COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m2, harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (ßadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Phase 2 Trial of the Farnesyltransferase Inhibitor Tipifarnib for Relapsed/Refractory Peripheral T Cell Lymphoma.

A phase 2, international, open-label, non-randomized, single-arm trial was conducted to evaluate the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, as monotherapy for relapsed/refractory peripheral T-cell lymphoma (PTCL) and to evaluate tumor mutation profile as a biomarker of response. Adults with relapsed/refractory PTCL received tipifarnib 300 mg orally twice daily for 21 days in a 28-day cycle. The primary endpoint was objective response rate (ORR); secondary endpoints included ORR, progression-free survival (PFS), duration of response (DOR), and adverse events (AEs) in specific subtypes. Sixty-five patients with PTCL were enrolled: n=38 angioimmunoblastic T-cell lymphoma (AITL), n=25 PTCL not otherwise specified (PTCL-NOS), and n=2 other T-cell lymphomas. The ORR was 39.7% (95% CI, 28.1-52.5) in all patients and 56.3% (95% CI, 39.3-71.8) for AITL. Median PFS was 3.5 months overall (954% CI, 2.1-4.4), and 3.6 months (95% CI, 1.9-8.3) for AITL. Median DOR was 3.7 months (95% CI, 2.0-15.3), and greatest in AITL patients (7.8 months; 95% CI, 2.0-16.3). The median overall survival was 32.8 months (95% CI, 14.4 to not applicable). Tipifarnib-related hematologic AEs were manageable and included: neutropenia (43.1%), thrombocytopenia (36.9%), and anemia (30.8%); other tipifarnib-related AEs included nausea (29.2%) and diarrhea (27.7%). One treatment-related death occurred. Mutations in RhoA, DNMT3A, and IDH2 were seen in 60%, 33%, and 27%, respectively, in the AITL tipifarnib responder group vs 36%, 9%, and 9% in the non-responder group. Tipifarnib monotherapy demonstrated encouraging clinical activity in heavily pre-treated relapsed/refractory PTCL, especially in AITL, with a manageable safety profile. ClinicalTrials.gov NCT02464228.

Physical activity shifts gut microbiota structure in aged subjects with overweight/obesity and metabolic syndrome.

We aimed to identify how physical activity (PA), within the context of a Mediterranean diet, affects metabolic variables and gut microbiota in older individuals with overweight/obesity and metabolic syndrome. Observational analysis was conducted as part of the PREDIMED-Plus study with 152 males and 145 females with overweight/obesity and metabolic syndrome. General assessments, anthropometric and biochemical measurements, and gut microbial 16S rRNA sequencing data were analyzed at baseline and 1-year of follow-up. Participants were stratified by tertiles of 1-year change in total PA-related energy expenditure ranging from -98.77 to 1099.99 METs (min/week). The total PA percentage of change was reduced in tertile 1 (-44.83 ± 24.94), increased in tertile 2 (28.96 ± 23.33) and tertile 3 (273.64 ± 221.42). Beta diversity analysis showed differences in the gut microbiota population within each tertile group. Significant differences were found at phylum, family, and genus levels in the gut microbiota of the three tertile groups at baseline and 1-year timepoint. Tertile 3, the group with the greatest increase in PA, was characterized by increases in their levels of Sutterella, Bilophila, and Lachnospira bacteria as well as a reduction in Collinsella. Moreover, this tertile showed a different pattern in its predicted metabolic capacities to the other groups. Our results have demonstrated that changes in PA such as lifestyle and Mediterranean diet induces specific variations in the gut microbiota profile. This modulation of gut microbiome populations and their metabolic capacities may contribute to the health of the aged individuals with overweight/obesity and metabolic syndrome.

More Adult Women than Men at High Cardiometabolic Risk Reported Worse Lifestyles and Self-Reported Health Status in the COVID-19 Lockdown.

BACKGROUND: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown. METHODS: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data. RESULTS: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001). CONCLUSIONS: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Machine learning allows robust classification of visceral fat in women with obesity using common laboratory metrics.

