Cost-Effectiveness Evaluation of Oral CGRP Antagonists, Atogepant and Rimegepant, for the Preventative Treatment of Episodic Migraine: Results from a US Societal Perspective Model.

BACKGROUND AND OBJECTIVES: Two oral calcitonin gene-related peptide (CGRP) antagonists, atogepant and rimegepant, were approved in 2021 for the preventive treatment of episodic migraine (EM), yet no formal cost-effectiveness analysis has been published. The objective of this study was to evaluate the cost-effectiveness of atogepant 60 mg and rimegepant 75 mg compared with placebo. METHODS: A decision tree model was constructed over a 1-year time horizon from a US societal perspective. Patient cohorts were simulated using baseline and change from baseline monthly migraine days (MMDs) reported in the trials to incorporate responder rates and within patient response into the model. Due to heterogeneity between the trial populations, each medication was compared with its respective trial's placebo group. Direct healthcare resource costs, productivity costs, acute medication costs, and quality-of-life values were obtained from the literature. RESULTS: The atogepant cohort experienced an incremental increase in healthcare plus productivity costs of $11,978 when compared with placebo, with a gain of 0.026 quality-adjusted life-years (QALYs). This yielded an incremental cost-effectiveness ratio (ICER) of more than $450,000/QALY. The rimegepant cohort experienced an incremental increase of $21,692 when compared with placebo, with a gain of 0.024 QALYs. This yields an ICER of more than $890,000/QALY when comparing rimegepant with placebo. Cost savings between atogepant and atogepant placebo were greatest with respect to acute medication costs at $735 of savings over 1 year, followed by savings of $135 for healthcare resource utilization and $34 for productivity costs. A similar relationship was seen between rimegepant and rimegepant placebo. One-way deterministic sensitivity analysis found that monthly acquisition costs of atogepant and rimegepant had the largest impact on the ICER, respectively. CONCLUSIONS: Atogepant and rimegepant were both unable to meet generally accepted cost-effectiveness thresholds < 150,0000/QALY. Additional studies are needed to better guide decision making regarding oral CGRPs' place in therapy.

Characterization of Regolith And Trace Economic Resources (CRATER): An Orbitrap-based laser desorption mass spectrometry instrument for in situ exploration of the Moon.

RATIONALE: Characterization of Regolith And Trace Economic Resources (CRATER), an Orbitrap™-based laser desorption mass spectrometry instrument designed to conduct high-precision, spatially resolved analyses of planetary materials, is capable of answering outstanding science questions about the Moon's formation and the subsequent processes that have modified its (sub)surface. METHODS: Here, we describe the baseline design of the CRATER flight model, which requires <20 000 cm3  volume, <10 kg mass, and <60 W peak power. The analytical capabilities and performance metrics of a prototype that meets the full functionality of the flight model are demonstrated. RESULTS: The instrument comprises a high-power, solid-state, pulsed ultraviolet (213 nm) laser source to ablate the surface of the lunar sample, a custom ion optical interface to accelerate and collimate the ions produced at the ablation site, and an Orbitrap mass analyzer capable of discriminating competing isobars via ultrahigh mass resolution and high mass accuracy. The CRATER instrument can measure elemental and isotopic abundances and characterize the organic content of lunar surface samples, as well as identify economically valuable resources for future exploration. CONCLUSION: An engineering test unit of the flight model is currently in development to serve as a pathfinder for near-term mission opportunities.

Hospital outcomes and costs for prostate cancer patients with comorbid heart failure by age group: An analysis of the US Nationwide Inpatient Sample.

