From cause and effect to causes and effects.

It is now-at least loosely-acknowledged that most health and clinical outcomes are influenced by different interacting causes. Surprisingly, medical research studies are nearly universally designed to study-usually in a binary way-the effect of a single cause. Recent experiences during the coronavirus disease 2019 pandemic brought to the forefront that most of our challenges in medicine and healthcare deal with systemic, that is, interdependent and interconnected problems. Understanding these problems defy simplistic dichotomous research methodologies. These insights demand a shift in our thinking from 'cause and effect' to 'causes and effects' since this transcends the classical way of Cartesian reductionist thinking. We require a shift to a 'causes and effects' frame so we can choose the research methodology that reflects the relationships between variables of interest-one-to-one, one-to-many, many-to-one or many-to-many. One-to-one (or cause and effect) relationships are amenable to the traditional randomized control trial design, while all others require systemic designs to understand 'causes and effects'. Researchers urgently need to re-evaluate their science models and embrace research designs that allow an exploration of the clinically obvious multiple 'causes and effects' on health and disease. Clinical examples highlight the application of various systemic research methodologies and demonstrate how 'causes and effects' explain the heterogeneity of clinical outcomes. This shift in scientific thinking will allow us to find the necessary personalized or precise clinical interventions that address the underlying reasons for the variability of clinical outcomes and will contribute to greater health equity.

Proposed solutions to anthropogenic climate change: A systematic literature review and a new way forward.

Humanity is now facing what may be the biggest challenge to its existence: irreversible climate change brought about by human activity. Our planet is in a state of emergency, and we only have a short window of time (7-8 years) to enact meaningful change. The goal of this systematic literature review is to summarize the peer-reviewed literature on proposed solutions to climate change in the last 20 years (2002-2022), and to propose a framework for a unified approach to solving this climate change crisis. Solutions reviewed include a transition toward use of renewable energy resources, reduced energy consumption, rethinking the global transport sector, and nature-based solutions. This review highlights one of the most important but overlooked pieces in the puzzle of solving the climate change problem - the gradual shift to a plant-based diet and global phaseout of factory (industrialized animal) farming, the most damaging and prolific form of animal agriculture. The gradual global phaseout of industrialized animal farming can be achieved by increasingly replacing animal meat and other animal products with plant-based products, ending government subsidies for animal-based meat, dairy, and eggs, and initiating taxes on such products. Failure to act will ultimately result in a scenario of irreversible climate change with widespread famine and disease, global devastation, climate refugees, and warfare. We therefore suggest an "All Life" approach, invoking the interconnectedness of all life forms on our planet. The logistics for achieving this include a global standardization of Environmental, Social, and Governance (ESG) or similar measures and the introduction of a regulatory body for verification of such measures. These approaches will help deliver environmental and sustainability benefits for our planet far beyond an immediate reduction in global warming.

'Medical Corona Science': Philosophical and systemic issues: Re-thinking medicine? On the epistemology of Corona medicine.

RATIONALE, AIMS, AND OBJECTIVES: The disciplinary profile and the quality of production of knowledge on Corona pandemic is studied. This scientific field is called 'Medical Corona Science'. METHODS: Criteria of analytical philosophy of science and science studies are systematically applied. RESULTS: It is shown that mainly auxiliary medical disciplines such as virology and epidemiology but not clinical disciplines provide Corona knowledge. We see a laboratory-centered, technology- and data-driven science, largely ignoring clinical issues. Therefore we call these approaches "Medical Corona Science" (MCS). We see the need to adapt to features of a 'post-normal science', a 'mode 2 science' and of 'Integration and Implementation Science', especially as clinical knowledge must be integrated. There is also a severe lack of theoretical considerations that could help to frame the pandemic as a complex dynamic system. CONCLUSIONS: We suggest a deeper meta-scientific discussion of the epistemic value of MCS and propose the application of tools from systems science.

Perspectives of (/memorandum for) systems thinking on COVID-19 pandemic and pathology.

