The association between pediatric mental health disorders and type 1 diabetes-related outcomes.

OBJECTIVE: Transition from pediatric to adult healthcare systems is a difficult process for young adults with Type 1 Diabetes (T1D) and most patients experience a deterioration in disease control. Mental health (MH) disorders are common in individuals with T1D and are believed to play a role in disease control and transition of care. We evaluated the association between the presence of pediatric MH disorder and measures of success in diabetes care in young adults who recently transitioned to adult care. RESEARCH DESIGN AND METHODS: Retrospective cohort study of young adults in a large adult endocrinology system who transitioned from a pediatric hospital system after 2009. MH disorders were diagnosed by clinical pediatric psychologists during routine care at the pediatric hospital. Measurements of Hemoglobin A1c, diabetes-related emergencies, clinic attendance and intervals in transition were assessed and compared between the pediatric and adult hospital systems. RESULTS: 237 young adults were identified and 100 (42%) of these were diagnosed with a MH disorder during pediatric care. Presence of a MH disorder was associated with higher Hemoglobin A1c levels prior to transition and increased rates of diabetes-related hospitalizations during the transition interval. Patients with a MH disorder were less likely to establish a pattern of consistent follow up after transition (p = 0.021). CONCLUSIONS: MH disorders are common and predict greater challenges with diabetes management and less effective transition into the adult endocrinology system. Early recognition of MH disorders may allow for allocation of more proactive and intensive support for affected patients.

Testing an Automated Approach to Identify Variation in Outcomes among Children with Type 1 Diabetes across Multiple Sites.

Introduction: Efficient methods to obtain and benchmark national data are needed to improve comparative quality assessment for children with type 1 diabetes (T1D). PCORnet is a network of clinical data research networks whose infrastructure includes standardization to a Common Data Model (CDM) incorporating electronic health record (EHR)-derived data across multiple clinical institutions. The study aimed to determine the feasibility of the automated use of EHR data to assess comparative quality for T1D. Methods: In two PCORnet networks, PEDSnet and OneFlorida, the study assessed measures of glycemic control, diabetic ketoacidosis admissions, and clinic visits in 2016-2018 among youth 0-20 years of age. The study team developed measure EHR-based specifications, identified institution-specific rates using data stored in the CDM, and assessed agreement with manual chart review. Results: Among 9,740 youth with T1D across 12 institutions, one quarter (26%) had two or more measures of A1c greater than 9% annually (min 5%, max 47%). The median A1c was 8.5% (min site 7.9, max site 10.2). Overall, 4% were hospitalized for diabetic ketoacidosis (min 2%, max 8%). The predictive value of the PCORnet CDM was >75% for all measures and >90% for three measures. Conclusions: Using EHR-derived data to assess comparative quality for T1D is a valid, efficient, and reliable data collection tool for measuring T1D care and outcomes. Wide variations across institutions were observed, and even the best-performing institutions often failed to achieve the American Diabetes Association HbA1C goals (<7.5%).

Adult growth hormone deficiency: Optimizing transition of care from pediatric to adult services.

OBJECTIVE: Most patients with childhood-onset growth hormone deficiency (CO-GHD) receive treatment with exogenous growth hormone (GH) to facilitate the attainment of their full potential adult height. Recent evidence suggests that continuing GH administration during the transition period between the end of linear growth and full adult maturity is necessary for proper body composition and bone and muscle health, and may also have beneficial effects on metabolic parameters, bone mineral density, and quality of life. The timing of this transition period coincides with the transfer of care from a pediatric to an adult endocrinologist, creating the potential for a care gap as a consequence of losing the patient to follow-up. DESIGN: An advisory board comprising both pediatric and adult endocrinologists was assembled to address current clinical unmet needs and to collaborate on a structured transitional plan for optimal management of patients with CO-GHD. INSIGHTS/CONCLUSION: The advisors suggest collaborative, multidisciplinary approaches to ensure continuity of care; ongoing testing and monitoring of GHD status into adulthood; and a clearly structured protocol that includes practical guidance for clinicians to establish best practices for transitioning older adolescents with persistent CO-GHD to adult care.

