Quality assessments of HMO diagnosis databases used to monitor childhood vaccine safety.

OBJECTIVE: To assess the quality of automated diagnoses extracted from medical care databases by the Vaccine Safety Datalink (VSD) study. METHODS: Two methods are used to assess quality of VSD diagnosis data. The first method compares common automated and abstracted diagnostic categories ("outcomes") in 1-2% simple random samples of study populations. The second method estimates positive predictive values of automated diagnosis codes used to identify potential cases of rare conditions (e.g., acute ataxia) for inclusion in nested case-control medical record abstraction studies. RESULTS: There was good agreement (64-68%) between automated and abstracted outcomes in the 1-2% simple random samples at 3 of the 4 VSD sites and poor agreement (44%) at 1 site. Overall at 3 sites, 56% of children with automated cerebella ataxia codes (ICD-9 = 334) and 22% with "lack of coordination" codes (ICD-9 = 781.3) met objective clinical criteria for acute ataxia. CONCLUSIONS: The misclassification error rates for automated screening outcomes substantially reduce the power of screening analyses and limit usefulness of screening analyses to moderate to strong vaccine-outcome associations. Medical record verification of outcomes is needed for definitive assessments.

Quality of HMO vaccination databases used to monitor childhood vaccine safety. Vaccine Safety DataLink Team.

The availability of large, population-based, automated, medical care databases provides unique opportunities for monitoring the safety of childhood vaccines. The authors assessed the quality of automated vaccination databases by comparing them with vaccinations documented in paper-based medical records at three large US West Coast health maintenance organizations (HMOs) participating in the Vaccine Safety DataLink (VSD) study, a Centers for Disease Control and Prevention collaborative study of childhood vaccine safety. The authors randomly selected 1% or 2% samples of VSD study populations (n = 1,224-2,577) for data quality analyses. Agreement between automated and abstracted vaccinations required identical triads of child identification number, vaccination date, and vaccine type. Separate analyses were conducted for each HMO and for each vaccine type administered between 1991 and 1995. Agreement was measured by three matching proportions: 1) the proportion of automated vaccinations present in the abstracted source, 2) the proportion of abstracted vaccinations present in the automated source, and 3) the proportion of vaccinations from either source present in both sources. Overall, for common childhood vaccines, proportion 1 ranged from 83% to 99%, proportion 2 ranged from 82% to 98%, and proportion 3 ranged from 70% to 97%. Lack of automated data was the most frequent type of discrepancy, followed by date mismatches and vaccine type mismatches. Vaccination exposure classification errors in the range reported here were found by mathematical modeling to only modestly bias measured medical outcome rate ratios toward the null hypothesis. The results of the data quality analyses support the usefulness of vaccination exposure data derived from these automated HMO vaccination databases.

Injuries among preschool children enrolled in day-care centers.

In this study, 423 injury incidents among preschool children enrolled in day-care centers reported to the Los Angeles Unified School District during the 2-year period 1983 to 1984 are reviewed. The relative risk of sustaining an injury between boys and girls was 1.5:1. Among sex and age groups, younger boys (2 to 3 years of age) showed the highest injury rate and older girls (4 to 5 years of age) showed the lowest. The overall incidence was 19.7 injuries per 1,000 child-years. The majority of the injuries were minor in severity, and medical attention was recommended in only 12.8% of the injuries. The highest incidence occurred during the late morning period (9 AM to 12 noon). A consumer product was involved in 53.7% of the incidents. Three of four injuries were considered preventable by training and/or education or by the Haddon injury reduction strategies. Additional prospective studies are needed to develop and implement preventive measures.

Transfer of 3H-cortisone and 3H-cortisol between the amniotic, allantoic, and fetal blood compartments in the rabbit at day 25 of gestation.

We have examined the rate of disappearance and the form of the radiolabel following the injection of either [1,2-3H]-cortisone (3H-E) or [1,2,6,7,n-3H]-cortisol (3H-F) into the amniotic sac of rabbits at day 25 of gestation. The half-life of 3H-E was approximately 35 min and was very much shorter than that of 3H-F. Concurrent with the disappearance of 3H-E was an increase in the amount of tritium in both the allantoic and the fetal blood compartments. Whereas following injection of 3H-E there was a rapid conversion of E to F that was reflected in all three compartments, following injection of 3H-F the vast majority of the tritium label remained as F. We conclude that amniotic E may act as a ready source of fetal F.

The physiological significance of 11 beta-hydroxysteroid dehydrogenase in the rat lung.

We have examined the interconversion of cortisone (E) and cortisol (F) in rat lung homogenate and microsomal fraction and in the isolated rat lung perfused with Krebs bicarbonate solution containing 4.5% albumin. In the perfused lung the apparent Km was 5.1 microM E and the Vmax was 9 nmol . g(-1) . min-1. The ability of the lung to reduce E to F was enhanced both by 7 days prior exposure of the rat to an ambient temperature of 2 degrees C and by starvation of the rat for 3 days. The activity was inhibited by adrenalectomy and castration of 7 days duration. Whereas little steroid oxidation occurred in the perfused lung, preparations of lung homogenates and microsomal fraction readily reduced or oxidised the 11-position of the corticoid molecule depending on the preponderance of either NADPH or NADP, respectively. We conclude, that the predominance of the reductive reaction in the whole rat lung under physiological conditions reflects the very active pentose-phosphate shunt in the lung, which produces NADPH. We suggest that this ability of the lung to activate E to F may exert a fine control over the arterial concentration of unbound, physiologically active, 11-hydroxylated steroid.

Cortisone and cortisol in maternal and fetal blood and in amniotic fluid during the final ten days of gestation in the rabbit.

We have used instant thin-layer chromatography and radioimmunoassay to measure the concentrations of total cortisone (E) and cortisol (F) in the fetal and maternal compartments of the rabbit. The concentration of F in fetal blood increased markedly at day 25; this is just prior to the rapid increase in the surfactant phospholipids in lung tissue in this species. This increase coincided with a peak in the concentration of E and F in the maternal blood and may reflect the maternal levels. There was no 'surge' in the concentration of total F in fetal blood at term. The concentration of E in fetal blood varied between 5 and 15 ng/ml during this last stage of gestation, hence providing ready substrate for the 11 beta-reductase present in lung and other tissues. The concentration of E and F in maternal blood was significantly higher and more variable than that in blood from nonpregnant female rabbits, and there was a pronounced peak in concentration at day 30 (term: 31 days). The concentrations of both E and F in amniotic fluid were lower than those in either maternal or fetal blood until day 30 when the concentration of F increased fivefold to 19.2 +/- 2.58 (mean +/- SEM of 6 samples).

Uptake of [14C]choline and incorporation into lung phospholipid by the isolated perfused rat lung.

We have used the isolated perfused lung (IPL) preparation from the rat to determine whether uptake of choline from the vascular compartment could limit the rate of synthesis of phosphatidyl-choline (PC). The uptake of choline was rapid and did not saturate at a concentration of 10 mM. The rate of incorporation of choline into phospholipid was saturated above 0.1 mM choline. Whereas, uptake and incorporation were depressed at 4 C, uptake was neither dependent on the extracellular sodium concentration nor inhibited by equimolar concentrations of hemicholinium-3 (HC-3). We could find no evidence that uptake might limit synthesis of lung lecithin and conclude that uptake is either by free diffusion, or by a carrier-mediated process with a very high Km.