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EVIDENCE BASED MEDICINE - 2 > 11b – Clinical Diagnosis II > Flashcards

11b – Clinical Diagnosis II Flashcards

1
Q

What happens as the prevalence drops in terms of PPV and NPV?

A
  • NPV increases to very HIGH levels
  • PPV falls dramatically
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2
Q

What does being a member of a high risk group (high prevalence group) due to PPV of a test for that disease?

A
  • Increases PPV
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3
Q

What are the best tests to RULE-OUT disease?

A
  • Negative test with high sensitivity and NPV
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4
Q

What are the best tests to CONFIRM (Rule-in) disease?

A
  • Positive test with high specificity and PPV
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5
Q

What can you change to get a better result?

A
  • Can NOT change the risk group of the patient
  • Can use other tools
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6
Q

At what values of prevalence of a disease do diagnostic tests provide the most insight?

A
  • 40-60%
  • INTERMEDIATE
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7
Q

What happens when prevalence decreases?

A
  • Increased NPV
  • Drops after the 40% point and then drops quickly
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8
Q

What happens when prevalence increases?

A
  • Increased PPV
  • Around/between 80-90: not much changes
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9
Q

When do diagnostic tests perform the best?

A
  • When used in the ‘toss-up’ scenario
  • *pretest probability of disease is near 50% and predictive values are maximized!
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10
Q

What happens if pre-test probability is very high?

A
  • Do NOT gain much info by testing
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11
Q

What happens if pre-test probability is very low?

A
  • Probably can’t justify even doing the testing
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12
Q

How do we optimize predictive value?

A
  • Use in situation where pre-test probability of disease is around 50%
  • After using one test, apply another more specific test to positive animals
  • *use 2 test concurrently
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13
Q

What is parallel testing?

A
  • 2+ different tests are performed and interpreted simultaneously
  • *Animal considered positive if reacts positively to one OR both tests
  • Increased sensitivity and NPV
  • *more confident in negative test results
  • Patient must prove it is healthy!
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14
Q

What is serial testing?

A
  • Test conducted sequentially based on results of previous test
  • Usually use one test, then apply a more specific test to those that test positive
  • *only classified as positive IF it is positive on BOTH tests
  • Maximizes specificity and improves PPV
  • *patient must prove it has the condition
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15
Q

What is repeat testing? Negative (herd) re-testing

A
  • Modification of serial testing
  • *intermittent testing
  • Test negative animals are re-tested with the same test at REGULAR INTERVALS
  • Forms the basis of test and removal programs designed to eradicate disease
  • Improves aggregate-level sensitivity
  • Ex. Johne’s disease, Trichomoniasis, Salmonella
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16
Q

Example: How many preputial scrapings and cultures should we do to be fairly confident that the bully is truly negative for trichomoniasis?

A
  • Figure out how confident you are if the test result comes up NEGATIVE
  • *immunity does not actually last that long
  • *need to test 3 times!
    o Don’t shed consistently
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17
Q

Young, yearling bull (5% pre-test probability)

A
  • 1st and 2nd test: 99% NPV
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18
Q

Bull (40% pre-test probability)

A
  • Takes 3 tests to get 99% NPV
  • 1st test: 90% (10% chance of losing calf crop)
  • 2nd test is only taking the negative bulls
    o 98% NPV
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19
Q

Older, mature bull (90% pre-test probability)

A
  • Don’t get 99% NPV until 4 tests
  • 1st: 41%
  • *likely wouldn’t test if the pre-test probability was that high!
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20
Q

Parallel testing example (ex. Johne’s disease)

A
  • Have multiple tests that could give good answers
  • *increase sensitivity in final stages of eradication program
  • Ex. test herd with ELISA and culture
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21
Q

2 signs for heat detection in dairy cows

A
  • Mounted
  • Vulvar
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22
Q

If you are trying to rule out a disease, what do you want your sensitivity or specificity to be? (EXAM)

A
  • High sensitivity
  • High negative predictive value
  • *works best when pre-test probability of disease is LOW
  • SnNOUT
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23
Q

If you are trying to rule in a disease, what do you want your sensitivity or specificity to be? (EXAM)

