 36.9 °C ± 1.0 °C, respectively. The shivering thresholds were significantly lower in the high-dose and low-dose groups than in the control group (P < 0.01). The thresholds were comparable between the high-dose and low-dose groups. CONCLUSIONS: Droperidol in high and low doses effectively reduced the shivering threshold in rabbits. Droperidol has been used in low doses as an antiemetic. Low doses of droperidol can reduce the incidence of shivering perioperatively and during the induction of therapeutic hypothermia.

Antiemetics and Apfel Scores in Orthopedic Surgery.

Background: Postoperative nausea and vomiting (PONV) is a common complication following surgery. Only a few risk factors have consistently been reported to be independent predictors for PONV. Aim: To report Apfel scores for orthopedic patients then correlate these scores to the number of antiemetics prescribed and subsequently administered in both the perioperative and post operative setting and determine if screening for Apfel scores is beneficial to predict PONV. Methods: A retrospective analysis of patients admitted under orthopedic units between 1st July 2020 and 31st July 2020 was conducted at a tertiary teaching hospital in Australia. Patients were screened and allocated an Apfel score and antiemetics agents prescribed and subsequently administered were recorded. Results: A total of 115 patients were screened for inclusion. Of these 4 patients met this exclusion criteria, resulting in a total sample size of 111 patients. An Apfel score of 2 was reported in 45.0% of patients, followed by 28.8% of patients scoring 3, with 12.6% scoring one. Only 5.4% of patients scored the highest risk of 4, with 8.2% of patients with no Apfel score documented. Conclusion: Orthopedic patients tend to score 2 or more in their Apfel score placing them at higher risk of postoperative nausea and/or vomiting according to the collectively validated Apfel's simplified risk score. There was no statistically significant relationship between the Apfel score and the number of antiemetic agents prescribed or administered from both the perioperative and post-operative setting following orthopedic surgery in this cohort of adult patients.

Association between early ondansetron administration and in-hospital mortality in critically ill patients: analysis of the MIMIC-IV database.

BACKGROUND: While ondansetron (OND) is widespread availability, the contribution of OND to improve patient outcomes among intensive care unit (ICU) patients has not been examined. This study aimed to illustrate the association between early OND use and in-hospital mortality in critically ill patients and investigate whether this association differed according to OND dose. METHODS: The MIMIC-IV database was employed to identify patients who had and had not received OND. Statistical approaches included multivariate logistic regression, propensity score matching (PSM), and propensity score-based inverse probability of treatment weighting (IPTW) models to ensure the robustness of our findings. RESULTS: In total, 51,342 ICU patients were included. A significant benefit in terms of in-hospital mortality was observed in the OND patients compared to the non-OND group in the early stage [odds ratio (OR) = 0.75, 95% CI 0.63-0.89, p < 0.001]. In the circulatory system group, the early OND administration was associated with improved in-hospital mortality in ICU patients (OR 0.48, 95% CI 0.34-0.66; P < 0.001). The risk of in-hospital mortality was also lower in early OND users than in non-OND users both in the medical admission group and the surgical ICU admission group, and ORs were 0.57 (95% CI 0.42-0.76; P < 0.001) and 0.79 (95% CI 0.62-0.91; P < 0.001), respectively. A positive role of daily low- and moderate-dose OND treatment in early-stage was showed on the in-hospital mortality in PSM cohort, and the ORs were 0.75 (95% CI 0.62-0.90; P < 0.001) and 0.63 (95% CI 0.43-0.91; P < 0.001), respectively. The relationship between the daily low- and moderate-dose of OND and in-hospital mortality was also significant in ICU patients with cardiovascular diseases, and ORs were 0.51(95% CI 0.36-0.73; P < 0.001), and 0.26(95% CI 0.11-0.65; P < 0.001), respectively. Daily low-to-moderate dose of OND was also associated with in-hospital mortality in ICU entire cohort. CONCLUSIONS: Early OND use is closely associated with lower in-hospital mortality in ICU patients. Daily low-to-moderate dose of OND application is protective against in-hospital mortality. This association is more evident in the circulatory system group.

Antiemetic prophylaxis for chemoradiotherapy-induced nausea and vomiting in locally advanced head and neck squamous cell carcinoma: a prospective phase II trial.

BACKGROUND: There is sparse research reporting effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). METHODS: Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m2 (33 mg/m2/days [d]1-3) every 3 weeks for two cycles. All patients were given oral aprepitant 125 mg once on d1, then 80 mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8 mg on d2-5. The primary endpoint was complete response (CR). Pursuant to δ = 0.2 and α = 0.05, the expected CR rate was 80%. RESULTS: A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% confidence interval [CI]: 72.1-94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9-96.1) and 89.2% (95% CI: 74.6-97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3-84.7). The emesis-free and nausea-free responses in the overall phase were 88.4% (95% CI: 74.9-96.1) and 60.5% (95% CI: 44.4-75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1-2. There was no grade 4 or 5 treatment-related toxicity with antiemetic usage. CONCLUSION: The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving radiotherapy and concomitant high-dose cisplatin chemotherapy.

Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial.

BACKGROUND: Clinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has on this experience. METHODS: In this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately. RESULTS: A total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk [RR]=0.79; 95% confidence interval [CI], 0.56-1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37-0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20-202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery. CONCLUSIONS: Administration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

A pooled analysis of adding olanzapine to guideline-recommended antiemetic therapy for breast cancer patients treated with an anthracycline and cyclophosphamide in prospective and retrospective studies.

PURPOSE: As an antipsychotic agent that targets multiple neurotransmitter receptors, olanzapine has been added to antiemetic therapies. For better understanding the application of olanzapine in antiemetic strategies for breast cancer patients who suffered anthracycline plus cyclophosphamide-induced nausea and vomiting, we comprehensively reviewed the antiemetic researches related to olanzapine and pooled-analyzed the results to confirm the efficacy and safety of olanzapine in breast cancer. METHODS: PubMed, Web of Science, EMBASE, and Cochrane CENTRAL databases were searched from inception through Sep 15, 2021. Both prospective and retrospective studies were eligible. The primary outcomes were complete response (defined as no vomiting and no use of rescue medications) and no nausea rate, and the secondary outcome was treatment-related adverse events. RESULTS: Four studies with 466 breast cancer patients were identified in the pooled analysis. In the acute period (0-24 h), the olanzapine group had significantly higher rates of complete response (71.3% vs 48.1%, odds ratio [OR]: 2.66, 95% confidence interval [CI] 1.39-5.11, p = 0.003) and no nausea (70.0% vs 43.0%, OR: 3.55, 95% CI 1.76-7.18, p = 0.04) than the placebo group, while in the delayed period, the olanzapine group was also superior to the placebo group in terms of the complete response (82.5% vs 63.3%, OR: 3.81, 95% CI 1.58-9.15, p = 0.003) and no nausea (66.3% vs 51.9%, OR: 2.08, 95% CI 1.03-4.21, p = 0.04) rates. During the overall period in prospective studies, the proportions of complete response (50.0% vs 34.2%, OR: 1.93, p = 0.04) and no nausea (51.3% vs 25.3%, OR: 3.40, p = 0.0006) in the olanzapine group were higher than those in the placebo group. CONCLUSION: Highly emetogenic chemotherapy breast patients could benefit from olanzapine-contained antiemetic therapy. Furthermore, since the cost is low, olanzapine is worth further clinical application and promotion.