Health-related quality of life and medication use among individuals with Angelman syndrome.

PURPOSE: The primary goal of this analysis is to describe the health-related quality of life (HRQoL), medical history, and medication use among adolescents and adults individuals with Angelman syndrome (AS). METHODS: The analysis uses baseline data collected during the STARS study, a double-blind placebo controlled trial of gaboxadol (OV101) in adolescents and adults with AS. The HRQoL was estimated using EuroQoL 5-Dimension 5-Level (EQ-5D) health questionnaire proxy 1 version, which was completed by the caregivers. EQ-5D consists of two parts, a 5-dimension descriptive and a visual analogue scale (VAS) component. The utility score derived from EQ-5D ranges from 0 to 1 (perfect health) and VAS ranges from 0 to 100 (perfect health). RESULTS: 87 individuals with AS were included in the present analysis. The mean utility score was 0.44 ± 0.20 and VAS score was 84 ± 1.5. The EQ-5D data indicated that the self-care, mobility and daily activities were most impacted. All adolescents (100%) and most adults (93%) had at least moderate problems with self-care activities, such as washing or dressing themselves. More than half (55%) of the adolescents and adults had at least moderate issues with mobility and usual activities. Approximately, 30% of adolescents and adults had moderate to extreme problems with anxiety/depression. High baseline concomitant use of medications was observed across both age groups with an average of 5 medications being used per person. CONCLUSION: This study highlights the impact of AS on HRQoL and medication utilization among adolescents and adults individuals with AS.

High-Performance On-Chip Silicon Beamsplitter Based on Subwavelength Metamaterials for Enhanced Fabrication Tolerance.

Efficient power splitting is a fundamental functionality in silicon photonic integrated circuits, but state-of-the-art power-division architectures are hampered by limited operational bandwidth, high sensitivity to fabrication errors or large footprints. In particular, traditional Y-junction power splitters suffer from fundamental mode losses due to limited fabrication resolution near the junction tip. In order to circumvent this limitation, we propose a new type of high-performance Y-junction power splitter that incorporates subwavelength metamaterials. Full three-dimensional simulations show a fundamental mode excess loss below 0.1 dB in an ultra-broad bandwidth of 300 nm (1400-1700 nm) when optimized for a fabrication resolution of 50 nm, and under 0.3 dB in a 350 nm extended bandwidth (1350-1700 nm) for a 100 nm resolution. Moreover, analysis of fabrication tolerances shows robust operation for the fundamental mode to etching errors up to ±20 nm. A proof-of-concept device provides an initial validation of its operation principle, showing experimental excess losses lower than 0.2 dB in a 195 nm bandwidth for the best-case resolution scenario (i.e., 50 nm).

An observational study of pediatric healthcare burden in Angelman syndrome: results from a real-world study.

BACKGROUND: The objective of this study is to describe variations in the healthcare resource utilization (HRU) among individuals with Angelman syndrome (AS) over the first 12 years of life. Data for this study were drawn from the AS Natural History study (ASNHS), which is an observational study on the developmental progress, behavior, and medical morbidity of individuals with AS conducted over eight years. Caregiver-reported information on hospitalization, surgery, and medication utilization was used to assess HRU. Repeated measures mixed effect models were used to assess the relationship between age and probability of hospitalization, surgery, and prescription medication utilization. RESULTS: Mean age at study enrollment was 6 years of age and both sexes were equally represented. The mean number of visits per participant was three. Results from this study suggest that individuals with AS have a high HRU burden. Hospitalization and surgery burden were highest in the first year of life. Use of medications for seizures and sleep disturbance increased over time. CONCLUSIONS: The study highlights the significant healthcare burden among individuals with AS. Future studies that estimate cost and caregiver burden associated with AS are needed to assess the lifelong economic impact of AS on families and healthcare system.

Healthcare burden among individuals with Angelman syndrome: Findings from the Angelman Syndrome Natural History Study.

BACKGROUND: The objective of this study is to describe healthcare resource utilization (HRU) and supportive therapy utilization (STU) among individuals with Angelman syndrome (AS), and to compare such usage by molecular etiology. METHODS: Participants were categorized into deletion and non-deletion genotypes. Statistical differences were assessed using an independent samples t test. RESULTS: Data were available on 302 individuals. Mean age of participants was 5.5 years, 92% of whom were less than 13 years, and 71% had the deletion etiology. About 68% of participants had at least one hospitalization since birth to enrollment in the study; the average number of hospitalizations during that time period was 2.3 and average length of stay was 4.5 days. The most common reasons for hospitalization were seizures, lower respiratory infections, and surgery. The most common reasons for surgery were myringotomy, strabismus surgery, tonsillectomy or adenoidectomy, and gastrostomy tube insertion/fundoplication. Anticonvulsants, gastroesophageal reflux disease, sleep, and behavioral medications were the most commonly prescribed drugs. STU was high among individuals with AS. CONCLUSIONS: This study shows that individuals with AS have high HRU/STU, and apart from a few differences, HRU/STU was similar across molecular etiology. These results reflect usage in younger individuals and studies that describe HRU/STU in older individuals are needed.

