Critical Examination of Modeling Approaches Used in Economic Evaluations of First-Line Treatments for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: A Systematic Literature Review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. NSCLC harboring an EGFR mutation has a dedicated treatment pathway, with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy often being the therapy of choice. OBJECTIVE: The aim of this study was to systemically review and summarize economic models of first-line treatments used for locally advanced or metastatic NSCLC harboring EGFR mutations, as well as to identify areas for improvement for future models. METHODS: Literature searches were conducted via Ovid in PubMed, MEDLINE, MEDLINE In-Process, Embase, Evidence-Based Medicine Reviews: Health Technology Assessment, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database, and EconLit. An initial search was conducted on 19 December 2022 and updated on 11 April 2023. Studies were selected according to predefined criteria using the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework. RESULTS: Sixty-seven articles were included in the review, representing 59 unique studies. The majority of included models were cost-utility analyses (n = 52), with the remaining studies being cost-effectiveness analyses (n = 4) and a cost-minimization analysis (n = 1). Two studies incorporated both a cost-utility and cost-minimization analysis. Although the model structure across studies was consistently reported, justification for this choice was often lacking. CONCLUSIONS: Although the reporting of economic models in NSCLC harboring EGFR mutations is generally good, many of these studies lacked sufficient reporting of justification for structural choices, performing extensive sensitivity analyses and validation in economic evaluations. In resolving such gaps, the validity of future models can be increased to guide healthcare decision making in rare indications.

Perception of Animal Abuse among Adolescents: Influence of Social and Demographic Factors.

Animal welfare is inherited in each society, shaped by the surrounding environment and upbringing of each individual. This influence becomes particularly significant during adolescence. Due to its cultural context, Spain is among the European Union nations with the highest number of cases of animal abuse. The Canary Islands, the scenario of this study, show the highest rates of intentional poisoning of wildlife and pets' abandonment. The aim of the present study was to explore the perception of animal welfare among adolescents, studying the influence of the main socio-demographic factors that may condition it. A validated questionnaire on animal abuse was used and distributed to adolescents aged 14-18 years in two public study centers. Animal abuse rates were correlated with socio-demographic variables. In total, 302 subjects answered the questionnaire. The perception of animal welfare was influenced by socio-demographic variables, gender being the most important. The demographic profile of the least responsive adolescent to animal abuse was a male engaged in sports, not owning a dog, and hailing from a family involved in hunting. Awareness should be raised at an early age, promoting artistic activities, encouraging contact with animals and sporting practices that do not generate a lack of empathy for animals.

Justifying the source of external comparators in single-arm oncology health technology submissions: a review of NICE and PBAC assessments.

Background: The drive to expedite patient access for diseases with high unmet treatment needs has come with an increasing use of single-arm trials (SATs), especially in oncology. However, the lack of control arms in such trials creates challenges to assess and demonstrate comparative efficacy. External control (EC) arms can be used to bridge this gap, with various types of sources available to obtain relevant data. Objective: To examine the source of ECs in single-arm oncology health technology assessment (HTA) submissions to the National Institute for Health and Care Excellence (NICE) and the Pharmaceutical Benefits Advisory Committee (PBAC) and how this selection was justified by manufacturers and assessed by the respective HTA body. Methods: Single-arm oncology HTA submission reports published by NICE (England) and PBAC (Australia) from January 2011 to August 2021 were reviewed, with data qualitatively synthesized to identify themes. Results: Forty-eight oncology submissions using EC arms between 2011 and 2021 were identified, with most submissions encompassing blood and bone marrow cancers (52%). In HTA submissions to NICE and PBAC, the EC arm was typically constructed from a combination of data sources, with the company's justification in data source selection infrequently provided (PBAC [2 out of 19]; NICE [6 out of 29]), although this lack of justification was not heavily criticized by either HTA body. Conclusion: Although HTA bodies such as NICE and PBAC encourage that EC source justification should be provided in submissions, this review found that this is not typically implemented in practice. Guidance is needed to establish best practices as to how EC selection should be documented in HTA submissions.

Navigating the unknown: how to best 'reflect' standard of care in indications without a dedicated treatment pathway in health technology assessment submissions.

