The future of evolutionary medicine: sparking innovation in biomedicine and public health

Evolutionary medicine - i.e. the application of insights from evolution and ecology to biomedicine - has tremendous untapped potential to spark transformational innovation in biomedical research, clinical care and public health. Fundamentally, a systematic mapping across the full diversity of life is required to identify animal model systems for disease vulnerability, resistance, and counter-resistance that could lead to novel clinical treatments. Evolutionary dynamics should guide novel therapeutic approaches that target the development of treatment resistance in cancers (e.g., via adaptive or extinction therapy) and antimicrobial resistance (e.g., via innovations in chemistry, antimicrobial usage, and phage therapy). With respect to public health, the insight that many modern human pathologies (e.g., obesity) result from mismatches between the ecologies in which we evolved and our modern environments has important implications for disease prevention. Life-history evolution can also shed important light on patterns of disease burden, for example in reproductive health. Experience during the COVID-19 (SARS-CoV-2) pandemic has underlined the critical role of evolutionary dynamics (e.g., with respect to virulence and transmissibility) in predicting and managing this and future pandemics, and in using evolutionary principles to understand and address aspects of human behavior that impede biomedical innovation and public health (e.g., unhealthy behaviors and vaccine hesitancy). In conclusion, greater interdisciplinary collaboration is vital to systematically leverage the insight-generating power of evolutionary medicine to better understand, prevent, and treat existing and emerging threats to human, animal, and planetary health

981-46 Impact of a Comprehensive Management Program on the Hospitalization Rate for Patients with Advanced Heart Failure

Patients with advanced heart failure have a course that is often characterized by frequent hospitalizations and progressive deterioration. These patients are commonly referred to specialized centers for consideration of heart transplantation (Tx). To assess the impact of the changes in therapy made in conjunction with heart transplantation evaluation on patient outcomes, we assessed the hospitalization rate and patient's functional status in the 6 months prior to referral compared to the 6 months after referral. Since 1/91, 214 patients were evaluated, accepted for Tx, and discharged having undergone adjustments in medical therapy and a comprehensive patient education program. At time of referral patients had mean LVEF 0.21, NYHA class 3.3, VO2 max 11.0ml/kg, and had undergone a total of 429 hospitalizations in the previous 6 months. During evaluation patients had their ACE inhibitor dose increased by a mean 91.5mg/day of captopril or the equivalent, were diuresed a mean 4.2 liters, were placed on a flexible regimen of loop diuretics, and were counseled on dietary management and home based progressive aerobic exercise. After 6 months of follow-up there were only 63 hospitalizations required (mean hospitalization rate per patient over the 6 months pre-evaluation 2.00±1.45 vs post-evaluation 0.29±0.53 p<0.00001). Patient's NYHA class improved to 2.4 (p<0.0001) and VO2 max increased to 15.2 (p<0.001). Excluding the 12 elective status Tx, 14 urgent status Tx, and 9 deaths within 6 months yielded similar results (344 pre vs 34 post-evaluation hospitalizations). 64 patients (30%) improved their functional status to the point that transplantation was deferred in favor of sustained medical therapy.Referral to a heart failure specialty program is associated with a dramatic occurred between day 10±1 and 3 month. 4 patients died after hospital discharge (no death directly related to thromboembolic disease). Thus no higher risk of PE can be seen in patients with free floating prox-DVT and anticoagulant therapy should be efficient to prevent recurrent PE in such patient

Did giraffe cardiovascular evolution solve the problem of heart failure with preserved ejection fraction?