A Conceptual Model of Angelman Syndrome and Review of Relevant Clinical Outcomes Assessments (COAs).

BACKGROUND: Angelman syndrome (AS) is a rare, neurological genetic disorder for which no clinical outcomes assessments (COAs) or conceptual models (CM) have been developed. OBJECTIVE: This study aimed to identify symptoms and impacts relevant and important in this patient population and develop a conceptual model of AS, and to evaluate the content validity of selected COA instruments with potential for inclusion in clinical studies of AS to capture treatment benefit. METHODS: For both concept elicitation (CE) and cognitive interviews (CI), caregivers of children, adolescents, and adults with AS and clinicians with AS experience were targeted. For CI, clinicians discussed the Modified Performance-Oriented Mobility Assessment (MPOMA-G) and ProtoKinetics Zeno Walkway™ and caregivers reviewed the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT), the Anxiety, Depression and Mood Scale (ADAMS), the Aberrant Behavior Checklist-Community (ABC-C), and the Morning Diary. RESULTS: Four clinicians and 34 caregivers participated in CE interviews; three clinicians and 36 caregivers participated in CI. A conceptual model, initially informed by literature, was refined based on interview data. Five domains of symptoms, signs, and characteristics of AS were identified: cognitive and executive functioning, social-emotional, emotional-expressive behavior, sensory-compulsive behavior, and physical. Patient impacts were identified in three domains: activities of daily living, school, and social/community. Caregiver impacts were identified in five domains: mental health, physical health, work, home, and social. While all instruments demonstrated the ability to provide relevant data for the AS population, each instrument either contained some items irrelevant to individuals with AS or was missing important concepts based on the interviews. No single instrument covered all relevant domains specific to AS. CONCLUSION: Future work should consider the adaptation of existing COAs and the development of a novel AS-specific instrument for use in clinical research to ensure outcomes important to this patient population are captured.

Semantic network function captured by word frequency in nondemented APOE ε4 carriers.

OBJECTIVE: Accurate identification of the earliest cognitive changes associated with Alzheimer's disease (AD) is critically needed. Item-level information within tests of category fluency, such as lexical frequency, harbors valuable information about the integrity of semantic networks affected early in AD. To determine the potential of lexical frequency as a cognitive marker of AD risk, we investigated whether lexical frequency of animal fluency output differentiated APOE ε4 carriers from noncarriers in a cross-sectional design among older African-American adults without dementia. METHOD: We analyzed animal fluency performance using mean number of items and mean lexical frequency among 230 cognitively normal African Americans with and without the APOE ε4 allele. RESULTS: Lexical frequency was higher in APOE ε4 carriers than noncarriers when analyzed as a mean score and within time bins. In contrast, we found no group difference in the number of items produced. Lexical frequency was particularly sensitive to ε4 status after the first 10 s of the 60-s animal fluency task. CONCLUSION: Our results suggest that psycholinguistic features may hold value as a cognitive biomarker for identifying people at high risk of AD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Unmet clinical needs and burden in Angelman syndrome: a review of the literature.

BACKGROUND: Angelman syndrome (AS) is a rare disorder with a relatively well-defined phenotype. Despite this, very little is known regarding the unmet clinical needs and burden of this condition, especially with regard to some of the most prevalent clinical features-movement disorders, communication impairments, behavior, and sleep. MAIN TEXT: A targeted literature review using electronic medical databases (e.g., PubMed) was conducted to identify recent studies focused on specific areas of the AS phenotype (motor, communication, behavior, sleep) as well as epidemiology, diagnostic processes, treatment, and burden. 142 articles were reviewed and summarized. Findings suggest significant impairment across the life span in all areas of function. While some issues may resolve as individuals get older (e.g., hyperactivity), others become worse (e.g., movement disorders, aggression, anxiety). There are no treatments focused on the underlying etiology, and the symptom-based therapies currently prescribed do not have much, if any, empirical support. CONCLUSIONS: The lack of standardized treatment protocols or approved therapies, combined with the severity of the condition, results in high unmet clinical needs in the areas of motor functioning, communication, behavior, and sleep for individuals with AS and their families.

Ethical issues in cross-cultural neuropsychology.

Clinical neuropsychologists who assess patients from diverse cultural and linguistic backgrounds face unique ethical challenges. In this article, we address 4 critical questions relevant to ethics of cross-cultural neuropsychology: (a) Should culture or race be considered in neuropsychological testing? (b) Should race- and ethnicity-specific normative data be used in the clinical neuropsychological evaluation? (c) Who is competent to design and translate tests for ethnic minority groups and non-English speakers and who is competent to administer and interpret them? and (d) Are neuropsychology training programs adequately preparing clinicians to be competent in the assessment of cross-cultural groups? The overall aims of the article are to highlight the complexity of these clinical and ethical issues, to provide comprehensive and balanced information to help guide clinician choices, and to stimulate future research in this area.