Clinical and economic impact of 'ROS1-testing' strategy compared to a 'no-ROS1-testing' strategy in advanced NSCLC in Spain.

BACKGROUND: Detection of the ROS1 rearrangement is mandatory in patients with advanced or metastatic non-small cell lung cancer (NSCLC) to allow targeted therapy with specific inhibitors. However, in Spanish clinical practice ROS1 determination is not yet fully widespread. The aim of this study is to determine the clinical and economic impact of sequentially testing ROS1 in addition to EGFR and ALK in Spain. METHODS: A joint model (decision-tree and Markov model) was developed to determine the cost-effectiveness of testing ROS1 strategy versus a no-ROS1 testing strategy in Spain. Distribution of ROS1 techniques, rates of testing, positivity, and invalidity of biomarkers included in the analysis (EGFR, ALK, ROS1 and PD-L1) were based on expert opinion and Lungpath real-world database. Treatment allocation depending on the molecular testing results was defined by expert opinion. For each treatment, a 3-states Markov model was developed, where progression-free survival (PFS) and overall survival (OS) curves were parameterized using exponential extrapolations to model transition of patients among health states. Only medical direct costs were included (€ 2021). A lifetime horizon was considered and a discount rate of 3% was applied for both costs and effects. Both deterministic and probabilistic sensitivity analyses were performed to address uncertainty. RESULTS: A target population of 8755 patients with advanced NSCLC (non-squamous or never smokers squamous) entered the model. Over a lifetime horizon, the ROS1 testing scenario produced additional 157.5 life years and 121.3 quality-adjusted life years (QALYs) compared with no-ROS1 testing scenario. Total direct costs were increased up to € 2,244,737 for ROS1 testing scenario. The incremental cost-utility ratio (ICUR) was 18,514 €/QALY. Robustness of the base-case results were confirmed by the sensitivity analysis. CONCLUSIONS: Our study shows that ROS1 testing in addition to EGFR and ALK is a cost-effective strategy compared to no-ROS1 testing, and it generates more than 120 QALYs in Spain over a lifetime horizon. Despite the low prevalence of ROS1 rearrangements in NSCLC patients, the clinical and economic consequences of ROS1 testing should encourage centers to test all advanced or metastatic NSCLC (non-squamous and never-smoker squamous) patients.

EpiGe: A machine-learning strategy for rapid classification of medulloblastoma using PCR-based methyl-genotyping.

Molecular classification of medulloblastoma is critical for the treatment of this brain tumor. Array-based DNA methylation profiling has emerged as a powerful approach for brain tumor classification. However, this technology is currently not widely available. We present a machine-learning decision support system (DSS) that enables the classification of the principal molecular groups-WNT, SHH, and non-WNT/non-SHH-directly from quantitative PCR (qPCR) data. We propose a framework where the developed DSS appears as a user-friendly web-application-EpiGe-App-that enables automated interpretation of qPCR methylation data and subsequent molecular group prediction. The basis of our classification strategy is a previously validated six-cytosine signature with subgroup-specific methylation profiles. This reduced set of markers enabled us to develop a methyl-genotyping assay capable of determining the methylation status of cytosines using qPCR instruments. This study provides a comprehensive approach for rapid classification of clinically relevant medulloblastoma groups, using readily accessible equipment and an easy-to-use web-application.t.

Contribution of cardio-vascular risk factors to depressive status in the PREDIMED-PLUS Trial. A cross-sectional and a 2-year longitudinal study.

BACKGROUND: Cardio-vascular disease and depression are thought to be closely related, due to shared risk factors. The aim of the study was to determine the association between cardio-vascular risk (CVR) factors and depressive status in a population (55-75 years) with metabolic syndrome (MetS) from the PREDIMED-Plus trial. METHODS AND FINDINGS: Participants were classified into three groups of CVR according to the Framingham-based REGICOR function: (1) low (LR), (2) medium (MR) or (3) high/very high (HR). The Beck Depression Inventory-II (BDI-II) was used to assess depressive symptoms at baseline and after 2 years. The association between CVR and depressive status at baseline (n = 6545), and their changes after 2 years (n = 4566) were evaluated through multivariable regression models (logistic and linear models). HR women showed higher odds of depressive status than LR [OR (95% CI) = 1.78 (1.26, 2.50)]. MR and HR participants with total cholesterol <160 mg/mL showed higher odds of depression than LR [OR (95% CI) = 1.77 (1.13, 2.77) and 2.83 (1.25, 6.42) respectively)] but those with total cholesterol ≥280 mg/mL showed lower odds of depression than LR [OR (95% CI) = 0.26 (0.07, 0.98) and 0.23 (0.05, 0.95), respectively]. All participants decreased their BDI-II score after 2 years, being the decrease smaller in MR and HR diabetic compared to LR [adjusted mean±SE = -0.52±0.20, -0.41±0.27 and -1.25±0.31 respectively). MR and HR participants with total cholesterol between 240-279 mg/mL showed greater decreases in the BDI-II score compared to LR (adjusted mean±SE = -0.83±0.37, -0.77±0.64 and 0.97±0.52 respectively). CONCLUSIONS: Improving cardiovascular health could prevent the onset of depression in the elderly. Diabetes and total cholesterol in individuals at high CVR, may play a specific role in the precise response. International Standard Randomized Controlled Trial (ISRCTN89898870).

