... group= needle thoracentesis or chest tube drainage ..

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Can We Simplify the Management of Complicated
Pneumonia in Children?
Samir S. Shah, MD, MSCE
Divisions of Infectious Diseases and General
Pediatrics The Childrens Hospital of
Philadelphia Departments of Pediatrics and
Biostatistics and Epidemiology University of
Pennsylvania School of Medicine
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Objectives

• Explore the use of administrative data to clarify
  the
• changing epidemiology of pneumonia and
  complicated pneumonia
• role of operative vs. non-operative interventions
  in the management of children with complicated
  pneumonia

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Background Pneumonia

• Community-acquired pneumonia (CAP) is a common
  serious bacterial infection in children
• gt600,000 hospitalizations in the U.S. each year
• Up to one-third of children hospitalized with CAP
  have a pleural effusion (complicated pneumonia)

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What do we mean by the term complicated pneumonia?
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Case

• 3-year-old boy with cough and fever
• Evaluated 2 weeks ago
• Diagnosed with asthma and clinical pneumonia
• Treated with albuterol and amoxicillin
• Returns with continued cough and fevers to 39.2C

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Case Chest X-ray
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Case Chest CT
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Changing Epidemiology of Invasive Pneumococcal
Disease

• Licensure of a 7-valent pneumococcal conjugate
  vaccine in 2000
• Decrease in invasive pneumococcal infections
• Subsequent increase in the rate of infections
  caused by
• penicillin-resistant S. pneumoniae
• serotypes not included in the current vaccine
• Increasing prevalence of infections caused by
  methicillin-resistant S. aureus

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National Hospital Discharges (all ages)
Bacteremia of any etiology ? Pneumococcal
bacteremia
Shah SS, et al. Clin Infect Dis 200642e1-5
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Pneumococcal Bacteremia By Serotype Category
?vaccine serotype vaccine-related
serotype ?non-vaccine serotype
Steenhoff A, Shah SS, et al. Clin Infect Dis
200642907-914
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Invasive Disease Caused by Penicillin-Susceptible
and Non-susceptible Pneumococci (ages lt2)
Kyaw MH, et al N Engl J Med 20063541455-1463
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What does this have to do with pneumonia?
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Have rates of pneumonia or complicated pneumonia
changed over time?
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Datasource National Hospital Discharge Survey
(NHDS)

• Created by the National Center for Health
  Statistics
• Includes only non-federal US hospitals
• All hospitals with gt1,000 beds
• Representative sample of others based on
  location, size specialty
• Includes 500 hospitals 250,000 discharges each
  year
• Weighting of records by hospital size/region
  allows for calculation of nationally
  representative estimates

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Eligibility

• Inclusion
• Ages 1-18 years
• Discharged 1993-2006
• Diagnosis of community-acquired pneumonia
• Exclusion
• Age lt1 to eliminate bronchiolitis
• Known underlying predisposition to pneumonia
  (e.g., malignancy, HIV, cystic fibrosis)

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Definitions of Pneumonia

• Community-acquired pneumonia (CAP)
• Pneumonia as 1diagnosis OR
• Pneumonia-related symptom as 1 diagnosis (e.g.,
  cough) pneumonia as 2 diagnosis OR
• Empyema or pleurisy as 1 diagnosis and pneumonia
  as 2 diagnosis
• Sensitivity of 89 and specificity of 80
  compared with medical record review

Whittle J, et al. Am J Med Qual 199712187-193
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Definitions of Complications
Abbreviations HUS, hemolytic-uremic syndrome
SIRS, systemic inflammatory response syndrome
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Challenges

• Accuracy of ICD-9 codes to identify conditions of
  interest
• Does our definition exclude the sickest patients?
• Change in ICD-9 codes over time (e.g., addition
  of 4th or 5th digits)
• Review annual ICD-9 addendum
• Complex survey statistics (i.e., sample weights)
  to calculate national estimates
• May limit accuracy of data for subpopulations
• Insufficient data in publicly available dataset
  to calculate standard errors for some
  subpopulations

