Validation of a predictive model for obstructive sleep apnea in people with Down syndrome.

Detecting obstructive sleep apnea (OSA) is important to both prevent significant comorbidities in people with Down syndrome (DS) and untangle contributions to other behavioral and mental health diagnoses. However, laboratory-based polysomnograms are often poorly tolerated, unavailable, or not covered by health insurance for this population. In previous work, our team developed a prediction model that seemed to hold promise in identifying which people with DS might not have significant apnea and, consequently, might be able to forgo a diagnostic polysomnogram. In this study, we sought to validate these findings in a novel set of participants with DS. We recruited an additional 64 participants with DS, ages 3-35 years. Caregivers completed the same validated questionnaires, and our study team collected vital signs, physical exam findings, and medical histories that were previously shown to be predictive. Patients then had a laboratory-based polysomnogram. The best modeling had a validated negative predictive value of 50% for an apnea-hypopnea index (AHI) > 1/hTST and 73.7% for AHI >5/hTST. The positive predictive values were 60% and 39.1%, respectively. As such, a clinically reliable screening tool for OSA in people with DS was not achieved. Patients with DS should continue to be monitored for OSA according to current healthcare guidelines.

A predictive model for obstructive sleep apnea and Down syndrome.

Obstructive sleep apnea (OSA) occurs frequently in people with Down syndrome (DS) with reported prevalences ranging between 55% and 97%, compared to 1-4% in the neurotypical pediatric population. Sleep studies are often uncomfortable, costly, and poorly tolerated by individuals with DS. The objective of this study was to construct a tool to identify individuals with DS unlikely to have moderate or severe sleep OSA and in whom sleep studies might offer little benefit. An observational, prospective cohort study was performed in an outpatient clinic and overnight sleep study center with 130 DS patients, ages 3-24 years. Exclusion criteria included previous adenoid and/or tonsil removal, a sleep study within the past 6 months, or being treated for apnea with continuous positive airway pressure. This study involved a physical examination/medical history, lateral cephalogram, 3D photograph, validated sleep questionnaires, an overnight polysomnogram, and urine samples. The main outcome measure was the apnea-hypopnea index. Using a Logic Learning Machine, the best model had a cross-validated negative predictive value of 73% for mild obstructive sleep apnea and 90% for moderate or severe obstructive sleep apnea; positive predictive values were 55% and 25%, respectively. The model included variables from survey questions, medication history, anthropometric measurements, vital signs, patient's age, and physical examination findings. With simple procedures that can be collected at minimal cost, the proposed model could predict which patients with DS were unlikely to have moderate to severe obstructive sleep apnea and thus may not need a diagnostic sleep study.

Thyroid dysfunction in patients with Down syndrome: Results from a multi-institutional registry study.

The goals of this undertaking were to assess the outcomes of thyroid screening tests and adherence to thyroid screening guidelines across five Down syndrome (DS) specialty clinics in various states. Data related to thyroid screening were collected for 663 individuals across five clinics specializing in the comprehensive care of individuals with DS for a period of 1 year. Of the 663 participants, 47.7% of participants had a TSH and free T4 ordered at their DS specialty clinic visit. Approximately 19.0% (60/316) had a new thyroid disorder diagnosis made. We conclude that a sizable proportion of the patients with DS are not up-to-date on current guidelines when they present to a DS specialty clinic, while adherence to thyroid screening guidelines helps facilitate early diagnoses. Hypothyroidism is prevalent in the population, consistent with reported literature. DS specialty clinics can help patients stay current on screening guidelines.

Detecting celiac disease in patients with Down syndrome.

