title: Weighted cumulative exposure models helped identify an association between early knee-pain consultations and future knee OA diagnosis.
abstract: To establish the association between prior knee-pain consultations and early diagnosis of knee osteoarthritis (OA) by weighted cumulative exposure (WCE) models.
  
  
  
  Data were from an electronic health care record (EHR) database (Consultations in Primary Care Archive). WCE functions for modeling the cumulative effect of time-varying knee-pain consultations weighted by recency were derived as a predictive tool in a population-based case-control sample and validated in a prospective cohort sample. Two WCE functions ([i] weighting of the importance of past consultations determined a priori; [ii] flexible spline-based estimation) were comprehensively compared with two simpler models ([iii] time since most recent consultation; total number of past consultations) on model goodness of fit, discrimination, and calibration both in derivation and validation phases.
  
  
  
  People with the most recent and most frequent knee-pain consultations were more likely to have high WCE scores that were associated with increased risk of knee OA diagnosis both in derivation and validation phases. Better model goodness of fit, discrimination, and calibration were observed for flexible spline-based WCE models.
  
  
  
  WCE functions can be used to model prediagnostic symptoms within routine EHR data and provide novel low-cost predictive tools contributing to early diagnosis.
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom. Electronic address: d.yu@keele.ac.uk.
authors.forename: Dahai
authors.initials: D
authors.lastname: Yu
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Peat
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Bedson
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom.
authors.forename: John J
authors.initials: JJ
authors.lastname: Edwards
authors.affiliation: Clinical Epidemiology Unit, Orthopaedics, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Turkiewicz
authors.affiliation: Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, Staffordshire ST5 5BG, United Kingdom.
authors.forename: Kelvin P
authors.initials: KP
authors.lastname: Jordan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015984:Causality; D015331:Cohort Studies; D018450:Disease Progression; D042241:Early Diagnosis; D004739:England; D005260:Female; D005544:Forecasting; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis*; D010146:Pain / Q000175:diagnosis* / Q000188:drug therapy*; D011446:Prospective Studies; D018570:Risk Assessment
keywords: Electronic health care record; Flexible modeling; Knee osteoarthritis; Knee pain; Primary health care; Risk prediction; Weighted cumulative exposure