Mass Spectrometry Evaluation of Biomarkers in the Vitreous Fluid in Gaucher Disease Type 3 with Disease Progression Despite Long-Term Treatment.

Intraocular lesions have been infrequently reported in patients with Gaucher disease type 3 (GD3). We previously reported siblings with GD3 who responded well to the combination of enzyme replacement therapy (ERT) and substrate reduction therapy (SRT). Here we report progressive bilateral vitreous and preretinal deposits with declining visual acuity requiring bilateral vitrectomies in one of these siblings. These ocular manifestations had progressed despite combined ERT and SRT with improvement in visual acuity after vitrectomies. Vitrectomy fluid analysis performed for the first time by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) identified a high concentration of glucosylceramide (GluCer) in the patient (262.842 nM) compared to a sample (0.428 nM from a patient without a lysosomal storage or known hereditary metabolic disorder). The GluCer detected in our patient was resolved into 12 different isoforms including two methylated ones. No evidence of galactosylceramide (GalCer) was detected. The development of these intraocular manifestations and their characterization by UPLC-MS/MS indicate a need for ongoing ophthalmologic evaluation of all GD patients and for new therapies that can cross the blood-retinal and blood-brain barriers for patients with GD and other neuropathic lysosomal storage disorders.

New York Community Health Centers' Population Health Activities: Findings from a Statewide Assessment.

The U.S. spends just 5% of its health care budget to prevent morbidity and mortality. This study surveyed N.Y. State community health centers' (CHCs) population health activities aligned with the N.Y. Prevention Agenda (response rate of 72%). More than half of CHCs considered population health a high priority. Chronic disease and reducing preventable infections were the leading activity areas. One third of activities were dedicated to patient treatment follow-up. Community health centers reported that more than two-thirds of all activities received no funding. Despite a commitment to population health among CHCs, widespread improvements in population health may remain limited without an increase in dedicated funding to support community-based prevention strategies.

Foreign service special care opportunity in SCDA.

A foreign service clinic in Guatemala caring for patients with special needs was initiated by joining SCDA efforts with the Open Wide Foundation. The trip included five SCDA members: two AEGD residents and three support staff. Open Wide participants included the Executive Director, the Clinical Director in Guatemala, as well as two dentists, dental support staff, and Guatemalan dental students. Two physician anesthesiologists provided general anesthesia. Care adjuncts included general anesthesia, oral sedation, and medical stabilization. LESSONS LEARNED: (1) Conducting a dental clinic for patients with special needs is possible and relatively easy to accomplish, given a partnership with a foundation that agrees with and facilitates this service; (2) advance planning is required to maximize the service provided; (3) committed and flexible team members can accomplish a significant amount of care in a short period of time; and (4) limited but invaluable training of in-country healthcare providers is possible. The Special Care Dentistry Association is long known for service and care delivery to patients with special needs by its members, and for its advocacy and organizational support for these activities. A foreign service opportunity in Guatemala, Central America, was sought out by members of the SCDA to further the outreach efforts of the organization, give members clinical experience in a foreign setting, and train in-country providers to deliver care to patients with special needs. This was the first effort by SCDA members to host a clinic to deliver care specifically to patients with special needs outside of North America.

Variation in practice and resource utilization associated with the diagnosis and management of appendicitis at freestanding children's hospitals: implications for value-based comparative analysis.

OBJECTIVE: To characterize the scope and magnitude of practice variation associated with the diagnosis and treatment of appendicitis at freestanding children's hospitals. BACKGROUND: Variation in care has been associated with poor outcomes and is believed to be a key driver of excess health care spending. METHODS: Retrospective cohort study of 13,328 patients treated with appendicitis at 34 children's hospitals (9/2010-9/2011). Patients were divided into complicated and uncomplicated cohorts and examined for interhospital variation in the use of diagnostic imaging (computed tomography or ultrasonography), laboratory tests, parenteral nutrition (PN), peripherally inserted central catheters (PICC), and hospital cost. The number and distribution of statistical outliers were calculated for all measures. RESULTS: Significant variation was found for all measures, including a 3.5-fold difference in preoperative imaging (aggregate rate: 49.0%, range across hospitals: 21.2%-73.5%, P < 0.001) and a 5-fold difference in preoperative laboratory utilization (aggregate median: 2 tests/encounter, range: 1-5 tests/encounter, P < 0.001). For patients with complicated appendicitis, we characterized a 12-fold difference in postoperative imaging (aggregate rate: 19.4%, range: 4.9%-61.6%, P < 0.001), a 48-fold difference in PICC lines (aggregate rate: 18.9%, range: 1.7%-81.8%, P < 0.001), and a 100-fold difference in PN utilization (aggregate rate: 9.3%, range: 0.4%-42.0%, P < 0.001). Median hospital cost differed 4-fold for patients with uncomplicated disease (aggregate median: $6804, range: $4200-$16,796, P < 0.001) and 4.6-fold for patients with complicated disease (aggregate median: $13,138, range: $5419-$24,779, P < 0.001). Statistical outliers on the basis of high and low utilization were identified for all measures. CONCLUSIONS: Significant variation exists in practice, resource utilization, and treatment-related cost associated with the management of appendicitis at freestanding children's hospitals. Value-based measures are needed for benchmarking and to prioritize collaborative quality improvement efforts.

