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Background: Errors related to medication seriously affect patient safety and the quality of healthcare. It has been widely argued that various types of such errors may be prevented by introducing Clinical Decision Support Systems (CDSSs) at the point of care. Objectives: Although significant research has been conducted in the field, still medication safety is a crucial issue, while few research outcomes are mature enough to be considered for use in actual clinical settings. In this paper, we present a clinical decision support framework targeting medication safety with major focus on adverse drug event (ADE) prevention. Methods: The novelty of the framework lies in its design that approaches the problem holistically, i.e., starting from knowledge discovery to provide reliable numbers about ADEs per hospital or medical unit to describe their consequences and probable causes, and next employing the acquired knowledge for decision support services development and deployment. Major design features of the framework's services are: a) their adaptation to the context of care (i.e. patient characteristics, place of care, and significance of ADEs), and b) their straightforward integration in the healthcare information technologies (IT) infrastructure thanks to the adoption of a service-oriented architecture (SOA) and relevant standards. Results: Our results illustrate the successful interoperability of the framework with two commercially available IT products, i.e., a Computerized Physician Order Entry (CPOE) and an Electronic Health Record (EHR) system, respectively, along with a Web prototype that is independent of existing healthcare IT products. The conducted clinical validation with domain experts and test cases illustrates that the impact of the framework is expected to be major, with respect to patient safety, and towards introducing the CDSS functionality in practical use. Conclusions: This study illustrates an important potential for the applicability of the presented framework in delivering con- textualized decision support services at the point of care and for making a substantial contribution towards ADE prevention. Nonetheless, further research is required in order to quantitatively and thoroughly assess its impact in medication safety. [ABSTRACT FROM AUTHOR]

Background: The Covid-19 pandemic has caused immense pressure on Intensive Care Units (ICU). In patients with severe ARDS due to Covid-19, respiratory mechanics are important for determining the severity of lung damage. Lung auscultation could not be used during the pandemic despite its merit. The main objective of this study was to investigate associations between lung auscultatory sound features and lung mechanical properties, length of stay (LOS) and survival, in adults with severe Covid-19 ARDS., Methods: Consecutive patients admitted to a large ICU between 2020 and 2021 (n = 173) were included. Digital stethoscopes obtained auscultatory sounds and stored them in an on-line database for replay and further processing using advanced AI techniques. Correlation and regression analysis explored relationships between digital auscultation findings and lung mechanics or the ICU outcome. The resulting annotated lung sounds database is also publicly available as supplementary material., Results: The presence of squawks was associated with the ICU LOS, outcome and 90-day mortality. Other features (age, SOFA score & oxygenation index upon admission, minimum crackle entropy) had significant impact on outcome. Additional features affecting the 90-d survival were age and mean crackle entropy. Multivariate logistic regression showed that survival was affected by age, baseline SOFA, baseline oxygenation index and minimum crackle entropy., Conclusions: Respiratory mechanics were associated with various adventitious sounds, whereas the lung sound analytics and the presence of certain adventitious sounds correlated with the ICU outcome and the 90-d survival. Spectral features of crackles sounds can serve as prognostic factors for survival, highlighting the importance of digital auscultation., (© 2024. The Author(s).)

Background: Developing trustworthy artificial intelligence (AI) models for clinical applications requires access to clinical and imaging data cohorts. Reusing of publicly available datasets has the potential to fill this gap. Specifically in the domain of breast cancer, a large archive of publicly accessible medical images along with the corresponding clinical data is available at The Cancer Imaging Archive (TCIA). However, existing datasets cannot be directly used as they are heterogeneous and cannot be effectively filtered for selecting specific image types required to develop AI models. This work focuses on the development of a homogenized dataset in the domain of breast cancer including clinical and imaging data., Methods: Five datasets were acquired from the TCIA and were harmonized. For the clinical data harmonization, a common data model was developed and a repeatable, documented "extract-transform-load" process was defined and executed for their homogenization. Further, Digital Imaging and COmmunications in Medicine (DICOM) information was extracted from magnetic resonance imaging (MRI) data and made accessible and searchable., Results: The resulting harmonized dataset includes information about 2,035 subjects with breast cancer. Further, a platform named RV-Cherry-Picker enables search over both the clinical and diagnostic imaging datasets, providing unified access, facilitating the downloading of all study imaging that correspond to specific series' characteristics (e.g., dynamic contrast-enhanced series), and reducing the burden of acquiring the appropriate set of images for the respective AI model scenario., Conclusions: RV-Cherry-Picker provides access to the largest, publicly available, homogenized, imaging/clinical dataset for breast cancer to develop AI models on top., Relevance Statement: We present a solution for creating merged public datasets supporting AI model development, using as an example the breast cancer domain and magnetic resonance imaging images., Key Points: • The proposed platform allows unified access to the largest, homogenized public imaging dataset for breast cancer. • A methodology for the semantically enriched homogenization of public clinical data is presented. • The platform is able to make a detailed selection of breast MRI data for the development of AI models., (© 2024. The Author(s).)