The excessive accumulation and malfunctioning of visceral adipose tissue (VAT) is a major determinant of increased risk of obesity-related comorbidities. Thus, risk stratification of people living with obesity according to their amount of VAT is of clinical interest. Currently, the most common VAT measurement methods include mathematical formulae based on anthropometric dimensions, often biased by human measurement errors, bio-impedance, and image techniques such as X-ray absorptiometry (DXA) analysis, which requires specialized equipment. However, previous studies showed the possibility of classifying people living with obesity according to their VAT through blood chemical concentrations by applying machine learning techniques. In addition, most of the efforts were spent on men living with obesity while little was done for women. Therefore, this study aims to compare the performance of the multilinear regression model (MLR) in estimating VAT and six different supervised machine learning classifiers, including logistic regression (LR), support vector machine and decision tree-based models, to categorize 149 women living with obesity. For clustering, the study population was categorized into classes 0, 1, and 2 according to their VAT and the accuracy of each MLR and classification model was evaluated using DXA-data (DXAdata), blood chemical concentrations (BLDdata), and both DXAdata and BLDdata together (ALLdata). Estimation error and R 2 were computed for MLR, while receiver operating characteristic (ROC) and precision-recall curves (PR) area under the curve (AUC) were used to assess the performance of every classification model. MLR models showed a poor ability to estimate VAT with mean absolute error ≥ 401.40 and R 2 ≤ 0.62 in all the datasets. The highest accuracy was found for LR with values of 0.57, 0.63, and 0.53 for ALLdata, DXAdata, and BLDdata, respectively. The ROC AUC showed a poor ability of both ALLdata and DXAdata to distinguish class 1 from classes 0 and 2 (AUC = 0.31, 0.71, and 0.85, respectively) as also confirmed by PR (AUC = 0.24, 0.57, and 0.73, respectively). However, improved performances were obtained when applying LR model to BLDdata (ROC AUC ≥ 0.61 and PR AUC ≥ 0.42), especially for class 1. These results seem to suggest that, while a direct and reliable estimation of VAT was not possible in our cohort, blood sample-derived information can robustly classify women living with obesity by machine learning-based classifiers, a fact that could benefit the clinical practice, especially in those health centres where medical imaging devices are not available. Nonetheless, these promising findings should be further validated over a larger population.

Hypothalamic Inflammation Improves Through Bariatric Surgery, and Hypothalamic Volume Predicts Short-Term Weight Loss Response in Adults With or Without Type 2 Diabetes.

OBJECTIVE: Preclinical research implicates hypothalamic inflammation (HI) in obesity and type 2 diabetes pathophysiology. However, their pathophysiological relevance and potential reversibility need to be better defined. We sought to evaluate the effect of bariatric surgery (BS) on radiological biomarkers of HI and the association between the severity of such radiological alterations and post-BS weight loss (WL) trajectories. The utility of cerebrospinal fluid large extracellular vesicles (CSF-lEVs) enriched for microglial and astrocyte markers in studying HI was also explored. RESEARCH DESIGN AND METHODS: We included 72 individuals with obesity (20 with and 52 without type 2 diabetes) and 24 control individuals. Participants underwent lumbar puncture and 3-T MRI at baseline and 1-year post-BS. We assessed hypothalamic mean diffusivity (MD) (higher values indicate lesser microstructural integrity) and the volume of the whole and main hypothalamic subregions. CSF-lEVs enriched for glial and astrocyte markers were determined by flow cytometry. RESULTS: Compared with control group, the obesity and type 2 diabetes groups showed a larger volume and higher MD in the hypothalamic tubular inferior region, the area encompassing the arcuate nucleus. These radiological alterations were positively associated with baseline anthropometric and metabolic measures and improved post-BS. A larger baseline tubular inferior hypothalamic volume was independently related to lesser WL 1 and 2 years after BS. CSF-lEVs did not differ among groups and were unrelated to WL trajectories. CONCLUSIONS: These findings suggest HI improvement after BS and may support a role for HI in modulating the WL response to these interventions.

Impact of bariatric surgery on ovarian reserve markers and its correlation with nutritional parameters and adipokines.

