Socio-Cognitive Determinants of Lifestyle Behavior in the Context of Dementia Risk Reduction: A Population-Based Study in the Netherlands.

Background: Unhealthy behavior increases the risk of dementia. Various socio-cognitive determinants influence whether individuals persist in or alter these unhealthy behaviors. Objective: This study identifies relevant determinants of behavior associated to dementia risk. Methods: 4,104 Dutch individuals (40-79 years) completed a screening questionnaire exploring lifestyle behaviors associated with dementia risk. Subsequently, 3,065 respondents who engaged in one or more unhealthy behaviors completed a follow-up questionnaire investigating socio-cognitive determinants of these behaviors. Cross-tables were used to assess the accuracy of participants' perceptions regarding their behavior compared to recommendations. Confidence Interval-Based Estimation of Relevance (CIBER) was used to identify the most relevant determinants of behavior based on visual inspection and interpretation. Results: Among the respondents, 91.3% reported at least one, while 65% reported two or more unhealthy lifestyle behaviors associated to dementia risk. Many of them were not aware they did not adhere to lifestyle recommendations. The most relevant determinants identified include attitudes (i.e., lacking a passion for cooking and finding pleasure in drinking alcohol or smoking), misperceptions on social comparisons (i.e., overestimating healthy diet intake and underestimating alcohol intake), and low perceived behavioral control (i.e., regarding changing physical inactivity, altering diet patterns, and smoking cessation). Conclusions: Individual-level interventions that encourage lifestyle change should focus on enhancing accurate perceptions of behaviors compared to recommendations, while strengthening perceived control towards behavior change. Given the high prevalence of dementia risk factors, combining interventions at both individual and environmental levels are likely to be the most effective strategy to reduce dementia on a population scale.

Cleverballoon: An integrated approach for developing a drug-coated balloon with everolimus.

Coronary artery disease (CAD) is a chronic disease associated with high mortality and morbidity. Although treatment with drug-eluting stents is the most frequent interventional approach for coronary artery disease, drug-coated balloons (DCBs) constitute an innovative alternative, especially in the presence of certain anatomical conditions in the local coronary vasculature. DCBs allow the fast and homogenous transfer of drugs into the arterial wall, during the balloon inflation. Their use has been established for treating in-stent restenosis caused by stent implantation, while recent clinical trials have shown a satisfactory efficacy in de novo small-vessel disease. Several factors affect DCBs performance including the catheter design, the drug dose and formulation. Cleverballoon focuses on the design and development of an innovative DCB with everolimus. For the realization of the development of this new DCB, an integrated approach, including in- vivo, in-vitro studies and in-silico modelling towards the DCB optimization, is presented.Clinical Relevance-The proposed study introduces the integration of in- vivo, in-vitro and in silico approaches in the design and development process of a new DCB, following the principles of 3R's for the replacement, reduction, and refinement of animal and clinical studies.

A comparison study on creating simulated patient data for individuals suffering from chronic coronary disorders.

An emerging area in data science that has lately gained attention is the virtual population (VP) and synthetic data generation. This field has the potential to significantly affect the healthcare industry by providing a means to augment clinical research databases that have a shortage of subjects. The current study provides a comparative analysis of five distinct approaches for creating virtual data populations from real patient data. The data set utilized for the current analyses involved clinical data collected among patients scheduled for elective coronary artery bypass graft surgery (CABG). To that end, the five computational techniques employed to augment the given dataset were: (i) Tabular Preset, (ii) Gaussian Copula Model (iii) Generative Adversarial Network based (GAN) Deep Learning data synthesizer (CTGAN), (iv) a variation of the CTGAN Model (Copula GAN), and (v) VAE-based Deep Learning data synthesizer (TVAE). The performance of these techniques was assessed against their effectiveness in producing high-quality virtual data. For this purpose, dataset correlation matrices, cosine similarity distance, density histograms, and kernel density estimation are employed to perform a comparative analysis of each attribute and the respective synthetic equivalent. Our findings demonstrate that Gaussian Copula Model prevails in creating virtual data with consistent distributions (Kolmogorov-Smirnov (KS) and Chi-Squared (CS) tests equal to 0.9 and 0.98, respectively) and correlation patterns (average cosine similarity equals to 0.95).Clinical Relevance- It has been shown that the use of a VP can increase the predictive performance of a ML model, i.e., above using a smaller non-augmented population.

LETHE: A Digital Intervention for Cognitive Decline.