Background and Objective: Respiratory diseases are among the most significant causes of morbidity and mortality worldwide, causing substantial strain on society and health systems. Over the last few decades, there has been increasing interest in the automatic analysis of respiratory sounds and electrical impedance tomography (EIT). Nevertheless, no publicly available databases with both respiratory sound and EIT data are available., Methods: In this work, we have assembled the first open-access bimodal database focusing on the differential diagnosis of respiratory diseases (BRACETS: Bimodal Repository of Auscultation Coupled with Electrical Impedance Thoracic Signals). It includes simultaneous recordings of single and multi-channel respiratory sounds and EIT. Furthermore, we have proposed several machine learning-based baseline systems for automatically classifying respiratory diseases in six distinct evaluation tasks using respiratory sound and EIT (A1, A2, A3, B1, B2, B3). These tasks included classifying respiratory diseases at sample and subject levels. The performance of the classification models was evaluated using a 5-fold cross-validation scheme (with subject isolation between folds)., Results: The resulting database consists of 1097 respiratory sounds and 795 EIT recordings acquired from 78 adult subjects in two countries (Portugal and Greece). In the task of automatically classifying respiratory diseases, the baseline classification models have achieved the following average balanced accuracy: Task A1 - 77.9±13.1%; Task A2 - 51.6±9.7%; Task A3 - 38.6±13.1%; Task B1 - 90.0±22.4%; Task B2 - 61.4±11.8%; Task B3 - 50.8±10.6%., Conclusion: The creation of this database and its public release will aid the research community in developing automated methodologies to assess and monitor respiratory function, and it might serve as a benchmark in the field of digital medicine for managing respiratory diseases. Moreover, it could pave the way for creating multi-modal robust approaches for that same purpose., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The purpose of the present study was to examine whether a visual stimuli program during soccer training can affect reaction time (RT), cognitive function, and physical fitness in adolescent soccer players. Thirty-eight male soccer players aged 10−15 were randomly assigned to either the intervention (Group A) or the control group (Group B). At baseline and at the end of the 6-month study FITLIGHT Trainer, the Cognitive Function Scanner Mobile Test Suite, a Virtual Reality (VR) game, and the ALPHA—Fitness and the Eurofit test batteries were used to measure participants’ abilities. After the baseline assessment, Group A followed their regular soccer training combined with a visual stimuli program, while Group B continued their regular soccer training program alone for 6 months. At the end of the 6-month study, Group A showed statistically significant improvements in simple RT by 11.8% (p = 0.002), repeated sprints by 13.4% (p ≤ 0.001), and Pen-to-Point Cognitive Function by 71.62% (p < 0.001) and 72.51% for dominant and non-dominant hands, respectively. However, a between-groups analysis showed that there was no statistically significant difference between the two groups in most of the measurements studied. In conclusion, a visual stimuli training program does not seem to add any value to the traditional soccer training program for adolescents. Nevertheless, this study helps to underline the potential of newly emerging technology as a tool for the assessment of RT.

Background: Electrocardiogram (ECG) is one of the most common noninvasive diagnostic tools that can provide useful information regarding a patient's health status. Deep learning (DL) is an area of intense exploration that leads the way in most attempts to create powerful diagnostic models based on physiological signals., Objective: This study aimed to provide a systematic review of DL methods applied to ECG data for various clinical applications., Methods: The PubMed search engine was systematically searched by combining "deep learning" and keywords such as "ecg," "ekg," "electrocardiogram," "electrocardiography," and "electrocardiology." Irrelevant articles were excluded from the study after screening titles and abstracts, and the remaining articles were further reviewed. The reasons for article exclusion were manuscripts written in any language other than English, absence of ECG data or DL methods involved in the study, and absence of a quantitative evaluation of the proposed approaches., Results: We identified 230 relevant articles published between January 2020 and December 2021 and grouped them into 6 distinct medical applications, namely, blood pressure estimation, cardiovascular disease diagnosis, ECG analysis, biometric recognition, sleep analysis, and other clinical analyses. We provide a complete account of the state-of-the-art DL strategies per the field of application, as well as major ECG data sources. We also present open research problems, such as the lack of attempts to address the issue of blood pressure variability in training data sets, and point out potential gaps in the design and implementation of DL models., Conclusions: We expect that this review will provide insights into state-of-the-art DL methods applied to ECG data and point to future directions for research on DL to create robust models that can assist medical experts in clinical decision-making., (©Georgios Petmezas, Leandros Stefanopoulos, Vassilis Kilintzis, Andreas Tzavelis, John A Rogers, Aggelos K Katsaggelos, Nicos Maglaveras. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 15.08.2022.)