The evolved adaptations of other species can be a source of insight for novel biomedical innovation. Limitations of traditional animal models for the study of some pathologies are fueling efforts to find new approaches to biomedical investigation. One emerging approach recognizes the evolved adaptations in other species as possible solutions to human pathology. The giraffe heart, for example, appears resistant to pathology related to heart failure with preserved ejection fraction (HFpEF)-a leading form of hypertension-associated cardiovascular disease in humans. Here, we postulate that the physiological pressure-induced left ventricular thickening in giraffes does not result in the pathological cardiovascular changes observed in humans with hypertension. The mechanisms underlying this cardiovascular adaptation to high blood pressure in the giraffe may be a bioinspired roadmap for preventive and therapeutic strategies for human HFpEF

Manipulating the exposome to enable better ageing

The sum total of life course exposures creates an exposome that has a significant impact on age-related health. Understanding the interplay between exposome factors and the (epi) genome, offers pertinent insights into the ageing process and its relationship with the accumulation of allostatic load. We propose to exploit this to develop a biomimetic approach that will provide insight into how evolution through natural selection in other species has solved many age related human health issues. In particular, we will emphasise the need to reconnect a more mechanistic approach to medical science with a broader natural sciences approach, using biomimetics to mitigate the global burden of age related ill health. In particular, we will discuss how such an approach indicates leverage of the activities of the Nrf 2 gene to enhance health span via reintroduction of the classical 'Food as Medicine' concept, including modulation of the microbiome and the creation of more salutogenic and biophilic environments. Additionally, we will discuss how this approach integrates with novel and developing senotherapies

Improving survival for patients with advanced heart failure: A study of 737 consecutive patients

Objectives.This study sought to determine whether survival and risk of sudden death have improved for patients with advanced heart failure referred for consideration for heart transplantation as advances in medical therapy were systematically implemented over an 8-year period.Background.Recent survival trials in patients with mild to moderate heart failure and patients after a myocardial infarction have shown that angiotensin-converting enzyme inhibitors are beneficial, type I antiarrhythmic drugs can be detrimental, and amiodarone may be beneficial in some groups. The impact of advances in therapy may be enhanced or blunted when applied to severe heart failure.Methods.One-year mortality and sudden death were determined in relation to time, baseline variables and therapeutics for 737 consecutive patients referred for heart transplantation and discharged home on medical therapy from 1986 to 1988, 1989 to 1990 and 1991 to 1993. Medical care was directed by a single team of physicians with policies established by consensus. From 1986 to 1990, the hydralazine/isosorbide dinitrate combination or angiotensin-converting enzyme inhibitors were the initial vasodilators, and class I antiarrhythmic drugs were allowed. After 1990, captopril was the initial vasodilator, given to 86% of patients compared with 46% of patients before 1989. After mid-1989, class I agents were routinely withdrawn, and amiodarone was used for frequent ventricular ectopic beats or atrial fibrillation (53% of patients after 1990 vs. 10% before 1989).Results.The total 1-year mortality rate decreased from 33% before 1989 to 16% after 1990 (p = 0.0001), and sudden death decreased from 20% to 8% (p = 0.0006). Adjusted for clinical and hemodynamic variables in multivariate proportional hazards models, total mortality and sudden death were lower after 1990.Conclusions.The large reduction in mortality, particularly in sudden death, from advanced heart failure since 1990 may reflect an enhanced impact of therapeutic advances shown in large randomized trials when they are incorporated into a comprehensive approach in this population. This improved survival supports the growing practice of maintaining potential heart transplant candidates on optimal medical therapy until clinical decompensation mandates transplantation

A Blueprint to Evaluate One Health

One Health (OH) positions health professionals as agents for change and provides a platform to manage determinants of health that are often not comprehensively captured in medicine or public health alone. However, due to the organization of societies and disciplines, and the sectoral allocation of resources, the development of transdisciplinary approaches requires effort and perseverance. Therefore, there is a need to provide evidence on the added value of OH for governments, researchers, funding bodies, and stakeholders. This paper outlines a conceptual framework of what OH approaches can encompass and the added values they can provide. The framework was developed during a workshop conducted by the “Network for Evaluation of One Health,” an Action funded by the European Cooperation in Science and Technology. By systematically describing the various aspects of OH, we provide the basis for measuring and monitoring the integration of disciplines, sectors, and stakeholders in health initiatives. The framework identifies the social, economic, and environmental drivers leading to integrated approaches to health and illustrates how these evoke characteristic OH operations, i.e., thinking, planning, and working, and require supporting infrastructures to allow learning, sharing, and systemic organization. It also describes the OH outcomes (i.e., sustainability, health and welfare, interspecies equity and stewardship, effectiveness, and efficiency), which are not possible to obtain through sectoral approaches alone, and their alignment with aspects of sustainable development based on society, environment, and economy

