The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action.

Non-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.

Psychometric properties of the MOBITEC-GP mobile application for real-life mobility assessment in older adults.

Aim of this study was to test the reliability and validity of the life-space measures and walking speed delivered by the MOBITEC-GP app. Participants underwent several supervised walking speed assessments as well as a 1-week life-space assessment during two assessment sessions 9 days apart. Fifty-seven older adults (47.4% male, mean age= 75.3 (±5.9) years) were included in the study. The MOBITEC-GP app showed moderate to excellent test-retest reliability (ICCs between 0.584 and 0.920) and validity (ICCs between 0.468 and 0.950) of walking speed measurements of 50 meters and above and of most 1-week life-space parameters, including life-space area, time spent out-of-home, and action range. The MOBITEC-GP app for Android is a reliable and valid tool for the assessment of real-life walking speed (at distances of 50 metres and above) and life-space parameters of older adults. Future studies should look into technical issues more systematically in order to avoid invalid measurements.

Validation of a Visually Aided Dietary Assessment Tool to Estimate Dietary Intake in an Adult Swiss Population.

Background: Accurately assessing dietary intake is crucial for understanding how diet affects a person's health. In large cohorts, paper-based dietary assessment tools (DAT) such as food recalls or food frequency questionnaires have emerged as valid tools with a low burden for participants. Objective: To validate a visually aided DAT for use in studies with Swiss adults against the gold standard of a weighed 7-day food record (7 d-FR). Design: Fifty-one adults (n = 24 women, n = 27 males) participated in the study and were recruited within two age groups (20-40 and 50-70 y). Each participant filled out the visually aided DAT, then the 7 d-FR. The DAT was compared to the 7 d-FR for total energy intake, macronutrients, sugar, water, and portions of fruits and vegetables. Pearson correlation and Bland-Altman analyses were used for statistical analyses. Results: Total correlations ranged from 0.288 (sugar, p < 0.05) to 0.729 (water, p < 0.01). The older age group showed higher correlations for total energy intake, protein, fats, carbohydrates, and sugar, but not for water (p < 0.05). Correlations were moderate at r > 0.5, whereas only water and protein reached those values in the young group. Both groups overestimated total calories in kcal (+14.0%), grams of protein (+ 44.6%), fats (+36.3%), and portions of fruits and vegetables (+16.0%) but strongly underestimated sugar intake (-50.9%). Conclusion: This DAT showed that all macronutrients and total energy intake were estimated more accurately by the older age group and therefore might be adequate to capture dietary habits in older Swiss adults.

Methodological aspects for accelerometer-based assessment of physical activity in heart failure and health.

BACKGROUND: For valid accelerometer-assessed physical activity (PA) data, several methodological aspects should be considered. We aimed to 1) visualize the applicability of absolute accelerometer cut-offs to classify PA intensity, 2) verify recommendations to measure PA over 7 days by examining inter-day variability and reactivity, 3) examine seasonal differences in PA, and 4) recommend during which 10 h day period accelerometers should be worn to capture the most PA in patients with heart failure (HEART) and healthy individuals (HEALTH). METHODS: Fifty-six HEART (23% female; mean age 66 ± 13 years) and 299 HEALTH (51% female; mean age 54 ± 19 years) of the COmPLETE study wore accelerometers for 14 days. Aim 1 was analyzed descriptively. Key analyses were performed using linear mixed models. RESULTS: The results yielded poor applicability of absolute cut-offs. The day of the week significantly affected PA in both groups. PA-reactivity was not present in either group. A seasonal influence on PA was only found in HEALTH. Large inter-individual variability in PA timing was present. CONCLUSIONS: Our data indicated that absolute cut-offs foster inaccuracies in both populations. In HEART, Sunday and four other days included in the analyses seem sufficient to estimate PA and the consideration of seasonal differences and reactivity seems not necessary. For healthy individuals, both weekend days plus four other days should be integrated into the analyses and seasonal differences should be considered. Due to substantial inter-individual variability in PA timing, accelerometers should be worn throughout waking time. These findings may improve future PA assessment. TRIAL REGISTRATION: The COmPLETE study was registered at clinicaltrials.gov ( NCT03986892 ).

Non-invasive Assessment of Neurovascular Coupling After Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Trial Using Retinal Vessel Analysis.