Introduction: A reduction in anti-müllerian hormone (AMH) levels at short-term after bariatric surgery (BS) has been previously described. However, an assessment of ovarian reserve at longer-follow up, and a comprehensive evaluation of the potentially implicated factors has not been reported. Design: Prospective cohort study. Materials and methods: Twenty women aged 18-40 years with BMI 43.95 kg/m2 undergoing BS were studied at baseline (BS0), and at 1 month (BS1), 4 months (BS2), 12 months (BS3), and 24-36 months (BS4) after the surgery. Anthropometrics, reproductive hormones (AMH, FSH, LH, estradiol, testosterone, SHBG, androstenedione), metabolic parameters (adiponectin, leptin, ghrelin, insulin), and nutritional blood parameters (markers of nutritional status, vitamins, and minerals) were obtained at each study time point. Antral follicular count (AFC) was assessed by ultrasonography at BS0, BS3, and BS4. Mixed models were used for analysis of longitudinal data. Results: The mean AMH level was 3.88 ng/mL at BS0, decreased at BS3 (mean= 2.59 ng/mL; p=0.009), and remained stable between BS3 and BS4 (mean= 2.96 ng/mL; p=0.409). We also observed a non-significant decrease in AFC at BS3 (mean=26.14 at BS0, mean 16.81 at BS3; p=0.088) that remained stable at BS4 (mean= 17.86; p=0.731). Mixed models analysis showed: (a) a decrease in 10 kg of body weight was associated with an average decrease of 0.357 ng/mL in AMH (p=0.014); (b) a decrease in 1 BMI point was associated with an average decrease of 0.109 ng/mL in AMH (p=0.005); (c) an increase in 1 µg/mL of adiponectin was associated with an average decrease of 0.091 ng/ml in AMH (p=0.041) Significant positive correlations were found between the AMH levels after BS and plasma concentrations of testosterone, free androgen index, insulin and HOMA index. No significant correlations were detected between AMH levels and nutritional parameters. Conclusions: Our results were in line with previous observations, showing that AMH levels decreased significantly at 12 months after bariatric surgery, in parallel with a non-significant reduction in AFC. Both ovarian reserve markers showed a later stabilization up to the end of the study. Of note, postoperative AMH levels were positively correlated with key androgen and insulin resistance-related parameters.

Effect of a nutritional intervention based on an energy-reduced Mediterranean diet on environmental impact.

OBJECTIVE: To estimate the environmental impact of a dietary intervention based on an energy-reduced Mediterranean diet (MedDiet) after one year of follow-up. METHODS: Baseline and 1-year follow-up data were used for 5800 participants aged 55-75 years with metabolic syndrome in the PREDIMED-Plus study. Food intake was estimated through a validated semiquantitative food consumption frequency questionnaire, and adherence to the MedDiet was estimated through the Diet Score. Using the EAT-Lancet Commission tables we assessed the influence of dietary intake on environmental impact (through five indicators: greenhouse gas emissions (GHG), land use, energy used, acidification and potential eutrophication). Using multivariable linear regression models, the association between the intervention and changes in each of the environmental factors was assessed. Mediation analyses were carried out to estimate to what extent changes in each of 2 components of the intervention, namely adherence to the MedDiet and caloric reduction, were responsible for the observed reductions in environmental impact. RESULTS: We observed a significant reduction in the intervention group compared to the control group in acidification levels (-13.3 vs. -9.9 g SO2-eq), eutrophication (-5.4 vs. -4.0 g PO4-eq) and land use (-2.7 vs. -1.8 m2). Adherence to the MedDiet partially mediated the association between intervention and reduction of acidification by 15 %, eutrophication by 10 % and land use by 10 %. Caloric reduction partially mediated the association with the same factors by 55 %, 51 % and 38 % respectively. In addition, adherence to the MedDiet fully mediated the association between intervention and reduction in GHG emissions by 56 % and energy use by 53 %. CONCLUSIONS: A nutritional intervention based on consumption of an energy-reduced MedDiet for one year was associated with an improvement in different environmental quality parameters.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.

BACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood. OBJECTIVES: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors. METHODS: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota. RESULTS: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors. CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

What is the evidence regarding the safety of new obesity pharmacotherapies.

