Comparing the Accuracy of Pyxis Medstation and Pyxis PARx Systems

Class of 2010 AbstractOBJECTIVES: The objective of this study is to compare the number of medication refill errors that occur between the Pyxis Medstation 3500 and the Pyxis PARx automated dispensing systems. The accuracy of refilling Pyxis Medstation 3500 automated dispensing machines by pharmacy technicians at the University Medical Center (UMC) was assessed during six days in July 2009. The accuracy was then reassessed over the course of five days in September 2009, one month after implementation of the new Pyxis PARx barcode technology in August. All medications in both the morning and afternoon Pyxis refill reports generated by the UMC inpatient pharmacy were audited during the chosen days. METHODS: The accuracy of refilling Pyxis Medstation 3500 automated dispensing machines by pharmacy technicians at a 350-bed, tertiary-care, teaching hospital with a total of 50 automated dispensing systems was assessed during five days in July 2009. The accuracy was then reassessed over the course of five days in September 2009, one month after implementation of the new Pyxis PARx barcode technology in August. It was assumed that the following types of medication refill errors would be reduced: 1)Wrong drug, Wrong strength 2) Wrong drug, Right strength 3) Right drug, Wrong strength 4) Filling error/Wrong pocket 5) Overfill of pocket 6) Expired medication 7) Right drug, Wrong form. This study was a prospective evaluation of medication refill errors between an older automated dispensing system (Pyxis Medstation) and a newer system (Pyxis PARx). The addition of PARx barcode technology automates the pick and delivery method in order to enhance security during the medication refill process. When the appropriate drawer is opened, the medication must be scanned using the handheld scanner to make sure the correct medication is being refilled. All medications from each Pyxis refill report on the chosen days were audited during pre and post implementation of the new Pyxis PARx barcode technology. Medications to be audited were identified by collecting data from each automated dispensing system listed on the refill reports for the previous day. Audits were performed on the following day (i.e., Monday’s refill reports was audited on Tuesday) by study investigators. Each completed refill was audited for the above medication errors and a brief description of any errors found was noted. RESULTS: A total of 825 refilled items were audited prior to PARx installation (from dates 7/14/09-7/19/09) and a total of five errors were found. Post PARx installation, 959 items were audited (from dates 9/24/09-9/29/09) and a total of two errors were found. Overall, the types of errors encountered were Right Drug/Wrong Form (1/7, 14.3%), Filling Error/Wrong Pocket (2/7, 28.6%), Overfill (1/7, 14.3%), Expired Medication (2/7, 28.6%) and Right Drug/Wrong Strength (1/7, 14.3%). A Chi-square analysis was done to compare pre and post-PARx implementation errors found. The Chi square value was found to be 1.79 with a p-value of 0.18, meaning that there is an 18% probability that any deviation from expected is due to chance. Thus, per our investigation the installation of PARx did not significantly decrease refill error rates. CONCLUSIONS: In ProgressThis item is part of the Pharmacy Student Research Projects collection, made available by the College of Pharmacy and the University Libraries at the University of Arizona. For more information about items in this collection, please contact Jennifer Martin, Librarian and Clinical Instructor, Pharmacy Practice and Science, [email protected]

Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression

CD4(+)CD25(+) regulatory T lymphocytes (Tregs) critically contribute to the mechanisms of cancer-induced tolerance. These cells suppress anti-tumoral CD8(+) and CD4(+) T lymphocytes and can also restrain the function of APCs. We have previously documented the immunostimulatory effects of a chaperone-rich cell lysate (CRCL) anti-cancer vaccine. Tumor-derived CRCL induces tumor immunity in vivo, partly by promoting dendritic cell (DC) and macrophage activation. In the current study, we evaluated the effects of CD4(+)CD25(+)forkhead box P3(+) Tregs isolated from mice bearing 12B1 bcr-abl(+) leukemia on DC and macrophages that had been activated by 12B1-derived CRCL. CRCL-activated DC and macrophages resisted Treg suppression, as the production of proinflammatory cytokines, the activation of transcription factor NF-kappaB, and their immunostimulatory potential was unaffected by Tregs. Our results thus highlight CRCL as a powerful adjuvant endowed with the capacity to overcome tumor-induced Treg-inhibitory effects on APCs

Natural killer cells play a key role in the antitumor immunity generated by chaperone-rich cell lysate vaccination

Tumor derived chaperone-rich cell lysate (CRCL) when isolated from tumor tissues is a potent vaccine that contains at least 4 of the highly immunogenic heat shock proteins (HSP) such as HSP70, HSP90, glucose related protein 94 and calreticulin. We have previously documented that CRCL provides both a source of tumor antigens and danger signals triggering dendritic cell (DC) activation. Immunization with tumor derived CRCL elicits tumor-specific T cell responses leading to tumor regression. In the current study, we further dissect the mechanisms by which CRCL simulates the immune system, and demonstrate that natural killer (NK) cells are required for effective antitumor effects to take place. Our results illustrate that CRCL directly stimulates proinflammatory cytokine and chemokine production by NK cells, which may lead to activation and recruitment of macrophages at the tumor site. Thus, this report provides further insight into the function of CRCL as an immunostimulant against cancer

Tumor-Derived Chaperone-Rich Cell Lysate (CRCL) Can Be Effectively Combined with Syngeneic Bone Marrow Transplantation to Treat Bcr-abl+ Leukemia in a Murine Model.