The relation among the various causal factors of obesity is not well understood, and there remains a lack of viable data to advance integrated, systems models of its etiology. The collection of big data has begun to allow the exploration of causal associations between behavior, built environment, and obesity-relevant health outcomes. Here, the traditional epidemiologic and emerging big data approaches used in obesity research are compared, describing the research questions, needs, and outcomes of 3 broad research domains: eating behavior, social food environments, and the built environment. Taking tangible steps at the intersection of these domains, the recent European Union project "BigO: Big data against childhood obesity" used a mobile health tool to link objective measurements of health, physical activity, and the built environment. BigO provided learning on the limitations of big data, such as privacy concerns, study sampling, and the balancing of epidemiologic domain expertise with the required technical expertise. Adopting big data approaches will facilitate the exploitation of data concerning obesity-relevant behaviors of a greater variety, which are also processed at speed, facilitated by mobile-based data collection and monitoring systems, citizen science, and artificial intelligence. These approaches will allow the field to expand from causal inference to more complex, systems-level predictive models, stimulating ambitious and effective policy interventions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Monitoring and treatment of severely ill COVID-19 patients in the ICU poses many challenges. The effort to understand the pathophysiology and progress of the disease requires high-quality annotated multi-parameter databases. We present CoCross, a platform that enables the monitoring and fusion of clinical information from in-ICU COVID-19 patients into an annotated database. CoCross consists of three components: (1) The CoCross4Pros native android application, a modular application, managing the interaction with portable medical devices, (2) the cloud-based data management services built-upon HL7 FHIR and ontologies, (3) the web-based application for intensivists, providing real-time review and analytics of the acquired measurements and auscultations. The platform has been successfully deployed since June 2020 in two ICUs in Greece resulting in a dynamic unified annotated database integrating clinical information with chest sounds and diagnostic imaging. Until today multisource data from 176 ICU patients were acquired and imported in the CoCross database, corresponding to a five-day average monitoring period including a dataset with 3477 distinct auscultations. The platform is well accepted and positively rated by the users regarding the overall experience.

The process of maintenance of an underlying semantic model that supports data management and addresses the interoperability challenges in the domain of telemedicine and integrated care is not a trivial task when performed manually. We present a methodology that leverages the provided serializations of the Health Level Seven International (HL7) Fast Health Interoperability Resources (FHIR) specification to generate a fully functional OWL ontology along with the semantic provisions for maintaining functionality upon future changes of the standard. The developed software makes a complete conversion of the HL7 FHIR Resources along with their properties and their semantics and restrictions. It covers all FHIR data types (primitive and complex) along with all defined resource types. It can operate to build an ontology from scratch or to update an existing ontology, providing the semantics that are needed, to preserve information described using previous versions of the standard. All the results based on the latest version of HL7 FHIR as a Web Ontology Language (OWL-DL) ontology are publicly available for reuse and extension.

