A Roadmap for Potential Improvement of Newborn Screening for Inherited Metabolic Diseases Following Recent Developments and Successful Applications of Bivariate Normal Limits for Pre-Symptomatic Detection of MPS I, Pompe Disease, and Krabbe Disease.

The mucopolysaccharidoses (MPS), Pompe Disease (PD), and Krabbe disease (KD) are inherited conditions known as lysosomal storage disorders (LSDs) The resulting enzyme deficiencies give rise to progressive symptoms. The United States Department of Health and Human Services' Recommended Uniform Screening Panel (RUSP) suggests LSDs for inclusion in state universal newborn screening (NBS) programs and has identified screening deficiencies in MPS I, KD, and PD NBS programs. MPS I NBS programs utilize newborn dried blood spots and assay alpha L-iduronidase (IDUA) enzyme to screen for potential cases.

Death rates in the U.S. due to Leukodystrophies with pediatric forms.

To use national mortality and state death certificate records to estimate disease specific mortality rates among pediatric and adult populations for 23 leukodystrophies (LDs) with pediatric forms. Additionally, to calculate yearly prevalence and caseload of the most severe LD cases that will eventually result in pediatric death (i.e.

Development of a newborn screening tool for mucopolysaccharidosis type I based on bivariate normal limits: Using glycosaminoglycan and alpha-L-iduronidase determinations on dried blood spots to predict symptoms.

Purpose: Current newborn screening (NBS) for mucopolysaccharidosis type I (MPSI) has very high false positive rates and low positive predictive values (PPVs). To improve the accuracy of presymptomatic prediction for MPSI, we propose an NBS tool based on known biomarkers, alpha-L-iduronidase enzyme activity (IDUA) and level of the glycosaminoglycan (GAG) heparan sulfate (HS).

Methods: We developed the NBS tool using measures from dried blood spots (DBS) of 5000 normal newborns from Gifu Prefecture, Japan.

Survey of quality of life, phenotypic expression, and response to treatment in Krabbe leukodystrophy.

Objectives: To develop a quality of life (QOL) survey for Krabbe disease (KD), and to thereby improve understanding of its phenotypic expression and response to treatment.

Methods: The survey, the Leukodystrophy Quality of Life Assessment (LQLA) and the Vineland Adaptive Behavior Scales were co-administered to 33 patients or their caretakers. These included the phenotypes of early infantile KD (EIKD; 0-6 months old at onset), late infantile cases (LIKD; 7-12 months old at onset), and cases that emerged after 12 months old, late onset (LOKD).

Development of a newborn screening tool based on bivariate normal limits: using psychosine and galactocerebrosidase determination on dried blood spots to predict Krabbe disease.

Purpose: Newborn screening for Krabbe disease (KD) originated in New York State in 2006 but has proven to have a high false positive rate and low positive predictive value. To improve accuracy of presymptomatic prediction, we propose a screening tool based on two biomarkers, psychosine and galactocerebrosidase enzyme activity (GalC).

Methods: We developed the tool using measures from dried blood spots of 166 normal newborns and tested it on dried blood spot measures from 15 newborns who later developed KD, 8 newborns identified as "high risk" by the New York screening protocol but were disease-free at follow-up, and 3 symptomatic children with onset before 4 years of age.

Evidence for improved survival in postsymptomatic stem cell-transplanted patients with Krabbe's disease.

Krabbe's disease (KD) is a severe neurodegenerative disorder affecting white matter in the brain and peripheral nerves. Transplantation of hematopoietic stem cells (HSCT), although not curative, has been shown to extend survival and alleviate neurodevelopmental symptoms when treatment precedes the onset of symptoms. Existing evidence, although not tested statistically, seems clearly to show that postsymptomatic transplantation does not improve neurodevelopmental outcomes.

Can psychosine and galactocerebrosidase activity predict early-infantile Krabbe's disease presymptomatically?

Krabbe's disease (KD) is a fatal neurodegenerative disorder, with the early-infantile form (EIKD) defined by onset of symptoms before age 6 months. Early and highly accurate identification of EIKD is required to maximize benefits of hematopoietic stem cell transplantation treatment. This study investigates the potential for accurate prediction of EIKD based on a novel newborn screening (NBS) tool developed from two biomarkers, galactocerebrosidase (GALC) enzyme activity and galactosylsphingosine concentration (psychosine [PSY]).

Mortality incidence estimation using federal death certificate and natality data with an application to Tay-Sachs disease.

For confidentiality reasons, US federal death certificate data are incomplete with regards to the dates of birth and death for the decedents, making calculation of total lifetime of a decedent impossible and thus estimation of mortality incidence difficult. This paper proposes the use of natality data and an imputation-based method to estimate age-specific mortality incidence rates in the face of this missing information. By utilizing previously determined probabilities of birth, a birth date and death date are imputed for every decedent in the dataset.

Patient and physician factors associated with participation in cervical and uterine cancer trials: an NRG/GOG247 study.

Purpose: The aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials.

Methods: Prospective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial.

Multiple indicators, multiple causes measurement error models.

