Bronchiolitis: an update on management and prophylaxis.

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children less than 2 years of age in the UK. Respiratory syncytial virus is the most common virus associated with bronchiolitis and has the highest disease severity, mortality and cost. Bronchiolitis is generally a self-limiting condition, but can have serious consequences in infants who are very young, premature, or have underlying comorbidities. Management of bronchiolitis in the UK is guided by the National Institute for Health and Care Excellence (2015) guidance. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Pharmacological interventions including nebulized bronchodilators, steroids and antibiotics generally have limited or no evidence of efficacy and are not advised by National Institute of Health and Care Excellence. Antiviral therapeutics remain in development. As treatments are limited, there have been extensive efforts to develop vaccines, mainly targeting respiratory syncytial virus. At present, the only licensed product is a monoclonal antibody for passive immunisation. Its cost restricts its use to those at highest risk. Vaccines for active immunisation of pregnant women and young infants are also being developed

Comparing Patient Outcomes of Academician-Preceptors, Hospitalist-Preceptors, and Hospitalists on Internal Medicine Services in an Academic Medical Center

BACKGROUND: Patient outcomes with hospitalist care have been studied in many settings, yet little is known about how hospitalist care interacts with trainee care to affect patient outcomes in teaching hospitals. OBJECTIVES: The aim of this study was to compare patient outcomes between hospitalist-preceptors and hospitalists working alone (isolating the effect of housestaff involvement), and between hospitalist-preceptors and academician-preceptors (isolating the effect of attending type, given housestaff involvement). DESIGN: A four-year retrospective cohort study of patients (n = 13,313) admitted to all internal medicine services at an academic medical center from July 2008 to June 2012. MAIN MEASURES: Using generalized estimating equations, we measured readmission within 30 days, hospital length of stay, cost of the index hospitalization, and cumulative cost including readmissions within 30 days. KEY RESULTS: In the adjusted models, 30-day readmission odds were higher for academic-preceptors (OR, 1.14 [95 % CI, 1.03 − 1.26]) and hospitalist-preceptors (OR, 1.10 [95 % CI, 1.002 − 1.21]) than for hospitalists working alone. Compared with hospitalists working alone, academic-preceptors were associated with shorter length of stay (mean difference, 0.27 days [95 % CI, 0.18 − 0.38]), lower index hospitalization costs (mean difference, $386 [95$192 − $576]), but similar cumulative inpatient costs within 30 days of discharge. Compared with hospitalists working alone, hospitalist-preceptors were associated with shorter length of stay (mean difference, 0.34 days [95$570 [95 % CI, $378 −$760]), and a trend toward lower cumulative cost (mean difference, $1347 [95$254 − $2,816]). CONCLUSIONS: Preceptor-led medicine services were associated with more readmissions within 30 days, shorter lengths of stay, and lower index admission-associated costs. However, when considering cumulative hospitalization costs, patients discharged by academician-preceptors incurred the highest cost and hospitalist-preceptors incurred the lowest cost. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11606-014-2982-y) contains supplementary material, which is available to authorized users

p53-driven apoptosis limits centrosome amplification and genomic instability downstream of NPM1 phosphorylation

Chromosome loss or gain is associated with a large number of solid cancers, providing genomic plasticity and thus adaptability to cancer cells(1,2). Numerical centrosome abnormalities arising from centrosome over-duplication or failed cytokinesis are a recognized cause of aneuploidy(3,4). In higher eukaryotic cells, the centrosome duplicates only once per cell cycle to ensure the formation of a bipolar mitotic spindle that orchestrates the balanced distribution of the sister chromatids to the respective daughter cells(5). Here we delineate the events that allow abnormal centrosome duplication, resulting in mitotic errors and incorrect chromosome segregation in cells with sustained cyclin-dependent kinase (CDK) activity. We have identified NPM1 as a substrate for CDK6 activated by the Kaposi's sarcoma herpesvirus (KSHV) D-type cyclin and shown that p53-driven apoptosis occurs downstream of NPM1 phosphorylation as a checkpoint mechanism that prevents accumulation of cells with supernumerary centrosomes. Our findings provide evidence that abnormal chromosome segregation in KSHV-infected cells is a direct consequence of NPM1 phosphorylation and predict that genomic instability is an inevitable consequence of latent KSHV infection