Objective: The objective of this study was to determine the 12-year incidence of open-angle glaucoma (OAG), with further classification into primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG), in an elderly White population., Design: A longitudinal, population-based study in urban Northern Greece., Participant: Surviving cohort of the 2554 Thessaloniki Eye Study subjects 60 years and above who had the baseline examination., Methods: The surviving cohort was re-examined 12 years after baseline, using the same methodology and the same standard operating procedures as in the baseline examination. The definitions of glaucoma and pseudoexfoliation were consistent throughout the study. The 12-year incidences of OAG, POAG, and PEXG with corresponding 95% confidence intervals (CIs) were calculated for the whole study population, consisting of clinic-visit and home-visit participants. The population at risk was defined as those who did not meet the study criteria for the diagnosis of glaucoma in either eye at baseline., Main Outcome Measures: Twelve-year incidence of OAG, with further classification into POAG and PEXG., Results: Of 1468 eligible subjects in the surviving cohort, 1092 were examined (participation rate 74%). Mean age at baseline was 68.9±4.6 years. Mean follow-up time was 11.6±1.6 years. The 12-year incidence of OAG was 4.4% (95% CI: 3.3-5.8); 0.37% per year. In the overall population the incidence of POAG and PEXG was 2.1% (95% CI: 1.3-3.2) and 2.3% (95% CI: 1.5-3.4), respectively. The corresponding incidence proportions were 2.9 (95% CI: 1.8-4.3) in those without PEX and 8.9 (95% CI: 5.8-12.9) in those with PEX at baseline and/or incidence. The latter was strongly associated with higher odds for incident glaucoma (odds ratio=3.34, 95% CI: 1.83-6.08, P<0.001). Of all incident OAG cases, 11.1% (95% CI: 4.4-24) had baseline intraocular pressure >21 mm Hg., Conclusions: The incidence of OAG was similar or higher compared with other White populations. The incidence of glaucoma in those with PEX was higher compared with the incidence of glaucoma in those without PEX., Competing Interests: Disclosure: P.F.: lecturing honorarium from Thea. A.H.: has received remuneration from Adom, Qlaris, and Luseed for serving as a consultant, and he serves on the board of Adom and Phileas Pharma. He also holds an ownership interest in AdOM, Luseed, Oxymap, Phileas Pharma, and QuLent. All relationships listed above are pursuant to Icahn School of Medicine’s policy on outside activities. F.T.: grants/research support from Pfizer, Novartis, Alcon, Thea, Bayer and Omikron; honoraria or consultation fees from Alcon, Novartis, Thea, Bayer, and Omikron. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Obesity is a major public health problem globally and in Europe. The prevalence of childhood obesity is also soaring. Several parameters of the living environment are contributing to this increase, such as the density of fast food retailers, and thus, preventive health policies against childhood obesity must focus on the environment to which children are exposed. Currently, there are no systems in place to objectively measure the effect of living environment parameters on obesogenic behaviors and obesity. The H2020 project "BigO: Big Data Against Childhood Obesity" aims to tackle childhood obesity by creating new sources of evidence based on big data., Objective: This paper introduces the Obesity Prevention dashboard (OPdashboard), implemented in the context of BigO, which offers an interactive data platform for the exploration of objective obesity-related behaviors and local environments based on the data recorded using the BigO mHealth (mobile health) app., Methods: The OPdashboard, which can be accessed on the web, allows for (1) the real-time monitoring of children's obesogenic behaviors in a city area, (2) the extraction of associations between these behaviors and the local environment, and (3) the evaluation of interventions over time. More than 3700 children from 33 schools and 2 clinics in 5 European cities have been monitored using a custom-made mobile app created to extract behavioral patterns by capturing accelerometer and geolocation data. Online databases were assessed in order to obtain a description of the environment. The dashboard's functionality was evaluated during a focus group discussion with public health experts., Results: The preliminary association outcomes in 2 European cities, namely Thessaloniki, Greece, and Stockholm, Sweden, indicated a correlation between children's eating and physical activity behaviors and the availability of food-related places or sports facilities close to schools. In addition, the OPdashboard was used to assess changes to children's physical activity levels as a result of the health policies implemented to decelerate the COVID-19 outbreak. The preliminary outcomes of the analysis revealed that in urban areas the decrease in physical activity was statistically significant, while a slight increase was observed in the suburbs. These findings indicate the importance of the availability of open spaces for behavioral change in children. Discussions with public health experts outlined the dashboard's potential to aid in a better understanding of the interplay between children's obesogenic behaviors and the environment, and improvements were suggested., Conclusions: Our analyses serve as an initial investigation using the OPdashboard. Additional factors must be incorporated in order to optimize its use and obtain a clearer understanding of the results. The unique big data that are available through the OPdashboard can lead to the implementation of models that are able to predict population behavior. The OPdashboard can be considered as a tool that will increase our understanding of the underlying factors in childhood obesity and inform the design of regional interventions both for prevention and treatment., (©Dimitris Filos, Irini Lekka, Vasileios Kilintzis, Leandros Stefanopoulos, Youla Karavidopoulou, Christos Maramis, Christos Diou, Ioannis Sarafis, Vasileios Papapanagiotou, Leonidas Alagialoglou, Ioannis Ioakeimidis, Maria Hassapidou, Evangelia Charmandari, Rachel Heimeier, Grace O'Malley, Shane O’Donnell, Gerardine Doyle, Anastasios Delopoulos, Nicos Maglaveras. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 09.07.2021.)

Background: Serious gaming has increasingly gained attention as a potential new component in clinical practice. Specifically, its use in the rehabilitation of motor dysfunctions has been intensively researched during the past three decades., Objective: The aim of this scoping review was to evaluate the current role of serious games in upper extremity rehabilitation, and to identify common methods and practice as well as technology patterns. This objective was approached via the exploration of published research efforts over time., Methods: The literature search, using the PubMed and Scopus databases, included articles published from 1999 to 2019. The eligibility criteria were (i) any form of game-based arm rehabilitation; (ii) published in a peer-reviewed journal or conference; (iii) introduce a game in an electronic format; (iv) published in English; and (v) not a review, meta-analysis, or conference abstract. The search strategy identified 169 relevant articles., Results: The results indicated an increasing research trend in the domain of serious gaming deployment in upper extremity rehabilitation. Furthermore, differences regarding the number of publications and the game approach were noted between studies that used commercial devices in their rehabilitation systems and those that proposed a custom-made robotic arm, glove, or other devices for the connection and interaction with the game platform. A particularly relevant observation concerns the evaluation of the introduced systems. Although one-third of the studies evaluated their implementations with patients, in most cases, there is the need for a larger number of participants and better testing of the rehabilitation scheme efficiency over time. Most of the studies that included some form of assessment for the introduced rehabilitation game mentioned user experience as one of the factors considered for evaluation of the system. Besides user experience assessment, the most common evaluation method involving patients was the use of standard medical tests. Finally, a few studies attempted to extract game features to introduce quantitative measurements for the evaluation of patient improvement., Conclusions: This paper presents an overview of a significant research topic and highlights the current state of the field. Despite extensive attempts for the development of gamified rehabilitation systems, there is no definite answer as to whether a serious game is a favorable means for upper extremity functionality improvement; however, this certainly constitutes a supplementary means for motivation. The development of a unified performance quantification framework and more extensive experiments could generate richer evidence and contribute toward this direction., (©Elisavet Koutsiana, Ioannis Ladakis, Dimitris Fotopoulos, Achilleas Chytas, Vassilis Kilintzis, Ioanna Chouvarda. Originally published in JMIR Serious Games (http://games.jmir.org), 11.12.2020.)

