Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. Two separate retrospective case–control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case–control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05–1.16) and mortality (OR 1.76, 95 % CI 1.67–1.84) among patients taking PPIs versus those not on PPIs. Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

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.

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. Three statewide databases were merged: 1998 Birth Vital Statistics; 1997-1998 Medicaid eligibility files; and 1998-2001 Children's Medical Services' Early Intervention Program (CMS-EIP) data. Infants who died within the first year of life and plural births were excluded. The final dataset consisted of 170,874 records. A child was determined to have a DDD if a developmental delay, or an established condition, such as sensory impairment, genetic, metabolic, neurological, or severe attachment disorders, was diagnosed through a multidisciplinary evaluation. Logistic regression models were used to relate BW to DDD, controlling for sociodemographic, behavioral, and perinatal variables. Adjusted odds ratios (OR) were calculated to describe the effects of BW on DDD. There was a significant effect of BW on DDD (Adjusted OR &equals 97.50, 40.01, 15.84, 3.29, 1.39, 1.00, 1.52 for BW categories 450-749, 750-999, 1000-1499, 1500- 2499, 2500-2999, 3000-4749, 4750-6050 g, respectively). In these categories, 70%, 56%, 36%, 11%, 4%, 3%, and 6% of surviving singleton infants, respectively, suffered a DDD in their first 3 years of life. Four medical, five sociodemographic, and two behavioral factors were significant in addition to BW. An equation for predicting the probability of DDD given these factors was obtained, and its use exemplified. BW is strongly associated with DDD. Over 60% of infants weighing < 1000 g and nearly half (46%) of those weighing < 1500 g at birth are diagnosed with a DDD before 3 years of age. The probability of DDD for a specific infant also varies by sociodemographic, other perinatal, and behavioral factors. The results of this paper suggest that all surviving infants of BW < 1000 g, and perhaps < 1500 g, should be automatically referred for evaluation.

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 diagn...

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. Glycosaminoglycans (GAGs) offer potential as a confirmatory test. KD NBS programs utilize galactocerebrosidase (GaLC) as an initial test, with psychosine (PSY) activity increasingly used as a confirmatory test for predicting onset of Krabbe disease, though with an excessive false positive rate. PD is marked by a deficiency in acid α-glucosidase (GAA), causing increased glycogen, creatine (CRE), and other biomarkers. Bivariate normal limit (BVNL) methods have been applied to GaLC and PSY activity to produce a NBS tool for KD, and more recently, to IDUA and GAG activity to develop a NBS tool for MPS I. A BVNL tool based on GAA and CRE is in development for infantile PD diagnosis. Early infantile KD, MPS I, and PD cases were pre-symptomatically identified by BVNL-based NBS tools. This article reviews these developments, discusses how they address screening deficiencies identified by the RUSP and may improve NBS more generally.