Programming Levels and Speech Perception in Pediatric Cochlear Implant Recipients With Enlarged Vestibular Aqueduct or GJB2 Mutation.

OBJECTIVE: To determine the relationship between hearing loss etiology, cochlear implant (CI) programming levels, and speech perception performance in a large clinical cohort of pediatric CI recipients. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care hospitals. PATIENTS: A total of 136 pediatric CI recipients (218 ears) were included in this study. All patients had diagnoses of either enlarged vestibular aqueduct (EVA) or GJB2 (Connexin-26) mutation confirmed via radiographic data and/or genetic reports. All patients received audiologic care at either Boston Children's Hospital or Massachusetts Eye and Ear in Boston, MA, between the years 1999 and 2020. MAIN OUTCOME MEASURES: Electrode impedances and programming levels for each active electrode and speech perception scores were evaluated as a function of etiology (EVA or GJB2 mutation). RESULTS: Children with EVA had significantly higher impedances and programming levels (thresholds and upper stimulation levels) than the children with GJB2 mutation. Speech perception scores did not differ as a function of etiology in this sample; rather, they were positively correlated with duration of CI experience (time since implantation). CONCLUSIONS: Differences in electrode impedances and CI programming levels suggest that the electrode-neuron interface varies systematically as a function of hearing loss etiology in pediatric CI recipients with EVA and those with GJB2 mutation. Time with the CI was a better predictor of speech perception scores than etiology, suggesting that children can adapt to CI stimulation with experience.

SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia.

Sphingolipids are a diverse family of lipids with critical structural and signalling functions in the mammalian nervous system, where they are abundant in myelin membranes. Serine palmitoyltransferase, the enzyme that catalyses the rate-limiting reaction of sphingolipid synthesis, is composed of multiple subunits including an activating subunit, SPTSSA. Sphingolipids are both essential and cytotoxic and their synthesis must therefore be tightly regulated. Key to the homeostatic regulation are the ORMDL proteins that are bound to serine palmitoyltransferase and mediate feedback inhibition of enzymatic activity when sphingolipid levels become excessive. Exome sequencing identified potential disease-causing variants in SPTSSA in three children presenting with a complex form of hereditary spastic paraplegia. The effect of these variants on the catalytic activity and homeostatic regulation of serine palmitoyltransferase was investigated in human embryonic kidney cells, patient fibroblasts and Drosophila. Our results showed that two different pathogenic variants in SPTSSA caused a hereditary spastic paraplegia resulting in progressive motor disturbance with variable sensorineural hearing loss and language/cognitive dysfunction in three individuals. The variants in SPTSSA impaired the negative regulation of serine palmitoyltransferase by ORMDLs leading to excessive sphingolipid synthesis based on biochemical studies and in vivo studies in Drosophila. These findings support the pathogenicity of the SPTSSA variants and point to excessive sphingolipid synthesis due to impaired homeostatic regulation of serine palmitoyltransferase as responsible for defects in early brain development and function.

A Modified Pediatric Ranked Order Speech Perception Score to Assess Speech Recognition Development in Children With Cochlear Implants.

PURPOSE: Characterizing and comparing speech recognition development in children with cochlear implants (CIs) is challenging because of variations in test type. This retrospective cohort study modified the Pediatric Ranked Order Speech Perception (PROSPER) scoring system to (a) longitudinally analyze the speech perception of children with CIs and (b) examine the role of age at CI activation, listening mode (i.e., unilateral or bilateral implantation), and interimplant interval. METHOD: Postimplantation speech recognition scores from 31 children with prelingual, severe-to-profound hearing loss who received CIs were analyzed (12 with unilateral CI [UniCI], 13 with sequential bilateral CIs [SEQ BiCIs], and six with simultaneous BiCIs). Data were extracted from the Massachusetts Eye and Ear Audiology database. A version of the PROSPER score was modified to integrate the varying test types by mapping raw scores from different tests into a single score. The PROSPER scores were used to construct speech recognition growth curves of the implanted ears, which were characterized by the slope of the growth phase, the time from activation to the plateau onset, and the score at the plateau. RESULTS: While speech recognition improved considerably for children following implantation, the growth rates and scores at the plateau were highly variable. In first implanted ears, later implantation was associated with poorer scores at the plateau (ß = -0.15, p = .01), but not growth rate. The first implanted ears of children with BiCIs had better scores at the plateau than those with UniCI (ß = 0.59, p = .02). Shorter interimplant intervals in children with SEQ BiCIs promoted faster speech recognition growth of the first implanted ears. CONCLUSION: The modified PROSPER score could be used clinically to track speech recognition development in children with CIs, to assess influencing factors, and to assist in developing and evaluating patient-specific intervention strategies. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.20113538.

