A key problem in Mental Health is that up to one third of patients suffering from major mental disorders develop resistance against drug therapy. However, patients showing early signs of treatment resistance (TR) do not receive adequate early intensive pharmacological treatment but instead they undergo a stepwise trial-and-error treatment approach. This situation originates from three major knowledge and translation gaps: i.) we lack effective methods to identify individuals at risk for TR early in the disease process, ii.) we lack effective, personalized treatment strategies grounded in insights into the biological basis of TR, and iii.) we lack efficient processes to translate scientific insights about TR into clinical practice, primary care and treatment guidelines. It is the central goal of PSYCH-STRATA to bridge these gaps and pave the way for a shift towards a treatment decision-making process tailored for the individual at risk for TR. To that end, we aim to establish evidence-based criteria to make decisions of early intense treatment in individuals at risk for TR across the major psychiatric disorders of schizophrenia, bipolar disorder and major depression. PSYCH-STRATA will i.) dissect the biological basis of TR and establish criteria to enable early detection of individuals at risk for TR based on the integrated analysis of an unprecedented collection of genetic, biological, digital mental health, and clinical data. ii.) Moreover, we will determine effective treatment strategies of individuals at risk for TR early in the treatment process, based on pan-European clinical trials in SCZ, BD and MDD. These efforts will enable the establishment of novel multimodal machine learning models to predict TR risk and treatment response. Lastly, iii.) we will enable the translation of these findings into clinical practice by prototyping the integration of personalized treatment decision support and patient-oriented decision-making mental health boards.

Heart attacks are common and can leave survivors suffering cardiogenic shock (CGS), with its extremely high risk of early death (42% versus 4% for non-CGS) and high incidence of chronic heart failure, with its associated socio-economic disease burden (ill-health, recurrent heart failure admissions, no return to full time activities, need for expensive therapeutic devices and life-long drugs). Outcomes from CGS are even worse in, females, the elderly (mortality>70%) and high risk sub-groups. The incidence of CGS in Europe alone is >50 000 patients pa. This unacceptably high mortality/morbidity rate represents a true unmet clinical need. No clear strategy exists to improve outcomes, with ad hoc therapies given too late in a spiralling, irrecoverable process. EURO SHOCK aims to improve outcomes for CGS patients. At its core is a robust phase3 randomised trial comparing a novel strategy of very early use of ECMO (Extracorporeal Membrane Oxygenation) to current standard of care. Evidence suggests very early ECMO will halt the spiral of decline and so significantly reduce 12 month death rate and need for heart failure re-admissions. Since both costs of CGS, and ECMO are high a health-economic cost efficacy analysis will be core. A cardiac magnetic resonance imaging sub-study will test novel protocols in sick patients and provide mechanistic data. We will test transfer networks for CGS patients and analyse ECG data to determine which patients benefit most from early transfer. Our multidisciplinary consortium comprises renowned physician-scientists, statisticians, health economists and technology providers, including specialised ECMO SME. EURO SHOCK will impact on heart attack survivors, healthcare providers and Europe`s medical technology sector by 1) reducing healthcare costs associated with CGS 2) provide novel cost effective framework for cardiac interventions 3) delivering innovative healthcare technologies and 4) informing guidelines for effective CGS intervention.