The use of gut-hormone receptors agonists as new therapeutic options for obesity and some of its related comorbidities, such as type 2 diabetes, has resulted in an unprecedented efficacy in the medical management of people living with obesity (PLWO). Appraisal of the safety of these drugs is of utmost importance considering the large number of PLWO, and the potentially long exposure to these pharmacotherapies. In this narrative review we summarize the evidence on the safety of liraglutide, semaglutide, and tirzepatide as derived from randomized clinical trials conducted in adults living with obesity. Additionally, the safety of these drugs is put into perspective with that of other drugs currently approved for the treatment of PLWO. Overall, the available data support a favorable efficacy versus safety balance for gut-hormone hormone receptor analogues in the treatment of these subjects. Nonetheless, it should be acknowledged that in the context of a chronic disease that has reached epidemic proportions, data from randomized clinical trials aimed primarily at proving the efficacy of these drugs may have been insufficient to unveil all the safety issues. Thus, continuous surveillance on the adverse effects of liraglutide, semaglutide, and tirzepatide is required as we use these drugs in a broader population than that represented in currently available clinical trials.

Comparación del desempeño comunicativo y pragmático de niñas y niños sordos con implante coclear y sus pares normo oyentes / Comparison of the communicative and pragmatic performance of deaf girls and boys with cochlear implants and their normal hearing peers

Durante las últimas décadas, con la masificación del Implante Coclear (IC), muchos niños con sordera de severa a profunda han tenido acceso a desarrollar habilidades lingüísticas orales y auditivas a edades cada vez más tempranas, con frecuencia, los esfuerzos tanto en terapia como en investigación se centran en mejorar las habilidades del lenguaje y de inteligibilidad del habla, existiendo limitadas investigaciones en el terreno de la pragmática en niños sordos con IC. El presente es un estudio piloto que se desarrolla en marco de la investigación del perfil lingüístico del centro de investigación GISTAL, que busca comparar el desempeño pragmático y comunicativo de niñas y niños sordos con implante coclear (data de implante mayor a dos años) con sus pares con audición típica (N=20) en tareas de conversación y denominación. Los resultados muestran un desempeño similar en ambos grupos en las medidas pragmáticas. Las principales diferencias se observaron en variables comunicativas y lingüísticas. A demás, los niños con IC muestran reducciones más significativas en la tarea de conversación que en denominación, lo que podría implicar para ellos, mayores desafíos en tareas con más carga pragmática que conceptual.(AU)

Comparación del desempeño comunicativo y pragmático de niñas y niños sordos con implante coclear y sus pares normo oyentes / Comparison of the communicative and pragmatic performance of deaf girls and boys with cochlear implants and their normal hearing peers

Durante las últimas décadas, con la masificación del Implante Coclear (IC), muchos niños con sordera de severa a profunda han tenido acceso a desarrollar habilidades lingüísticas orales y auditivas a edades cada vez más tempranas, con frecuencia, los esfuerzos tanto en terapia como en investigación se centran en mejorar las habilidades del lenguaje y de inteligibilidad del habla, existiendo limitadas investigaciones en el terreno de la pragmática en niños sordos con IC. El presente es un estudio piloto que se desarrolla en marco de la investigación del perfil lingüístico del centro de investigación GISTAL, que busca comparar el desempeño pragmático y comunicativo de niñas y niños sordos con implante coclear (data de implante mayor a dos años) con sus pares con audición típica (N=20) en tareas de conversación y denominación. Los resultados muestran un desempeño similar en ambos grupos en las medidas pragmáticas. Las principales diferencias se observaron en variables comunicativas y lingüísticas. A demás, los niños con IC muestran reducciones más significativas en la tarea de conversación que en denominación, lo que podría implicar para ellos, mayores desafíos en tareas con más carga pragmática que conceptual.(AU)

Dieta mediterránea hipocalórica y factores de riesgo cardiovascular: análisis transversal de PREDIMED-Plus / Adherence to an energy-restricted Mediterranean diet score and prevalence of cardiovascular risk factors in the PREDIMED-plus: a cross-sectional study