Is data-driven analysis sufficient for understanding the COVID-19 pandemic and for justifying public health regulations? In this paper, we argue that such analysis is insufficient. Rather what is needed is the identification and implementation of over-arching hypothesis-related and/or theory-based rationales to conduct effective SARS-CoV2/COVID-19 (Corona) research. To that end, we analyse and compare several published recommendations for conceptual and methodological frameworks in medical research (e.g., public health, preventive medicine and health promotion) to current research approaches in medical Corona research. Although there were several efforts published in the literature to develop integrative conceptual frameworks before the COVID-19 pandemic, such as social ecology for public health issues and systems thinking in health care, only a few attempts to utilize these concepts can be found in medical Corona research. For this reason, we propose nested and integrative systemic modelling approaches to understand Corona pandemic and Corona pathology. We conclude that institutional efforts for knowledge integration and systemic thinking, but also for integrated science, are urgently needed to avoid or mitigate future pandemics and to resolve infection pathology.

The Quest for System-Theoretical Medicine in the COVID-19 Era.

Precision medicine and molecular systems medicine (MSM) are highly utilized and successful approaches to improve understanding, diagnosis, and treatment of many diseases from bench-to-bedside. Especially in the COVID-19 pandemic, molecular techniques and biotechnological innovation have proven to be of utmost importance for rapid developments in disease diagnostics and treatment, including DNA and RNA sequencing technology, treatment with drugs and natural products and vaccine development. The COVID-19 crisis, however, has also demonstrated the need for systemic thinking and transdisciplinarity and the limits of MSM: the neglect of the bio-psycho-social systemic nature of humans and their context as the object of individual therapeutic and population-oriented interventions. COVID-19 illustrates how a medical problem requires a transdisciplinary approach in epidemiology, pathology, internal medicine, public health, environmental medicine, and socio-economic modeling. Regarding the need for conceptual integration of these different kinds of knowledge we suggest the application of general system theory (GST). This approach endorses an organism-centered view on health and disease, which according to Ludwig von Bertalanffy who was the founder of GST, we call Organismal Systems Medicine (OSM). We argue that systems science offers wider applications in the field of pathology and can contribute to an integrative systems medicine by (i) integration of evidence across functional and structural differentially scaled subsystems, (ii) conceptualization of complex multilevel systems, and (iii) suggesting mechanisms and non-linear relationships underlying the observed phenomena. We underline these points with a proposal on multi-level systems pathology including neurophysiology, endocrinology, immune system, genetics, and general metabolism. An integration of these areas is necessary to understand excess mortality rates and polypharmacological treatments. In the pandemic era this multi-level systems pathology is most important to assess potential vaccines, their effectiveness, short-, and long-time adverse effects. We further argue that these conceptual frameworks are not only valid in the COVID-19 era but also important to be integrated in a medicinal curriculum.

Nutrigenetics/Nutrigenomics, Personalized Nutrition, and Precision Healthcare.

PURPOSE OF REVIEW: The purposes of the present review are to examine the emergence of nutrigenetics/nutrigenomics, to analyze the relationship between nutrigenetics and nutrigenomics, to explore the impact of nutrigenetics/nutrigenomics on healthcare with respect to noncommunicable diseases, and to discuss the challenges facing the implementation of nutrigenetics/nutrigenomics within healthcare. RECENT FINDINGS: Nutrigenetics/nutrigenomics is certainly a thriving specialty given the sharp increase of publications over the last two decades. The relationship between nutrigenetics and nutrigenomics is proposed as complementary. The current clinical and research literature supports the significant impact nutrigenetics/nutrigenomics has on treating and preventing noncommunicable diseases. Although several challenges face the implementation of nutrigenetics/nutrigenomics into healthcare, they are not insurmountable. Nutrigenetics/nutrigenomics plays an important role not only in treating diseases and illnesses but also in promoting health and wellness through both basic and clinical research; and it is critical for the future of both personalized nutrition and precision healthcare.

