TOP 10 PEM Studies

1
TOP 10 PEM Studies

• Antonia Stang MD, MBA
• Division of Emergency Medicine
• Alberta Childrens Hospital

2
Disclosure

• I do not have an affiliation (financial or
  otherwise) with any commercial organization that
  may have a direct or indirect connection to the
  content of my presentation.

3
Objectives

• After this session participants will be able to
• Briefly outline an approach to translating
  evidence based medicine into clinical practice
• Categorize the quality of medical evidence
• Discuss some of the latest evidence on the
  diagnosis and treatment of pediatric patients
  relevant for Emergency Physicians

4
Search Strategy

• Relevance to emergency physicians treating
  pediatric patients
• Methodological quality
• Potential to impact practice

5
The Quality of Medical Evidence
AAP Clinical Practice Guideline Diagnosis and
Management of Bronchiolitis. Pediatrics 2006
118( 4) 1774-1793.
6
Journals

• Pediatrics
• Pediatrics
• J Pediatr
• Arch Pediat Adol Med
• Pediatr Infect Dis J
• Arch Dis Child
• Surgery
• Ann Surg
• Surgery
• Medicine
• New Engl J Med
• Lancet
• JAMA
• Can Med Assoc J

• Emergency Medicine
• Ann Emerg Med
• Resuscitation
• Acad Emerg Med
• Injury
• Am J Emerg Med
• Emerg Med J
• Emerg Med Clin N Am
• Pediatr Emerg Care
• CJEM

7
Framework

• Ask a pertinent and answerable clinical question
• Track down articles
• Three basic questions
• Are the results of the study valid?
• What are the results?
• Will the results help me in caring for my
  patients?

• Oxman AD, Sackett DL, Guyatt GH. How to Get
  Started. JAMA. 1993270(17)2093-2095.

8
Clinical Question 1

• Would nebulized epinephrine and/or oral
  corticosteroids prevent hospital admission in a
  10 month old infant with bronchiolitis?

9
Epinephrine and Dexamethasone in Children with
Bronchiolitis

• Plint A et al. N Engl J Med 2009360(20)
  2079-2089.

10
Objective and Methods

• Objective To determine whether treatment with
  nebulized epinephrine, a short course of oral
  dexamethasone, or both resulted in a clinically
  important decrease in hospital admissions among
  infants with bronchiolitis who were seen in the
  ED
• Methods Multi-center, randomized, double-blind,
  placebo-controlled, clinical trial with a
  factorial design
• Primary outcome hospital admission up to 7 days
  after enrollment

Plint A et al. N Engl J Med 2009360 2079-2089
11
Results

• 800 patients enrolled

Plint A et al. N Engl J Med 2009360 2079-2089
12
Frequency and Relative Risk of Hospital Admission
Frequency and Relative Risk of Hospital Admission
on the Day of the Initial Emergency Department
Visit, by Day 7, and by Day 22
Plint A et al. N Engl J Med 20093602079-2089
Plint A et al. N Engl J Med 2009360 2079-2089
13
Cumulative Admissions during the First 7 Days
after the Initial Emergency Department Visit
Plint A et al. N Engl J Med 2009360 2079-2089
14
Conclusions

• Among infants with bronchiolitis treated in the
  emergency department, combined therapy with
  dexamethasone and epinephrine may significantly
  reduce hospital admissions
• Confirmation by a study powered specifically to
  compare combined epinephrine and dexamethasone
  therapy with placebo is needed

Plint A et al. N Engl J Med 2009360 2079-2089
15
Clinical Question 2

• Would oral corticosteroids shorten the duration
  of hospitalization in a 2 year old child with
  acute viral induced wheezing?

16
Oral Prednisolone for Preschool Children with
Acute Virus-Induced Wheezing

• Panickar, J et al. N Engl J Med
  2009360(4)329-338.

17
Objective and Methods

• Objective to assess the efficacy of a short
  course of therapy with oral prednisolone in
  children presenting to a hospital with virus
  induced wheezing
• Methods Multi-centre, randomized, double-blind,
  placebo controlled trial
• Primary outcome duration of hospitalization

Panickar J et al. N Engl J Med 2009360329-338
18
Results

• 700 patients randomized (343 prednisolone, 344
  placebo)
• Duration of hospitalization (median)
• Prednisolone 13.9 hours
• Placebo 11.0 hours
• Difference -1.9 (95 CI -8.7 to 2.4)
• No difference for secondary outcomes or number of
  adverse events

Panickar J et al. N Engl J Med 2009360329-338
19
Conclusions

• In preschool children with mild-to-moderate
  wheezing associated with a viral infection, oral
  prednisolone was not superior to placebo
• Results suggest that oral prednisolone should not
  be given to pre-school children presenting to the
  hospital with acute, mild-to-moderate
  virus-induced wheezing

Panickar J et al. N Engl J Med 2009360329-338
20
Conflicting Results?