There is an urgent need for expedited approval and access for new health technologies targeting rare and very rare diseases, some of which are associated with high unmet treatment needs. Once a new technology achieves regulatory approval, the technology needs to be assessed by health technology assessment (HTA) bodies to inform coverage and reimbursement decisions. This assessment quantitatively examines the clinical effectiveness, safety and/or economic impact of the new technology relative to standard of care (SoC) in a specific market. However, in rare and very rare diseases, the patient populations are small and there is often no established treatment pathway available to define 'SoC'. In these situations, several challenges arise to assess the added benefit of a new technology - both clinically and economically - due to lack of established SoC to guide an appropriate comparator selection. These challenges include: How should 'SoC' be defined and characterized in HTA submissions for new technologies aiming to establish new treatment standards? What is usual care without an established clinical pathway? How should the evidence for the comparator 'SoC' (i.e., usual care) arm be collected in situations with low patient representation and, sometimes, limited disease-specific clinical knowledge in certain geographies? This commentary outlines the evidence generation challenges in designing clinical comparative effectiveness for a new technology when there is a lack of established SoC. The commentary also proposes considerations to facilitate the reliable integration of real-world evidence into HTA and decision-making based on the collective experience of the authors.

Differences in Body Weight According to Skin Color and Sex in Mexican Adults.

OBJECTIVES: 1) To analyze the differences in body weight according to skin color in Mexican adults. 2) Identify mediator variables that could explain possible differences in body weight according to skin color. METHODS: A nationally representative survey of Mexican adults was analyzed (n = 12,021). People with obesity were identified (body mass index, BMI > 30) based on self-reported weight and height. Skin color was measured by self-report using a chromatic scale. The mediator variables were socioeconomic level, height, neighborhood public services, public safety, and discrimination based on skin color. RESULTS: Compared to white-skinned women, brown-skinned women had higher BMI and a higher probability of being obese. These differences in weight by skin color are related to the lower level of education and more discrimination experiences of brown-skinned women. In men, there were no differences in weight according to skin color. CONCLUSIONS: In Mexican women (but not in men), darker skin color was associated with a higher probability of being obese, and the examined social factors partially explained this disparity.

Reliability Testing of a Low-Cost, Multi-Purpose Arduino-Based Data Logger Deployed in Several Applications Such as Outdoor Air Quality, Human Activity, Motion, and Exhaust Gas Monitoring.

This contribution shows the possibilities of applying a low-cost, multi-purpose data logger built around an Arduino Mega 2560 single-board computer. Most projects use this kind of hardware to develop single-purpose data loggers. In this work, a data logger with a more general hardware and software architecture was built to perform measurement campaigns in very different domains. The wide applicability of this data logger was demonstrated with short-term monitoring campaigns in relation to outdoor air quality, human activity in an office, motion of a journey on a bike, and exhaust gas monitoring of a diesel generator. In addition, an assessment process and corresponding evaluation framework are proposed to assess the credibility of low-cost scientific devices built in-house. The experiences acquired during the development of the system and the short measurement campaigns were used as inputs in the assessment process. The assessment showed that the system scores positively on most product-related targets. However, unexpected events affect the assessment over the longer term. This makes the development of low-cost scientific devices harder than expected. To assure stability and long-term performance of this type of design, continuous evaluation and regular engineering corrections are needed throughout longer testing periods.

Optical Detection of Cancer Cells Using Lab-on-a-Chip.

The global need for accurate and efficient cancer cell detection in biomedicine and clinical diagnosis has driven extensive research and technological development in the field. Precision, high-throughput, non-invasive separation, detection, and classification of individual cells are critical requirements for successful technology. Lab-on-a-chip devices offer enormous potential for solving biological and medical problems and have become a priority research area for microanalysis and manipulating cells. This paper reviews recent developments in the detection of cancer cells using the microfluidics-based lab-on-a-chip method, focusing on describing and explaining techniques that use optical phenomena and a plethora of probes for sensing, amplification, and immobilization. The paper describes how optics are applied in each experimental method, highlighting their advantages and disadvantages. The discussion includes a summary of current challenges and prospects for cancer diagnosis.

[Chemical pollution, exposome and health in the Canary Islands population: An assessment of the situation.] / Contaminación química, exposoma y salud en la población de las Islas Canarias: una revisión sistemática de los estudios realizados y análisis de la situación.

