Randy L. Carter

An Empirical Comparison of Statistical Models for Value-Added Assessment of School Performance

Hierarchical Linear Models (HLM) have been used extensively for value-added analysis, adjusting for important student and school-level covariates such as socioeconomic status. A recently proposed alternative, the Layered Mixed Effects Model (LMEM) also analyzes learning gains, but ignores sociodemographic factors. Other features of LMEM, such as its ability to apportion credit for learning gains among multiple schools and its utilization of incomplete observations, make it appealing. A third model that is appealing due to its simplicity is the Simple Fixed Effects Models (SFEM). Statistical and computing specifications are given for each of these models. The models were fitted to obtain value-added measures of school performance by grade and subject area, using a common data set with two years of test scores. We investigate the practical impact of differences among these models by comparing their value-added measures. The value-added measures obtained from the SFEM were highly correlated with those from the LMEM. Thus, due to its simplicity, the SFEM is recommended over LMEM. Results of comparisons of SFEM with HLM were equivocal. Inclusion of student level variables such as minority status and poverty leads to results that differ from those of the SFEM. The question of whether to adjust for such variables is, perhaps, the most important issue faced when developing a school accountability system. Either inclusion or exclusion of them is likely to lead to a biased system. Which bias is most tolerable may depend on whether the system is to be a high-stakes one.

Developmental intervention program for high-risk premature infants: effects on development and parent-infant interactions.

Developmental follow-up studies have documented that low birth weight infants are at high risk for mental and physical disabilities, despite recent advances in neonatal intensive care. Moreover, parent-infant bonding is hampered by the barriers created by technical equipment. This study evaluated a program of hospital and home-based developmental interventions designed to enhance the development of high-risk, preterm infants and the quality of communication between infants and their caregivers. Treatment and contrast groups consisted of 41 premature infants weighing < 1800 g at birth. Treatment took a preventive approach, consisting of daily multimodal interventions in-hospital and twice-monthly interventions by child development specialists in the childs home, through 12 months adjusted age. Infants in the contrast group received traditional, remedially oriented care. The Bayley Scales of Infant Development were used to measure mental and psychomotor development, and the Greenspan-Lieberman Observations System (GLOS) was used to analyze the behavioral characteristics of infant-caregiver interactions. Developmental interventions had positive, significant effects on mental development and on the quality of caregiver-infant interactions. Changes in mental development were not independent of changes in the GLOS. J Dev Behav Pediatr 9:73–78, 1988. Index terms: high-risk neonates, premature infants, developmental intervention.

Educational Disabilities of Neonatal Intensive Care Graduates

Objective. To determine the relationship between perinatal and sociodemographic factors in low birth weight and sick infants hospitalized at regional neonatal intensive care units (NICUs) and subsequent educational disabilities. Method. NICU graduates born between 1980 and 1987 at nine statewide regionalized level III centers were located in Florida elementary schools (kindergarten through third grade) during academic year 1992–1993 (n = 9943). Educational disability was operationalized as placement into eight mutually exclusive types of special education (SE) classifications determined by statewide standardized eligibility criteria: physically impaired, sensory impaired (SI), profoundly mentally handicapped, trainable mentally handicapped, educable mentally handicapped, specific learning disabilities, emotionally handicapped, and speech and language impaired (SLI). Logistic regression was used to estimate the odds of placement in SE for selected perinatal and sociodemographic variables. Results. Placement into SE ranged from .8% for SI to 9.9% for SLI. Placement was related to four perinatal factors (birth weight, transport, medical conditions [congenital anomalies, seizures or intraventricular hemorrhage] and ventilation), and five sociodemographic factors (childs sex, mothers marital status, mothers race, mothers educational level, and family income). Perinatal factors primarily were associated with placement in physically impaired, SI, profoundly mentally handicapped, and trainable mentally handicapped. Perinatal and sociodemographic factors both were associated with placement in educable mentally handicapped and specific learning disabilities whereas sociodemographic factors primarily were associated with placement in emotionally handicapped and SLI. Conclusions. Educational disabilities of NICU graduates are influenced differently by perinatal and sociodemographic variables. Researchers must take into account both sets of these variables to ascertain the long-term risk of educational disability for NICU graduates. Birth weight alone should not be used to assess NICU morbidity outcomes.

