Diagnostic Reasoning I and II

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Diagnostic Reasoning I and II

  1. 1. Author(s): Rajesh Mangrulkar, M.D., 2011License: Unless otherwise noted, this material is made available under the terms ofthe Creative Commons Attribution–Non-commercial–Share Alike 3.0 License:http://creativecommons.org/licenses/by-nc-sa/3.0/We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, andadapt it. The citation key on the following slide provides information about how you may share and adapt this material.Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions, corrections, orclarification regarding the use of content.For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use.Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement formedical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questionsabout your medical condition.Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
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  3. 3. Patients and Populations Medical Decision-Making: Diagnostic Reasoning I and II Rajesh S. Mangrulkar, M.D. University of Michigan Department of Internal Medicine Division of General MedicineFall 2011
  4. 4. Industry Relationship Disclosures Industry Supported Research and Outside Relationships• None
  5. 5. Thread 1: Information Retrieval Ask Acquire Apply Appraise
  6. 6. PICO: A Tool to Structure the Foreground Question Therapy DiagnosisP Patient Pop DiseaseI Intervention TestC Comparison Gold StandardO Outcome Accuracy
  7. 7. Foreground Questions - CaseUsing the PICO model, jot down 1 foreground question with your partner that will help you care for this patient:A 42 year old woman comes to her primary care practitioner’s office for follow up of her diabetes. She is currently on glyburide 10 mg twice daily. However, her blood sugars still stay elevated. After you see this patient, your attending asks whether you think she should add metformin to her regimen.Patient - Intervention - Comparison - Outcome
  8. 8. Foreground Questions - Therapy• In type II diabetics, is metformin and glyburide better than glyburide alone at lowering blood sugar?• Among women with type II diabetes, are there more instances of low blood sugar events in patients on both metformin and glyburide, compared to glyburide alone?
  9. 9. Sources for Foreground Questions• MEDLINE• Practice Guidelines• Evidence Based-Databases – Cochrane Library – ACP Journal Club
  10. 10. AskAcquire Apply Thread 3: Diagnostic Reasoning Appraise
  11. 11. Initial Diagnostic Reasoning The Odyssey Reloaded The Mechanic The Clinician• Failure to entertain • Entertain all important all possibilities possibilities• Failure to pay • Elicit and pay attention attention to all to description of all symptoms symptoms• Failure to inform • Inform and involve customer patients• Failure to perform • Perform effective diagnostic tests diagnostic tests
  12. 12. The Odyssey: Conclusion 50 Prime, flickrInitial Possibilities#1: Trunk latch defect (recall pending)#2: Ajar sensing defect on side door#3: Side door not closing properly
  13. 13. The Odyssey: Conclusion 50 Prime, flickrInitial Possibilities The Answer#1: Trunk latch defect (recall pending)#2: Ajar sensing defect on #2: Ajar sensing defect on side door side door#3: Side door not closing properly
  14. 14. Learning ObjectivesBy the end of this lecture, you will…•demonstrate diagnostic question formulation•define and calculate sensitivity, specificity, andpredictive values for diagnostic tests•explain how risk factors drive priorprobabilities, and how this concept relates toprevalence•modify probabilities from test results through2x2 table calculations, Bayesian reasoning, andLikelihood Ratios
  15. 15. Case: Diagnostic Reasoning• The case: A 60 year old man without heart disease presents with sudden onset of shortness of breath.• Description of the problem: Yesterday, after flying in from California the day before, the patient awoke at 3AM with sudden shortness of breath. His breathing is not worsened while lying down.
  16. 16. Diagnostic Reasoning: Your Intake• Q: “What other symptoms were you feeling at the time?”• A: He has had no chest pain, no leg pain, no swelling. He just returned yesterday from a long plane ride. He has no history of this problem before. He takes an aspirin every day. He smokes a pack of cigarettes a day.
  17. 17. Diagnostic Reasoning: First StepsThe differential diagnosisBasic Tasks:• Assign likelihoods to each possibility – E.g. P(X) = probability that “X” is the cause of the patient’s symptoms• Place the possibilities in descending order of likelihood• State why (rationale)
  18. 18. My listMy differential diagnosis – Pulmonary embolism – Congestive heart failure – Emphysema exacerbation – Asthma exacerbation
  19. 19. Probabilities (1) PE P(PE) = 40% (2) CHF P(CHF) = 30% (3) Emphysema P(emphysema) = 20% (4) Asthma P(asthma) = 10% • What is the probability that the shortness of breath is due to either PE or CHF? 70%**provided that both do not happen simultaneously (i.e., they are “mutually exclusive”). If there is a 10% chance that 2 events may happen, then this number is 60% (make sure you understand why).
