The organizational structure of an intensive care unit influences treatment of hypotension among critically ill patients: A retrospective cohort study.

PURPOSE: Prior studies report that weekend admission to an intensive care unit is associated with increased mortality, potentially attributed to the organizational structure of the unit. This study aims to determine whether treatment of hypotension, a risk factor for mortality, differs according to level of staffing. METHODS: Using the Multiparameter Intelligent Monitoring in Intensive Care database, we conducted a retrospective study of patients admitted to an intensive care unit at Beth Israel Deaconess Medical Center who experienced one or more episodes of hypotension. Episodes were categorized according to the staffing level, defined as high during weekday daytime (7 am-7 pm) and low during weekends or nighttime (7 pm-7 am). RESULTS: Patients with a hypotensive event on a weekend were less likely to be treated compared with those that occurred during the weekday daytime (P = .02). No association between weekday daytime vs weekday nighttime staffing levels and treatment of hypotension was found (risk ratio, 1.02; 95% confidence interval, 0.98-1.07). CONCLUSION: Patients with a hypotensive event on a weekend were less likely to be treated than patients with an event during high-staffing periods. No association between weekday nighttime staffing and hypotension treatment was observed. We conclude that treatment of a hypotensive episode relies on more than solely staffing levels.

Mutations in yeast replication proteins that increase CAG/CTG expansions also increase repeat fragility.

Expansion of trinucleotide repeats (TNRs) is the causative mutation in several human genetic diseases. Expanded TNR tracts are both unstable (changing in length) and fragile (displaying an increased propensity to break). We have investigated the relationship between fidelity of lagging-strand replication and both stability and fragility of TNRs. We devised a new yeast artificial chromomosme (YAC)-based assay for chromosome breakage to analyze fragility of CAG/CTG tracts in mutants deficient for proteins involved in lagging-strand replication: Fen1/Rad27, an endo/exonuclease involved in Okazaki fragment maturation, the nuclease/helicase Dna2, RNase HI, DNA ligase, polymerase delta, and primase. We found that deletion of RAD27 caused a large increase in breakage of short and long CAG/CTG tracts, and defects in DNA ligase and primase increased breakage of long tracts. We also found a correlation between mutations that increase CAG/CTG tract breakage and those that increase repeat expansion. These results suggest that processes that generate strand breaks, such as faulty Okazaki fragment processing or DNA repair, are an important source of TNR expansions.