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Author (up) Hudgins, J.D.; Goldberg, V.; Fell, G.L.; Puder, M.; Eisenberg, M.A.
Title Reducing Time to Antibiotics in Children With Intestinal Failure, Central Venous Line, and Fever Type Journal Article
Year 2017 Publication Pediatrics Abbreviated Journal Pediatrics
Volume 140 Issue 5 Pages
Keywords Anti-Bacterial Agents/*administration & dosage; Bacteremia/diagnosis/drug therapy/epidemiology; Central Venous Catheters/microbiology; Child, Preschool; Cohort Studies; Female; Fever/diagnosis/*drug therapy/*epidemiology; Humans; Intestinal Diseases/diagnosis/drug therapy/epidemiology; Length of Stay/*trends; Male; Short Bowel Syndrome/diagnosis/*drug therapy/*epidemiology; Time-to-Treatment
Abstract BACKGROUND: Children with intestinal failure (IF) on parenteral nutrition (PN) are at high risk for bacteremia, and delays in antibiotic administration have been associated with increased morbidity and mortality. We designed an emergency department (ED) quality improvement (QI) initiative to reduce time to administration of intravenous antibiotics in febrile children with IF on PN. METHODS: Our aim was to decrease the mean time for febrile children with IF on PN to receive intravenous antibiotics by 50% to <60 minutes over a 12-month period. Secondary outcome measures were ED, hospital, and ICU length of stay (LOS). Our process measure was the rate of ordering recommended antibiotics, and our balancing measure was the rate of hypoglycemia. Interventions included increasing provider knowledge of IF, streamlining order entry, providing individualized feedback, and standardizing the triage process. Results were analyzed by using statistical process control methodology and time series analysis. RESULTS: We identified 149 eligible ED patients, of which 62 (41.6%) had bacteremia. The mean time to antibiotics decreased after the onset of the QI initiative from 112 to 39 minutes, and the ED LOS decreased from 286 to 247 minutes, but the total length of hospital and ICU stays were unchanged. The rate of hypoglycemia was also unchanged. CONCLUSIONS: Our QI intervention for febrile children with IF on PN shortened the time to receive antibiotics. Larger studies are needed to demonstrate the impact on overall LOS and mortality.
Address Division of Emergency Medicine and
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0031-4005 ISBN Medium
Area Expedition Conference
Notes PMID:29066581 Approved no
Call Number ref @ user @ Serial 98935
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Author (up) Hudgins, J.D.; Goldberg, V.; Fell, G.L.; Puder, M.; Eisenberg, M.A.
Title Reducing Time to Antibiotics in Children With Intestinal Failure, Central Venous Line, and Fever Type Journal Article
Year 2017 Publication Pediatrics Abbreviated Journal Pediatrics
Volume 140 Issue 5 Pages
Keywords Anti-Bacterial Agents/*administration & dosage; Bacteremia/diagnosis/drug therapy/epidemiology; Central Venous Catheters/microbiology; Child, Preschool; Cohort Studies; Female; Fever/diagnosis/*drug therapy/*epidemiology; Humans; Intestinal Diseases/diagnosis/drug therapy/epidemiology; Length of Stay/*trends; Male; Short Bowel Syndrome/diagnosis/*drug therapy/*epidemiology; Time-to-Treatment
Abstract BACKGROUND: Children with intestinal failure (IF) on parenteral nutrition (PN) are at high risk for bacteremia, and delays in antibiotic administration have been associated with increased morbidity and mortality. We designed an emergency department (ED) quality improvement (QI) initiative to reduce time to administration of intravenous antibiotics in febrile children with IF on PN. METHODS: Our aim was to decrease the mean time for febrile children with IF on PN to receive intravenous antibiotics by 50% to <60 minutes over a 12-month period. Secondary outcome measures were ED, hospital, and ICU length of stay (LOS). Our process measure was the rate of ordering recommended antibiotics, and our balancing measure was the rate of hypoglycemia. Interventions included increasing provider knowledge of IF, streamlining order entry, providing individualized feedback, and standardizing the triage process. Results were analyzed by using statistical process control methodology and time series analysis. RESULTS: We identified 149 eligible ED patients, of which 62 (41.6%) had bacteremia. The mean time to antibiotics decreased after the onset of the QI initiative from 112 to 39 minutes, and the ED LOS decreased from 286 to 247 minutes, but the total length of hospital and ICU stays were unchanged. The rate of hypoglycemia was also unchanged. CONCLUSIONS: Our QI intervention for febrile children with IF on PN shortened the time to receive antibiotics. Larger studies are needed to demonstrate the impact on overall LOS and mortality.