  20. 20. Prior Probabilities• Based on many factors: – Clinician experience – Patient demographics – Characteristics of the patient presentations (history and physical exam) – Previous testing – Basic science knowledge• Quite variable but can be standardized – Clinical Prediction Rules – http://medcalc3000.com/PulmonaryEmbRiskPisa.htm
  21. 21. More information• Family history: he has had a DVT in the past (age 40)• Physical Exam: – His blood oxygen saturation is normal on room air – His respiratory rate is 16, but his pulse rate is 105 beats per minute – Examination of his lungs reveals some crackles and wheezes, but no pleural rub or evidence of consolidation. – Swollen right leg, with firm vein below the knee• CXR: normal• EKG: sinus tachycardia http://medcalc3000.com/PulmonaryEmbRiskPisa.htm
  22. 22. Diagnostic Reasoning: Testing• If a Test existed that could “rule in” PE as the diagnosis with 100% certainty: then P(PE | Test+) = 100%• Two questions: – What is this test called? Gold Standard – Does P(CHF | Test+) = 0%? No
  23. 23. Diagnostic Testing• Facilitates the modification of probabilities.• Can include any/all of the following: – Further history taking – Physical Examination maneuver – Simple testing (laboratory analysis, radiographs) – Complex technology (stress testing, $$$ angiography, CT/MRI, nuclear scans)
  24. 24. PICO: The Anatomy of a Diagnostic Foreground Question D P • Patient: define the clinical condition or disease clearly. I T • Intervention: define the diagnostic test clearly G C • Comparison group: define the accepted gold standard diagnostic test to compare the results against. O P • Outcomes of interest: the outcomes of interest are the properties of the test itself (e.g., performance and others we’ll discuss).
  25. 25. Practice PICOCase: A 60 year old man without heart disease presents with sudden onset of shortness of breath. Considering PE.Diagnostic Test to consider: Ventilation / Perfusion ScanningGold standard: Pulmonary angiographyNeed: Diagnostic performance
  26. 26. Practice PICOCase: A 60 year old man without heart disease presents with sudden onset of shortness of P breath. Considering PE.Diagnostic Test to consider: Ventilation / Perfusion ScanningGold standard: Pulmonary angiographyNeed: Diagnostic performance
  27. 27. Practice PICOCase: A 60 year old man without heart disease presents with sudden onset of shortness of P breath. Considering PE.Diagnostic Test to consider: Ventilation / Perfusion Scanning IGold standard: Pulmonary angiographyNeed: Diagnostic performance
  28. 28. Practice PICOCase: A 60 year old man without heart disease presents with sudden onset of shortness of P breath. Considering PE.Diagnostic Test to consider: Ventilation / Perfusion Scanning I CGold standard: Pulmonary angiographyNeed: Diagnostic performance
  29. 29. Practice PICOCase: A 60 year old man without heart disease presents with sudden onset of shortness of P breath. Considering PE.Diagnostic Test to consider: Ventilation / Perfusion Scanning I CGold standard: Pulmonary angiography ONeed: Diagnostic performance
  30. 30. Can the test be used? Step 1 - Accuracy and Precision• Accuracy - The result of the test corresponds consistently with the true result. – The test yields the correct value• Precision - The measure of the test’s reproducibility when repeated on the same sample. – The test yields the same value
  31. 31. Accuracy vs. Precision
  32. 32. Accuracy vs. PrecisionProceed to Step 2
  33. 33. Accuracy vs. PrecisionProceed to Step 2 Calibrate Equipment
  34. 34. Accuracy vs. PrecisionProceed to Step 2 Calibrate Equipment Start Over
  35. 35. Can the test be used? Step 2 - Diagnostic Performance1. A well-defined group of people being evaluated for a condition undergo: - an experimental test, and - the gold standard test.2. Comparison is made between the result of the new test and that of the gold standard.
