Comparison of prophylaxis strategy for postoperative nausea and vomiting and its incidence before and after the implementation of 5-hydroxytryptamine 3 in surgical setting: a single-center, retrospective study.

PURPOSE: To investigate the association between adherence to guideline-recommended risk-based postoperative nausea and vomiting (PONV) prophylaxis, the antiemetics used for PONV prophylaxis, and the incidence of PONV in patients who were underwent general anesthesia before and after 5-HT3 receptor antagonists became available. METHODS: Patients (≥ 20 years old) who were extubated after scheduled surgery and returned to general wards between January 2021 and February 2022 and between June 2022 and July 2023 were included. Risk factors included age < 50, female, motion sickness, nonsmoker, surgical factors, and postoperative opioid use. Two and three or more prophylaxis were recommended for patients with one or two and three or more risk factors, respectively. The primary outcome was the number of patients who received adequate prophylaxis, and the secondary outcomes were antiemetic agents used during anesthesia and the incidence of PONV on postoperative days 0 and 1. PONV was defined as documented PONV or rescue antiemetic administration. RESULTS: From January 2021 to February 2022 and from June 2022 to July 2023, 2342 and 2682 patients were included, respectively. Before ondansetron became available, more D2 receptor antagonists were used (p < 0.001), and after ondansetron became available, both ondansetron (p < 0.001) and propofol (p < 0.001) were given more frequently. Before and after ondansetron became available, the number of patients with adequate prophylaxis was 3.7% and 9.2%, respectively (p < 0.001), and the incidence of PONV on postoperative days 0 and 1 was 44.6% and 44.0%, respectively (p = 0.67). CONCLUSION: The availability of ondansetron increased the number of patients with adequate PONV prophylaxis, but did not decrease the incidence of PONV.

Multi-dose Oral Ondansetron for Pediatric Gastroenteritis: study Protocol for the multi-DOSE oral ondansetron for pediatric Acute GastroEnteritis (DOSE-AGE) pragmatic randomized controlled trial.

BACKGROUND: There are limited treatment options that clinicians can provide to children presenting to emergency departments with vomiting secondary to acute gastroenteritis. Based on evidence of effectiveness and safety, clinicians now routinely administer ondansetron in the emergency department to promote oral rehydration therapy success. However, clinicians are also increasingly providing multiple doses of ondansetron for home use, creating unquantified cost and health system resource use implications without any evidence to support this expanding practice. METHODS/DESIGN: DOSE-AGE is a randomized, placebo-controlled, double-blinded, six-center, pragmatic clinical trial being conducted in six Canadian pediatric emergency departments (EDs). In September 2019 the study began recruiting children aged 6 months to 18 years with a minimum of three episodes of vomiting in the 24 h preceding enrollment, <72 h of gastroenteritis symptoms and who were administered a dose of ondansetron during their ED visit. We are recruiting 1030 children (1:1 allocation via an internet-based, third-party, randomization service) to receive a 48-h supply (i.e., six doses) of ondansetron oral solution or placebo, administered on an as-needed basis. All participants, caregivers and outcome assessors will be blinded to group assignment. Outcome data will be collected by surveys administered to caregivers 24, 48 and 168 h following enrollment. The primary outcome is the development of moderate-to-severe gastroenteritis in the 7 days following the ED visit as measured by a validated clinical score (the Modified Vesikari Scale). Secondary outcomes include duration and frequency of vomiting and diarrhea, proportions of children experiencing unscheduled health care visits and intravenous rehydration, caregiver satisfaction with treatment and safety. A preplanned economic evaluation will be conducted alongside the trial. DISCUSSION: Definitive data are lacking to guide the clinical use of post-ED visit multidose ondansetron in children with acute gastroenteritis. Usage is increasing, despite the absence of supportive evidence. The incumbent additional costs associated with use, and potential side effects such as diarrhea and repeat visits, create an urgent need to evaluate the effect and safety of multiple doses of ondansetron in children focusing on post-emergency department visit and patient-centered outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03851835. Registered on 22 February 2019.