OBJECTIVE: The set of exposures to chemical substances and their role as a cause of disease gives rise to the concept of the exposome, partially made up of chemical pollutants to which an individual is exposed, which is why, unlike the genome, it is an a priori modifiable factor, its study being crucial in terms of Public Health. The population of the Canary Islands has been studied in terms of its levels of chemical contamination, with numerous biomonitoring studies, which makes it necessary to characterise its exposome and its consequences in terms of disease, in order to implement specific corrective measures to minimize the impact on its health. METHODS: A review of scientific literature (MEDLINE and Scopus) was made, according to PRISMA criteria and PICO methodology, to include studies on biomonitoring of pollutants, or evaluating the effect of pollutants on diseases prevalent in the archipelago. RESULTS: Twenty-five studies, both population-based and hospital-based, were selected. The results show that the exposome is made up of at least 110 compounds or elements, 99 of which appear to be present from the intrauterine stage. The presence of chlorinated pollutants and metals stands out, which seems to be related to the high incidence of metabolic diseases (diabetes), cardiovascular diseases (hypertension) and certain types of neoplasms (breast cancer). In short, the consequences are conditioned by the genome of the exposed population, reinforcing the enormous importance of genome-exposome interactions in the development of pathologies. CONCLUSIONS: Our results indicate that it is necessary to establish corrective measures on the sources of pollution that modify the exposome of this population.

OBJETIVO: El conjunto de exposiciones a sustancias químicas y su papel como causa de enfermedad da lugar al concepto de exposoma, conformado parcialmente por contaminantes químicos a los que un individuo se ve expuesto. Por ello, a diferencia del genoma, es un factor a priori modificable, siendo su estudio crucial en materia de Salud Pública. La población del archipiélago canario ha sido estudiada en cuanto a sus niveles de contaminación química, con numerosos estudios de biomonitorización, lo que hace necesario caracterizar el exposoma de ésta y sus consecuencias en términos de enfermedad, para poder implementar medidas correctoras específicas que minimicen el impacto en su salud. METODOS: Se realizó una revisión de la literatura científica (MEDLINE y Scopus) de acuerdo con los criterios PRISMA y siguiendo la metodología PICO, para incluir estudios de biomonitorización de contaminantes, o que evaluaran el efecto de éstos en enfermedades prevalentes en el archipiélago. RESULTADOS: Se seleccionaron veinticinco estudios, tanto de base poblacional como de base hospitalaria. Los resultados demuestran que el exposoma lo conforman, como mínimo, 110 compuestos o elementos, 99 de los cuales parecen estar presentes desde la etapa intrauterina. Destaca la presencia de contaminantes clorados y metales, lo que parece relacionarse con la alta incidencia de enfermedades metabólicas (diabetes), cardiovasculares (hipertensión) y ciertos tipos de neoplasias (cáncer de mama). Aunque tales consecuencias vienen condicionadas por el genoma de la población expuesta, reforzando la enorme importancia de las interacciones genoma-exposoma en el desarrollo de patologías. CONCLUSIONES: Nuestros resultados indican que es necesario establecer medidas correctoras sobre las fuentes de contaminación que modifiquen el exposoma de esta población.

The budget impact of introducing mobocertinib for the postplatinum treatment of advanced non-small cell lung cancer harboring epidermal growth factor receptor exon 20 insertion mutations.

