Multidimensional Biomechanics-Based Score to Assess Disease Progression in Duchenne Muscular Dystrophy.

(1) Background: Duchenne (DMD) is a rare neuromuscular disease that progressively weakens muscles, which severely impairs gait capacity. The Six Minute-Walk Test (6MWT), which is commonly used to evaluate and monitor the disease's evolution, presents significant variability due to extrinsic factors such as patient motivation, fatigue, and learning effects. Therefore, there is a clear need for the establishment of precise clinical endpoints to measure patient mobility. (2) Methods: A novel score (6M+ and 2M+) is proposed, which is derived from the use of a new portable monitoring system capable of carrying out a complete gait analysis. The system includes several biomechanical sensors: a heart rate band, inertial measurement units, electromyography shorts, and plantar pressure insoles. The scores were obtained by processing the sensor signals and via gaussian-mixture clustering. (3) Results: The 6M+ and 2M+ scores were evaluated against the North Star Ambulatory Assessment (NSAA), the gold-standard for measuring DMD, and six- and two-minute distances. The 6M+ and 2M+ tests led to superior distances when tested against the NSAA. The 6M+ test and the 2M+ test in particular were the most correlated with age, suggesting that these scores better characterize the gait regressions in DMD. Additionally, the 2M+ test demonstrated an accuracy and stability similar to the 6M+ test. (4) Conclusions: The novel monitoring system described herein exhibited good usability with respect to functional testing in a clinical environment and demonstrated an improvement in the objectivity and reliability of monitoring the evolution of neuromuscular diseases.

Implementing mHealth-Enabled Integrated Care for Complex Chronic Patients With Osteoarthritis Undergoing Primary Hip or Knee Arthroplasty: Prospective, Two-Arm, Parallel Trial.

BACKGROUND: Osteoarthritis is a disabling condition that is often associated with other comorbidities. Total hip or knee arthroplasty is an effective surgical treatment for osteoarthritis when indicated, but comorbidities can impair their results by increasing complications and social and economic costs. Integrated care (IC) models supported by eHealth can increase efficiency through defragmentation of care and promote patient-centeredness. OBJECTIVE: This study aims to assess the effectiveness and cost-effectiveness of implementing a mobile health (mHealth)-enabled IC model for complex chronic patients undergoing primary total hip or knee arthroplasty. METHODS: As part of the Horizon 2020 Personalized Connected Care for Complex Chronic Patients (CONNECARE) project, a prospective, pragmatic, two-arm, parallel implementation trial was conducted in the rural region of Lleida, Catalonia, Spain. For 3 months, complex chronic patients undergoing total hip or knee arthroplasty and their caregivers received the combined benefits of the CONNECARE organizational IC model and the eHealth platform supporting it, consisting of a patient self-management app, a set of integrated sensors, and a web-based platform connecting professionals from different settings, or usual care (UC). We assessed changes in health status (12-item short-form survey [SF-12]), unplanned visits and admissions during a 6-month follow-up, and the incremental cost-effectiveness ratio. RESULTS: A total of 29 patients were recruited for the mHealth-enabled IC arm, and 30 patients were recruited for the UC arm. Both groups were statistically comparable for baseline characteristics, such as age; sex; type of arthroplasty; and Charlson index, American Society of Anesthesiologists classification, Barthel index, Hospital Anxiety and Depression scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Pfeiffer mental status questionnaire scores. Patients in both groups had significant increases in the SF-12 physical domain and total SF-12 score, but differences in differences between the groups were not statistically significant. IC patients had 50% fewer unplanned visits (P=.006). Only 1 hospital admission was recorded during the follow-up (UC arm). The IC program generated savings in different cost scenarios, and the incremental cost-effectiveness ratio demonstrated cost-effectiveness. CONCLUSIONS: Chronic patients undergoing hip or knee arthroplasty can benefit from the implementation of patient-centered mHealth-enabled IC models aimed at empowering patients and facilitating transitions from specialized hospital care to primary care. Such models can reduce unplanned contacts with the health system and reduce overall health costs, proving to be cost-effective. Overall, our findings support the notion of system-wide cross-organizational care pathways supported by mHealth as a successful way to implement IC for patients undergoing elective surgery.