The main purposes of this undertaking were to determine how often patients with Down syndrome (DS) are screened for celiac disease (CD) across five DS specialty clinics, which symptoms of CD are most often reported to DS specialty providers at these clinics, and, how many individuals were diagnosed with CD by these clinics. This was accomplished by following 663 individuals with DS for 1 year, across five clinics in different states specializing in the comprehensive care of people with DS. Of the 663 participants, 114 individuals were screened for CD at their visit to a DS specialty clinic. Protracted constipation (43.2%) and refractory behavioral problems (23.7%) were symptoms most often reported to DS specialty providers. During the 1 year study period, 13 patients screened positive for CD by serology. Of those, eight underwent duodenal biopsy, and three were diagnosed with CD. We conclude that CD is an important consideration in the comprehensive care of individuals with DS. However, while symptoms are common, diagnoses are infrequent in DS specialty clinics. © 2016 Wiley Periodicals, Inc.

National down syndrome patient database: Insights from the development of a multi-center registry study.

The Down Syndrome Study Group (DSSG) was founded in 2012 as a voluntary, collaborative effort with the goal of supporting evidenced-based health care guidelines for individuals with Down syndrome (DS). Since then, 5 DS specialty clinics have collected prospective, longitudinal data on medical conditions that co-occur with DS. Data were entered by clinical staff or trained designees into the National Down Syndrome Patient Database, which we created using REDCap software. In our pilot year, we enrolled 663 participants across the U.S., ages 36 days to 70 years, from multiple racial and ethnic backgrounds. Here we report: (i) the demographic distribution of participants enrolled, (ii) a detailed account of our database infrastructure, and (iii) lessons learned during our pilot year to assist future researchers with similar goals for other patient populations.

Building bridges: an innovative academic-service partnership.

Academic and service entities can create sustainable models of collaboration that realign relationships and resources to enhance the critical competencies essential for entry into practice. Our hospital and school collaborated to implement an innovative academic-service partnership model in which the academic and the care delivery enterprises intersected to accomplish goals of mutual interest and enhance and enrich the practice environment. Two existing resources-the staff nurse and faculty-were used to realign the educational process with the realities of nursing practice in an interpretive, contextual, live unfolding clinical environment that was relevant and memorable. The students were better integrated into the clinical operations and showed increased levels of critical thinking, clinical decision-making, and clinical inquiry skills. The model holds promise to improve transition to practice, make better use of existing resources, and foster collaborative relationships among the academic, practice, and regulatory enterprises.

A Randomized, Double-Blind, Placebo-Controlled, Phase II Study of Oral ELND005 (scyllo-Inositol) in Young Adults with Down Syndrome without Dementia.

BACKGROUND: ELND005 (scyllo-Inositol; cyclohexane-1,2,3,4,5,6-hexol) has been evaluated as a potential disease-modifying treatment for Alzheimer's disease (AD). Individuals with Down syndrome (DS) have an increased risk for developing AD dementia. OBJECTIVE: To evaluate the safety and tolerability of ELND005 and to determine its pharmacokinetics (PK) and relationship between PK parameters, safety outcome measures, and exploratory efficacy outcome measures in young adults with DS without dementia. METHODS: This was a prospective, randomized, double-blind, placebo-controlled, parallel-group, three-arm, multicenter Phase II study of the safety and pharmacokinetics of ELND005 administered orally for 4 weeks (ClinicalTrials.gov NCT01791725). Participants who met study eligibility criteria were randomly assigned in a 2 : 1:1 ratio to receive ELND005 at either 250 mg twice daily (BID) or 250 mg once daily (QD) or matching placebo for 4 weeks. RESULTS: There were no apparent treatment group-related trends on cognitive or behavioral measures and there were no SAEs and no deaths in the study. Overall, mean changes from baseline in clinical laboratory parameters, vital sign measurements, electrocardiogram results, and other physical findings were unremarkable. ELND005 accumulation averaged approximately 2-fold with QD dosing, and 3- to 4-fold with BID dosing. CONCLUSION: Overall, treatment of adults with DS with ELND005 at both doses was well tolerated, achieved measurable blood levels and demonstrated no safety findings. Further studies will be needed to test efficacy.