Person:

Katz, Joel

BACKGROUND Although sleep deprivation has been shown to impair neurobehavioral performance, few studies have measured its effects on medical errors.

METHODS We conducted a prospective, randomized study comparing the rates of serious medical errors made by interns while they were working according to a traditional schedule with extended (24 hours or more) work shifts every other shift (an “every third night” call schedule) and while they were working according to an intervention schedule that eliminated extended work shifts and reduced the number of hours worked per week. Incidents were identified by means of a multidisciplinary, four-pronged approach that included direct, continuous observation. Two physicians who were unaware of the interns' schedule assignments independently rated each incident.

RESULTS During a total of 2203 patient-days involving 634 admissions, interns made 35.9 percent more serious medical errors during the traditional schedule than during the intervention schedule (136.0 vs. 100.1 per 1000 patient-days, P<0.001), including 56.6 percent more nonintercepted serious errors (P<0.001). The total rate of serious errors on the critical care units was 22.0 percent higher during the traditional schedule than during the intervention schedule (193.2 vs. 158.4 per 1000 patient-days, P<0.001). Interns made 20.8 percent more serious medication errors during the traditional schedule than during the intervention schedule (99.7 vs. 82.5 per 1000 patient-days, P=0.03). Interns also made 5.6 times as many serious diagnostic errors during the traditional schedule as during the intervention schedule (18.6 vs. 3.3 per 1000 patient-days, P<0.001).

CONCLUSIONS Interns made substantially more serious medical errors when they worked frequent shifts of 24 hours or more than when they worked shorter shifts. Eliminating extended work shifts and reducing the number of hours interns work per week can reduce serious medical errors in the intensive care unit.

The recent discovery of dideoxymycobactin (DDM) as a ligand for CD1a demonstrates how a nonribosomal lipopeptide antigen is presented to T cells. DDM contains an unusual acylation motif and a peptide sequence present only in mycobacteria, but its discovery raises the possibility that ribosomally produced viral or mammalian proteins that commonly undergo lipidation might also function as antigens. To test this, we measured T cell responses to synthetic acylpeptides that mimic lipoproteins produced by cells and viruses. CD1c presented an N-acyl glycine dodecamer peptide (lipo-12) to human T cells, and the response was specific for the acyl linkage as well as the peptide length and sequence. Thus, CD1c represents the second member of the CD1 family to present lipopeptides. lipo-12 was efficiently recognized when presented by intact cells, and unlike DDM, it was inactivated by proteases and augmented by protease inhibitors. Although lysosomes often promote antigen presentation by CD1, rerouting CD1c to lysosomes by mutating CD1 tail sequences caused reduction in lipo-12 presentation. Thus, although certain antigens require antigen processing in lysosomes, others are destroyed there, providing a hypothesis for the evolutionary conservation of large CD1 families containing isoforms that survey early endosomal pathways.

The recent discovery of dideoxymycobactin (DDM) as a ligand for CD1a demonstrates how a nonribosomal lipopeptide antigen is presented to T cells. DDM contains an unusual acylation motif and a peptide sequence present only in mycobacteria, but its discovery raises the possibility that ribosomally produced viral or mammalian proteins that commonly undergo lipidation might also function as antigens. To test this, we measured T cell responses to synthetic acylpeptides that mimic lipoproteins produced by cells and viruses. CD1c presented an N-acyl glycine dodecamer peptide (lipo-12) to human T cells, and the response was specific for the acyl linkage as well as the peptide length and sequence. Thus, CD1c represents the second member of the CD1 family to present lipopeptides. lipo-12 was efficiently recognized when presented by intact cells, and unlike DDM, it was inactivated by proteases and augmented by protease inhibitors. Although lysosomes often promote antigen presentation by CD1, rerouting CD1c to lysosomes by mutating CD1 tail sequences caused reduction in lipo-12 presentation. Thus, although certain antigens require antigen processing in lysosomes, others are destroyed there, providing a hypothesis for the evolutionary conservation of large CD1 families containing isoforms that survey early endosomal pathways.