GATEKEEPER's Strategy for the Multinational Large-Scale Piloting of an eHealth Platform: Tutorial on How to Identify Relevant Settings and Use Cases.

BACKGROUND: The World Health Organization's strategy toward healthy aging fosters person-centered integrated care sustained by eHealth systems. However, there is a need for standardized frameworks or platforms accommodating and interconnecting multiple of these systems while ensuring secure, relevant, fair, trust-based data sharing and use. The H2020 project GATEKEEPER aims to implement and test an open-source, European, standard-based, interoperable, and secure framework serving broad populations of aging citizens with heterogeneous health needs. OBJECTIVE: We aim to describe the rationale for the selection of an optimal group of settings for the multinational large-scale piloting of the GATEKEEPER platform. METHODS: The selection of implementation sites and reference use cases (RUCs) was based on the adoption of a double stratification pyramid reflecting the overall health of target populations and the intensity of proposed interventions; the identification of a principles guiding implementation site selection; and the elaboration of guidelines for RUC selection, ensuring clinical relevance and scientific excellence while covering the whole spectrum of citizen complexities and intervention intensities. RESULTS: Seven European countries were selected, covering Europe's geographical and socioeconomic heterogeneity: Cyprus, Germany, Greece, Italy, Poland, Spain, and the United Kingdom. These were complemented by the following 3 Asian pilots: Hong Kong, Singapore, and Taiwan. Implementation sites consisted of local ecosystems, including health care organizations and partners from industry, civil society, academia, and government, prioritizing the highly rated European Innovation Partnership on Active and Healthy Aging reference sites. RUCs covered the whole spectrum of chronic diseases, citizen complexities, and intervention intensities while privileging clinical relevance and scientific rigor. These included lifestyle-related early detection and interventions, using artificial intelligence-based digital coaches to promote healthy lifestyle and delay the onset or worsening of chronic diseases in healthy citizens; chronic obstructive pulmonary disease and heart failure decompensations management, proposing integrated care management based on advanced wearable monitoring and machine learning (ML) to predict decompensations; management of glycemic status in diabetes mellitus, based on beat to beat monitoring and short-term ML-based prediction of glycemic dynamics; treatment decision support systems for Parkinson disease, continuously monitoring motor and nonmotor complications to trigger enhanced treatment strategies; primary and secondary stroke prevention, using a coaching app and educational simulations with virtual and augmented reality; management of multimorbid older patients or patients with cancer, exploring novel chronic care models based on digital coaching, and advanced monitoring and ML; high blood pressure management, with ML-based predictions based on different intensities of monitoring through self-managed apps; and COVID-19 management, with integrated management tools limiting physical contact among actors. CONCLUSIONS: This paper provides a methodology for selecting adequate settings for the large-scale piloting of eHealth frameworks and exemplifies with the decisions taken in GATEKEEPER the current views of the WHO and European Commission while moving forward toward a European Data Space.

Erythrocyte Membrane Nanomechanical Rigidity Is Decreased in Obese Patients.

This work intends to describe the physical properties of red blood cell (RBC) membranes in obese adults. The hypothesis driving this research is that obesity, in addition to increasing the amount of body fat, will also modify the lipid composition of membranes in cells other than adipocytes. Forty-nine control volunteers (16 male, 33 female, BMI 21.8 ± 5.6 and 21.5 ± 4.2 kg/m2, respectively) and 52 obese subjects (16 male and 36 female, BMI 38.2± 11.0 and 40.7 ± 8.7 kg/m2, respectively) were examined. The two physical techniques applied were atomic force microscopy (AFM) in the force spectroscopy mode, which allows the micromechanical measurement of penetration forces, and fluorescence anisotropy of trimethylammonium diphenylhexatriene (TMA-DPH), which provides information on lipid order at the membrane polar-nonpolar interface. These techniques, in combination with lipidomic studies, revealed a decreased rigidity in the interfacial region of the RBC membranes of obese as compared to control patients, related to parallel changes in lipid composition. Lipidomic data show an increase in the cholesterol/phospholipid mole ratio and a decrease in sphingomyelin contents in obese membranes. ω-3 fatty acids (e.g., docosahexaenoic acid) appear to be less prevalent in obese patient RBCs, and this is the case for both the global fatty acid distribution and for the individual major lipids in the membrane phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS). Moreover, some ω-6 fatty acids (e.g., arachidonic acid) are increased in obese patient RBCs. The switch from ω-3 to ω-6 lipids in obese subjects could be a major factor explaining the higher interfacial fluidity in obese patient RBC membranes.