Objective: Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus. Methods: Static and dynamic RVA were performed using a Retinal Vessel Analyzer (IMEDOS Systems GmbH, Jena) in 70 aSAH patients during the early (d0-4), critical (d5-15), late (d16-23) phase, and at follow-up (f/u > 6 weeks) after the ictus. For comparison, an age-matched cohort of 42 healthy subjects was also included in the study. Vessel diameters were quantified in terms of the central retinal arterial and venous equivalent (CRAE, CRVE) and the retinal arterio-venous-ratio (AVR). Vessel responses to flicker light excitation (FLE) were quantified by recording the maximum arterial and venous dilation (MAD, MVD), the time to 30% and 100% of maximum dilation (tMAD30, tMVD30; tMAD, tMVD, resp.), and the arterial and venous area under the curve (AUCart, AUCven) during the FLE. For subgroup analyses, patients were stratified according to the development of DCI and clinical outcomes after 12 months. Results: Vessel diameter (CRAE, CRVE) was significantly smaller in aSAH patients and showed little change throughout the whole observation period (p < 0.0001 vs. control for all time periods examined). In addition, aSAH patients exhibited impaired arterial but not venous responses to FLE, as reflected in a significantly lower MAD [2.2 (1.0-3.2)% vs. 3.6 (2.6-5.6)% in control subjects, p = 0.0016] and AUCart [21.5 (9.4-35.8)%*s vs. 51.4 (32.5-69.7)%*s in control subjects, p = 0.0001] on d0-4. However, gradual recovery was observed during the first 3 weeks, with close to normal levels at follow-up, when MAD and AUCart amounted to 3.0 [2.0-5.0]% (p = 0.141 vs. control, p = 0.0321 vs. d5-15) and 44.5 [23.2-61.1]%*s (p = 0.138 vs. control, p < 0.01 vs. d0-4 & d5-15). Finally, patients with clinical deterioration (DCI) showed opposite changes in the kinetics of arterial responses during early and late phase, as reflected in a significantly lower tMAD30 on d0-4 [4.0 (3.0-6.8) s vs. 7.0 (5.0-8.0) s in patients without DCI, p = 0.022) and a significantly higher tMAD on d16-23 (24.0 (21.0-29.3) s vs. 18.0 (14.0-21.0) s in patients without DCI, p = 0.017]. Conclusion: Our findings confirm and extend previous observations that aSAH results in sustained impairments of NVC in the retina. DCI may be associated with characteristic changes in the kinetics of retinal arterial responses. However, further studies will be required to determine their clinical implications and to assess if they can be used to identify patients at risk of developing DCI. Trial Registration: ClinicalTrials.gov Identifier: NCT04094155.

Map-based assessment of older adults' life space: validity and reliability.

BACKGROUND: Map-based tools have recently found their way into health-related research. They can potentially be used to quantify older adults' life-space. This study aimed to evaluate the validity (vs. GPS) and the test-retest reliability of a map-based life-space assessment (MBA). METHODS: Life-space of one full week was assessed by GPS and by MBA. MBA was repeated after approximately 3 weeks. Distance-related (mean and maximum distance from home) and area-related (convex hull, standard deviational ellipse) life-space indicators were calculated. Intraclass correlations (MBA vs. GPS and test-retest) were calculated in addition to Bland-Altman analyses (MBA vs. GPS). RESULTS: Fifty-eight older adults (mean age 74, standard deviation 5.5 years; 39.7% women) participated in the study. Bland-Altman analyses showed the highest agreement between methods for the maximum distance from home. Intraclass correlation coefficients ranged between 0.19 (95% confidence interval 0 to 0.47) for convex hull and 0.72 (95% confidence interval 0.52 to 0.84) for maximum distance from home. Intraclass correlation coefficients for test-retest reliability ranged between 0.04 (95% confidence interval 0 to 0.30) for convex hull and 0.43 (95% confidence interval 0.19 to 0.62) for mean distance from home. CONCLUSIONS: While acceptable validity and reliability were found for the distance-related life-space parameters, MBA cannot be recommended for the assessment of area-related life-space parameters.

Physical Activity Interventions for Primary Prevention in Adults: A Systematic Review of Randomized Controlled Trial-Based Economic Evaluations.

