RESUMO
Oculocutaneous albinism type 1 (OCA1) is caused by pathogenic variants in the TYR (tyrosinase) gene which encodes the critical and rate-limiting enzyme in melanin synthesis. It is the most common OCA subtype found in Caucasians, accounting for ~50% of cases worldwide. The apparent 'missing heritability' in OCA is well described, with ~25-30% of clinically diagnosed individuals lacking two clearly pathogenic variants. Here we undertook empowered genetic studies in an extensive multigenerational Amish family, alongside a review of previously published literature, a retrospective analysis of in-house datasets, and tyrosinase activity studies. Together this provides irrefutable evidence of the pathogenicity of two common TYR variants, p.(Ser192Tyr) and p.(Arg402Gln) when inherited in cis alongside a pathogenic TYR variant in trans. We also show that homozygosity for the p.(Ser192Tyr)/p.(Arg402Gln) TYR haplotype results in a very mild, but fully penetrant, albinism phenotype. Together these data underscore the importance of including the TYR p.(Ser192Tyr)/p.(Arg402Gln) in cis haplotype as a pathogenic allele causative of OCA, which would likely increase molecular diagnoses in this missing heritability albinism cohort by 25-50%.
RESUMO
PURPOSE: This quality improvement project developed a community nursing case management program to decrease preventable readmissions to the hospital and emergency department by providing telephonic case management and, if needed, onsite assessment and treatment by a clinical nurse specialist (CNS) with prescriptive authority. BACKGROUND: As more people reach Medicare age, the number of individuals with worsening chronic diseases with dramatically increases unless appropriate disease management programs are developed. RATIONALE: Care transitions can result in breakdown in continuity of care, resulting in increased preventable readmissions, particularly for indigent patients. The CNS is uniquely educated to managing care transitions and coordination of community resources to prevent readmissions. DESCRIPTION: After a thorough SWOT (strengths, weaknesses, opportunities, and threats) analysis, we developed and implemented a cost-avoidance model to prevent readmissions in our uninsured and underinsured patients. OUTCOMES: The project CNS used a wide array of interventions to decrease readmissions. In the last 2 years, there have been a total of 22 less than 30-day readmissions to the emergency department or hospital in 13 patients, a significant decrease from readmissions in these patients prior to the program. Three of them required transfer to a larger hospital for a higher level of care. CONCLUSION: Using advanced practice nurses in transitional care can prevent readmissions, resulting in cost avoidance. The coordination of community resources during transition from hospital to home is a job best suited to CNSs, because they are educated to work within organizations/systems. IMPLICATIONS: The money we saved with this project more than justified the cost of hiring a CNS to lead it. More research is needed into this technology. Guidelines for this intervention need to be developed. Replicating our cost-avoidance transitional care model can help other facilities limit that loss.
