The Well-Defined Pediatric ICU: Active Surveillance Using Nonmedical Personnel to Capture Less Serious Safety Events.

BACKGROUND: Adverse events, diverse and often costly, commonly occur in pediatric intensive care units (PICUs). Serious safety events (SSEs) are captured through well-developed systems, typically by voluntary reporting. Less serious safety events (LSSEs), including close calls, however, occur at a higher frequency than those that result in immediate harm or death but are underestimated by standard reporting systems. LSSEs can reveal system defects and precede serious events resulting in patient or provider harm. METHODS: A unique active surveillance program was created at Children's Hospitals and Clinics of Minnesota to quantify and categorize, and, ultimately reduce, LSSEs, in PICUs. Premedical college graduates without formal health care training daily canvassed the PICUs and facilitated reporting of LSSEs at the point of care. Events were recorded on a Web application and stored in a relational database management system. Events were enumerated and categorized according to distinctive characteristics (Theme Index) and real or potential harm (Harm Index). RESULTS: Some 1,980 PICU patients, representing 10,766 PICU patient-days in a 15-month period (June 1, 2013- August 31, 2014) experienced 2,465 LSSEs-5.4 LSSEs/ day or 0.23 LSSEs/patient-day. Such events resulted in a patient intervention 38% of the time. Some 158 quality/safety improvement projects were initiated during the observation period, 74 of which have been completed. Quality/safety information was broadcasted to providers, local leadership, and hospital management. CONCLUSIONS: LSSEs occur frequently in our PICUs. Non-health care providers can cost-effectively facilitate reporting by actively canvassing PICU providers on a daily basis and can contribute to quality/safety improvement projects and local safety culture. Reported events can serve as a focus for quality/safety improvement projects. A Web application and mobile tablet interfaces are efficient tools to record events.

Triptolide and its prodrug minnelide suppress Hsp70 and inhibit in vivo growth in a xenograft model of mesothelioma.

Malignant mesothelioma is a devastating disease with a poor prognosis for which there is a clear need for more successful therapeutic approaches. Triptolide, a diterpenoid triepoxide, is a highly effective agent against several cancer types in animal models. Owing to triptolide's poor solubility in water, a water-soluble analog, minnelide, was synthesized. Minnelide is a prodrug of triptolide and is activated by exposure to phosphatases that are found in all body tissues, including blood. Mesothelioma cells were treated in vitro with minnelide or its parent compound, triptolide. Minnelide and triptolide were both found to significantly reduce mesothelioma cell viability and induce apoptosis. The level of Hsp70, a protein that promotes cancer cell survival, was measured in mesothelioma cells before and after treatment with triptolide. Hsp70 levels were decreased in a dose-dependent manner. In addition, triptolide sensitized cells to gemcitabine and pemetrexed as measured by cell viability. Mice bearing mesothelioma flank tumors were treated with daily injections (28 d) of minnelide or saline solution and xenograft tumor growth recorded. Mice displayed significantly reduced tumor burden. These findings support the clinical evaluation of minnelide therapy for mesothelioma.

Measles vaccine strains for virotherapy of non-small-cell lung carcinoma.

INTRODUCTION: Oncolytic virus therapy is a promising therapy for numerous tumor types. Edmonston-strain measles virus (MV) has been tested in clinical trials for ovarian cancer, glioma, and myeloma. Therefore, the antitumor activity of MV against non-small-cell lung cancer (NSCLC) was assessed. METHODS: Human NSCLC cells and immortalized lung epithelial cell lines, Beas2B, were infected with either MV-producing green fluorescent protein or MV-producing carcinoembryonic antigen. Cells were assessed for viability, induction of apoptosis by caspase and poly-ADP ribose polymerase cleavage, and for viral transgene production. The dependency of MV entry on CD46 and nectin-4 were determined using blocking antibodies. The role of host translational activity on viral replication was assessed by overexpression of eIF4E and translation inhibition. Antitumor activity was assessed by measuring treated NSCLC xenografts from flanks of nude mice. RESULTS: MV infection of NSCLC cells results in potent cell killing in most of the cell lines compared with immortalized Beas2B cells and induces apoptosis. MV infection was prevented by blocking of CD46, however independent of nectin-4 blockade. Tumor weights are diminished after intratumoral injections of MV-producing carcinoembryonic antigen in one of two cell lines and result in detectable viral transgene in serum of mice. CONCLUSIONS: These data indicate that MV is oncolytic for human NSCLC and this was independent of nectin-4 expression. Dysregulated protein translational machinery may play a role in determining tumor tropism in NSCLC. MV combined with gemcitabine could be explored further as chemovirotherapy for NSCLC.