Health and Disease Are Dynamic Complex-Adaptive States Implications for Practice and Research.

Interoception, the ability to convey one's overall physiological state, allows people to describe their health along an experiential continuum, from excellent, very good, good, fair to poor. Each health state reflects a distinct pattern of one's overall function. This assay provides a new frame of understanding health and disease as complex-adaptive system states of the person as-a-whole. It firstly describes how complex patterns can emerge from simple equations. It then discusses how clinical medicine in certain domains has started to explore the pattern characteristics resulting in the heterogeneity of disease, and how this better understanding has improved patient management. The experiential state of health can be surprising to the observer-some are in good health with disabling disease, others are in poor health without the evidence of any. The main part of the assay describes the underlying complexity principles that contribute to health, and synthesizes available evidence from various research perspectives to support the philosophic/theoretical proposition of the complex-adaptive nature of health. It shows how health states arise from complex-adaptive system dynamics amongst the variables of a hierarchically layered system comprising the domains of a person's macro-level external environment to his nano-level biological blueprint. The final part suggests that the frame of health as a dynamic complex-adaptive state defines a new paradigm, and outlines ways of translating these expanded understandings to clinical practice, future research, and health system design.

Health and Disease-Emergent States Resulting From Adaptive Social and Biological Network Interactions.

Health is an adaptive state unique to each person. This subjective state must be distinguished from the objective state of disease. The experience of health and illness (or poor health) can occur both in the absence and presence of objective disease. Given that the subjective experience of health, as well as the finding of objective disease in the community, follow a Pareto distribution, the following questions arise: What are the processes that allow the emergence of four observable states-(1) subjective health in the absence of objective disease, (2) subjective health in the presence of objective disease, (3) illness in the absence of objective disease, and (4) illness in the presence of objective disease? If we consider each individual as a unique biological system, these four health states must emerge from physiological network structures and personal behaviors. The underlying physiological mechanisms primarily arise from the dynamics of external environmental and internal patho/physiological stimuli, which activate regulatory systems including the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Together with other systems, they enable feedback interactions between all of the person's system domains and impact on his system's entropy. These interactions affect individual behaviors, emotional, and cognitive responses, as well as molecular, cellular, and organ system level functions. This paper explores the hypothesis that health is an emergent state that arises from hierarchical network interactions between a person's external environment and internal physiology. As a result, the concept of health synthesizes available qualitative and quantitative evidence of interdependencies and constraints that indicate its top-down and bottom-up causative mechanisms. Thus, to provide effective care, we must use strategies that combine person-centeredness with the scientific approaches that address the molecular network physiology, which together underpin health and disease. Moreover, we propose that good health can also be promoted by strengthening resilience and self-efficacy at the personal and social level, and via cohesion at the population level. Understanding health as a state that is both individualized and that emerges from multi-scale interdependencies between microlevel physiological mechanisms of health and disease and macrolevel societal domains may provide the basis for a new public discourse for health service and health system redesign.

'Multimorbidity' as the manifestation of network disturbances.

We argue that 'multimorbidity' is the manifestation of interconnected physiological network processes within an individual in his or her socio-cultural environment. Networks include genomic, metabolomic, proteomic, neuroendocrine, immune and mitochondrial bioenergetic elements, as well as social, environmental and health care networks. Stress systems and other physiological mechanisms create feedback loops that integrate and regulate internal networks within the individual. Minor (e.g. daily hassles) and major (e.g. trauma) stressful life experiences perturb internal and social networks resulting in physiological instability with changes ranging from improved resilience to unhealthy adaptation and 'clinical disease'. Understanding 'multimorbidity' as a complex adaptive systems response to biobehavioural and socio-environmental networks is essential. Thus, designing integrative care delivery approaches that more adequately address the underlying disease processes as the manifestation of a state of physiological dysregulation is essential. This framework can shape care delivery approaches to meet the individual's care needs in the context of his or her underlying illness experience. It recognizes 'multimorbidity' and its symptoms as the end product of complex physiological processes, namely, stress activation and mitochondrial energetics, and suggests new opportunities for treatment and prevention. The future of 'multimorbidity' management might become much more discerning by combining the balancing of physiological dysregulation with targeted personalized biotechnology interventions such as small molecule therapeutics targeting specific cellular components of the stress response, with community-embedded interventions that involve addressing psycho-socio-cultural impediments that would aim to strengthen personal/social resilience and enhance social capital.

The trajectory of life. Decreasing physiological network complexity through changing fractal patterns.