RATIONALE, AIMS, AND OBJECTIVES: The prevalence of patients hospitalized with comorbid prostate cancer (PC) and heart failure (HF) has been steadily increasing. Both diseases share a set of common risk factors, with the most prominent being age. This study aimed to examine the outcomes and costs for patients with comorbid PC and HF, stratified by age. METHODS: We analyzed 41,340 hospitalization events of patients with PC using the US National Inpatient Sample from 2015 to 2018. Associations of HF with in-hospital mortality, length of stay (LOS), and hospital costs per hospitalization were measured using multivariable logistic regression, negative binomial regression, and generalized linear regression with log-link and gamma distribution, respectively, controlling for covariates. Subgroup analyses were performed for age groups <65 and ≥65. RESULTS: Visits of comorbid HF patients made up 2.3% (n = 952) of the PC study sample. Compared with PC patients without HF, those with HF had higher in-hospital mortality rates (odds ratio = 1.33, 95% confidence interval [CI] = 0.96-1.84, p = 0.085), longer hospital stays (incidence rate ratio = 1.32, 95% CI = 1.21-1.44, p < 0.001), and higher hospital costs (cost ratio = 1.17, 95% CI = 1.07-1.27, p = 0.001), controlling for covariates. On average, this amounted to a higher in-hospital mortality rate of 2.10%, an increased LOS of 1.73 days, and higher hospital costs of $2110 per patient. While in-hospital mortality did not differ significantly in patients aged <65 (p = 0.900), patients aged ≥65 had a 41% increased risk of in-hospital mortality compared with those without HF (p = 0.047). CONCLUSIONS: In comparison to those without HF, PC patients with comorbid HF showed higher rates of in-hospital mortality, LOS, and hospital costs, with mortality showing a significant difference exclusively in the ≥65 population. Effective management of older patients with PC is needed to improve outcomes and decrease costs.

Cost effectiveness of a 1-hour high-sensitivity troponin-T protocol: An analysis of the RAPID-TnT trial.

BACKGROUND: To understand the economic impact of an accelerated 0/1-hour high-sensitivity troponin-T (hs-cTnT) protocol. OBJECTIVE: To conduct a patient-level economic analysis of the RAPID-TnT randomised trial in patients presenting with suspected acute coronary syndrome (ACS). METHODS: An economic evaluation was conducted with 3265 patients randomised to either the 0/1-hour hs-cTnT protocol (n = 1634) or the conventional 0/3-hour standard-of-care protocol (n = 1631) with costs reported in Australian dollars. The primary clinical outcome was all-cause mortality or new/recurrent myocardial infarction. RESULTS: Over 12-months, mean per patient costs were numerically higher in the 0/1-hour arm compared to the conventional 0/3-hour arm (by $472.49/patient, 95% confidence interval [95 %CI]: $-1,380.15 to $2,325.13, P = 0.617) with no statistically significant difference in primary outcome (0/1-hour: 62/1634 [3.8%], 0/3-hour: 82/1631 [5.0%], HR: 1.32 [95 %CI: 0.95-1.83], P = 0.100). The mean emergency department (ED) length of stay (LOS) was significantly lower in the 0/1-hour arm (by 0.62 h/patient, 95 %CI: 0.85 to 0.39, P < 0.001), but the subsequent 12-month unplanned inpatient costs was numerically higher (by $891.22/patient, 95 %CI: $-96.07 to 1,878.50, P = 0.077). Restricting the analysis to patients with hs-cTnT concentrations ≤ 29 ng/L, mean per patient cost remained numerically higher in the 0/1-hour arm (by $152.44/patient, 95 %CI:$-1,793.11 to $2,097.99, P = 0.988), whilst the reduction in ED LOS was more pronounced (by 0.70 h/patient, 95 %CI: 0.45-0.95, P < 0.001). CONCLUSIONS: There were no differences in resource utilization between the 0/1-hour hs-cTnT protocol versus the conventional 0/3-hour protocol for the assessment of suspected ACS, despite improved initial ED efficiency. Further refinements in strategies to improve clinical outcomes and subsequent management efficiency are needed.

Cost-effectiveness analyses of targeted therapy and immunotherapy for advanced non-small cell lung cancer in the United States: a systematic review.

Introduction: Mutation-targeting and immuno-oncology drugs are revolutionizing the treatment of advanced non-small cell lung cancer (NSCLC). Cost-effectiveness analyses (CEA) of these drugs have been conducted using various analytical methods and cost-effectiveness thresholds. This systematic review provides a comprehensive summary of the available evidence.Area covered: PubMed, Embase, and Cochrane Library were used to select for CEA of targeted therapies for NSCLC in the United States published between 2008 and 2020. Among the 28 included studies, a majority were published from 2017 to 2020 (n = 18) and more than half targeted non-squamous NSCLC (n = 15). The most frequently evaluated therapy was pembrolizumab (n = 11), followed by bevacizumab (n = 8) and erlotinib (n = 4). After 2009, all included studies applied $100,000 or more thresholds. Thresholds of studies supported by industry (median = $150,000) were more distributed than those of studies supported by nonprofits (median = $100,000).Expert commentary: Medications of interest have changed and are individualized to particular mutations. The cost-effectiveness thresholds varied among sponsors but generally trended to increase over time. This review provides an overview of the available cost-effectiveness findings for stakeholders and contributes to evidence-based practice.