Abstract We have previously reported that purified tumor derived chaperone-rich cell lysate (CRCL) containing multiple heat shock proteins (HSPs) is a promising cancer vaccine, capable of generating tumor-specific T cell responses and protective immunity in different animal tumor models. In this study, we have explored the therapeutic applicability of CRCL in the context of syngeneic bone marrow transplantation (BMT) to treat preexisting leukemia. BALB/c mice received a 10-fold LD100 dose of bcr-abl+ leukemia cells (12B1) subcutaneously (s.c.) on day -7. On day -1, 900cGy of total body irradiation (TBI) was given followed by syngeneic bone marrow transplantation (BMT) on day 0. Transplanted mice received 20X106 bone marrow cells along with 50X106 splenocytes (SPC) intravenously (i.v.). We have demonstrated that BMT/SPC prolonged survival of mice by a median time of 7 days (median survival time [MST] from tumor inoculation of no BMT versus BMT/SPC =19 vs 26 days), however, all mice eventually died of disseminated leukemia. When recipients received BMT and SPC from syngeneic donors that had been previously immunized with 12B1-derived CRCL (immune BMT/SPC) the MST was increased to 29 days with 26.1% of transplanted mice surviving without tumor (p&amp;lt;0.01 immune BMT/SPC vs naive BMT/SPC). Vaccination of immune BMT/SPC recipients with 20 mg 12B1-derived CRCL in the early post-transplant period (day +1 and day +6) increased MST to 32 days (p&amp;lt;0.01 vs naïve BMT/SPC control) but did not significantly improve overall survival (26.3%) when compared to immune BMT/SPC mice not receiving post transplant 12B1-CRCL vaccine. Eleven to 17 weeks later, mice with no evidence of disease were re-challenged with 12B1 cells in one groin and A20 B cell leukemia cells in the opposite groin. Eighty percent of the mice demonstrated long term tumor specific immunity by rejecting the 12B1 rechallenge while 100% of the mice developed A20 tumors. Our results indicate that CRCL is a promising vaccine that can be used to generate specific anti-tumor immunity that can be effectively transferred to a host via BMT.</jats:p

Tumor-derived CD4+CD25+ regulatory T cell suppression of dendritic cell function involves TGF-β and IL-10

CD4+CD25+ regulatory T cells have been characterized as a critical population of immunosuppressive cells. They play a crucial role in cancer progression by inhibiting the effector function of CD4+ or CD8+ T lymphocytes. However, whether regulatory T lymphocytes that expand during tumor progression can modulate dendritic cell function is unclear. To address this issue, we have evaluated the inhibitory potential of CD4+CD25+ regulatory T cells from mice bearing a BCR–ABL+ leukemia on bone marrow-derived dendritic cells. We present data demonstrating that CD4+CD25+FoxP3+ regulatory T cells from tumor-bearing animals impede dendritic cell function by down-regulating the activation of the transcription factor NF-κB. The expression of the co-stimulatory molecules CD80, CD86 and CD40, the production of TNF-α, IL-12, and CCL5/RANTES by the suppressed DC is strongly down-regulated. The suppression mechanism requires TGF-β and IL-10 and is associated with induction of the Smad signaling pathway and activation of the STAT3 transcription factor

A chaperone protein-enriched tumor cell lysate vaccine generates protective humoral immunity in a mouse breast cancer model

We have documented previously that a multiple chaperone protein vaccine termed chaperone-rich cell lysate (CRCL) promotes tumor-specific T-cell responses leading to cancer regression in several mouse tumor models. We report here that CRCL vaccine generated from a mouse breast cancer (TUBO, HER2/neu positive) is also capable of eliciting humoral immunity. Administration of TUBO CRCL triggered anti-HER2/neu antibody production and delayed the progression of established tumors. This antitumor activity can be transferred through the serum isolated from TUBO CRCL-immunized animals and involved both B cells and CD4(+) T lymphocytes. Further evaluation of the mechanisms underlying TUBO CRCL-mediated humoral immunity highlighted the role of antibody-dependent cell-mediated cytotoxicity. These results suggest that tumor-derived CRCL vaccine has a wider applicability as a cancer vaccine because it can target both T-cell- and B-cell-specific responses and may represent a promising approach for the immunotherapy of cancer