Dementia is the main cause of disability in elderly populations. It has been shown that the risk factors of dementia are a mixture of pathological, lifestyle and heritable factors, with some of those being provably modifiable. Early diagnosis of dementia and approaches to slow down its evolution are currently the most prominent management methodologies due to lack of a cure. For that reason, a plethora of home-based assistive technologies for dementia management do exist, with most of them focusing on the improvement of memory and thinking. The main objective of LETHE is prevention in the whole spectrum of cognitive decline in the elderly population at risk reaching from asymptomatic to subjective or mild cognitive impairment to prodromal Dementia. LETHE will provide a Big Data collection platform and analysis system, that will allow prevention, personalized risk detection and intervention on cognitive decline. Through the subsequent 2-year clinical trial, the LETHE system, as well as the respective knowledge gained will be evaluated and validated. The scope of the current paper is to introduce the LETHE study and its respective novel platform as a holistic approach to multidomain lifestyle intervention trial studies. The present work depicts the architectural perspective and extends beyond state-of-the-art guidelines and approaches to health management systems and cloud platform development.Clinical Relevance - Patient Management Systems as well as lifestyle management platforms have significant clinical relevance as they allow for remote and continuous monitoring of patients' health status. LETHE aims to improve patient outcomes by providing predictive models for cognitive decline and patient adherence to the multimodal lifestyle intervention, enabling prompt and appropriate medical decisions.

Safety and Efficacy of an Innovative Everolimus-Coated Balloon in a Swine Coronary Artery Model.

BACKGROUND: Drug-coated balloons have been used as a non-stenting treatment in coronary and peripheral artery disease. Until recently, only sirolimus- and paclitaxel-coated balloons have been investigated in clinical trials. We evaluated the safety and efficacy of an innovative everolimus-coated balloon (ECB) in a swine coronary artery model. METHODS: thirty-two swine coronary arteries were prepared through dilatation with a non-coated angioplasty balloon in a closed-chest model. During a period of 90 days, the following four groups (four animals per group, two coronary arteries per animal) were compared for safety and efficacy: A, Rontis ECB with 2.5 µg/mm2 of drug per balloon surface; B, Rontis ECB with 7.5 µg/mm2; C, Rontis Europa Ultra bare balloon; and D, Magic Touch, Concept Medical, sirolimus-coated balloon with a drug load of 1.3 µg/mm2. RESULTS: Differences in local biological effects (arterial reaction scores) and surface of intimal area (mm2) were not statistically significant between the treatment groups. Numerically, group A showed the lowest intimal area and intimal mean thickness, while group B showed the lowest stenosis among all groups. CONCLUSIONS: ECB was safe and effective in a porcine coronary artery model. The dose of everolimus may play a role in the biocompatibility of the balloon.

Public Perspectives on Lifestyle-Related Behavior Change for Dementia Risk Reduction: An Exploratory Qualitative Study in The Netherlands.

BACKGROUND: There is accumulating evidence that addressing modifiable risk and protective factors has an impact on dementia rates. Insight into the public's perspectives on dementia risk reduction is needed to inform future individual-level interventions and public health approaches. OBJECTIVE: This study explores the publics' openness towards dementia risk reduction and willingness towards changing lifestyle behavior to reduce the future risk for dementia. METHODS: Using a screening questionnaire, participants were purposively selected based on lifestyle behaviors that are associated with dementia risk. One-on-one interviews were used to explore their openness towards dementia risk reduction and willingness towards behavior change. Independently, two researchers performed an inductive content analysis. RESULTS: Interviews were conducted with 23 participants aged from 40 to 79 years. Main themes that were identified from the data were: 1) abstractness of dementia risk reduction, 2) ambivalence towards changing behavior, 3) negative self-image and low behavioral control, and 4) all-or-nothing thinking about lifestyle change. CONCLUSIONS: The concept of dementia risk reduction seems difficult to translate to the personal context, particularly if individuals perceive that dementia would occur decades in the future. This is problematic because a large proportion of the public needs a healthier lifestyle to reduce the incidence of dementia. Translating healthy intentions into behavior is complex and involves overcoming a variety of barriers that complicate dementia risk reduction initiatives. Support is needed for individuals who experience additional obstacles that obstruct commencing to a healthier lifestyle (e.g., negative self-image, engaging in multiple unhealthy behaviors, unrealistic perceptions about lifestyle change).

Computational modelling of Human Femur after Total Hip Arthroplasty.

This paper presents the workflow for creating a 3D finite element model of a cementless femur-implant when in single leg-stance, using state-of-the-art computer-aided design software and a finite element solver. The model consists of two geometries for the cortical and trabecular bone tissue of the femur bone, and two geometries for the stem and femoral head of a commercial implant. Each part is assumed to behave as linear isotropic material. Although relatively simplistic in its form, the presented 3D finite element model can capture the area of higher Von Misses stress concentration compared to other models in the literature.

Investigation of crimping effects on the stent deployment through in silico modeling.