Introducción y objetivos: Los beneficios cardiovasculares de la dieta mediterránea se han evaluado bajo supuestos de ingesta total de energía ad libitum (sin restricción de energía). En el presente trabajo se estudia basalmente la cohorte de un gran ensayo en marcha denominado PREDIMED-Plus y la asociación entre la adherencia a la dieta mediterránea hipocalórica según la escala de 17 puntos (MedDiet) de este ensayo con la prevalencia inicial de factores de riesgo cardiovascular (FRCV). Métodos: Evaluación transversal de los participantes de PREDIMED-Plus (6.874 adultos mayores con sobrepeso/obesidad y síndrome metabólico). Se evaluó a los participantes para determinar la prevalencia de 4 FRCV (hipertensión, obesidad, diabetes, dislipemia). Se estimaron diferencias de medias y razones de prevalencia para FRCV individuales y agrupados con modelos multivariables. Resultados: Una mejor adhesión al patrón MedDiet se asoció significativamente con niveles más bajos de triglicéridos, índice de masa corporal y perímetro abdominal. Comparado con una baja adhesión (≤ 7 puntos en el score de 17 puntos), una mejor adhesión a la MedDiet (11-17 puntos) mostró asociaciones inversas con hipertensión (razón de prevalencia=0,97; IC95%, 0,94-1,00) y obesidad (razón de prevalencia=0,96; IC95% 0,92-1,00), pero se observaron asociaciones positivas con diabetes (razón de prevalencia=1,19; IC95% 1,07-1,32). Comparado con el tercil más bajo de adhesión, las mujeres en el tercil superior mostraron un riesgo menor para la agrupación de 3 o más FRCV (razón de prevalencia=0,91; IC95% 0,83-0,98). Conclusiones: Entre participantes con alto riesgo cardiovascular, la mejor adhesión a MedDiet se asoció a mejores perfiles lipídicos y medidas de adiposidad, y entre las mujeres mostró asociaciones inversas significativas con la agregación de FRCV

Introduction and objectives: The cardiovascular benefits of the Mediterranean diet have usually been assessed under assumptions of ad libitum total energy intake (ie, no energy restriction). In the recently launched PREDIMED-Plus, we conducted exploratory analyses to study the baseline associations between adherence to an energy-restricted Mediterranean diet (MedDiet) and the prevalence of cardiovascular risk factors (CVRF). Methods: Cross-sectional assessment of all PREDIMED-Plus participants (6874 older adults with overweight/obesity and metabolic syndrome) at baseline. The participants were assessed by their usual primary care physicians to ascertain the prevalence of 4 CVRF (hypertension, obesity, diabetes, and dyslipidemia). A 17-point PREDIMED-Plus score was used to measure adherence to the MedDiet. Multivariable models were fitted to estimate differences in means and prevalence ratios for individual and clustered CVRF. Results: Better adherence to a MedDiet pattern was significantly associated with lower average triglyceride levels, body mass index, and waist circumference. Compared with low adherence (≤ 7 points in the 17-point score), better adherence to the MedDiet (11-17 points) showed inverse associations with hypertension (prevalence ratio=0.97; 95%CI, 0.94-1.00) and obesity (prevalence ratio=0.96; 95%CI, 0.92-1.00), but positive associations with diabetes (prevalence ratio=1.19; 95%CI, 1.07-1.32). Compared with the lowest third of adherence, women in the upper third showed a significantly lower prevalence of the clustering of 3 or more CVRF (prevalence ratio=0.91; 95%CI, 0.83-0.98). Conclusions: Among participants at high cardiovascular risk, better adherence to a MedDiet showed significant inverse associations with CVRF among women, and improved lipid profiles and adiposity measures

Identificando políticas públicas: Defensoria Pública e homens infratores da Lei Maria da Penha / Identificación de políticas públicas: Defensoría Pública y hombres infractores de la Ley Maria da Penha / Identifying public policies: Public Defenders and men who broke the Maria da Penha Law