Aortic dissection in hospitalized children and young adults: a multiinstitutional study.

OBJECTIVE: To describe the incidence, characteristics, and outcomes of hospitalized children and young adults with aortic dissection (AD). DESIGN: Retrospective review. SETTING: The Pediatric Health Information System database, a multiinstitutional administrative database. PATIENTS: All index cases of patients <30 years old hospitalized with AD between January 2004 and June 2011. OUTCOME MEASURES: The primary outcome measure was inpatient mortality. RESULTS: Of 3 800 964 hospitalizations, AD was identified in 124 (<1%), accounting for 110 patients (69% male, P = .003) at a median age of 12.9 (interquartile range 3.9-16.8) years with a bimodal distribution in infancy and late adolescence. Associated diagnoses included congenital heart disease (CHD) (38%), trauma (24%), connective tissue disease (CTD) (16%), and isolated hypertension (HTN) (8%). Common CHD diagnoses included aortic arch (24%) and valve (21%) disease, hypoplastic left heart syndrome (10%), and transposition of the great arteries (10%). CHD patients were younger and more likely to undergo inpatient non-AD-related cardiovascular procedures compared with other diagnostic groups (P < .001 for both). Marfan and Ehlers-Danlos syndrome were present in 72% and 11% of CTD patients, respectively. Overall in-hospital mortality in patients with AD was 13% compared with 1% in the database population (odds ratio 12.0, 95% confidence interval 6.9-21.1). By diagnostic category, mortality was 22% in HTN, 22% in CTD, 12% in CHD, and 4% in trauma. CONCLUSIONS: AD is rare in children and young adults but most commonly occurs in CHD and CTD and in males. AD is associated with high inpatient mortality.

Variation in practice patterns and resource utilization surrounding management of intussusception at freestanding Children's Hospitals.

PURPOSE: To characterize variation in practice patterns and resource utilization associated with the management of intussusception at Children's Hospitals. METHODS: A retrospective cohort study (1/1/09-6/30/11) of 27 Children's Hospitals participating in the Pediatric Health Information System database was performed. Hospitals were compared with regard to their rates of operative management following attempted enema reduction, prophylactic antibiotic utilization, same-day discharge for those successfully managed non-operatively, 48-h readmission rates, and case-related cost and charges. RESULTS: 2544 patients were identified (median: 93 cases/center) with a median age of 17 months. The rate of operation following attempted enema reduction varied significantly across hospitals (overall rate: 21.1%: range: 11%-62.8%; p<0.0001). For patients managed non-operatively, significant variability was found for prophylactic antibiotic utilization (overall rate: 23.3%; range: 1.4%-93.2%; p<0.0001), same-day discharge (overall rate: 15.2%; range: 0%-83.8%; p<0.0001), readmission rates (overall rate: 17.5%; range: 5.3%-32.1%; p<0.0001), treatment-related costs (overall median: $2490; range: $829-$5905; p<0.0001), and charges (overall median: $6350; range: $2497-$10,306; p<0.0001). Variability in costs and charges was even greater when analyzing all patients (operative and non-operative) with intussusception (overall cost median: $2865; range: $1574-$6763; p<0.0001; overall charge median: $7110; range: $3544-$22,097; p<0.0001). CONCLUSION: Significant variation in practice patterns and resource utilization exists between Children's Hospitals in the management of intussusception. Prospective analysis of practice variation and appropriately risk-adjusted outcomes through a collaborative quality-improvement platform could accelerate the dissemination of best-practice guidelines for optimizing cost-effective care.

Variation in risk-adjusted hospital readmission after treatment of appendicitis at 38 children's hospitals: an opportunity for collaborative quality improvement.

