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Journal Club February 25, 2010 : Kestenbaum et al. Defining CSF white blood cell count reference values in neonates and young infants. Pediatrics 2010;125:257-264. David H. Rubin, MD Chairman and Program Director, Pediatrics St Barnabas Hospital

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Journal Club February 25, 2010: Kestenbaum et al. Defining CSF white blood cell count reference values in neonates and young infants. Pediatrics 2010;125:257-264.

David H. Rubin, MD

Chairman and Program Director, Pediatrics

St Barnabas Hospital

Professor of Clinical Pediatrics, Albert Einstein College of Medicine


Objectives of seminar
OBJECTIVES OF SEMINAR

  • Aim

  • Hypothesis

  • Methods and statistical strategies

  • Conclusion

  • Competency based evaluation


Competency based objectives
COMPETENCY BASED OBJECTIVES

  • Medical Knowledge

    • knowledge about the established and evolving biomedical, clinical, and cognate (epidemiological and social-behavioral) sciences and their application to patient care


Competency based objectives1
COMPETENCY BASED OBJECTIVES

  • Patient Care

    • family centered patient care developmentally and age appropriate compassionate and effective for treatment of health care problems and promotion of health


Competency based objectives2
COMPETENCY BASED OBJECTIVES

  • Practice Based Learning

    • investigation and evaluation of patient care, and the assimilation of scientific evidence

  • Communication Skills

    • interpersonal and communication skills resulting in effective information exchange and learning with patients, families and professional associates


Competency based objectives3
COMPETENCY BASED OBJECTIVES

  • System Based Practice

    • understanding systems of health care organization, financing, and delivery, and the relationship of one’s local practice and these larger systems

  • Professionalism

    • carrying out professional responsibilities, adherence to ethical principles, and sensitivity to diverse patient populations


Introduction
INTRODUCTION

  • CSF reference values are extremely important – especially for neonates in the 0-28 day and 29-56 day groups

  • Prospective studies are unethical

    • RCT where healthy children 0-60 days of age are randomized to either LP or no LP

  • SO…”normal” values are obtained by examination of infants who have LPs because they are ill


Introduction1
INTRODUCTION

  • Prior studies have problems

    • Based on children considered “healthy” after initial evaluation for CNS infection

    • No uniform exclusion criteria

    • PCR not previously available

    • Small numbers, poor power

  • Past studies have included subjects with

    • Traumatic LP

    • Seizures

    • Sepsis

    • Congenital infections

    • Low BW


Aim of study
AIM OF STUDY

  • Not really stated, but……….

  • Assume: determine the extent of normal v abnormal regarding CSF white cell counts


Methods
METHODS

  • Cross sectional study

  • Eligible if LP performed “as part of ED evaluation between 1/1/2005 and 6/30/2007 at CHOP

  • LP procedure identified by

    • ED order entry records for all infants with CSF testing

    • Clinical virology lab testing records

    • (Had to have both to be eligible)


Methods1
METHODS

  • Exclusion criteria (very important; see page 259, Figure 1)

    • Traumatic LP

    • SBI (VGE, bacteremia, UTI, osteo, septic arthritis, pneumonia)

  • Those that remained:

    • Classified on basis of enteroviral CSF testing – whether or not it was performed and whether test was positive or negative

    • “Because viral meningitis can cause CSF pleocytosis, patients with pos EV PCR were excluded”

  • Primary analysis combined preterm and term infants (?justified)


Methods2
METHODS

  • Data Collection: abstraction from medical records; ?verification

  • WHO did the abstraction – 1 or more authors?

  • Data analysis

    • Continuous variables – mean, median, interquartile range, 90th ,95th %-ile

    • Comparison with Wilcoxon rank sum test


Wilcoxon rank sum test
WILCOXON RANK SUM TEST

  • Like the t-test for correlated samples, the Wilcoxon signed-ranks test applies to two-sample designs involving repeated measures, matched pairs, or "before" and "after" measures.

