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1. Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

Author

Underwood, Jonathan, De Francesco, Davide, Cole, James H, Caan, Matthan W A, van Zoest, Rosan A, Schmand, Ben A, Sharp, David J, Sabin, Caroline A, Reiss, Peter, Winston, Alan Coolaboratori: Reiss P, Wit FWNM, Schouten J, Kooij KW, van Zoest RA, Elsenga BC, Janssen FR, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra NA, Harskamp-Holwerda AM, Maurer I, Mangas Ruiz MM, Girigorie AF, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand BA, Geurtsen GJ, Ter Stege JA, Klein Twennaar M, Majoie CBLM, Caan MWA, Su T, Weijer K, Bisschop PHLT, Kalsbeek A, Wezel M, Visser I, Ruhé HG, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall'Olio F, Chiricolo M, Salvioli S, Hoeijmakers J, Pothof J, Prins M, Martens M, Moll S, Berkel J, Totté M, Kovalev S, Gisslén M, Fuchs D, Zetterberg H, Winston A, Underwood J, McDonald L, Stott M, Legg K, Lovell A, Erlwein O, Doyle N, Kingsley C, Sharp DJ, Leech R, Cole JH, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, Burger D, de Graaff-Teulen M, Guaraldi G, Bürkle A, Sindlinger T, Moreno-Villanueva M, Keller A, Sabin C, de Francesco D, Libert C, Dewaele S, Boffito M, Mallon P, Post F, Sachikonye M, Anderson J, Asboe D, Garvey L, Pozniak A, Vera J, Williams I, Campbell L, Yurdakul S, Okumu S, Pollard L, Otiko D, Phillips L, Laverick R, Fisher M, Clarke A, Bexley A, Richardson C, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Johnson M, Ngwu N, Hemat N, Jones M, Carroll A, Whitehouse A, Burgess L, Babalis D, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C., Underwood, Jonathan, De Francesco, Davide, Cole, James H, Caan, Matthan W A, van Zoest, Rosan A, Schmand, Ben A, Sharp, David J, Sabin, Caroline A, Reiss, Peter, Winston, Alan Coolaboratori: Reiss P, Wit FWNM, Schouten J, Kooij KW, van Zoest RA, Elsenga BC, Janssen FR, Heidenrijk M, Zikkenheiner W, van der Valk M, Kootstra NA, Harskamp-Holwerda AM, Maurer I, Mangas Ruiz MM, Girigorie AF, Villaudy J, Frankin E, Pasternak A, Berkhout B, van der Kuyl T, Portegies P, Schmand BA, Geurtsen GJ, Ter Stege JA, Klein Twennaar M, Majoie CBLM, Caan MWA, Su T, Weijer K, Bisschop PHLT, Kalsbeek A, Wezel M, Visser I, Ruhé HG, Franceschi C, Garagnani P, Pirazzini C, Capri M, Dall'Olio F, Chiricolo M, Salvioli S, Hoeijmakers J, Pothof J, Prins M, Martens M, Moll S, Berkel J, Totté M, Kovalev S, Gisslén M, Fuchs D, Zetterberg H, Winston A, Underwood J, McDonald L, Stott M, Legg K, Lovell A, Erlwein O, Doyle N, Kingsley C, Sharp DJ, Leech R, Cole JH, Zaheri S, Hillebregt MMJ, Ruijs YMC, Benschop DP, Burger D, de Graaff-Teulen M, Guaraldi G, Bürkle A, Sindlinger T, Moreno-Villanueva M, Keller A, Sabin C, de Francesco D, Libert C, Dewaele S, Boffito M, Mallon P, Post F, Sabin C, Sachikonye M, Winston A, Anderson J, Asboe D, Boffito M, Garvey L, Mallon P, Post F, Pozniak A, Sabin C, Sachikonye M, Vera J, Williams I, Winston A, Post F, Campbell L, Yurdakul S, Okumu S, Pollard L, Williams I, Otiko D, Phillips L, Laverick R, Fisher M, Clarke A, Vera J, Bexley A, Richardson C, Mallon P, Macken A, Ghavani-Kia B, Maher J, Byrne M, Flaherty A, Anderson J, Mguni S, Clark R, Nevin-Dolan R, Pelluri S, Johnson M, Ngwu N, Hemat N, Jones M, Carroll A, Whitehouse A, Burgess L, Babalis D, Winston A, Garvey L, Underwood J, Stott M, McDonald L, Boffito M, Asboe D, Pozniak A, Higgs C, Seah E, Fletcher S, Anthonipillai M, Moyes A, Deats K, Syed I, Matthews C., Molecular Genetics, Biomedical Engineering and Physics, Radiology and Nuclear Medicine, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, ACS - Microcirculation, AMS - Restoration & Development, Amsterdam Neuroscience - Brain Imaging, Amsterdam Neuroscience - Neurovascular Disorders, Graduate School, AII - Infectious diseases, APH - Aging & Later Life, Medical Psychology, Amsterdam Neuroscience - Neurodegeneration, Global Health, Infectious diseases, APH - Mental Health, APH - Methodology, Commission of the European Communities, Imperial College Healthcare NHS Trust- BRC Funding, and National Institute for Health Research