An overview of intravenous amisulpride as a new therapeutic option for the prophylaxis and treatment of postoperative nausea and vomiting.

Introduction: Current therapies of postoperative nausea and vomiting (PONV) are based on a combination of antiemetics from different pharmacological classes. Dopamine receptor antagonists are one of the cornerstones of such multimodal antiemetic approach, with droperidol being the best studied representative of this group. Droperidol's use has significantly declined after the FDA's black-box warning in 2001 due to its QT-prolonging properties. Amisulpride is a promising antiemetic agent which could fill this gap.Areas covered: In this review, the authors discuss the pharmacological profile as well as clinical safety and efficacy of intravenous amisulpride and its relevance in the management of PONV. The article is based on a Medline, ClinicalTrials.gov, and Cochrane Library search for studies on amisulpride conducted so far.Expert opinion: Promising clinical results on Barhemsys®, an intravenous formulation of amisulpride, make it a potential future drug of choice from the dopamine receptor antagonist group, replacing droperidol after its safety concerns. Amisulpride's success on the market will mostly be determined by its cost-effectiveness and it will likely find a brighter use on the US-market, where the black-box warning led to droperidol's withdrawal, while in many European countries, droperidol is still being used as an antiemetic.

Netupitant plus palonosetron is a cost-effective treatment for the prophylaxis of chemotherapy-induced nausea and vomiting in highly and moderately emetogenic cancer treatment.

Introduction: The analysis was conducted to assess a cost-efficacy analysis of new antiemetic drugs (netupitant plus palonosetron (NEPA)) for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in highly and moderately emetogenic chemotherapy for cancer treatment. Areas covered:The present evaluation was restricted to pivotal phase III randomized controlled trials (RCTs) of NEPA versus (vs.) palonosetron for the prophylaxis of CINV. We calculated the pharmacological costs necessary to get the benefit in complete response (CR), for each trial. Our analysis evaluated 2 RCTs, including 1720 patients. Referring to both highly and moderately emetogenic chemotherapy, NEPA plus DEX was economic superior to palonosetron (PALO) plus DEX, with 13 312 € and 7885 € gain in medical costs every 100 patients treated, respectively. The cost-effectiveness ratios (CERs) (€/CR) in highly emetoge nic risk were 1.24 and 13.23 for the NEPA and PALO group, respectively and 1.49 and 15.20 for the same groups in moderately emetogenic risk. The incremental cost-effectiveness ratio (ICER) between the groups was 1016.18 €/CR and 1024.03 €/CR in highly and moderately emetogenic risk, respectively. Expert opinion:The combination of NEPA plus DEX is cost-effective for preventing CINV in highly and moderately (AC-based) emetogenic cancer treatment.

Comparative Cost-utility Analysis Between Aprepitant- and Fosaprepitant-containing Regimens To Prevent Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy in Japan.