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Regional Variation in Pediatric CAP
Hospitalizations (Pennsylvania)
Gorton CP, et al. Pediatrics 2006117176-180
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The epidemiology of pneumonia and complicated
pneumonia is complex and changing
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Evolution of Empyema

• Exudative
• Neutrophil migration into pleural space
• Fibrinopurulent
• Fibrin deposition
• Loculations impair lung expansion
• Organizing
• Fibroblast formation produces an inelastic
  membrane or fibrinous peel

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Management of Empyema

• Radiologic assessment
• CXR (upright decubitus)
• Ultrasound
• CT scan

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Management of Empyema

• Surgical options
• Thoracentesis (needle aspiration)
• Tube thoracostomy ( fibrinolysis)
• Video-assisted thoracoscopy
• Thoracotomy

Require post-procedure thoracostomy tube
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Management of Empyema

• No consensus on optimal initial drainage strategy
• Technique?
• Timing?

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Why use administrative data to study complicated
pneumonia?

• Sonnappa et al.
• Kurt et al.
• Avansino et al.
• Li et al.
• Shah et al.

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Sonnappa et al.

• 1st randomized study of VATS vs. thoracostomy
  tube drainage
• 60 patients enrolled from January 2002 to
  February 2005
• Groups similar in
• Age Sex
• Preadmission symptoms
• Effusion stage
• Causative bacteria (mostly S. pneumoniae)

Sonnappa S. Am J Respir Crit Care Med
20006174221-227
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Sonnappa et al.
Kurt BA, et al. Pediatrics 2006118e547-e553
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Kurt et al.

• 1st randomized study of VATS vs. thoracostomy
  tube drainage in U.S.
• 18 patients enrolled from November 2003-May 2005
• Groups similar in
• Age sex
• Preadmission symptoms antibiotics
• Effusion size
• Presence of loculation

Kurt BA, et al. Pediatrics 2006118e547-e553
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Kurt et al.
Kurt BA, et al. Pediatrics 2006118e547-e553
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Key Differences

• Differences
• Kurt et al. used substantially larger chest tubes
  (16-24 Fr vs. 8-10 Fr)
• Sonnappa et al. used more aggressive fibrinolysis
• LOS presented as mean (Kurt) or median (Sonnappa)
  
• Limitations
• Single centers
• Few patients

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Can a meta-analysis more address this issue more
definitively?
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Avansino et al.

• Systematic review of therapy for empyema (outcome
  data from 3781 children)

Avansino JR. Pediatrics 20051151652-1659
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Avansino et al.

• In the pooled analysis, primary operative therapy
  reduced
• LOS by 45 (199 patients, 4 studies)
• Repeat procedures by 90 (492 patients, 9
  studies)
• Results biased towards favoring operative therapy
• Non-operative group needle thoracentesis or
  chest tube drainage

Avansino JR, et al. Pediatrics 20051151652-9
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Avansino et al. - Limitations

• Poor study quality
• No randomized studies performed at time of review
• Inclusion only of small (all lt70 patients)
  observational studies with heterogeneous study
  designs
• Primary outcome of interest therapeutic failure
  not chosen a priori
• Failure to adjust for confounding variables
• Timing of intervention
• Chemical fibrinolysis
• Empiric antibiotic therapy

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Where do things stand?

• Randomized studies
• Small single center
• Multicenter studies difficult to conduct because
  prevailing personal institutional dogmas
• Pooled analyses
• Few high quality studies
• Administrative data
• Seriously?

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Li et al.

• 2003 Kids Inpatient Database
• Inclusions
• Age 0-18 years
• ICD-9 codes for empyema (510.0 510.9)
• Exclusions
• Co-morbid illness
• Transfer from another hospital

Li ST. Arch Pediatr Adolesc Med 200816244-48
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Li et al.