Validation of the Healthcare Transition Outcomes Inventory for Young Adults With Type 1 Diabetes.

OBJECTIVE: We recently developed and content validated the Healthcare Transition Outcomes Inventory (HCTOI), a stakeholder vetted, multidimensional measure of the outcomes of the transition from pediatric to adult healthcare for young adults (YA) with type 1 diabetes (T1D). In this study, we aimed to evaluate the psychometric properties of the HCTOI. METHODS: We collected and analyzed cross-sectional data from 128 YA (18-25 years old) with T1D to evaluate the psychometric properties of the HCTOI. We conducted confirmatory factor analysis (CFA), item analysis, and examined reliability and validity in relation to measures of quality of life, diabetes distress, regimen adherence, and glycemic control. RESULTS: CFA supported a five-factor solution: integration of T1D into emerging adult roles, balance of parental support with T1D autonomy, establishing and maintaining continuity of care, forming a collaborative patient-provider relationship, and ownership of T1D. We reduced the HCTOI from 54 to 34 items. The HCTOI demonstrated adequate internal consistency (α's = 0.62-0.87) and significant correlations demonstrated construct (quality of life, diabetes distress) and criterion validity (adherence, glycemic control). CONCLUSIONS: The HCTOI demonstrated promising initial psychometric properties. As the first measure of the multiple dimensions of healthcare transition outcomes, the HCTOI provides a means to examine longitudinal relations between transition readiness and outcomes and to assess the efficacy or effectiveness of interventions and programs designed to improve the transition process for YA with T1D.

Development and content validation of the Healthcare Transition Outcomes Inventory for young adults with type 1 diabetes.

BACKGROUND: The literature on the specification and measurement of the outcomes of the healthcare transition from pediatric to adult centered-care is scarce and methodologically weak. To address these gaps, we conducted a series of studies to develop a multidimensional, multi-informant (young adults, parents, and healthcare providers) measure of healthcare transition outcomes for young adults with type 1 diabetes (T1D), the Healthcare Transition Outcomes Inventory (HCTOI). The current study describes the development and refinement of the HCTOI item pool. METHODS: Following Patient Reported Outcomes Measurement Information System (PROMIS) standards, the research team conducted qualitative interviews to define six content domains of healthcare transition outcomes from the perspectives of multiple stakeholders, developed an initial item pool of the HCTOI based on the six domains, analyzed expert item ratings and feedback for content validation, and conducted cognitive interviews with informants (patients, parents, and healthcare providers) for further item pool refinement. RESULTS: Qualitative findings revealed six healthcare transition outcome domains: 1) Biomedical markers of T1D control; 2) Navigation of a new health care system; 3) Possession of T1D self-management skills and knowledge; 4) Integration of T1D care into emerging adult roles; 5) Balance of parental involvement with autonomy; and 6) Attainment of T1D "ownership." An initial pool of 88 items focused on the extent to which a young adult with T1D is successful on each of the six domains. Experts rated all content domains and all but six items as relevant. In addition to suggesting additional items, experts were concerned about the length of the measure, response burden, and whether every informant type would have sufficient knowledge to rate items in particular content domains. Cognitive interviews resulted in retaining all six content domains, but dropping some items and yielded fewer items for the healthcare provider version (47 items versus 54 items for the young adult- and parent-versions). CONCLUSIONS: Expert review and cognitive interviews confirmed that all six domains of HCT outcomes were relevant and both procedures resulted in retaining a sufficient number of clear and representative items for each content domain. The HCTOI represents the first multi-informant, rigorously developed item pool that comprehensively measures the multiple components of the transition from pediatric to adult specialty healthcare.

Diagnostic Accuracy of Ultrasound With Color Flow Doppler in Children With Thyroid Nodules.

