title: Prodromal symptoms in knee osteoarthritis: a nested case-control study using data from the Osteoarthritis Initiative.
abstract: OBJECTIVE
  In order to gain a better understanding of the timing of emergent symptoms of osteoarthritis, we sought to investigate the existence, duration and nature of a prodromal symptomatic phase preceding incident radiographic knee osteoarthritis (ROA).
  
  
  METHODS
  Data were from the incidence cohort of the Osteoarthritis Initiative (OAI) public use datasets. Imposing a nested case-control design, ten control knees were selected for each case of incident tibiofemoral ROA between 2004 and 2010 from participants aged 45-79 years. Candidate prodromal symptoms were Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) and Knee injury and Osteoarthritis Outcome Score (KOOS) subscale scores and individual items, available up to 4 years prior to the time of incident ROA. Multi-level models were used to estimate the length of the prodromal phases.
  
  
  RESULTS
  The prodromal phase for subscale scores ranged from 29 months (KOOS Other Symptoms) to 37 months (WOMAC Pain). Pain and difficulty on activities associated with higher dynamic knee loading were associated with longer prodromal phases (e.g., pain on twisting/pivoting (39 months, 95% confidence interval: 13, 64) vs pain on standing (25 months: 7, 42)).
  
  
  CONCLUSIONS
  Our analysis found that incident ROA is preceded by prodromal symptoms lasting at least 2-3 years. This has potential implications for understanding phasic development and progression of osteoarthritis and for early recognition and management.
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire, United Kingdom. Electronic address: r.l.case@keele.ac.uk.
authors.forename: R
authors.initials: R
authors.lastname: Case
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire, United Kingdom. Electronic address: elainethomas37@hotmail.co.uk.
authors.forename: E
authors.initials: E
authors.lastname: Thomas
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire, United Kingdom. Electronic address: e.clarke@keele.ac.uk.
authors.forename: E
authors.initials: E
authors.lastname: Clarke
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire, United Kingdom. Electronic address: g.m.peat@keele.ac.uk.
authors.forename: G
authors.initials: G
authors.lastname: Peat
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis* / Q000453:epidemiology* / Q000503:physiopathology; D010146:Pain / Q000453:epidemiology / Q000209:etiology; D010147:Pain Measurement / Q000379:methods; D062706:Prodromal Symptoms; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013997:Time Factors; D014481:United States / Q000453:epidemiology
keywords: Case–control; Epidemiology; Knee osteoarthritis; Prodrome; Symptoms
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