BackgroundUsher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.MethodsWe sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).ResultsBiallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.ConclusionsBased on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.

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IntroductionEmergency physicians frequently perform endotracheal intubation and mechanical ventilation. The impact of instituting early post-intubation interventions on patients boarding in the emergency department (ED) is not well studied. We sought to determine the impact of post-intubation interventions (arterial blood gas sampling, obtaining a chest x-ray (CXR), gastric decompression, early sedation, appropriate initial tidal volume, and quantitative capnography) on outcomes of mortality, ventilator-associated pneumonia (VAP), ventilator days, and intensive care unit (ICU) length-of-stay (LOS).MethodsThis was an observational, retrospective study of patients intubated in the ED at a large tertiary-care teaching hospital and included patients in the ED for greater than two hours post-intubation. We excluded them if they had incomplete data, were designated “do not resuscitate,” were managed primarily by the trauma team, or had surgery within six hours after intubation.ResultsOf 169 patients meeting criteria, 15 died and 10 developed VAP. The mortality odds ratio (OR) in patients receiving CXR was 0.10 (95% CI 0.01 to 0.98), and 0.11 (95% CI 0.03 to 0.46) in patients receiving early sedation. The mortality OR for patients with 3 or fewer interventions was 4.25 (95% CI 1.15 to 15.75) when compared to patients with 5 or more interventions. There was no significant relationship between VAP rate, ventilator days, or ICU LOS and any of the intervention groups.ConclusionThe performance of a CXR and early sedation as well as performing five or more vs. three or fewer post-intubation interventions in boarding adult ED patients was associated with decreased mortality.

Diabetes medication management and survival skills education for uncontrolled diabetes may be safely initiated in the ED, as demonstrated by the multidisciplinary STEP-DC intervention, which effectively enabled glycemic control in this pilot study.