In this position paper, we submit a synthesis of theoretical models based on physiology, non-equilibrium thermodynamics, and non-linear time-series analysis. Based on an understanding of the human organism as a system of interconnected complex adaptive systems, we seek to examine the relationship between health, complexity, variability, and entropy production, as it might be useful to help understand aging, and improve care for patients. We observe the trajectory of life is characterized by the growth, plateauing and subsequent loss of adaptive function of organ systems, associated with loss of functioning and coordination of systems. Understanding development and aging requires the examination of interdependence among these organ systems. Increasing evidence suggests network interconnectedness and complexity can be captured/measured/associated with the degree and complexity of healthy biologic rhythm variability (e.g., heart and respiratory rate variability). We review physiological mechanisms linking the omics, arousal/stress systems, immune function, and mitochondrial bioenergetics; highlighting their interdependence in normal physiological function and aging. We argue that aging, known to be characterized by a loss of variability, is manifested at multiple scales, within functional units at the small scale, and reflected by diagnostic features at the larger scale. While still controversial and under investigation, it appears conceivable that the integrity of whole body complexity may be, at least partially, reflected in the degree and variability of intrinsic biologic rhythms, which we believe are related to overall system complexity that may be a defining feature of health and it's loss through aging. Harnessing this information for the development of therapeutic and preventative strategies may hold an opportunity to significantly improve the health of our patients across the trajectory of life.

A personalized systems medicine approach to refractory rumination.

RATIONALE, AIMS AND OBJECTIVES: As with many functional disorders, rumination syndrome poses a great dilemma when approached via standard of care. This case report illustrates how rumination syndrome may be effectively approached using the systems medicine. METHOD: The patient's treatment involved two distinctively different treatment cycles. Initially she was treated in an academic tertiary inpatient and outpatient multidisciplinary program with a primary symptom-based focus with little improvement. She subsequently sought care at a systems-based integrative medicine clinic within an academic family medicine centre, which identified the inciting events, diagnosed the current pathology and developed a stepwise treatment plan. RESULTS: The patient is now rumination free. CONCLUSION: Chronic or refractory diseases, especially when regarded as 'functional' may be approached by a systems medicine methodology, which allows physicians to fine-tune the vast amount of specific pieces of knowledge to achieve an integrated approach to managing the whole person.

Knowing--in medicine.

In this paper we argue that knowledge in health care is a multidimensional dynamic construct, in contrast to the prevailing idea of knowledge being an objective state. Polanyi demonstrated that knowledge is personal, that knowledge is discovered, and that knowledge has explicit and tacit dimensions. Complex adaptive systems science views knowledge simultaneously as a thing and a flow, constructed as well as in constant flux. The Cynefin framework is one model to help our understanding of knowledge as a personal construct achieved through sense making. Specific knowledge aspects temporarily reside in either one of four domains - the known, knowable, complex or chaotic, but new knowledge can only be created by challenging the known by moving it in and looping it through the other domains. Medical knowledge is simultaneously explicit and implicit with certain aspects already well known and easily transferable, and others that are not yet fully known and must still be learned. At the same time certain knowledge aspects are predominantly concerned with content, whereas others deal with context. Though in clinical care we may operate predominately in one knowledge domain, we also will operate some of the time in the others. Medical knowledge is inherently uncertain, and we require a context-driven flexible approach to knowledge discovery and application, in clinical practice as well as in health service planning.

Systems and complexity thinking in general practice: part 1 - clinical application.

Many problems encountered in general practice cannot be sufficiently explained within the Newtonian reductionist paradigm. Systems and complexity thinking - already widely adopted in most nonmedical disciplines - describes and explores the contextual nature of questions posed in medicine, and in general practice in particular. This article briefly describes the framework underpinning systems and complexity sciences. A case study illustrates how systems and complexity thinking can help to better understand the contextual nature of patient presentations, and how different approaches will lead to different outcomes.

Rethinking general practice for the 21st century. The patient counts!

BACKGROUND: Increasingly, reforms to health care systems appear to interfere with the traditional (healer) role of the general practitioner, and are perceived to disrupt patient care and the therapeutic relationship. OBJECTIVE: To outline measures for the survival and future development of the discipline of general practice in Australia. DISCUSSION: In order to preserve longitudinal relationship centred care and high level primary care clinical expertise, health bureaucracies and general practice itself, must re-focus care on the individual and community, integrating new developments rather than allowing 'new ideas and system pressures' to continually distort functional general practice.