BACKGROUND: Physical inactivity is a worldwide pandemic associated with major chronic diseases. Given limited resources, policy makers are in need of physical activity interventions that provide best value for money. OBJECTIVE: To summarize evidence from RCT-based economic evaluations of primary prevention physical activity interventions in adult populations outside the workplace setting. DESIGN: Systematic review of health economic evaluations. Incremental cost-effectiveness ratios (ICERs) in US$ per MET-hour gained were estimated on the basis of mean differences in intervention costs and standardized effects between intervention and control groups. DATA SOURCES: Identification of relevant studies via systematic searches in electronic databases (MEDLINE, Embase and NHSEED). ELIGIBILITY CRITERIA: Cost-effectiveness analyses in which all data (except unit costs) came from one RCT investigating physical activity interventions for primary prevention or health promotion in an adult population in high-income countries. RESULTS: In twelve eligible studies, 22 interventions were investigated. Interventions were based on advice, goal setting and follow-up support, exercise classes, financial incentives or teaching on behavioral change. The ICER varied widely among the interventions and four interventions showed an ICER below the applied benchmark of US$0.44 to US$0.63 per MET-hour gained. These four interventions were based on individualized advice via print or web. CONCLUSION: We found evidence from RCTs indicating cost-effectiveness of some physical activity interventions for primary prevention in adults. However, the majority of interventions assessed would not be cost-effective according to the benchmark applied. Furthermore, our study showed that trial-based evidence on cost-effectiveness of physical activity interventions is scarce. Therefore, we recommend that future studies investigating the efficacy or effectiveness of such interventions consider costs as an additional outcome and assess cost-effectiveness.

MOBIlity assessment with modern TEChnology in older patients' real-life by the General Practitioner: the MOBITEC-GP study protocol.

BACKGROUND: Mobility limitations in older adults are associated with poor clinical outcomes including higher mortality and disability rates. A decline in mobility (including physical function and life-space) is detectable and should be discovered as early as possible, as it can still be stabilized or even reversed in early stages by targeted interventions. General practitioners (GPs) would be in the ideal position to monitor the mobility of their older patients. However, easy-to-use and valid instruments for GPs to conduct mobility assessment in the real-life practice setting are missing. Modern technologies such as the global positioning system (GPS) and inertial measurement units (IMUs) - nowadays embedded in every smartphone - could facilitate monitoring of different aspects of mobility in the GP's practice. METHODS: This project's aim is to provide GPs with a novel smartphone application that allows them to quantify their older patients' mobility. The project consists of three parts: development of the GPS- and IMU-based application, evaluation of its validity and reliability (Study 1), and evaluation of its applicability and acceptance (Study 2). In Study 1, participants (target N = 72, aged 65+, ≥2 chronic diseases) will perform a battery of walking tests (varying distances; varying levels of standardization). Besides videotaping and timing (gold standard), a high-end GPS device, a medium-accuracy GPS/IMU logger and three different smartphone models will be used to determine mobility parameters such as gait speed. Furthermore, participants will wear the medium-accuracy GPS/IMU logger and a smartphone for a week to determine their life-space mobility. Participants will be re-assessed after 1 week. In Study 2, participants (target N = 60, aged 65+, ≥2 chronic diseases) will be instructed on how to use the application by themselves. Participants will perform mobility assessments independently at their own homes. Aggregated test results will also be presented to GPs. Acceptance of the application will be assessed among patients and GPs. The application will then be finalized and publicly released. DISCUSSION: If successful, the MOBITEC-GP application will offer health care providers the opportunity to follow their patients' mobility over time and to recognize impending needs (e.g. for targeted exercise) within pre-clinical stages of decline.

Breath Sensors for Health Monitoring.

Breath sensors can revolutionize medical diagnostics by on-demand detection and monitoring of health parameters in a noninvasive and personalized fashion. Despite extensive research for more than two decades, however, only a few breath sensors have been translated into clinical practice. Actually, most never even left the scientific laboratories. Here, we describe key challenges that currently impede realization of breath sensors and highlight strategies to overcome them. Specifically, we start with breath marker selection (with emphasis on metabolic and inflammatory markers) and breath sampling. Next, the sensitivity, stability, and selectivity requirements for breath sensors are described. Concepts are elaborated to systematically address these requirements by material design (focusing on chemoresistive metal oxides), orthogonal arrays, and filters. Finally, aspects of portable device integration, user communication, and clinical applicability are discussed.

Physical inactivity caused economic burden depends on regional cultural differences.