Professing clinical medicine in an evolving health care network.

For at least the past several decades, medicine has been embroiled in a crisis concerning the nature of its professionalism. The fundamental questions that drive this ongoing crisis are primarily three. First, what is the nature of medical professionalism? Second, who are medical professionals? Third, what does medicine or these professionals profess or promise? In this paper, the professionalism crisis vis-à-vis these questions is examined and analyzed chiefly in terms of both Francis Peabody's and Edmund Pellegrino's writings. Based on their writings, I introduce a conceptual framework for professionalism to address the crisis. In addition, I contend that to address the professionalism crisis adequately, medicine's position within an evolving health care network must also be considered. To that end, I first discuss the genesis of the crisis in terms of the Flexner Report and especially Peabody's response to it. Next, I explore how the crisis intensified during the twentieth century, particularly in terms of medicine's ultimate scientification and eventual commercialization, and how Pellegrino reacted to this. I then propose a health care professionalism cycle and a care-competence cycle to provide a conceptual framework for addressing the crisis. I conclude that medicine's position is no longer as the center of health care but rather as another node within a wider evolving health care network. And the resolution of medicine's professionalism crisis depends on medicine's positioning and defining itself in terms of the professionalism for each of the other professions within the health care network.

A Century of Heparin.

The year 2018 was the centennial of the naming of heparin by Emmett Holt and William Howell and the 102nd anniversary of Jay McLean's discovery of an anticoagulant heparphosphatide at Johns Hopkins Hospital in Baltimore. This article discusses recently discovered historical artifacts that shed new light on heparin's christening, including McLean's unpublished letter written in 1950 that represents one of the most complete accounts of heparin's discovery before his untimely death. In addition, the article describes the finding of a plaque dedicated to McLean and explores the circumstances of its removal from public display, as learned from interviews with present and former staff members.

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, P4 medicine and holism.

RATIONALE, AIMS AND OBJECTIVES: Multimorbidity is a serious challenge to providing patients with quality health care. Sturmberg et al. propose a P4 or whole-person medical model based on a holistic approach to deliver such care. The aim of this commentary is to examine critically their P4 model and holistic approach. METHODS: The P4 model and holistic approach of Sturmberg et al. are analysed conceptually in terms of an effective strategy or sequence for framing P4 medicine and with respect to different philosophical notions of holism for grounding it. RESULTS: Instead of a P4 medicine strategy or sequence that emphasizes the predictive and preventive aspects of health care from a biomedical perspective, as Sturmberg et al. do, a more effective strategy or sequence for framing P4 medicine to deliver quality health care is to accentuate the personalized and participatory aspects from a humanistic perspective. The basis of this proposed strategy for P4 medicine is not a technoscientific holism that emphasizes mechanisms to define the whole utilizing bottom-up causation, as Sturmberg et al. ground their biomedical P4 model, but rather a phenomenological holism that also incorporates the person's illness experience and top-down causation. CONCLUSIONS: The proposal of Sturmberg et al. to treat patient multimorbidity through P4 medicine and a holistic approach is certainly a move in the right direction. However, to achieve their goal requires an alternative strategy for P4 medicine and a more robust notion of holism.

Caring for patients during challenging clinical encounters.