Context: Thyroid nodules are increasingly recognized in children and are associated with a greater risk for thyroid cancer compared with adults. Thyroid ultrasound is the favored tool for evaluation of thyroid nodules; however, there are limited data regarding the accuracy of thyroid ultrasound to confirm features associated with a low risk of thyroid cancer in children. Objectives: We examined whether thyroid ultrasound is capable of accurately identifying thyroid nodules at a low risk of malignancy in children. Design and Setting: Using a retrospective cohort study design, we identified children age ≤18 years with thyroid nodules and adequate follow-up. Ultrasound images were reviewed independently by two blinded expert radiologists, and ultrasound characteristics were analyzed to determine optimal predictive value and reliability. Patients and Results: A total of 417 subjects were found to have thyroid nodules, and 152 subjects had adequate follow-up; 59 (38.8%) of these were diagnosed with thyroid cancer. We evaluated 236 individual nodules. Features most consistent with benign nodules included small size, isoechoic echogenicity, partially cystic structure, sharp or noninfiltrative margins, absent Doppler flow, and absent calcifications. Significant variability was found between expert interpretations of ultrasound features. Thyroid nodule composition appears to be the most sensitive and reliable feature for stratifying the risk of thyroid cancer. Ultrasound accurately identified benign thyroid nodules in 80.9% of subjects (95% confidence interval, 74-86.6). Conclusions: Ultrasonography is useful for the evaluation of thyroid nodules, but we found no combination of ultrasound features sufficient to exclude thyroid cancer without a biopsy.

Operating Range for a Combined, Building-Scale Liquid Air Energy Storage and Expansion System: Energy and Exergy Analysis.

This paper presents the results of an ideal theoretical energy and exergy analysis for a combined, building scale Liquid Air Energy Storage (LAES) and expansion turbine system. This work identifies the upper bounds of energy and exergy efficiency for the combined LAES-expansion system which has not been investigated. The system uses the simple Linde-Hampson and pre-cooled Linde-Hampson cycles for the liquefaction subsystem and direct expansion method, with and without heating above ambient temperature, for the energy production subsystem. In addition, the paper highlights the effectiveness of precooling air for liquefaction and heating air beyond ambient temperature for energy production. Finally, analysis of the system components is presented with an aim toward identifying components that have the greatest impact on energy and exergy efficiencies in an ideal environment. This work highlights the engineering trade-space and serves as a prescription for determining the merit or measures of effectiveness for an engineered LAES system in terms of energy and exergy. The analytical approach presented in this paper may be applied to other LAES configurations in order to identify optimal operating points in terms of energy and exergy efficiencies.

Health Care Transition for Young Adults With Type 1 Diabetes: Stakeholder Engagement for Defining Optimal Outcomes.

Objectives: Research on the transition to adult care for young adults with type 1 diabetes (T1D) emphasizes transition readiness, with less emphasis on transition outcomes. The relatively few studies that focus on outcomes use a wide variety of measures with little reliance on stakeholder engagement for measure selection. Methods: This study engaged multiple stakeholders (i.e., young adults with T1D, parents, pediatric and adult health care providers, and experts) in qualitative interviews to identify the content domain for developing a multidimensional measure of health care transition (HCT) outcomes. Results: The following constructs were identified for a planned measure of HCT outcomes: biomedical markers of T1D control; T1D knowledge/skills; navigation of a new health care system; integration of T1D into emerging adult roles; balance of parental involvement with autonomy; and "ownership" of T1D self-management. Discussion: The results can guide creation of an initial item pool for a multidimensional profile of HCT outcomes.

Cinacalcet monotherapy in neonatal severe hyperparathyroidism: a case study and review.