Racial and Socioeconomic Disparities in Cardiotoxicity Among Women With HER2-Positive Breast Cancer.

Breast cancer and cardiovascular-specific mortality are higher among blacks compared with whites, but disparities in cancer therapy-related adverse cardiovascular outcomes have not been well studied. We assessed for the contribution of race and socioeconomic status on cardiotoxicity among women with HER2-positive breast cancer. This retrospective cohort analysis studied women diagnosed with stage I-III HER2-positive breast cancer from 2004-2013. All underwent left ventricular ejection fraction assessment at baseline and at least one follow-up after beginning trastuzumab. Multivariable logistic regression was used to assess the association between race and socioeconomic status (SES) on cardiotoxicity, defined by clinical heart failure (New York Heart Association class III or IV) or asymptomatic left ventricular ejection fraction decline (absolute decrease ≥ 10% to < 53%, or ≥ 16%). Blacks had the highest prevalence of hypertension, diabetes, and increased BMI. Neighborhood-level SES measures including household income and educational attainment were lower for blacks compared with whites and others. The unadjusted cardiotoxicity risk was significantly higher in black compared with white women (OR, 2.10; 95% CI, 1.42 to 3.10). In a multivariable analysis, this disparity persisted after controlling for relevant cardiovascular risk factors (adjusted OR, 1.88; 95% CI, 1.25 to 2.84). Additional models adjusting for SES factors of income, educational attainment, and insurance status did not significantly alter the association between race and cardiotoxicity. In conclusion, black women are at increased risk of cardiotoxicity during HER2-targeted breast cancer therapy. Future etiologic analyses, particularly studies exploring biologic or genetic mechanisms, are needed to further elucidate and reduce racial disparities in cardiotoxicity.

Long-term follow-up assessment of cardiac safety in SAFE-HEaRt, a clinical trial evaluating the use of HER2-targeted therapies in patients with breast cancer and compromised heart function.

PURPOSE: HER2-targeted therapies are associated with cardiotoxicity which is usually asymptomatic and reversible. We report the updated cardiac safety assessment of patients with compromised heart function receiving HER2-targeted therapy for breast cancer, enrolled in the SAFE-HEaRt trial, at a median follow-up of 3.5 years. METHODS: Thirty patients with stage I-IV HER2-positive breast cancer receiving trastuzumab with or without pertuzumab, or ado-trastuzumab emtansine (T-DM1), with asymptomatic LVEF (left ventricular ejection fraction) 40-49%, were started on cardioprotective medications, with the primary endpoint being completion of HER2-targeted therapy without cardiac events (CE) or protocol-defined asymptomatic worsening of LVEF. IRB-approved follow-up assessment included 23 patients. RESULTS: Median follow-up as of June 2020 is 42 months. The study met its primary endpoint with 27 patients (90%) completing their HER2-targeted therapies without cardiac issues. Of the 23 evaluable patients at long-term f/u, 14 had early stage breast cancer, and 9 had metastatic disease, 8 of whom remained on HER2-targeted therapies. One patient developed symptomatic heart failure with no change in LVEF. There were no cardiac deaths. The mean LVEF improved to 52.1% from 44.9% at study baseline, including patients who remained on HER2-targeted therapy, and those who received prior anthracyclines. CONCLUSIONS: Long-term follow-up of the SAFE-HEaRt study continues to provide safety data of HER2-targeted therapy use in patients with compromised heart function. The late development of cardiac dysfunction is uncommon and continued multi-disciplinary oncologic and cardiac care of patients is vital for improved patient outcomes.

Assessment of dog owners' knowledge relating to the diagnosis and treatment of canine food allergies.