• Differences in study population
• Age
• Infants 6 weeks -12 months vs. children 10 to 60
  months of age
• Etiologic heterogeneity
• Bronchiolitis first episode of wheezing
• Episodic (viral) wheeze
• Multiple trigger wheeze
• Severity of disease
• Mild disease (PRAM 4)
• Moderate disease (RDAI 8)
• Synergism between corticosteroids and
  beta-agonists
• Dose
• 1mg/kg then .6mg/kg dexamethasone
• Prednisolone 10mg 10 -24 months, 20 mg for older
  children

21
Clinical Question 3

• In an 8 year old child with functional
  constipation what dose of polyethylene glycol
  (PEG) 3350 (Miralax) should be started to
  increase the frequency of BMs?

22
PEG 3350 in the Treatment of Childhood
Constipation A Multicenter, Double-Blinded,
Placebo-Controlled Trial

• Nurko, S. J Pediatr 2008153254-261.

23
Objective and Methods

• Objective
• to establish the efficacy and best starting dose
  of polyethylene glycol (PEG) 3350 in the short
  term treatment of children with functional
  constipation
• Methods
• Prospective, randomized, multi-center,
  double-blinded, placebo controlled dose ranging
  study
• Placebo, 0.2 g/kg per day, 0.4 g/kg, 0.8 g/kg
• 1 week run in, 2 weeks of treatment
• Primary outcome Proportion of patients who
  responded to treatment ( 3 BM during second week
  of treatment)
• All received behavior modification

Nurko, S. J Pediatr 2008153254-261
24
Results
Bowl movement frequency before and after
administration of PEG 3350
Nurko, S. J Pediatr 2008153254-261
25
Conclusions

• This study confirms the efficacy and safety of
  PEG 3350 for the short term treatment of children
  with functional constipation
• Recommend a starting dose of 0.4 g/kg/day
• The effect of behavior modification is significant

Nurko, S. J Pediatr 2008153254-261
26
Clinical Question 4

• Would Lansoprazole (PPI) decrease the number of
  crying episodes in a 4 month old infant with
  symptoms of Gastroesophageal Reflux Disease?

27
Multicenter, Double-Blind, Randomized,
Placebo-Controlled Trial Assessing the Efficacy
and Safety of Proton Pump Inhibitor Lansoprazole
in Infants with Symptoms of Gastroesophageal
Reflux Disease

• Orenstein SR et al. J Pediatr 2009154514-520.

28
Objective

• Objective
• To assess the efficacy and safety of lansoprazole
  in treating infants with symptoms attributed to
  GERD that have persisted despite a 1 week
  course of nonpharmacologic management

Orenstein SR et al. J Pediatr 2009154514-520
29
Methods

• Phase 3, multicenter, randomized, double-blind,
  placebo-controlled study
• 3 periods pretreatment (1-2 weeks before
  randomization), treatment (max 4 weeks), post
  treatment
• 0.2 to 0.3 mg/kg/day for infants 10 weeks, 1.0
  to 1.5 mg/kg/day gt 10 weeks vs. placebo
• Primary outcome daily diary documented number
  and duration of crying episodes during or 1
  hour after feeding

Orenstein SR et al. J Pediatr 2009154514-520
30
Results

• Responder rate (N )
• Lansoprazole 44 (54)
• Placebo 44 (54)
• No difference in individual symptoms or global
  severity assessment
• Serious adverse events (N )
• Lansoprazole 10 (12)
• Placebo 2 (2)
• P-value .032

Orenstein SR et al. J Pediatr 2009154514-520
31
Conclusion

• This study found no difference in efficacy
  between lansoprazole and placebo in treating
  infants with symptomatic GERD
• SAEs, particularly lower respiratory tract
  infections, occurred more frequently with
  double-blind lansoprazole than with placebo

Orenstein SR et al. J Pediatr 2009154514-520
32
Clinical Question 5

• Would IV ondansetron reduce vomiting associated
  with IV Ketamine in an 8 year old male undergoing
  sedation in the ED?