BACKGROUND: Lung cancer is a leading cause of cancer morbidity and death in the United States. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, and oncogenic mutations in the gene encoding the epidermal growth factor receptor (EGFR) are among its most common genetic causes. Although NSCLC tumors harboring more common oncogenic EGFR mutations can be effectively treated with EGFR tyrosine kinase inhibitors (TKIs), those harboring EGFR exon 20 insertion mutations respond poorly to treatment with therapies approved for advanced NSCLC, including TKIs. Mobocertinib, a first-in-class potent, oral, irreversible TKI, is effective in this population. OBJECTIVE: To estimate the budget impact, for a US health plan with 10 million members, of introducing mobocertinib for the treatment of patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations who have been previously treated with platinum-based chemotherapy. METHODS: A budget impact model was developed to compare 2 scenarios: a reference scenario in which 50% of patients received amivantamab and 50% received physician's choice/usual care therapy and an alternative scenario in which mobocertinib replaced the physician's choice/usual care option. The model had a 5-year time horizon in the base case. The model included epidemiologic inputs to estimate the size of the treatment-eligible population; clinical inputs to estimate treatment duration and efficacy, as well as adverse event frequency; and cost inputs for treatment acquisition and administration, management of adverse events, monitoring, and terminal care. The duration and cost of subsequent therapies were also considered. Budget impact was reported as a total cost, as per-member per-year costs, and as per-member per-month (PMPM) costs. To assess the robustness of model estimates and identify cost drivers, one-way sensitivity analyses and a range of scenario analyses were conducted. RESULTS: The model estimated an eligible treatment population of 55 patients (11 per year) over a 5-year time horizon. In the base case, the estimated budget impact of introducing mobocertinib was $5,615,808, or $0.01 PMPM. Model findings were robust to one-way sensitivity analyses and a range of sensitivity analyses; none of these analyses led to a PMPM budget impact of more than $0.06. Cost drivers included the percentage of eligible patients, the median duration of physician's choice/usual care therapy, patient weight, and the percentage of patients who undergo molecular testing. CONCLUSIONS: The estimated budget impact of mobocertinib is low, primarily because NSCLC harboring EGFR exon 20 insertion mutations is rare. DISCLOSURES: Dr Hernandez is an employee of Takeda Pharmaceuticals America, Inc. Dr Young was an employee of Takeda Pharmaceuticals America, Inc., at the time this study was conducted. This study and the editorial assistance were funded by Takeda Pharmaceuticals America, Inc.

Energy Expenditure in Free-Living Physical Activities and Sedentary Behaviors in Mexican Schoolchildren.

Purpose: Metabolic equivalents for youth (METy) are derived using the estimated basal metabolic rate (BMR). However, is unknown whether this METy can be different when measured resting energy expenditure (REE) is used. The purposes of this article are to: (a) To determine whether there is equivalence between METy values calculated using measured REE (METy-mea) and METy using predicted BMR (METy-est). (b) To determine whether METy values of different activities are dependent on age, sex, and body composition. Methods: A cross-sectional study with a sample of 122 Mexican children (5-11 years old) was conducted. With indirect calorimetry, energy expenditure was measured at rest and during 16 sedentary- to vigorous-intensity physical activities. METy were obtained in two forms: METy-mea and METy-est. Equivalence testing was used to compare METy-mea and METy-est. To examine the individual-level agreement, Bland-Altman plots were graphed, and intra-class correlation coefficients (ICC) were calculated. Linear regression models were estimated having METy as the outcome. Results: For 15 activities, there was equivalence between METy-mea and METy-est (t > 2.05, p < 0.050). However, at the individual-level, for 7 activities the agreement between METy-eREE and METy-mREE was inadequate (ICC<0.75). In the Bland-Altman plots was evident that in 8 activities METy-est was biased compared to METy-mea, METy-est had more correlations with body mass index and body fat. Conclusions: In conclusion, at group-level, for most activities METy-mea and METy-est were equivalent. However, at the individual level, METy-est of many activities is not a valid estimate of METy-mea. METy-est of many physical activities were dependent on adiposity, which could be an artifact introduced when BMR is predicted.

External validation of a prediction model for estimating fat mass in children and adolescents in 19 countries: individual participant data meta-analysis.

