title: Slowing Down of Recovery as Generic Risk Marker for Acute Severity Transitions in Chronic Diseases.
abstract: OBJECTIVE
  We propose a novel paradigm to predict acute attacks and exacerbations in chronic episodic disorders such as asthma, cardiac arrhythmias, migraine, epilepsy, and depression. A better generic understanding of acute transitions in chronic dynamic diseases is increasingly important in critical care medicine because of the higher prevalence and incidence of these chronic diseases in our aging societies.
  
  
  METHODS
  PubMed, Medline, and Web of Science.
  
  
  METHODS
  We selected studies from biology and medicine providing evidence of slowing down after a perturbation as a warning signal for critical transitions.
  
  
  METHODS
  Recent work in ecology, climate, and systems biology has shown that slowing down of recovery upon perturbations can indicate loss of resilience across complex, nonlinear biologic systems that are approaching a tipping point. This observation is supported by the empiric studies in pathophysiology and controlled laboratory experiments with other living systems, which can flip from one state of clinical balance to a contrasting one. We discuss examples of such evidence in bodily functions such as blood pressure, heart rate, mood, and respiratory regulation when a tipping point for a transition is near.
  
  
  CONCLUSIONS
  We hypothesize that in a range of chronic episodic diseases, indicators of critical slowing down, such as rising variance and temporal correlation, may be used to assess the risk of attacks, exacerbations, and even mortality. Identification of such early warning signals over a range of diseases will enhance the understanding of why, how, and when attacks and exacerbations will strike and may thus improve disease management in critical care medicine.
authors.affiliation: 1Department of Geriatrics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.2Integrative Ecology Group, Bascompte Lab, Consejo Superior de Investigaciones Científicas, Estación Biológica de Doñana, CSIC, Sevilla, Spain.3Emory Center for Critical Care, Woodruff Health Sciences Center, Emory University, Atlanta, GA.4Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.5Department of Physiology, McGill University, Montreal, Quebec, Canada.6Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.7Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ.8Aquatic Ecology and Water Quality Management, Wageningen University, Wageningen, The Netherlands.9Scripps Institution of Oceanography, University Centre San Diego, San Diego, CA.10Department of Neurology and Leiden Center for Translational Neuroscience, Leiden University Medical Centre, Leiden, The Netherlands.11Department of Internal Medicine, Haga Hospital, Den Haag, The Netherlands.
authors.forename: Marcel G M
authors.initials: MG
authors.lastname: Olde Rikkert
authors.forename: Vasilis
authors.initials: V
authors.lastname: Dakos
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Buchman
authors.forename: Rob de
authors.initials: Rd
authors.lastname: Boer
authors.forename: Leon
authors.initials: L
authors.lastname: Glass
authors.forename: Angélique O J
authors.initials: AO
authors.lastname: Cramer
authors.forename: Simon
authors.initials: S
authors.lastname: Levin
authors.forename: Egbert
authors.initials: E
authors.lastname: van Nes
authors.forename: George
authors.initials: G
authors.lastname: Sugihara
authors.forename: Michel D
authors.initials: MD
authors.lastname: Ferrari
authors.forename: Else A
authors.initials: EA
authors.lastname: Tolner
authors.forename: Ingrid
authors.initials: I
authors.lastname: van de Leemput
authors.forename: Joep
authors.initials: J
authors.lastname: Lagro
authors.forename: René
authors.initials: R
authors.lastname: Melis
authors.forename: Marten
authors.initials: M
authors.lastname: Scheffer
mesh_terms: D002908:Chronic Disease; D003422:Critical Care / Q000379:methods*; D005246:Feedback; D006801:Humans; D008954:Models, Biological; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012720:Severity of Illness Index