Search

Background There are early indications that lifestyle behaviors, specifically physical activity and sleep, may be associated with the onset and progression of Huntington disease (HD). Wearable activity trackers offer an exciting opportunity to collect long-term activity data to further investigate the role of lifestyle, physical activity, and sleep in disease modification. Given how wearable devices rely on user acceptance and long-term adoption, it is important to understand users’ perspectives on how acceptable any device might be and how users might engage over the longer term. Objective This study aimed to explore the perceptions, motivators, and potential barriers relating to the adoption of wearable activity trackers by people with HD for monitoring and managing their lifestyle and sleep. This information intended to guide the selection of wearable activity trackers for use in a longitudinal observational clinical study. Methods We conducted a mixed methods study; this allowed us to draw on the potential strengths of both quantitative and qualitative methods. Opportunistic participant recruitment occurred at 4 Huntington’s Disease Association meetings, including 1 international meeting and 3 United Kingdom–based regional meetings. Individuals with HD, their family members, and carers were invited to complete a user acceptance questionnaire and participate in a focus group discussion. The questionnaire consisted of 35 items across 8 domains using a 0 to 4 Likert scale, along with some additional demographic questions. Average questionnaire responses were recorded as positive (score>2.5), negative (score Results A total of 105 completed questionnaires were analyzed (47 people with HD and 58 family members or carers). All sections of the questionnaire produced median scores >2.5, indicating a tendency toward positive opinions on wearable activity trackers, such as the devices being advantageous, easy and enjoyable to use, and compatible with lifestyle and users being able to understand the information from trackers and willing to wear them. People with HD reported a more positive attitude toward wearable activity trackers than their family members or caregivers (P=.02). A total of 15 participants participated in 3 focus groups. Device compatibility and accuracy, data security, impact on relationships, and the ability to monitor and self-manage lifestyle behaviors have emerged as important considerations in device use and user preferences. Conclusions Although wearable activity trackers were broadly recognized as acceptable for both monitoring and management, various aspects of device design and functionality must be considered to promote acceptance in this clinical cohort.

Additional file 1: Table S1. Descriptive data for all baseline measurements. Table S2. Descriptive data for home visit assessments at home visit one. Table S3. Descriptive data of home visit assessments for home visit two. Table S4. Descriptive data for all outcome measurements.

Background and Purpose: We studied the development and delivery of a 14-week complex physical activity intervention for people with Huntington disease, where detailed information about the intervention was fully embedded in the trial design process.\ud \ud Methods: Intervention Development: The intervention was developed through a series of focus groups. The findings from the focus groups informed the development of a logic model for the physical activity intervention that was broadly consistent with the framework of self-determination theory. Intervention Delivery: Key components underpinning the delivery of the intervention were implemented including a defined coach training program and intervention fidelity assessment methods. Training of coaches (physical therapists, occupational therapists, research nurses, and exercise trainers) was delivered via group and 1:1 training sessions using a detailed coach's manual, and with ongoing support via video calls, and e-mail communication as needed. Detailed documentation was provided to determine costs of intervention development and coach training.\ud \ud Results: Intervention delivery coaches at 8 sites across the United Kingdom participated in the face-to-face training. Self-report checklists completed by each of the coaches indicated that all components of the intervention were delivered in accordance with the protocol. Mean (standard deviation) intervention fidelity scores (n = 15), as measured using a purpose-developed rating scale, was 11 (2.4) (out of 16 possible points). Coaches' perceptions of intervention fidelity were similarly high. The total cost of developing the intervention and providing training was [pounds]30,773 ($47,042 USD).\ud \ud Discussion and Conclusions: An important consideration in promoting translation of clinical research into practice is the ability to convey the detailed components of how the intervention was delivered to facilitate replication if the results are favorable. This report presents an illustrative example of a physical activity intervention, including the development and the training required to deliver it. This approach has the potential to facilitate reproducibility, evidence synthesis, and implementation in clinical practice.

