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Across the globe, the healthcare sector is experiencing transformations (cultural, social, digital and economic). This is due to the age and varying patient needs that are driving a shift in the healthcare landscape. At the same time, chronic diseases, social determinants and resource limitations continue to add pressure. Healthcare has thus shifted from paternalistic mode of care to patient centered care (PCC). The growing multiple divergent medical cases denote a need to collaboratively understand clinical issues and effectively determine the best course of action. With PCC, a patient is recognized as a unique human being before forming a diagnosis. This implies that there is a need for multifaceted decision-making. In this study, we use a co-construction participatory modeling approach to understand the complexities in collaboratively managing knowledge for multi-morbid chronic patients on Advance Care Plan (ACP). To achieve this, focus group discussions (FGD) with 12 participants (five healthcare professionals, three health managers and three healthcare key decision makers) from Basque Public Health System (Osakidetza), in Spain were involved in identifying the key challenges and developing a systemic thinking model. As a result, three key challenges were identified i.e. 1) culture (citizens are not willing to talk about death, 2) healthcare professionals’ challenge to change attitude and perspectives, and 3) changing the current system towards holistic and a shared care model. From the developed Causal loop diagrams (CLDs), it is noted that perpetuation of fragmented and paternalistic care is likely to get worse without recognition of the ACP as a social need and a crucial part of the clinical practice part change.

Introduction: Population longevity, morbidity and high consumption of medicines, have become polypharmacy a priority health problem due to its high prevalence and problems that can cause: lack of adherence, increased adverse effects and drug interactions, or functional deterioration. Treatment review in polymedicated patients is an essential activity to improve the appropriateness of treatments and avoid potential prescription-related safety problems.In the EU-funded GATEKEEPER project, the Basque Country region is running the use case “management of people with chronic diseases and polypharmacy”. It has implemented an intervention through a mobile application and web solution for the management of polypharmacy in multimorbid patients. Aims, Objectives, Theory And Methods: This quasi-experimental study (non-randomised, concurrent and controlled study) aimed to assess the effectiveness and user experience of two applications to optimize the detection of inappropriate therapeutic prescriptions (CheckTheMeds) and to improve adherence to treatment in patients (My Treatment) with chronic diseases and polypharmacy.The intervention is being carried out in 11 Integrated Healthcare Organizations from Osakidetza Basque Health Service. The target is to recruit 1,000 elderly people (500-intervention group and 500 control group) that fits with the inclusion criteria (aged more than 70 years or older, with more than 2 chronic diseases, and more than 9 drugs prescribed). Highlights Or Results Or Key Findings: Trained Primary Care healthcare professionals will contact 500 candidates for the intervention group, who will be invited to participate in the study and informed about it. After signing the informed consent form, their health status, prescribed drugs, and the adherence to the treatment will be revised and monitored for 9 months. Piloting will last since December 2021 to September 2022. A mixed methods approach will be employed, integrating quantitative and qualitative technics. Data obtained through different approaches (Questionnaires, administrative data, usage metrics, interviews information), will provide a broad understanding of what each approach has achieved and how or why results have been produced. Se invitará al paciente a utilizar la App corporativa ""Mi Tratamiento"" que fomentará la adherencia al tratamiento y hará que los pacientes y/o cuidadores sean conscientes de la medicación que tienen prescrita, se hagan cargo de su tratamiento y tengan comunicación con los profesionales sanitarios.Conclusions: This study pretends to give evidence how a treatment appropriateness, together with greater therapeutic adherence, will result in more effective treatments with fewer drug-related problems and health complications, and thus in improved efficiency in the use of healthcare resources and also increase quality of life of these patients.Implications For Applicability/Transferability/Sustainability: The use of CheckThemeds and App “Mi Tratamiento” tools will improve the adherence and prescription through the review of medicines that detect potentially inappropriate prescriptions and increase the rate of therapeutic compliance.Osakidetza Basque Health Service will integrate these platforms in the clinical practice as part of the multimorbid patient’s pathway.

