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The risk for breast cancer is significantly reduced in persons who engage in greater amounts of physical activity, and greater physical activity before or after diagnosis associates with reduced disease-specific mortality. Previous mechanistic studies indicate that components of innate immunity can mediate an inhibitory effect of physical activity on several types of tumor. However, in breast cancer specifically, the myeloid compartment of innate immunity is thought to exhibit high propensity for an immunosuppressive role that obstructs anti-tumor immunity. Thus, we tested the notion that greater physical activity alters mononuclear phagocytes in mammary tissue when inhibiting nascent tumor in a murine model of breast cancer. To model greater physical activity, we placed an angled running wheel in each mouse's home cage for two weeks before tumor engraftment with EO771 mammary cancer cells that express luciferase for bioluminescent detection. Fully immunocompetent mice and mice with compromised adaptive immunity showed significantly less mammary tumor signal when given access to running wheels, although the effect size was smaller in this latter group. To investigate the role of the myeloid compartment, mononuclear phagocytes were ablated by systemic injection of clodronate liposomes at 24 h before tumor engraftment and again at the time of tumor engraftment, and this treatment reversed the inhibition in wheel running mice. However, clodronate also inhibited mammary tumor signal in sedentary mice, in conjunction with an expected decrease in gene and protein expression of the myeloid antigen, F4/80 (Adgre1), in mammary tissue. Whole transcriptome digital cytometry with CIBERSORTx was used to analyze myeloid cell populations in mammary tissue following voluntary wheel running and clodronate treatment, and this approach found significant changes in macrophage and monocyte populations. In exploratory analyses, whole transcriptome composite scores for monocytic myeloid-derived suppressor cell (M-MDSC), macrophage lactate timer, and inflammation resolution gene expression programs were significantly altered. Altogether, the results support the hypothesis that physical activity inhibits nascent mammary tumor growth by enhancing the anti-tumor potential of mononuclear phagocytes in mammary tissue.

A computerized laboratory alerting system (CLAS) was developed using the decision-making capabilities of the HELP computer system at LDS Hospital in Salt Lake City, Utah. The CLAS generated alerts on life-threatening conditions indicated by laboratory test results and other patient data stored in HELP's computerized patient database. An effective alert feedback mechanism was developed which promoted quick review and acknowledgement of alerts by health care personnel. An evaluation of the effect of the CLAS on patient care and outcome was carried out. Results of the evaluation showed that general nursing floor patients with alerts for hypokalemia, falling potassium, hyperkalemia, hypokalemia--patient on digoxin, hyponatremia, falling sodium, hypernatremia, hypoglycemia and hyperglycemia were treated appropriately 68.1% of the time before CLAS implementation ('pre' study period) and 83.8% of the time after CLAS implementation ('post' study period, p = 0.017). The average number of hours which patients spent in the life-threatening conditions decreased from 30.4 hours in the 'pre' study period to 15.7 hours in the 'post' study period (p = 0.0125). The average patient length of stay also decreased from 350.6 hours in the 'pre' study period to 211.9 hours in the 'post' study period (p = 0.025). Results of the evaluation did not show significant differences in the number of times patients were handled appropriately, or in patient length of stay for general nursing floor patients generating alerts for metabolic acidosis. There was, however, a significant decrease in the average number of hours spent in the life-threatening condition (44.3 hours in the 'pre' study period vs. 26.5 hours in the 'post' study period, p = 0.033) for patients with metabolic acidosis alerts on the general nursing floors. Nurses were the major users of the CLAS (53.0%), followed by physicians (28.5%), ward clerks (11.5%), and other users (7.0%). The overall assessment of the value of the CLAS by users was positive. The CLAS was classified as very useful by 25.6% of users, frequently useful by 24.4% of users, somewhat useful by 34.6% of users, seldom useful by 7.7% of users, and not useful by 7.7% of users.

Problems associated with acute patient care include 1) information overload, 2) complexity of patient data, 3) data communication, 4) delays in treatment leading to critical illness, and 5) absence of attending physicians when decisions are required. Because of their speed and information processing capabilities, computers have been increasingly employed to help overcome these problems. At LDS Hospital, a comprehensive computer system called HELP has been developed. This system acquires, stores and manages patient data, and provides decision-making capabilities. HELP's capabilities have been applied to develop a tool for identifying life-threatening conditions in patients based on laboratory test results. Once a life-threatening condition is identified by the computer, the computer sends an alert message so that appropriate treatment may be rapidly instituted. Preliminary results from our evaluation of the expert system show that it does affect patient care by increasing the number of times that patients are treated for life-threatening conditions. Patient outcome is benefited by shortening the time needed for the patients laboratory test values to return within normal limits.

Ongoing efforts have been made to improve the efficiency and quality of care available in ICU's at LDS Hospital. ICU's have been computerized, and patient data collection, storage and presentation have been improved. Nurse care plans and charting have been computerized, and effects of these changes have been evaluated.