Canine food allergies are the result of an immune-mediated hypersensitivity reaction to dietary proteins and can manifest as a variety of dermatologic and/or gastrointestinal clinical signs. Food elimination trials followed by provocation tests are used to diagnose food allergies; however, no research has been conducted to determine whether elimination trials and provocation tests are being properly implemented by pet owners. The objectives of this study were to determine the level of knowledge of dog owners regarding food allergies, and to investigate how dog owners approach diagnosis and treatment with their veterinarians. This information will provide veterinary teams with insight on how to work with dog owners to obtain successful diagnosis and treatment. The results indicate that appropriate diet selection for the food elimination trial, owner education on compliance during the trial, and re-challenging with the previous diet should be the focal points for veterinarians suspecting food allergies in a canine patient.

Évaluation des connaissances des propriétaires de chiens portant sur le diagnostic et le traitement des allergies alimentaires canines. Les allergies alimentaires canines sont le résultat d'une réaction d'hypersensibilité à médiation immunitaire face aux protéines alimentaires et elles peuvent se manifester par divers signes cliniques dermatologiques et/ou gastro-intestinaux. Les essais d'élimination d'aliments suivis de tests de provocation sont utilisés pour diagnostiquer les allergies alimentaires. Cependant, aucune recherche n'a été réalisée pour déterminer si les essais d'élimination et les tests de provocation sont mis en place de façon adéquate par les propriétaires. Les objectifs de cette étude étaient de déterminer le niveau de connaissances des propriétaires de chiens concernant les allergies alimentaires et d'étudier la façon dont les propriétaires de chiens envisagent le diagnostic et le traitement avec leur médecin vétérinaire. Ces renseignements permettront aux équipes vétérinaires de constater comment travailler avec les propriétaires de chiens afin d'obtenir un diagnostic et un traitement réussi. Les résultats indiquent que le bon choix d'alimentation pour les essais d'élimination des aliments, l'éducation des propriétaires pour la conformité durant les essais et de nouveaux tests avec l'alimentation antérieure devraient être les principaux sujets pour les médecins vétérinaires soupçonnant des allergies alimentaires chez un patient canin.(Traduit par Isabelle Vallières).

Assessment of Early Radiation-Induced Changes in Left Ventricular Function by Myocardial Strain Imaging After Breast Radiation Therapy.

BACKGROUND: Radiation therapy (RT)-induced cardiotoxicity is among the concerning sequelae of breast cancer (BCA) treatment, particularly in HER2-positive BCA patients who receive anthracyclines and trastuzumab-based therapy. The aim of this study was to assess for early RT-induced changes in echocardiographic and circulating biomarkers of left ventricular (LV) function and evaluate their association with radiation dose to the heart among patients with HER2-positive BCA treated with contemporary RT. METHODS: A total of 47 women with HER2-positive BCA who were treated with an anthracycline, trastuzumab, and RT to the breast and/or chest wall ± regional lymph nodes were included in this study. Two-dimensional echocardiography with speckle-tracking imaging was performed at baseline (prechemotherapy), prior to and after RT (pre-RT and post-RT), and 6 months post-RT. High-sensitivity troponin I (hsTnI) was measured pre-RT and post-RT. Associations between mean heart dose (MHD) and changes in LV function after RT were examined in multivariable linear regression models. RESULTS: The MHD was 1.8 ± 1.5 Gy for patients receiving left-sided RT (n = 26) and 1.1 ± 1.3 Gy for patients receiving right-sided RT (n = 21). Pre-RT, post-RT, and 6-month post-RT echocardiograms were performed at median (interquartile range) of 49 days (27, 77) before and 54 days (25, 78) and 195 days (175, 226) after RT, respectively. Compared with pre-RT, a minimal decrease in LV ejection fraction was observed post-RT (61% ± 7% vs 59% ± 8%; P = .003) without any significant change in global longitudinal, circumferential, or radial strain or diastolic indices at the post-RT timepoint. Median (interquartile range) concentrations of hsTnI decreased from 5.7 pg/mL (3.0, 8.7) pre-RT to 3.7 pg/mL (2.0, 5.9) post-RT. There was no significant change in systolic or diastolic indices of LV function at 6 months post-RT compared with pre-RT. MHD was not associated with changes in echocardiographic parameters of LV function after RT. CONCLUSIONS: Breast RT using contemporary techniques can be delivered without evidence of early subclinical LV dysfunction or injury as measured by echocardiography and hsTnI in patients treated with anthracyclines and trastuzumab. Future studies should focus on identifying alternative biomarkers to elucidate early RT-induced cardiovascular effects and further characterizing long-term cardiovascular outcomes associated with contemporary breast RT.