A detailed demographic description of the cohort. Table S2. Previous cytogenetic and molecular testing in the cohort. (DOCX 17Â kb)

The recommended treatment of side effects that may occur when receiving everolimus. (PDF 41 kb)

Frequency categories of adverse reactions reported in the pooled analysis considered for the safety pooling. (PDF 76 kb)

SPIRIT checklist of key issues addressed in the trial protocol. (PDF 59 kb)

Neuropsychological assessment schedule of all neuropsychological assessments to be carried out as part of the trial. (PDF 53 kb)

Study assessment schedule of all assessments to be carried out as part of the trial. (PDF 46 kb)

Background Copy number variants (CNVs) have been linked to neurodevelopmental disorders such as intellectual disability (ID), autism, epilepsy and psychiatric disease. There are few studies of CNVs in patients with both ID and epilepsy. Methods We evaluated the range of rare CNVs found in 80 Welsh patients with ID or developmental delay (DD), and childhood-onset epilepsy. We performed molecular cytogenetic testing by single nucleotide polymorphism array or microarray-based comparative genome hybridisation. Results 8.8 % (7/80) of the patients had at least one rare CNVs that was considered to be pathogenic or likely pathogenic. The CNVs involved known disease genes (EHMT1, MBD5 and SCN1A) and imbalances in genomic regions associated with neurodevelopmental disorders (16p11.2, 16p13.11 and 2q13). Prompted by the observation of two deletions disrupting SCN1A we undertook further testing of this gene in selected patients. This led to the identification of four pathogenic SCN1A mutations in our cohort. Conclusions We identified five rare de novo deletions and confirmed the clinical utility of array analysis in patients with ID/DD and childhood-onset epilepsy. This report adds to our clinical understanding of these rare genomic disorders and highlights SCN1A mutations as a cause of ID and epilepsy, which can easily be overlooked in adults. Electronic supplementary material The online version of this article (doi:10.1186/s12881-016-0294-2) contains supplementary material, which is available to authorized users.

High resolution RNA analysis using next-generation sequencing (RNA-seq) is a rapidly growing application in cancer research. Formalin-fixed paraffin-embedded (FFPE) tissue is a ubiquitous resource for clinical studies. However, the ability to generate high quality libraries is confounded by the low quality and yield of RNA extracted from FFPE specimen. To enable optimal interrogation of such a clinically-relevant tissue resource, it is critical to identify RNA-seq library construction workflows that improve performance using challenging and degraded sample types. In this study, the effects of RNA type, quality, and quantity on RNA-seq library construction are assessed, and expectations regarding sequencing data quality are addressed. Included are recommendations for quality control measures and input-specific modifications that may improve performance Three workflows employing either bead-based or enzymatic strategies for the removal of ribosomal RNA content were used to prepare RNA-seq libraries from degraded paired breast normal and tumor samples. Enzymatic depletion followed by library preparation using the KAPA RNA HyperPrep1 workflow identified the highest number of transcripts for each sample, translating to a 4.9-fold increase in number of differentially expressed transcripts detected between normal and tumor samples. Of the transcripts identified as differentially expressed exclusively by Kapa, 174 are protein-coding RNAs, many of which are frequently dysregulated in breast cancer. In contrast, only two protein-coding RNAs were identified exclusively by the alternative workflows. RealTime Ready Custom panels were used for independent quantitative rt-PCR assessment. Of a subset of 71 transcripts identified exclusively by Kapa, up to 69 (97%) were validated as differentially expressed. Additional performance improvements of the KAPA RNA HyperPrep workflow include coverage balance across transcripts, lower duplication rate, technical replicate reproducibility, agreement across input quantities, and gene expression concordance between paired fresh frozen and FFPE samples. 1For Research Use Only. Not for use in diagnostic procedures. Citation Format: Nancy H. Nabilsi, Drew Cheney, Leendert Cloete, Ida van Jaarsveld, Rachel Kasinskas, Jennifer Pavlica. Demonstrated improvements in tumor profiling with enzymatic ribosomal RNA depletion and streamlined RNA-sequencing library preparation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5411. doi:10.1158/1538-7445.AM2017-5411