Implementing Mobile Health-Enabled Integrated Care for Complex Chronic Patients: Intervention Effectiveness and Cost-Effectiveness Study.

BACKGROUND: Integrated care can generate health and social care efficiencies through the defragmentation of care and adoption of patient-centered preventive models. eHealth can be a key enabling technology for integrated care. OBJECTIVE: The aim of this study was to assess the effectiveness and cost-effectiveness of the implementation of a mobile health (mHealth)-enabled integrated care model for complex chronic patients. METHODS: As part of the CONNECARE Horizon 2020 project, a prospective, pragmatic, two-arm, parallel implementation trial was held in a rural region of Catalonia, Spain. During 3 months, elderly patients with chronic obstructive pulmonary disease or heart failure and their carers experienced the combined benefits of the CONNECARE organizational integrated care model and the eHealth platform supporting it, consisting of a patient self-management app, a set of integrated sensors, and a web-based platform connecting professionals from different settings, or usual care. We assessed changes in health status with the 12-Item Short-Form Survey (SF-12), unplanned visits and admissions during a 6-month follow up, and the incremental cost-effectiveness ratio (ICER). RESULTS: A total of 48 patients were included in the integrated care arm and 28 patients receiving usual care were included in the control arm (mean age 82 years, SD 7 years; mean Charlson index 7, SD 2). Integrated care patients showed a significant increase in the SF-12 physical domain with a mean change of +3.7 (SD 8.4) (P=.004) and total SF-12 score with a mean change of +5.8 (SD 12.8) (P=.003); however, the differences in differences between groups were not statistically significant. Integrated care patients had 57% less unplanned visits (P=.004) and 50% less hospital admissions related to their main chronic diseases (P=.32). The integrated care program generated savings in different cost scenarios and the ICER demonstrated the cost-effectiveness of the program. CONCLUSIONS: The implementation of a patient-centered mHealth-enabled integrated care model empowering the patient, and connecting primary, hospital, and social care professionals reduced unplanned contacts with the health system and health costs, and was cost-effective. These findings support the notion of system-wide cross-organizational care pathways supported by mHealth as a successful way to implement integrated care.

Implementing Mobile Health-Enabled Integrated Care for Complex Chronic Patients: Patients and Professionals' Acceptability Study.

BACKGROUND: Integrated care (IC) can promote health and social care efficiency through prioritization of preventive patient-centered models and defragmentation of care and collaboration across health tiers, and mobile health (mHealth) can be the cornerstone allowing for the adoption of IC. OBJECTIVE: This study aims to assess the acceptability, usability, and satisfaction of an mHealth-enabled IC model for complex chronic patients in both patients and health professionals. METHODS: As part of the CONNECARE Horizon 2020 project, a prospective, pragmatic, 2-arm, parallel, hybrid effectiveness-implementation trial was conducted from July 2018 to August 2019 in a rural region of Catalonia, Spain. Home-dwelling patients 55 years and older with chronic conditions and a history of hospitalizations for chronic obstructive pulmonary disease or heart failure (use case [UC] 1), or a scheduled major elective hip or knee arthroplasty (UC2) were recruited. During the 3 months, patients experienced an mHealth-enabled IC model, including a self-management app for patients, a set of integrated sensors, and a web-based platform connecting professionals from different settings or usual care. The Person-Centered Coordinated Care Experience Questionnaire (P3CEQ) and the Nijmegen Continuity Questionnaire (NCQ) assessed person-centeredness and continuity of care. Acceptability was assessed for IC arm patients and staff with the Net Promoter Score (NPS) and the System Usability Scale (SUS). RESULTS: The analyses included 77 IC patients, 58 controls who completed the follow-up, and 30 health care professionals. The mean age was 78 (SD 9) years in both study arms. Perception of patient-centeredness was similarly high in both arms (usual care: mean P3CEQ score 16.1, SD 3.3; IC: mean P3CEQ score 16.3, SD 2.4). IC patients reported better continuity of care than controls (usual care: mean NCQ score 3.7, SD 0.9; IC: mean NCQ score 4.0, SD 1; P=.04). The scores for patient acceptability (UC1: NPS +67%; UC2: NPS +45%) and usability (UC1: mean SUS score 79, SD 14; UC2: mean SUS score 68, SD 24) were outstanding. Professionals' acceptability was low (UC1: NPS -25%; UC2: NPS -35%), whereas usability was average (UC1: mean SUS score 63, SD 20; UC2: mean SUS score 62, SD 19). The actual use of technology was high; 77% (58/75) of patients reported physical activity for at least 60 days, and the ratio of times reported over times prescribed for other sensors ranged from 37% for oxygen saturation to 67% for weight. CONCLUSIONS: The mHealth-enabled IC model showed outstanding results from the patients' perspective in 2 different UCs but lacked maturity and integration with legacy systems to be fully accepted by professionals. This paper provides useful lessons learned through the development and assessment process and may be of use to organizations willing to develop or implement mHealth-enabled IC for older adults.