33
Effect of Ondansetron on the Incidence of
Vomiting Associated With Ketamine Sedation in
Children A Double-Blind, Randomized,
Placebo-Controlled Trial

• Lanston W et al. Ann Emerg Med 200852(1)30-34.

34
Objective

• To determine whether vomiting associated with
  intravenous (IV) ketamine may be reduced or
  eliminated by the addition of prophylactic
  ondansetron
• Study design randomized, double blind, placebo
  controlled trial
• Primary outcomes vomiting in the ED and after
  discharge
• Secondary outcomes length of ED stay, parent or
  guardian satisfaction with the sedation

Lanston W et al. Ann Emerg Med 200852(1)30-34
35
Results

• No significant difference in ED length of stay or
  parental or guardian satisfaction with sedation

Lanston W et al. Ann Emerg Med 200852(1)30-34
36
Conclusion

• IV ondansetron significantly reduces the
  incidence of vomiting associated with IV ketamine
  procedural sedation in children
• Sites that experience a higher rate of vomiting
  may consider pretreatment with ondansetron,
  especially for children aged 5 years and older

Lanston W et al. Ann Emerg Med 200852(1)30-34
37
Clinical Question 6

• Would procalcitonin help in identifying serious
  bacterial infection in a 2 month old infant with
  fever without a source?

38
Procalcitonin in Young Febrile Infants for the
Detection of Serious Bacterial Infections

• Maniaci V et al. Pediatrics 2008122701-710.

39
Objectives

• To study the test performance of procalcitonin
  for indentifying serious bacterial infections in
  febrile infants 90 days of age without an
  identifiable bacterial source
• To determine an optimal cutoff value to identify
  infants at low risk for serious bacterial
  infection

Maniaci V et al. Pediatrics 2008122701-710
40
Methods

• Prospective cohort study
• Eligible infants age 90 days and measured
  temperature 38 seen in an urban, academic,
  pediatric hospital
• Outcome
• Definite SBI
• Possible SBI
• No SBI

Maniaci V et al. Pediatrics 2008122701-710
41
Results

• Definite SBI (N 30)
• 4 bacteremia, 2 bacteremia/UTI, 24 UTI
• Procalcitonin level 2.21 /- 3.89
• Definite and Possible SBI (N42)
• 7 UTI, 5 bacterial pneumonia
• Procalcitonin level 2.48 /- 4.59
• No SBI (N192)
• Procalcitonin level 0.38 /- 1.04

Maniaci V et al. Pediatrics 2008122701-710
42
Results

• A cutoff value of 0.12 ng/ml
• sensitivity of 95.2
• specificity of 25.5
• negative predictive value of 96.1
• negative likelihood ratio of 0.19

Maniaci V et al. Pediatrics 2008122701-710
43
Post-test probability
44
Conclusion

• Procalcitonin has favorable test characteristics
  for detecting serious bacterial infections in
  young febrile infants
• Procalcitonin measurements performed well in
  detecting the most serious occult infections
• The future utility of procalcitonin likely
  depends on its combination with other clinical
  data

Maniaci V et al. Pediatrics 2008122701-710
45
Clinical Question 7

• Will Acetaminophen use for fever in a 6 month old
  infant increase the risk of asthma symptoms when
  aged 6-7 years old?

46
Association Between Paracetamol Use in Infancy
and Childhood, and risk of asthma,
rhinoconjunctivitis, and eczema in children aged
6-7 years analysis from Phase Three of the ISAAC
Programme

• Beasley R et al. Lancet 20083721039-1048.

47
Objective

• To analyze the association between acetaminophen
  use and parent-reported symptoms of asthma in 6-7
  year-old children
• To explore the consistency of the association
  between acetaminophen use and asthma by examining
  the associations with symptoms of
  rhinoconjunctivitis

Beasley R et al. Lancet 20083721039-1048
48
Methods

• ISAAC (International Study of Asthma and
  Allergies in Childhood) Phase 3
• Multicentre, cross-sectional study of school
  children from a random sample of schools
• Two standardized questionnaires completed by
  parent or guardian of the child
• Primary Outcome association between
  acetaminophen use for fever in the first year of
  life and asthma symptoms at 6-7 years of age

Beasley R et al. Lancet 20083721039-1048
49
Results

• 205,487 children aged 6-7 years from 73 centres
  in 31 countries
• Association between Acetaminophen use for fever
  in the first year of life and symptoms at age 6-7
  years