  36. 36. Diagnostic Performance: Statistical Significance• Statistical significance: strength of the association between… – Diagnostic study results (for the diagnosis of a particular disease) – Gold standard results (for the diagnosis of the same disease, in the same population)• Strength = degree of correlation
  37. 37. Diagnostic Performance: Clinical Significance• Clinical significance: how likely is the diagnostic test going to affect patient care? – Magnitude of the association between test results and the accepted gold standard – Other literature (including those of the gold standard) – Cost of the test, reproducibility of test – Disease characteristics (will the test result affect management of the disease?)
  38. 38. What are the results - Diagnosis Diagnostic performance is an association between test result and diagnosis of a condition (as assessed by the gold standard) Disease + Disease - BONUS Test + A BWhat type of variable is TP FP FN TN disease state? Test - C D
  39. 39. Which test characteristics?• There are prevalence-dependent and prevalence-independent measures in diagnostic tests.• Prevalence-independent: sensitivity and specificity.• Prevalence-dependent: positive and negative predictive values.
  40. 40. Test Characteristics: SeNsitivitySensitivity:• The probability that the test will be positive when the disease is present. P (Test + | Disease +)• Of all the people WITH the disease, the percentage that will test positive.• A seNsitive test is one that will detect most of the patients who have the disease (low false-Negative rate).
  41. 41. Test Characteristics: SPecificitySpecificity:• The probability that the test will be negative when the disease is absent. P (Test - | Disease -)• Of all the people WITHOUT the disease, the percentage that will test negative.• A sPecific test is one that will rarely be positive in patients who don’t have the disease (low false-Positive rate).
  42. 42. Test Characteristics: Predictive Values• Positive predictive value: the probability that a patient has a disease, given a positive result on a test. P (Disease + | Test +)• Negative predictive value: the probability that a patient does not have a disease, given a negative result on a test. P (Disease - | Test -)
  43. 43. Diagnostic Test Characteristics• Sens = A/(A+C) Dx+ Dx-• Spec = D/(B+D) T+ A B• PPV = A/(A+B) T- C D• NPV = D/(C+D) A+C B+D
  44. 44. To reflect upon... Why? Sensitivity and SpecificityPrevalence-Independent characteristicsPositive and Negative Predictive Values Prevalence-Dependent characteristics
  45. 45. Let’s try it outCase: To determine the diagnostic V/Q scan performance of V/Q scans for detecting pulmonary embolism, a study was conducted where 300 patients underwent both a V/Q and pulmonary angiogram. 150 patients were found to have a PE by PA gram. Of those, 75 Pulmonary Angiogram patients had a high probability VQ scan. Of the 150 patients without a PE, 125 had a non- high probability VQ scan.
  46. 46. Let’s try it outCase: To determine the diagnostic performance of V/Q PE+ PE- scans for detecting pulmonary embolism, a study was conducted where 300 patients VQ hi 75 25 underwent both a V/Q and pulmonary angiogram. 150 patients were found to have a VQ PE by PA gram. Of those, 75 patients had a high probability other 75 125 VQ scan. Of the 150 patients without a PE, 125 did not have a high probability VQ scan (VQ other). 150 150
  47. 47. Let’s try it out PE+ PE- • Sens = 75/(75+75) = 50%VQ hi 75 25 • Spec = 125/(125+25) = 83% VQ • PPV = 75/(75+25) 75 125 = 75%other • NPV = 125/(125+75) 150 150 = 63%
  48. 48. Modification of Probability Pretest Test resultProbability Test changes theP (Disease) Result probability of disease P (Disease|Test Result)
  49. 49. Test Characteristics and Prevalence• Sens = A/(A+C) Dx+ Dx-• Spec = D/(B+D) T+ A B• PPV = A/(A+B) T- C D• NPV = D/(C+D) Disease A+C B+D Prevalence
  50. 50. Prevalence PE+ PE- • Sens = 50%VQ hi 75 25 • Spec = 83% • PPV = 75% VQ • NPV = 63%other 75 125 • Prevalence = 50% ??? 150 150
  51. 51. Populations and PatientsPopulation view Patient view• Prevalence reflects • Same concept the number of implies how likely an people with the individual patient disease at a given has the disease moment • P (Disease)
  52. 52. Modification of Probability Pretest Test resultProbability Test changes theP (Disease) Result probability of disease P (Disease|Test Result) DiseasePrevalence
  53. 53. An Important Question and Assumption Question: Are certain test characteristics fixed? Answer: Generally, yes. Sensitivity and specificity are constants, regardless of the prevalence of the disease in the studied population (prevalence-INdependent)**Exceptions and caveats to this assumption are real, but are beyond the scope of this course
  54. 54. Modification of Probability Pretest Test resultProbability Test changes theP (Disease) Result probability of disease P (Disease|Test Result) Disease sensitivityPrevalence specificity
  55. 55. Importance of Pre-Test Probability• Hi-prob V/Q: Sens = 50%, Spec = 83% Post-TP PV D+ D- Pre-TP/Prev PPV NPV T+ 75 25 50% 75% 63% T- 75 125 How do our predictive values relate to our probability after the test result is obtained (our post-test probabilities)?