PURPOSE: Clinical trials have shown that the addition of aprepitant (APR) or a phosphorylated prodrug of aprepitant, fosaprepitant (FosAPR) as prophylactic antiemetic therapy consisting of a 5-hydrotryptamine-3 receptor antagonist and dexamethasone is effective in patients receiving highly emetogenic chemotherapy. These combination therapies have been commonly used in Japan. In the present study, we performed a cost-utility analysis of APR and FosAPR in the context of the Japanese medical insurance system, and economic efficiency was compared. METHODS: Data from randomized controlled trials that examined the efficacy of APR and FosAPR in the Japanese population were used. A decision tree was constructed to estimate the effectiveness of chemotherapy for 5 days from the day of the treatment and the cost associated with outpatient chemotherapy from the perspective of a payer. Health outcome was expressed in quality-adjusted life-years (QALYs), and costs were estimated based on medical fees and drug prices from 2018. An incremental cost-effectiveness ratio (ICER) was calculated for each regimen containing either APR or FosAPR. The robustness of the model was assessed using 1-way and probabilistic sensitivity analysis. FINDINGS: The base-case analysis estimated that the addition of APR or FosAPR would have incremental effects of 0.00166 and 0.00143 QALY and incremental costs of 8305 and 11,348 JPY (74 and 101 USD [1 USD = 112.17 JPY]), resulting in ICERs of 4,992,172 and 7,955,560 JPY/QALY (44,505 and 70,924 USD/QALY), respectively. Sensitivity analysis revealed that the probability of a complete response for delayed chemotherapy-induced nausea and vomiting had the most influence on the ICERs. Reductions in the drug costs of APR and FosAPR also had an effect on the ICERs. According to the probabilistic sensitivity analysis, APR and FosAPR were dominant in terms of cost-effectiveness in 48.7% and 8.55% of cases, respectively. IMPLICATIONS: The ICER of outpatient prophylactic antiemetic therapy in patients receiving highly emetogenic chemotherapy was calculated in the context of the Japanese medical insurance system. Assuming the willingness-to-pay of 5,000,000 JPY/QALY based on the calculated ICER, our findings suggest that although the addition of APR is cost-effective, FosAPR is not cost-effective.

Real-world effectiveness of palonosetron-based antiemetic regimens: preventing chemotherapy-induced nausea and vomiting.

Aim: To evaluate real-world effectiveness of guideline-recommended palonosetron-containing antiemetic regimens in patients receiving highly (HEC) or moderately emetogenic (MEC) chemotherapy. Patients & methods: This retrospective analysis used records of adults receiving first-line chemotherapy and a three-drug palonosetron-containing antiemetic regimen for HEC or palonosetron-containing antiemetic regimen for MEC (carboplatin). Results: A total of 1587 records were evaluated. For HEC and MEC, respectively, chemotherapy-induced nausea and vomiting (CINV) occurred in 40 versus 44% of patient cycles (p = 0.01), and unscheduled iv. antiemetics in 41 versus 35% (p < 0.05). A total of 48% of HEC patients versus 42% of MEC patients had CINV-related clinic visits (p = 0.05). Conclusion: Palonosetron-containing antiemetic regimens may provide insufficient CINV control. Alternative regimens may improve patient quality of life and reduce healthcare resource utilization.

Randomized Phase II Trial to Compare the Efficacy of Haloperidol and Olanzapine in the Control of Chemotherapy-Induced Nausea and Vomiting in Nepal.

PURPOSE: The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP). RESULTS: Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7% v 71.8%; P = .78). In the acute period (day 1) and the delayed period (days 2 to 5), CNP was similar between OLN and HAL (acute: 84.3% v 81.2%; delayed: 68.7% v 75%). No difference was identified in the rate of CEP during the overall period (81.2% with OLN v 78.1% with HAL; P = .75), during the acute period (93.7% with OLN v 90.6% with HAL), or during the delayed period (84.3% with OLN v 84.3% with HAL). No difference in toxicities was noted between treatment arms. CONCLUSION: In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.

Characterizing and assessing antiemetic underuse in patients initiating highly emetogenic chemotherapy.