Beasley R et al. Lancet 20083721039-1048
50
Results

• Association between acetaminophen use in the past
  12 months and symptoms in children age 6-7 years
• Population attributable risk (PAR) for asthma
  symptoms due to acetaminophen use for fever in
  the first year of life was 21
• PAR(risk in exposed-risk in unexposed)
  prevalence of exposure to risk factor in the
  population
• The reduction of risk in the total population if
  the exposure were removed

Beasley R et al. Lancet 20083721039-1048
51
Conclusion

• This study provides further worldwide evidence
  that the use of acetaminophen in childhood can
  increase the risk of developing asthma and
  related allergic disorders
• Evidence in insufficient to advise parents and
  health care workers of the risk-benefit of taking
  acetaminophen in childhood

Beasley R et al. Lancet 20083721039-1048
52
Clinical Question 8

• Would ondansetron decrease the risk of hospital
  admission in a 6 year male with vomiting and
  moderate dehydration?

53
Use of Antiemetic Agents in Acute Gastroenteritis

• DeCamp LR et al. Arch Pediatr Adolesc Med
  2008162(9)858-865.

54
Objective

• To perform a systematic review and meta-analysis
  to determine whether taking antiemetic drugs
  reduces vomiting and decreases the need for
  further intervention in children with
  gastroenteritis without causing significant
  adverse effects

DeCamp LR et al. Arch Pediatr Adolesc Med
2008162(9)858-865
55
Methods

• Search strategy prospective English language
  controlled trials
• Quality assessment
• Statistical analysis 2 X 2 tables were created
  for dichotomous outcomes (contacted authors when
  necessary)
• Main outcomes
• Hospital admission, IVF administration, Cessation
  of Vomiting in the ED, Return to Care, Adverse
  effects

DeCamp LR et al. Arch Pediatr Adolesc Med
2008162(9)858-865
56
Hospital Admission

• NNT 14 (95 CI, 9-44)

DeCamp LR et al. Arch Pediatr Adolesc Med
2008162(9)858-865
57
IV Fluids

• NNT 5 (95 CI, 4-8)

DeCamp LR et al. Arch Pediatr Adolesc Med
2008162(9)858-865
58
Persistent Emesis in the ED

• NNT 5 (95 CI, 4-7)
• Return to care RR 1.34 (CI 0.77-2.35)
• Increased diarrhea in treatment group

DeCamp LR et al. Arch Pediatr Adolesc Med
2008162(9)858-865
59
Conclusion

• Ondansetron therapy decreases the risk of
  persistent vomiting, the use of intravenous
  fluid, and hospital admissions in children with
  vomiting due to gastroenteritis
• Other antiemetic drugs have not demonstrated
  consistent effectiveness and, therefore, should
  not be used
• No available evidence exists demonstrating the
  efficacy of ondansetron in individuals with mild
  disease or in standard office settings

DeCamp LR et al. Arch Pediatr Adolesc Med
2008162(9)858-865
60
Clinical Question 9

• Is a blood culture looking for occult bacteremia
  necessary in a 4 month old infant presenting to
  the ED with fever and no other source?

61
Prevalence of Occult Bacteremia in Children Aged
3 to 36 Months Presenting to the Emergency
Department with Fever in the Postpneumoccal
Conjugate Vaccine Era

• Wilkinson M et al. Acad Emerg Med 200916220-225.

62
Objective and Methods

• Objective to identify the prevalence of occult
  bacteremia in well-appearing previously healthy
  children aged 3 to 36 months who present to the
  ED with fever in the post-PCV era
• Study Design Retrospective cohort study
• Inclusion criteria age 3-36 months, febrile,
  previously healthy, no source of infection on
  exam, had blood culture drawn, discharged from ED
• Outcome rates of occult bacteremia and
  contaminant rates

Wilkinson M et al. Acad Emerg Med 200916220-225
63
Results

• Between July 1 2004 and June 30, 2007, 10,043
  children met inclusion criteria

64
Results and Discussion

• With S. Pneumonia prevalence of 0.17 would need
  to test 588 children to detect one case

Wilkinson M et al. Acad Emerg Med 200916220-225
65
Canadian Pneumococcal Infection Rate
66
Conclusion

• Given the current rate of occult bacteremia in
  the post-PCV era, it may no longer be cost
  effective to send blood cultures on
  well-appearing, previously healthy children aged
  3 to 36 months who have fever without source
• If a child is known to be unimmunized it may
  still be wise to screen for OB as per pre-PCV
  recommendations

Wilkinson M et al. Acad Emerg Med 200916220-225
67
Clinical Question 10

• How accurate is my ability to detect the absence
  of a pulse and the need to start chest
  compressions for cardiac arrest in a collapsed 1
  month old infant?