  56. 56. Importance of Pre-Test Probability• Hi-prob V/Q: Sens = 50%, Spec = 83% Post-TP PV D+ D- Pre-TP/Prev PPV NPV T+ 75 25 50% 75% 63% T- 75 125• If our Pre-test Probability was 50%, and we obtain a hi-prob V/Q scan on this patient, what is our Post-test probability? 75%
  57. 57. Importance of Pre-Test Probability• Hi-prob V/Q: Sens = 50%, Spec = 83% Post-TP PV D+ D- Pre-TP/Prev PPV NPV T+ 75 25 50% 75% 63% T- 75 125• If our Pre-test Probability was 50%, and we obtain a V/Q-other scan on this patient, what is our Post-test probability? 37% (tricky: 1-63%)
  58. 58. What did we just do? 100 75% = P(PE|T+) hi VQ50% VQ o ther 37% = P(PE|T-) 0 P (PE) P (PE | Test)
  59. 59. Modification of Probability Pretest Test resultProbability Test changes theP (Disease) Result probability of disease P (Disease|Test Result) Disease sensitivityPrevalence specificity Predictive Values (Positive and Negative)
  60. 60. Fundamental AssumptionsSensitivity and specificity are constants, regardless of the prevalence of the disease in the studied population (prevalence-INdependent)*Positive and Negative Predictive Values are dependent on the prevalence of the disease in the studied population (prevalence-DEpendent)*with exceptions
  61. 61. Now, what do we do? *clickers 75% = P(PE|T+) Q1: Choices: a)Treat as if patient has PE b)Decide to get another test c)Decide that patient does not have a PEWhat factors do you consider when making the next decision?
  62. 62. Now, what do we do? *clickers Q2: Choices: a)Treat as if patient has PE b)Decide to get another test c)Decide that patient does not have a PE 37% = P(PE|T-)What factors do you consider when making the next decision?
  63. 63. Now, what do we do? Choices: •Treat as if patient has PE 75% = P(PE|T+) •Decide to get another test •Decide that patient does not have a PE Choices: 37% = P(PE|T-) •Treat as if patient has PE •Decide to get another test •Decide that patient does not have a PEWhat factors do you consider when making the next decision?
  64. 64. What if we change our pretest probability?• In essence, we are simultaneously changing the prevalence: – Original pre-TP = P(PE) = 50% HIGH RISK – New pre-TP = P(PE) = 25% MED RISK• Assuming that sensitivity and specificity are fixed…then we must recalculate our predictive values to determine our new post-test probabilities.