Health Outcomes from Home Hospitalization: Multisource Predictive Modeling.

BACKGROUND: Home hospitalization is widely accepted as a cost-effective alternative to conventional hospitalization for selected patients. A recent analysis of the home hospitalization and early discharge (HH/ED) program at Hospital Clínic de Barcelona over a 10-year period demonstrated high levels of acceptance by patients and professionals, as well as health value-based generation at the provider and health-system levels. However, health risk assessment was identified as an unmet need with the potential to enhance clinical decision making. OBJECTIVE: The objective of this study is to generate and assess predictive models of mortality and in-hospital admission at entry and at HH/ED discharge. METHODS: Predictive modeling of mortality and in-hospital admission was done in 2 different scenarios: at entry into the HH/ED program and at discharge, from January 2009 to December 2015. Multisource predictive variables, including standard clinical data, patients' functional features, and population health risk assessment, were considered. RESULTS: We studied 1925 HH/ED patients by applying a random forest classifier, as it showed the best performance. Average results of the area under the receiver operating characteristic curve (AUROC; sensitivity/specificity) for the prediction of mortality were 0.88 (0.81/0.76) and 0.89 (0.81/0.81) at entry and at home hospitalization discharge, respectively; the AUROC (sensitivity/specificity) values for in-hospital admission were 0.71 (0.67/0.64) and 0.70 (0.71/0.61) at entry and at home hospitalization discharge, respectively. CONCLUSIONS: The results showed potential for feeding clinical decision support systems aimed at supporting health professionals for inclusion of candidates into the HH/ED program, and have the capacity to guide transitions toward community-based care at HH discharge.

The Aging Imageomics Study: rationale, design and baseline characteristics of the study population.

Biomarkers of aging are urgently needed to identify individuals at high risk of developing age-associated disease or disability. Growing evidence from population-based studies points to whole-body magnetic resonance imaging's (MRI) enormous potential for quantifying subclinical disease burden and for assessing changes that occur with aging in all organ systems. The Aging Imageomics Study aims to identify biomarkers of human aging by analyzing imaging, biopsychosocial, cardiovascular, metabolomic, lipidomic, and microbiome variables. This study recruited 1030 participants aged ≥50 years (mean 67, range 50-96 years) that underwent structural and functional MRI to evaluate the brain, large blood vessels, heart, abdominal organs, fat, spine, musculoskeletal system and ultrasonography to assess carotid intima-media thickness and plaques. Patients were notified of incidental findings detected by a certified radiologist when necessary. Extensive data were also collected on anthropometrics, demographics, health history, neuropsychology, employment, income, family status, exposure to air pollution and cardiovascular status. In addition, several types of samples were gathered to allow for microbiome, metabolomic and lipidomic profiling. Using big data techniques to analyze all the data points from biological phenotyping together with health records and lifestyle measures, we aim to cultivate a deeper understanding about various biological factors (and combinations thereof) that underlie healthy and unhealthy aging.