CONTEXT: Neonatal severe hyperparathyroidism (NSHPT) is a severe form of familial hypocalciuric hypercalcemia characterized by severe hypercalcemia and skeletal demineralization. In most cases, NSHPT is due to biallelic loss-of-function mutations in the CASR gene encoding the calcium-sensing receptor (CaSR), but some patients have heterozygous mutations. Conventional treatment consists of iv saline, bisphosphonates, and parathyroidectomy. OBJECTIVE: The aim of this project was to characterize the molecular basis for NSHPT in an affected newborn and to describe the response to monotherapy with cinacalcet. METHODS: Clinical and biochemical features were monitored as cinacalcet therapy was initiated and maintained. Genomic DNA was obtained from the proband and parents. The CASR gene was amplified by PCR and sequenced directly. RESULTS: The patient was a full-term male who developed hypotonia and respiratory failure soon after birth. He was found to have multiple fractures and diffuse bone demineralization, with a marked elevation in serum ionized calcium (1.99 mmol/L) and elevated serum levels of intact PTH (1154 pg/mL); serum 25-hydroxyvitamin D was low, and fractional excretion of calcium was reduced. The serum calcium level was not reduced by iv saline infusion. Based on an extensive family history of autosomal dominant hypercalcemia, a diagnosis of NSHPT was made, and cinacalcet therapy was initiated with a robust and durable effect. Molecular studies revealed a heterozygous R185Q missense mutation in the CASR in the patient and his father, whereas normal sequences for the CASR gene were present in the patient's mother. CONCLUSIONS: We describe the first use of cinacalcet as monotherapy for severe hypercalcemia in a newborn with NSHPT. The rapid and durable response to cinacalcet suggests that a trial of calcimimetic therapy should be considered early in the course of NSHPT.

Oxidative stress in Dahl salt-sensitive hypertension.

The role of oxidative stress in the long-term regulation of arterial pressure, renal hemodynamics, and renal damage was studied in Dahl salt-sensitive rats. Twenty-eight Dahl S/Rapp strain rats, equipped with indwelling arterial and venous catheters, were subjected to a 3-week intravenous infusion of either low Na (0.9 mmol/d) or high Na (20.6 mmol/d) or the superoxide dismutase mimetic, 4-hydroxyl-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), at 125 micromol x kg(-1) x h(-1) plus low Na or high Na. After 21 days, mean arterial pressure was 140+/-3 mm Hg in the high-Na group, 118+/-1 mm Hg (P<0.05) in the high-Na/Tempol group, and unchanged in the low-Na/Tempol and low-Na groups. Tempol did not change renal blood flow, glomerular filtration rate, or glomerular cross-sectional area in rats subjected to the high-Na intake but did decrease urinary protein excretion, the percentage of sclerotic glomeruli, and the kidney weight to body weight ratio. In 15 additional Dahl S rats subjected to high or low Na intake for 3 weeks, renal cortical and medullary O2*- release increased significantly in the high-Na group when compared with the low-Na group. Tempol decreased both renal cortical and medullary O2*- release in the high- and low-Na rats, but the decrease in O2*- release was greater in high-Na rats. The data suggest that oxidative stress contributes to Dahl salt-sensitive hypertension and the accompanying renal damage.

Mechanisms of salt-sensitive hypertension: role of renal medullary inducible nitric oxide synthase.

The goal of this study was to determine the role of renal medullary inducible nitric oxide synthase (iNOS) in the arterial pressure, renal hemodynamic, and renal excretory changes that occur in Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats during high Na intake. Forty R and S rats, equipped with indwelling arterial, venous, and renal medullary catheters, were subjected to high (8%) Na intake, and selective iNOS inhibition was achieved with continuous intravenous or renal medullary interstitial infusion of aminoguanidine (AG; 3.075 mg. kg(-1). h(-1)). After 5 days of AG, mean arterial pressure increased to 132 +/- 2% control in the S rats with high Na intake and intramedullary AG compared with 121 +/- 4% control (P < 0.05) in the S rats with high Na intake alone and 121 +/- 2% control (P < 0.05) in the S rats with high Na intake and intravenous AG. AG did not change arterial pressure in R rats. AG also caused little change in renal hemodynamics, urinary Na, or H(2)O excretion or ACh-induced aortic vasorelaxation in R or S rats. The data suggest that during high Na intake, nitric oxide produced by renal medullary iNOS helps to prevent excessive increases in arterial pressure in the Dahl S rat but not the R rat.