The relationship between shift work, sleep, and cognition in career emergency physicians.

OBJECTIVES: The 24-hour physician coverage of the emergency department (ED) requires shift work, which can result in desynchronosis and cognitive decline. We measured changes in cognition and sleep disturbance in attending emergency physicians (EPs) before and after day and overnight shifts. METHODS: Thirteen EPs were tested before and after day and overnight shifts using the Paced Auditory Serial Addition Test (PASAT), the University of Southern California Repeatable Episodic Memory Test (REMT), the Trail Making Test (TMT), and the Stroop Color-Word Test. Sleep quality and fatigue were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Chalder Fatigue Questionnaire (CFQ). Saliva samples were collected from each physician immediately before and after day shifts and night shifts for neurohormonal assays. RESULTS: Significantly fewer words were recalled on the REMT after both day (-2.4, 95% confidence interval [CI] = -4.4 to -0.4) and overnight shifts (-4.6, 95% CI = -6.4 to -2.8). There was a significant postshift increase in words recalled from the last third of the REMT list after overnight shifts (6.6, 95% CI = 2.8 to 10.4). Sleep quality was worse in EPs (mean PSQI = 4.8, SD ± 2.5) compared to the normal population, with 31% of subjects reporting poor sleep quality. Postshift fatigue was correlated with the perceived difficulty of the shift. Salivary cortisol and melatonin demonstrated diurnal variation consistent with normal circadian rhythms. Morning cortisol peak was decreased or delayed in samples from physicians after a night shift. CONCLUSIONS: These data indicate that short-term memory appears to decline after day and overnight shifts and confirms the high incidence of disturbed sleep in this population.

Emergency physicians' risk attitudes in acute decompensated heart failure patients.

OBJECTIVES: Despite the existence of various clinical prediction rules, no data exist defining what frequency of death or serious nonfatal outcomes comprises a realistic "low-risk" group for clinicians. This exploratory study sought to identify emergency physicians' (EPs) definition of low-risk acute decompensated heart failure (ADHF) emergency department (ED) patients. METHODS: Surveys were mailed to full-time physicians (n = 88) in a multihospital EP group in southwestern Pennsylvania between December 2004 and February 2005. Participation was voluntary, and each EP was asked to define low risk (low risk of all-cause 30-day death and low risk of either hospital death or other serious medical complications) and choose a risk threshold at which they might consider outpatient management for those with ADHF. A range of choices was offered (<0.5, <1, <2, <3, <4, and <5%), and demographic data were collected. RESULTS: The response rate was 80%. Physicians defined low risk both for all-cause 30-day death and for hospital death or other serious complications, at <1% (38.8 and 40.3%, respectively). The decision threshold to consider outpatient therapy was <0.5% risk both for all-cause 30-day death (44.6%) and for hospital death or serious medical complications (44.4%). CONCLUSIONS: Emergency physicians in this exploratory study define low-risk ADHF patients as having less than a 1% risk of 30-day death or inpatient death or complications. They state a desire to have and use an ADHF clinical prediction rule that can identify low-risk ADHF patients who have less than a 0.5% risk of 30-day death or inpatient death or complications.

Expression, purification, and kinetic characterization of recombinant rat cysteine dioxygenase, a non-heme metalloenzyme necessary for regulation of cellular cysteine levels.

Cysteine dioxygenase (CDO, EC 1.13.11.20) is a non-heme mononuclear iron enzyme that oxidizes cysteine to cysteinesulfinate. CDO catalyzes the first step in the pathway of taurine synthesis from cysteine as well as the first step in the catabolism of cysteine to pyruvate and sulfate. Previous attempts to purify CDO have been associated with partial or total inactivation of CDO. In an effort to obtain highly purified and active CDO, recombinant rat CDO was heterologously expressed and purified, and its activity profile was characterized. The protein was expressed as a fusion protein bearing a polyhistidine tag to facilitate purification, a thioredoxin tag to improve solubility, and a factor Xa cleavage site to permit removal of the entire N-terminus, leaving only the 200 amino acids inherent to the native protein. A multi-step purification scheme was used to achieve >95% purity of CDO. The approximately 40.3 kDa full-length fusion protein was purified to homogeneity using a three-column scheme, the fusion tag was then removed by digestion with factor Xa, and a final column step was used to purify homogeneous approximately 23 kDa CDO. The purified CDO had high specific activity and kinetic parameters that were similar to those for non-purified rat liver homogenate, including a Vmax of approximately 1880 nmol min-1 mg-1 CDO (kcat=43 min-1) and a Km of 0.45 mM for L-cysteine. The expression and purification of CDO in a stable, highly active form has yielded significant insight into the kinetic properties of this unique thiol dioxygenase.