Purpose: To identify factors associated with retinal capillary density as measured with Confocal Scanning Laser Doppler Flowmetry (Heidelberg retina flowmeter (HRF)) in the Thessaloniki Eye Study (TES)., Methods: Participants of the TES (age ≥60 years, cross-sectional population-based study) were assessed for active capillary density in the superior and inferior peripapillary retina using the HRF. Pixel-by-pixel analysis was performed to quantify the percentage of zero flow pixels (ZFPs; surrogate for % retinal area with non-active capillaries). Multivariable regression analyses were performed to assess the association of non-active vascular density with ophthalmic and systemic variables. Glaucoma, late age-related macular degeneration and diabetic retinopathy subjects were excluded., Results: 1189 subjects were included in the analysis. Older age (per year) was associated with higher percentage of ZFP in both the superior (slope estimate (SE)=0.0020) and the inferior (SE=0.0019) peripapillary retina (p<0.0001). History of migraine was associated with lower percentage of ZFP (SE=-0.0166) compared with no history of migraine in the superior peripapillary retina only (p<0.05). Higher intraocular pressure ((IOP) per mm Hg) and height (per cm) were associated with higher percentage of ZFP in the inferior peripapillary retina only (SE=0.0012, p<0.05 and SE=0.0005, p<0.05, respectively). The group consuming vegetables one to three times per week compared with the group consuming vegetables at least once a day had higher percentage of ZFP only in the inferior peripapillary retina (SE=0.0080, p<0.05)., Conclusion: At a population level, our study revealed associations of older age, higher IOP and taller height with lower active retinal capillary density and of migraine with higher capillary density. Looking further into these associations may provide insight into disease mechanisms., Competing Interests: Competing interests: AH would like to disclose that he receives remuneration from CIPLA, AdOM and Shire for serving as a consultant. AH also holds an ownership interest in AdOM and Oxymap. All relationships listed above are pursuant to Indiana University’s policy on outside activities. FT (corresponding author) reports grants from Center for Eye Epidemiology, UCLA, California, USA, grants from Health Future Foundation, Creighton University, Omaha, Nebraska, USA, grants from International Glaucoma Association, UK, grants from Texas Tech University, Texas, USA, grants from Pfizer, New York, USA, grants from Merck and Co, New Jersey, USA, grants from Pharmacia Hellas, Athens, Greece, grants from Novartis Hellas, Athens, Greece, during the conduct of the study; other (advisory board) from Aerie, grants from Pfizer, grants from Thea, grants from Alcon, grants and other (advisory board) from Novartis, grants from Rheon, grants and other (lecture fees) from Omikron, grants from Pharmathen, grants from IDx, USA, other (advisory board) from Zeiss, outside the submitted work. PF would like to disclose that she has contributed as a co-author to the European Glaucoma Society Terminology and Guidelines for Glaucoma 4th edition. The rest of the authors have nothing to disclose., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Obesity is a complex disease and its prevalence depends on multiple factors related to the local socioeconomic, cultural and urban context of individuals. Many obesity prevention strategies and policies, however, are horizontal measures that do not depend on context-specific evidence. In this paper we present an overview of BigO (http://bigoprogram.eu), a system designed to collect objective behavioral data from children and adolescent populations as well as their environment in order to support public health authorities in formulating effective, context-specific policies and interventions addressing childhood obesity. We present an overview of the data acquisition, indicator extraction, data exploration and analysis components of the BigO system, as well as an account of its preliminary pilot application in 33 schools and 2 clinics in four European countries, involving over 4,200 participants.

One of the most widely acknowledged standards in health informatics is HL7 (Health Level 7 International). HL7 FHIR® (Fast Healthcare Interoperability Resources) is a new HL7 standard for exchanging electronic health data. It builds upon previous HL7 data format standards, but also leverages more modern technical concepts and approaches, aiming to be more developer-friendly. We present a developed ontology that, not only represents the domain entities of a personal health record (PHR) focusing on tele-health and integrated care, but also stores the actual data as instances of the defined ontology classes. Inspired and based on HL7 FHIR we defined a methodology for representing FHIR data types and FHIR resources in OWL and we have extended or restricted the resources to match specific domain needs. Additionally, since HL7 FHIR is a developing standard, we present a methodology for maintaining backward compatibility as the ontology is updated to match the latest definition of the standard. All the effort is represented as an OWL-DL ontology that is publicly available for reuse and extension.