BACKGROUND: Patients initiating highly emetic chemotherapy (HEC) are at a 90% risk of chemotherapy-induced nausea and vomiting (CINV). Despite guideline-concordant antiemetic prescribing preventing CINV in up to 80% of patients, studies suggest that guideline-concordant antiemetic regimen use by patients initiating HEC is sub-optimal. However, these studies have been limited to single-site or single-cancer type with limited generalizability. The objective of this study was to describe antiemetic fill regimens and to assess predictors of underuse in the USA. METHODS: Our study population was adult patients under the age of 65 with cancer initiating intravenous HEC between 2013 and 2015 with employer-sponsored insurance in the IBM Watson/Truven MarketScan Commercial Claims database (N = 31,923). Descriptive statistics were used to explain antiemetic prescribing patterns, including antiemetic underuse. Modified Poisson regression was used to identify factors associated with antiemetic underuse. RESULTS: Among individuals initiating HEC, 49% underused guideline-concordant antiemetics. Most classified as under-using lacked an NK1 fill. While dexamethasone and 5HT3A uptake was over 80%, olanzapine use was minimal. Having lower generosity for prescription and medical benefits (paying more versus less than 20% out-of-pocket) increased the underuse risk by 3% and 4% (RR,1.03; 95% CI,1.01-1.05; P = 0.01 and RR,1.04; CI, 1.00-1.09; P = 0.03), respectively. Additionally, compared to receiving chemotherapy in the physician office setting, patients were at a 28% (RR, 1.28; 95% CI, 1.25-1.30; P < 0.0001) higher underuse risk in the outpatient hospital setting. CONCLUSION: Antiemetic underuse is high in patients initiating HEC, potentially leading to avoidable CINV events. We found that insurance generosity has a minimal effect on antiemetic guideline concordance in this population, suggesting discordance may be the result of site of care as well as gaps in provider knowledge or accountability.

CARer-ADministration of as-needed subcutaneous medication for breakthrough symptoms in homebased dying patients (CARiAD): study protocol for a UK-based open randomised pilot trial.

BACKGROUND: While the majority of seriously ill people wish to die at home, only half achieve this. The likelihood of someone dying at home often depends on the availability of able and willing lay carers to support them. Dying people are usually unable to take oral medication. When top-up symptom relief medication is required, a clinician travels to the home to administer injectable medication, with attendant delays. The administration of subcutaneous injections by lay carers, though not widespread practice in the UK, has proven key in achieving home deaths in other countries. Our aim is to determine if carer-administration of as-needed subcutaneous medication for four frequent breakthrough symptoms (pain, nausea, restlessness and noisy breathing) in home-based dying patients is feasible and acceptable in the UK. METHODS: This paper describes a randomised pilot trial across three UK sites, with an embedded qualitative study. Dyads of adult patients/carers are eligible, where patients are in the last weeks of life and wish to die at home, and lay carers who are willing to be trained to give subcutaneous medication. Dyads who do not meet strict risk assessment criteria (including known history of substance abuse or carer ability to be trained to competency) will not be approached. Carers in the intervention arm will receive a manualised training package delivered by their local nursing team. Dyads in the control arm will receive usual care. The main outcomes of interest are feasibility, acceptability, recruitment rates, attrition and selection of the most appropriate outcome measures. Interviews with carers and healthcare professionals will explore attitudes to, experiences of and preferences for giving subcutaneous medication and experience of trial processes. The study has obtained full ethical approval. DISCUSSION: This study will rehearse the procedures and logistics which will be undertaken in a future definitive randomised controlled trial and will inform the design of such a study. Findings will illuminate methodological and ethical issues pertaining to researching last days of life care. The study is funded by the National Institute for Health Research (Health Technology Assessment [HTA] project 15/10/37). TRIAL REGISTRATION: ISRCTN, ISRCTN 11211024 . Registered on 27 September 2016.

Effectiveness of Antiemetic Regimens for Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Network Meta-Analysis.

BACKGROUND: It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis. METHODS: Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided. RESULTS: We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56-1.97, and OR, 2.25; 95% CrI, 1.66-3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR. CONCLUSION: Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients. IMPLICATIONS FOR PRACTICE: Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

Preoperative Risk Assessment to Guide Prophylaxis and Reduce the Incidence of Postoperative Nausea and Vomiting.

