Comorbidities and Syndemics in the COVID-19 Age: Challenges and Opportunities for Bringing Separated Branches of Medicine Closer to Each Other.

The Corona Virus Disease 2019 (COVID-19) as a unique disaster has stressed the extreme importance of the three issues for medicine, society and humanity in general: comorbidity, pandemic and syndemic. There are many reasons why the study of comorbidities and syndemics of COVID-19 is of great importance for researchers, clinicians and health policy makers who are responsible for health care organization and funding in a bid to develop more effective and efficient prevention and treatment. Thinking about COVID-19 through a syndemics concept and taking biological, psychological, social and spiritual dimensions into account, physicians could be more effective in clinical practice and community-based interventions. The outcome of SARS-CoV-2 infection is determined by the virus-host interaction, with pathogenicity of SARS-CoV-2 being related to the presence of comorbid diseases. The risk for severe COVID-19 clinical manifestations and death increases with age of patients and comorbidity. General mechanisms of multi-system dysfunction and multi-organ damage reported in COVID-19 are probably related to ubiquitous expression of ACE2 in many tissues and its important role in the renin-angiotensin-aldosterone system (RAAS) functioning. Physicians all over the world should be aware of COVID-19 related comorbidities, multisystem disorders and syndemics, as well as treatment and preventive strategies. COVID-19 age is a right time to reconsider the state of science and practice in comorbidity medicine field from the both epistemological and treatment perspective. Comorbidities and multimorbidities are indifferent to medical specializations, so the integrative and complementary medicine is an imperative in the both education and practice. Shifting the paradigm from vertical and mono-morbid interventions to comorbidity, multimorbidity and multi-system disease approaches enhances effectiveness and efficiency of human resources utilization. The aim of this review is to summarize the theoretical concepts and clinical experience and research regarding comorbidity in general, and specifically related to the COVID-19 pandemic, syndemics and infodemic.

Rationale and design of the AFFIRM-AHF trial: a randomised, double-blind, placebo-controlled trial comparing the effect of intravenous ferric carboxymaltose on hospitalisations and mortality in iron-deficient patients admitted for acute heart failure.

AIMS: Iron deficiency (ID) is a common co-morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM-AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron-deficient patients hospitalised for AHF. METHODS: AFFIRM-AHF is a multicentre, randomised (1:1), double-blind, placebo-controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100-299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety-related outcomes. CONCLUSION: The AFFIRM-AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron-deficient patients hospitalised for AHF.

Pharmacological therapy in adult congenital heart disease: growing need, yet limited evidence.

Congenital heart disease (CHD) is the most common inborn defect. Due to advances in paediatric care, surgical, and catheter procedures the number of adults with CHD has grown remarkably in recent years. Most of these patients, however, have residua from their original operation/s and require life-long care, many of them are subjected to further haemodynamic and electrophysiological interventions during adulthood. While such re-do surgical or catheter interventions together with device therapy and transplantation play a key therapeutic role, increasingly, adults with CHD require drug therapy for late complications namely heart failure (HF), arrhythmias, pulmonary and systemic hypertension, thromboembolic events, etc. Unlike other cardiovascular areas, drug therapy in adult CHD is based on scarce clinical data and remains largely empiric. Consequently, pharmacological therapies are individualized to ameliorate patients' symptoms and/or degree of haemodynamic impairment. Thus far, recommendations have been difficult to make and formalized guidelines on drug therapy are lacking. We review herewith the rationale, limited evidence and knowledge gaps regarding drug therapy in this growing cardiovascular field and discuss pharmacotherapy options in specific conditions namely HF, arrhythmias, thrombosis, pulmonary arterial hypertension, contraception, and pregnancy.

Person-centered medicine versus personalized medicine: is it just a sophism? A view from chronic pain management.

The main aim of this brief overview is to explore the concepts of person-centered medicine and personalized medicine in the areas of chronic pain research and management. Through several definitions and paradigms of pain, the authors introduce the complexity of pain phenomenology in order to establish the challenge of person-centered and personalized medicine in everyday practice. By providing deeper insight into fibromyalgia, its presentation, biology and treatment, several questions are addressed, ranging from person-centered diagnosis to personalizing the various processes of the fibromyalgia spectrum complex. By reviewing current treatment options and evaluating treatment pitfalls derived from methodological flaws in current research, the authors discuss various possibilities of personalizing treatment and, therefore, propose how the use of these two paradigms could enhance outcomes in chronic pain management. If we wish to make comments about enhanced outcomes we need to talk about outcomes of pain treatments, we need to discuss what successful treatment is from the patient's point of view as well as in the reviewed models.

Comorbidity, multimorbidity and personalized psychosomatic medicine: epigenetics rolling on the horizon.

This review focuses first on conceptual chaos and different connotations in psychosomatic medicine, then on new perspectives on comorbidity and multimorbidity, especially from epigenetics perspective. Comorbidity is one of the greatest research and clinical challenges to contemporary psychiatry and psychosomatic medicine. Recently altered gene expression due to epigenetic regulation has been implicated in the development of multifarious mental disorders and somatic diseases. The potential relevance of epigenetics for better understanding and more successful treatment of comorbidity and multimorbidity is described.

Mental disorders, treatment response, mortality and serum cholesterol: a new holistic look at old data.

BACKGROUND: The importance of cholesterol for physical and psychological well-being has been recognized for several decades. Changes in serum cholesterol levels may have a direct impact on mental performance, behavior, treatment response, survival and expected lifetime duration. OBJECTIVES: To examine the association between various mental disorders (schizophrenia, bipolar disorder, depression, generalized anxiety disorder, panic disorders, post-traumatic stress disorder and other mental disorders) and cholesterol levels, and to discuss the possible treatment implications. METHOD: A MEDLINE search, citing articles from 1966 onward, supplemented by a review of bibliographies, was conducted to identify relevant studies. Criteria used to identify studies included (1) English language, (2) published studies with original data in peer-reviewed journals. RESULTS: Clinical investigations of cholesterolemia in patients with major mental disorders have produced very conflicting results. Hypercholesterolemia has been reported in patients with schizophrenia, obsessive-compulsive disorders, panic disorder, generalized anxiety disorder, PTSD. Low cholesterol level has been reported in patients with major depression, dissociative disorder, antisocial personality disorder, borderline personality disorder. It seems that both high and low serum total cholesterol may be associated with a higher risk of the premature death. CONCLUSION: Our current knowledge on the relation between cholesterolemia and mental disorders is poor and controversial. No definite or reliable insight into a pathophysiological link between cholesterol levels and mental disorders, treatment response and mortality rate is available. The lipoprotein profile, rather than total cholesterol levels, seems to be important.