Evaluation of integrated care services in Catalonia: population-based and service-based real-life deployment protocols.

BACKGROUND: Comprehensive assessment of integrated care deployment constitutes a major challenge to ensure quality, sustainability and transferability of both healthcare policies and services in the transition toward a coordinated service delivery scenario. To this end, the manuscript articulates four different protocols aiming at assessing large-scale implementation of integrated care, which are being developed within the umbrella of the regional project Nextcare (2016-2019), undertaken to foster innovation in technologically-supported services for chronic multimorbid patients in Catalonia (ES) (7.5 M inhabitants). Whereas one of the assessment protocols is designed to evaluate population-based deployment of care coordination at regional level during the period 2011-2017, the other three are service-based protocols addressing: i) Home hospitalization; ii) Prehabilitation for major surgery; and, iii) Community-based interventions for frail elderly chronic patients. All three services have demonstrated efficacy and potential for health value generation. They reflect different implementation maturity levels. While full coverage of the entire urban health district of Barcelona-Esquerra (520 k inhabitants) is the main aim of home hospitalization, demonstration of sustainability at Hospital Clinic of Barcelona constitutes the core goal of the prehabilitation service. Likewise, full coverage of integrated care services addressed to frail chronic patients is aimed at the city of Badalona (216 k inhabitants). METHODS: The population-based analysis, as well as the three service-based protocols, follow observational and experimental study designs using a non-randomized intervention group (integrated care) compared with a control group (usual care) with a propensity score matching method. Evaluation of cost-effectiveness of the interventions using a Quadruple aim approach is a central outcome in all protocols. Moreover, multi-criteria decision analysis is explored as an innovative method for health delivery assessment. The following additional dimensions will also be addressed: i) Determinants of sustainability and scalability of the services; ii) Assessment of the technological support; iii) Enhanced health risk assessment; and, iv) Factors modulating service transferability. DISCUSSION: The current study offers a unique opportunity to undertake a comprehensive assessment of integrated care fostering deployment of services at regional level. The study outcomes will contribute refining service workflows, improving health risk assessment and generating recommendations for service selection. TRIALS REGISTRATION: NCT03130283 (date released 04/06/2018), NCT03768050 (date released 12/05/2018), NCT03767387 (date released 12/05/2018).

Class Imbalance Impact on the Prediction of Complications during Home Hospitalization: A Comparative Study.

Home hospitalization (HH) is presented as a healthcare alternative capable of providing high standards of care when patients no longer need hospital facilities. Although HH seems to lower healthcare costs by shortening hospital stays and improving patient's quality of life, the lack of continuous observation at home may lead to complications in some patients. Since blood tests have been proven to provide relevant prognosis information in many diseases, this paper analyzes the impact of different sampling methods on the prediction of HH outcomes. After a first exploratory analysis, some variables extracted from routine blood tests performed at the moment of HH admission, such as hemoglobin, lymphocytes or creatinine, were found to unmask statistically significant differences between patients undergoing successful and unsucessful HH stays. Then, predictive models were built with these data, in order to identify unsuccessful cases eventually needing hospital facilities. However, since these hospital admissions during HH programs are rare, their identification through conventional machine-learning approaches is challenging. Thus, several sampling strategies designed to face class imbalance were herein overviewed and compared. Among the analyzed approaches, over-sampling strategies, such as ROSE (Random Over-Sampling Examples) and conventional random over-sampling, showed the best performances. Nevertheless, further improvements should be proposed in the future so as to better identify those patients not benefiting from HH.

Protocol for regional implementation of collaborative self-management services to promote physical activity.

