Time-of-day changes in physician clinical decision making: A retrospective study.

BACKGROUND: Time of day has been associated with variations in certain clinical practices such as cancer screening rates. In this study, we assessed how more general process measures of physician activity, particularly rates of diagnostic test ordering and diagnostic assessments, might be affected by time of day. METHODS: We conducted a retrospective chart review of 3,342 appointments by 20 attending physicians at five outpatient clinics, matching appointments by physician and comparing the average diagnostic tests ordered and average diagnoses assessed per appointment in the first hour of the day versus the last hour of the day. Statistical analyses used sign tests, two-sample t-tests, Wilcoxon tests, Kruskal Wallis tests, and multivariate linear regression. RESULTS: Examining physicians individually, four and six physicians, respectively, had statistically significant first- versus last-hour differences in the number of diagnostic tests ordered and number of diagnoses assessed per patient visit (p ≤ 0.04). As a group, 16 of 20 physicians ordered more tests on average in the first versus last hour (p = 0.012 for equal chance to order more in each time period). Substantial intra-clinic heterogeneity was found in both outcomes for four of five clinics (p < 0.01). CONCLUSIONS: There is some statistical evidence on an individual and group level to support the presence of time-of-day effects on the number of diagnostic tests ordered per patient visit. These findings suggest that time of day may be a factor influencing fundamental physician behavior and processes. Notably, many physicians exhibited significant variation in the primary outcomes compared to same-specialty peers. Additional work is necessary to clarify temporal and inter-physician variation in the outcomes of interest.

Electrical Integration of Human Embryonic Stem Cell-Derived Cardiomyocytes in a Guinea Pig Chronic Infarct Model.

BACKGROUND: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were recently shown to be capable of electromechanical integration following direct injection into intact or recently injured guinea pig hearts, and hESC-CM transplantation in recently injured hearts correlated with improvements in contractile function and a reduction in the incidence of arrhythmias. The present study was aimed at determining the ability of hESC-CMs to integrate and modulate electrical stability following transplantation in a chronic model of cardiac injury. METHODS AND RESULTS: At 28 days following cardiac cryoinjury, guinea pigs underwent intracardiac injection of hESC-CMs, noncardiac hESC derivatives (non-CMs), or vehicle. Histology confirmed partial remuscularization of the infarct zone in hESC-CM recipients while non-CM recipients showed heterogeneous xenografts. The 3 experimental groups showed no significant difference in the left ventricular dimensions or fractional shortening by echocardiography or in the incidence of spontaneous arrhythmias by telemetric monitoring. Although recipients of hESC-CMs and vehicle showed a similar incidence of arrhythmias induced by programmed electrical stimulation at 4 weeks posttransplantation, non-CM recipients proved to be highly inducible, with a ∼3-fold greater incidence of induced arrhythmias. In parallel studies, we investigated the ability of hESC-CMs to couple with host myocardium in chronically injured hearts by the intravital imaging of hESC-CM grafts that stably expressed a fluorescent reporter of graft activation, the genetically encoded calcium sensor GCaMP3. In this work, we found that only ∼38% (5 of 13) of recipients of GCaMP3+ hESC-CMs showed fluorescent transients that were coupled to the host electrocardiogram. CONCLUSIONS: Human embryonic stem cell-derived cardiomyocytes engraft in chronically injured hearts without increasing the incidence of arrhythmias, but their electromechanical integration is more limited than previously reported following their transplantation in a subacute injury model. Moreover, non-CM grafts may promote arrhythmias under certain conditions, a finding that underscores the need for input preparations of high cardiac purity.