Subjects
Multivariate statistics, medicine.medical_specialty, COmorBidity in Relation to AIDS (COBRA) Collaboration and the Pharmacokinetic and clinical Observations in PePle over fiftY (POPPY) Study Group, Immunology, Human immunodeficiency virus (HIV), Audiology, medicine.disease_cause, Microbiology, 03 medical and health sciences, 0302 clinical medicine, multivariate, SDG 3 - Good Health and Well-being, Neuroimaging, Medicine and Health Sciences, medicine, Major Article, OLDER-PEOPLE, 030212 general & internal medicine, VALIDITY, Cognitive impairment, cognitive impairment, Science & Technology, neuroimaging, SCORES, business.industry, Biology and Life Sciences, HIV, MEN, Cognition, Mental health, White matter microstructure, PREVALENCE, 3. Good health, Infectious Diseases, Oncology, REGISTRATION, business, Life Sciences & Biomedicine, Neurocognitive, 030217 neurology & neurosurgery
Abstract

Background The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. Methods Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. Results The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05). There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. Conclusion Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach., We have previously described a novel multivariate method (NMM) with theoretical statistical advantages over existing methods, which we assessed here in 3 cohorts of people living with HIV. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status.

Published
2019

2. New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality

Author

Lin, John C, Spinella, Philip C., Fitzgerald, Julie C., Tucci, Marisa, Bush, Jenny L., Nadkarni, Vinay M., Thomas, Neal J., Weiss, Scott L., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., Mcinnes, A., Mcarthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Thomas, N., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Pineres Olave, B. E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Cruces, P., De Clety, S. Clement, Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, Paola, Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Garcia Iniguez, J. P., Revilla, P., Urbano, J., Lopez Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Brierley, J., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Levin, R., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., Mccorkell, J., Fortune, P., Macdonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Schibler, A., Erickson, S., Mceneiry, J., Long, D., Dorofaeff, T., Coulthard, M., Millar, J., Delzoppo, C., Williams, G., Morritt, M., Watts, N., Beca, J., Sherring, C., and Bushell, T.

Subjects
Male, medicine.medical_specialty, Adolescent, Cross-sectional study, Multiple Organ Failure, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Prevalence, children, epidemiology, multiple organ dysfunction syndrome, severe sepsis, Pediatrics, Perinatology and Child Health, Critical Care and Intensive Care Medicine, 030204 cardiovascular system & hematology, Global Health, Intensive Care Units, Pediatric, Pediatrics, Article, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Epidemiology, medicine, Humans, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, Child, Intensive care medicine, Prospective cohort study, Septic shock, business.industry, Infant, Newborn, Infant, Perinatology and Child Health, Prognosis, medicine.disease, Clinical trial, Cross-Sectional Studies, Phenotype, Child, Preschool, Disease Progression, Female, Multiple organ dysfunction syndrome, business
Abstract

Copyright © 2016 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.Objectives: To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Design: Secondary analysis of a prospective, cross-sectional, point prevalence study. Setting: International, multicenter PICUs. Patients: Pediatric patients with severe sepsis identified on five separate days over a 1-year period. Interventions: None. Measurements and Main Results: Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Conclusions: Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints.