BACKGROUND: Chronic diseases are generating a major health and societal burden worldwide. Healthy lifestyles, including physical activity (PA), have proven efficacy in the prevention and treatment of many chronic conditions. But, so far, national PA surveillance systems, as well as strategies for promotion of PA, have shown low impact. We hypothesize that personalized modular PA services, aligned with healthcare, addressing the needs of a broad spectrum of individual profiles may show cost-effectiveness and sustainability. METHODS: The current manuscript describes the protocol for regional implementation of collaborative self-management services to promote PA in Catalonia (7.5 M habitants) during the period 2017-2019. The protocols of three implementation studies encompassing a broad spectrum of individual needs are reported. They have a quasi-experimental design. That is, a non-randomized intervention group is compared to a control group (usual care) using propensity score methods wherein age, gender and population-based health risk assessment are main matching variables. The principal innovations of the PA program are: i) Implementation of well-structured modular interventions promoting PA; ii) Information and communication technologies (ICT) to facilitate patient accessibility, support collaborative management of individual care plans and reduce costs; and iii) Assessment strategies based on the Triple Aim approach during and beyond the program deployment. DISCUSSION: The manuscript reports a precise roadmap for large scale deployment of community-based ICT-supported integrated care services to promote healthy lifestyles with high potential for comparability and transferability to other sites. TRIAL REGISTRATION: This study protocol has been registered at ClinicalTrials.org ( NCT02976064 ). Registered November 24th, 2016.

A qualitative study adopting a user-centered approach to design and validate a brain computer interface for cognitive rehabilitation for people with brain injury.

Cognitive rehabilitation is established as a core intervention within rehabilitation programs following a traumatic brain injury (TBI). Digitally enabled assistive technologies offer opportunities for clinicians to increase remote access to rehabilitation supporting transition into home. Brain Computer Interface (BCI) systems can harness the residual abilities of individuals with limited function to gain control over computers through their brain waves. This paper presents an online cognitive rehabilitation application developed with therapists, to work remotely with people who have TBI, who will use BCI at home to engage in the therapy. A qualitative research study was completed with people who are community dwellers post brain injury (end users), and a cohort of therapists involved in cognitive rehabilitation. A user-centered approach over three phases in the development, design and feasibility testing of this cognitive rehabilitation application included two tasks (Find-a-Category and a Memory Card task). The therapist could remotely prescribe activity with different levels of difficulty. The service user had a home interface which would present the therapy activities. This novel work was achieved by an international consortium of academics, business partners and service users.

A Multifunctional Brain-Computer Interface Intended for Home Use: An Evaluation with Healthy Participants and Potential End Users with Dry and Gel-Based Electrodes.

Current brain-computer interface (BCIs) software is often tailored to the needs of scientists and technicians and therefore complex to allow for versatile use. To facilitate home use of BCIs a multifunctional P300 BCI with a graphical user interface intended for non-expert set-up and control was designed and implemented. The system includes applications for spelling, web access, entertainment, artistic expression and environmental control. In addition to new software, it also includes new hardware for the recording of electroencephalogram (EEG) signals. The EEG system consists of a small and wireless amplifier attached to a cap that can be equipped with gel-based or dry contact electrodes. The system was systematically evaluated with a healthy sample, and targeted end users of BCI technology, i.e., people with a varying degree of motor impairment tested the BCI in a series of individual case studies. Usability was assessed in terms of effectiveness, efficiency and satisfaction. Feedback of users was gathered with structured questionnaires. Two groups of healthy participants completed an experimental protocol with the gel-based and the dry contact electrodes (N = 10 each). The results demonstrated that all healthy participants gained control over the system and achieved satisfactory to high accuracies with both gel-based and dry electrodes (average error rates of 6 and 13%). Average satisfaction ratings were high, but certain aspects of the system such as the wearing comfort of the dry electrodes and design of the cap, and speed (in both groups) were criticized by some participants. Six potential end users tested the system during supervised sessions. The achieved accuracies varied greatly from no control to high control with accuracies comparable to that of healthy volunteers. Satisfaction ratings of the two end-users that gained control of the system were lower as compared to healthy participants. The advantages and disadvantages of the BCI and its applications are discussed and suggestions are presented for improvements to pave the way for user friendly BCIs intended to be used as assistive technology by persons with severe paralysis.