Incorporating one health into medical education

One Health is an emerging concept that stresses the linkages between human, animal, and environmental health, as well as the need for interdisciplinary communication and collaboration to address health issues including emerging zoonotic diseases, climate change impacts, and the human-animal bond. It promotes complex problem solving using a systems framework that considers interactions between humans, animals, and their shared environment. While many medical educators may not yet be familiar with the concept, the One Health approach has been endorsed by a number of major medical and public health organizations and is beginning to be implemented in a number of medical schools. In the research setting, One Health opens up new avenues to understand, detect, and prevent emerging infectious diseases, and also to conduct translational studies across species. In the clinical setting, One Health provides practical ways to incorporate environmental and animal contact considerations into patient care. This paper reviews clinical and research aspects of the One Health approach through an illustrative case updating the biopsychosocial model and proposes a basic set of One Health competencies for training and education of human health care providers

Existential Loneliness and end-of-life care: A Systematic Review

Contains fulltext : 88662.pdf (publisher's version ) (Closed access)Patients with a life-threatening illness can be confronted with various types of loneliness, one of which is existential loneliness (EL). Since the experience of EL is extremely disruptive, the issue of EL is relevant for the practice of end-of-life care. Still, the literature on EL has generated little discussion and empirical substantiation and has never been systematically reviewed. In order to systematically review the literature, we (1) identified the existential loneliness literature; (2) established an organising framework for the review; (3) conducted a conceptual analysis of existential loneliness; and (4) discussed its relevance for end-of-life care. We found that the EL concept is profoundly unclear. Distinguishing between three dimensions of EL-as a condition, as an experience, and as a process of inner growth-leads to some conceptual clarification. Analysis of these dimensions on the basis of their respective key notions-everpresent, feeling, defence; death, awareness, difficult communication; and inner growth, giving meaning, authenticity-further clarifies the concept. Although none of the key notions are unambiguous, they may function as a starting point for the development of care strategies on EL at the end of life.1 april 201

A Physician’s View of One Health: Challenges and Opportunities

One Health is one of the most important movements and emerging concepts in health today. The convergence of the fields of human and animal medicine has the potential to generate novel scientific hypotheses, create effective new therapies and potentially transform how physicians, veterinarians and their patients understand health and disease. Despite this potential, One Health has not yet gained significant awareness or traction in human medical communities. From its inception, One Health, sometimes also called One Medicine, has been piloted primarily by leaders from the world of veterinary medicine. Although the specific term was coined perhaps 10 years ago, comparative medicine has been quietly evident on university campuses with veterinary and medical schools for decades longer. Although a few physicians have played major leadership roles in One Health, in the United States, despite over ten years of the movement’s robust growth, many have still not heard of it. Furthermore, physicians with some awareness of One Health often believe it to be primarily and exclusively about zoonotic infections and global health. The much broader scope and potential of One Health as also including comparative physiology and medicine is not being communicated effectively. Consequently, the human medical community remains largely disengaged. This is problematic because without significant engagement from physicians, nurses and other human health care professionals, the potential of One Health cannot be realized. To advance One Health it is imperative that we first understand the roots of under-engagement of the human medical community. This, in turn, can guide the development of novel and engaging opportunities for physician which demonstrate the power relevance of One Health’s comparative, collaborative and cooperative approach.[...