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The Norfolk Arthritis Register

The Norfolk Arthritis Register

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The Norfolk Arthritis Register

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  1. The Norfolk Arthritis Register Alan Silman arc Epidemiology Unit University of Manchester UK

  2. Manchester

  3. The Norfolk Arthritis Register A primary care based inception cohort study of patients with inflammatory polyarthritis

  4. Norfolk

  5. Why Norfolk? • Geographically ‘isolated’ • Stable population • Single central major hospital • Excellent links primary to secondary care • Local enthusiasm

  6. Topics The NOAR methodology Key results • Classification of RA • Environmental risk factors • Outcome • Predictors of outcome • Treatment effects

  7. NOAR : Recruitment Entry criteria - age > 16 years - registered with local GP - swelling of > 2 joints Manchester - duration > 4 weeks - onset since 1/1/90 Norwich Metrology assessment Apply ACR criteria

  8. Metrologist Assessment

  9. Anniversary 0 1 2 3 4 5 7 10 Occupation         Reproductive         Co-morbidity         Drugs         Manikin - activity     -  - - - deformity     -    HAQ         SF36 - - - - -  -  Pain score - - - - -    Blood tests  () () - -  -  X-rays - () () - -  - () Data Collected

  10. The Norfolk Arthritis Register (NOAR) Initial aims To establish the incidence of IP and subset with RA To identify risk factors for the development of IP and RA To study the natural history of treated IP and RA To identify predictors of outcome in IP and RA

  11. The Norfolk Arthritis Register (NOAR) Current Major Aims To investigate the epidemiology of cardiovascular disease in patients with IP (risk factors, incidence and outcome) To identify predictors of treatment response and non-response

  12. Key results Incidence of IP and RA

  13. ACR criteria applied at baseline ACR criteria applied over 5 years Estimates of the incidence of RA:Application of ACR criteria Females Males Incidence rate per 100,00 Age Age

  14. Issues of Classification IP vs RA

  15. Concept Early IP Another disease Established RA Recovery

  16. Concept Early IP Another disease Established RA Recovery ? Treatment

  17. Does early RA exist?

  18. Are there differences between IP destined to differentiate into RA and other ‘causes’ of IP?

  19. Can we distinguish early RA from other forms of early arthritis? Immunisation X Parvovirus X Psoriasis X

  20. Leiden model: prediction of outcome Goal: To discriminate at first visit between patients who will go on to have: • self-limiting arthritis • persistent non-erosive arthritis • persistent erosive arthritis

  21. Leiden model: 7 variables Symptom duration at presentation Morning stiffness > 1 hour Arthritis of > 3 joints Bilateral compression pain of MTPs Rheumatoid factor Anti-cyclic citrullinated peptide antibody Erosions in hands or feet

  22. Validation of Leiden modelerosive vs non-erosive arthritis In presence of persistence Radiological criterion omitted Leiden NOAR (n= 526)(n=486) Prediction model ROC 0.83 0.76 ACR criteria ROC 0.77 0.66

  23. Key results Risk factors for the development of IP and RA

  24. Sources of Data Descriptive Analysis

  25. Local Clustering of RA Silmanet al., 1999

  26. Onset of Disease by Month 1990-92 All cases 30 UIP 25 RA 20 Number of new cases 15 10 5 0 June June June Jan Jan Jan 1990 1991 1992 Month of onset Silmanet al., 1997

  27. Observed & Expected Events in Relation to Time & Distance 0 -5e7 D -1e8 400 1500 300 1000 200 500 Time 100 Distance Silmanet al., 1997

  28. Socioeconomic Deprivation vs RA Incidence by census ward Bankhead et al., J Rheum 1996

  29. Socioeconomic Deprivation & RA Incidence /100,000 * Social Class * IV & V combined for men Bankhead et al., J Rheum 1996

  30. Case control studies 1. Internal NOAR Cases 1992 (n=165) : aged 18-70 symptom duration < 12 months Controls: 2 per case from referring primary care Sources of data

  31. Lifestyle Factors 20 10 5 4 3 2 1 Obesity Smoking

  32. Association of Smoking with Severe RA: Rheumatoid Nodules 20 10 Odds Ratio (95% CI) 4 2 1 0.4 Never Ex Current Harrison et al., Arth Rheum 2003

  33. Hormonal Risk Factors 8 6 4 2 1 .8 .6 .4 .2 .1 Miscarriage Oral Contraceptive Termination

  34. Association between Prior Blood Transfusion and RA 20 15 % 10 5 0 Cases Controls Symmons et al., 1997

  35. 2. NOAR EPIC Link

  36. Co-occurrence of NOAR & EPIC in same population Area for new cases of IP referred to NOAR EPIC practices                                   

  37. Baseline assessments European Prospective study of the Incidence of Cancer (EPIC-Norfolk) Random sample (n= 25,000) 45 – 75 years Recruited 1993 – 1997 Health and lifestyle questionnaire Height and weight

  38. Free of IP at baseline Subsequent registration with NOAR 2 per case Matched: - age (± 3 years) - gender - within 3 months of baseline assessment Prospective ‘nested’ case control study Controls 73 Cases

  39. EPIC Diet Survey • 7 day detailed food diary with portion sizes

  40. Fruit Intake (g) and Development of IP Odds Ratio (95% CI)* 8 6 4 2 1 .8 .6 .4 Lowest Middle Highest (ref) .2 Tertile *Adjusted for energy intake, smoking, red meat intake Pattison et al., ARD 2004

  41. Tertiles of Vitamin C Intake (mg) Odds Ratio (95% CI)* 8 6 4 2 1 .8 .6 .4 Lowest Middle Highest (ref) Tertile .2 *Adjusted for energy intake, smoking, protein intake Pattison et al., ARD 2004

  42. Tertiles of -cryptoxanthin Intake (µg) Odds Ratio (95% CI)* 3 2 1 .5 .3 .2 Lowest (ref) Middle Highest .1 Tertile *Adjusted for energy intake, smoking, protein intake Pattison et al. 2005

  43. RA and Dietary Zeaxanthin Intake Odds Ratio (95% CI)* 3 2 1 .7 .5 .3 .2 Lowest (ref) Middle Highest .1 Tertile *Adjusted for energy intake, protein, smoking Pattison et al 2005

  44. Red Meat & Meat Products and Development of IP Odds Ratio (95% CI)* 8 6 4 2 1 .8 .6 Lowest (ref) Middle Highest *Adjusted for energy intake, smoking, fruit intake Pattison et al., A & R 2004

  45. Are the Diet Effects Independent? Odds Ratio (95% CI)* 8 8 6 6 4 4 2 2 1 1 .8 .8 .6 .6 .4 .4 .2 .2 .1 .1 Low Middle High Low Middle High Vitamin C mg/day Red Meat g/day

  46. Key results The natural history of treated IP and RA

  47. Outcomes investigated Persistence Radiological damage Physical function (HAQ) Economic costs Health status (SF-36) Co-morbidity Work disability Mortality

  48. Work disability Year of onset