RATIONALE, AIMS AND OBJECTIVES: Challenging clinical encounters can often be frustrating and demoralizing not only for clinicians but also for patients. The paper's aims are twofold. The first is to analyse the nature and origins of such encounters. The second is to appraise the CALMER and REBELS models for managing them. METHODS: After reviewing the medical literature on challenging clinical encounters, a clinical case is briefly reconstructed from it. The reconstructed case is then used to analyse the nature and origins of challenging encounters and to evaluate the two models for handling them. RESULTS: The reconstructed clinical case is an apt example for examining and evaluating the medical literature on challenging clinical encounters. In terms of what challenging encounters are and what elicits them, the literature captures their frustrating, demoralizing, demanding and, at times, insufferable dimensions - as well as the role of patients in their origins - as the clinical case also illustrates. With respect to managing them, the CALMER and REBELS models are effective strategies for handling challenging encounters - again, as the clinical case exemplifies. CONCLUSIONS: Although the clinical case supports the medical literature on challenging clinical encounters, the literature fails to provide an adequate account of their nature and origins. Specifically, challenging encounters are a type of dysfunction - not pathophysiological but existential - in a clinical setting, with their origins not only in patients but also in clinicians and health care systems. Finally, based upon the dysfunctional nature of such encounters, revisions of the CALMER and REBELS models are proposed for better managing these encounters.

The role of emotions in clinical reasoning and decision making.

What role, if any, should emotions play in clinical reasoning and decision making? Traditionally, emotions have been excluded from clinical reasoning and decision making, but with recent advances in cognitive neuropsychology they are now considered an important component of them. Today, cognition is thought to be a set of complex processes relying on multiple types of intelligences. The role of mathematical logic (hypothetico-deductive thinking) or verbal linguistic intelligence in cognition, for example, is well documented and accepted; however, the role of emotional intelligence has received less attention-especially because its nature and function are not well understood. In this paper, I argue for the inclusion of emotions in clinical reasoning and decision making. To that end, developments in contemporary cognitive neuropsychology are initially examined and analyzed, followed by a review of the medical literature discussing the role of emotions in clinical practice. Next, a published clinical case is reconstructed and used to illustrate the recognition and regulation of emotions played during a series of clinical consultations, which resulted in a positive medical outcome. The paper's main thesis is that emotions, particularly in terms of emotional intelligence as a practical form of intelligence, afford clinical practitioners a robust cognitive resource for providing quality medical care.

An integrated model of clinical reasoning: dual-process theory of cognition and metacognition.

RATIONALE AND AIM: Clinical reasoning is an important component for providing quality medical care. The aim of the present paper is to develop a model of clinical reasoning that integrates both the non-analytic and analytic processes of cognition, along with metacognition. METHOD: The dual-process theory of cognition (system 1 non-analytic and system 2 analytic processes) and the metacognition theory are used to develop an integrated model of clinical reasoning. RESULTS: In the proposed model, clinical reasoning begins with system 1 processes in which the clinician assesses a patient's presenting symptoms, as well as other clinical evidence, to arrive at a differential diagnosis. Additional clinical evidence, if necessary, is acquired and analysed utilizing system 2 processes to assess the differential diagnosis, until a clinical decision is made diagnosing the patient's illness and then how best to proceed therapeutically. Importantly, the outcome of these processes feeds back, in terms of metacognition's monitoring function, either to reinforce or to alter cognitive processes, which, in turn, enhances synergistically the clinician's ability to reason quickly and accurately in future consultations. CONCLUSIONS: The proposed integrated model has distinct advantages over other models proposed in the literature for explicating clinical reasoning. Moreover, it has important implications for addressing the paradoxical relationship between experience and expertise, as well as for designing a curriculum to teach clinical reasoning skills.

The role of prudent love in the practice of clinical medicine.

RATIONALE: Virtues are an important component in the practice of clinical medicine. Prudence or wisdom and charity or love are often viewed as crucial for virtuous practice. Generally, the two virtues are discussed separately, with no connection between them; however, a synergy exists between the two virtues as a compound virtue of prudent love in which the properties of the compound virtue transcend those of the individual virtues. AIMS AND OBJECTIVES: To examine the nature of prudent love and to discuss its role in the practice of clinical medicine. METHODS: Philosophical and conceptual analyses. RESULTS: Prudent love exhibits properties, which are the result of a synergistic interaction between the two individual virtues. Succinctly, prudent love synergism is an outcome of a particular structural relationship between the two virtues in which motivational love prompts the prudent clinician to acquire and utilize clinical competence, which then allows the loving clinician to take care of an individual patient's health care needs. In turn, the virtuous clinician's ability to meet those needs successfully feedbacks onto the motivation to satisfy them initially, thereby encouraging and enhancing the clinician to fulfil them even more prudently and lovingly, not only for the individual patient but also for other patients. CONCLUSIONS: The compound virtue of prudent love provides a comprehensive approach to practising medicine that meets not only the needs of patients but also fulfils the physician's sense as healer. Although challenges face teaching virtues in the medical curriculum, strategies are available for incorporating training in virtues into the curriculum.