A
  • High specificity
  • High PPV
  • *works best when pre-test probability of disease is HIGH
  • SpPIN
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24
Q

What is the cost of a FALSE NEGATIVE test? (ex. exotic disease (FMD)=disastrous consequences) (EXAM)

A
  • Highly sensitive tests, even at the cost of specificity
  • Avoid FALSE NEGATIVES at all costs
  • *multiple tests should be interpreted in PARALLEL
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25
Q

What is the cost of a FALSE POSTIVE test? (EXAM)

A
  • High treatment costs
  • Treatment that are potentially dangerous
  • Euthanasia of valuable animal might be possible
  • *use highly SPECIFIC tests
  • *multiple tests should be interpreted in SERIES
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26
Q

What happens when you do parallel or negative re-testing?

A
  • False negatives are DECREASED
  • Sensitivity increases
  • NPV increases
27
Q

What happens when you do serial testing?

A
  • False positives are DECREASED
  • Specificity must increase
  • PPV increases
28
Q

Choosing a cut-point

A
  • Continuous outcome for a diagnostic test (Ex. enzyme or Ig levels)
  • Distribution of test results OVERLAP
  • *Impossible to find a cut off point which PERFECTLY discriminates between 2 groups
  • FLEXIBLE
  • Intermediate zone: if in this zone=re-tested after a certain time period
29
Q

What happens if you select a low cut off value?

A
  • Get good SENSITIVITY
  • False negatives are NOT acceptable
  • False positives can be controlled by a 2nd more specific test on initial positive results
    o Consequences of false positives are NOT severe
  • Disease can be treated
    o UNTREATED cases are FATAL
30
Q

What happens if you select a high cut off value?

A
  • Get a good SPECIFICITY
  • False positive results are NOT acceptable
  • False negatives results are controlled by using a second test in parallel
  • False negatives consequences are NOT severe
  • Disease is SEVERE, but confirmation has little impact on therapy and prevention
31
Q

Lead poisoning

A
  • Accumulates in bone
  • Transferred across placental barrier
  • Excreted in urine, bile, feces and milk
  • *can not put lead in food chain
    o Some have high lead blood levels, BUT no clinical signs
32
Q

What can you use to set cut points?

A
  • Receiver operator characteristic (ROC) curve
33
Q

What is a receiver operator characteristic (ROC) curve?

A
  • True-positive rate on vertical (sensitivity)
  • False-positive rate on horizonal (1-specificity)
  • *point closet to top LEFT CORNER will maximize sensitivity and specificity
    o Should consider costs of false positives and false negatives when selecting a cut-off point
    o WANT THE LARGEST AREA UNDER THE CURVE
34
Q

ROC curve with a diagonal line

A
  • 50/50 coin flip!
35
Q

What is mass screening?

A
  • Sampling volunteers or a sample of the population to detect disease
  • Ex. Brucellosis testing
  • Ex. Bovine TB testing
36
Q

What is case finding?

A
  • Seeking an EARLY diagnosis when a client brings animal to vet for unrelated reasons
    o Routine physical exams
    o Routine fecal exams
    o Feline leukemia virus
    o Heartworm testing
    o CMT testing of quarter milk
    o Meat inspection
    o EIA serologic testing
37
Q

At what point are you trying to intervene?

A
  • Close to early diagnosis being possible
  • *before animal gets sick and clinical diagnosis!
38
Q

What tests should be used for screening tests?

A
  • Hard to estimate sensitivity
  • SPECIFICITY is most important
  • PPV is only measuring diagnostic test performance, not EFFICACY of screening
39
Q

How do you tell if a disease can be detected before routine diagnosis and it’s early detection is worth our effort?

A
  • Patient lives longer
  • Quality of life improves
  • Treatment costs decreases
  • *early diagnosis will almost always IMPROVE survival even if the therapy applied is useless
40
Q

How can you evaluate screening programs?

A
  • Randomized clinical trials
  • Randomize patients to receive screening test or not
  • *caution in interpretation of outcomes
41
Q

What are some types of biases? (EXAM)

A
  • Volunteer effect
  • Zero time shift or lead time bias
  • Length time bias
42
Q

What is the volunteer effect?

