Innovations in patient care: changing clinical practice and improving quality.

BACKGROUND: In the traditional hospital organization, administrators supply the resources while physicians determine their use. Given this dichotomy, a partnership between clinicians and hospital management is essential for efforts to enhance the quality of care while controlling costs. To foster this partnership, in 1986 the University of Rochester's Strong Memorial Hospital developed its Innovations in Patient Care (IPC) program, which several other medical centers have duplicated. CURRENT STATUS AND LOGISTICS: Hospital operating revenues of approximately $175,000 per year are provided to both fund proposals and support core IPC staff. Clinical staff submit proposals to study innovations to promote higher quality care and/or the efficient and appropriate use of diagnostic and therapeutic services. Many of the 77 projects funded to date have led to important changes in clinical practice. CASE STUDIES: One study, whose principal investigator was assistant director of emergency medicine, showed that structured, condition-specific (for example, asthma, pharyngitis, lacerations, and isolated closed-head injury) quicksheets improved documentation of clinical findings, resource use, and clinical practice. A study organized by the leadership of surgical nursing revealed that a nursing case management model led to reductions in patient length of stay and increases in nurse satisfaction. Another study, designed by a fellow in neonatalogy, developed and tested guidelines for the use of head ultrasounds in screening very-low-birthweight infants for intraventricular hemorrhage. CONCLUSIONS: IPC programs, which integrate well with initiatives in total quality management, can be effectively used to change clinical practice and improve the quality and efficiency of patient care.

Regulatory issues in clinical applications of cytokines and growth factors.

This article describes the drug approval process at the Center for Biologics Evaluation and Research (CBER), FDA, for cytokines and growth factors that would be licensed for clinical use in the U.S.A. CBER is responsible for setting policy, providing guidance to industry and to academic investigators as they develop and evaluate these new products, and for recommendations about the approvability of license applications. Product development generally parallels clinical development, and the expectations at each stage of the IND (Investigational New Drug) process are discussed. FDA involvement continues beyond licensure to the post marketing phase. The goal is to assure that new cytokines and growth factors are safe and effective and available in a timely manner.

Relationship between 5-fluoro-2'-deoxyuridylate, 2'-deoxyuridylate, and thymidylate synthase activity subsequent to 5-fluorouracil administration, in xenografts of human colon adenocarcinomas.

5-Fluorouracil (FUra) has been administered to mice bearing xenografts of human colon adenocarcinomas. In two tumor lines, HxGC3 and HxVRC5, intrinsically resistant to FUra, 2'-deoxyuridylate (dUMP) accumulated 13.4- and 23.9-fold above basal levels. In HxELC2 xenografts, which demonstrated some sensitivity to FUra, there was a decrease in dUMP concentration after drug administration. Maximal intratumor levels of 5-fluoro-2'-deoxyuridylate (FdUMP) were found at 1 hr, but decreased in all tumor lines by 4 hr after administration of FUra. Data derived in tumor cytosols suggested that FdUMP levels in situ were not rate-limiting for formation of covalent ternary complex, but that accumulation of dUMP would retard the rate of complex formation. Subsequent to administration of FUra, thymidylate synthase activity was reduced greater than 75% in all tumors, but it recovered rapidly in tumors resistant to FUra. In addition, the pretreatment level of activity of thymidylate synthase was 12.7-fold greater in HxVRC5 tumors than in HxELC2 tumors. This elevated activity in HxVRC5 tumors appears not to be a consequence of gene amplification. Formation of FdUMP or the accumulation of dUMP did not correlate with the activity of phosphatases measured at pH 5.8 or pH 9.2 in each tumor line. Further, inhibition of phosphatase activity did not alter, significantly, the net rate of dissociation of the FdUMP-thymidylate synthase-[6R]-CH2-H4PteGlu complex.

Increased lung compliance in mice exposed to sulfur dioxide.

Mice exposed 6-9 days to 40 ppm. SO2 lost 21% of body weight, but static lung compliance increased 37% (P less than or equal to 0.01). Slopes of saline volume-pressure curves increased 8% (non-sig) pointing to a decrease in surface tension rather than tissue elasticity. Alveolar stability, lung weight and lung wet/dry ratio decreased 2 to 6%, whereas trapped gas in-increased 17%, but none were statistically significant.