Clinical Models in Venous Thromboembolism:

1. Clinical Models in Venous Thromboembolism: How to make the most of your history and physical exam or Eddy Lang CCFP(EM) CSPQ McGill Emergency Rounds October 2001

2. Clinical Scenario #1: Mr. Tremblay • 63 year old male with severe cough x 1 day • No significant PMHx, non smoker • Tachypnic able to speak complete sentences: • VS: HR 105 BP 140/90 T 38.1C - rectal O2 Sat 93% RA • No preceding URI Sx • Central chest discomfort initially -now resolved • Some decreased A/E left base • CXR: small left-sided pleural effusion, minimal airspace disease

3. Clinical Scenario #2: Ms. Jones • 22 year old female • 2 hour history of chest pressure and SOB • Appears apprehensive, wearing oxygen starting to feel better • VS: 120/90 RR 22/min Sat 100% HR 90 T = 36.9 • Smoker, OCPs • Remote history of panic attacks; similar but not as severe • No associated symptoms • Unremarkable physical

4. Test and Treatment Thresholds in the Diagnostic Process No further testing necessary Treatment commences

5. Survey 1. Would you order a ventilation/perfusion scan or helical CT in this patient (I don't need to know which)? 2. Would you order a D-Dimer test on this patient (assume non-elisa)? 3. Would you use the D-Dimer result to determine whether you would order any imaging i.e. helical CT or V/Q?

6. Survey Results

7. Survey Results • Mr. Tremblay • 5/7 get V/Q • 2/7 get D-dimer • 3/7 incorporate D-dimer in decision to image • Ms Jones • 2/7 get V/Q • 5/7 get D-dimer • 4/7 incorporate D-dimer in decision to image

8. Clinical Question In patients who present with symptoms and signs suggestive of PE, can elements of the clinical examination in combination with simple tests allow me to determine which patients can be safely discharged without imaging procedures?

9. Clinical Question In patients who present with a syndrome suggestive of PE, can a clinical prediction rule allow me to determine which patients need further work-up?

10. Educational Objectives • Review the rationale for the development of clinical prediction rules in venous thromboembolism (VTE) • Conduct structured critical appraisal of the best prediction rule / clinical model research in VTE • Explore issues related to test selection in patients suspected of VTE

11. Top 10 List

12. Top Ten Reasons to Dislike Clinical Prediction Rules 6. I don’t practice cookbook medicine 7. I refuse to do any math during my shift especially if I need a calculator 8. I’m way too busy to use these things 9. My “gestalt” clinical judgement is better than any prediction rule could be 10. They are just too damned complicated to use

13. Top Ten Reasons to Dislike Clinical Prediction Rules 1. Everyone knows the H and P stinks, let’s just get an MRI 2. Developed by nerdy academics who haven’t examined a patient in 30 years 3. I don’t believe in fortune telling 4. Except for Christian, everything from Ottawa annoys me! 5. They are a government plot designed to make us cut costs

14. Finding the evidence

25. Use of a Clinical Model for Safe Management of Patients with Suspected Pulmonary Embolism Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

26. Inclusion Criteria: • Consecutive inpatients and outpatients with suspected pulmonary embolism whose symptoms had lasted less than 30 days were potentially eligible • 5 centers, 16 physicians • Exclusion Criteria: • Duration of Sx > 3 days • Anticoag > 72hrs. • Survival < 3 months • Suspected upper extremity DVT Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

27. Probability Model  = 0.86 Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

28. Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

29. 1885 eligible patients Study Flow • Prolonged • anticoagulation • expected survival • < 3 mos. 484 ineligible 1401 eligible patients • 147 declined • to consent • 13 lost to • follow-up 150 lost 1239 evaluable patients 734 low PTP 3.4% PE 403 mod. PTP 28% PE 102 high PTP 78% PE

30. Rates of Pulmonary Embolism According to Pretest Probability of Pulmonary Embolism and Results of Ventilation-Perfusion Lung Scanning Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