Address Division of Emergency Medicine and
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0031-4005 ISBN Medium
Area Expedition Conference
Notes PMID:29066581 Approved no
Call Number ref @ user @ Serial 99965
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Author (up) Jahan, N.; Lee, J.M.; Shah, K.; Wakimoto, H.
Title Therapeutic targeting of chemoresistant and recurrent glioblastoma stem cells with a proapoptotic variant of oncolytic herpes simplex virus Type Journal Article
Year 2017 Publication International Journal of Cancer Abbreviated Journal Int J Cancer
Volume 141 Issue 8 Pages 1671-1681
Keywords Animals; Apoptosis/physiology; Brain Neoplasms/drug therapy/*therapy/virology; Cell Line, Tumor; Cohort Studies; Dacarbazine/analogs & derivatives/pharmacology; Drug Resistance, Neoplasm; Glioblastoma/drug therapy/*therapy/virology; HEK293 Cells; Humans; Mice; Neoplasm Recurrence, Local/drug therapy/therapy/virology; Neoplastic Stem Cells/drug effects/pathology/*virology; Oncolytic Virotherapy/*methods; Simplexvirus/genetics/*physiology; TNF-Related Apoptosis-Inducing Ligand/biosynthesis/genetics; TNF-related apoptosis inducing ligand (TRAIL); glioblastoma; oncolytic herpes simplex virus; recurrence; temozolomide
Abstract Temozolomide (TMZ) chemotherapy, in combination with maximal safe resection and radiotherapy, is the current standard of care for patients with glioblastoma (GBM). Despite this multimodal approach, GBM inevitably relapses primarily due to resistance to chemo-radiotherapy, and effective treatment is not available for recurrent disease. In this study we identified TMZ resistant patient-derived primary and previously treated recurrent GBM stem cells (GSC), and investigated the therapeutic activity of a pro-apoptotic variant of oHSV (oHSV-TRAIL) in vitro and in vivo. We show that oHSV-TRAIL modulates cell survival and MAP Kinase proliferation signaling pathways as well as DNA damage response pathways in both primary and recurrent TMZ-resistant GSC. Utilizing real time in vivo imaging and correlative immunohistochemistry, we show that oHSV-TRAIL potently inhibits tumor growth and extends survival of mice bearing TMZ-insensitive recurrent intracerebral GSC tumors via robust and selective induction of apoptosis-mediated death in tumor cells, resulting in cures in 40% of the treated mice. In comparison, the anti-tumor effects in a primary chemoresistant GSC GBM model exhibiting a highly invasive phenotype were significant but less prominent. This work thus demonstrates the ability of oHSV-TRAIL to overcome the therapeutic resistance and recurrence of GBM, and provides a basis for its testing in a GBM clinical trial.
Address Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0020-7136 ISBN Medium
Area Expedition Conference
Notes PMID:28567859 Approved no
Call Number ref @ user @ Serial 96584
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Author (up) Jara-Samaniego, J.; Perez-Murcia, M.D.; Bustamante, M.A.; Paredes, C.; Perez-Espinosa, A.; Gavilanes-Teran, I.; Lopez, M.; Marhuenda-Egea, F.C.; Brito, H.; Moral, R.