68
Reliability of Pulse Palpation by Healthcare
Personnel to Diagnose Paediatric Cardiac Arrest

• Tibbals J and Russel P. Resuscitation
  20088061-64.

69
Objective and Methods

• Objective to determine the reliability of pulse
  check to diagnose paediatric cardiac arrest
• Methods
• Doctors and nurses were asked to attempt pulse
  detection (within 10s) on an infant or child
  provided with non-pulsatile circulation with
  veno-arterial extracorporeal membrane oxygenation
  or left ventricular assistance for cardiac arrest
  or failure
• Rescuer decision pulse present or pulse
  absent compared with concurred decision of
  investigators and bedside nurse

Tibbals J and Russel P. Resuscitation
20088061-64
70
Results

• 209 doctors and nurses
• Pulse palpation was conducted on 16 infants and
  children (average age 1.8 years, range 1 week to
  13 years)
• 179 (86) were able to decide if a pulse was
  present or absent within 10 s

Tibbals J and Russel P. Resuscitation
20088061-64
71
Results
Tibbals J and Russel P. Resuscitation
20088061-64
72
Conclusion

• This study suggests that pulse palpation is an
  unreliable method by healthcare personnel to
  determine the presence or absence of circulation
  when cardiac arrest is suspected in children

Tibbals J and Russel P. Resuscitation
20088061-64
73
Take Home Points

• Using a structured framework, the results of
  medical research can be translated into clinical
  practice
• The treatment of wheezing in infants and children
  is likely to differ based on age, severity and
  etiology
• PEG 3350 (combined with behavior modification)
  appears to be safe and efficacious for the
  treatment of functional constipation in children
• We overprescribe antireflux medications for
  infants with GERD
• Consider pretreatment with ondansetron for
  ketamine sedation

74
Take Home Points

• Be on the look out for the incorporation of
  procalcitonin in the work up of fever without a
  source
• Be aware of the potential risks of the casual use
  of acetaminophen (and all drugs) in otherwise
  healthy children
• Consider ondansetron in the ED setting in
  children with vomiting and moderate dehydration
• Blood cultures may not be necessary in immunized,
  well appearing, previously healthy children age 3
  to 36 months with fever without a source
• When in doubt regarding the presence or absence
  of a pulse in a pediatric cardiac arrest, start
  compressions

75
References

• Users Guide to the Medical Literature
• Oxman AD, Sackett DL, Guyatt GH. How to Get
  Started. JAMA. 1993270(17)2093-2095.
• Guyatt G. H. et al. EBM Principles of Applying
  Users Guides to Patient Care.JAMA.
  2000284(10)1290-1296.
• Guyatt GH, Sackett, D, Cook, DJ. How to Use an
  Article About Therapy or Prevention.
  JAMA1993270(21)2598-2601 and
  1994271(1)59-63.
• Jaeschke,R et al. How to Use an Article About a
  Diagnostic Test. JAMA 1994271(5)389-391 and
  1994271(9)703-707.
• Levine et al. How to Use an Article about Harm.
  JAMA271(20)1615-1619.
• Oxman AD, Cook, DJ, Guyatt, GH. How to Use and
  Overview. JAMA1994272(17)1367-71.
• Available online http//www.cche.net/usersguides/m
  ain.asp (accessed May 25, 2009).

76
References

• Assessing the Quality of Evidence
• Downs SH and Black N. The feasibility of creating
  a checklist for the assessment of the
  methodological quality both of randomized and
  non-randomised studies of health care
  interventions. J Epidemiol Community Health
  199852377-384.
• Verhagen AP et al. The Delphi list a criteria
  list for quality assessment of randomized
  clinical trials for conducting systematic reviews
  developed by Delphi consensus. J Clin Epidemiol.
  199851(12) 1235-41.
• West, S. et al. Systems to Rate the Strength of
  Scientific Evidence, Evidence Report/Technology
  Assessment No. 47. AHRQ Publication No. 02-E016.
  Rockville, MD Agency for Healthcare Research and
  Quality. April 2002. http//www.ncbi.nlm.nih.gov/b
  ooks/bv.fcgi?ridhstat1.chapter.70996 (accessed
  05/09)
• AAP Clinical Practice Guideline. Diagnosis and
  Management of Bronchiolitis. Pediatrics
  2006118(4)1774-1793.