Monitoring and Prognosis System Based on the ICF for People with Traumatic Brain Injury.

The objective of this research is to provide a standardized platform to monitor and predict indicators of people with traumatic brain injury using the International Classification of Functioning, Disability and Health, and analyze its potential benefits for people with disabilities, health centers and administrations. We developed a platform that allows automatic standardization and automatic graphical representations of indicators of the status of individuals and populations. We used data from 730 people with acquired brain injury performing periodic comprehensive evaluations in the years 2006-2013. Health professionals noted that the use of color-coded graphical representation is useful for quickly diagnose failures, limitations or restrictions in rehabilitation. The prognosis system achieves 41% of accuracy and sensitivity in the prediction of emotional functions, and 48% of accuracy and sensitivity in the prediction of executive functions. This monitoring and prognosis system has the potential to: (1) save costs and time, (2) provide more information to make decisions, (3) promote interoperability, (4) facilitate joint decision-making, and (5) improve policies of socioeconomic evaluation of the burden of disease. Professionals found the monitoring system useful because it generates a more comprehensive understanding of health oriented to the profile of the patients, instead of their diseases and injuries.

Brain Computer Interface on Track to Home.

The novel BackHome system offers individuals with disabilities a range of useful services available via brain-computer interfaces (BCIs), to help restore their independence. This is the time such technology is ready to be deployed in the real world, that is, at the target end users' home. This has been achieved by the development of practical electrodes, easy to use software, and delivering telemonitoring and home support capabilities which have been conceived, implemented, and tested within a user-centred design approach. The final BackHome system is the result of a 3-year long process involving extensive user engagement to maximize effectiveness, reliability, robustness, and ease of use of a home based BCI system. The system is comprised of ergonomic and hassle-free BCI equipment; one-click software services for Smart Home control, cognitive stimulation, and web browsing; and remote telemonitoring and home support tools to enable independent home use for nonexpert caregivers and users. BackHome aims to successfully bring BCIs to the home of people with limited mobility to restore their independence and ultimately improve their quality of life.

Simulation environment and graphical visualization environment: a COPD use-case.

BACKGROUND: Today, many different tools are developed to execute and visualize physiological models that represent the human physiology. Most of these tools run models written in very specific programming languages which in turn simplify the communication among models. Nevertheless, not all of these tools are able to run models written in different programming languages. In addition, interoperability between such models remains an unresolved issue. RESULTS: In this paper we present a simulation environment that allows, first, the execution of models developed in different programming languages and second the communication of parameters to interconnect these models. This simulation environment, developed within the Synergy-COPD project, aims at helping and supporting bio-researchers and medical students understand the internal mechanisms of the human body through the use of physiological models. This tool is composed of a graphical visualization environment, which is a web interface through which the user can interact with the models, and a simulation workflow management system composed of a control module and a data warehouse manager. The control module monitors the correct functioning of the whole system. The data warehouse manager is responsible for managing the stored information and supporting its flow among the different modules. CONCLUSION: It has been proved that the simulation environment presented here allows the user to research and study the internal mechanisms of the human physiology by the use of models via a graphical visualization environment. A new tool for bio-researchers is ready for deployment in various use cases scenarios.

Biomedical research in a Digital Health Framework.

This article describes a Digital Health Framework (DHF), benefitting from the lessons learnt during the three-year life span of the FP7 Synergy-COPD project. The DHF aims to embrace the emerging requirements--data and tools--of applying systems medicine into healthcare with a three-tier strategy articulating formal healthcare, informal care and biomedical research. Accordingly, it has been constructed based on three key building blocks, namely, novel integrated care services with the support of information and communication technologies, a personal health folder (PHF) and a biomedical research environment (DHF-research). Details on the functional requirements and necessary components of the DHF-research are extensively presented. Finally, the specifics of the building blocks strategy for deployment of the DHF, as well as the steps toward adoption are analyzed. The proposed architectural solutions and implementation steps constitute a pivotal strategy to foster and enable 4P medicine (Predictive, Preventive, Personalized and Participatory) in practice and should provide a head start to any community and institution currently considering to implement a biomedical research platform.