  65. 65. Importance of Pre-Test Probability • Hi-prob V/Q: Sens = 50%, Spec = 83% D+ D- Post-TP T+ 75 25 Pre-TP/Prev PPV NPV T- 75 125 hi risk 50% 75% 63% D+ D- med risk 25% 50% 83% 38/(38+38) 187/(187+37) T+ 38 38Our Pre-test Probability was 25%, we obtain a V/Q-other scan T- 37 187 on this patient, our Post-test probability is now…17%
  66. 66. Decision time *clickers Q3: Choices: a)Treat as if patient has PE b)Decide to get another test c)Decide that patient does not have a PE50% = P(PE|T+)
  67. 67. Decision time *clickers Q4: Choices: a)Treat as if patient has PE b)Decide to get another test c)Decide that patient does not have a PE17% = P(PE|T-)
  68. 68. Decision time Choices: •Treat as if patient has PE •Decide to get another test •Decide that patient does not have a PE50% = P(PE|T+) Choices: •Treat as if patient has PE •Decide to get another test17% = P(PE|T-) •Decide that patient does not have a PE
  69. 69. Let’s change it again…• Again, we are changing the prevalence: – Young woman, no risk factors, some dyspnea, no history, normal exam – If we consult our clinical prediction rule: • New pre-TP = P(PE) = 5%: LOW RISK
  70. 70. Importance of Pre-Test Probability • Hi-prob V/Q: Sens = 50%, Spec = 83% D+ D- Pred Val T+ 75 25 Pre-TP/Prev PPV NPV T- 75 125hi risk 50% 75% 63% D+ D-lo risk 5% 15% 97% 8/(8+47) 238/(238+7) T+ 8 47 T- 7 238
  71. 71. What did we just do? Observation As prevalence (pre-test probability) decreases, positive tests are more likely to be false-positives 75% = P(PE|T+) hi VQ50% VQ o ther 37% = P(PE|T-) VQ h i 15% = P(PE|T+) 5% 0 VQ other 3% = P(PE|T-) P (PE) P (PE | Test)
  72. 72. Fundamentally...Question: If you get a high probability V/Q scan for the diagnosis of pulmonary embolism, is it more likely to represent a false positive test if the patient presented with…(a) many clinical features of PE (shortness of breath, chest pain, long plane ride), or(b) no clinical features of PE (no shortness of breath, no chest pain, no leg swelling, no long plane ride)?
  73. 73. Alternative Vocabulary - Rates• True Positive Rate = sensitivity• False Positive Rate = 1-specificity• False Negative Rate = 1-sensitivity• True Negative Rate = specificity
  74. 74. Combining Rates - Methods• Likelihood Ratios• ROC Curves
  75. 75. Combining Rates - Method 1 Likelihood Ratios (LR)• Concept - LRs depict the relationship between true and false rates – TPR/FPR = LR for a positive test result – FNR/TNR = LR for a negative test result TPR sens FNR 1-sens LR = --------- = ------------- LR = --------- = ------------- FPR 1-spec TNR spec Typically >1, excellent >10 Typically <1, excellent <0.1
  76. 76. Application Likelihood Ratios (LR)Key Concept: LRs can be Remember our scenario: combined with pre-test High risk pt - 50% (PreTP) odds to get post-test 0.50 odds LR (VQ hi) = --------- = 2.94 1-0.83Pre * Pre x LR = Post * PostTP TO TO TP50% 1.0 2.94 2.94 75% *converting odds to probability and vice and versa - many references online
  77. 77. Combining Rates - Method 2 ROC Curves Visual depiction of LR • Tests with continuous values only • Sensitivity-specificity tradeoff at different cutoffs • TPR plotted against FPR
  78. 78. Application ROC CurvesROC Curves• Area under the curve determines overall utility of the test• Inflection point reflects optimal threshold• More in Small Group Exercise – Assignment 3
  79. 79. Take Home Points• Research studies of diagnostic tests give you test characteristics, not predictive values.• Relationships between sensitivity and specificity can be captured in ROC curves (for tests with thresholds) and Likelihood Ratios (LRs)• Appropriate use of tests stem from large differences between pre-test and post-test probabilities, resulting from LRs that strongly deviate from 1.• If your pre-test probability is very low (<10%) or very high (>90%), it is rare that a single test can help.
  80. 80. Diagnostic Reasoning The Odyssey Returns The Mechanic The Clinician• Failure to entertain • Entertain all important all possibilities possibilities• Failure to pay • Elicit and pay attention attention to all to description of all symptoms symptoms• Failure to inform • Inform and involve customer patients• Failure to perform • Perform effective diagnostic tests diagnostic tests
  81. 81. Ask 50 Prime, flickrAcquire Apply Appraise
  82. 82. Additional Source Information for more information see: http://open.umich.edu/wiki/AttributionPolicySlide 09: http://www.ncbi.nlm.nih.gov/pubmed/ ; http://www.guideline.gov/Slide 12: 50 Prime, flickr, http://www.flickr.com/photos/pernett/1544045987/, CC: BY http://creativecommons.org/licenses/by/2.0/deed.enSlide 73: 50 Prime, flickr, http://www.flickr.com/photos/pernett/1544045987/, CC: BY http://creativecommons.org/licenses/by/2.0/deed.en

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