title: A predictive model for fatigue and its etiologic associations in primary biliary cirrhosis.
abstract: OBJECTIVE
  Excessive day-time somnolence and autonomic dysfunction are biological processes prevalent in Primary Biliary Cirrhosis (PBC) that associate with fatigue. Here we explore how these biological associates inter-relate, and their cumulative impact upon typical clinical cohorts.
  
  
  METHODS
  A predictive model for daytime hypersomnolence (Epworth Sleepiness Scale (ESS)) and autonomic dysfunction (Orthostatic Grading Scale (OGS)) was developed in a derivation cohort (n=124) and subsequently validated in a second cohort (n=114). Subjects also completed the disease specific quality of life tool, the PBC-40.
  
  
  RESULTS
  A composite predictive criterion (presence of either ESS > or =10 or OGS > or =4) for the presence of fatigue in PBC patients had a sensitivity of 0.71 (95% confidence intervals 0.59-0.81) and specificity 0.8 (0.67-0.9) (positive predictive value (PV); 0.84 (0.72-0.92), negative PV; 0.66 (0.53-0.78) for moderate or severe fatigue). Ninety-seven percent of severely fatigued patients (0% of non-fatigued) met the aetiology predictive criterion (chi(2) 49.6, P<.0001). Expression of both significant daytime somnolence and autonomic dysfunction was not associated with more severe fatigue, suggesting that there is a threshold effect for fatigue in PBC. When applied to a second independent cohort, the composite criterion retained strongly significant predictive value for fatigue.
  
  
  CONCLUSIONS
  A significant proportion of fatigue in PBC associates with one or both of autonomic dysfunction (OGS > or =4) and sleep disturbance (ESS > or =10). Those meeting both ESS and OGS criteria were not more severe fatigued than those meeting the diagnostic criterion for either OGS or ESS alone. A threshold effect for fatigue has implications for potential therapeutic interventions.
authors.affiliation: Liver Research Group, Institute of Cellular Medicine, Newcastle University, United Kingdom.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Newton
authors.forename: Jessie
authors.initials: J
authors.lastname: Pairman
authors.forename: Kathryn
authors.initials: K
authors.lastname: Sutcliffe
authors.forename: Katharine
authors.initials: K
authors.lastname: Wilton
authors.forename: David E J
authors.initials: DE
authors.lastname: Jones
mesh_terms: D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000175:diagnosis; D006970:Disorders of Excessive Somnolence / Q000175:diagnosis; D005221:Fatigue / Q000175:diagnosis*; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000150:complications*; D008875:Middle Aged; D011788:Quality of Life; D011795:Surveys and Questionnaires