Objective
Rett syndrome (RTT) and epileptic encephalopathy (EE) are devastating neurodevelopmental disorders with distinct diagnostic criteria. However, highly heterogeneous and overlapping clinical ...features often allocate patients into the boundary of the two conditions, complicating accurate diagnosis and appropriate medical interventions. Therefore, we investigated the specific molecular mechanism that allows an understanding of the pathogenesis and relationship of these two conditions.
Methods
We screened novel genetic factors from 34 RTT‐like patients without MECP2 mutations, which account for ∼90% of RTT cases, by whole‐exome sequencing. The biological function of the discovered variants was assessed in cell culture and Xenopus tropicalis models.
Results
We identified a recurring de novo variant in GABAB receptor R2 (GABBR2) that reduces the receptor function, whereas different GABBR2 variants in EE patients possess a more profound effect in reducing receptor activity and are more responsive to agonist rescue in an animal model.
Interpretation
GABBR2 is a genetic factor that determines RTT‐ or EE‐like phenotype expression depending on the variant positions. GABBR2‐mediated γ‐aminobutyric acid signaling is a crucial factor in determining the severity and nature of neurodevelopmental phenotypes. Ann Neurol 2017;82:466–478
Preference-based measures (PBM) for health-related quality of life (HRQoL) are essential in assessing the cost-utility of different treatment options. The preference-based Parkinson's disease Index ...(PB-PDI) is being developed for people with Parkinson's disease (PD). The aim of this study was to refine the PB-PDI through cognitive interviews with people with PD. Cognitive debriefing was conducted to assess patients’ interpretation of items, both in English and French. Participants’ feedback guided the iterative modification of the PB-PDI and items were accepted for final inclusion if they were endorsed by three consecutive participants. A total of 16 participants provided feedback on the items, refined the response options, and discussed how to clarify questions. They selected a 2-week timeframe for the PB-PDI recall period. At the end of the cognitive interviews, all seven items and their response options were endorsed in both languages. The cognitive interview process allowed us to refine items and ensure that they were clear in terms of instructions and response options from the perspective of people with PD. The next step will be to elicit preference weights to develop a scoring algorithm and assess its measurement properties.
This study aimed to synthesise information concerning the potential benefits and risks related to cochlear implants (CIs) versus hearing aids (HAs) in children with residual hearing.
A systematic ...review of articles published from January 2003 to January 2019 was conducted.
Our review included studies that compared the benefits and risks of CIs versus HAs in children (≤18 years old) with residual hearing. A total of 3265 citations were identified; 8 studies met inclusion criteria.
Children with CIs showed significantly better speech perception scores post-CI than pre-CI. There was limited evidence related to improvement in everyday auditory performance, and the results showed non-significant improvement in speech intelligibility. One study on social-emotional functioning suggested benefits from CIs. In four studies, 37.2% (16/43) of children showed loss of residual hearing and 14.0% (8/57) had discontinued or limited use of their device.
Children with CIs showed improvement in speech perception outcomes compared to those with HAs. However, due to the limited number of studies and information to guide decision-making related to other areas of development, it will be important to conduct further research of both benefits and risks of CIs in this specific population to facilitate decision-making.
Permanent hearing loss affects 1 to 3 per 1000 children and interferes with typical communication development. Early detection through newborn hearing screening and hearing technology provide most ...children with the option of spoken language acquisition. However, no consensus exists on optimal interventions for spoken language development.
To conduct a systematic review of the effectiveness of early sign and oral language intervention compared with oral language intervention only for children with permanent hearing loss.
An a priori protocol was developed. Electronic databases (eg, Medline, Embase, CINAHL) from 1995 to June 2013 and gray literature sources were searched. Studies in English and French were included.
Two reviewers screened potentially relevant articles.
Outcomes of interest were measures of auditory, vocabulary, language, and speech production skills. All data collection and risk of bias assessments were completed and then verified by a second person. Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to judge the strength of evidence.
Eleven cohort studies met inclusion criteria, of which 8 included only children with severe to profound hearing loss with cochlear implants. Language development was the most frequently reported outcome. Other reported outcomes included speech and speech perception.
Several measures and metrics were reported across studies, and descriptions of interventions were sometimes unclear.
Very limited, and hence insufficient, high-quality evidence exists to determine whether sign language in combination with oral language is more effective than oral language therapy alone. More research is needed to supplement the evidence base.
Cochlear implants (CI) candidacy criteria have expanded to include children with more residual hearing. This study explored the clinical profiles and outcomes of children with CIs who had ...preoperative residual hearing in at least one ear.
A retrospective chart review was conducted to collect clinical characteristics and speech perception data. Pre- and post-CI auditory and speech perception data were analysed using a modified version of the Pediatric Ranked Order Speech Perception (PROSPER) score.
This study included all children with residual hearing who received CIs in one Canadian paediatric centre from 1992 to 2018.
A total of 100 of 389 (25.7%) children with CIs had residual hearing (median 77.6 dB HL, better ear). The proportion of children with residual hearing increased from 1992 to 2018. Children who had auditory behaviour and speech perception tests (n = 83) showed higher modified PROSPER scores post-CI compared to pre-CI. Phonologically Balanced Kindergarten (PBK) test scores were available for 71 children post-CI; 81.7% (58/71) of children achieved > 80% on the PBK.