Multiple indicators, multiple causes (MIMIC) models are often employed by researchers studying the effects of an unobservable latent variable on a set of outcomes, when causes of the latent variable are observed. There are times, however, when the causes of the latent variable are not observed because measurements of the causal variable are contaminated by measurement error. The objectives of this paper are as follows: (i) to develop a novel model by extending the classical linear MIMIC model to allow both Berkson and classical measurement errors, defining the MIMIC measurement error (MIMIC ME) model; (ii) to develop likelihood-based estimation methods for the MIMIC ME model; and (iii) to apply the newly defined MIMIC ME model to atomic bomb survivor data to study the impact of dyslipidemia and radiation dose on the physical manifestations of dyslipidemia.

Renal function, calcium regulation, and time to hospitalization of patients with chronic kidney disease.

Background: Chronic kidney disease is associated with disruption of the endocrine system that distorts the balance between calcitriol, calcium, phosphate and parathyroid hormone in the calcium regulation system. This can lead to calcification of the arterial tree and increased risk of cardiovascular disease and death. In this study we develop a health metric, based on biomarkers involved in the calcium regulation system, for use in identifying patients at high risk for future high-cost complications.

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.

A modified Latent Class Model assessment of human papillomavirus-based screening tests for cervical lesions in women with atypical glandular cells: a Gynecologic Oncology Group study.

Purpose: In the absence of gold standard diagnoses, we estimate age-specific false-positive and false-negative prediction rates of HPV-, cytology-, and histology-based tests for significant cervical lesions (SCL) in US women with AGC-NOS Pap smear diagnoses.

Methods: Modified Latent Class Model (LCM) analyses, with prevalence of SCL modeled as a function of age, were applied to GOG-0171 study data (n = 122). The accuracies of several HPV-based tests, including Hybrid Capture II high-risk HPV (HC2 H-HPV); carbonic anhydrase IX (CA-IX); and invasive histological diagnosis, were compared.

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.

Predicting hospital cost in CKD patients through blood chemistry values.

Background: Controversy exists in predicting costly hospitalization in patients with chronic kidney disease and co-morbid conditions. We therefore tested associations between serum chemistry values and the occurrence of in-patient hospital costs over a thirteen month study period. Secondarily, we derived a linear combination of variables to estimate probability of such occurrences in any patient.

Relating illness complexity to reimbursement in CKD patients.

Background: Despite significant investments of federal and state dollars to transition patient medical records to an all-electronic system, a chasm still exists between health care quality and payment for it. A major reason for this gap is the difficulty in evaluating health care outcomes based on claims data. Since both payers and patients may not appreciate how illness complexity impacts treatment outcomes, it is difficult to determine fair provider compensation.

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.

Music and video as distractors for boys with ADHD in the classroom: comparison with controls, individual differences, and medication effects.

This study examined the effects of music and video on the classroom behavior and performance of boys with and without attention deficit hyperactivity disorder (ADHD) and examined the effects of 0.3 mg/kg methylphenidate (MPH). In one study, 41 boys with ADHD and 26 controls worked in the presence of no distractor, music, or video.

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.

Standardized risk and description of results from multivariable modeling of a binary response.

Descriptions of significant associations found from a logistic regression analysis typically are based on adjusted odds ratios. Unfortunately, odds ratios provide no information about the prevalence of response. In this paper, we justify and recommend using standardized risks, i.

Risk factors for infant maltreatment: a population-based study.

Context: Of the approximately 900,000 children who were determined to be victims of abuse or neglect by US child protective services in 2002, the birth-to-3 age group had the highest rate of victimization (1.6%) and children younger than 1 accounted for the largest percentage of victims (9.6%).

Patency of autogenous and polytetrafluoroethylene upper extremity arteriovenous hemodialysis accesses: a systematic review.

Objective: Patency rates for autogenous accesses are presumed to be better than for polytetrafluoroethylene (PTFE) accesses, although the strength of the supporting evidence is limited. We undertook this study to test the hypothesis that patency rates for upper extremity autogenous hemodialysis arteriovenous accesses in adults are superior to those for PTFE counterparts.

Methods: A systematic review of relevant literature and meta-analysis of the patency data were performed.

A population-based study of the effects of birth weight on early developmental delay or disability in children.

Improving medical treatment of extremely low-birth-weight infants over the last 20 to 30 years resulted in increased survival rates. The developmental sequela of salvaged infants is of great interest to perinatologists. The primary purposes of the current study were to assess the effect of birth weight (BW) on developmental delay or disability (DDD) in the first three years of life and determine whether there is a BW threshold below which all infants should be evaluated to determine if intervention services for children with DDD should be received.

A risk assessment screening test for very low birth weight.

Objectives: To develop a risk-assessment screening tool for very low birth weight (VLBW) and to compare our empirically derived tool to the nonempirically derived screening tool used by the State of Florida.

Methods: Birth records from the State of Florida Vital Statistics between 04/01/92 and 12/07/94 were matched with State Healthy Start prenatal records, reported from 04/01/92 through 03/31/94. Known and additional potentially important risk factors were identified from both sources.

A prospective analysis of stress and fatigue in recurrent low back pain.

The purpose of the present study was to determine whether patients with recurrent low back pain display a different pattern of mood fluctuations across days than matched healthy controls and whether these mood states are related to pain occurrence and/or magnitude using a prospective design. The questions addressed are whether mood states prior to a pain episode are associated with the episode or whether mood relates to pain as a secondary reaction. Similarly, the relationship between mood state recorded prior to, during or following pain and magnitude of pain experienced was investigated.