9/6/2018 Best Tests for Differential Diagnosis What are the Metrics Chad Cook PhD, PT, MBA, FAAOMPT of Diagnosis? Professor and Program Director Duke University Duke Clinical Research Institute For Diagnosis, There are Analytic Diagnostic Test Metrics Metrics • Diagnostic accuracy • Reliability • Diagnostic accuracy relates to the ability of • Sensitivity a test to discriminate between the target condition and another competing condition. • Specificity • Positive and Negative Predictive Value • Positive and Negative Likelihood Ratios Does Reliability Matter? Sensitivity and Specificity No worries, The you will Sensitivity: Percentage of people who test positive for a condition • be fine is fatal specific disease among a group of people who have the disease • Specificity: Percentage of people who test negative for a specific disease among a group of people who do not have the disease Kappa Intraclass Correlation www.zillowblog.com Coefficient 5 1 9/6/2018 Sensitivity Example Specificity Example • 50 patients with arm pain associated • 50 patients with no arm pain with cervical radiculopathy associated with a cervical strain • Test was positive in 40 of the 50 • Test was positive in 5 of the 50 cases cases • Sensitivity = 40/50 or 80% • Specificity = 45/50 or 90% • Correct 80% of the time in cases • Correct 90% of the time in cases that were cervical radiculopathy that were NOT cervical radiculopathy http://www.triggerpointbook.com/infrasp2.gif http://www.triggerpointbook.com/infrasp2.gif Likelihood Ratios • A high LR+ influences post-test probability with a positive finding • A value of >1 rules in a diagnosis • A low LR- influences post-test probability with a negative finding • A value closer to 0 is best and rules out Bossuyt P, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: the STARD initiative. Family Practice. 2004;21:4-10. Clinical Utility Fagen’s Nomogram (LR+) • Cervical • The ability of the metrics to influence post-test probability Radiculopathy (either in ruling out the condition or ruling it in) • Pretest • Or just improving your likelihood of being correct prob=18% • Spurling’s LR+=4.8 • Post test prob of a positive finding= 52% 2 9/6/2018 Fagen’s Nomogram (LR-) Confidence Intervals? • Cervical • Wainner’s CPR for Radiculopathy CTS • Pretest prob=18% • 34% pre-test prob • ULTT (LR- = 0.14) • <4/5 of the tests • Post test prob of a • LR+ = 4.6 (95%CI negative finding = 2.5, 8.7) 2.98% • Post-test probability = 70% (56.3%, 81.7%) Tests Should be Used in Proper Examination in Series Order R/O R/I • Some tests should High Sensitivity High Specificity typically be used early Low LR- High LR+ • E.g., SLR, ULTT, Hawkins Kennedy, • Some late in the examination R/O R/I • Spurlings, Hoffmann’s test, Intake Observation Movement Exam MMT/Endurance Well leg Raise Patient History Screening Palpation/Exam Confirmatory Tests OTHERWISE YOUR RESULTS WILL BE BIASED 15 Fagen’s Nomogram Example One-Screening (LR-) • Hoffmann’s test (sign) for • Cervical myelopathy Myelopathy • Sensitivity = 50% and a negative • Pretest prob=5% likelihood ratio of 0.74 • Hoffmann’s LR- • Negative finding is of interest =0.74 • 50% will have a negative, but will • Post test prob of have the disease a negative finding= 4% 3 9/6/2018 Fagen’s Nomogram (LR+) Example Two-Confirming • Straight leg raise • Lumbar • Sensitivity is about 90% Radiculopathy • Specificity is about 15% and • Pretest positive likelihood ratio is 1.24 prob=25% • This means that it is positive in • SLR LR+=1.24 those that have radiculopathy • Post test prob of and those that don’t have it a negative finding= 27% Calculations Influencing Decision Making • Positive Likelihood Ratio= (sensitivity)/(1-specificity) • Negative Likelihood Ratio= (1-sensitivity)/(specificity) Cook C. Orthopedic Manual Therapy. An Evidence Based Approach. Prentice Hall; Upper Saddle River, NJ: 2007. 22 What if You Don’t Care to Follow This? Diagnostic Clinical Utility • You run the risk of • To what extent diagnostic testing “ruling out” improves health outcomes relative conditions that are to the current best alternative, actually present which could be some other form • You run the risk of of testing, or not testing at all. “confirming” conditions that are not really there Bossuyt et al. Beyond diagnostic accuracy: the clinical utility of diagnostic tests. Clin Chem. 2012 Jun 33 It increases the risks of an error [Epub ahead of print] 24 4 9/6/2018 Screening • (Technically) Screening is performed to detect the presence of a specific disease. The individual or Red Flags, Triage, and group of individuals (as in mass screenings) does not Screening present any symptoms of the disease. • The correct use involves screening of healthy Chad Cook PT, PhD, MBA, FAAOMPT subjects Professor Duke Doctor of Physical Therapy Division Duke Clinical Research Institute Duke University Natural History of Disease Spot Diagnosis or Triage Screening • Differential assessment for red flags in individual Latency Period *Detectable patients by a clinician using special tests or Sojourn Time* Preclinical standardized examinations in order to identify Period individuals needing special intervention. Biological Detectable Symptoms Diagnosed Becomes Onset by testing begin w/ disease disabling Dx Test Primary Secondary Tertiary Sizer P, Brismee JM, Cook C. Medical screening for red flags in the diagnosis and management of Prevention Prevention Prevention 27 musculoskeletal spine pain. Pain Pract. 