clinical approach to the diagnosis of sars joshua p. metlay, md, phd va medical center division of...
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![Page 1: Clinical Approach to the Diagnosis of SARS Joshua P. Metlay, MD, PhD VA Medical Center Division of General Internal Medicine Center for Clinical Epidemiology](https://reader035.vdocuments.net/reader035/viewer/2022062423/56649f0e5503460f94c22e92/html5/thumbnails/1.jpg)
Clinical Approach to the Diagnosis of SARS
Joshua P. Metlay, MD, PhD
VA Medical Center
Division of General Internal Medicine
Center for Clinical Epidemiology and Biostatistics
Philadelphia, PA
CCEB
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Overview of Talk
• Clinical approach to the diagnosis of acute respiratory tract infections
• Case example: Evaluation of diagnostic tests for pneumococcal pneumonia
• Implications for the development and application of SARS diagnostic tests
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Applications of Diagnostic Testing
Physician Perspective:• Determining need
for antimicrobial Rx• Targeting
antimicrobial Rx• Risk stratification for
site of care
Public Health Perspective:• Disease surveillance• Infection control• Clinical studies
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Characteristics of Diagnostic Tests
Physician perspective:• Rapid detection• Bedside capability• Examples:
– Antigen assays– DNA amplification
Public Health perspective:• Time insensitive• Centralized testing• Examples:
– Micro cultures– Serology
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Diagnostic Test Pathogen RxAlternative Dx
0 100
Probability of Specific Pathogen:
No Test/Test Test/Treat
Determining the Optimal Use of Diagnostic Tests for Patients with Acute Respiratory Infections
X Y
Adapted from Pauker and Kassirer. NEJM. 1980
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Calculating the No Test/Test Threshold
(1-Specificity) x R((1-Specificity) x R) + (Sensitivity x B)
Where R=Risk and B=Benefit of Treatment
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Calculating the Test/Treatment Threshold
Specificity x R(Specificity x R)+((1-Sensitivity) x B)
Where R=Risk and B=Benefit of Treatment
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Diagnostic Test Pathogen RxAlternative Dx
0 100
Probability of S. pneumoniae:
No Test/Test Test/Treat
Diagnostic Test Thresholds for Patients with Suspected Pneumococcal Pneumonia
X Y
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Factors Influencing the Clinical Decision to Use a Diagnostic Test
• Pretest probability of disease
• Test costs (clinical and financial)
• Test sensitivity and specificity
• Treatment risks and benefits
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Pretest Probability
• Population based estimates
• Modified for individual patient characteristics– Presenting symptoms– Presenting signs
• Modified for temporal and geographic trends
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Estimating the probability of pneumonia in patients with acute cough illness
Diagnosis % of Total Annual # Visits (in millions)
Acute Bronchitis 40 4.2 URI 19 1.9 Sinusitis 10 1.0 Asthma 7 0.7 Pneumonia 4 0.4 Pharyngitis 2 0.2
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Pretest Probability
• Population based estimates
• Modified for individual patient characteristics– Probability of pneumonia– Probability of pneumococcal pneumonia
• Modified for temporal and geographic trends
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Identifying Pneumonia based on Signs and Symptoms
0 10 20 30 40 50 60 70 80 90 100
Revised Probability
Tachycardia
Fever
Crackles
Dullness to Percussion
Cough only with normal vital signs
Cough, Fever, Tachycardia, and Crackles
Ex
am
ina
tio
n F
ind
ing
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Identifying the Pathogen based on History and Physical Exam
• Once the diagnosis of pneumonia is established, the H&P is of little value in targeting antimicrobial therapy
• Both IDSA and ATS guidelines advise against targeted therapy based on H&P
• Clinical associations of signs and symptoms are rarely sufficient to guide therapy
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Pretest Probability of Specific Pathogens in Patients with ARIs
• 30 million cough visits per year in the US
• 5% of patients with ARIs will have CAP
• 30% - 50% of patients with CAP have S. pneumoniae
• 1% of cough patients have pneumococcal pneumonia
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Factors Influencing the Clinical Decision to Use a Diagnostic Test
• Pretest probability of disease
• Test costs (clinical and financial)
• Test sensitivity and specificity
• Treatment risks and benefits
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Accuracy of Rapid Diagnostic Tests
Pathogen Assay Sensitivity Specificity
S. pneumoniae Urine antigen
86% 94%
S. pneumoniae Gram stain 60% 85%
Influenza Sputum antigen
85% 95%
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Estimating the Risks and Benefits of Treatment
• For most antimicrobial drugs, placebo controlled data on efficacy is missing
• For most antimicrobial drugs, premarketing information on risk is limited
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Mortality Assessment in PneumoniaMortality Assessment in Pneumonia
0
10
20
30
40
50
60
70
Inpatientsand
Outpatients
InpatientsOnly
BacteremicPatients
ICUPatients
Pre-antibiotics
Antibiotics
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Testing thresholds for Pneumococcal Detection using Gram Stain
• Treatment benefit 10-15%
• Treatment risk 1%
• No Test/Test threshold: 2%
• Test/Treat threshold: 14%
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Diagnostic Test Pathogen RxAlternative Dx
0 100
Probability of S. pneumoniae:
No Test/Test Test/Treat
Diagnostic Test Thresholds for Patients with Suspected Pneumococcal Pneumonia
2 14
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Lessons learned from the pneumococcal pneumonia example
• Until the pretest probability is > 1%, diagnostic testing is unlikely to be indicated in routine practice
• Unless the diagnostic test has excellent operating characteristics, the testing window will be narrow.
• Effective treatments for high risk illnesses have low thresholds unless treatment risk is high.
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Identifying the Optimal Clinical Settings for a Diagnostic Test
PreTest Probability
Po
stT
es
t P
rob
ab
ility
0 100
01
00
+ Result
- Result
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PCR/EIA InterventionAlternative Dx
0 100
Probability of SARS:
No Test/Test Test/Treat
Determining the Optimal Use of Diagnostic Tests for Patients with Suspected SARS
X Y
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SARS Case Definition: A potential population for diagnostic testing
• Severe respiratory illness:– Cough illness with fever– Pneumonia/ARDS on CXR
• Exposure history– Travel– Close contact
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SARS Diagnosis in Primary Care
• We must emphasize importance of local surveillance and disease reporting.
• Absent local cases, diagnostic testing will not be supported without epidemiological exposures
• Given competing respiratory pathogens, it is unlikely that signs and symptoms will further modify pretest probability