Medical cure and progress: the case of type-1 diabetes.

Medicine often defines progress in terms of medical cures; however, such cures are rare. At best, medical progress generally consists of managing patients more efficiently or competently, especially in terms of relieving their symptoms. Today, medicine stands on the edge of curing a number of diseases. However, before achieving such cures, biomedical scientists need to understand in finer detail the mechanisms of physiological and pathological processes, especially from a systems perspective, and students of biomedical studies need to understand more precisely what a medical cure is conceptually or philosophically. This article utilizes type-1 diabetes to explore the issues surrounding medical progress with respect to defining medical cure, especially in terms of distinguishing it from managing a patient's illness.

Care and competence in medical practice: Francis Peabody confronts Jason Posner.

In this paper, I discuss the role of care and competence, as well as their relationship to one another, in contemporary medical practice. I distinguish between two types of care. The first type, care(1), represents a natural concern that motivates physicians to help or to act on the behalf of patients, i.e. to care about them. However, this care cannot guarantee the correct technical or right ethical action of physicians to meet the bodily and existential needs of patients, i.e. to take care of them-care(2). To that end, physicians must be competent in the practice of medicine both as evidence-based science (technical competence) and as patient-centered art (ethical competence). Only then, I argue, can physicians take care of (care(2)) patients' bodily and existential needs in a compassionate and comprehensive manner. Importantly, although care(1) precedes competence, competence--both technical and ethical--is required for genuine care(2), which in turn reinforces an authentic care(1). I utilize the play Wit, especially the character Jason Posner, and Francis Peabody's exposition on caring for patients, to illustrate the role of care and competence in contemporary medical practice.

The epistemically virtuous clinician.

Today, modern Western medicine is facing a quality-of-care crisis that is undermining the patient-physician relationship. In this paper, a notion of the epistemically virtuous clinician is proposed in terms of both the reliabilist and responsibilist versions of virtue epistemology, in order to help address this crisis. To that end, a clinical case study from the literature is first reconstructed. The reliabilist intellectual virtues, including the perceptual and conceptual virtues, are then discussed and applied to the case study. Next, a similar method is employed to examine the responsibilist intellectual virtues, including curiosity, courage, honesty, and humility, and to apply them to the case study. To round out the discussion, the love of knowledge and both theoretical and practical wisdom are explored and applied to the case study. The paper concludes with a brief discussion of how the notion of an epistemically virtuous clinician addresses the quality-of-care crisis, in terms of the connection between ethical and intellectual virtues, and of the notion's implications for medical education.

Reflections on humanizing biomedicine.

Although biomedicine is responsible for the "miracles" of modern medicine, paradoxically it has also led to a quality-of-care crisis in which many patients feel disenfranchised from the health-care industry. To address this crisis, several medical commentators make an appeal for humanizing biomedicine, which has led to shifts in the philosophical boundaries of medical knowledge and practice. In this paper, the metaphysical, epistemological, and ethical boundaries of biomedicine and its humanized versions are investigated and compared to one another. Biomedicine is founded on a metaphysical position of mechanistic monism, an epistemology of objective knowing, and an ethic of emotionally detached concern. In humanizing modern medicine, these boundaries are often shifted to a metaphysical position of dualism/holism, an epistemology of subject knowing, and an ethic of empathic care. In a concluding section, the question is discussed whether these shifts in the philosophical boundaries are adequate to resolve the quality-of-care crisis.