Published
2017

3. Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment

Author

Underwood, J, de Francesco, D, Cole, JH, Caan, MWA, van Zoest, RA, Schmand, BA, Sharp, DJ, Sabin, CA, Reiss, P, Winston, A, Wit, FWNM, Schouten, J, Kooij, KW, Elsenga, BC, Janssen, FR, Heidenrijk, M, Zikkenheiner, W, van der Valk, M, Kootstra, NA, Harskamp-Holwerda, AM, Maurer, I, Ruiz, MMM, Girigorie, AF, Villaudy, J, Frankin, E, Pasternak, A, Berkhout, B, van der Kuyl, T, Portegies, P, Geurtsen, GJ, ter Stege, JA, Twennaar, MK, Majoie, CBLM, Su, T, Weijer, K, Bisschop, PHLT, Kalsbeek, A, Wezel, M, Visser, I, Ruhe, HG, Franceschi, C, Garagnani, P, Pirazzini, C, Capri, M, Dall'Olio, F, Chiricolo, M, Salvioli, S, Hoeijmakers, J, Pothof, J, Prins, M, Martens, M, Moll, S, Berkel, J, Totte, M, Kovalev, S, Gisslen, M, Fuchs, D, Zetterberg, H, McDonald, L, Stott, M, Legg, K, Lovell, A, Erlwein, O, Doyle, N, Kingsley, C, Leech, R, Zaheri, S, Hillebregt, MMJ, Ruijs, YMC, Benschop, DP, Burger, D, de Graaff-Teulen, M, Guaraldi, G, Buerkle, A, Sindlinger, T, Moreno-Villanueva, M, Keller, A, Sabin, C, Libert, C, Dewaele, S, Boffito, M, Mallon, P, Post, F, Sachikonye, M, Anderson, J, Asboe, D, Garvey, L, Pozniak, A, Vera, J, Williams, I, Campbell, L, Yurdakul, S, Okumu, S, Pollard, L, Otiko, D, Phillips, L, Laverick, R, Fisher, M, Clarke, A, Bexley, A, Richardson, C, Macken, A, Ghavani-Kia, B, Maher, J, Byrne, M, Flaherty, A, Mguni, S, Clark, R, Nevin-Dolan, R, Pelluri, S, Johnson, M, Ngwu, N, Hemat, N, Jones, M, Carroll, A, Whitehouse, A, Burgess, L, Babalis, D, Higgs, C, Seah, E, Fletcher, S, Anthonipillai, M, Moyes, A, Deats, K, Syed, I, Matthews, C, Underwood, J, de Francesco, D, Cole, JH, Caan, MWA, van Zoest, RA, Schmand, BA, Sharp, DJ, Sabin, CA, Reiss, P, Winston, A, Wit, FWNM, Schouten, J, Kooij, KW, Elsenga, BC, Janssen, FR, Heidenrijk, M, Zikkenheiner, W, van der Valk, M, Kootstra, NA, Harskamp-Holwerda, AM, Maurer, I, Ruiz, MMM, Girigorie, AF, Villaudy, J, Frankin, E, Pasternak, A, Berkhout, B, van der Kuyl, T, Portegies, P, Geurtsen, GJ, ter Stege, JA, Twennaar, MK, Majoie, CBLM, Su, T, Weijer, K, Bisschop, PHLT, Kalsbeek, A, Wezel, M, Visser, I, Ruhe, HG, Franceschi, C, Garagnani, P, Pirazzini, C, Capri, M, Dall'Olio, F, Chiricolo, M, Salvioli, S, Hoeijmakers, J, Pothof, J, Prins, M, Martens, M, Moll, S, Berkel, J, Totte, M, Kovalev, S, Gisslen, M, Fuchs, D, Zetterberg, H, McDonald, L, Stott, M, Legg, K, Lovell, A, Erlwein, O, Doyle, N, Kingsley, C, Leech, R, Zaheri, S, Hillebregt, MMJ, Ruijs, YMC, Benschop, DP, Burger, D, de Graaff-Teulen, M, Guaraldi, G, Buerkle, A, Sindlinger, T, Moreno-Villanueva, M, Keller, A, Sabin, C, Libert, C, Dewaele, S, Boffito, M, Mallon, P, Post, F, Sachikonye, M, Anderson, J, Asboe, D, Garvey, L, Pozniak, A, Vera, J, Williams, I, Campbell, L, Yurdakul, S, Okumu, S, Pollard, L, Otiko, D, Phillips, L, Laverick, R, Fisher, M, Clarke, A, Bexley, A, Richardson, C, Macken, A, Ghavani-Kia, B, Maher, J, Byrne, M, Flaherty, A, Mguni, S, Clark, R, Nevin-Dolan, R, Pelluri, S, Johnson, M, Ngwu, N, Hemat, N, Jones, M, Carroll, A, Whitehouse, A, Burgess, L, Babalis, D, Higgs, C, Seah, E, Fletcher, S, Anthonipillai, M, Moyes, A, Deats, K, Syed, I, and Matthews, C

Abstract

BACKGROUND: The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient- reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. METHODS: Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. RESULTS: The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment ( P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres ( P < .05), as well as smaller brain volumes ( P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. CONCLUSION: Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.