In this paper we present the methodology and decisions behind an implementation of a telehealth data management framework, aiming to support integrated care services for chronic and multimorbid patients. The framework leverages an OWL ontology, built upon HL7 FHIR resources, to provide storage and representation of semantically enriched EHR data following Linked Data principles. This is presented along with the realization of the persistent storage solution and communication web services that allow the management of EHR data, ensuring the validity and integrity of the exchanged patient data as self-describing ontology instances. The framework concentrates on flexibility and reusability, which is addressed by regarding the aforementioned ontology as a single point of change. This solution has been implemented in the scope of the EU project WELCOME for managing data in a telemonitoring system for patients with COPD and co-morbidities and was also successfully deployed for the INLIFE EU project with minimal effort. The results of the two applications suggest it can be adopted and properly adapted in a series of integrated care scenarios with minimal effort., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To measure the inter- and intraobserver repeatability and reproducibility of choroidal thickness measurements taken by the enhanced depth imaging of spectral-domain optical coherence tomography (EDI-OCT) in randomly selected subjects using two different protocols., Methods: Twenty subjects of the Thessaloniki Eye Study database were randomly selected. The participants underwent EDI-OCT, and the choroidal thickness was measured on EDI images using two different protocols. All images were assessed by two examiners independently in two sessions in different days., Results: The interobserver intraclass correlation coefficient (ICC) for average choroidal thickness was 0.944. The average ICC for central, Cmin, and Cmax choroidal thickness was 0.899, 0.863, and 0.955, respectively. The interobserver ICC for average choroidal volume was 0.932. Intraobserver repeatability ICC for grader 1 ranged between 0.925 and 0.9720 and for grader 2 between 0.913 and 0.994., Conclusion: Choroidal thickness measurements by EDI-OCT showed a high inter- and intraobserver reproducibility.

Purpose: To identify the factors associated with retinal vessel diameters in the population of the Thessaloniki Eye Study., Methods: Cross-sectional population-based study (age ≥ 60 years). Subjects with glaucoma, late age-related macular degeneration, and diabetic retinopathy were excluded from the analyses. Retinal vessel diameters were measured using the IVAN software, and measurements were summarized to central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole to venule ratio (AVR)., Results: The analysis included 1614 subjects. The hypertensive group showed lower values of CRAE (P = 0.033) and AVR (P = 0.0351) compared to the normal blood pressure (BP) group. On the contrary, the group having normal BP under antihypertensive treatment did not have different values compared to the normal BP group. Diastolic BP (per mm Hg) was negatively associated with CRAE (P < 0.0001) and AVR (P < 0.0001), while systolic BP (per mm Hg) was positively associated with CRAE (P = 0.001) and AVR (P = 0.0096). Other factors significantly associated included age, sex, alcohol, smoking, cardiovascular disease history, ophthalmic medication, weight, and IOP; differences were observed in a stratified analysis based on BP medication use., Conclusions: Our study confirms previous reports about the association of age and BP with vessel diameters. The negative correlation between BP and CRAE seems to be guided by the effect of diastolic BP as higher systolic BP is independently associated with higher values of CRAE. The association of BP status with retinal vessel diameters is determined by diastolic BP status in our population. Multiple other factors are also independently associated with retinal vessel diameters.

Purpose: To assess the overdiagnosis of open-angle glaucoma (OAG) and to investigate associated factors., Methods: This was a cross-sectional, population-based study of an urban Caucasian population in northern Greece. Randomly selected subjects ≥60 years (n = 2554) participated in the Thessaloniki Eye Study. The definition of OAG required the presence of structural and functional damage, irrespective of intraocular pressure (IOP). Non-OAG subjects were classified as overdiagnosed with OAG if they had reported at least one of the following (self-reported glaucoma): (i) prior diagnosis of glaucoma, (ii) prior laser for glaucoma, (iii) prior glaucoma surgery. Factors associated with the overdiagnosis of OAG were investigated using a logistic regression model., Results: Of 57 (2.2%) subjects with self-reported glaucoma, 34 (60%) were overdiagnosed with OAG, corresponding to a prevalence of 1.3% (34/2554). In a logistic regression model among non-OAG subjects, worse visual acuity (VA) (20/200 or worse versus 20/25 or better; odds ratio (OR) = 4.30, 95% Confidence Intervals (CI), 1.13-16.35), family history of glaucoma (OR = 8.69, 95% CI, 2.83-26.67) and history of cataract surgery (OR = 11.50, 95% CI, 3.85-34.36) were statistically significantly associated with the overdiagnosis of OAG. Age, sex, higher IOP, higher vertical cup-to-disc ratio and pseudoexfoliation were not statistically significant., Conclusion: The overdiagnosis of OAG was substantial in this elderly, Caucasian population. The overdiagnosis of glaucoma has not been previously addressed in population-based studies and needs to be further explored., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aims: To provide population-based data on the maximum tolerable rate of progression to avoid visual impairment (maxTRoP&#95;VI) and blindness (maxTRoP&#95;BL) from open-angle glaucoma (OAG)., Methods: Participants with OAG in the Thessaloniki Eye Study (cross-sectional, population-based study in a European population) were included in the analysis. Visual impairment was defined as mean deviation (MD) equal to or worse than -12dB and blindness as MD equal to or worse than -24dB. Additional thresholds for visual impairment were tested. For each participant maxTRoP&#95;VI was defined as the rate of progression which would not lead to visual impairment during expected lifetime. MaxTRoP&#95;BL was defined accordingly. Both parameters were calculated for each OAG subject using age, sex, MD and life expectancy data. The eye with the better MD per subject was included in the analysis., Results: Among 135 subjects with OAG, 123 had reliable visual fields and were included in the analysis. The mean age was 73±6 years and the median MD was -3.65±5.28dB. Among those, 69.1% would have a maxTRoP&#95;VI slower than -1dB/year and 18.7% would have a maxTRoP&#95;VI between -1 and -2dB/year. Also, 72.4% would have a maxTRoP&#95;BL slower than -2dB/year. For all tested thresholds for visual impairment, approximately 86% of the OAG study participants would not be able to tolerate a rate of progression equal to or faster than -2dB/year., Conclusions: The majority of patients with glaucoma in our study would have a maximum tolerable rate of progression slower than -1dB/year in their better eye. Patient-tailored strategies to monitor the visual field are important, but raise the issue of feasibility with regard to the number of visual field tests needed., Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form (available on request from the corresponding author) and declare no support from any organisation for the submitted work. AS has nothing to disclose. PF is a contributor to the extant European Glaucoma Society Guidelines and contributor and chapter co-author of the World Glaucoma Association consensus series published in 2016. VK has nothing to disclose. AA has nothing to disclose. EA has received grants from Allergan, Thea and Novartis and an honorarium from Allergan outside the submitted work. TP has received honoraria from Allergan and Novartis outside the submitted work. AR has nothing to disclose. FT has received grants and personal fees from Alcon, Novartis, Thea and Pfizer and personal fees from Bayer, Allergan and Santen outside the submitted work; he is also a member and chapter editor of the extant European Glaucoma Society Guidelines Development Task Force and a contributor and chapter editor of the extant World Glaucoma Association consensus series published in 2016, Lead of the Education Theme European Glaucoma Society (2016), Chair of the Program Planning Committee of the European Glaucoma Society and Co-Chair of the Education Committee of the European Glaucoma Society (2012), Member of the International Council of Ophthalmology Residency Curriculum Panel (2012), General Secretary of the Greek Glaucoma Society Board (2013), Member of the Committee of the European Board of Ophthalmology (EBO) Glaucoma Subspecialty examination (2015), Section Leader Glaucoma Education Center of the American Academy of Ophthalmology (2016), Co-Chair of the Program Planning Committee of the Glaucoma Research Society (2016) and Associate Editor of the Journal of Glaucoma (2017)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