Early infantile Krabbe disease: results of the World-Wide Krabbe Registry

New York State began screening for Krabbe disease in 2006 to identify infants with Krabbe disease before symptom onset. Because neither galactocerebrosidase activity nor most genotypes reliably predict phenotype, the World Wide Registry was developed to determine whether other clinical/neurodiagnostic data could predict early infantile Krabbe disease in the newborn screening population. Data on disease course, galactocerebrosidase activity, DNA mutations, and initial neurodiagnostic studies in 67 symptomatic children with early infantile Krabbe disease were obtained from parent questionnaires and medical records. Initial signs included crying/irritability, cortical fisting, and poor head control. Galactocerebrosidase activity was uniformly low. Eight of 17 manifested novel mutations. Ninety-two percent (n = 25) exhibited elevated cerebrospinal fluid protein; 76% (n = 42) demonstrated abnormal magnetic resonance images; 67% (n = 15) exhibited abnormal computed tomography findings; 43% (n = 28) produced abnormal electroencephalogram findings; 100% (n = 5) demonstrated abnormal nerve conduction velocities; 83% (n = 6) produced abnormal brainstem evoked responses; and 50% (n = 6) exhibited abnormal visual evoked responses. One, 2, and 3 year survivals were 60%, 26%, and 14%, respectively. Although most symptomatic patients with the early infantile phenotype manifested abnormal cerebrospinal fluid protein, magnetic resonance imaging, brainstem evoked responses, and nerve conduction velocities, studies of affected children may be normal. Other biomarkers are needed to predict phenotype in the newborn screening population.

Later Onset Phenotypes of Krabbe Disease: Results of the World-Wide Registry

The majority of newborns screening positive for Krabbe disease have not exhibited the expected early infantile phenotype, with most clinically normal despite low galactocerebrosidase activity and two mutations. Most are expected to develop the later onset phenotypes. The World-Wide Krabbe Registry was developed in part to expand our understanding of the natural history of these rare variants. As of June 2011, 122 patients were enrolled in the registry: 62% manifested early infantile onset (previously reported), 10% manifested onset at 7-12 months (late infantile), 22% manifested onset at 13 months to 10 years (later onset), and 5% manifested adolescent/adult onset. Data on disease course, galactocerebrosidase activity, DNA mutations, and results of neurodiagnostic studies were obtained from questionnaires and medical records. Initial signs (late infantile) included loss of milestones and poor feeding, whereas later onset and adolescent/adult phenotypes presented with changes in gait. Elevated cerebrospinal fluid protein and abnormal magnetic resonance imaging results were present in most, but not all, patients at diagnosis. Phenotypic variability occurred in four sibships. Five-year and 10-year survivals for all later onset phenotypes were at least 50%. The later onset Krabbe phenotypes differ from those with early infantile disease, but no specific predictor of phenotype was identified.

Effects of birth weight and sociodemographic variables on mental development of neonatal intensive care unit survivors

Neonatal intensive care unit survivors (N = 494) from 10 tertiary care centers were evaluated over the first 4 to 5 years of life to determine the relative contributions of birth weight and sociodemographic factors to mental development. Six sociodemographic factors were studied: sex, race, family income, and mothers marital status, age, and educational level; the last five factors also are known to be associated with premature birth. Mental development was measured with the Bayley Scales of Infant Development (12 to 24 months) and the Stanford Binet Intelligence Test (4 to 5 years). Each factors influence was assessed by multivariate analysis. Birth weight had limited long-term implications; at 4 to 5 years, only infants with birth weights less than 1000 gm had significantly lower scores than those in other birth weight categories. Sociodemographic variables had a greater impact on mental development, with age-dependent differences found between nonwhite and white children and between children with mothers of low, medium, and high educational levels.

Mortality rates due to gynecologic cancers in New York state by demographic factors and proximity to a Gynecologic Oncology Group member treatment center: 1979–2001

OBJECTIVE To describe trends in mortality rates, in New York State, due to cervical, endometrial and ovarian cancer and to assess how these rates varied with proximity to a comprehensive cancer treatment center or population density (rural/urban). METHODS Data were obtained from the Centers for Disease Control and Prevention (CDC)s Compressed Mortality Files, Census Bureau records, and online maps. Poisson regression models were fitted to estimate death rates (mean number of deaths per 100,000 women per year) due to gynecologic cancer type. Trends in death rates were compared with respect to driving time to the nearest comprehensive cancer treatment center and population density, controlling for race, county income level, and age at death. RESULTS Cervical and endometrial but not ovarian death rates declined over time. For both cervical and endometrial cancers, death rates varied significantly with driving time and between rural and urban counties. In the case of cervical cancer, the decline over time was steeper in rural than in urban counties. For endometrial cancer, the decline steepened with increasing distance from a treatment center. CONCLUSION Improvements in cervical and endometrial cancer mortality from 1979 to 2001 followed increases in gynecologic cancer treatment research efforts, number of specialists trained to treat such cases, and in the emphasis on gynecologic cancer in the training of physicians in general. Our results are consistent with an interpretation that the progressive actions by leaders in the gynecologic oncology profession during the late 1960s and early 1970s contributed to improvements in mortality rates in subsequent decades.