Published
2019

4. Risk Factors for Mortality in Pediatric Postsurgical versus Medical Severe Sepsis

Author

Thakkar, Rajan K., primary, Weiss, Scott L., additional, Fitzgerald, Julie C., additional, Keele, Luke, additional, Thomas, Neal J., additional, Nadkarni, Vinay M., additional, Muszynski, Jennifer A., additional, Hall, Mark W., additional, Fontela, P., additional, Tucci, M., additional, Dumistrascu, M., additional, Skippen, P., additional, Krahn, G., additional, Bezares, E., additional, Puig, G., additional, Puig-Ramos, A., additional, Garcia, R., additional, Villar, M., additional, Bigham, M., additional, Polanski, T., additional, Latifi, S., additional, Giebner, D., additional, Anthony, H., additional, Hume, J., additional, Galster, A., additional, Linnerud, L., additional, Sanders, R., additional, Hefley, G., additional, Madden, K., additional, Thompson, A., additional, Shein, S., additional, Gertz, S., additional, Han, Y., additional, Williams, T., additional, Hughes-Schalk, A., additional, Chandler, H., additional, Orioles, A., additional, Zielinski, E., additional, Doucette, A., additional, Zebuhr, C., additional, Wilson, T., additional, Dimitriades, C., additional, Ascani, J., additional, Layburn, S., additional, Valley, S., additional, Markowitz, B., additional, Terry, J., additional, Morzov, R., additional, Mcinnes, A., additional, McArthur, J., additional, Woods, K., additional, Murkowski, K., additional, Spaeder, M., additional, Sharron, M., additional, Wheeler, D., additional, Beckman, E., additional, Frank, E., additional, Howard, K., additional, Carroll, C., additional, Nett, S., additional, Jarvis, D., additional, Patel, V., additional, Higgerson, R., additional, Christie, L., additional, Typpo, K., additional, Deschenes, J., additional, Kirby, A., additional, Uhl, T., additional, Rehder, K., additional, Cheifetz, I., additional, Wrenn, S., additional, Kypuros, K., additional, Ackerman, K., additional, Maffei, F., additional, Bloomquist, G., additional, Rizkalla, N., additional, Kimura, D., additional, Shah, S., additional, Tigges, C., additional, Su, F., additional, Barlow, C., additional, Michelson, K., additional, Wolfe, K., additional, Goodman, D., additional, Campbell, L., additional, Sorce, L., additional, Bysani, K., additional, Monjure, T., additional, Evans, M., additional, Totapally, B., additional, Chegondi, M., additional, Rodriguez, C., additional, Frazier, J., additional, Steele, L., additional, Viteri, S., additional, Costarino, A., additional, Thomas, N., additional, Spear, D., additional, Hirshberg, E., additional, Lilley, J., additional, Rowan, C., additional, Rider, C., additional, Kane, J., additional, Zimmerman, J., additional, Greeley, C., additional, Lin, J., additional, Jacobs, R., additional, Parker, M., additional, Culver, K., additional, Loftis, L., additional, Jaimon, N., additional, Goldsworthy, M., additional, Fitzgerald, J., additional, Weiss, S., additional, Nadkarni, V., additional, Bush, J., additional, Diliberto, M., additional, Allen, C., additional, Gessouroun, M., additional, Sapru, A., additional, Lang, T., additional, Alkhouli, M., additional, Kamath, S., additional, Friel, D., additional, Daufeldt, J., additional, Hsing, D., additional, Carlo, C., additional, Pon, S., additional, Scimeme, J., additional, Shaheen, A., additional, Hassinger, A., additional, Qiao, H., additional, Giuliano, J., additional, Tala, J., additional, Vinciguerra, D., additional, Fernandez, A., additional, Carrero, R., additional, Hoyos, P., additional, Jaramillo, J., additional, Posada, A., additional, Izquiierdo, L., additional, Olave, B.E. Piñeres, additional, Donado, J., additional, Dalmazzo, R., additional, Rendich, S., additional, Palma, L., additional, Lapadula, M., additional, Acuna, C., additional, Cruces, P., additional, De