Predictive medicine: outcomes, challenges and opportunities in the Synergy-COPD project.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is a major challenge for healthcare. Heterogeneities in clinical manifestations and in disease progression are relevant traits in COPD with impact on patient management and prognosis. It is hypothesized that COPD heterogeneity results from the interplay of mechanisms governing three conceptually different phenomena: 1) pulmonary disease, 2) systemic effects of COPD and 3) co-morbidity clustering. OBJECTIVES: To assess the potential of systems medicine to better understand non-pulmonary determinants of COPD heterogeneity. To transfer acquired knowledge to healthcare enhancing subject-specific health risk assessment and stratification to improve management of chronic patients. METHOD: Underlying mechanisms of skeletal muscle dysfunction and of co-morbidity clustering in COPD patients were explored with strategies combining deterministic modelling and network medicine analyses using the Biobridge dataset. An independent data driven analysis of co-morbidity clustering examining associated genes and pathways was done (ICD9-CM data from Medicare, 13 million people). A targeted network analysis using the two studies: skeletal muscle dysfunction and co-morbidity clustering explored shared pathways between them. RESULTS: (1) Evidence of abnormal regulation of pivotal skeletal muscle biological pathways and increased risk for co-morbidity clustering was observed in COPD; (2) shared abnormal pathway regulation between skeletal muscle dysfunction and co-morbidity clustering; and, (3) technological achievements of the projects were: (i) COPD Knowledge Base; (ii) novel modelling approaches; (iii) Simulation Environment; and, (iv) three layers of Clinical Decision Support Systems. CONCLUSIONS: The project demonstrated the high potential of a systems medicine approach to address COPD heterogeneity. Limiting factors for the project development were identified. They were relevant to shape strategies fostering 4P Medicine for chronic patients. The concept of Digital Health Framework and the proposed roadmap for its deployment constituted relevant project outcomes.

Synergy-COPD: a systems approach for understanding and managing chronic diseases.

Chronic diseases (CD) are generating a dramatic societal burden worldwide that is expected to persist over the next decades. The challenges posed by the epidemics of CD have triggered a novel health paradigm with major consequences on the traditional concept of disease and with a profound impact on key aspects of healthcare systems. We hypothesized that the development of a systems approach to understand CD together with the generation of an ecosystem to transfer the acquired knowledge into the novel healthcare scenario may contribute to a cost-effective enhancement of health outcomes. To this end, we designed the Synergy-COPD project wherein the heterogeneity of chronic obstructive pulmonary disease (COPD) was addressed as a use case representative of CD. The current manuscript describes main features of the project design and the strategies put in place for its development, as well the expected outcomes during the project life-span. Moreover, the manuscript serves as introductory and unifying chapter of the different papers associated to the Supplement describing the characteristics, tools and the objectives of Synergy-COPD.

Automatic assessment of socioeconomic impact on cardiac rehabilitation.

Disability-Adjusted Life Years (DALYs) and Quality-Adjusted Life Years (QALYs), which capture life expectancy and quality of the remaining life-years, are applied in a new method to measure socioeconomic impacts related to health. A 7-step methodology estimating the impact of health interventions based on DALYs, QALYs and functioning changes is presented. It relates the latter (1) to the EQ-5D-5L questionnaire (2) to automatically calculate the health status before and after the intervention (3). This change of status is represented as a change in quality of life when calculating QALYs gained due to the intervention (4). In order to make an economic assessment, QALYs gained are converted to DALYs averted (5). Then, by inferring the cost/DALY from the cost associated to the disability in terms of DALYs lost (6) and taking into account the cost of the action, cost savings due to the intervention are calculated (7) as an objective measure of socioeconomic impact. The methodology is implemented in Java. Cases within the framework of cardiac rehabilitation processes are analyzed and the calculations are based on 200 patients who underwent different cardiac-rehabilitation processes. Results show that these interventions result, on average, in a gain in QALYs of 0.6 and a cost savings of 8,000 €.