SEM-EDX linear scanning: a new tool for morpho-compositional analysis of growth bands in urinary stones.

The genesis and growth of calculi are imprinted in their structure, so the pathogenesis of lithiasis could potentially be read via proper analytical techniques. In this study, electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX) is used to obtain a description of the morphology and compositional structure of a single bladder stone. This technique establishes the chemical and crystalline architecture of the urolith to assess the effect of the chemical environment on its growth. Scanning electron microscopy-backscattered electrons (SEM-BSE) images clearly show that the stone has a multilayered structure. These layers and Liesegang ring-like structures are characterized by one predominant chemical component but also by slighter compositional changes. The mean crystalline components are determined by X-ray diffraction (DRX), infrared spectroscopy (FT-IR), and Raman analysis (RMN). Elemental analysis along a radial trajectory of the calculus by EDX linear scanning (EDX-LS) also reveals the compositional structure of the layers and the spatial distribution of the main chemical components. EDX-LS data processing reveals concentration profiles that clearly show morpho-compositional growth bands, which correspond to precipitation waves and urinary concentration peaks. The width of the growth bands is independent of the radial position, layer, and element analyzed. We conclude that the bands observed are a consequence of slight changes in the biochemical composition of the urine and consequently reflect a short-term biological cycle of the renal system. This non-specific growth rate suggests that stone formation is a kinetically controlled phenomenon in which promoters of crystal cluster aggregation may have played a key role.

[Lesions detected in a colorectal cancer screening program in the Basque Country: first round (2009-2011)]. / Lesiones detectadas en el programa de cribado de cáncer colorrectal en el País Vasco: primera ronda 2009-2011.

UNLABELLED: Colorectal cancer (CRC) is a major public health problem due to its incidence and mortality. In May 2008, the Basque Country approved the implementation of a population-based colorectal cancer screening program, using the immunochemical fecal occult blood test (FOBT), in persons aged 50-69 years. Patients with a positive result were invited to undergo colonoscopy with sedation. OBJECTIVE: To describe the main results of the first round of the CRC screening program with FOBT (2009-2011) in terms of the detection rates and positive predictive value (PPV). METHOD: Retrospective study of participation rates and colonoscopic findings in persons with a positive FOBT result. RESULTS: Invitations to attend screening were sent to 230.505 persons. A total of 148.249 FOBT tests were processed. The mean participation rate was 64.3% (95% CI: 64.1-64.5) and was higher in women than in men. The FOBT test was positive in 6.7% (95% CI: 6.6-6.8). Positive results were more frequent in men. Among persons with a positive result, colonoscopy was performed in 93.1%. There were significant differences between women and men in the detection rate of high-risk adenomas (OR: 0,45 95% CI 0,41-0,49), which, as with CRC (OR: 0,80 95% CI 0,66-0,96), were more frequent in men. The PPV for adenoma of any type was significantly higher in men (72.4 95% CI, 71.2-73.5) than in women (48.8% 95% CI 47.2-50.5), with differences by age group and type of adenoma. CONCLUSIONS: Participation rates and detection of advanced lesions and CRC were high. Because men have a higher risk of developing CRC, efforts should be made to increase their participation. The impact of the CRC screening program should be evaluated in the medium to long term.

Altered Red Blood Cell Fatty Acid and Serum Adipokine Profiles in Subjects with Obesity.

BACKGROUND: Adipokines, as well as the fatty acid profile of red blood cell (RBC) membranes, are known to play important roles in the development and progression of metabolic complications induced by obesity. Thus, the objective of this study is to compare the serum adipokine profile and the RBC membrane fatty acid profile of normal-weight and obese adults, and to analyze their relationship with serum biochemical parameters. METHODS: An observational case-control study was performed in 75 normal-weight and obese adult subjects. Biochemical serum parameters, eight serum adipokines and the RBC membrane fatty acid profiles were measured. Associations between parameters were established using regression analysis. RESULTS: Subjects with obesity showed increased levels of leptin, fibroblast growth factor 21 (FGF21) and overexpressed nephroblastoma (NOV/CCN3), decreased adiponectin, and similar levels of vaspin and chemerin compared to normal-weight subjects. Significant positive and negative correlations were found with triglycerides and high-density lipoprotein-cholesterol (HDL-c), respectively. An increase in the total ω-6 fatty acids in the RBC membrane fatty acid profiles in subjects with obesity was observed, because of higher levels of both dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), and decreased total ω-3 fatty acids, mainly due to lower levels of docosahexaenoic acid (DHA). The ω-6/ω-3 ratio in the RBCs was significantly higher, suggesting an inflammatory status, as was also suggested by a reduced adiponectin level. A negative association between DGLA and adiponectin, and a positive association between DHA and serum triglycerides, was observed. CONCLUSIONS: Important alterations in serum adipokine and RBC fatty acid profiles are found in subjects with obesity.