• 1173 patients
• Primary operative management (POM) vs.
  Non-operative management (NM)
• POM decortication within 2 days of admission
• NM everything else, including decortication 3 or
  more days after admission

Li ST. Arch Pediatr Adolesc Med 200816244-48
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Li et al.
Li ST. Arch Pediatr Adolesc Med 200816244-48
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Li et al. - Limitations

• ICD-9 codes incomplete
• Other codes that suggest effusion were not
  included
• 511.1 effusion, with mention of bacterial cause
  other than tuberculosis
• 513.0 abscess of lung
• Diagnosis of pneumonia not required
• Potential for inclusion of effusions not related
  to pneumonia (e.g., post-op)
• NM group heterogeneous
• For example, those drained early by chest tube
  may be different than those drained late by VATS
  and those never drained

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Shah et al.

• Pediatric Health Information System (PHIS)
• Inpatient data from 27 not-for-profit, tertiary
  care, U.S. childrens hospitals
• Inclusions
• Age 12 months to 18 years of age
• Discharged between 2001-2005
• ICD-9 codes 510.0, 510,9, 511.1, or 513.0 as
  primary diagnosis plus pneumonia (480-486)
• Pleural fluid drainage within 48 h of
  hospitalization
• Exclusion
• Co-morbid illness

Shah SS. Arch Pediatr Adolesc Med 2008162675-681
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Shah et al. - PHIS Study Population
Shah SS. Arch Pediatr Adolesc Med
2008162675-681
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Shah et al. - Initial Procedure
Shah SS. Arch Pediatr Adolesc Med
2008162675-681
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Shah et al. - Procedure Variation by Hospital
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Shah et al. - Variation in LOS by Hospital
7 of patients had a LOS gt28 days
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Shah et al. - Change in LOS
Shah SS. Arch Pediatr Adolesc Med 2008162675-681
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Shah et al. - Repeat Procedure

• Repeat procedure
• 298 (31) overall required a repeat procedure
• Percent requiring repeat procedure
• 34 with primary chest tube
• 8 with primary VATS
• 24 with primary thoracotomy

Shah SS. Arch Pediatr Adolesc Med
2008162675-681
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Shah et al. - Variation in Repeat Procedures by
Hospital
R E P E A T P R O C E D U R E
Hospital
Shah SS. Arch Pediatr Adolesc Med
2008162675-681
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Shah et al. - Repeat Procedure
Shah SS. Arch Pediatr Adolesc Med 2008162675-681
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Shah et al. - Summary

• Among the subset of children with complicated
  pneumonia who undergo early pleural drainage,
  VATS is associated with
• 20 shorter LOS
• Fewer repeat procedural interventions

Shah SS. Arch Pediatr Adolesc Med
2008162675-681
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But which strategy is more cost-effective?
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Background

• VATS is more expensive than primary chest tube
  placement in terms of physician and procedural
  costs
• Are these additional costs are offset by
  associated reductions in length of stay and
  repeat procedures?
• A recent decision analysis concluded that chest
  tube with fibrinolysis was the preferred strategy

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Shah et al.

• Pediatric Health Information System (PHIS)
• Inpatient data from 27 not-for-profit, tertiary
  care, U.S. childrens hospitals
• Inclusions
• Age 12 months to 18 years of age
• Discharged between 2001-2005
• ICD-9 codes 510.0, 510,9, 511.1, or 513.0 as
  primary diagnosis plus pneumonia (480-486)
• Pleural fluid drainage within 48 h of
  hospitalization
• Exclusion
• Co-morbid illness

Shah SS. Arch Pediatr Adolesc Med 2008162675-681
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Shah et al. Resource Utilization (Unadjusted
data)
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Analytic approaches

• Children undergoing VATS vs. chest tube likely
  differ in many respects
• How can one handle confounding in an
  observational study?
• Restriction
• Matching
• Adjustment in a regression model
• Propensity scores