Resumo A avaliação dos serviços de assistência prestados pela Defensoria Pública possibilita a identificação de demandas e problemas que constituirão a origem de futuras políticas públicas. Este artigo apresenta os resultados de uma observação na qual se avaliaram os serviços de assistência prestados pelo Núcleo de Atendimento ao Homem Autor de Violência Doméstica e Familiar (Neah), a partir de depoimentos dos assistidos e de suas companheiras. Como resultado, identificam-se futuros serviços e políticas públicas voltados à prevenção, autorreflexão e mudança de percepção dos homens agressores. Os resultados da observação empírica ressaltam o paradoxo das políticas públicas de atendimento a homens acusados de violência doméstica: enquanto a avaliação dos serviços de assistência prestados pela DP-PA e do atendimento policial por parte das mulheres cônjuges manifesta uma insatisfação pelos resultados do atendimento recebido na DP-PA, com relação aos seus parceiros. Os homens que participaram do grupo terapêutico manifestaram nas entrevistas haver experimentado uma mudança de comportamento com relação às suas cônjuges e sobre a visão da mulher.

Resumen La evaluación de los servicios de asistencia prestados por la Defensoría Pública permite identificar demandas y problemas que constituirán el origen de futuras políticas públicas. Este artículo presenta los resultados de una observación en la que se evaluaron los servicios de asistencia prestados por el Núcleo de Atención al Hombre Autor de Violencia Doméstica y Familiar (Neah) a partir de testimonios de los asistidos y sus cónyuges. Como resultado, se identifican futuros servicios y políticas públicas dirigidas a la prevención, autorreflexión y cambio de percepción de los hombres agresores. Los resultados de la observación empírica resaltan la paradoja de las políticas públicas de atención a los hombres acusados de violencia doméstica: mientras que la evaluación de los servicios de asistencia ofrecidos por la DP-PA y de la atención policial por parte de las mujeres cónyuges manifiesta una insatisfacción por los resultados de la atención recibida en la DP-PA con relación a sus compañeros. Los hombres que participaron en el grupo terapéutico manifestaron en las entrevistas que habían experimentado un cambio de comportamiento con relación a sus cónyuges y sobre la visión de la mujer.

Abstract The evaluation of the assistance services provided by the Public Defender's Office allows to identify demands and problems for public policies. This article presents the results of an observation research that evaluated the services of the Núcleo de Atendimento ao Homem Autor de Violência Doméstica e Familiar (Neah) (Support Center for men who committed Domestic and Family Violence), considering the testimonies of people assisted by the institution and their partners. From the results, it is possible to identify future actions and public policies aimed to prevent, promote self-reflection, and change the perception related to aggressive men. The results of the empirical observation highlight the paradox of the public policies of assistance to men accused of domestic violence, since the spouses' evaluation about the police assistance and the assistance services offered by the DP-PA shows a dissatisfaction with the results of the services their partners receive. Men who participated in the therapeutic group expressed during the interviews that they experienced a change in behavior toward their spouses and their view about women.

Uma análise da produção acadêmica sobre a evolução do fenômeno da judicialização da saúde no Brasil / An analysis of the academic production on the evolution of the phenomenon of health judicialization in Brazil

Objetivo: Analisar a produção acadêmica sobre a evolução do fenômeno da judicialização da saúde no Brasil. Metodologia: Realizou-se revisão narrativa, com levantamento bibliográfico e documental em que se procedeu a coleta de artigos e jurisprudências em sites eletrônicos Resultados: A expansão da eficácia normativa constitucional proporcionou o acesso à saúde por meio do crescimento das demandas judiciais. A atividade jurisprudencial do STF evoluiu para compreender a necessidade de critérios em concessões judiciais de medicamentos. Aliado a isso, a constatação de que as demandas judiciais desorganizam a gestão publica da assistência farmacêutica. Conclusões: A literatura revela que o fenômeno da Judicialização da saúde nos tribunais resulta, e é resultado, da desorganização dos sistemas sociais. Para a literatura, o CNJ tem tido a função de organizar procedimentos de gestão em que os juízes devem aperfeiçoar de forma racionalizada o ato de julgar em observância às ações de governança que vem sendo desenvolvidas na saúde. (AU)