Clety, S. Clement, additional, Dujardin, M., additional, Berghe, C., additional, Renard, S., additional, Zurek, J., additional, Steinherr, H., additional, Mougkou, K., additional, Critselis, E., additional, Di Nardo, M., additional, Picardo, S., additional, Tortora, F., additional, Rossetti, E., additional, Fragasso, T., additional, Cogo, P., additional, Netto, R., additional, Dagys, A., additional, Gurskis, V., additional, Kevalas, R., additional, Neeleman, C., additional, Lemson, J., additional, Luijten, C., additional, Wojciech, K., additional, Pagowska-Klimek, I., additional, Szczepanska, M., additional, Karpe, J., additional, Nunes, P., additional, Almeida, H., additional, Rios, J., additional, Vieira, M., additional, Iniguez, J. P. Garcia, additional, Revilla, P., additional, Urbano, J., additional, Lopez-Herce, J., additional, Bustinza, A., additional, Palacios, A., additional, Hofheinz, S., additional, Rodriguez-Nunez, A., additional, Sanagustin, S., additional, Gonzalez, E., additional, Riaza, M., additional, Piaya, R., additional, Soler, P., additional, Esteban, E., additional, Laraudogoitia, J., additional, Monge, C., additional, Herrera, V., additional, Granados, J., additional, Gonzalez, C., additional, Koroglu, T., additional, Ozcelik, E., additional, Baines, P., additional, Plunkett, A., additional, Davis, P., additional, George, S., additional, Tibby, S., additional, Harris, J., additional, Agbeko, R., additional, Lampitt, R., additional, Brierley, J., additional, Peters, M., additional, Jones, A., additional, Dominguez, T., additional, Thiruchelvam, T., additional, Deep, A., additional, Ridley, L., additional, Bowen, W., additional, Levin, R., additional, Macleod, I., additional, Gray, M., additional, Hemat, N., additional, Alexander, J., additional, Ali, S., additional, Pappachan, J., additional, McCorkell, J., additional, Fortune, P., additional, MacDonald, M., additional, Hudnott, P., additional, Suyun, Q., additional, Singhi, S., additional, Nallasamy, K., additional, Lodha, R., additional, Shime, N., additional, Tabata, Y., additional, Saito, O., additional, Ikeyama, T., additional, Kawasaki, T., additional, Lum, L., additional, Abidin, A., additional, Kee, S., additional, Tang, S., additional, Jalil, R., additional, Guan, Y., additional, Yao, L., additional, Lin, K., additional, Ong, J., additional, Salloo, A., additional, Doedens, L., additional, Mathivha, L., additional, Reubenson, G., additional, Moaisi, S., additional, Pentz, A., additional, Green, R., additional, Schibler, A., additional, Erickson, S., additional, McEneiry, J., additional, Long, D., additional, Dorofaeff, T., additional, Coulthard, M., additional, Millar, J., additional, Delzoppo, C., additional, Williams, G., additional, Morritt, M., additional, Watts, N., additional, Beca, J., additional, Sherring, C., additional, and Bushell, T., additional

