Usher syndrome (USH) is an autosomal recessively inherited disease characterized by sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP) with or without vestibular dysfunction. It is highly heterogeneous both clinically and genetically. Recently, variants in the arylsulfatase G (ARSG) gene have been reported to underlie USH type IV. This distinct type of USH is characterized by late-onset RP with predominantly pericentral and macular changes, and late onset SNHL without vestibular dysfunction. In this study, we describe the USH type IV phenotype in three unrelated subjects. We identified three novel pathogenic variants, two novel likely pathogenic variants, and one previously described pathogenic variant in ARSG. Functional experiments indicated a loss of sulfatase activity of the mutant proteins. Our findings confirm that ARSG variants cause the newly defined USH type IV and support the proposed extension of the phenotypic USH classification.
Background Tinnitus is a phantom sensation of sound, which can have a negative impact on quality of life of those affected. No curative treatments are currently known. Neuromodulation by vagus nerve stimulation has emerged as a new treatment option for tinnitus, though till date the effectiveness remains unclear. Therefore, we aim to review the effect of vagus nerve stimulation on tinnitus distress and tinnitus symptom severity in patients with chronic tinnitus. Methods We searched Pubmed, Embase and the Cochrane Library systematically for RCTs, observational studies and case studies on the effect of VNS treatment for tinnitus on October 29, 2019. Studies including adult patients with subjective tinnitus, comparing transcutaneous or implantable VNS to placebo or no treatment or before and after application of VNS treatment on tinnitus distress and tinnitus symptom severity measured with a validated questionnaire were eligible. The risk of bias was assessed with the appropriate tool for each type of study. Results Our search identified 9 primary studies of which 2 RCTs, 5 cohort studies and 2 case series or reports. 5 studies used transcutaneous VNS treatment and 4 used implanted VNS treatment. 6 studies combined VNS treatment with sound therapy. There was a serious risk of bias in all studies, especially on confounding. Most studies reported a small decrease in tinnitus distress or tinnitus symptom severity. Conclusion Due to methodological limitations and low reporting quality of the included studies, the effect of VNS on tinnitus remains unclear. To draw conclusions for which patient population and to what extent (t)VNS is beneficial in the treatment of tinnitus, a randomised controlled trial should be considered.
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
WHAT THIS PAPER ADDS This study shows that hybrid revascularisation is feasible and safe in symptomatic patients with an extracranial carotid artery tandem stenosis. This study provides data on purely symptomatic patients including a long-term clinical and imaging follow up period of more than six years. In the future, these surgical outcomes need to be offset against the natural course in patients with a symptomatic carotid tandem lesion. Objectives: Carotid tandem lesions are a multilevel significant (>50%) atherosclerotic disease involving both the internal carotid artery (ICA) and either the ipsilateral common carotid artery (CCA) or the innominate artery (IA). These lesions may be challenging to treat. Current guidelines offer no definitive recommendation on the optimal treatment algorithm. The aim of this analysis was to assess the long-term outcome of patients undergoing surgical revascularisation for tandem lesions. Methods: In two centres, consecutive patients who underwent carotid endarterectomy (CEA) for a symptomatic carotid artery stenosis between 2003 and 2017 were screened retrospectively for the presence of a carotid artery tandem lesion. All eligible patients were treated by a hybrid approach, consisting of retrograde stenting of the proximal CCA or IA followed by CEA. All patients had a yearly clinical check up including duplex ultrasound. The primary outcome was occurrence of any stroke, death, myocardial infarction (MI), or transient ischaemic attack (TIA) within 30 days. Secondary outcomes were any stroke, death, MI, or TIA and occurrence of restenosis 50% during follow up. Results: Sixteen of 2368 symptomatic patients were included. Besides a high grade ICA stenosis, patients had a significant ipsilateral stenosis of the CCA (n ¼ 13) or IA (n ¼ 3). Within 30 days there were no deaths, strokes, or TIAs. Two patients had a clinical MI. During a median follow up of 73 (interquartile range 22e85) months, three patients died. One patient developed a symptomatic restenosis of the ICA (ipsilateral TIA). Two patients (without restenosis) developed an ipsilateral stroke and a MI. Conclusions: In this small case series, hybrid revascularisation of carotid tandem lesions in symptomatic patients seems feasible and safe. Long-term data show a relatively high number of any adverse events. These surgical outcomes need to be offset against the natural course in patients with a symptomatic carotid tandem lesion.