Due to population ageing and medical advances, people with advanced chronic diseases (ACD) live longer. Such patients are even more likely to face either temporary or permanent reduced functional reserve, which typically further increases their healthcare resource use and the burden of care on their caregiver(s). Accordingly, these patients and their caregiver(s) may benefit from integrated supportive care provided via digitally supported interventions. This approach may either maintain or improve their quality of life, increase their independence, and optimize the healthcare resource use from early stages. ADLIFE is an EU-funded project, aiming to improve the quality of life of older people with ACD by providing integrated personalized care via a digitally enabled toolbox. Indeed, the ADLIFE toolbox is a digital solution which provides patients, caregivers, and health professionals with digitally enabled, integrated, and personalized care, supporting clinical decisions, and encouraging independence and self-management. Here we present the protocol of the ADLIFE study, which is designed to provide robust scientific evidence on the assessment of the effectiveness, socio-economic, implementation, and technology acceptance aspects of the ADLIFE intervention compared to the current standard of care (SoC) when applied in real-life settings of seven different pilot sites across six countries. A quasi-experimental trial following a multicenter, non-randomized, non-concurrent, unblinded, and controlled design will be implemented. Patients in the intervention group will receive the ADLIFE intervention, while patients in the control group will receive SoC. The assessment of the ADLIFE intervention will be conducted using a mixed-methods approach.

Motivated by the aging trend, much effort is being invested into implementing ICT (Information 19 and Communications Technology)-enabled systems to provide a better quality of life and support 20 the independent living of older people. As a result, many systems, often labeled as eHealth or AAL 21 (Ambient/Active Assisted Living), were developed over the years. In creating such systems, that 22 very often serve various needs, different architectures have emerged. This work focuses on analyz-23 ing and comparing the work and architectures from seven (six of which are in progress) EU-funded 24 healthcare projects, with a total budget of 126MEUR in which we participate. After establishing the 25 theoretical foundation by defining core concepts, we give a brief background on architectures in 26 eHealth and AAL. We elaborate on the chosen analysis method based on three established 27 healthcare and AAL taxonomies we identified by performing a literature survey and the selected 28 Reference Architecture Model (RAM). Since there is no standard way of describing architectures in 29 the eHealth and AAL domain, we conducted the online survey during August and September 2020 30 and identified CREATE-IoT 3D RAM as the most appropriate option. We present a classification of 31 selected projects based on established taxonomies and map projects' architectures to CREATE-IoT 32 3D RAM, which we also propose as standard RAM for future digital healthcare and AAL projects. 33 During our analysis, we identify the most common types of assistance: communication support, 34 reminders, monitoring, and guidance to address health and communication issues. We conclude 35 that proper ecosystems are critical for lowering entry barriers and facilitating sustainable solutions 36 for smart and healthy living.

Assessment of disease burden and drug efficacy is achieved preclinically using high resolution micro computed tomography (CT). However, micro-CT is not applicable to clinical human imaging due to operating at high dose. In addition, the technology differences between micro-CT and standard clinical CT prevent direct translation of preclinical applications. The current proof-of-concept study presents spectral photon-counting CT as a clinically translatable, molecular imaging tool by assessing contrast uptake in an ex-vivo mouse model of pulmonary tuberculosis (TB). Iodine, a common contrast used in clinical CT imaging, was introduced into a murine model of TB. The excised mouse lungs were imaged using a standard micro-CT subsystem (SuperArgus) and the contrast enhanced TB lesions quantified. The same lungs were imaged using a spectral photoncounting CT system (MARS small-bore scanner). Iodine and soft tissues (water and lipid) were materially separated, and iodine uptake quantified. The volume of the TB infection quantified by spectral CT and micro-CT was found to be 2.96 mm3 and 2.83 mm3, respectively. This proof-of-concept study showed that spectral photon-counting CT could be used as a predictive preclinical imaging tool for the purpose of facilitating drug discovery and development. Also, as this imaging modality is available for human trials, all applications are translatable to human imaging. In conclusion, spectral photon-counting CT could accelerate a deeper understanding of infectious lung diseases using targeted pharmaceuticals and intrinsic markers, and ultimately improve the efficacy of therapies by measuring drug delivery and response to treatment in animal models and later in humans.

