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PurposeUse of genomic sequencing is increasing at a pace that requires technological solutions to effectively meet the needs of a growing patient population. We developed GUÍA, a web-based application, to enhance the delivery of genomic results and related clinical information to patients and families.MethodsGUÍA development occurred in 5 phases: formative research, content development, user interface design, stakeholder/community member input, and web application development. Development was informed by qualitative research involving parents (N=22) whose children underwent genomic testing. Participants enrolled in the NYCKidSeq pilot study (N=18) completed structured feedback interviews post-result disclosure using GUÍA. Genetic specialists, researchers, patients, and community stakeholders provided their perspectives on GUÍA’s design to ensure technical, cultural, and literacy appropriateness.ResultsNYCKidSeq participants responded positively to the use of GUÍA to deliver their children’s results. All participants (N=10) with previous experience with genetic testing felt GUÍA improved result disclosure, and 17 (94%) participants said the content was clear.ConclusionsGUÍA communicates complex genomic information in an understandable and personalized manner. Initial piloting demonstrated GUÍA’s utility for families enrolled NYCKidSeq pilot study. Findings from the NYCKidSeq clinical trial will provide insight into GUÍA’s effectiveness in communicating results among diverse, multilingual populations.

Background Staphylococcus aureus protein A (spa) typing can be used to expand characterization of the epidemiology of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in neonatal intensive care units (NICU). Methods From January 2017 to June 2018, twice-monthly surveillance for S. aureus was performed in an academically affiliated NICU. Decolonization of infants colonized with S. aureus included chlorhexidine gluconate bathing and/or mupirocin for those with mupirocin-susceptible strains. Spa typing and mupirocin-resistance testing were performed. Demographic and clinical characteristics were compared between infants colonized with MSSA vs MRSA and infants with and without the most common MSSA spa type, MSSA-t279. Results Overall, 14% and 2% of 1556 hospitalized infants had positive surveillance cultures for MSSA and MRSA, respectively. Thirty-six infants harbored unique MSSA spa types, 5 infants harbored unique MRSA spa types, and 30 MSSA and 6 MRSA spa types were identified in ≥2 infants. No outbreaks were identified during the study period. MSSA-t279 was isolated from 3% of infants and largely detected from infants hospitalized in one section of the NICU; 96% of t279 isolates were mupirocin resistant. Infection rates, length of hospitalization, and mortality were similar among infants initially colonized with t279 vs other MSSA spa types. Conclusions The MSSA colonization burden was 5-fold larger than that of MRSA. Numerous unique spa types were identified. The most common spa type, MSSA-t279, was not associated with increased morbidity or mortality but was mupirocin resistant and associated with clustered NICU beds. This suggests potential transmission from the environment, shared staff, and/or workflow issues requiring further study. Other decolonization strategies for S. aureus in the NICU are needed.

Nonalcoholic fatty liver disease is the most prevalent liver disease in the world. Metabolic syndrome and obesity are associated risk factors. The inflammatory subtype, nonalcoholic steatohepatitis (NASH), which can progress to cirrhosis, is predicted to become the primary indication for liver transplantation within the next decade. Although there are no approved medications for NASH, there are ongoing multicenter trials aimed at targeting aspects of fat accumulation, inflammation, and fibrosis throughout the disease process. Nurse practitioners should focus on identifying patients at risk for NASH, while using guidelines for the management of nonalcoholic fatty liver disease and the comorbidities contributing to disease progression.

We conducted a consented pilot newborn screening (NBS) for Pompe, Gaucher, Niemann–Pick A/B, Fabry, and MPS 1 to assess the suitability of these lysosomal storage disorders (LSDs) for public health mandated screening. At five participating high–birth rate, ethnically diverse New York City hospitals, recruiters discussed the study with postpartum parents and documented verbal consent. Screening on consented samples was performed using multiplexed tandem mass spectrometry. Screen-positive infants underwent confirmatory enzymology, DNA testing, and biomarker quantitation when available. Affected infants are being followed for clinical management and long-term outcome. Over 4 years, 65,605 infants participated, representing an overall consent rate of 73%. Sixty-nine infants were screen-positive. Twenty-three were confirmed true positives, all of whom were predicted to have late-onset phenotypes. Six of the 69 currently have undetermined disease status. Our results suggest that NBS for LSDs is much more likely to detect individuals at risk for late-onset disease, similar to results from other NBS programs. This work has demonstrated the feasibility of using a novel consented pilot NBS study design that can be modified to include other disorders under consideration for public health implementation as a means to gather critical evidence for evidence-based NBS practices.

