Complications

associated with
A retrospective multi-center cohort study of the off-label use of recombinant factor
VIIa in tertiary care pediatric hospitals across the United States was completed by
Witmer et al from the Children’s Hospital of Philadelphia and the University of Penn-
off-label use of sylvania School of Medicine. Studying children 18 years of age or younger who re-
ceived this therapy between 2000 and 2007, the authors identified 4942 eligible
recombinant admissions, of which 74% represented off-label use of the factor. They demonstrated
factor VIIa a ten-fold increase in the annual rate of off-label admissions during this time period, in
spite of an absence of adequate clinical trials demonstrating safety and efficacy. This is
—Robert W. Wilmott, MD of concern because the mortality rate in the off-label group was 34%, and thrombotic
events occurred in 11% in the off-label admissions. Given these high rates of throm-
bosis and mortality in patients receiving off-label recombinant factor VIIa, further
studies are needed to determine the causes of these adverse events and the safety of
this therapy.
Article page 820<

Hypocarbia and
HIE/neonatal
T he hypothermia neuro-protection trials for neonatal hypoxic ischemic encephalop-
athy (HIE) added an important treatment to our therapeutic armamentarium. The
secondary analyses of these trials continue to uncover new variables (eg, the preven-
encephalopathy: How tion of hyperthermia) that appear to impact neonatal outcomes. In this issue of The
Journal, Pappas et al present their secondary analysis of the NICHD Neonatal Research
low can you go? Network trial of whole body cooling. They found that both minimum PCO2 and cu-
—Ronald I. Clyman, MD mulative PCO2 <35mmHg (within the first 16 hours of birth) were associated with
poor outcome at 18 to 22 months of age. There is biological plausibility for hypocarbia
to exacerbate brain injury: low CO2 tension may impact cerebral perfusion, oxygena-
tion, and removal of potentially neurotoxic metabolites. This study raises important
questions regarding the complexity of early postnatal ventilatory management of ne-
onates with HIE. Is hypocarbia a modifiable risk factor or simply a marker of poor out-
come? Should cooled infants be started on lower initial ventilator settings or weaned
more rapidly in view of their lower metabolic rate (and consequent lower CO2 produc-
tion)? Will avoidance of hypocarbia improve outcome? The answers to these questions
will certainly alter the way we treat infants with this condition in the future.
Article page 752<

Simple
dietary-physical
I n this year-long study of 795 Israeli children of lower socioeconomic status enrolled
in 30 kindergartens, investigators prospectively assessed the impact of an educational
and physical activities program on nutritional knowledge, food preferences, anthropo-
activity intervention metric measures, and physical fitness. Kindergartens were randomly assigned in toto
to 15 intervention and 15 control sites. Teaching and physical activities were predom-
in kindergarten inantly delivered by teachers and their assistants. Compared with the control groups,
promotes health intervention groups had significantly improved knowledge of nutrition, physical ac-
tivity, and healthy food preferences; they also had improved fitness, increased height
—Sarah S. Long, MD growth, and decreased percentage of overweight children.
Although increasing or just sustaining ‘‘gains’’ over additional time must be studied,
this seemingly is a doable and effective good start in the war against obesity, which we
now know must begin before school.
Article page 796<

A2 Vol. 158, No. 5