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Diagnostic Tests. How to crunch the numbers for clinical practice David Nguyen PGY-1 Anaesthesiology University of Calgary. This requires some math, but it’s not too bad. Overview. Diagnostic process Basics Epistats 2 x 2 table

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## Diagnostic Tests

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**Diagnostic Tests**How to crunch the numbers for clinical practice David Nguyen PGY-1 Anaesthesiology University of Calgary**Overview**• Diagnostic process • Basics Epistats • 2 x 2 table • Definitions - Sensitivity, specificity, PPV, NPV, prevalence • Interpreting Diagnostic Tests • SPIN SNOUT • Likelihood ratios • Going beyond sensitivity and specificity**Cases**• Strep throat • Iron deficiency Anemia**2 x 2 tables**• Let’s say we are performing a diagnostic test for a disease on a given population. • The test has dichotomous results (positive or negative) • A proportion of this population has the disease**Definitions**• Stating it mathematically: • Sensitivity = the probability of obtaining a positive test, GIVEN that a person is diseased • Specificity = the probability of obtaining a negative test, GIVEN that a person is not diseased**The Validity of Screening Tests**• The validity of a test refers to how well it can distinguish diseased people from non-diseased people. • Measures of validity are expressed quantitatively: sensitivity (SN) and specificity (SP). • As SN and SP approaches 100% the validity of the test improves the better the test performs on population level studies which probably means the test will be more useful clinically**Other very important terminology**• Positive predictive value (PPV) = the probability of being diseased GIVEN that a test is positive • Negative predictive value (NPV) = the probability of being non-diseased GIVEN that a test is negative**What’s the difference between SN/SP and PPV/NPV**• Sensitivity and specificity are inherent characteristics of a diagnostic test • PPV and NPV are not inherent characteristics of a diagnostic test. • PPV and NPV depends on sensitivity, specificity and prevalence of disease (aka pre-test probability).**Why do we order diagnostic tests?**• To help rule in a disease • To help rule out a disease *Others will argue that the point of ordering diagnostic test is to improve patient health. Ideally, your test changes your management plan.**SPIN**SNOUT**SPINSpecific, Positive, rule IN**SNOUT Sensitive, Negative, Rule OUT**Probabilities**• Pre-test probability = defined as the probability a person has a disease prior to performing the diagnostic test (often synonymous to prevalence of disease) • Post-test probability = defined as the probability a person has a disease after performing the diagnostic test**Step 1: Estimating Pre-test probability**• Estimated through • History • Physical examination • Investigations • Clinical prediction tools • Others – knowing the prevalence of disease, clinical experience**Step 1: Estimate pre-test probability**Step 2: Convert pre-test probability to pre-test odds: Step 3: Calculate likelihood ratios from SN and SP Step 4: Convert pre-test odds to post-test odds: Step 5: Convert post-test odds to post-test probability:**General rule of thumb**Are strong! These can often lead to conclusive changes from pretest to posttest probability. LR = 1 is useless.**Practice Case #1**• 15 year old male presents with a 3 day history of sudden onset sore throat and fever. • No cough, no rhinorrhea, no conjunctivitis. • Physical examination = 37.9C, tender anterior cervical lymphadenopathy, swollen tonsils with exudate, no hepatosplenomegaly, no rashes**Group A Strep Pharyngitis is high on your differential.**• You performed a swab throat and culture. Several days later, the test comes back positive. • A literature search shows one study that found throat swabs have an 85% sensitivity and 95% specificity. • How do you interpret this?