2007 (in press). Clinical Triage Examples Differences? Screening Sport Diagnosis or Triage • Canadian C-Spine Rules are used to determine who doesn’t need an x-ray ( sensitivity-99%) X-ray is used to diagnose fracture ( specificity) • Ottawa Ankle Rules are used to determine who doesn’t need an x-ray ( sensitivity) X-ray is used to diagnose fracture ( specificity) Healthy Population/Population based Patient Population www-chaos.umd.edu http://www.providencecare.ca/objects/rte/Image/images/patients-main-pg-final.jpg 5 9/6/2018 Triage: Sinister Disorders (Red What is a Red Flag? Flags) • Signs and Symptoms found in the patient history and clinical • Rare, but occasionally examination that may tie a disorder to a serious pathology. present (<1% of cases) • Sometimes is identified as a finding that is reflective of a • Most guidelines suggest delayed or poor outcome. that “when something • We call this a prognostic red flag. seems wrong, it might be wrong” is the best process Sizer P, Brismee JM, Cook C. Medical screening for red flags in the diagnosis and management of musculoskeletal spine Underwood M, Buchbinder R. Red flags for back pain. BMJ. 2013 Dec 12;347:f7432. doi: 10.1136/bmj.f7432. pain. Pain Pract. 2007. 31 • Clinicians do not actually screen for red Rethinking Red Flags flags, they manage the findings; • Based on these findings, we propose that clinicians consider: • Red flag symptomology negates the utility of • (1) the importance of watchful waiting; clinical findings; • (2) the value-based care does not support clinical examination • Tests lack the negative driven by red flag symptoms; likelihood ratio to serve as a screen; • (3) the recognition that red flag symptoms may have a stronger • Clinical practice relationship with prognosis than diagnosis. guidelines do not include specific processes that aid decision-making. Cook CE, George SZ, Reiman MP. Red flag screening for low back pain: nothing to see here, move along: a narrative review. Cook CE, George SZ, Reiman MP. Red flag screening for low back pain: nothing to see here, move along: a narrative review. Br J Sports Med. 2017 Sep 18. pii: bjsports-2017-098352. Br J Sports Med. 2017 Sep 18. pii: bjsports-2017-098352. Categorizing Red Flags Category I: • Category I: Factors which Require Immediate Medical • Blood in Sputum Attention • Elevated Sedimentation Rate • Category II: Factors which Require Subjective Questioning • Loss of Consciousness or Altered mental state and Precautionary Examination and Treatment Procedures • Bowel and Bladder Dysfunction • Category III: Factors which Require Further Physical Testing and Differentiation Analysis • Severe Non-mechanical pain • Progressive Neurological Deficit • Heart-Related Symptoms Cook C. Orthopedic Manual Therapy. An Evidence Based Approach. Prentice Hall; Upper Saddle River, NJ: Cook C. Orthopedic Manual Therapy. An Evidence Based Approach. Prentice Hall; Upper Saddle River, NJ: 2007. 35 2007, 2012. 36 6 9/6/2018 Category II: Category III: • Age > 50 • Impairment precipitated by recent • Myelopathic Symptoms trauma • Clonus • Abnormal Reflexes • Long-term corticosteroid use • Fever • Bilateral or Unilateral Radiculopathy or Paresthesia • Gait Deficits • Long-term worker’s compensation • Unexplained Referred Pain • History of a disorder with • Non-healing sores or wounds predilection for infection or • Recent history of unexplained • Unexplained Significant Upper or Lower Limb Weakness hemorrhage weight loss • History of a metabolic bone • Writhing pain disorder • History of cancer Cook C. Orthopedic Manual Therapy. An Evidence Based Approach. Prentice Hall; Upper Saddle River, NJ: 2007. Cook C. Orthopedic Manual Therapy. An Evidence Based Approach. Prentice Hall; Upper Saddle River, NJ: 2007, 37 38 2012. Best Tests for Upper Quarter Red Flags Fractures Chad Cook PT, PhD, MBA, FAAOMPT Professor Duke Doctor of Physical Therapy Division Duke Clinical Research Institute Duke University Canadian C-Spine Canadian C-Spine Rules Rules • Sensitivity of the Canadian C-spine rule ranged from 0.90 to 1.00 with negative predictive values ranging from 99 to 100%. Sensitivity = 99 • Inter-rater reliability of the Canadian C-spine rule varied from k = 0.60 between nurses and physicians to k = 0.93 among paramedics. Stiell et al. Canadian CT head rule study for patients with minor head injury: methodology for phase II (validation and Moser et al. Validity and reliability of clinical prediction rules used to screen for cervical spine injury in alert low-risk economic analysis). Ann Emerg Med. 2001;38(3):317-22. 41 patients with blunt trauma to the neck: part 2. Eur Spine J.