OBJECTIVE: To evaluate the performance of a UK based prediction model for estimating fat-free mass (and indirectly fat mass) in children and adolescents in non-UK settings. DESIGN: Individual participant data meta-analysis. SETTING: 19 countries. PARTICIPANTS: 5693 children and adolescents (49.7% boys) aged 4 to 15 years with complete data on the predictors included in the UK based model (weight, height, age, sex, and ethnicity) and on the independently assessed outcome measure (fat-free mass determined by deuterium dilution assessment). MAIN OUTCOME MEASURES: The outcome of the UK based prediction model was natural log transformed fat-free mass (lnFFM). Predictive performance statistics of R2, calibration slope, calibration-in-the-large, and root mean square error were assessed in each of the 19 countries and then pooled through random effects meta-analysis. Calibration plots were also derived for each country, including flexible calibration curves. RESULTS: The model showed good predictive ability in non-UK populations of children and adolescents, providing R2 values of >75% in all countries and >90% in 11 of the 19 countries, and with good calibration (ie, agreement) of observed and predicted values. Root mean square error values (on fat-free mass scale) were <4 kg in 17 of the 19 settings. Pooled values (95% confidence intervals) of R2, calibration slope, and calibration-in-the-large were 88.7% (85.9% to 91.4%), 0.98 (0.97 to 1.00), and 0.01 (-0.02 to 0.04), respectively. Heterogeneity was evident in the R2 and calibration-in-the-large values across settings, but not in the calibration slope. Model performance did not vary markedly between boys and girls, age, ethnicity, and national income groups. To further improve the accuracy of the predictions, the model equation was recalibrated for the intercept in each setting so that country specific equations are available for future use. CONCLUSION: The UK based prediction model, which is based on readily available measures, provides predictions of childhood fat-free mass, and hence fat mass, in a range of non-UK settings that explain a large proportion of the variability in observed fat-free mass, and exhibit good calibration performance, especially after recalibration of the intercept for each population. The model demonstrates good generalisability in both low-middle income and high income populations of healthy children and adolescents aged 4-15 years.

Main Retailers In Which Mexican Households Acquire Their Food Supply.

OBJECTIVE: To describe the frequency of food and beverages purchased made by Mexican households at different types of grocery retailers. DESIGN: A national cross-sectional survey. SETTING: Mexico. PARTICIPANTS: A representative sample of Mexican households (n = 70,311). MAIN OUTCOME MEASURE(S): Household food and beverages purchases. ANALYSIS: The association between amounts of food and beverages supply bought in different food retailers (as outcome) and households' sociodemographic characteristics (as covariates) was assessed using logistic and linear regression models. RESULTS: Mexican households acquired their food and beverages primarily from abarrotes stores, followed by supermarkets and mercados and tianguis. Abarrotes stores and supermarkets were sources of unprocessed and processed foods. Specialized stores, mercados, and tianguis were primary sources of unprocessed foods. Households with low socioeconomic status and those in the central or southern regions acquired more foods from abarrotes stores, mercados and tianguis, and specialized stores. Households with high socioeconomic status and living in the northern region acquired more foods from supermarkets and convenience stores. CONCLUSIONS AND IMPLICATIONS: Abarrotes stores are the primary source of food and beverages for Mexican households; however, some interventions are needed to increase their supply of unprocessed foods. Public health interventions aiming at increasing access to unprocessed foods could be done through traditional retailers.

Assessment of Simultaneous Global Optimization of Geometry and Total Spin of Small Iron Clusters.

In this work, simultaneous global optimization of geometry and total spin of small iron clusters Fen (3 ≤ n ≤ 40) is assessed using Simulated Annealing (SA) simulations with forces calculated at the DFT-based Tight-Binding (DFTB) level of theory. In order to optimize the total spin, the occupancies of α and ß densities were allowed to relax at each SA step, resulting in a continuous variation of the total spin along the trajectory. The behavior and performance of the procedure were investigated running two series of 10 independent "long" molecular dynamics simulations and one series of 100 independent "short" simulations. Cluster structures optimized with the assessed methodology reproduced geometries and magnetic moments reported in a previous work very well where multiple fixed total spin and geometries of iron clusters were individually probed, and for some clusters, more stable global minima were found. Other properties such as binding energies and second energy differences were also calculated in order to compare with previously reported theoretical and experimental values. The few mismatches were found to be driven by quasi degenerated ground states with different magnetic moments or by states with crossing free energies at high temperatures.

Understanding how socioeconomic inequalities drive inequalities in COVID-19 infections.

Across the world, the COVID-19 pandemic has disproportionately affected economically disadvantaged groups. This differential impact has numerous possible explanations, each with significantly different policy implications. We examine, for the first time in a low- or middle-income country, which mechanisms best explain the disproportionate impact of the virus on the poor. Combining an epidemiological model with rich data from Bogotá, Colombia, we show that total infections and inequalities in infections are largely driven by inequalities in the ability to work remotely and in within-home secondary attack rates. Inequalities in isolation behavior are less important but non-negligible, while access to testing and contract-tracing plays practically no role because it is too slow to contain the virus. Interventions that mitigate transmission are often more effective when targeted on socioeconomically disadvantaged groups.