  • Beginning with a set of paired values of Xa and Xb, this page will take the absolute difference |Xa—Xb| for each pair;

  • Omit from consideration those cases where |Xa—Xb|=0;

  • Rank the remaining absolute differences, from smallest to largest, employing tied ranks where appropriate;

  • Assign to each such rank a "+" sign when Xa—Xb>0 and a "—" sign when Xa—Xb<0;

  • Calculate the value of W for the Wilcoxon test, which in the present version of the procedure is equal to the sum of the signed ranks.


Results
RESULTS

  • 1064 infants identified for the study; 380 (36%) met inclusion criteria – see Fig 1 page 259.

  • Infants 0-28 days had median CSF WBC of 3/L with a 95th %ile value of 19/L

  • Infants 29-56 days had median CSF WBC of 2/L with a 95th %ile value of 9/L

    • P<.001 for difference (Table 2, page 260)


Results1
RESULTS

  • Within the 2 age groups, comparison was made between

    • Patients who tested negative for EV PCR compared with patients who did not have EV PCR testing

      • In younger group (0-28days) group with negative EV PCR had median CSF WBC of 4/L – significantly higher than those who did not have testing (see Table 3, p 260).

      • Older group NS


Results2
RESULTS

  • Comparison regarding CSF WBC counts with and without fever were NS

  • Preterm infants

    • NO effect on 0-28 or 29-56 day old groups


Discussion
DISCUSSION

  • “Our study establishes reference values for CSF WBC counts in neonates and young children…”

  • YES or NO?

  • Limitations cited by author

    • #1: Not all infants and neonates had EV testing (see Table 3)

      • 0-28 days (n=142): 37/142 had EV testing = 26%

      • 29-56 days (n=238): 38/238 had EV testing = 16%

      • Total EV testing: 75/380 = 20%


Discussion1
DISCUSSION

  • #2: Viral testing not performed

  • #3: “Certain patients received antibiotics before lumbar puncture…”

  • #4: Observational study so that physicians (who – attendings, residents, students?) selected who had LP (no protocol)

  • #5: Single center study may limit generalizability

  • #6: Preemies included  ?effect


Discussion2
DISCUSSION

  • Other issues

    • Chart abstraction – verification?

    • Level of training of “decision maker” not specified

    • Only ½ year of data – why?

    • Median used – why not mean and SD, confidence intervals

    • Figure 2 (page 261) is a migraine headache


Discussion3
DISCUSSION

  • Strengths of the study

    • Interesting question, important

    • What are other methods to examine this issue?


Competency based objectives4
COMPETENCY BASED OBJECTIVES

  • Medical Knowledge

    • knowledge about the established and evolving biomedical, clinical, and cognate (epidemiological and social-behavioral) sciences and their application to patient care

      • What are normal values of CSF WBC by age?


Competency based objectives5
COMPETENCY BASED OBJECTIVES

  • Patient Care

    • family centered patient care developmentally and age appropriate compassionate and effective for treatment of health care problems and promotion of health

      • Presentation and management of disease by age

      • Importance of information for family regarding signs and symptoms of problem


Competency based objectives6
COMPETENCY BASED OBJECTIVES

  • Practice Based Learning

    • investigation and evaluation of patient care, and the assimilation of scientific evidence

      • Scientific evaluation of hypothesis, methods, and conclusion of article

  • Communication Skills

    • interpersonal and communication skills resulting in effective information exchange and learning with patients, families and professional associates


Competency based objectives7
COMPETENCY BASED OBJECTIVES

  • System Based Practice

    • understanding systems of health care organization, financing, and delivery, and the relationship of one’s local practice and these larger systems

      • Referral systems, consultation

  • Professionalism

    • carrying out professional responsibilities, adherence to ethical principles, and sensitivity to diverse patient populations

      • Patient education in diverse cultures


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