Impact of Empirical-Therapy Selection on Outcomes of Intravenous Drug Users with Infective Endocarditis Caused by Methicillin-Susceptible Staphylococcus aureus▿

This study compares beta-lactam and vancomycin among intravenous drug users with infective endocarditis caused by methicillin-susceptible Staphylococcus aureus. Patients who received vancomycin had higher infection-related mortality, even if they were switched to beta-lactam once culture results became available; this relationship persisted after logistic regression analysis controlling for clinical characteristics

An Evaluation of the Cost Effectiveness of Drotrecogin Alfa (Activated) Relative to the Number of Organ System Failures

Background: While drotrecogin alfa (activated) was shown to decrease absolute 28-day mortality by 6.1% in patients with severe sepsis in the Recombinant Human Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study, no mortality benefit was observed in the subset of patients with only one organ system failure. Consequently, some institutions restrict drotrecogin alfa (activated) use to patients with severe sepsis with >=2 organ system failures. Objective: To measure the cost effectiveness of drotrecogin alfa (activated) for treatment of severe sepsis in relation to the number of organ system failures and determine the economic impact of restricting drotrecogin alfa (activated) use based on the number of organ system failures. Perspective: Policy perspective specific to our 340-bed, level I trauma centre. Methods: A Monte Carlo simulation analysis was conducted to evaluate a hypothetical cohort of 10 Results: With increasing number of organ system failures, the proportion of lives saved with drotrecogin alfa (activated) increased, and consequently the ICER decreased. Restriction of drotrecogin alfa (activated) to patients with >=4 organ system failures was the most cost-effective scenario (0.11 lives saved; $US56 Conclusion: While restriction of drotrecogin alfa (activated) use to patients with sepsis with >=4 organ system failures is the most cost-effective alternative, restriction to those with >=2 organ system failures is the preferred alternative for our institution according to the number of lives saved and available financial resources.Cost-effectiveness, Drotrecogin-alfa, Sepsis

A hypomorphic PALB2 allele gives rise to an unusual form of FA-N associated with lymphoid tumour development

Patients with biallelic truncating mutations in PALB2 have a severe form of Fanconi anaemia (FA-N), with a predisposition for developing embryonal-type tumours in infancy. Here we describe two unusual patients from a single family, carrying biallelic PALB2 mutations, one truncating, c.1676_1677delAAinsG;(p.Gln559ArgfsTer2), and the second, c.2586+1G>A; p.Thr839_Lys862del resulting in an in frame skip of exon 6 (24 amino acids). Strikingly, the affected individuals did not exhibit the severe developmental defects typical of FA-N patients and initially presented with B cell non-Hodgkin lymphoma. The expressed p.Thr839_Lys862del mutant PALB2 protein retained the ability to interact with BRCA2, previously unreported in FA-N patients. There was also a large increased chromosomal radiosensitivity following irradiation in G2 and increased sensitivity to mitomycin C. Although patient cells were unable to form Rad51 foci following exposure to either DNA damaging agent, U2OS cells, in which the mutant PALB2 with in frame skip of exon 6 was induced, did show recruitment of Rad51 to foci following damage. We conclude that a very mild form of FA-N exists arising from a hypomorphic PALB2 allele