Published
2019
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5. Comparison of Pediatric Severe Sepsis Managed in U.S. and European ICUs

Author

Giuliano, John S, Markovitz, Barry P., Brierley, Joe, Levin, Richard, Williams, Gary, Lum, Lucy Chai See, Dorofaeff, Tavey, Cruces, Pablo, Bush, Jenny L., Keele, Luke, Nadkarni, Vinay M., Thomas, Neal J., Fitzgerald, Julie C., Weiss, Scott L., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., Mcinnes, A., Mcarthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Thomas, N., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Fitzgerald, J., Weiss, S., Nadkarni, V., Bush, J., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Piñeres Olave, B. E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Cruces, P., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, Paola, Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Revilla, P., Urbano, J., Lopez Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Brierley, J., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Levin, R., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., Mccorkell, J., Fortune, P., Macdonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Schibler, A., Erickson, S., Mceneiry, J., Long, D., Dorofaeff, T., Coulthard, M., Millar, J., Delzoppo, C., Williams, G., Morritt, M., Watts, N., Beca, J., Sherring, C., and Bushell, T.

Subjects
Male, Pediatrics, Cross-sectional study, shock, Critical Care and Intensive Care Medicine, Severity of Illness Index, 0302 clinical medicine, Prevalence, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, Practice Patterns, Physicians', Child, Prospective cohort study, Pediatric intensive care unit, Perinatology and Child Health, Europe, Treatment Outcome, Child, Preschool, outcome, children, management, pediatric intensive care unit, Pediatrics, Perinatology and Child Health, Female, medicine.symptom, medicine.medical_specialty, Adolescent, Critical Care, Intensive Care Units, Pediatric, Sepsis, 03 medical and health sciences, Intensive care, Severity of illness, medicine, Humans, Healthcare Disparities, business.industry, Organ dysfunction, Infant, Newborn, Infant, 030208 emergency & critical care medicine, Health Status Disparities, medicine.disease, United States, Clinical trial, Cross-Sectional Studies, Multivariate Analysis, Emergency medicine, business
Abstract

Copyright © 2016 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.Objectives: Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. Design: We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. Setting: European and U.S. PICUs. Patients: Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. Conclusions: Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after adjusting for patient characteristics suggests that the approach to care between regions, perhaps related to PICU bed availability, needs to be considered in the design of future international clinical trials in pediatric severe sepsis.

Published
2016

6. Comparison of Pediatric Severe Sepsis Managed in US and European ICUs

Author

Giuliano, J.S., Markovitz, B.P., Brierley, J., Levin, R., Williams, G., Lum, L.C.S., Dorofaeff, T., Cruces, P., Bush, J.L., Keele, L., Nadkarni, V.M., Thomas, N.J., Fitzgerald, J.C., Weiss, S.L., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., McInnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Fitzgerald, J., Nadkarni, V., Bush, J., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Piñeres Olave, B.E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban-Torne E, Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Schibler, A., Erickson, S., McEneiry, J., Long, D., Coulthard, M., Millar, J., Delzoppo, C., Morritt, M., Watts, N., Beca, J., Sherring, C., and Bushell, T.

Published
2016

7. Acute kidney injury in pediatric severe sepsis : An independent risk factor for death and new disability

Author

Fitzgerald, Julie C., Basu, Rajit K., Akcan-Arikan, Ayse, Izquierdo, Ledys M., Piñeres Olave, Byron E., Hassinger, Amanda B., Szczepanska, Maria, Deep, Akash, Williams, Duane, Sapru, Anil, Roy, Jason A., Nadkarni, Vinay M., Thomas, Neal J., Weiss, Scott L., Furth, Susan, Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebne, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., Mcinnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Bush, J., Diliberto, M., Allen, C., Gessouroun, M., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Cruces, P., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Garcia Iniguez, JP, Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Palacios, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Brierley, J., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Ridley, L., Bowen, W., Levin, R., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Schibler, A., Long, D., Fitzgerald, Julie C., Basu, Rajit K., Akcan-Arikan, Ayse, Izquierdo, Ledys M., Piñeres Olave, Byron E., Hassinger, Amanda B., Szczepanska, Maria, Deep, Akash, Williams, Duane, Sapru, Anil, Roy, Jason A., Nadkarni, Vinay M., Thomas, Neal J., Weiss, Scott L., Furth, Susan, Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebne, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., Mcinnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Bush, J., Diliberto, M., Allen, C., Gessouroun, M., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Cruces, P., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Garcia Iniguez, JP, Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Palacios, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Brierley, J., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Ridley, L., Bowen, W., Levin, R., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Schibler, A., and Long, D.

Abstract

Objectives: The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Design: Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. Setting: One hundred twenty-eight PICUs in 26 countries. Patients: Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. Conclusions: In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.

Published
2016

8. Comparison of pediatric severe sepsis managed in U.S. and European ICUs

Author

Giuliano, John S., Markovitz, Barry P., Brierley, Joe, Levin, Richard, Williams, Gary, Lum, Lucy Chai See, Dorofaeff, Tavey, Cruces, Pablo, Bush, Jenny L., Keele, Luke, Nadkarni, V., Thomas, Neal J., Fitzgerald, Julie C., Weiss, Scott L., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Terry, J., Morzov, R., McInnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Piñeres Olave, B. E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., Green, R., Giuliano, John S., Markovitz, Barry P., Brierley, Joe, Levin, Richard, Williams, Gary, Lum, Lucy Chai See, Dorofaeff, Tavey, Cruces, Pablo, Bush, Jenny L., Keele, Luke, Nadkarni, V., Thomas, Neal J., Fitzgerald, Julie C., Weiss, Scott L., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig-Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes-Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Terry, J., Morzov, R., McInnes, A., McArthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbell, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Piñeres Olave, B. E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, P., Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska-Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Revilla, P., Urbano, J., Lopez-Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez-Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., McCorkell, J., Fortune, P., MacDonald, M., Hudnott, P., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Abidin, A., Kee, S., Tang, S., Jalil, R., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., and Green, R.