Background Increasingly, genomics is informing clinical practice, but challenges remain for medical professionals lacking genetics expertise, and in access to and clinical utility of genomic testing for minority and underrepresented populations. The latter is a particularly pernicious problem due to the historical lack of inclusion of racially and ethnically diverse populations in genomic research and genomic medicine. A further challenge is the rapidly changing landscape of genetic tests and considerations of cost, interpretation, and diagnostic yield for emerging modalities like whole-genome sequencing. Methods The NYCKidSeq project is a randomized controlled trial recruiting 1130 children and young adults predominantly from Harlem and the Bronx with suspected genetic disorders in three disease categories: neurologic, cardiovascular, and immunologic. Two clinical genetic tests will be performed for each participant, either proband, duo, or trio whole-genome sequencing (depending on sample availability) and proband targeted gene panels. Clinical utility, cost, and diagnostic yield of both testing modalities will be assessed. This study will evaluate the use of a novel, digital platform (GUÍA) to digitize the return of genomic results experience and improve participant understanding for English- and Spanish-speaking families. Surveys will collect data at three study visits: baseline (0 months), result disclosure visit (ROR1, + 3 months), and follow-up visit (ROR2, + 9 months). Outcomes will assess parental understanding of and attitudes toward receiving genomic results for their child and behavioral, psychological, and social impact of results. We will also conduct a pilot study to assess a digital tool called GenomeDiver designed to enhance communication between clinicians and genetic testing labs. We will evaluate GenomeDiver’s ability to increase the diagnostic yield compared to standard practices, improve clinician’s ability to perform targeted reverse phenotyping, and increase the efficiency of genetic testing lab personnel. Discussion The NYCKidSeq project will contribute to the innovations and best practices in communicating genomic test results to diverse populations. This work will inform strategies for implementing genomic medicine in health systems serving diverse populations using methods that are clinically useful, technologically savvy, culturally sensitive, and ethically sound. Trial registration ClinicalTrials.govNCT03738098. Registered on November 13, 2018 Trial Sponsor: Icahn School of Medicine at Mount Sinai Contact Name: Eimear Kenny, PhD (Principal Investigator) Address: Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Pl., Box 1003, New York, NY 10029 Email: eimear.kenny@mssm.edu

Patients with jaundice and abdominal pain should be assessed immediately for biliary obstruction. The development of cholangitis, or an inflammation of the bile ducts, can lead to infection. A nurse practitioner must complete a thorough health history and physical examination to assist in differentiating potential causes of jaundice.

Background. RAF inhibitors are an effective therapy for patients with BRAF-mutant melanoma and brain metastasis. Efficacy data are derived from clinical studies enriched with physiologically fit patients; therefore, it is of interest to assess the real-world experience of vemurafenib in this population. Tumor-specific genetic variants that influence sensitivity to RAF kinase inhibitors also require investigation. Methods. Records of patients with BRAF-mutant melanoma and brain metastases who were treated with vemurafenib were reviewed. Clinical data were extracted to determine extracranial and intracranial objective response rates, progression-free survival (PFS), overall survival (OS), and safety. A bait-capture, next-generation sequencing assay was used to identify mutations in pretreatment tumors that could explain primary resistance to vemurafenib. Results. Among patients with intracranial disease treated with vemurafenib, 27 were included in survival analyses and 22 patients were assessable for response. The extracranial and intracranial objective response rates were 71% and 50%, respectively. Discordant responses were observed between extracranial and intracranial metastatic sites in 4 of 19 evaluable patients. Median PFS was 4.1 months (95% confidence interval [CI]: 2.6–7.9); median intracranial PFS was 4.6 months (95% CI: 2.7–7.9), median OS was 7.5 months (95% CI: 4.3–not reached), with a 30.4% 1-year OS rate. Outcomes were influenced by performance status. Vemurafenib was tolerable, although radiation-induced dermatitis occurred in some patients who received whole-brain radiotherapy. Adequate samples for next-generation sequencing analysis were available for seven patients. Melanomas categorized as “poorly sensitive” (≥20% tumor growth, new lesions, or ≤50% shrinkage for Conclusion. Vemurafenib is highly active in BRAF-mutant melanoma brain metastases but has limited activity in patients with poor performance status. The safety and efficacy of concurrent radiotherapy and RAF inhibition requires careful clinical evaluation. Combination strategies blocking the MAPK and PI3K-AKT pathway may be warranted in a subset of patients. Implications for Practice: Vemurafenib is active for BRAF-mutant intracranial melanoma metastases in an unselected patient population typical of routine oncologic practice. Patients with poor performance status appear to have poor outcomes despite vemurafenib therapy. Preliminary data indicate that co-occurring or secondary alterations in the phosphatidylinositol 3-kinase-AKT (PI3K-AKT) pathway are involved in resistance to RAF inhibition, thus providing a rationale for dual MAPK and PI3K-AKT pathway inhibition in this patient population.

Background While several studies have documented the importance of hand washing in the university setting, the added role of environmental hygiene remains poorly understood. The purpose of this study was to characterize the personal and environmental hygiene habits of college students, define the determinants of hygiene in this population, and assess the relationship between reported hygiene behaviors, environmental contamination, and health status. Methods 501 undergraduate students completed a previously validated survey assessing baseline demographics, hygiene habits, determinants of hygiene, and health status. Sixty survey respondents had microbiological samples taken from eight standardized surfaces in their dormitory environment. Bacterial contamination was assessed using standard quantitative bacterial culture techniques. Additional culturing for coagulase-positive Staphylococcus and coliforms was performed using selective agar. Results While the vast majority of study participants (n = 461, 92%) believed that hand washing was important for infection prevention, there was a large amount of variation in reported personal hygiene practices. More women than men reported consistent hand washing before preparing food (p = .002) and after using the toilet (p = .001). Environmental hygiene showed similar variability although 73.3% (n = 367) of subjects reported dormitory cleaning at least once per month. Contamination of certain surfaces was common, with at least one third of all bookshelves, desks, refrigerator handles, toilet handles, and bathroom door handles positive for >10 CFU of bacteria per 4 cm2 area. Coagulase-positive Staphylococcus was detected in three participants' rooms (5%) and coliforms were present in six students' rooms (10%). Surface contamination with any bacteria did not vary by frequency of cleaning or frequency of illness (p>.05). Conclusions Our results suggest that surface contamination, while prevalent, is unrelated to reported hygiene or health in the university setting. Further research into environmental reservoirs of infectious diseases may delineate whether surface decontamination is an effective target of hygiene interventions in this population.