Platform Image Processing Applied to the Study of Retinal Vessels

Recent studies have found retinal vessel caliber to be related to the risk of hypertension, left ventricular hypertrophy, metabolic syndrome, stroke and others coronary artery diseases. The vascular system in the human retina is easily perceived in its natural living state by the use of a retinal camera. Nowadays, there is general experimental agreement on the analysis of the patterns of the retinal blood vessels in the normal human retina. The development of automated tools designed to improve performance and decrease interobserver variability, therefore, appears necessary. This paper presents a study focused on developing a technological platform specialized in assessing retinal vessel caliber and describing the relationship of the results obtained to cardiovascular risk

Cumulative exposure to tacrolimus and incidence of cancer after liver transplantation

Cancer is the leading cause of death after liver transplantation (LT). This multicenter case–control nested study aimed to evaluate the effect of maintenance immunosuppres sion on post-LT malignancy. The eligible cohort included 2495 LT patacrolimus-based immunosuppression. After 13 922 person/years follow-up, 425 patients (19.7%) developed malignancy (cases) and were matched with 425 controls by propensity score based on age, gender, smoking habit, etiology of liver disease, and hepatocellular carcinoma (HCC) before LT. The independent predictors of post-LT malignancy were older age (HR = 1.06 [95% CI 1.05–1.07]; p < .001), male sex (HR = 1.50 [95% CI 1.14–1.99]), smoking habit (HR = 1.96 [95% CI 1.42–2.66]), and alcoholic liver disease (HR = 1.53 [95% CI 1.19–1.97]). In selected cases and controls (n = 850), the immunosuppression protocol was similar (p = .51). An increased cumulative exposure to tacrolimus (CET), calculated by the area under curve of trough concentrations, was the only immunosuppression-related predictor of post-LT malignancy after controlling for clinical features and baseline HCC (CET at 3 months p = .001 and CET at 12 months p = .004). This effect was consistent for de novo malignancy (after excluding HCC recurrence) and for internal neoplasms (after excluding non-melanoma skin cancer). Therefore, tacrolimus minimization, as monitored by CET, is the key to modulate immunosuppression in order to prevent cancer after LT

Relationship between intima-media thickness of the common carotid artery and arterial stiffness in subjects with and without type 2 diabetes: a case-series report

Background: We examined the relationship between the intima-media thickness of the common carotid artery (CCA-IMT) and arterial stiffness, assessed by pulse wave velocity (PWV), the ambulatory arterial stiffness index (AASI) and the augmentation index (AIx) in subjects with and without type 2 diabetes. Methods: A case-series study was made in 366 patients (105 diabetics and 261-non-diabetics). Ambulatory blood pressure monitoring was performed on a day of standard activity with the SpaceLabs 90207 system. AASI was calculated as "1-slope" from the within-person regression of diastolic-on-systolic ambulatory blood pressure readings. PWV and AIx were measured with the SphygmoCor system, and a Sonosite Micromax ultrasound unit was used for automatic measurements of CCA-IMT. Results: PWV, AASI and CCA-IMT were found to be greater in diabetic patients, while no differences in AIx were observed between the two groups. CCA-IMT was independently correlated to the three measures of arterial stiffness in both groups. We found an increase in CCA-IMT of 0.40, 0.24 and 0.36 mm in diabetics, and of 0.48, 0.17 and 0.55 mm in non-diabetics for each unit increase in AASI, AIx and PWV. The variability of CCA-IMT was explained mainly by AASI, AIx and gender in diabetic patients, and by age, gender, AASI and PWV in non-diabetic patients. Conclusions: CCA-IMT showed a positive correlation to PWV, AASI and AIx in subjects with and without type 2 diabetes. However, when adjusting for age, gender and heart rate, the association to PWV was lost in diabetic patients, in the same way as the association to Alx in non-diabetic patients. The present study demonstrates that the three measures taken to assess arterial stiffness in clinical practice are not interchangeable, nor do they behave equally in all subjects

Usefulness of circulating microRNAs miR-146a and miR-16-5p as prognostic biomarkers in community-acquired pneumonia

