Predictive preventive personalized medicine Liver cancer is the fifth most common form of cancer worldwide [1], with an incidence rate almost equals the mortality rate and ranks 3 rd among causes of cancer related death [2]. The coexistence of two life threatening conditions, cancer and liver cirrhosis makes the staging challenging. However, there are some staging systems, e.g. the Barcelona staging system for Hepatocellular carcinoma (HCC) [3], that suggest treatment options and management. Whereas diagnosis in early stages gives hope for a curative outcome, the treatment regime for around 80 % [2] of the patients classified as severe stages only gears towards palliation [4]. An intra-arterial radiation approach, radioembolisation (RE) is ubiquitously applied as one of palliative approaches. Although, in general RE shows promising results in intermediate and advanced stage HCC [5], individual treatment outcomes are currently unpredictable. Corresponding stratification criteria are still unclear. We hypothesised that individual radioresistance/radiosensitivity may play a crucial role in treatment response towards RE strongly influencing individual outcomes. Further, HCC represents a highly heterogeneous group of patients which requires patient stratification according to clear criteria for treatment algorithms to be applied individually. Multilevel diagnostic approach (MLDA) is considered helpful to set-up optimal predictive and prognostic biomarker panel for individualised application of radioembolisation. Besides comprehensive medical imaging, our MLDA includes non-invasive multi-omics and sub-cellular imaging. Individual patient profiles are expected to give a clue to targeting shifted molecular pathways, individual RE susceptibility, treatment response. Hence, a dysregulation of the detoxification pathway (SOD2/Catalase) might indicate possible adverse effects of RE, and highly increased systemic activities of matrix metalloproteinases indicate an enhanced tumour aggressiveness and provide insights into molecular mechanisms/targets. Consequently, an optimal set-up of predictive and prognostic biomarker panels may lead to the changed treatment paradigm from untargeted "treat and wait" to the cost-effective predictive, preventive and personalised approach, improving the life quality and life expectancy of HCC patients. Keywords: Market access, Value, Strategy, Companion diagnostics, Cost-effectiveness, Reimbursement, Health technology assessment, Economic models, Predictive preventive personalized medicine Achieving and sustaining seamless "drug -companion diagnostic" market access requires a sound strategy throughout a product life cycle, which enables timely creation, substantiation and communication of value to key stakeholders [1, 2]. The study aims at understanding the root-cause of market access inefficiencies of companies by gazing at the "Rx-CDx" co-development process through the prism of "value", and developing a perfect co-development scenario based on the literature review and discussions with the ...

The United Nations has recognized the devastating consequences of “unpredictable, unpreventable and impersonal” disasters—at least US $2 trillion in economic damage and more than 1.3 million lives lost from natural disasters in the last two decades alone. In many disasters (both natural and man-made) hundreds—and in major earthquakes, thousands—of lives are lost in the first days following the event because of the lack of medical/surgical facilities to treat those with potentially survivable injuries. Disasters disrupt and destroy not only medical facilities in the disaster zone but also infrastructure (roads, airports, electricity) and potentially local healthcare personnel as well. To minimize morbidity and mortality from disasters, medical treatment must begin immediately, within minutes ideally, but certainly within 24 h (not the days to weeks currently seen in medical response to disasters). This requires that all resources—medical equipment and support, and healthcare personnel—be portable and readily available; transport to the disaster site will usually require helicopters, as military medical response teams in developed countries have demonstrated. Some of the resources available and in development for immediate medical response for disasters—from portable CT scanners to telesurgical capabilities—are described. For immediate deployment, these resources—medical equipment and personnel—must be ready for deployment on a moment’s notice and not require administrative approvals or bureaucratic authorizations from numerous national and international agencies, as is presently the case. Following the “trauma center/stroke center” model, disaster response incorporating “disaster response centers” would be seamlessly integrated into the ongoing daily healthcare delivery systems worldwide, from medical education and specialty training (resident/registrar) to acute and subacute intensive care to long-term rehabilitation. The benefits of such a global disaster response network extend far beyond the lives saved: universal standards for medical education and healthcare delivery, as well as the global development of medical equipment and infrastructure, would follow. Capitalizing on the humanitarian nature of disaster response—with its suspension of the cultural, socioeconomic and political barriers that often paralyze international cooperation and development—disaster response can be predictable, loss of life can be preventable and benefits can be both personal and societal.

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Trauma/stroke centres optimise acute 24/7/365 surgical/critical care in high-income countries (HICs). Concepts from low-income and middle-income countries (LMICs) offer additional cost-effective healthcare strategies for limited-resource settings when combined with the trauma/stroke centre concept. Mass casualty centres (MCCs) integrate resources for both routine and emergency care—from prevention to acute care to rehabilitation. Integration of the various healthcare systems—governmental, non-governmental and military—is key to avoid both duplication and gaps. With input from LMIC and HIC personnel of various backgrounds—trauma and subspecialty surgery, nursing, information technology and telemedicine, and healthcare administration—creative solutions to the challenges of expanding care (both daily and disaster) are developed. MCCs are evolving initially in Chile and Pakistan. Technologies for cost-effective healthcare in LMICs include smartphone apps (enhance prehospital care) to electronic data collection and analysis (quality improvement) to telemedicine and drones/robots (support of remote regions and resource optimisation during both daily care and disasters) to resilient, mobile medical/surgical facilities (eg, battery-operated CT scanners). The co-ordination of personnel (within LMICs, and between LMICs and HICs) and the integration of cost-effective advanced technology are features of MCCs. Providing quality, cost-effective care 24/7/365 to the 5 billion who lack it presently makes MCCs an appealing means to achieve the healthcare-related United Nations Sustainable Development Goals for 2030.

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It has been well-documented recently that 5 billion people globally lack surgical care. Also well-documented is the need to improve mass casualty disaster response. Many of the United Nations (UN) Sustainable Development Goals (SDGs) for 2030—healthcare and economic milestones—require significant improvement in global surgical care, particularly in low-income and middle-income countries. Trauma/stroke centres evolved in high-income countries with evidence that 24/7/365 surgical and critical care markedly improved morbidity and mortality for trauma and stroke and for cardiovascular events, difficult childbirth, acute abdomen. Duplication of emergency services, especially civilian and military, often results in suboptimal, expensive care. By combining all healthcare resources within the ongoing healthcare system, more efficient care for both individual emergencies and mass casualty situations can be achieved. We describe progress in establishing mass casualty centres in Chile and Pakistan. In both locations, planning among the stakeholders (primarily civilian and military) indicates the feasibility of such integrated surgical and emergency care. We also review other programmes and initiatives to provide integrated mass casualty disaster response. Integrated mass casualty centres are a feasible means to improve both day-to-day surgical care and mass casualty disaster response. The humanitarian aspect of mass casualty disasters facilitates integration among stakeholders—from local healthcare systems to military resources to international healthcare organisations. The benefits of mass casualty centres—both healthcare and economic—can facilitate achieving the 2030 UN SDGs.

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