Title Development of organic fertilizers from food market waste and urban gardening by composting in Ecuador Type Journal Article
Year 2017 Publication PloS one Abbreviated Journal PLoS One
Volume 12 Issue 7 Pages e0181621
Keywords Analysis of Variance; Carbon/analysis; *Cities; Ecuador; Feasibility Studies; *Fertilizers/analysis/economics; *Food; *Gardening/economics/methods; Nitrogen/analysis; Plants; Recycling/economics/methods; *Soil/chemistry; Temperature; Waste Management/economics/*methods
Abstract Currently, the management of urban waste streams in developing countries is not optimized yet, and in many cases these wastes are disposed untreated in open dumps. This fact causes serious environmental and health problems due to the presence of contaminants and pathogens. Frequently, the use of specific low-cost strategies reduces the total amount of wastes. These strategies are mainly associated to the identification, separate collection and composting of specific organic waste streams, such as vegetable and fruit refuses from food markets and urban gardening activities. Concretely, in the Chimborazo Region (Ecuador), more than 80% of municipal solid waste is dumped into environment due to the lack of an efficient waste management strategy. Therefore, the aim of this study was to develop a demonstration project at field scale in this region to evaluate the feasibility of implanting the composting technology not only for the management of the organic waste fluxes from food market and gardening activities to be scaled-up in other developing regions, but also to obtain an end-product with a commercial value as organic fertilizer. Three co-composting mixtures were prepared using market wastes mixed with pruning of trees and ornamental palms as bulking agents. Two piles were created using different proportions of market waste and prunings of trees and ornamental palms: pile 1 (50:33:17) with a C/N ratio 25; pile 2: (60:30:10) with C/N ratio 24 and pile 3 (75:0:25) with C/N ratio 33), prepared with market waste and prunings of ornamental palm. Throughout the process, the temperature of the mixtures was monitored and organic matter evolution was determined using thermogravimetric and chemical techniques. Additionally, physico-chemical, chemical and agronomic parameters were determined to evaluate compost quality. The results obtained indicated that all the piles showed a suitable development of the composting process, with a significant organic matter decomposition, reached in a shorter period of time in pile 3. At the end of the process, all the composts showed absence of phytotoxicity and suitable agronomic properties for their use as organic fertilizers. This reflects the viability of the proposed alternative to be scaled-up in developing areas, not only to manage and recycle urban waste fluxes, but also to obtain organic fertilizers, including added value in economic terms related to nutrient contents.
Address Dept. of Agrochemistry and Environment, Miguel Hernandez University, Orihuela, Alicante, Spain
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1932-6203 ISBN Medium
Area Expedition Conference
Notes PMID:28727757 Approved no
Call Number ref @ user @ Serial 98013
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Author (up) Jensen, S.S.; Petterson, S.A.; Halle, B.; Aaberg-Jessen, C.; Kristensen, B.W.
Title Effects of the lysosomal destabilizing drug siramesine on glioblastoma in vitro and in vivo Type Journal Article
Year 2017 Publication BMC Cancer Abbreviated Journal BMC Cancer
Volume 17 Issue 1 Pages 178
Keywords Brain slice cultures; Cancer stem cell; Glioblastoma; Lysosomes; Siramesine; Spheroids
Abstract BACKGROUND: Glioblastoma is the most frequent and most malignant brain tumor with the patients having a median survival of only 14.6 months. Although glioblastoma patients are treated with surgery, radiation and chemotherapy recurrence is inevitable. A stem-like population of radio- and chemoresistant brain tumor-initiating cells combined with the invasive properties of the tumors is believed to be critical for treatment resistance. In the present study, the aim was to investigate the effect of a novel therapeutic strategy using the lysosomotropic detergent siramesine on glioblastomas. METHODS: Standard glioma cell lines and patient-derived spheroids cultures with tumor-initiating stem-like cells were used to investigate effects of siramesine on proliferation and cell death. Responsible mechanisms were investigated by inhibitors of caspases and cathepsins. Effects of siramesine on migrating tumor cells were investigated by a flat surface migration assay and by implanting spheroids into organotypic rat brain slice cultures followed by confocal time-lapse imaging. Finally the effect of siramesine was investigated in an orthotopic mouse glioblastoma model. Results obtained in vitro and in vivo were confirmed by immunohistochemical staining of histological sections of spheroids, spheroids in brain slice cultures and tumors in mice brains. RESULTS: The results showed that siramesine killed standard glioma cell lines in vitro, and loss of acridine orange staining suggested a compromised lysosomal membrane. Co-treatment of the cell lines with inhibitors of caspases and cathepsins suggested differential involvement in cell death. Siramesine caused tumor cell death and reduced secondary spheroid formation of patient-derived spheroid cultures. In the flat surface migration model siramesine caused tumor cell death and inhibited tumor cell migration. This could not be reproduced in the organotypic three dimensional spheroid-brain slice culture model or in the mice xenograft model. CONCLUSIONS: In conclusion the in vitro results obtained with tumor cells and spheroids suggest a potential of lysosomal destabilizing drugs in killing glioblastoma cells, but siramesine was without effect in the organotypic spheroid-brain slice culture model and the in vivo xenograft model.
Address Institute of Clinical Research, University of Southern Denmark, Winslowparken 19.3, 5000, Odense C, Denmark. bjarne.winther.kristensen@rsyd.dk
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1471-2407 ISBN Medium
Area Expedition Conference
Notes PMID:28270132 Approved no
Call Number ref @ user @ Serial 96603
Permanent link to this record