Introduction Patients with community-acquired pneumonia (CAP) undergo a dysregulated host response that is related to mortality. MicroRNAs (miRNAs) participate in this response, but their expression pattern and their role as biomarkers in CAP have not been fully characterized. Methods A prospective observational study was performed in a cohort of 153 consecutive patients admitted to hospital with CAP. Clinical and analytical variables were collected, and the main outcome variable was 30-day mortality. Small RNA was purified from plasma of these patients obtained on the first day of admission, and miRNA expression was analyzed by RTPCR. Univariate and multivariate analyses were carried out through the construction of a logistic regression model. The proposed model was compared with established prognostic clinical scales using ROC curve analysis. Results The mean age of the patients included was 74.7 years [SD 15.9]. Their mean PSI was 100.9 [SD 34.6] and the mean modified Charlson index was 2.9 [SD 3.0]. Both miR-146a and miR- 16-5p showed statistically significant association with 30-day mortality after admission due to CAP (1.10 vs. 0.23 and 51.74 vs. 35.23, respectively), and this association remained for miR-16-5p in the multivariate analysis adjusted for age, gender and history of bronchoaspiration (OR 0.95, p = 0.021). The area-under-the-curve (AUC) of our adjusted multivariate model (AUC = 0.954 95%CI [0.91–0.99]), was better than those of prognostic scales such as PSI (AUC = 0.799 [0.69–0.91]) and CURB-65 (AUC = 0.722 [0.58–0.86]). Conclusions High levels of miR-146a-5p and miR-16-5p upon admission due to CAP are associated with lower mortality at 30 days of follow-up. Both miRNAs could be used as biomarkers of good prognosis in subjects hospitalized with CAPThis work has been funded by the Carlos III Health Institute (ERDF, European Regional Development Fund), by the Spanish Society of Pneumology and Thoracic Surgery and by the Ministry of Science, Innovation and Universities of Spain

Sedentary behaviour patterns and carotid intima-media thickness in Spanish healthy adult population

Objective: The aim of this study was to analyze the association between sedentary behaviour, as assessed by an accelerometer, and mean carotid intima-media thickness (IMT). Methods: The study included 263 healthy subjects belonging to the EVIDENT study (59.3% women). Carotid IMT was measured by carotid ultrasonography. Sedentary behaviour was measured objectively over 7 days using ActiGraph accelerometers. Thresholds of 10 consecutive minutes were used to establish sedentary bouts, and assess the number (n/day), and length 10 min (min/day). Results: Total sedentary time and sedentary time in bouts 10 min was higher in participants with a larger mean carotid IMT (>P75). Otherwise, this sedentary time in bouts 10 min parameter was weakly associated with augmented carotid IMT injury in the logistic regression model. Conclusion: Total sedentary time and sedentary time in bouts 10 min, as assessed by accelerometer, was positively but weakly associated with carotid IMT. Equally, this sedentary time in bouts 10 min was associated with carotid injury, but disappears after adjusting for potential confounders. These findings support that reducing sedentary time and increasing breaks in bouts of sedentary time might represent a useful additional strategy in the cardiovascular disease prevention. Trial Registration: Clinical Trials.gov Identifier: NCT01083082.The EVIDENT Grou

Behavioural intervention to reduce disruptive behaviours in adult day care centres users: A randomizsed clinical trial (PROCENDIAS study)

[ENG]Aim: This study assesses the effect of an intervention to reduce the disruptive behaviours (DB) presented by care recipient users of adult day care centres (ADCC), thereby reducing caregiver overload. While ADCC offer beneficial respite for family caregivers, the DB that many care recipients show promote resistance to attending these centres, which can be a great burden on their family caregivers. Design: Randomized controlled clinical trial. Methods: The study was carried out with 130 family caregivers of people attending seven ADCC in the municipality of Salamanca (Spain), randomly distributed into intervention and control groups. The intervention was applied across eight sessions, one per week, in groups of 8–10 people where caregivers were trained in the Antecedent- Behavior-Consequence (ABC) model of functional behaviour analysis. The primary outcome was the reduction of DB measured with the Revised Memory and Behavior Problems Checklist (RMBPC). Results: An average reduction in the RMBPC of 4.34 points was obtained in the intervention group after applying the intervention (p < 0.01 (U de Mann–Whitney); Cohen d = 1.00); furthermore, differences were found in the Center for Epidemiologic Studies Depression Scale (CES-D) (U = −2.67; p = 0.008; Cohen d = 0.50) and in the Short Zarit Burden Interview (Short ZBI) (t = −4.10; p < 0.01; Cohen d = 0.98). Conclusion: The results obtained suggest that the implementation of this intervention could reduce both the frequency of DB occurrence and the reaction of the caregiver to their appearance. Improvement was also noted in the results regarding overload and emotional state of the family caregiver. Impact: To our knowledge, this is the first randomized clinical trial to show that an intervention based on the ABC model could reduce the frequency and reaction of DB of care recipients in ADCC increasing their quality of life, and improving the mental health and overload of their family caregivers

Abdominal obesity as a mediator of the influence of physical activity on insulin resistance in Spanish adults