Abstract

Objectives: Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. Design: We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. Setting: European and U.S. PICUs. Patients: Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. Conclusions: Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after

Published
2016

9. Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Author

Weiss, Scott L, Fitzgerald, Julie C., Maffei, Frank A., Kane, Jason M., Rodriguez Nunez, Antonio, Hsing, Deyin D., Franzon, Deborah, Kee, Sze Ying, Bush, Jenny L., Roy, Jason A., Thomas, Neal J., Nadkarni, Vinay M., Fontela, P., Tucci, M., Dumistrascu, M., Skippen, P., Krahn, G., Bezares, E., Puig, G., Puig Ramos, A., Garcia, R., Villar, M., Bigham, M., Polanski, T., Latifi, S., Giebner, D., Anthony, H., Hume, J., Galster, A., Linnerud, L., Sanders, R., Hefley, G., Madden, K., Thompson, A., Shein, S., Gertz, S., Han, Y., Williams, T., Hughes Schalk, A., Chandler, H., Orioles, A., Zielinski, E., Doucette, A., Zebuhr, C., Wilson, T., Dimitriades, C., Ascani, J., Layburn, S., Valley, S., Markowitz, B., Terry, J., Morzov, R., Mcinnes, A., Mcarthur, J., Woods, K., Murkowski, K., Spaeder, M., Sharron, M., Wheeler, D., Beckman, E., Frank, E., Howard, K., Carroll, C., Nett, S., Jarvis, D., Patel, V., Higgerson, R., Christie, L., Typpo, K., Deschenes, J., Kirby, A., Uhl, T., Rehder, K., Cheifetz, I., Wrenn, S., Kypuros, K., Ackerman, K., Maffei, F., Bloomquist, G., Rizkalla, N., Kimura, D., Shah, S., Tigges, C., Su, F., Barlow, C., Michelson, K., Wolfe, K., Goodman, D., Campbel, L., Sorce, L., Bysani, K., Monjure, T., Evans, M., Totapally, B., Chegondi, M., Rodriguez, C., Frazier, J., Steele, L., Viteri, S., Costarino, A., Thomas, N., Spear, D., Hirshberg, E., Lilley, J., Rowan, C., Rider, C., Kane, J., Zimmerman, J., Greeley, C., Lin, J., Jacobs, R., Parker, M., Culver, K., Loftis, L., Jaimon, N., Goldsworthy, M., Fitzgerald, J., Weiss, S., Nadkarni, V., Bush, J., Diliberto, M., Alen, C., Gessouroun, M., Sapru, A., Lang, T., Alkhouli, M., Kamath, S., Friel, D., Daufeldt, J., Hsing, D., Carlo, C., Pon, S., Scimeme, J., Shaheen, A., Hassinger, A., Qiao, H., Giuliano, J., Tala, J., Vinciguerra, D., Fernandez, A., Carrero, R., Hoyos, P., Jaramillo, J., Posada, A., Izquiierdo, L., Piñeres Olave, B. E., Donado, J., Dalmazzo, R., Rendich, S., Palma, L., Lapadula, M., Acuna, C., Cruces, P., Clement De Clety, S., Dujardin, M., Berghe, C., Renard, S., Zurek, J., Steinherr, H., Mougkou, K., Critselis, E., Di Nardo, M., Picardo, S., Tortora, F., Rossetti, E., Fragasso, T., Cogo, Paola, Netto, R., Dagys, A., Gurskis, V., Kevalas, R., Neeleman, C., Lemson, J., Luijten, C., Wojciech, K., Pagowska Klimek, I., Szczepanska, M., Karpe, J., Nunes, P., Almeida, H., Rios, J., Vieira, M., Revilla, P., Urbano, J., Lopez Herce, J., Bustinza, A., Cuesta, A., Hofheinz, S., Rodriguez Nunez, A., Sanagustin, S., Gonzalez, E., Riaza, M., Piaya, R., Soler, P., Esteban, E., Laraudogoitia, J., Monge, C., Herrera, V., Granados, J., Gonzalez, C., Koroglu, T., Ozcelik, E., Baines, P., Plunkett, A., Davis, P., George, S., Tibby, S., Harris, J., Agbeko, R., Lampitt, R., Bierley, J., Peters, M., Jones, A., Dominguez, T., Thiruchelvam, T., Deep, A., Ridley, L., Bowen, W., Levin, R., Macleod, I., Gray, M., Hemat, N., Alexander, J., Ali, S., Pappachan, J., Mccorkell, J., Schibler, A., Fortune, P., Macdonald, M., Hudnott, P., Erickson, S., Millar, J., Delzoppo, C., Williams, G., Morritt, M., Mceneiry, J., Long, D., Dorofaeff, T., Coulthard, M., Watts, N., Suyun, Q., Singhi, S., Nallasamy, K., Lodha, R., Shime, N., Tabata, Y., Saito, O., Ikeyama, T., Kawasaki, T., Lum, L., Abidin, A., Kee, S., Tang, S., Jalil, R., Beca, J., Sherring, C., Bushell, T., Guan, Y., Yao, L., Lin, K., Ong, J., Salloo, A., Doedens, L., Mathivha, L., Reubenson, G., Moaisi, S., Pentz, A., and Green, R.

