Differential expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase and neural lineage markers correlate with glioblastoma xenograft infiltration and patient survival.

PURPOSE: Glioblastoma multiforme (GBM) is a poorly treated human brain cancer with few established clinically useful molecular prognostic markers. We characterized glioblastoma stem-like cells (GSC) according to developmental neural lineage markers and correlated their expression with patient survival. EXPERIMENTAL DESIGN: Immunoblot array of neural lineage markers classified five independently isolated human GSC lines into three classes exhibiting differential expression of oligodendrocyte progenitor cells (OPC), astrocyte progenitor cells (APC), and neural progenitor cells (NPC) markers. Immunodeficient mice were orthotopically implanted with each cell line to evaluate tumor infiltration and recipient survival. 2',3'-Cyclic-nucleotide 3'-phosphodiesterase (CNP) antigenic expression was used to evaluate a clinically annotated GBM tissue microarray with 115 specimens. RESULTS: We report that molecular classification of patient-derived GSCs using neural lineage markers show association with differential xenograft invasiveness, and also show significant correlation to survival in both the mouse model and human patients. Orthotopic implantation into immunodeficient mice showed Ki-67 proliferative index independent xenograft infiltration: class I GSCs (OPC and NPC positive) established focal lesions, class II GSCs (NPC positive) formed minimally invasive lesions, and class III GSCs (APC positive) established highly infiltrative lesions. The OPC marker, CNP also exhibited high expression in focal xenografts versus low expression in invasive xenografts. Differential CNP expression correlated with mouse model survival, and CNP immunoassay of a large GBM tissue microarray also showed significant differential patient survival. CONCLUSIONS: GSC classification with developmental neural lineage markers revealed CNP as a novel and potentially useful clinical prognosis marker, and suggests clinical importance for patient-specific GSC analysis.

Systematic review of time studies evaluating physicians in the hospital setting.

BACKGROUND: Time studies, first developed in the late 19th century, are now being used to evaluate and improve worker efficiency in the hospital setting. This is the first review of hospital time study literature of which we are aware. PURPOSE: We performed a systematic review of the literature to better understand the available time study literature describing the activities of hospital physicians. DATA SOURCES: We searched MEDLINE, EMBASE, EMBASE Classic, PsycINFO, Cochrane Library, CINAHL, and Web of Science. We also manually reviewed the reference lists of retrieved articles and consulted experts in the field to identify additional articles for review. STUDY SELECTION: We selected studies that used time-motion or work-sampling performed via direct observation, included physicians, medical residents, or interns in their study population, and were performed on an inpatient hospital ward. DATA EXTRACTION: We abstracted data on subject population, study site, collection tools, and percentage of time spent on key categories of activity. DATA SYNTHESIS: Our search produced 11 time-motion and 2 work-sampling studies that met our criteria. These studies focused primarily on academic hospitals (92%) and the activities of physicians in training (69%). Other results varied widely. A lack of methodological standardization and dissimilar activity categorizations inhibited our efforts to summarize detailed findings across studies. However, we consistently found that activities indirectly related to a patient's care took more of hospital physicians' time than direct interaction with hospitalized patients. CONCLUSIONS: Time studies, when properly performed, have a great deal to offer in helping us understand and reengineer hospital care.

Where did the day go?--a time-motion study of hospitalists.

BACKGROUND: Within the last decade hospitalists have become an integral part of inpatient care in the United States and now care for about half of all Medicare patients requiring hospitalization. However, little data exists describing hospitalist workflow and their activities in daily patient care. OBJECTIVE: To clarify how hospitalists spend their time and how patient volumes affect their workflow. DESIGN: Observers continuously shadowed each of 24 hospitalists for two complete shifts. Observations were recorded using a handheld computer device with customized data collection software. SETTING: Urban, tertiary care, academic medical center. RESULTS: : Hospitalists spent 17% of their time on direct patient contact, and 64% on indirect patient care. For 16% of all time recorded, more than one activity was occurring simultaneously (i.e., multitasking). Professional development, personal time, and travel each accounted for about 6% of their time. Communication and electronic medical record (EMR) use, two components of indirect care, occupied 25% and 34% of recorded time respectively. Hospitalists with above average patient loads spent less time per patient communicating with others and working with the EMR than those hospitalists with below average patient loads, but reported delaying documentation until later in the evening or next day. Patient load did not change the amount of time hospitalists spent with each patient. CONCLUSIONS: Hospitalists spend more time reviewing the EMR and documenting in it, than directly with the patient. Multi-tasking occurred frequently and occupied a significant portion of each shift.