Objective: To analyse of the academic production on the evolution of the phenomenon of health judicialization in Brazil. Methodology: A narrative review was carried out, with a bibliographical and documentary survey in which articles and jurisprudence were collected in electronic websites Results: The expansion of constitutional normative effectiveness provided access to health through the growth of judicial demands. The jurisprudential activity of the Supreme Court has evolved to understand the need for criteria in judicial drug awards. Along with this, the finding that the lawsuits disrupt the public management of pharmaceutical care. Conclusions: The literature reveals that the phenomenon of the Judicialization of health in the courts results, and is a result, of the disorganization of social systems. For the literature, the CNJ has had the function of organizing management procedures in which the judges must improve in a rationalized way the act of judging in observance of the actions of governance that are being developed in health. (AU)

Objetivo: Análisis de la producción académica sobre la evolución del fenómeno de la judicialización de la salud en Brasil. Metodología: La metodología se realizó con la revisión bibliográfica y documental en la que se procedió a la recolección de artículos y jurisprudencias en sitios electrónicos. Resultados: La expansión de la eficacia normativa constitucional proporcionó el acceso a la salud a través del crecimiento de las demandas judiciales. La actividad jurisprudencial del STF evolucionó para comprender la necesidad de criterios en concesiones judiciales de medicamentos. Aliado a ello, la constatación de que las demandas judiciales desorganizan la gestión pública de la asistencia farmacéutica. Conclusiones: La literatura revela que el fenómeno de la Judicialización de la salud en los tribunales resulta, y es resultado, de la desorganización de los sistemas sociales. Para la literatura, el CNJ ha tenido la función de organizar procedimientos de gestión en que los jueces deben perfeccionar de forma racionalizada el acto de juzgar en observancia a las acciones de gobernanza que vienen siendo desarrolladas en la salud. (AU)

Uma análise da produção acadêmica sobre a evolução do fenômeno da judicialização da saúde no Brasil / An analysis of the academic production on the evolution of the phenomenon of health judicialization in Brazil / Un análisis de la producción académica sobre la evolución del fenómeno de la judicialización de la salud en Brasil

Objetivo: Analisar a produção acadêmica sobre a evolução do fenômeno da judicialização da saúde no Brasil. Metodologia: Realizou-se revisão narrativa, com levantamento bibliográfico e documental em que se procedeu a coleta de artigos e jurisprudências em sites eletrônicos Resultados: A expansão da eficácia normativa constitucional proporcionou o acesso à saúde por meio do crescimento das demandas judiciais. A atividade jurisprudencial do STF evoluiu para compreender a necessidade de critérios em concessões judiciais de medicamentos. Aliado a isso, a constatação de que as demandas judiciais desorganizam a gestão publica da assistência farmacêutica. Conclusões: A literatura revela que o fenômeno da Judicialização da saúde nos tribunais resulta, e é resultado, da desorganização dos sistemas sociais. Para a literatura, o CNJ tem tido a função de organizar procedimentos de gestão em que os juízes devem aperfeiçoar de forma racionalizada o ato de julgar em observância às ações de governança que vem sendo desenvolvidas na saúde.

Objective: To analyse of the academic production on the evolution of the phenomenon of health judicialization in Brazil. Methodology: A narrative review was carried out, with a bibliographical and documentary survey in which articles and jurisprudence were collected in electronic websites Results: The expansion of constitutional normative effectiveness provided access to health through the growth of judicial demands. The jurisprudential activity of the Supreme Court has evolved to understand the need for criteria in judicial drug awards. Along with this, the finding that the lawsuits disrupt the public management of pharmaceutical care. Conclusions: The literature reveals that the phenomenon of the Judicialization of health in the courts results, and is a result, of the disorganization of social systems. For the literature, the CNJ has had the function of organizing management procedures in which the judges must improve in a rationalized way the act of judging in observance of the actions of governance that are being developed in health.

