A common feature of autoantibody-positive autoimmune disease is that the disease-associated autoimmunity often appears many years prior to clinical onset and can hence be used to identify risk groups for future disease development. Autoantibody-positive (seropositive) rheumatoid arthritis (RA) provides a unique setting due to recent insights in the longitudinal development of the disease, suggesting that autoantibodies develop in genetic susceptible individuals as a consequence of specific environmental challenges (such as smoking) to only later on target the joints. The main objectives of the current program are: (1). To dissect the longitudinal development of seropositive RA and gain a detailed understanding of the processes responsible for autoantibody generation outside the joints, and specifically at the mucosal sites. (2). To develop new ways to identify seropositive disease-susceptible individuals and map targetable life style factors and immune events responsible for this susceptibility. (3). To elucidate the mechanisms by which systemic autoimmunity targets the joints to first induce bone loss and pain and only in a second phase chronic joint inflammation. If successful our project will not only allow efficient identification of RA-susceptible individuals, but also deliver new tools for risk estimation in each of these individuals and novel ways of intervention in order to delay, or in the best case prevent disease development. By shifting the time (to phases before joint damage and disability occurs) and the ways (to drugs targeting early previously unknown pathogenic mechanisms) of interventions, expected results from the current project are beyond the current state of the art in RA.

In extracorporeal organ support (ECOS), one or more organ functions fail and are replaced by an artificial device. Kidney failure requires hemodialysis, at least until transplantation. Temporary lung- and/or heart-failure may be treated by Extracorporeal Membrane Oxygenation (ECMO). About 1.5 Million patients require hemodialysis worldwide. ECMO has an essential life-saving role during the ongoing COVID-19 pandemic, as during the Influenzae H1N1 pandemic in 2009. In ECOS, two or more accesses are used; one for blood drainage and another to return oxygenated blood. The flow rate in the cannula and the cannulated blood vessels is often significantly higher than physiologically experienced. The high flow velocity implies larger forces (stress) acting on the blood cells and the vessel walls. Thromboembolism and morphological and mechanical changes in the affected blood vessel are common complications in ECOS. This project focus on the impact of blood flow on these complications. Patient-specific data (CT, MRI and Ultrasound based) will be used to construct laboratory and simulation relevant frameworks. Set-ups for measurement of flow and mixing in-vitro will be used. Simulations will include modeling of transport of chemical species and blood cells along with modeling of platelet activation and risk for thrombus formation. The different tools will enable a considerably better understanding of the underlying pathological processes. The results will support further model development of these processes and facilitate improved cannulation techniques and new devices. These propositions are to be assessed by our clinical partners. Therefore, the project group includes, fluid mechanical expertise, and also clinical specialist in nephrology, intensive care/ECMO, and radiology. The outcome of research will enable device development and clinical decision-making reducing overall treatment complications.

Safest, reliable, individualised care of patients at-risk of deterioration needs patients themselves to play an active role in their care whenever possible: late detection or escalation of deterioration causes avoidable harms, and deaths. In this project we will challenge industry to develop robust monitoring and communications systems that connect patients, carers and health professionals, provide early warning of acute deterioration in and out of hospital, and learn and adapt to different individuals in different situations. Wearable sensor technology allows dynamic monitoring of vital signs that indicate health status, while bidirectional video communication allows interaction with the patient and in depth assessment. Self-learning adaptive algorithms interfaced with Electronic Medical Records can provide reliable early warning with few false alarms; and data about individual responses to different therapies.We will first target known at-risk patients such as those on general hospital floors after discharge from Intensive Care or following major surgery, and the frail elderly. This will also enable the safe care of many patients at home, e.g., patients seen in the Emergency Room but judged not to need hospital admission, or those with serious chronic conditions. Reliable, robust monitoring and communication systems will improve patient safety in hospital and after discharge, will decrease avoidable harms and deaths, reduce length of stay and readmissions, and help maintain patient’s independence; providing reassurance of wellness and early warning of deterioration. Analysis of collected ‘big data’ will increase understanding of treatment of specific patient groups, and provide spinoffs such as eHealth applications for chronic conditions. Once mature and integrated in European health care systems, the procured technology can truly transform healthcare by engaging with and empowering all at-risk patients, and enabling their connection with health professionals

Lifestyle factors of the patient (e.g. smoking, hazardous alcohol drinking and malnutrition) are proven to be independent risk factors negatively impacting health outcome in the perioperative process. Evidence suggests that the implementation of intensive lifestyle intervention programs can significantly reduce the post-surgery complication risk and rehabilitation time . However, implementation of and compliance to such programs are today poor. In addition, possibilities to optimize the patients’ mental and physical state throughout the perioperative process are insufficient. LIVE INCITE aims to move beyond the current state of general information being provided about risks and post-surgery activities, to translating statistics and data to individual-specific information, making the individual plan “real” for the patient. We believe it is possible to leverage f i existing and new data, best practice behavioral change concepts, intuitive and easy-to-use user experience, modern communication and collaboration channels to integrate not only patients and care providers but also the patient’s family and friends, and new technology for continuous monitoring of and feedback on patient activities related to her defined plan. But, no matter which concepts and solutions the market will suggest, sustainability and scalability (related to the likely changing needs and pre-requisites of the specific procurer as well as the dissemination in and uptake from a European-wide procurer community) has to be enforced through principles related to interoperability, open architecture, and use of international standards. Through its consortia including specialized care hospitals, academia, patient organizations as well as collaboration and innovation platforms the project has the critical mass of knowledge to reach a truly innovative solution together with the supply side.