Subjects
Male, medicine.medical_specialty, Biomedical Research, Adolescent, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Practice Patterns, macromolecular substances, Critical Care and Intensive Care Medicine, Sepsis, Intensive care, Epidemiology, Severity of illness, Clinical endpoint, Prevalence, Medicine, Humans, Practice Patterns, Physicians', Preschool, Intensive care medicine, Child, Pediatric intensive care unit, Observer Variation, Physicians', business.industry, Research, Organ dysfunction, Infant, Newborn, Infant, Child, Preschool, Female, Treatment Outcome, Newborn, medicine.disease, 3. Good health, Clinical trial, medicine.symptom, business
Abstract

Introduction Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients Results Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (κ ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician’s diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis.

Published
2015

10. Unveiling the potential role of gibberellic acid, melatonin and indole acetic acid on parthenocarpy, physiological traits and phytochemical responses in Hibiscus sabdariffa L.

Author

Hemat N, Meftahizadeh H, Ghorbanpour M, Dehestani-Ardakani M, and Gholamnezhad J

Subjects
Flowers drug effects, Plant Growth Regulators pharmacology, Plant Growth Regulators metabolism, Phytochemicals, Antioxidants, Seeds drug effects, Seeds growth & development, Gibberellins metabolism, Gibberellins pharmacology, Indoleacetic Acids metabolism, Melatonin pharmacology, Melatonin metabolism, Hibiscus drug effects, Hibiscus chemistry
Abstract

The economic part of the Hibiscus sabdariffa L. (Malvaceae) plant is the sepal. One of the main challenges in harvesting this product is separating its seeds, which are surrounded by sepals. If the parthenocarpy process occurs without seeds, the labor costs are reduced and the profits from the production of this plant are increased. In current study, the effect of gibberellic acid (GA 3 ), melatonin (M), and indole acetic acid (IAA) on the induction of parthenocarpy in H. sabdariffa plants was investigated. The study was conducted as a factorial experiment in the form of randomized complete block design with three replications. Different concentrations of GA 3 (0 (control), 700, 800, and 900 ppm), M (0 (control), 100, 200, and 400 ppm), and IAA (0 (control), 1000, 1200, and 1400 ppm) were foliar sprayed after the emergence of the flower bud on the 50th, 60th, and 70th days of planting, and the control plants were also sprayed with distilled water. Various measurements were taken including the number of seeds per boll, parthenocarpy percentage, capsule volume, number of bolls per plant, number of mature seeds, and phytochemical parameters such as anthocyanin, chlorophyll and carotenoid content, antioxidant value, total phenol and flavonoid content, and soluble solids. The application of GA 3 at 800 and 900 ppm along with IAA at 1000 ppm and M at 100 and 200 ppm led to the production of parthenocarpy fruits and showed the best results in the induction of parthenocarpy. The control group indicated the highest number of mature seeds per boll. The highest amount of phenol and flavonoid contents were obtained in plants treated with GA 3 at 800 ppm. For anthocyanin, the control group showed the highest value (1.63 mg g -1 ), and in the case of the antioxidant trait, plants exposed to 100 ppm M showed the highest IC50 (40.68%). Hence, the application of plant growth regulators with appropriate concentrations can be effective in inducing parthenocarpy in H. sabdariffa plants. Additionally, parthenocarpy-induced by GA 3 , IAA, and M had different impacts on fruit quality and quantity, suggesting that the effect depends on the type of employed hormones used and their concentrations., (© 2024. The Author(s).)

Published
2024
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