**Step 1 - 5**Step 1 – pre-test probability Step 2 – pre-test odds Step 3– calculate LR Step 4 – post-test odds Step 5 – post-test probability**Practice case #1: Step 1 – estimating the pre-test**probability • You decide to use the Strep Pharyngitis Score (a clinical prediction tool!) to estimate the pre-test probability • Pre-test probability = 35% McIsaac, Warren J., et al. "A clinical score to reduce unnecessary antibiotic use in patients with sore throat." Canadian Medical Association Journal 158.1 (1998): 75-83.**Step 1 - 5**Step 1 – pre-test probability Step 2 – pre-test odds Step 3– calculate LR Step 4 – post-test odds Step 5 – post-test probability 35%**Step 1 - 5**Step 1 – pre-test probability Step 2 – pre-test odds Step 3– calculate LR Step 4 – post-test odds Step 5 – post-test probability 35%**Step 1 - 5**Step 1 – pre-test probability Step 2 – pre-test odds Step 3– calculate LR Step 4 – post-test odds Step 5 – post-test probability 35%**Step 1 - 5**Step 1 – pre-test probability Step 2 – pre-test odds Step 3– calculate LR Step 4 – post-test odds Step 5 – post-test probability 35%**Step 1 - 5**Step 1 – pre-test probability Step 2 – pre-test odds Step 3– calculate LR Step 4 – post-test odds Step 5 – post-test probability 35%**Practice #2**• Let’s suppose another patient comes in complaining of pharyngitis • You determine their pre-test probability is 1% based on a pharyngitis score of 1 • The guideline does not recommend throat swabs for this prevalence. • What if you decide to swab anyways? What would be their post-test probability?**Likelihood ratio nomogram**Post-test probability if positive = 14.7%**Practice #3**• 2 year old boy presents to GP office for pallor • Active, no fatigue, no change in activity or sleep. No blood, black, tar in stool. • Picky eater – little meats and vegetables. Drinks mostly milk (8 bottles per day). • Physical: T 37, BP 90/50, P 145, RR 16, Height 85.5 cm (50th %ile), Weight 13.2 kg (75th %ile). Appears pale, active toddler and tearing. HEENT: dental caries. Resp: normal. CVS: Mild tachycardia, II/VI syst ejection murmur heard best over the upper left sternal border. Abdomen normal. Rectal: Dark brown, soft stool, negative for occult blood. http://www.hawaii.edu/medicine/pediatrics/pedtext/s11c01.html**CBC = 6.2 g/dl (anemic)**• Serum ferritin was ordered. Knowing that the cutoff for a positive test is < 12, how will you interpret the results if the serum ferritin comes back: • Serum ferritin = 5 • Serum ferritin = 13 • Serum ferritin = 101**You estimate the pre-test probability of this child’s**anemia is due to iron deficiency anemia at 50%. Baker, Robert D., and Frank R. Greer. "Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0–3 years of age)." Pediatrics 126.5 (2010): 1040-1050.**Diagnostic Tools for Iron-Deficiency Anemia**Data adapted and modified for purposes of this presentation: Guyatt, Gordon H., et al. "Laboratory diagnosis of iron-deficiency anemia." Journal of general internal medicine 7.2 (1992): 145-153.**Diagnostic Tools for Iron-Deficiency Anemia**Guyatt, Gordon H., et al. "Laboratory diagnosis of iron-deficiency anemia." Journal of general internal medicine 7.2 (1992): 145-153.**Back to our question**• CBC = 6.2 g/dl (anemic) • Serum ferritin was ordered. Knowing that the sensitivity = 59% and specificity = 99% and the cutoff for a positive test is < 12, how will you interpret the results if the serum ferritin comes back: • Serum ferritin = 5 • Serum ferritin = 13 • Serum ferritin = 101**Step 1 - 5**Step 1 – pre-test probability Step 2 – pre-test odds Step 3– calculate LR Step 4 – post-test odds Step 5 – post-test probability 40% 0.67 LR(+) = 59 LR( - ) = 0.41 Post-test odds (< 12) = 39.3 Post-test odds ( 12) = 0.41 Post-test probability (pos, <12) = 98% Post-test probability (neg, 12) = 22%**Calculating Post-test probability from stratified likelihood**ratios 98% for positive test (<12) or 22% for negative test (12)

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