In rehabilitation, exergames and serious games are widely usedin order to motivate patients in the therapeutic procedure. Patients are asked to modify their incorrect motor patterns or reinforce the proper ones through activity rather than exercise. Interactive applications as such, can have a huge impact on a patient's motivation making repetitive physical exercises into pleasant experiences, thus maximizing the gains of therapy. In this paper we present the design and implementation of a serious game platform based on virtual 3D game environment and leap motion controller for interaction. For each session, achieved goals and response to stimuli is recorded and analyzed. Preliminary analysis results from evaluating the game with healthy subjects are encouraging.

The objective of the presented cross-sectional-evaluation-screening study is the clinical evaluation of high-risk(hr)HPVE7-protein detection as a triage method to colposcopy for hrHPV-positive women, using a newly developed sandwich-ELISA-assay. Between 2013-2015, 2424 women, 30-60 years old, were recruited at the Hippokratio Hospital, Thessaloniki/Greece and the Im Mare Klinikum, Kiel/Germany, and provided a cervical sample used for Liquid Based Cytology, HPV DNA genotyping, and E7 detection using five different E7-assays: "recomWell HPV16/18/45KJhigh", "recomWell HPV16/18/45KJlow", "recomWell HPV39/51/56/59", "recomWell HPV16/31/33/35/52/58" and "recomWell HPVHRscreen" (for 16,18,31,33,35,39,45,51,52,56,58,59 E7), corresponding to different combinations of hrHPVE7-proteins. Among 1473 women with eligible samples, those positive for cytology (ASCUS+ 7.2%), and/or hrHPV DNA (19.1%) were referred for colposcopy. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 27 women (1.8%). For HPV16/18-positive women with no triage, sensitivity, positive predictive value (PPV) and the number of colposcopies needed to detect one case of CIN2+ were 100.0%, 11.11% and 9.0 respectively. The respective values for E7-testing as a triage method to colposcopy ranged from 75.0-100.0%, 16.86-26.08% and 3.83-5.93. Sensitivity and PPV for cytology as triage for hrHPV(non16/18)-positive women were 45.45% and 27.77%; for E7 test the respective values ranged from 72.72-100.0% and 16.32-25.0%. Triage of HPV 16/18-positive women to colposcopy with the E7 test presents better performance than no triage, decreasing the number of colposcopies needed to detect one CIN2+. In addition, triage of hrHPV(non16/18)-positive women with E7 test presents better sensitivity and slightly worse PPV than cytology, a fact that advocates for a full molecular screening approach., (© 2017 UICC.)