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Propensity Score

• Represents the probability of treatment
• Estimated using logistic regression
• Outcome Treatment (i.e., VATS vs. chest tube)
• Exposures Measured characteristics of the
  study patients
• In theory, patients with similar propensity
  scores should have a similar distribution of
  measured covariates

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1.) Indications for Propensity Scores

• Theoretical advantages
• Confounding by indication may cause treatment
  groups to differ dramatically
• Comparison of propensity scores in exposed and
  unexposed subjects can identify these areas of
  non-overlap

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2.) Indications for Propensity Scores

• Useful for matching subjects
• Matching on propensity score outperforms other
  matching strategies with many covariates
• Balance achieved will mimic randomization (for
  measured variables)

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3.) Indications for Propensity Scores

• Improved estimation with few outcomes
• Reliable estimates not possible with
  multivariable modeling when there are many
  covariates and few outcomes

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4.) Indications for Propensity Scores

• Propensity score by treatment interactions
• Can address possibility that the effectiveness of
  a drug may vary according to the strength of the
  indication for its use

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5.) Indications for Propensity Scores

• Propensity score calibration to correct for
  measurement errors
• A specific (and complicated) method that allows
  one to account for multiple unobserved
  confounders
• Propensity score 1st created in a subgroup of
  patients that have detailed information available
• This gold-standard propensity score is used to
  correct the main study effect of the drug on
  outcome

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Rationale for Analytic Approach

• 1 Theoretical advantages
• Confounding by indication may cause treatment
  groups to differ dramatically
• Comparison of propensity scores in exposed and
  unexposed subjects can identify these areas of
  non-overlap
• 2 Useful for matching subjects
• Matching on propensity score outperforms other
  matching strategies with many covariates
• Balance achieved will mimic randomization (for
  measured variables)

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Approaches to Propensity Score Analysis

• Restriction
• Restrict analysis to participants with sufficient
  overlap in scores
• Matching
• A science unto itself
• Stratified analysis
• Stratify analysis by score categories (e.g.,
  quintiles)
• Weighting
• Case weightscore control weightinverse of 1
  minus their score then apply sample weights in
  regression model
• Regression
• Treat propensity score as model covariate with
  treatment

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Approaches to Propensity Score Analysis

• All methods should produce similar results
• What if there are differences?
• Figure out why
• Present the best analysis (i.e., the one
  perceived to be most accurate)

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Practical Considerations

• Determine area under the ROC curve for propensity
  score
• Rough rule of thumb, perhaps 0.7-0.9 is ok
• Very high values suggest non-overlap of
  distribution of propensity scores between
  subjects
• Visually compare propensity score distributions

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Distribution of Propensity Scores

• AUC 0.70

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Distribution of Propensity Scores

• Poor overlap of propensity scores between the 2
  groups at the extreme quintiles
• Restriction
• Matching
• Stratified analysis
• Weighting
• Regression

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Matched vs. Unmatched Example
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Total Hospital Charges VATS vs. Chest Tube
Multivariable model included age, race, sex,
season, asthma, steroids, fibrinolysis, and
empiric vancomycin receipt. Propensity score
created using all of these variables. 48 VATS
patients matched with 7 patients, 1 matched with
5, 1 matched with 4
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Propensity Analysis

• Bottom line VATS does not cost more than chest
  tube placement despite higher physician charges
  and additional operating room charges

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Can We Simplify the Management of Complicated
Pneumonia in Children?
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What we think we know

• Early intervention reduces duration of
  hospitalization
• Compared with chest tube placement, VATS
• Modestly decreases LOS
• Substantially decreases repeat procedures
• Does not cost more
• Chemical fibrinolysis does not affect key
  outcomes

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What we dont know

• Short-term outcomes
• Affect of various procedures on frequency of
  local, systemic and metastatic complications
• Long-term outcomes
• Correlation with short-term outcomes
• Impact of Impact of early vs. late intervention
• Impact of early VATS vs. tube thoracostomy
• Impact of changing epidemiology on short- and
  long-term outcomes

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Thank You