Objective. The aim of the study was to analyze the relationship between moderate-to-vigorous physical activity (MVPA) and insulin resistance (IR) in Spanish adults and to examine whether this relationship is mediated by abdominal obesity (waist circumference —WC). Methods. The cross-sectional study included 1162 healthy subjects belonging to the EVIDENT study (mean age 55.0±13.3 years; 61.8%women) from six different Spanish provinces. Moderate-to-vigorous physical activiity (MVPA) was measured objectively over 7 days using Actigraph accelerometers, collecting data in 60-second epochs, and retaining respondents with ≥4 valid days for the analysis. The homeostasis model of assessment (HOMA-IR) was used to determine IR, and its individual components – fasting glucose and insulin – were determined using standard protocols. Linear regressionmodelswere fitted according to Baron and Kenny's procedures for mediation analysis. Results. Fasting insulin and HOMA-IR levels were significantly worse in adults who spent fewer minutes in MVPA (first quartile ≤ 30.1 and 22.7 min/day in men and women, respectively) after adjusting for age, sex, smoking habits, drinking habits, accelerometer wear time, sedentary time, and Mediterranean diet adherence. However,when WC was added to the ANCOVA models as a covariate, the effects disappeared.Mediation analysis reported that WC acts as a fullmediator in the relationship between MVPA and IR (HOMA-IR and fasting insulin). Conclusion. These findings show that WC plays a pivotal role in the relationship between MVPA and IR, and therefore highlights that decreasing abdominal obesity might be considered as an intermediate outcome for evaluating interventions aimed at preventing diabetes mellitus.The Evident Grou

EVIDENT 3 study: A randomized, controlled clinical trial to reduce inactivity and caloric intake in sedentary and overweight or obese people using a smartphone application study protocol

FUNDAMENTOS: La tecnología móvil, cuando se incluye dentro de las intervenciones de componentes múltiples, podría contribuir a una pérdida de peso más efectiva. El objetivo de este proyecto es evaluar el impacto de añadir el uso de la aplicación EVIDENT 3, diseñada para promover la salud a los hábitos de vida, a las estrategias de modificación tradicionales empleadas para la pérdida de peso. También se evaluarán otras conductas específicas (caminar, ingesta de calorías, tiempo sentado) y resultados (calidad de vida, marcadores inflamatorios, mediciones del envejecimiento arterial). MÉTODOS: Ensayo clínico aleatorio y multicéntrico con 2 grupos paralelos. El estudio se llevará a cabo en el ámbito de la atención primaria e incluirá 700 sujetos de 20 a 65 años, con un índice de masa corporal (27,5-40kg/m2), que están clínicamente clasificados como sedentarios. El resultado primario será la pérdida de peso. Los resultados secundarios incluirán cambios en la forma de caminar (pasos/d), el tiempo de permanencia sentado (min/sem), la ingesta calórica (kcal/d), la calidad de vida, el envejecimiento arterial (índice de aumento) y los niveles de marcadores proinflamatorios. Los resultados se medirán en la línea de base, después de 3 meses y después de 1 año. Los participantes serán asignados aleatoriamente al grupo de intervención (IG) o al grupo de control (CG). Ambos grupos recibirán el asesoramiento tradicional de estilo de vida de atención primaria antes de la asignación al azar. A los sujetos del IG se les prestará un teléfono inteligente y una banda inteligente por un período de 3 meses, correspondiente a la duración de la intervención. La aplicación del EVIDENTE 3 integra la información recogida por la banda inteligente sobre la actividad física y la información autodeclarada por los participantes sobre la ingesta diaria de alimentos. Utilizando esta información, la aplicación genera recomendaciones y objetivos personalizados para la pérdida de peso. DISCUSIÓN: Hay una gran diversidad en las aplicaciones utilizadas obteniendo diferentes resultados en la mejora del estilo de vida y la pérdida de peso. Las poblaciones estudiadas no son homogéneas y generan resultados diferentes. Los resultados de este estudio ayudarán a nuestra comprensión de la eficacia de las nuevas tecnologías, combinadas con el asesoramiento tradicional, para reducir la obesidad y permitir estilos de vida más saludables.INTRODUCTION: Mobile technology, when included within multicomponent interventions, could contribute to more effective weight loss. The objective of this project is to assess the impact of adding the use of the EVIDENT 3 application, designed to promote healthy living habits, to traditional modification strategies employed for weight loss. Other targeted behaviors (walking, caloric-intake, sitting time) and outcomes (quality of life, inflammatory markers, measurements of arterial aging) will also be evaluated. METHODS: Randomized, multicentre clinical trial with 2 parallel groups. The study will be conducted in the primary care setting and will include 700 subjects 20 to 65 years, with a body mass index (27.5–40kg/m2), who are clinically classified as sedentary. The primary outcome will be weight loss. Secondary outcomes will include change in walking (steps/d), sitting time (min/wk), caloric intake (kcal/d), quality of life, arterial aging (augmentation index), and pro-inflammatory marker levels. Outcomes will be measured at baseline, after 3 months, and after 1 year. Participants will be randomly assigned to either the intervention group (IG) or the control group (CG). Both groups will receive the traditional primary care lifestyle counseling prior to randomization. The subjects in the IG will be lent a smartphone and a smartband for a 3-month period, corresponding to the length of the intervention. The EVIDENT 3 application integrates the information collected by the smartband on physical activity and the self-reported information by participants on daily food intake. Using this information, the application generates recommendations and personalized goals for weight loss. DISCUSSION: There is a great diversity in the applications used obtaining different results on lifestyle improvement and weight loss. The populations studied are not homogeneous and generate different results. The results of this study will help our understanding of the efficacy of new technologies, combined with traditional counseling, towards reducing obesity and enabling healthier lifestyles.• Ministerio de Ciencia e Innovación y el Instituto de Salud Carlos III/Europa y Fondo de Desarrollo Regional (FEDER). Proyectos PI16/00101, PI16/00952, PI16/00765, PI16/00659, PI16/00421, PI16/00170 • Junta de Castilla y León. Ayuda GRS 1277/B/16peerReviewe