Purpose: The purpose of the presented PIPAVIR (persistent infections with human papillomaviruses; http://www.pipavir.com ) subanalysis is to assess the performance of high-risk (hr) HPV-DNA genotyping as a method of primary cervical cancer screening and triage of HPV positive women to colposcopy compared to liquid-based cytology (LBC) in an urban female population., Methods: Women, aged 30-60, provided cervicovaginal samples at the Family-Planning Centre, Hippokratio Hospital of Thessaloniki, Greece, and the Department of Gynecology and Obstetrics in Mare Klinikum, Kiel, Germany. Cytology and HPV genotyping was performed using LBC and HPV Multiplex Genotyping (MPG), respectively. Women positive for cytology [atypical squamous cells of undetermined significance (ASC-US) or worse] or hrHPV were referred for colposcopy., Results: Among 1723/1762 women included in the final analysis, hrHPV and HPV16/18 prevalence was 17.7 and 9.6%, respectively. Cytology was ASCUS or worse in 7.6%. Cervical Intraepithelial Neoplasia grade 2 or worse (CIN2+) was detected in 28 women (1.6%). Sensitivity of cytology (ASCUS or worse) and HPV DNA testing for the detection of CIN2+ was 50.0 and 100%, and specificity was 94.49 and 85.49%, respectively. The screening approach according to which only women positive for HPV16/18 and for hrHPV(non16/18) with ASCUS or worse were referred to colposcopy presented 78.57% sensitivity and 13.17% positive predictive value (PPV)., Conclusions: HPV testing represents a more sensitive methodology for primary cervical cancer screening compared to cytology. For triage of HPV positive women to colposcopy, partial HPV genotyping offers better sensitivity than cytology, at the cost of higher number of colposcopies.

INLIFE is a project cofounded from the European Union aiming in prolonging independent living of elderly people with cognitive impairment based on open, seamless ICT services supporting communication, daily activities, providing health services and professional care to the elderly. The main innovation stems from ICT solutions offering 19 different services adapted on specific characteristics elderly people with mild cognitive impairment, early and later stages of Dementia, cognitive impairment and co-morbid condition, as well as their formal and informal caregivers. All services have different focus areas and are incorporated into a unified system based on cloud architecture implemented in patients of 6 European countries, including Greece. More than 1200 patients, caregivers and healthcare providers participate in the pilot testing of the project. Primary parameter for assessing the effectiveness of the interventions is their impact on the quality of life of the elderly patients and their caregivers, contributing to prolonging independent living of the affected. A special digital platform has been developed in the Greek pilot site aiming to adapt and monitor all the implemented applications. This includes a medical decision support system that receives biosignals from patients and interaction interfaces in which all participants are involved. Recruitment and patients' participation has already started in the pilot site of Thessaloniki for the services that are to be tested in Greece.

Purpose: To compare Heidelberg Retina Tomograph (HRT) optic disc parameters and structure-function correlation between primary open-angle glaucoma (POAG) and pseudoexfoliative glaucoma (PEXG)., Design: Prospective, observation case series., Patients and Methods: A total of 54 POAG and 33 PEXG cases, consecutively recruited from a University Glaucoma Service, underwent a comprehensive ophthalmic examination, including HRT optic disc imaging. Glaucoma definition required the presence of both structural and functional damage. One eye per subject was included in the analysis. T test, Mann-Whitney U test, and analysis of covariance were used to compare HRT parameters between POAG and PEXG, adjusting for age, mean deviation (MD) in the visual field, intraocular pressure, and disc area. The correlation between HRT and MD was assessed in each group., Results: Cup area (P=0.048), height variation contour (P=0.016), and cup/disc area ratio (P=0.023) were higher in POAG, whereas the mean retinal nerve fiber layer thickness (P=0.048), retinal nerve fiber layer cross-section area (P=0.044), and rim area (P=0.048) were lower in POAG, compared with PEXG. The correlation of HRT parameters with MD was significant only in the POAG group., Conclusions: At a similar level of functional damage, POAG subjects presented with more pronounced structural damage than PEXG subjects. The correlation between HRT and visual field parameters was more evident in POAG, compared with PEXG.

Integrated care and connected health are two fast evolving concepts that have the potential to leverage personalised health. From the one side, the restructuring of care models and implementation of new systems and integrated care programs providing coaching and advanced intervention possibilities, enable medical decision support and personalized healthcare services. From the other side, the connected health ecosystem builds the means to follow and support citizens via personal health systems in their everyday activities and, thus, give rise to an unprecedented wealth of data. These approaches are leading to the deluge of complex data, as well as in new types of interactions with and among users of the healthcare ecosystem. The main challenges refer to the data layer, the information layer, and the output of information processing and analytics. In all the above mentioned layers, the primary concern is the quality both in data and information, thus, increasing the need for filtering mechanisms. Especially in the data layer, the big biodata management and analytics ecosystem is evolving, telemonitoring is a step forward for data quality leverage, with numerous challenges still left to address, partly due to the large number of micro-nano sensors and technologies available today, as well as the heterogeneity in the users' background and data sources. This leads to new R&D pathways as it concerns biomedical information processing and management, as well as to the design of new intelligent decision support systems (DSS) and interventions for patients. In this paper, we illustrate these issues through exemplar research targeting chronic patients, illustrating the current status and trends in PHS within the integrated care and connected care world.