PURPOSE: This article describes the implementation of a postoperative nausea and vomiting (PONV) risk prediction and prophylaxis protocol. DESIGN: This is a retrospective pre/post implementation quality improvement project. METHODS: This project used chart reviews to assess the impact of the implemented PONV assessment and prophylaxis in a sample population of adult females undergoing gynecologic surgical procedures. FINDINGS: The mean number of prophylactic antiemetics administered significantly increased during the postimplementation period from 3.64 (SD, 0.878) in the preimplementation period to 4.07 (SD, 1.021) in the postimplementation period (P < .001). The greatest increase in antiemetic administration occurred in the moderate-risk (risk score, 4) and the high-risk (risk score, 5 to 6) groups. The incidence of PONV decreased from 32.3% in the preimplementation period to 28.9% in the postimplementation period; however, this reduction did not meet statistical significance. Antiemetic administration compliance increased from 37% in the preimplementation group to 61% in the postimplementation group (P < .001). CONCLUSIONS: The results of this project suggest that a risk-tailored approach to PONV prophylaxis using a risk assessment tool along with treatment recommendations is effective at reducing the incidence of PONV. The effectiveness of this approach is limited by the involvement of the anesthesia providers responsible for completing the assessments and administering PONV prophylaxis.

Cost analysis of enhanced recovery after surgery in microvascular breast reconstruction.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways have been shown in multiple surgical specialties to decrease hospital length of stay (LOS) after surgery. ERAS in breast reconstruction has been found to decrease hospital LOS and inpatient opioid use. ERAS protocols can facilitate a patient's recovery and can potentially increase the quality of care while decreasing costs. METHODS: A standardized ERAS pathway was developed through multidisciplinary collaboration. It addressed all phases of surgical care for patients undergoing free-flap breast reconstruction utilizing an abdominal donor site. In this retrospective cohort study, clinical variables associated with hospitalization costs for patients who underwent free-flap breast reconstruction with the ERAS pathway were compared with those of historical controls, termed traditional recovery after surgery (TRAS). All patients included in the study underwent surgery between September 2010 and September 2014. Predicted costs of the study groups were compared using generalized linear modeling. RESULTS: A total of 200 patients were analyzed: 82 in the ERAS cohort and 118 in the TRAS cohort. Clinical variables that were identified to potentially affect costs were found to have a statistically significant difference between groups and included unilateral versus bilateral procedures (p = 0.04) and the need for postoperative blood transfusion (p = 0.03). The cost regression analysis on the two cohorts was adjusted for these significant variables. Adjusted mean costs of patients with ERAS were found to be $4,576 lesser than those of the TRAS control group ($38,688 versus $43,264). CONCLUSIONS: Implementation of the ERAS pathway was associated with significantly decreased costs when compared to historical controls. There has been a healthcare focus toward prudent resource allocation, which dictates the need for plastic surgeons to recognize economic evaluation of clinical practice. The ERAS pathway can increase healthcare accountability by improving quality of care while simultaneously decreasing the costs associated with autologous breast reconstruction.

Antiemetic Prophylaxis as a Marker of Health Care Disparities in the National Anesthesia Clinical Outcomes Registry.

BACKGROUND: US health care disparities persist despite repeated countermeasures. Research identified race, ethnicity, gender, and socioeconomic status as factors, mediated through individual provider and/or systemic biases; little research exists in anesthesiology. We investigated antiemetic prophylaxis as a surrogate marker for anesthesia quality by individual providers because antiemetics are universally available, indicated contingent on patient characteristics (gender, age, etc), but independent of comorbidities and not yet impacted by regulatory or financial constraints. We hypothesized that socioeconomic indicators (measured as insurance status or median income in the patients' home zip code area) are associated with the utilization of antiemetic prophylaxis (as a marker of anesthesia quality). METHODS: We tested our hypothesis in several subsets of electronic anesthesia records from the National Anesthesia Clinical Outcomes Registry (NACOR), fitting frequentist and novel Bayesian multilevel logistic regression models. RESULTS: NACOR contained 12 million cases in 2013. Six institutions reported on antiemetic prophylaxis for 441,645 anesthesia cases. Only 173,133 cases included details on insurance information. Even fewer (n = 92,683) contained complete data on procedure codes and provider identifiers. Bivariate analysis, multivariable logistic regression, and our Bayesian hierarchical model all showed a large and statistically significant association between socioeconomic markers and antiemetic prophylaxis (ondansetron and dexamethasone). For Medicaid versus commercially insured patients, the odds ratio of receiving the antiemetic ondansetron is 0.85 in our Bayesian hierarchical mixed regression model, with a 95% Bayesian credible interval of 0.81-0.89 with similar inferences in classical (frequentist) regression models. CONCLUSIONS: Our analyses of NACOR anesthesia records raise concerns that patients with lower socioeconomic status may receive inferior anesthesia care provided by individual anesthesiologists, as indicated by less antiemetics administered. Effects persisted after we controlled for important patient characteristics and for procedure and provider influences. Findings were robust to sensitivity analyses. Our results challenge the notion that anesthesia providers do not contribute to health care disparities.