Atherosclerosis is one of the most mortal diseases that affects the arterial vessels, due to accumulation of plaque, altering the hemodynamic environment of the artery by preventing the sufficient delivery of blood to other organs. Stents are expandable tubular wires, used as a treatment option. In silico studies have been extensively exploited towards examining the performance of such devices by employing Finite Element Modeling. This study models the crimping stage during stent implantation to examine the effect of inclusion of pre-stress state of the stent. The results show that modeling of the crimping stress state of the stent prior to the deployment results in under-expansion of the stent, due to the indirect inclusion of strain-induced hardening effects. As a result, it is evident that the compressive stent stress configuration is important to be considered in the computational modeling approaches of stent deployment.

A proof-of-concept study for the simulation of blood flow in a post arterial segment for different blood rheology models.

Cardiovascular disease (CVD) and especially atherosclerosis are chronic inflammatory diseases which cause the atherosclerotic plaque growth in the arterial vessels and the blood flow reduction. Stents have revolutionized the treatment of this disease to a great extent by restoring the blood flow in the vessel. The present study investigates the performance of the blood flow after stent implantation in patient-specific coronary artery and demonstrates the effect of using Newtonian vs. non-Newtonian blood fluid models in the distribution of endothelial shear stress. In particular, the Navier-Stokes and continuity equations were employed, and three non-Newtonian fluid models were investigated (Carreau, Carreau-Yasuda and the Casson model). Computational finite elements models were used for the simulation of blood flow. The comparison of the results demonstrates that the Newtonian fluid model underestimates the calculation of Endothelial Shear Stress, while the three non-Newtonian fluids present similar distribution of shear stress. Keywords: Blood flow dynamics, stented artery, non-Newtonian fluid. Clinical Relevance- This work demonstrates that when blood flow modeling is performed at stented arteries and predictive models are developed, the non-Newtonian nature of blood must be considered.

Investigation of the drug release time from the biodegrading coating of an everolimus eluting stent.

This case-study examines the release time of the everolimus drug from an experimental biodegrading coating of a Rontis corp. drug eluting stent (DES). The controlled drug release is achieved by the degradation of the coating, which consists of a mixture of polylactic co-glycolic acid (PLGA) and everolimus (55:45). In our analysis, we used the outcome of another study, which contains the geometry of an in-silico deployed Rontis corp. stent in a 3D reconstructed coney arterial segment. Using this geometry as input, the everolimus release was simulated using a computational model that includes: i) modeling of the blood flow dynamics, ii) modeling of PLGA degradation, and iii) modeling of the everolimus advection and diffusion towards both the lumen and the arterial wall. The results show the rapid release of everolimus. This is justified due to the high porosity of the coating, which is caused by the initial high concentration of everolimus in the coating.Clinical Relevance - The methodology presented in this work is an additional step towards predicting accurately drug release from DES. Also, the results of our work prove that high drug concentration in the coating causes its rapid release, which could be used as input in the design of new DES.

Investigation of Drug Eluting Stents performance in human atherosclerotic artery through in silico modeling.

Atherosclerosis is a chronic inflammatory disease associated with heart attack and stroke. It causes the growth of atherosclerotic plaques inside the arterial vessels, which in turn results to the reduction of the blood flow to the different organs. Drug-Eluting Stents (DES) are mesh-like wires, carrying pharmaceutical coating, designed to dilate and support the arterial vessel, restore blood flow and through the controlled local drug delivery inhibit neo-intimal thickening. In silico modeling is an efficient method of accurately predicting and assessing the performance of the stenting procedure. The present in silico study investigates the performance of two different stents (Bare Metal Stent, Drug-Eluting Stent) in a patient-specific coronary artery and assesses the effect of stent coating, considering that the same procedural approach is followed by the interventional cardiologist. The results demonstrate that even if small differences are obtained in the two models, the incorporation of the stent coatings (in DES) does not significantly affect the outcomes of the stent deployment, the stresses and strains in the scaffold and the arterial tissue. Nevertheless, it is suggested that regarding the DES expansion, higher pressure should be applied at the inner surface of the stent.

Prediction of the development of coronary atherosclerotic plaques using computational modeling in 3D reconstructed coronary arteries.

In this work we present a novel method for the prediction and generation of atherosclerotic plaques. This is performed in a two-step approach, by employing first a multilevel computational plaque growth model and second a correlation between the model's results and the 3D reconstructed follow-up plaques. In particular, computer tomography coronary angiography (CTCA) data and blood tests were collected from patients at two time points. Using the baseline data, the plaque growth is simulated using a multi-level computational model which includes: i) modeling of the blood flow dynamics, ii) modeling of low and high density lipoproteins and monocytes' infiltration in the arterial wall, and the species reactions during the atherosclerotic process, and iii) modeling of the arterial wall thickening. The correlation between the followup plaques and the simulated plaque density distribution resulted to the extraction of a threshold of the plaque density, that can be used to identify plaque areas.Clinical Relevance- The methodology presented in this work is a first step to the prediction of the plaque shape and location of patients with atherosclerosis and could be used as an additional tool for patient-specific risk stratification.