31. Rates of venous thromboembolic events during the 3-month follow-up • normal perfusion scans and normal initial ultrasonograms: • 2 of 332 [0.6%; 95% CI, 0.3% to 3.0%] • non-high-probability ventilation-perfusion scans, low or moderate pretest probability, and normal serial ultrasonograms • 3 of 665 [0.5%; 95% CI, 0.1% to 1.3%] Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

32. Cause of Death According to Whether Pulmonary Embolism Was Initially Diagnosed Wells, Ginsberg, Anderson et al. Annals of Internal Medicine - 1998

33. Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. Wells, Anderson, Rodger, Stiell et al. Annals of Int. Med. 2001

34. Inclusion Criteria: • Consecutive emergency department patients (adults) with suspected pulmonary embolism whose symptoms had lasted less than 30 days were potentially eligible • 4 centers, 43 physicians • Exclusion Criteria: • Suspected upper extremity DVT • No Sx within 72 hrs • Anticoag > 24 hrs. • Expected survival < 3 mos. • Contraindication to contrast • Pregnancy • Geographic inaccessibility Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

35. Interventions: • Application of a clinical model • SimpliRED whole-blood agglutination D-dimer • Primary Outcome: • Proportion of patients with VTE during 3-month follow-up • Methodology • Intention to treat analysis • Upper range 95% CI = 1% VTE rate • Sample size 930 Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

36. Clinical Model • Hemoptysis - 1.0 pt. • Malignancy 1.0 pt. • HR > 100 - 1.5 pts. • Immobilization ( 3 consec. Days) or surgery within 4 weeks - 1.5 pts. • Previous DVT/PE - 1.5 pts. • Clinical signs and Sx of DVT - 3.0 pts. • PE as likely or more likely than alternate Dx - 3.0 pts. Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

37. Clinical Model:Scoring • Low PTP < 2.0 points • Moderate PTP  2.0 but < 6.0 • High PTP  6.0 Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

38. Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

40. Clinical Model:Performance • Low PTP 527 pts. (57%); 7 VTE events (1.3%) • Moderate PTP 339 pts. (36%); 55 VTE events (16.2%) • High PTP 64 pts. (7%); 24 VTE events (40.6%) Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

41. Follow-up Data on 849 patients with VTE ruled out • 17 suspected events; 6 low PTP, 9 mod PTP, 2 high PTP • VTE confirmed in 5 (0.6% 95% CI 0.2 to 1.4%) • Low PTP • 4 suspected PE, 2 DVT; 1 PE confirmed (day 16) • Mod PTP • 4 suspected PE, 5 DVT; 3 DVT confirmed • High PTP • 2 suspected PE; 1 PE confirmed Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

42. Compliance with Algorithm • 92 patients had fewer tests than called for • 4/5 confirmed events occurred in this group • Among 81 patients initially diagnosed with PE: 7 patients labeled as a result of extra testing • 2/7 from low PTP group Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

43. Wells, Anderson, Rodger, Stiell et al. Annals of Internal Medicine - 2001

44. Do we believe this?

47. Methodologic Standards for Development of a Clinical Prediction Rule: The Researcher’s Perspective • Is there a need for the decision rule? • Was the rule derived according to methodologic standards? • Has the rule been prospectively validated and refined? • Has the rule been successfully implemented into clinical practice? • Would use of the rule be cost effective? • How would the rule be disseminated and implemented? Stiell IG and Wells GA APRIL 1999 33:4 ANNALS OF EMERGENCY MEDICINE

49. Methodologic Standards for Validation of a Clinical Prediction Rule: The Clinician’s perspective • Were the patients chosen in an unbiased fashion and do they represent a wide spectrum of the severity of the disease? • Was there a blinded assessment of the criterion standard for all patients? • Was there an explicit and accurate interpretation of the predictor variables and the actual rule without knowledge of the outcome? • Was there 100% follow-up of the patients enrolled? Users Guide 2000 AMA press

50. Were the patients chosen in an unbiased fashion and do they represent a wide spectrum of the severity of the disease? • “consecutive symptomatic patients” • 86 ultimately diagnosed with PE (9.5%) • Rule in rate of 17% in patients undergoing imaging