One in four children who received CIs had residual hearing, and most of them had severe hearing loss at pre-CI. These children showed a high level of speech perception with CIs.
Cochlear implant (CI) decision-making is particularly challenging for families of children who have residual hearing. Parents of these children may be uncertain about whether the potential benefits ...of CIs outweigh the risks. This study aimed to understand parents' decisional needs during the decision-making process for children with residual hearing.
Semi-structured interviews were conducted with parents of 11 children who had received CIs. Open-ended questions were asked to encourage parents to share their experiences about the decision-making process, their values/preferences, and their needs. The interviews were transcribed verbatim and analyzed using thematic analysis.
Data were organized according to three key themes: (1) Parents' decisional conflict, (2) values and preferences, (3) decision support and parents' needs. We found that overall parents were satisfied with their decision-making process and the decision support from practitioners. However, parents stressed the importance of receiving more personalized information that considers their specific concerns, values and preferences related to family's circumstances.
Our research provides additional evidence to guide the CI decision-making process for children with residual hearing. Additional collaborative research with audiology and decision-making experts specifically on facilitating shared decision-making is needed to provide better decision coaching for these families.
Background
Family caregivers see firsthand the progression of their care recipient’s dementia and know every aspect of their lives and needs. They make important decisions on interventions and care. ...Currently, there are no measures that account for caregivers’ perspectives when evaluating the impact of dementia or interventions. The aim of this study was to explore the perspectives of caregivers’ of people living with dementia across Canada to generate domains for a new caregiver‐reported measure.
Method
Participants were recruited across Canada. Listening sessions were conducted virtually over three months, using open‐ended questions to encourage participants to share their perspectives. A semi‐structured interview guide was developed to facilitate the sessions. The interviewer asked questions to encourage caregivers to share their experiences on providing care, dementia monitoring, treatment impact and seeking alternative care. The data were coded and analyzed using NVivo. A thematic analysis approach was applied by two reviewers to analyze the data.
Result
Seven listening sessions were conducted with 34 caregivers who were providing care to their loved ones with dementia. Seventy‐four percent of the participants were women and 59% had 6 or more years of caregiving experience. Each listening session included three to six caregivers and was approximately one hour long. Example of codes included gait limitations, distance walked, difficulties with memory, and changes in behaviour. Overall, data were organized into three broad themes (i) psychosocial impact of dementia, (ii) physical and emotional changes for dementia monitoring and treatment, (iii) symptomalogy changes for dementia monitoring and treatment.
Conclusion
This study explored the perspective of caregivers across Canada, the activities and symptoms that are important to assess when evaluating dementia progression. It also questioned caregivers on how best to evaluate treatment effects. These findings may help identify strategies to better support caregivers and improve the quality of life of individuals living with dementia. Furthermore, the findings of this study can be a resource to help healthcare professionals, communities, and policymakers to provide better support for caregivers and the lives of individuals with dementia.
Cochlear implants (CIs) are increasingly considered for children with residual hearing who benefit from hearing aids (HAs). However, the decision-making process for families of these children and for ...practitioners is particularly challenging because there is no clear audiological cut point for CI candidacy. This study aimed to understand Canadian practitioners' perspectives of the CI decision-making process and how they guide families of children with residual hearing.
Semistructured interviews were conducted with a total of 17 practitioners through four focus groups and one individual interview. Interviews were transcribed verbatim, and a thematic analysis was carried out.
Data were organized into five broad domains: candidacy issues for children with residual hearing, practitioners' roles in decision support, additional considerations affecting decision making, factors facilitating decision making, and practitioners' needs.
This study found that practitioners' confidence in determining candidacy and supporting parents has increased due to their experiences with positive outcomes for these children. Practitioners indicated that there was a need for more research to guide the decision-making process.
Children with mild bilateral and unilateral hearing loss are now commonly identified early through newborn hearing screening initiatives. There remains considerable uncertainty about how to support ...parents and about which services to provide for children with mild bilateral and unilateral hearing loss. The goal of this study was to learn about parents' experiences and understand, from their perspectives, the impact of hearing loss in the mild range on the child's functioning. Parents of 20 children in Ontario, Canada, participated in the study. The median age of identification of hearing loss was 4.6 months (interquartile range: 3.6, 10.8). Parents appreciated learning early about hearing loss, but their experiences with the early process were mixed. Parents felt that professionals minimized the importance of milder hearing loss. There was substantial uncertainty about the need for hearing aids and the findings suggest that parents need specific guidance. Parents expressed concerns about the potential impact of hearing loss on their child's development, particularly at later ages.
Abstract
Following the establishment of newborn hearing screening programs, age of identification and length of time before receiving interventions has been reduced for children, including those with ...milder degrees of hearing loss who were previously not identified until school age. This population of early-identified children requires new support programs for parents. Although literature is emerging on how parents experience the initial years, there is limited information on support needs during early school years. The objectives were to gain insights into parents’ experiences with services during the early period of identification until early school years, as well as their perceptions of the consequences of hearing loss on their child’s overall development. A qualitative research design informed by Interpretive Description was employed. Individual semi-structured interviews were conducted with 12 parents of children identified with mild hearing loss. Transcripts were analyzed using a constant comparative method. Four themes emerged from the data: early experiences with services and hearing technology, effects of hearing loss on social functioning, effects of hearing loss on language and academics, and experiences in early school years. From parents’ perspectives, more support during the early school years is needed to help ensure academic success.
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