Patterns of Progression and Feasibility of Re-biopsy After First-line Erlotinib for Advanced EGFR Mutation-positive Non-small-cell Lung Cancer.

AIM: To assess the patterns of disease progression in advanced/metastatic epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) on first-line treatment with erlotinib and identify potential prognostic factors for progression-free survival (PFS). PATIENTS AND METHODS: Patients with stage IIIB/IV EGFR-mutation-positive NSCLC receiving first-line erlotinib were followed-up until 24 months after the last patient was enrolled or until premature withdrawal for any cause. RESULTS: A total of 127 evaluable patients were enrolled. The median PFS and overall survival were 8.8 and 19.1 months, respectively. Disease progression was asymptomatic in 57.6% of patients and 53.3% developed new sites of metastasis. The presence of liver metastasis was identified as an independent prognostic factor for poor PFS. CONCLUSION: Metastatic progression with asymptomatic disease seems to be the predominant pattern of disease progression on first-line erlotinib in real-life practice in patients with advanced/metastatic EGFR-mutant NSCLC. Additionally, the presence of liver metastases may negatively affect PFS in these patients.

Changes in fatty liver index after consuming a Mediterranean diet: 6-year follow-up of the PREDIMED-Malaga trial. / Cambios en el Índice de Hígado Graso con una intervención con dieta mediterránea: seguimiento de 6 años del ensayo PREDIMED-Málaga.

OBJECTIVE: To analyze the effect of an intervention with a Mediterranean diet supplemented with either extra virgin olive oil or nuts, on the fatty liver index (FLI), compared to a low-fat control diet. METHODS: Participants of the PREDIMED-Malaga trial, free from cardiovascular disease at baseline, but with a high risk to develop it, were included in this study. Anthropometric measurements were assessed and blood samples were taken to calculate participants' FLI at study baseline and after one, 3, 5 and 6 years. Mixed linear models were used to explore the fixed effects of the 3 intervention groups on the FLI as well as their interaction with time. RESULTS: A total of 276 participants were included in the study. Average participant age was 67 years, with 66% of participants being women. The baseline prevalence of NAFL was 57%. The change in the FLI of the control group increased significantly over time (1.13±0.41; P=.006). In the MedDiet+EVOO group, the time trend of the change in the FLI was similar to that of the control group, although it was seen to be lower (-3.90±1.9; P=.038). In the MedDiet+Nuts group, the trend was significantly lower than that of the control group (-1.63±0.62; P=.009). In the MedDiet+Nuts group, the trend of changes in participants' BMI was 0.100 points lower per year compared to the control group (P=.004). In the control group, the change in waist circumference increased significantly over time (0.61±0.16cm/year; P<.001) in contrast to the MedDiet+EVOO group, in which this variable remained stable (-0.51±0.22; P=.019). CONCLUSIONS: A dietary intervention consisting of a Mediterranean diet could delay or slow down the natural progression of NAFL, thus, being beneficial for its prevention and treatment. However, further studies supporting these conclusions have yet to be carried out.

Análisis del disfrute de los participantes en evento no competitivo: Gimnastrada de Extremadura / Analysis of the enjoyment of participants in a non-competitive event: Gimnastrada de Extremadura

La sociedad actual vive a un ritmo frenético, la preocupación por la imagen corporal, por la calidad de vida y por los hábitos saludables, conforman nuevos estilos de vida. Múltiples estudios inciden en la necesidad de crear hábitos de vida saludables desde la infancia. El objetivo de este trabajo fue medir, el grado de disfrute al participar en una manifestación deportiva no competitivo como la Gimnastrada de Extremadura, utilizando para ello la Physical Activity Enjoyment Scale (PACES). Los resultados muestran que el grado de disfrute ha sido positivo y elevado además de confirmar la evolución en cuanto a número de participantes, procedencia y público. Es por ello, que se debe incentivar, apoyar y difundir todas aquellas actividades físicas, deportivas y artísticas que, a nivel escolar, extraescolar y fuera del ámbito educativo se promuevan, para así favorecer y asegurar la práctica posterior que procurará en el individuo un mayor bienestar físico y psicológico y por tanto ser más felices