Development and Interrater Reliability of a Street Food Stand Assessment Tool.

OBJECTIVE: To design and test the interrater reliability of a Street Food Stand Assessment Tool (SFSAT). DESIGN: Variables were adapted from validated assessment tools, field observations, and the Mexican Dietary Guidelines. Two researchers tested the SFSAT by observing street food stands (SFS) in 3 middle- to high-income neighborhoods. SETTING: Mexico City. PARTICIPANTS: Fifty-two SFS. VARIABLES MEASURED: The SFSAT contains 14 items for SFS characteristics and 44 items for food and beverages. ANALYSIS: Percent agreement and kappa interrater reliability scores were calculated for each variable. RESULTS: Almost perfect kappa interrater reliability scores (0.81-1.00) were reported for 62.7% of SFS characteristic items. Interrater reliability scores for food and beverage availability and variety ranged from 0.00-1.00, whereas the percent agreement for these items ranged from 59.6%-100.0%. CONCLUSIONS AND IMPLICATIONS: The SFSAT is a reliable assessment tool to measure the availability and variety of street foods and beverages in Mexico City. Future research can update and adapt the SFSAT to the street food environment of other cities-in Mexico and abroad.

Nutritional Evaluation and Risk Assessment of the Exposure to Essential and Toxic Elements in Dogs and Cats through the Consumption of Pelleted Dry Food: How Important Is the Quality of the Feed?

Dry feed for pets lacks specific legislation regarding maximum residue limits for inorganic elements. The aim of the present study was to determine the content of 43 inorganic elements in dog and cat feed, studying whether there were differences according to the supposed quality of the food and performing the risk assessment for health. Thirty-one and thirty packages of pelleted dry food for cats and dogs, respectively, were analyzed. After acidic microwave-assisted digestion, elements were detected and quantified by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). In general, we did not observe important differences in the content of elements according to the supposed quality of the brand. Among trace elements, selenium and manganese are above the dietary reference value. Arsenic and mercury showed the highest acute hazard indexes, which make them risk factors for the health of dogs and cats. Aluminum, uranium, antimony and vanadium contents were above the toxic reference value and showed the highest acute hazard indexes. It is necessary to improve the legislation regarding the food safety of pets, for their health and to protect the rights of consumers.

Predictors of healthcare mistreatment among transgender and gender diverse individuals: Are there different patterns by patient race and ethnicity?

Using data from the 2015 United States Transgender Survey, this study investigates which patient sociodemographic characteristics and psychosocial risks are associated with likelihood of transgender mistreatment in healthcare and how patterns vary for patients of color. Numerous predictors, including alignment of identity documents, were associated with healthcare mistreatment. Among subgroups of transgender patients of color, psychosocial risks were more consistently significant than sociodemographic characteristics in predicting mistreatment. National and international health organizations are called to enact clear policies that affirm transgender patients and patients of color and establish a commitment to effectively serving these populations within their ethical codes.

Association Between Overt and Subtle Experiences of Discrimination and Violence and Mental Health in Homosexual and Bisexual Men in Mexico.

The aim of this study was to determine whether the experiences of direct or subtle forms of discrimination and violence are associated with mental health in Mexican gay, homosexual, and bisexual (GHB) men. A cross-sectional survey was conducted online; the sample consisted of 4,827 GHB men. Ten forms of overt and subtle sexual orientation-based discrimination and violence (SO-DV) were assessed. Linear and logistic regression models were used to evaluate the association between SO-DV experiences and mental health outcomes. Physical violence was reported less frequently than the other forms of SO-DV. As the number of settings in which SO-DV were experienced increased, a stronger association with negative mental health outcomes was observed. Experiences of subtle SO-DV were associated with increased distress, lower vitality, and increased risk of suicidal ideation. Disapproval of gender nonconformity was associated with negative mental health outcomes independently of violence based on sexual orientation. Subtle forms of SO-DV are more common than direct and overt forms. Both types of SO-DV could negatively affect mental health. Studies investigating these negative experiences are required to gain an understanding of the health inequalities faced by non-heterosexual populations.