Introduction Persons with Advanced Chronic Diseases can greatly benefit from digitally supported interventions to improve or maintain their health, avoid unnecessary deterioration, extend their independence and optimize health resources utilization. Digitalisation is expected to lead a profound transformation of health services. It is important to evaluate its impact. The coronavirus disease (COVID-19) pandemic has pushed forward the paradigm shift towards telehealth, highlighting the need worldwide for enabling and promoting digital care. Theory/Methods The project ADLIFE (H2020, SC1-DTH-11-2019, 875209) aims to provide innovative integrated intelligent personalized care to aged patients with complex chronic diseases. Care will be supported by an ICT solution, the ADLIFE Toolbox. The target population is senior (55+) patients with severe Heart failure and/or COPD. In total in the seven pilot sites, 882 patients, 1243 caregivers and 577 healthcare professionals from specialized and primary care services will be involved in pilot operation and evaluation activities. Care delivery models, level of integration, scope and content of the Clinical Decision Support Services (CDSS) and health outcomes has been explored and defined involving relevant stakeholders at each pilot site. Results and Discussion Each pilot has identified improvement areas required to enable the delivery of care proposed in ADLIFE. A conceptual framework has been developed to that includes and categorize health outcomes. Data will be used for evaluation and CDSS. A set of PROMs has been proposed to capture the information on the effectiveness and the quality of the care delivered as perceived by the patients. CDSS are based on computable flowcharts as defined in evidence based clinical guidelines (single disease and reconciled for multimorbidity). AI algorithms will be developed and trained to identify Potentially Preventable Situations. Conclusions (comprising key findings) The project seeks to demonstrate that a personalized care model that integrates clinical and patient stakeholders´ analysis with ICT tools is effective and flexible and can be deployed and replicated in different health care systems. Lessons learned Assessing care models and having trusted personalised digital solutions are key for ADLIFE implementation and operation in the seven ICT health systems. Limitations Multimorbidity covers a wide range of conditions. ADLIFE focuses on COPD and/or Heart Failure with or without co morbidities. Further analytical and development work will be needed to be done. Suggestions for future research The effectiveness and efficiency of deploying digitally enabled holistic and integrated supportive care will be assessed by evaluating health gain, quality of life, use of resources and economic costs. The authors are on behalf of the ADLIFE Consortium. The ADLIFE project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 875209.

Hollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray&-based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases. The research leading to these results received funding from the Innovative Medicines Initiative (www.imi.europa.eu) Joint Undertaking under grant agreement no. 115337, whose resources comprise funding from the European Union Seventh Framework Programme (FP7/2007–2013) and EFPIA companies in kind contribution. This work was partially funded by projects RTC-2015-3772-1, TEC2015-73064-EXP and TEC2016-78052-R from the Spanish Ministry of Economy, TOPUS S2013/MIT-3024 project from the regional government of Madrid and by the Department of Health, UK. This study (was supported by the Instituto de Salud Carlos III (Plan Estatal de I + D + i 2013–2016) and co-financed by the European Social Fund (ESF) “ESF investing in your future”. The authors thank Dr.Guembe from CIMA-Universidad de Navarra for preparing and staining the tissue sections, and to Dr. Guerrero-Aspizua and Prof. Conti of the Department of Bioengineering, Universidad Carlos III de Madrid for the pathology evaluation.

The sensitivity of in vivo low-dose high-resolution micro-computed tomography imaging enables monitoring the lung damage caused by tuberculosis. Here, we propose a radiological score integrated in the experimental workflow that enables longitudinal monitoring for prospective efficacy studies in drug development programs. The score is based on an automatic measurement of total unaffected lung volume in vivo normalized for inter-subject comparison. It was validated on well-characterized progression of chronic tuberculosis in Erdman and H37Rv strains in C3HeB/FeJ-based models. We demonstrated that a decrease in the score value indicates increasing adverse effects and vice versa. The colony-forming units count confirmed the variability in the host response suggested by the score values. The correlation between changes in the mice's weight and the score is consistent with disease progression. The classification of disease extent by k-means clustering of the score values provided the definition of the lung damage severity according to the bacillus strain. The proposed score will reduce sources of bias and improve the statistical robustness of studies by the attrition of non-infected subjects or subjects with a weak immune response. Readily available quantifications allow for a fast assessment of the therapeutic potential in drug-resistant tuberculosis strains.

In this work we describe a method for producing a tissue-detailed phantom of a mouse thorax, by means of durable and easy-to-get materials. We report the material selection and an implementation that involves mimicking tuberculosis lung granulomas and the surrounding tissues.