Death rates in the U.S. due to Krabbe disease and related leukodystrophy and lysosomal storage diseases

Leukodystrophies (LD) and lysosomal storage disorders (LSD) have generated increased interest recently as targets for newborn screening programs. Accurate epidemiological benchmarks are needed in the U.S. Age‐specific mortality rates were estimated for Krabbe disease (KD) and nine related disorders. U.S. mortality records with E75.2 cause of death code during 1999–2004 were collected from 11 open record states. All E75.2 deaths in the United States were distributed into specific disease type based on proportions observed in these states. Yearly population sizes were obtained from the CDC and averaged. Mortality rates (per million individuals per year) by age group for the specific diseases were (for <5 or ≥5 years): Pelizaeus‐Merzbacher (0.037/0.033); sudanophilic leukodystrophy (SLD) (0.037/0.004); Canavan (0.037/0.011), Alexander (0.147/0.022); Krabbe (0.994/0.007); metachromatic leukodystrophy (0.331/0.135); Fabry (0.000/0.124); Gaucher (0.221/0.073); Niemann–Pick (NP) (0.442/0.088); multiple sulfatase (0.000/0.004). This is the first report of mortality rates for the LD/LSD diseases in the U.S. Approximated birth prevalence rate for the early infantile Krabbe phenotype (onset 0–6 months) was based on the <5 year old mortality rate of one early infantile case per 244,000 births, which matches the 1 in 250,000 observed in the NYS newborn screening program as of 2011. It should be noted however that the NYS calculation refers only to the early infantile phenotype and does not include the majority of babies identified in the program with low GALC and two mutations who have remained clinically normal. It is presumed that most, if not all, will develop later onset forms of the disease, but this is by no means certain.

Does Galactocerebrosidase Activity Predict Krabbe Phenotype

This study sought to determine whether galactocerebrosidase activity is predictive of Krabbe onset age, or of survival from onset when controlling for age at onset of signs. We analyzed data on 55 symptomatic patients from the Hunter James Kelly Research Institutes World-Wide Registry. They were tested for galactocerebrosidase activity at Jefferson Medical College (Philadelphia, PA), using survival models in a path model context. Higher galactocerebrosidase activity was predictive of later symptom onset times (P = 0.0011), but did not predict survival after symptom onset (P = 0.9064) when controlling for the logarithm of age at onset. No child with early infantile (aged 0-6 months) phenotype demonstrated galactocerebrosidase activity >0.1 nmol/hour/mg protein. Survival times within a given phenotype did not vary with galactocerebrosidase activity. Although low galactocerebrosidase activity does not predict phenotype, higher activity in the abnormal range (>0.1 nmol/hour/mg protein in this sample) was not identified in the early infantile variant. Galactocerebrosidase activity may be important to consider when predicting phenotype in the newborn screening population. Our findings provide empiric evidence that the upper end (0.15 nmol/hour/mg protein) of the high-risk galactocerebrosidase group in the New York State newborn screening program is conservatively appropriate.

Lifetime risk estimators in epidemiological studies of Krabbe Disease: Review and Monte Carlo comparison.

This review addresses difficulties arising in estimating epidemiological parameters of leukodystrophies and lysosomal storage disorders, with special focus on Krabbe disease. Although multiple epidemiological studies of Krabbe disease have been published, these studies are difficult to reconcile since they have used different study populations and varying methods of calculation. Confusion exists regarding which epidemiological parameters have been estimated; the current review shows that most previous estimates can be properly interpreted as lifetime risk at birth. One of the most common estimation methods is shown to be inaccurate, while two other methods are shown to be approximately accurate. Based on the results of the current paper, recommendations are made that are expected to improve the quality of future studies of Krabbe disease. It is anticipated that these recommendations will be applicable to epidemiological studies of other lysosomal storage disorders, as well as any other rare diseases diagnosed with enzymatic screening.