Objetivo: Análisis de la producción académica sobre la evolución del fenómeno de la judicialización de la salud en Brasil. Metodología: La metodología se realizó con la revisión bibliográfica y documental en la que se procedió a la recolección de artículos y jurisprudencias en sitios electrónicos. Resultados: La expansión de la eficacia normativa constitucional proporcionó el acceso a la salud a través del crecimiento de las demandas judiciales. La actividad jurisprudencial del STF evolucionó para comprender la necesidad de criterios en concesiones judiciales de medicamentos. Aliado a ello, la constatación de que las demandas judiciales desorganizan la gestión pública de la asistencia farmacéutica. Conclusiones: La literatura revela que el fenómeno de la Judicialización de la salud en los tribunales resulta, y es resultado, de la desorganización de los sistemas sociales. Para la literatura, el CNJ ha tenido la función de organizar procedimientos de gestión en que los jueces deben perfeccionar de forma racionalizada el acto de juzgar en observancia a las acciones de gobernanza que vienen siendo desarrolladas en la salud.

Diagnóstico y tratamiento del déficit de hierro, con o sin anemia, pre y poscirugía bariátrica / Diagnosis and treatment of iron deficiency, with or without anemia, before and after bariatric surgery

La cirugía bariátrica es una modalidad terapéutica para la obesidad grave que se utiliza cada vez con más frecuencia, y permite que el paciente consiga una pérdida de peso mantenida en el tiempo y una resolución o mejoría de la mayor parte de las enfermedades asociadas. Una de las principales complicaciones a medio y a largo plazo es el déficit de hierro y la anemia ferropénica, que puede afectar hasta al 50% de los casos, y deteriora de manera importante la calidad de vida del paciente. Estas alteraciones pueden estar presentes desde el preoperatorio. El objetivo de la presente revisión es elaborar unos esquemas de diagnóstico y tratamiento del déficit de hierro y la anemia ferropénica en el pre y postoperatorio de la cirugía bariátrica (AU)

Bariatric surgery (BS) is an increasingly used therapeutic option for severe obesity which allows patients to achieve sustained weight loss over time and resolution or improvement in most associated pathological conditions. Major mid- and long-term complications of BS include iron deficiency and iron-deficient anemia, which may occur in up to 50% of cases and significantly impair patient quality of life. These changes may be present before surgery. The aim of this review was to prepare schemes for diagnosis and treatment of iron deficiency and iron-deficient anemia before and after bariatric surgery (AU)

Modulación del efecto incretina en el tratamiento de la diabetes / Modulation of the incretin effect in the treatment of diabetes

La modulación del efecto incretina ha abierto una nueva estrategia en el tratamiento de la diabetes mellitus tipo 2 (DM2). La potenciación de este mecanismo fisiológico se ha conseguido hasta la fecha por dos vías. De una parte, la inhibición farmacológica de la enzima que degrada fisiológicamente a péptido similar al glucagón-1 (GLP-1), la dipeptidil peptidasa-4 (DPP-4). Por otra, el desarrollo de moléculas agonistas del receptor de GLP-1 (arGLP-1) resistentes a la acción de la DPP-4. Distintos ensayos clínicos han demostrado la mayor eficacia clínica de los arGLP-1, lo cual parecería ligado al alcance de mayores niveles circulantes de GLP-1. En contrapartida, esta parece ser la base también de la mayor tasa de efectos adversos asociados al tratamiento con arGLP-1 en comparación con la inhibición de DPP-4. La valoración de estas y otras características diferenciadoras de ambas familias de fármacos deberá marcar nuestra elección en el tratamiento personalizado de la hiperglucemia en el paciente con DM2 (AU)

Modulation of the incretin effect has opened up a new strategy in the treatment of diabetes mellitus type 2 (DM2). To date, this physiological mechanism has been boosted in two ways: firstly, by pharmacological inhibition of the enzyme that physiologically degrades glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP4); secondly, through the development of GLP-1 agonists (GLP-1a) that are resistant to the action of DPP-4. Several clinical trials have shown the clinical superiority of GLPa, which seems to be linked to higher circulating levels of GLP-1. On the other hand, this higher efficacy also seems to be associated with the higher rate of adverse effects associated with aGLP-1 therapy compared with DPP-4 inhibition. These and other differentiating characteristics of the two drug families will determine the choice of drug therapy in the personalized treatment of hyperglycemia in patients with DM2 (AU)