The Relationship Between Impedance, Programming and Word Recognition in a Large Clinical Dataset of Cochlear Implant Recipients.

Cochlear implant programming typically involves measuring electrode impedance, selecting a speech processing strategy and fitting the dynamic range of electrical stimulation. This study retrospectively analyzed a clinical dataset of adult cochlear implant recipients to understand how these variables relate to speech recognition. Data from 425 implanted post-lingually deafened ears with Advanced Bionics devices were analyzed. A linear mixed-effects model was used to infer how impedance, programming and patient factors were associated with monosyllabic word recognition scores measured in quiet. Additional analyses were conducted on subsets of data to examine the role of speech processing strategy on scores, and the time taken for the scores of unilaterally implanted patients to plateau. Variation in basal impedance was negatively associated with word score, suggesting importance in evaluating the profile of impedance. While there were small, negative bivariate correlations between programming level metrics and word scores, these relationships were not clearly supported by the model that accounted for other factors. Age at implantation was negatively associated with word score, and duration of implant experience was positively associated with word score, which could help to inform candidature and guide expectations. Electrode array type was also associated with word score. Word scores measured with traditional continuous interleaved sampling and current steering speech processing strategies were similar. The word scores of unilaterally implanted patients largely plateaued within 6-months of activation. However, there was individual variation which was not related to initially measured impedance and programming levels.

Research Techniques Made Simple: Workflow for Searching Databases to Reduce Evidence Selection Bias in Systematic Reviews.

Clinical trials and basic science studies without statistically significant results are less likely to be published than studies with statistically significant results. Systematic reviews and meta-analyses that omit unpublished data are at high risk of distorted conclusions. Here, we describe methods to search beyond bibliographical databases to reduce evidence selection bias in systematic reviews. Unpublished studies may be identified by searching conference proceedings. Moreover, clinical trial registries-databases of planned and ongoing trials-and regulatory agency websites such as the European Medicine Agency (EMA) and the United States Food and Drug Administration (FDA) may provide summaries of efficacy and safety data. Primary and secondary outcomes are prespecified in trial registries, thus allowing the assessment of outcome reporting bias by comparison with the trial report. The sources of trial data and documents are still evolving, with ongoing initiatives promoting broader access to clinical study reports and individual patient data. There is currently no established methodology to ensure that the multiple sources of information are incorporated. Nonetheless, systematic reviews must adapt to these improvements and cover the new sources in their search strategies.

Validation of the global resource of eczema trials (GREAT database).