Chemotherapy-Induced Nausea and Vomiting: Incidence and Management in Jordan.

Cancer patients experience a considerable number of symptoms during the course of their disease. Of these symptoms, chemotherapy-induced nausea and vomiting (CINV) is one of the most reported and it increases the cancer burden on patients. This study aims to assess the current status of CINV among Jordanian cancer patients, with regard to its incidence and management. A descriptive cross-sectional survey design was used. The study sample was 185 cancer patients. The mean age of participants was 46.6 years ( SD = 15.5, range = 18-76) and were mainly female (56.8%). The incidence of nausea and vomiting was high at 71.4% and 57.3%, respectively. Most of the patients (89.7%) received a 5-HT3 antagonist therapy combined with corticosteroids therapy (81.1%). This study demonstrated a high incidence rate of all types of CINV, which was undertreated. Antiemetic treatment could be improved by encouraging nurses to introduce the internationally agreed guidelines into their daily clinical practice.

Comparison of treatment patterns and economic outcomes among metastatic pancreatic cancer patients initiated on nab-paclitaxel plus gemcitabine versus FOLFIRINOX.

BACKGROUND: The economic burden of metastatic pancreatic cancer (mPC) is substantial while treatment options are limited. Little is known about the treatment patterns and healthcare costs among mPC patients who initiated first-line gemcitabine plus nanoparticle albumin-bound paclitaxel (nab-P + G) and FOLFIRINOX. METHODS: The MarketScan® claims databases were used to identify adults with ≥2 claims for pancreatic cancer, 1 claim for a secondary malignancy, completed ≥1 cycle of nab-P + G or FOLFIRINOX during 4/1/2013 and 3/31/2015, and had continuous plan enrollment for ≥6 months pre- and 3 months after the first-line treatment. Duration of therapy, per patient per month (PPPM) costs of total healthcare, mPC-related treatment, and supportive care were measured during first-line therapy. RESULTS: 550 mPC patients met selection criteria (nab-P + G, n = 294; FOLFIRINOX, n = 256). There was no difference in duration of therapy (p = 0.60) between nab-P + G and FOLFIRINOX. Compared with FOLFIRINOX, patients with nab-P + G had higher chemotherapy drug costs but lower treatment administration costs and supportive care costs (all p < 0.01). CONCLUSIONS: Patients treated with nab-P + G (vs FOLFIRINOX) had similar treatment duration but lower costs of outpatient prescriptions, treatment administration and supportive care. Lower supportive care costs in the nab-P + G cohort were mainly driven by lower utilization of pegfilgrastim and anti-emetics.

Assessment of absorption of transdermal ondansetron in normal research cats.