A
  • Clients that bring animals for screening tests are NOT the same as those that don’t
    o Better management
    o Improved health status
  • *more likely to LIVE LONGER
43
Q

What is zero time shift or lead time bias?

A
  • Comparing survival times after early diagnosis to survival times after conventional diagnosis
44
Q

What is the ‘zero point’ for survival time?

A
  • Time of diagnosis
45
Q

What is lead time bias?

A
  • If early diagnosis takes place before conventional diagnosis
  • *lead time is NOT taken into account
    o May be creating an extra year ‘backwards’ of disease NOT a year more of survival
46
Q

What is length time bias?

A
  • Long pre-clinical phase diseases usually have a long clinical phase
  • Short pre-clinical phase disease usually have a short clinical phase
  • *disease that are more likely to be detected by screening tests will SURVIVE LONGER THAN THOSE THAT ARE NOT
    o Going to find those with the ‘less severe’ disease
    o Miss those severe ones as they aren’t around as long!
47
Q

What are the hazards of early diagnosis?

A
  • Need to be sure of efficacy when marketing our treatment to clients
  • False positive risk: especially important if there is a debilitating treatment involved
  • Labeling
48
Q

Diagnostic panels

A
  • Each test has it’s own sensitivity and specificity
  • *probability of a false positive occurring on at least one of two tests can be calculated!
49
Q

What are the objectives of herd testing?

A
  • Determine prevalence of infected herds
  • Certify herds as disease negative for eradication or trade
  • Examine risk factors for herd level disease
50
Q

What are the differences between herd and individual testing?

A
  • Uncertainty around individual Se and Sp is AMPLIFED in HSe and HSp
  • Bias in AMPLIFIED
  • *impact of false results if generally GREATER
51
Q

A positive test on a herd basis is not a

A
  • Positive diagnosis
  • *false positives can occur in clean herds
  • Disease prevalence drops in the herd, PPV of screening PROGRESSIVELY gets worse
  • *need tests with VERY HIGH specificity when prevalence is low
52
Q

What happens to HSe and HSp when you increase the number tested?

A
  • HSe increases
  • HSp decreases
53
Q

What happens to HPPV and HNPV when you increase the number tested?

A
  • HPPV decreases
  • HNPV increases
54
Q

What happens to HSe and HSp when you increase the required reactors to be considered positive? (‘number needed to determine the herd is positive)

A
  • HSe decreases
  • HSp increases
55
Q

What happens to HPPV and HNPV when you increase the required reactors to be considered positive?

A
  • HPPV increases
  • HNVP decreases
56
Q

When are pooled samples ideal?

A
  • When within-herd prevalence is LOW
57
Q

What are the pros of pooled samples?

A
  • Decreased laboratory cost
  • Increased HSe due to increase n (sample number)
58
Q

What are the cons of pooled samples?

A
  • Risk of decreased Se due to dilution
  • Logistical challenges of mixing sample
  • If one sample is contaminated (example blood + feces are inhibitors of PCR) than it will affect all of them
59
Q

What can you do to evaluate a test if there is not gold standard?

A
  • Comparing 2 tests
  • Comparing agreement between 2 clinicians
  • Comparing agreement within clinicians (will they give the same diagnosis if given same data more than once?)
60
Q

What is the kappa statistic?

A
  • PROPORTION of agreement measured BEYOND THAT EXPECTED BY CHANCE ALONE
  • Don’t need to know the formula
61
Q

What is another option if there is no gold standard?

A
  • Index test is compared to a reference standard
    o Se and Sp obtained relative to reference test
62
Q

What are 2 latent class analysis?

A
  • Maximum likelihood estimation (MLE)
  • Bayesian
63
Q

Maximum likelihood estimation (MLE)

A
  • Independence between tests required
  • Observed data
64
Q

Bayesian

A
  • Allows for correlated tests
  • Prior information and data
  • Ex. serology for ‘historical’ exposure and culture for current exposure status

EVIDENCE BASED MEDICINE - 2 (3 decks)

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