An interprofessional approach to reducing the overutilization of stress ulcer prophylaxis in adult medical and surgical intensive care units.

BACKGROUND: Overutilization of stress ulcer prophylaxis (SUP) in the intensive care unit (ICU) is common. Acid-suppressive therapies routinely used for SUP are best reserved for patients with greatest risk of clinically important bleeding as they have been associated with nosocomial pneumonia, Clostridium difficile infection and increased hospital cost. OBJECTIVE: The primary objective was to reduce inappropriate utilization of SUP in 2 adult medical and surgical ICU settings at the University of California, San Francisco Medical Center. Secondary objectives included reduction of inappropriate continuation of SUP at ICU and hospital discharge. METHODS: To attain the study objective, an interprofessional team developed a bundled quality improvement initiative, including an institution SUP guideline, pharmacist-led intervention, and an education and awareness campaign. To assess the impact of these interventions, we conducted a retrospective cohort study comparing data on prescribing practices at baseline before and after the intervention. Since computerized prescriber order entry (CPOE) was implemented during this time frame, preintervention data collection consisted of 2 periods, one before and one after CPOE implementation. RESULTS: The incidence of the inappropriate use of SUP was not significantly different between the pre-CPOE and post-CPOE groups (20 and 19 per 100 patient-days, respectively; P = .88), but the incidence of inappropriate use of SUP was significantly lower in the postintervention group versus the post-CPOE group (9 and 19 per 100 patient-days, respectively; P = .03). At ICU discharge, 4% of patients in the post-intervention group were discharged inappropriately on SUP compared with 8% in the post-CPOE group (P = .54). At hospital discharge, none of the patients in the postintervention group were discharged inappropriately on SUP compared with 7% in the post-CPOE group (P = .22). CONCLUSIONS: Implementation of an interprofessional bundled quality improvement initiative is effective in decreasing inappropriate use of SUP in adult medical and surgical ICUs at a university-affiliated, tertiary care academic medical center.

Peramivir: an intravenous neuraminidase inhibitor for the treatment of 2009 H1N1 influenza.

OBJECTIVE: To review the efficacy and safety of peramivir, an unapproved neuraminidase inhibitor recently granted an Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) for the treatment of 2009 H1N1 influenza in select patients. DATA SOURCES: Literature was accessed via MEDLINE (1950-April 2010) using the search terms peramivir, BCX-1812, RWJ 270201, influenza H1N1, swine influenza, and neuraminidase inhibitors. The manufacturer of peramivir, BioCryst Pharmaceuticals, was contacted for unpublished data and information presented at recent scientific meetings. Information was obtained from the Centers for Disease Control and Prevention (CDC) and FDA Web sites. The mandatory requirements for the EUA for peramivir were also consulted. STUDY SELECTION AND DATA EXTRACTION: Available English-language literature was reviewed and selected based on relevance, as was information from the CDC, FDA, and the drug manufacturer. DATA SYNTHESIS: The 2009 H1N1 influenza pandemic has necessitated the selective use of intravenous peramivir, an unapproved neuraminidase inhibitor. Intravenous peramivir has been studied in 4 clinical trials, 2 of which compared the drug to oseltamivir. Dose adjustments are required in pediatric patients and in those with impaired renal function. Clinicians wishing to use peramivir must request authorization from the CDC to confirm patient characteristics warranting its use and to verify the prescriber's understanding of dosing considerations and unapproved status. CONCLUSIONS: Peramivir has shown efficacy for the treatment of 2009 H1N1 influenza; however, it has yet to receive FDA approval. Peramivir is used in hospitalized adult and pediatric patients with suspected or laboratory-confirmed 2009 H1N1 influenza meeting specific criteria, including those unable to receive inhaled or oral neuraminidase inhibitors, those who have not responded to other neuraminidase inhibitors, or when drug delivery by a route other than intravenous is not feasible.

The laminin alpha-1 chain derived peptide, AG73, increases fibronectin levels in breast and melanoma cancer cells.

Laminin-111 promotes the malignant phenotype, and a 12-mer synthetic peptide (AG73, RKRLQVQLSIRT) from the carboxyl terminus of the alpha1 chain increases B16F10 melanoma metastasis to the lung and liver. Using an antibody array, fibronectin was identified as an up-regulated protein in B16F10 cells after incubation with this peptide. The increased fibronectin is cell-associated with no increase in soluble fibronectin. The AG73 peptide increased the number and size of bone metastases with both B16F10 melanoma and MDA-231 breast carcinoma cells in an intracardiac injection model. Using siRNA transfection, we found that a reduction in fibronectin expression did not reduce bone metastasis in the presence of the metastasis-promoting peptide AG73. We conclude that the laminin peptide AG73 increases metastasis independently of fibronectin expression.

Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis.

Skeletal metastases occur with high incidence in patients with breast cancer and cause long-term skeletal morbidity. Osteonectin (SPARC, BM-40) is a bone matrix factor that is an in vitro chemoattractant for breast and prostate cancer cells. Increased expression of osteonectin is found in malignant breast tumors. We infected MDA-231 breast cancer cells with an adenovirus expressing osteonectin to examine the role of osteonectin expression in breast cancer cells and its effect on metastasis, in particular to bone. Expression of osteonectin did not affect MDA-231 cell proliferation, apoptosis, migration, cell aggregation, or protease cleavage of collagen IV. However, in vitro invasion of these osteonectin-infected cells through Matrigel and colony formation on Matrigel was decreased. Interestingly, high osteonectin expression in MDA-231 cells inhibited metastasis in a dose-dependent manner to many different organs including bone. The reduction in metastasis may be due to decreased platelet-tumor cell aggregation, because exogenous osteonectin inhibited platelet aggregation in vitro and the high osteonectin expression in MDA-231 cells reduced tumor cell-induced thrombocytopenia in vivo compared with control-infected cells. These studies suggest that high endogenous expression of osteonectin in breast cancer cells may reduce metastasis via reduced invasive activity and reduced tumor cell-platelet aggregation.