Predictors of Health Utility in Relapsing-Remitting and Secondary-Progressive Multiple Sclerosis: Implications for Future Economic Models of Disease-Modifying Therapies.

BACKGROUND: Decision-analytic models used in economic evaluations of disease-modifying therapies for relapsing-remitting multiple sclerosis (RRMS) have characterized disease progression and accrue quality-adjusted life-years from utility values based on the Expanded Disability Status Scale (EDSS), the occurrence of relapses, and progression to secondary-progressive multiple sclerosis (SPMS). The EDSS, used to characterize disability progression, has several limitations. If the EDSS is the only disability measure used in economic evaluations, the long-term clinical and economic implications of disease-modifying therapies may not be properly assessed. OBJECTIVE: The objective of this study was to explore if supplementary disability measures including the Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and Paced Auditory Serial Addition Test (PASAT) significantly contribute additional information on health utility in RRMS and SPMS otherwise not captured by the EDSS and relapses and, therefore, should be considered in future economic evaluations of disease-modifying therapies. METHODS: Short-Form Six-Dimension utility scores were derived from the RAND 36-Item Health Survey 1.0 individual-level data available in the Multiple Sclerosis Outcome Assessment Consortium (MSOAC) Placebo Database. Repeated-measures mixed-effects models were conducted to estimate the effects of EDSS, T25FW, 9HPT (dominant and non-dominant hand), PASAT, and relapses on changes in utility over time, controlling for demographics. RESULTS: A higher level of EDSS, longer time to complete the T25FW test, and a recent relapse were significant predictors of lower utility in people with RRMS and SPMS. 9HPT and PASAT were not significant predictors. CONCLUSIONS: This study suggests that in addition to EDSS and recent relapses, T25FW significantly predicts utility in RRMS and SPMS. These findings support the use of T25FW to supplement the EDSS and the occurrence of relapses to characterize the course of disease progression and to more accurately accrue quality-adjusted life-years in future economic evaluations of disease-modifying therapies for the treatment of RRMS.

Economic Implications of Preventing Major Cardiovascular and Limb Events with Rivaroxaban plus Aspirin in Patients with Coronary or Peripheral Artery Disease in the United States.

BACKGROUND: Patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) have increased risks for cardiovascular (CV)-related morbidity and mortality. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) clinical trial of such patients, rivaroxaban plus aspirin demonstrated a significant reduction in major adverse CV events (MACE), a composite of stroke, myocardial infarction, and CV death, and major adverse limb events (MALE), a composite of chronic and acute limb ischemia, and major amputation resulting from vascular events, versus aspirin alone. OBJECTIVE: To estimate the 1-year economic implications of preventing MACE and MALE with the use of rivaroxaban plus aspirin versus aspirin alone among patients with chronic CAD and/or PAD in a US commercial health plan. METHOD: A cost-consequence model was developed to evaluate the economic impact of rivaroxaban plus aspirin in a hypothetical 1-million-member health plan. The model inputs were taken from the COMPASS study (ie, the efficacy and safety of rivaroxaban plus aspirin vs aspirin), Optum Integrated Database (ie, the prevalence of chronic CAD and/or PAD, incidence rates, and healthcare costs of MACE, MALE, and major bleeding), and the RED BOOK (ie, wholesale drug acquisition costs). The cost inputs were in 2019 US dollars. One-way sensitivity analyses and subgroup analyses were conducted. RESULTS: A 1-year treatment with rivaroxaban plus aspirin resulted in reductions of MACE and MALE, which balance the increased risk for bleeding versus aspirin alone and indicate a net health benefit for this drug regimen. These reductions were achieved at an incremental per-member per-month (PMPM) cost of $0.16, mainly because of rivaroxaban's acquisition cost. In patients with ≥2 MACE or MALE risk factors, the incremental PMPM cost was $0.09, given the increased offset in rivaroxaban's acquisition cost by reduced rates of MACE or MALE. CONCLUSIONS: In an era of emerging thrombocardiology, treatment with rivaroxaban plus aspirin offers an effective thrombotic risk management strategy for healthcare stakeholders in the management of chronic CAD and/or PAD. The contribution of rivaroxaban would be greater in patients with ≥2 risk factors for MACE or MALE.