OBJECTIVES: To identify risk factors associated with readmission for children treated with appendicitis, and to characterize variation in risk-adjusted readmission rates between children's hospitals. BACKGROUND DATA: Hospital readmission has been increasingly targeted as a marker for quality of care, yet little is known regarding risk factors associated with readmission or the degree of performance variation that exists between hospitals for this cohort of patients. METHODS: Retrospective cohort study of 47,866 patients treated at 38 children's hospitals (2006-2010). Multivariate regression was used to examine and adjust for the influence of risk factors on 30-day readmission rates. Hospitals were considered performance outliers if their readmission rate and 95% confidence interval (CI) did not include the overall rate. RESULTS: Factors associated with readmission included disease severity [high vs. low: odds ratio (OR) 4.57, 95% CI: 3.72-5.60; moderate vs. low: OR 2.29, 95% CI: 2.00-2.61] and insurance status (public vs. private: OR 1.14, 95% CI: 1.0-1.29). After adjustment for these factors, the relative decile-based performance rankings changed for 17 (45%) of the 38 hospitals and six (16%) hospitals changed the outlier status based on their standardized readmission rates. A 3.8-fold variation in standardized readmission rates was found across the 38 hospitals after adjustment (overall rate: 8.9%, range: 4.1%-15.4%, P < 0.0001), and 24 (63%) hospitals were identified as outliers (12 low performers and 12 high performers). CONCLUSION: Significant variation in risk-adjusted readmission rates exists among children's hospitals after treatment of appendicitis, and outliers can be identified at both ends of the performance spectrum. These findings may have important implications for the identification and dissemination of "best practices" from exemplar hospitals.

Hospital readmission after management of appendicitis at freestanding children's hospitals: contemporary trends and financial implications.

INTRODUCTION: The purpose of this study was to characterize epidemiologic trends and cost implications of hospital readmission after treatment of pediatric appendicitis. METHODS: We conducted a 5-year retrospective cohort analysis of 30-day readmission rates for 52,054 patients admitted with appendicitis at 38 children's hospitals participating in the Pediatric Health Information System database. Patients were categorized as "uncomplicated" (postoperative length of stay [LOS] ≤ 2 days) or "complicated" (LOS ≥ 3 days and ≥ 4 consecutive days of antibiotics) and analyzed for demographic data, treatment received during the index admission, readmission rates, and excess LOS and hospital-related costs attributable to readmission encounters. RESULTS: The aggregate 30-day readmission rate was 8.7%, and this varied significantly by disease severity and management approach (uncomplicated appendectomy, 5.6%; complicated appendectomy, 12.8%; drainage, 22.6%; antibiotics only, 24.6%; P < .0001). The median hospital cost per case attributable to readmission was $3401 (reflecting a 44% relative increase in cumulative treatment-related cost), and this varied significantly by disease severity and management approach (uncomplicated appendectomy, $1946 [31% relative increase]; complicated appendectomy, $6524 [53% increase]; drainage, $6827 [48% increase]; antibiotics only, $5835 [58% increase]; P < .0001). CONCLUSION: In freestanding children's hospitals, readmission after treatment of pediatric appendicitis is a relatively common and costly occurrence. Collaborative efforts are needed to characterize patient, treatment, and hospital-related risk factors as a basis for developing preventative strategies.

Tuberin haploinsufficiency is associated with the loss of OGG1 in rat kidney tumors.

BACKGROUND: Tuberous sclerosis complex (TSC) is caused by defects in one of two tumor suppressor genes, TSC-1 or TSC-2. TSC-2 gene encodes tuberin, a protein involved in the pathogenesis of kidney tumors. Loss of heterozygosity (LOH) at the TSC2 locus has been detected in TSC-associated renal cell carcinoma (RCC) and in RCC in the Eker rat. Tuberin downregulates the DNA repair enzyme 8-oxoguanine DNA-glycosylase (OGG1) with important functional consequences, compromising the ability of cells to repair damaged DNA resulting in the accumulation of the mutagenic oxidized DNA, 8-oxo-dG. Loss of function mutations of OGG1 also occurs in human kidney clear cell carcinoma and may contribute to tumorgenesis. We investigated the distribution of protein expression and the activity of OGG1 and 8-oxo-dG and correlated it with the expression of tuberin in kidneys of wild type and Eker rats and tumor from Eker rat. RESULTS: Tuberin expression, OGG1 protein expression and activity were higher in kidney cortex than in medulla or papilla in both wild type and Eker rats. On the other hand, 8-oxo-dG levels were highest in the medulla, which expressed the lowest levels of OGG1. The basal levels of 8-oxo-dG were also higher in both cortex and medulla of Eker rats compared to wild type rats. In kidney tumors from Eker rats, the loss of the second TSC2 allele is associated with loss of OGG1 expression. Immunostaining of kidney tissue shows localization of tuberin and OGG1 mainly in the cortex. CONCLUSION: These results demonstrate that OGG1 localizes with tuberin preferentially in kidney cortex. Loss of tuberin is accompanied by the loss of OGG1 contributing to tumorgenesis. In addition, the predominant expression of OGG1 in the cortex and its decreased expression and activity in the Eker rat may account for the predominant cortical localization of renal cell carcinoma.