Nowadays, society operates at a frenetic pace. Concerns about body image, quality of life, and healthy habits are giving rise to new lifestyles and habits. There are currently multiple studies that focus on the need to encourage and adopt healthy habits in early childhood. The aim of this study was to measure the joy that children experienced while participating in non-competitive sport manifestation, such as the Gimnastrada of Extremadura, by using the Physical Activity Enjoyment Scale (PACES). The results of this study were incredibly positive, confirming high participant enjoyment, as well as increased engagement and participation in students from diverse nationalities and socioeconomic backgrounds. Given these results, Physical Education should be incentivized both in and outside of the classroom. Professionals must take the lead by encouraging and providing support for the numerous physical, artistic, and sport-related activities that are available both in and outside of school. In this way, we may increase subsequent participation in these activities, which will contribute to greater

Cambios en el Índice de Hígado Graso con una intervención con dieta mediterránea: seguimiento de 6 años del ensayo PREDIMED-Málaga / Changes in fatty liver index after consuming a Mediterranean diet: 6-year follow-up of the PREDIMED-Malaga trial

Objetivo: Analizar el efecto sobre el Índice de Hígado Graso (FLI, Fatty Liver Index) de la intervención con dieta mediterránea enriquecida con aceite de oliva virgen extra o frutos secos frente a un grupo control con una dieta baja en grasas. Metodología: Participantes del ensayo PREDIMED-Málaga, libres de enfermedad cardiovascular basalmente, pero con alto riesgo de desarrollarla. Al inicio, al año y a los 3, 5 y 6 años se les realizó mediciones antropométricas y toma de muestras de sangre para calcular el FLI. Se usaron modelos lineales mixtos para explorar los efectos fijos de los 3 grupos de intervención sobre el FLI, y sus interacciones con el tiempo. Resultados: Cumplían los criterios de participación en el estudio 276 participantes. La edad media fue de 67 años, con un 66% de mujeres. La prevalencia basal de HGNA estimado fue del 57%. El cambio temporal del FLI en el grupo control aumentó con el tiempo (1,13±0,4; p=0,006). En el grupo DietMed+AOVE la evolución fue similar a la de este, aunque por debajo (−3,90±1,9; p=0,038), y en DietMed+FS fue significativamente menor (−1,63±0,62; p=0,009). En el DietMed+FS la evolución del cambio del IMC fue 0,100 puntos menor al año en comparación con el grupo control (p=0,004). En el grupo de control, el cambio del perímetro de cintura aumentó significativamente con el tiempo (0,61±0,16cm/año; p<0,001) en contraste con DietMed+AOVE(−0,51±0,22; p=0,019). Conclusiones: La intervención dietética con dieta mediterránea podría retrasar o enlentecer la progresión natural del HGNA, siendo beneficiosa para la prevención y el tratamiento del mismo. No obstante, se necesitan estudios que ayuden a corroborar las conclusiones obtenidas (AU)

Objective: To analyze the effect of an intervention with a Mediterranean diet supplemented with either extra virgin olive oil or nuts, on the fatty liver index (FLI), compared to a low-fat control diet. Methods: Participants of the PREDIMED-Malaga trial, free from cardiovascular disease at baseline, but with a high risk to develop it, were included in this study. Anthropometric measurements were assessed and blood samples were taken to calculate participants’ FLI at study baseline and after one, 3, 5 and 6 years. Mixed linear models were used to explore the fixed effects of the 3 intervention groups on the FLI as well as their interaction with time. Results: A total of 276 participants were included in the study. Average participant age was 67 years, with 66% of participants being women. The baseline prevalence of NAFL was 57%. The change in the FLI of the control group increased significantly over time (1.13±0.41; P=.006). In the MedDiet+EVOO group, the time trend of the change in the FLI was similar to that of the control group, although it was seen to be lower (−3.90±1.9; P=.038). In the MedDiet+Nuts group, the trend was significantly lower than that of the control group (−1.63±0.62; P=.009). In the MedDiet+Nuts group, the trend of changes in participants’ BMI was 0.100 points lower per year compared to the control group (P=.004). In the control group, the change in waist circumference increased significantly over time (0.61±0.16cm/year; P<.001) in contrast to the MedDiet+EVOO group, in which this variable remained stable (−0.51±0.22; P=.019). Conclusions: A dietary intervention consisting of a Mediterranean diet could delay or slow down the natural progression of NAFL, thus, being beneficial for its prevention and treatment. However, further studies supporting these conclusions have yet to be carried out (AU)