77
Hierarchy of Evidence

• Strength of Evidence for Treatment Decisions
• N of 1 randomized trial
• Systematic reviews of randomized trials
• Single randomized trial
• Systematic review of observational studies
  addressing patient-important outcomes
• Single observational study addressing
  patient-important outcomes
• Physiological studies
• Unsystematic clinical observations

78
Users' Guides for an Article About Therapy

• Are the results of the study valid?
• Was the assignment of patients to treatments
  randomized?
• Were all patients who entered the trial properly
  accounted for and attributed at its conclusion?
• Was follow-up complete?
• Were patients analyzed in the groups to which
  they were randomized?
• Were patients, health workers, and study
  personnel "blind" to treatment?
• Were the groups similar at the start of the
  trial?
• Aside from the experimental intervention, were
  the groups treated equally?

• What were the results?
• How large was the treatment effect?
• How precise was the estimate of the treatment
  effect?
• Will the results help me in caring for my
  patients?
• Can the results be applied to my patient care?
• Were all clinically important outcomes
  considered?
• Are the likely treatment benefits worth the
  potential harms and costs?

79
Guides for Selecting Articles

• Primary Studies
• Therapy
• Was the assignment of patients to treatments
  randomized
• Were all of the patients who entered the trial
  properly accounted for and attributed at its
  conclusion?
• Diagnosis
• Was there an independent, blind comparison with a
  reference standard?
• Did the patients sampled include an appropriate
  spectrum of the sort of patients to whom the
  diagnostic test will be applied in clinical
  practice?

80
Guides for Selecting Articles

• Primary Studies
• Harm
• Were there clearly identified comparison groups
  that were similar with respect to important
  determinants of outcome (other than the one of
  interest)?
• Were outcomes and exposures measured in the same
  way in the groups being compared
• Integrative Studies
• Overview
• Did the review address a clearly focused
  question?
• Were the criteria used to select articles for
  inclusion appropriate

• Oxman AD, Sackett DL, Guyatt GH. How to Get
  Started. JAMA. 1993270(17)2093-2095.

81
Changes in Clinical Characteristics of Patients
and Time to Discharge
Plint AC et al. N Engl J Med 20093602079-2089
82
Median Days to Symptom Resolution, with Ratio to
Placebo Value
Plint AC et al. N Engl J Med 20093602079-2089
83
Enrollment and Outcomes
Enrollment and Outcomes
Panickar J et al. N Engl J Med 2009360329-338
Panickar J et al. N Engl J Med 2009360329-338
84
Baseline Characteristics of the Patients
Panickar J et al. N Engl J Med 2009360329-338
85
Secondary Outcomes during Hospitalization
Panickar J et al. N Engl J Med 2009360329-338
86
Duration of Hospitalization
Duration of Hospitalization (Primary Outcome)
Panickar J et al. N Engl J Med 2009360329-338
Panickar J et al. N Engl J Med 2009360329-338
87
Secondary Outcomes after Discharge
Panickar J et al. N Engl J Med 2009360329-338
88
Kaplan-Meier Estimates of the Proportion of
Children Remaining in the Hospital
Panickar J et al. N Engl J Med 2009360329-338
89
Temporal Patterns of Wheeze

• Episodic (viral wheeze) wheezing during discrete
  time periods, often in association with clinical
  evidence of a viral cold, with absence of wheeze
  between episodes.
• Multiple-trigger wheeze Wheezing that shows
  discrete exacerbations, but also symptoms between
  episodes

Brand PLP et al. Definition, assessment and
treatment of wheezing disorders in preschool
children an evidence based approach. Eur Resp J
2008321096-110.
90
Results
Orenstein SR et al. J Pediatr 2009154514-520
91
Results
92
Lanston W et al. Ann Emerg Med 200852(1)30-34
93
Results

• 234 eligible patients with procalcitonin
  measurements

94
Quality Assessment
Verhagen AP et al. J Clin Epidemiol. 199851(12)
1235-1241.
95
(No Transcript)
96
DeCamp LR et al. Arch Pediatr Adolesc Med
2008162(9)858-865