Background Exome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report describes the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey. Methods The North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing (NCGENES) 2 study is an interdisciplinary, multi-site Phase III randomized controlled trial of two interventions: educational pre-visit preparation (PVP) and offer of first-line ES. In this full-factorial design, parent-child dyads are randomly assigned to one of four study arms (PVP + usual care, ES + usual care, PVP + ES + usual care, or usual care alone) in equal proportions. Participants are recruited from Pediatric Genetics or Neurology outpatient clinics in three North Carolina healthcare facilities. Eligible pediatric participants are < 16 years old and have a first visit to a participating clinic, a suspected genetic condition, and an eligible parent/guardian to attend the clinic visit and complete study measures. The study oversamples participants from underserved and under-represented populations. Participants assigned to the PVP arms receive an educational booklet and question prompt list before clinical interactions. Randomization to offer of first-line ES is revealed after a child’s clinic visit. Parents complete measures at baseline, pre-clinic, post-clinic, and two follow-up timepoints. Study clinicians provide phenotypic data and complete measures after the clinic visit and after returning results. Reportable study-related research ES results are confirmed in a CLIA-certified clinical laboratory. Results are disclosed to the parent by the clinical team. A community consultation team contributed to the development of study materials and study implementation methods and remains engaged in the project. Discussion NCGENES 2 will contribute valuable knowledge concerning technical, clinical, psychosocial, and health economic issues associated with using early diagnostic ES to shorten the diagnostic odyssey of pediatric patients with likely genetic conditions. Results will inform efforts to engage diverse populations in genomic medicine research and generate evidence that can inform policy, practice, and future research related to the utility of first-line diagnostic ES in health care. Trial registration ClinicalTrials.govNCT03548779. Registered on June 07, 2018.

Objective Limited data exist describing possible delays in patient transfer from the emergency department (ED) as a result of language barriers and the effects of interpretation services. We described the differences in ED length of stay (LOS) before intensive care unit (ICU) arrival and mortality based on availability of telephone or in‐person interpretation services. Methods Using an ICU database from an urban academic tertiary care hospital, ED patients entering the ICU were divided into groups based on primary language and available interpretation services (in‐person vs telephone). Non‐parametric tests were used to compare ED LOS and mortality between groups. Results Among 22,422 included encounters, English was recorded as the primary language for 51% of patients (11,427), and 9% of patients (2042) had a primary language other than English. Language was not documented for 40% of patients (8953). Among encounters with patients with non‐English primary languages, in‐person interpretation was available for 63% (1278) and telephone interpretation was available for 37% (764). In the English‐language group, median ED LOS was 292 minutes (interquartile range [IQR], 205–412) compared with 309 minutes (IQR, 214–453) for patients speaking languages with in‐person interpretation available and 327 minutes (IQR, 225–463) for patients speaking languages with telephone interpretation available. Mortality was higher among patients with telephone (15%) or in‐person (11%) interpretation available compared with patients who primarily spoke English (9%). Conclusions Patients with primary languages other than English who were critically ill spent a median of 17 to 35 more minutes in the ED before ICU arrival and experienced higher mortality rates compared with patients who spoke English as a primary language.

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Background: Exome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report describes the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey. Methods: The North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing (NCGENES) 2 study is an interdisciplinary, multi-site Phase III randomized controlled trial of two interventions: educational pre-visit preparation (PVP) and offer of first-line ES. In this full-factorial design, parent-child dyads are randomly assigned to one of four study arms (PVP+usual care, ES+usual care, PVP+ES+usual care, or usual care alone) in equal proportions. Participants are recruited from Pediatric Genetics or Neurology outpatient clinics in three North Carolina healthcare facilities. Eligible pediatric participants are <16 years old and have a first visit to a participating clinic, a suspected genetic condition, and an eligible parent/guardian to attend the clinic visit and complete study measures. The study oversamples participants from underserved and under-represented populations. Participants assigned to the PVP arms receive an educational booklet and question prompt list before clinical interactions. Randomization to offer of first-line ES is revealed after a child’s clinic visit. Parents complete measures at baseline, pre-clinic, post-clinic, and two follow-up timepoints. Study clinicians provide phenotypic data and complete measures after the clinic visit and after returning results. Reportable study-related research ES results are confirmed in a CLIA-certified clinical laboratory. Results are disclosed to the parent by the clinical team. A community consultation team contributed to the development of study materials and study implementation methods and remains engaged in the project.Discussion: NCGENES 2 will contribute valuable knowledge concerning technical, clinical, psychosocial, and health economic issues associated with using early diagnostic ES to shorten the diagnostic odyssey of pediatric patients with likely genetic conditions. Results will inform efforts to engage diverse populations in genomic medicine research and generate evidence that can inform policy, practice, and future research related to the utility of first-line diagnostic ES in health care.Trial registration (date): clinicaltrials.gov Identifier: NCT03548779 (06/07/2018)

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