Physical inactivity is a major risk factor for numerous non-communicable diseases which dominate the overall burden of disease in Switzerland. We aimed to estimate the burden attributable to adult physical inactivity in Switzerland and its three culturally different language regions from a societal perspective in terms of disability-adjusted life years (DALYs), medical costs, and productivity losses. The burden of physical inactivity was estimated with a population attributable fractions (PAFs) approach. PAFs were calculated based on the prevalence of physical inactivity in the Swiss Health Survey and literature-based adjusted risk ratios of disease incidence. These PAFs were then applied to the total burden of the diseases related to physical inactivity. Physical inactivity was responsible for 2.0% (95%CI 1.7%-2.2%) of total DALYs lost and 1.2% (95%CI 1.0%-1.3%) of total medical costs in 2013. This is equivalent to 116 (95%CI 99-135) Swiss francs per capita per year. Productivity losses were valued at 117 (95%CI 94-142) Swiss francs per capita per year. The two diseases which caused the highest economic burden were low back pain and depression. The analysis of regional differences revealed that the per capita burden of physical inactivity is about twice as high in the French- and Italian-speaking regions compared to the German-speaking region. Reasons include a higher prevalence of physical inactivity, higher per capita health care spending, and higher disease prevalence. Cost-effectiveness analysis of related interventions should consider regional differences for optimal resource allocation in physical activity promotion policies.

Feasibility of oscillometric aortic pressure and stiffness assessment using the VaSera VS-1500: comparison with a common tonometric method.

OBJECTIVES: A number of operator-independent oscillometric devices to measure hemodynamics and arterial stiffness became available recently, but some and in particular VaSera VS-1500 do not provide estimates of aortic pressures and aortic pulse wave velocity (aPWV). The aim of this work was the retrospective application of the ARCSolver algorithm to pulse wave signals acquired with the VaSera VS-1500 device to estimate central systolic blood pressure (cSBP) and aPWV. MATERIALS AND METHODS: ARCSolver estimates of cSBP and aPWV, on the basis of brachial cuff measurements, were compared pair-wise with results from the tonometric SphygmoCor device in 68 individuals (mean age 51±18 years). We used variation estimates, correlation coefficients, age group-related t-tests, and the Bland-Altman method to analyze the reproducibility and agreement of the two methods. RESULTS: cSBP reproducibility expressed as variability was 14.9% for ARCSolver and 11.6% for SphygmoCor. PWV reproducibility was better for ARCSolver, with a variation estimate of 6.5%, compared with 20.9% using SphygmoCor. The mean cSBP difference was 0.5 mmHg (SD 6.9 mmHg) and 0.32 m/s (SD 1.20 m/s) for PWV, respectively. The age-related differences between ARCSolver and SphygmoCor are in line with previous studies. Bland-Altman plots showed considerable agreement between the two methods without signs of systematic bias. CONCLUSION: These results show that the combined application of the ARCSolver method with the VaSera VS-1500 device is feasible and the results are comparable with tonometric determination of cSBP and aPWV. This successful application of the ARCSolver may potentially help to improve cardiovascular risk stratification and prevention at an early stage in a community setting.

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: Endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) Society.

While risk scores are invaluable tools for adapted preventive strategies, a significant gap exists between predicted and actual event rates. Additional tools to further stratify the risk of patients at an individual level are biomarkers. A surrogate endpoint is a biomarker that is intended as a substitute for a clinical endpoint. In order to be considered as a surrogate endpoint of cardiovascular events, a biomarker should satisfy several criteria, such as proof of concept, prospective validation, incremental value, clinical utility, clinical outcomes, cost-effectiveness, ease of use, methodological consensus, and reference values. We scrutinized the role of peripheral (i.e. not related to coronary circulation) noninvasive vascular biomarkers for primary and secondary cardiovascular disease prevention. Most of the biomarkers examined fit within the concept of early vascular aging. Biomarkers that fulfill most of the criteria and, therefore, are close to being considered a clinical surrogate endpoint are carotid ultrasonography, ankle-brachial index and carotid-femoral pulse wave velocity; biomarkers that fulfill some, but not all of the criteria are brachial ankle pulse wave velocity, central haemodynamics/wave reflections and C-reactive protein; biomarkers that do no not at present fulfill essential criteria are flow-mediated dilation, endothelial peripheral arterial tonometry, oxidized LDL and dysfunctional HDL. Nevertheless, it is still unclear whether a specific vascular biomarker is overly superior. A prospective study in which all vascular biomarkers are measured is still lacking. In selected cases, the combined assessment of more than one biomarker may be required.