The relationship of the atlantic diet with cardiovascular risk factors and markers of arterial stiffness in adults without cardiovascular disease

[EN]Abstract: Background: Studying the adherence of the population to the Atlantic Diet (AD) could be simplified by an easy and quickly applied dietary index. The aim of this study is to analyse the relationship of an index measuring compliance with recommendations regarding the Atlantic diet and physical activity with cardiovascular disease risk factors, cardiovascular risk factors, obesity indexes and arterial stiffness markers. Methods: We included 791 individuals from the EVIDENT study (lifestyles and arterial ageing), (52.3 ± 12 years, 61.7% women) without cardiovascular disease. Compliance with recommendations on AD was collected through the responses to a food frequency questionnaire, while physical activity was measured by accelerometer. The number of recommendations being met was estimated using a global scale between 0 and 14 points (a higher score representing greater adherence). Blood pressure, plasma lipid and glucose values and obesity rates were measured. Cardiovascular risk was estimated with the Framingham equation. Results: In the overall sample, 184 individuals (23.3%) scored between 0–3 on the 14-point index we created, 308 (38.9%) between 4 and 5 points, and 299 (37.8%) 6 or more points. The results of multivariate analysis yield a common tendency in which the group with an adherence score of at least 6 points shows lower figures for total cholesterol (p = 0.007) and triglycerides (p = 0.002). Similarly, overall cardiovascular risk in this group is the lowest (p < 0.001), as is pulse wave velocity (p = 0.050) and the mean values of the obesity indexes studied (p < 0.05 in all cases). Conclusion: The rate of compliance with the Atlantic diet and physical activity shows that greater adherence to these recommendations is linked to lower cardiovascular risk, lower total cholesterol and triglycerides, lower rates of obesity and lower pulse wave velocity values.This study was funded by the Spanish Ministry of Science and Innovation (MICINN) and the Carlos III Health Institute/European Regional Development Fund (ERDF) (FIS: PI13/00618, PI13/01526, PI13/00058, PI13/01635, PI13/02528, PI12/01474; RETICS: RD12/0005, RD16/0007), the Regional Health Administration of Castilla and León (GRS 1191/B/15, GRS 909/B/14, GRS 770/B/13) and the Infosalud Foundation. None of the funders were involved in the design, implementation, analysis or interpretation of the data

Altair: Automatic Image Analyzer to Assess Retinal Vessel Caliber

The scope of this work is to develop a technological platform specialized in assessing retinal vessel caliber and describing the relationship of the results obtained to cardiovascular risk. Population studies conducted have found retinal vessel caliber to be related to the risk of hypertension, left ventricular hypertrophy, metabolic syndrome, stroke, and coronary artery disease. The vascular system in the human retina has a unique property: it is easily observed in its natural living state in the human retina by the use of a retinal camera. Retinal circulation is an area of active research by numerous groups, and there is general experimental agreement on the analysis of the patterns of the retinal blood vessels in the normal human retina. The development of automated tools designed to improve performance and decrease interobserver variability, therefore, appears necessary