Complications associated with off-label use of recombinant factor VIIa —Robert W. Wilmott, MD 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- 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 admissions, of which 74% represented off-label use of the factor. They demonstrated 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 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 encephalopathy: How low can you go? —Ronald I. Clyman, MD T he hypothermia neuro-protection trials for neonatal hypoxic ischemic encephalopathy (HIE) added an important treatment to our therapeutic armamentarium. The secondary analyses of these trials continue to uncover new variables (eg, the preven- 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 Network trial of whole body cooling. They found that both minimum PCO2 and cu- 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 CO 2 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 outcome? Should cooled infants be started on lower initial ventilator settings or weaned more rapidly in view of their lower metabolic rate (and consequent lower CO 2 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 activity intervention in kindergarten promotes health —Sarah S. Long, MD 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- metric measures, and physical fitness. Kindergartens were randomly assigned in toto to 15 intervention and 15 control sites. Teaching and physical activities were predom- inantly delivered by teachers and their assistants. Compared with the control groups, intervention groups had significantly improved knowledge of nutrition, physical activity, and healthy food preferences; they also had improved fitness, increased height 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

Hypocarbia and HIE/neonatal encephalopathy: How low can you go?

Download PDF Report

Upload
ronald-i-clyman
View
212
Download
0

Embed Size (px)

Citation preview

Page 1: Hypocarbia and HIE/neonatal encephalopathy: How low can you go?

Complicationsassociated withoff-label use of

recombinantfactor VIIa

—Robert W. Wilmott, MD

A retrospective multi-center cohort study of the off-label use of recombinant factorVIIa 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-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 eligibleadmissions, of which 74% represented off-label use of the factor. They demonstrateda ten-fold increase in the annual rate of off-label admissions during this time period, inspite of an absence of adequate clinical trials demonstrating safety and efficacy. This isof concern because the mortality rate in the off-label group was 34%, and thromboticevents 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, furtherstudies are needed to determine the causes of these adverse events and the safety ofthis therapy.

Article page 820<

Hypocarbia andHIE/neonatal

encephalopathy: Howlow can you go?—Ronald I. Clyman, MD

The 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-tion of hyperthermia) that appear to impact neonatal outcomes. In this issue of TheJournal, Pappas et al present their secondary analysis of the NICHDNeonatal ResearchNetwork trial of whole body cooling. They found that both minimum PCO2 and cu-mulative PCO2 <35mmHg (within the first 16 hours of birth) were associated withpoor outcome at 18 to 22 months of age. There is biological plausibility for hypocarbiato exacerbate brain injury: low CO2 tension may impact cerebral perfusion, oxygena-tion, and removal of potentially neurotoxic metabolites. This study raises importantquestions regarding the complexity of early postnatal ventilatory management of ne-onates with HIE. Is hypocarbia amodifiable risk factor or simply a marker of poor out-come? Should cooled infants be started on lower initial ventilator settings or weanedmore rapidly in view of their lower metabolic rate (and consequent lower CO2 produc-tion)?Will avoidance of hypocarbia improve outcome? The answers to these questionswill certainly alter the way we treat infants with this condition in the future.

Article page 752<

Simpledietary-physical

activity interventionin kindergartenpromotes health

—Sarah S. Long, MD

In this year-long study of 795 Israeli children of lower socioeconomic status enrolledin 30 kindergartens, investigators prospectively assessed the impact of an educational

and physical activities program on nutritional knowledge, food preferences, anthropo-metric measures, and physical fitness. Kindergartens were randomly assigned in tototo 15 intervention and 15 control sites. Teaching and physical activities were predom-inantly delivered by teachers and their assistants. Compared with the control groups,intervention groups had significantly improved knowledge of nutrition, physical ac-tivity, and healthy food preferences; they also had improved fitness, increased heightgrowth, and decreased percentage of overweight children.

Although increasing or just sustaining ‘‘gains’’ over additional timemust be studied,this seemingly is a doable and effective good start in the war against obesity, which wenow know must begin before school.

Article page 796<

Vol. 158, No. 5