The aim of this study is to contribute to a better description of the genotypic and phenotypic spectrum of DFNA6/14/38 and aid in counseling future patients identified with this variant. Therefore, we describe the genotype and phenotype in a large Dutch–German family (W21-1472) with autosomal dominant non-syndromic, low-frequency sensorineural hearing loss (LFSNHL). Exome sequencing and targeted analysis of a hearing impairment gene panel were used to genetically screen the proband. Co-segregation of the identified variant with hearing loss was assessed by Sanger sequencing. The phenotypic evaluation consisted of anamnesis, clinical questionnaires, physical examination and examination of audiovestibular function. A novel likely pathogenic WFS1 variant (NM_006005.3:c.2512C>T p.(Pro838Ser)) was identified in the proband and found to co-segregate with LFSNHL, characteristic of DFNA6/14/38, in this family. The self-reported age of onset of hearing loss (HL) ranged from congenital to 50 years of age. In the young subjects, HL was demonstrated in early childhood. At all ages, an LFSNHL (0.25–2 kHz) of about 50–60 decibel hearing level (dB HL) was observed. HL in the higher frequencies showed inter-individual variability. The dizziness handicap inventory (DHI) was completed by eight affected subjects and indicated a moderate handicap in two of them (aged 77 and 70). Vestibular examinations (n = 4) showed abnormalities, particularly in otolith function. In conclusion, we identified a novel WFS1 variant that co-segregates with DFNA6/14/38 in this family. We found indications of mild vestibular dysfunction, although it is uncertain whether this is related to the identified WFS1 variant or is an incidental finding. We would like to emphasize that conventional neonatal hearing screening programs are not sensitive to HL in DFNA6/14/38 patients, because high-frequency hearing thresholds are initially preserved. Therefore, we suggest screening newborns in DFNA6/14/38 families with more frequency-specific methods.
Background: Spin refers to reporting practices that could distort the interpretation and mislead readers by being more optimistic than the results justify, thereby possibly changing the perception of clinicians and influence their decisions. Because of the clinical importance of accurate interpretation of results and the evidence of spin in other research fields, we aim to identify the nature and frequency of spin in published reports of tinnitus randomized controlled trials (RCTs) and to assess possible determinants and effects of spin.Methods: We searched PubMed systematically for RCTs with tinnitus-related outcomes published from 2015 to 2019. All eligible articles were assessed on actual and potential spin using prespecified criteria.Results: Our search identified 628 studies, of which 87 were eligible for evaluation. A total of 95% of the studies contained actual or potential spin. Actual spin was found mostly in the conclusion of articles, which reflected something else than the reported point estimate (or CI) of the outcome (n = 34, 39%) or which was selectively focused (n = 49, 56%). Linguistic spin (“trend,” “marginally significant,” or “tendency toward an effect”) was found in 17% of the studies. We were not able to assess the association between study characteristics and the occurrence of spin due to the low number of trials for some categories of the study characteristics. We found no effect of spin on type of journal [odds ratio (OR) −0.13, 95% CI −0.56–0.31], journal impact factor (OR 0.17, 95% CI −0.18–0.51), or number of citations (OR 1.95, CI −2.74–6.65).Conclusion: There is a large amount of spin in tinnitus RCTs. Our findings show that there is room for improvement in reporting and interpretation of results. Awareness of different forms of spin must be raised to improve research quality and reduce research waste.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.