BACKGROUND: Eczema (syn. Atopic Eczema or Atopic Dermatitis) is a chronic, relapsing, itchy skin condition which probably results from a combination of genetic and environmental factors. The Global Resource of EczemA Trials (GREAT) is a collection of records of randomised controlled trials (RCTs) for eczema treatment produced from a highly sensitive search of six reference databases. We sought to assess the sensitivity of the GREAT database as a tool to save future researchers repeating extensive bibliographic searches. METHODS: All Cochrane systematic review on treatments for eczema and five non-Cochrane systematic reviews on eczema were identified as a reference set to assess the utility of the GREAT database in identifying randomised controlled trials (RCTs). RCTs included in the systematic reviews were checked for inclusion in the GREAT database by two independent authors. A third author resolved any disagreements. RESULTS: Five Cochrane and six non-Cochrane systematic reviews containing a total of 105 RCTs of eczema treatments were included. Of these, 95 fitted the inclusion criteria for the GREAT database and 88 were published from 2000 onwards. Of the 88 eligible studies, 92% were found in the GREAT database. Seven trials were not included in the GREAT database - two of these were reported within a review paper and one as an abstract with no trial results. CONCLUSIONS: The sensitivity of the GREAT database for trials from 2000 onwards was high (75/88 trials, 94%). Sensitivity for the period prior to 2000 was less sensitive, due to differences in how the trials were identified prior to this time. 'Dual' filtering for new records has recently become part of the GREAT database methodology and should further improve the sensitivity of the database in time. The GREAT database can be considered as a primary source for future systematic reviews including randomised controlled trials of eczema treatments, but searches should be supplemented by checking reference lists for eligible trials, searching trial registries and contacting pharmaceutical companies for unpublished studies.

The Cochrane Skin Group: a vanguard for developing and promoting evidence-based dermatology.

AIM: The Cochrane Skin Group (CSG) is part of the international Cochrane Collaboration (http://www.cochrane.org/). The CSG prepares, maintains and disseminates high quality evidence-based summaries on the prevention, diagnosis and treatment of skin diseases. We present a synopsis of the history, scope and priorities of the CSG. In addition, we report outcomes of CSG reviews and critically assess clinical value. METHODS: Descriptive analysis of systematic reviews published by the CSG since its inception including output, impact factor, associated methodological studies, and influence in clinical guidelines, promoting patient and public engagement and in triggering new primary research. RESULTS: The CSG started in 1997, and has published 61 reviews, 34 protocols and 31 registered titles by August 2013. The CSG scope includes 1000 skin diseases; 80% of reviews cover the top ten diagnoses and 40% of reviews provide clear guidance for clinical practice. CSG reviews had an impact factor of 6.1 in 2011 which places it alongside top dermatology journals. CSG reviews are typically broad in focus and have been shown to be of better quality than non-Cochrane reviews. They are highly cited in clinical guidelines. Several reviews have identified evidence gaps that have led to better primary research. CONCLUSIONS: The CSG has emerged as a vanguard of evidence-based dermatology by growing a community interested in applying best external evidence to the care of skin patients and by identifying topics for research. CSG reviews are high impact, clinically relevant and have tangibly influenced international dermatology clinical practice guidelines and new research.

Mapping systematic reviews on atopic eczema--an essential resource for dermatology professionals and researchers.

BACKGROUND: Many research studies have been published on atopic eczema and these are often summarised in systematic reviews (SRs). Identifying SRs can be time-consuming for health professionals, and researchers. In order to facilitate the identification of important research, we have compiled an on-line resource that includes all relevant eczema reviews published since 2000. METHODS: SRs were searched for in MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Database of Systematic Reviews, DARE and NHS Evidence. Selected SRs were assessed against the pre-defined eligibility criteria and relevant articles were grouped by treatment category for the included interventions. All identified systematic reviews are included in the Global Resource of EczemA Trials (GREAT) database (www.greatdatabase.org.uk) and key clinical messages are summarised here. RESULTS: A total of 128 SRs reviews were identified, including three clinical guidelines. Of these, 46 (36%) were found in the Cochrane Library. No single database contained all of the SRs found. The number of SRs published per year has increased substantially over the last thirteen years, and reviews were published in a variety of clinical journals. Of the 128 SRs, 1 (1%) was on mechanism, 37 (29%) were on epidemiology, 40 (31%) were on eczema prevention, 29 (23%) were on topical treatments, 31 (24%) were on systemic treatments, and 24 (19%) were on other treatments. All SRs included searches of MEDLINE in their search methods. One hundred six SRs (83%) searched more than one electronic database. There were no language restrictions reported in the search methods of 52 of the SRs (41%). CONCLUSIONS: This mapping of atopic eczema reviews is a valuable resource. It will help healthcare practitioners, guideline writers, information specialists, and researchers to quickly identify relevant up-to-date evidence in the field for improving patient care.