Objectives The objective of this study was to assess the absorption of transdermal ondansetron in healthy cats. Methods Five research cats with unremarkable complete blood count, biochemistry and urinalysis were used for both single- and multiple-dose application studies. For single-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied once to the internal ear pinna. Blood samples were collected via jugular catheter over a 48 h period following administration (0, 15 mins, 30 mins, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h). For multiple-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied for five consecutive days before blood samples were obtained in the same manner. Serum was separated and frozen prior to analysis. Ondansetron was measured via liquid chromatography coupled to tandem mass spectrometry. Results Analysis revealed no clinically relevant drug levels in serum after either single- or multiple-dose administration of 4 mg transdermal ondansetron. Conclusions and relevance Transdermal application of 4 mg ondansetron does not result in clinically relevant serum concentrations of drug. Despite characteristics of the drug that imply suitability for transdermal application, this does not appear to be an acceptable method of drug delivery for this medication at this dose. This study highlights the importance of assessing the suitability of each medication for transdermal administration.

Changes in Antiemetic Overuse in Response to Choosing Wisely Recommendations.

IMPORTANCE: Antiemetics are used to prevent chemotherapy-induced nausea and vomiting in patients with cancer. Newer antiemetic agents (serotonin and neurokinin-1 receptor antagonists) have increased efficacy but are expensive. The American Society of Clinical Oncology's first guideline in the 2013 Choosing Wisely (CW) campaign discouraged overuse of expensive antiemetics in patients with low risk of chemotherapy-induced nausea and vomiting. However, little is known about patterns or trends in antiemetic overuse or whether any change has occurred with the publication of the CW recommendations. OBJECTIVE: To estimate the baseline prevalence, trends, determinants, and costs of antiemetic overuse from January 1, 2008, through March 31, 2015. DESIGN, SETTING, AND PARTICIPANTS: From January 1, 2008, through March 31, 2015, this observational study applied descriptive (univariate and bivariate) and multivariable logistic regression analyses to longitudinal health insurance enrollment and nationwide MarketScan insurance claims data for 678 220 privately insured patients receiving chemotherapy before and after the October 29, 2013, announcement of the CW guidelines. The baseline prevalence, trends, determinants, and costs of antiemetic overuse were estimated in cases stratified by risk for chemotherapy-induced nausea and vomiting. MAIN OUTCOMES AND MEASURES: Antiemetic use, overuse measure, and expenses before and after the publication of the CW recommendation, with adjustment for patient and health care professional characteristics. RESULTS: The sample included 678 220 adults who started chemotherapy during the observation period. The average age of the sample was 59.5 years, with 58.2% (n = 394 724) female. Antiemetic overuse occurred in 24.1% (n = 163 451) of patients, with highest rates among those receiving intravenous chemotherapy with high chemotherapy-induced nausea and vomiting risk (32.4% [n = 106 795]). Compared with baseline before the CW, patients had 7.0% lower odds of antiemetic overuse (95% CI, 4.4%-9.5%) during the 6 months after the CW, but this decrease was transitory: the odds of antiemetic overuse were 7.4% (95% CI, 4.6%-10.2%) higher than baseline at 6 months after the CW. Low-risk intravenous chemotherapy agents had overuse that continued to decrease 6 months after the CW. Antiemetic overuse was associated with higher costs. Reducing antiemetic overuse could have paid for 6.1% (95% CI, 5.8%-6.4%) of the chemotherapy drug costs. CONCLUSIONS AND RELEVANCE: Antiemetic overuse is prevalent and results in unnecessary spending associated with systemic chemotherapy treatment. Short-term decreases in antiemetic overuse were associated with the CW recommendation, but sustained decreases occurred in only one risk group.

Prescription of Prophylactic Antiemetic Drugs for Patients Receiving Chemotherapy With Minimal and Low Emetic Risk.