Incidence of diabetes mellitus and associated risk factors in the adult population of the Basque country, Spain.

The aim of this study was to estimate the incidence of diabetes mellitus in the Basque Country and the risk factors involved in the disease by reassessing an adult population after 7 years of follow-up. In the previous prevalence study, 847 people older than 18 years were randomly selected from all over the Basque Country and were invited to answer a medical questionnaire, followed by a physical examination and an oral glucose tolerance test. In the reassessment, the same variables were collected and the resulting cohort comprised 517 individuals of whom 43 had diabetes at baseline. The cumulative incidence of diabetes was 4.64% in 7 years and the raw incidence rate was 6.56 cases/1000 person-years (95%CI: 4.11-9.93). Among the incident cases, 59% were undiagnosed. The most strongly associated markers by univariate analyses were age > 60 years, dyslipidaemia, prediabetes and insulin resistance. We also found association with hypertension, obesity, family history of diabetes and low education level. Multivariate analysis adjusted for age and sex showed that a set of risk factors assessed together (dyslipidaemia, waist-to-hip-ratio and family history of diabetes) had great predictive value (AUC-ROC = 0.899, 95%CI: 0.846-0.953, p = 0.942), which suggests the need for early intervention before the onset of prediabetes.

SARS-CoV-2 Infection Dysregulates the Metabolomic and Lipidomic Profiles of Serum.

COVID-19 is a systemic infection that exerts significant impact on the metabolism. Yet, there is little information on how SARS-CoV-2 affects metabolism. Using NMR spectroscopy, we measured the metabolomic and lipidomic serum profile from 263 (training cohort) + 135 (validation cohort) symptomatic patients hospitalized after positive PCR testing for SARS-CoV-2 infection. We also established the profiles of 280 persons collected before the coronavirus pandemic started. Principal-component analysis discriminated both cohorts, highlighting the impact that the infection has on overall metabolism. The lipidomic analysis unraveled a pathogenic redistribution of the lipoprotein particle size and composition to increase the atherosclerotic risk. In turn, metabolomic analysis reveals abnormally high levels of ketone bodies (acetoacetic acid, 3-hydroxybutyric acid, and acetone) and 2-hydroxybutyric acid, a readout of hepatic glutathione synthesis and marker of oxidative stress. Our results are consistent with a model in which SARS-CoV-2 infection induces liver damage associated with dyslipidemia and oxidative stress.

[Prevalence of urinary tract infection in infants with high fever in the emergency department]. / Prevalencia de las infecciones del tracto urinario en niños menores de 2 años con fiebre alta en los servicios de urgencias.

INTRODUCTION: There is no current data on the prevalence of urinary tract infection (UTI) in infants and toddlers with high fever. We conducted this study to assess the point prevalence of UTI in children aged less than 2 years presenting with high fever to the emergency department. METHOD: We conducted a prospective, multicentre, observational study including febrile children aged less than 2 years in whom urinalysis was performed to rule out UTI over a 1-year period in seven paediatric emergency departments in Spain. Boys younger than 1 year and girls younger than 2 years of age were eligible for the study if they had a rectal temperature greater than 39°C, were not taking antibiotics, and there was no identifiable source of fever. The diagnosis of UTI was based on the presence of leukocyturia and positive urine culture results. RESULTS: We included a total of 1675 patients. Two hundred sixty infants (15.5%; 95% CI, 13.8-17.3) received a diagnosis of UTI. The point prevalence of UTI was 32.9% (95% CI, 26.6-39.9) in febrile boys aged less than 6 months and 19.3% (95% CI, 16.1-22.9) in febrile girls aged less than 12 months. The point prevalence of UTI was 13% (95% CI, 10.8-15.6) in children with a duration of fever of less than 24hours, compared to 17.5% (95% CI, 15.2-20.1) in those with a longer duration of fever (p = 0.014). CONCLUSIONS: The point prevalence of UTI in infants and toddlers with fever without source greater than 39°C was higher in our study compared to previous studies of UTI prevalence, especially in male infants aged less than 6 months and female infants aged less than 12 months. Our findings suggest that clinicians need to carefully assess for UTI in infants with unexplained fever greater than 39°C.