IMPORTANCE: The use of antiemetic drugs for patients receiving chemotherapy with low or minimal emetic risk has been recognized as a growing concern for health care costs and patients' welfare. Relatively few studies have examined antiemetic prophylaxis or treatment of emesis associated with chemotherapy with lower emetic risk. OBJECTIVE: To describe the pattern in Japan of overprescribing prophylactic antiemetic drugs to patients who have received intravenous chemotherapy with minimal or low emetic risk. DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis of a health insurance claims database linked with the hospital-based cancer registry of 122 designated cancer care hospitals covered the period from September 1, 2010, to December 31, 2012. Data were included from patients who (1) were diagnosed with breast, lung, colorectal, stomach, cervical, or prostate cancer; (2) were 20 years or older at the time of the diagnosis; and (3) received intravenous chemotherapy with minimal or low emetic risk. The data from patients with advanced stage cancer (stage IV) were excluded. Data were analyzed from March 20, 2014, to June 30, 2016. MAIN OUTCOMES AND MEASURES: The percentage of chemotherapy administration involving patients prescribed prophylactic antiemetic drugs, namely, a neurokinin 1 receptor antagonist, serotonin receptor antagonist, and/or dexamethasone, was calculated. The costs of potentially unnecessary antiemetic drugs were estimated using the National Health Insurance drug price list for 2011. RESULTS: A total of 8545 patients (5886 women [68.9%] and 2659 men [31.1%]; mean [SD] age, 61.9 [12.8] years) undergoing 73 577 administrations of chemotherapy with minimal emetic risk (2464 patients; 22 619 administrations) or low emetic risk (6081 patients; 50 958 administrations) were identified. Of these, patients who received 24 373 administrations of chemotherapy with a low emetic risk (47.8%) and 633 administrations of chemotherapy with a minimal emetic risk (2.8%) were prescribed serotonin receptor antagonists and dexamethasone. Outpatients in the low emetic risk group underwent more frequent administration of chemotherapy that included prescription of both drugs (53.1% of the chemotherapy; 95% CI, 51.6%-54.7%) compared with inpatients (33.7% of the chemotherapy; 95% CI, 31.7%-35.9%). Consequently, approximately ¥170 million (US $1.6 million) was unnecessarily spent on prophylactic antiemetic drugs for these patients. CONCLUSIONS AND RELEVANCE: A substantial number of patients receiving chemotherapy with minimal and low emetic risk were prescribed potentially unnecessary prophylactic antiemetic drugs. The judicious use of these drugs could spare the burden of extra costs and the potential risk for adverse effects for patients.

Economic evaluation of 5-HT3 receptor antagonists in combination with dexamethasone for the prevention of 'overall' nausea and vomiting following highly emetogenic chemotherapy in Chinese adult patients.

Background Two pivotal Phase III trials compared the efficacy of palonosetron, ondansetron and granisetron, combined with dexamethasone, for the prevention of nausea and vomiting following highly emetogenic chemotherapy. However, an economic evaluation of these three regimens in the real-world setting of Chinese adult patients has not been determined. Objectives To estimate, from the perspective of the Chinese healthcare system, which of these frequently used strategies consisting of 0.25 mg palonosetron (0.25P), 16 mg ondansetron (Onda), and 3 mg granisetron (Gran), is the most cost-effective option in patients following highly emetogenic chemotherapy. Methods A Markov decision-analytic model was developed. The health and economic outcomes of the three strategies; 0.25P, Onda, and Gran were investigated. The clinical and utility data were taken from published studies. The cost data were calculated according to current local Chinese practices. Sensitivity analyses were performed to determine the impact of uncertainty regarding the results. Results The base-case analysis showed that the 0.25P strategy yielded maximum health benefits compared with the other two strategies. However, the probabilistic sensitivity analysis demonstrated that the Gran strategy was the most cost-effective approach when the willingness-to-pay threshold was not more than US$22,515/quality-adjusted life year. Moreover, palonosetron is not cost-effective in preventing 'overall' nausea and vomiting following highly emetogenic chemotherapy in Chinese patients. Conclusions Our analysis suggests that, compared with palonosetron and ondansetron, 3 mg granisetron may be a cost-effective treatment option in the current Chinese healthcare setting.