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3. Long-term outcomes with haloperidol versus placebo in acutely admitted adult ICU patients with delirium

Author

Mortensen, C, Andersen-Ranberg, N, Poulsen, L, Granholm, A, Rasmussen, B, Kjær, M, Lange, T, Ebdrup, B, Collet, M, Andreasen, A, Bestle, M, Uslu, B, Pedersen, H, Nielsen, L, Hästbacka, J, Jensen, T, Damgaard, K, Sommer, T, Morgen, M, Dey, N, Citerio, G, Estrup, S, Egerod, I, Samuelson, K, Perner, A, Mathiesen, O, Mortensen, Camilla Bekker, Andersen-Ranberg, Nina Christine, Poulsen, Lone Musaeus, Granholm, Anders, Rasmussen, Bodil Steen, Kjær, Maj-Brit Nørregaard, Lange, Theis, Ebdrup, Bjørn H., Collet, Marie Oxenbøll, Andreasen, Anne Sofie, Bestle, Morten Heiberg, Uslu, Bülent, Pedersen, Helle Scharling, Nielsen, Louise Gramstrup, Hästbacka, Johanna, Jensen, Troels Bek, Damgaard, Kjeld, Sommer, Trine, Morgen, Matthew, Dey, Nilanjan, Citerio, Giuseppe, Estrup, Stine, Egerod, Ingrid, Samuelson, Karin, Perner, Anders, Mathiesen, Ole, Mortensen, C, Andersen-Ranberg, N, Poulsen, L, Granholm, A, Rasmussen, B, Kjær, M, Lange, T, Ebdrup, B, Collet, M, Andreasen, A, Bestle, M, Uslu, B, Pedersen, H, Nielsen, L, Hästbacka, J, Jensen, T, Damgaard, K, Sommer, T, Morgen, M, Dey, N, Citerio, G, Estrup, S, Egerod, I, Samuelson, K, Perner, A, Mathiesen, O, Mortensen, Camilla Bekker, Andersen-Ranberg, Nina Christine, Poulsen, Lone Musaeus, Granholm, Anders, Rasmussen, Bodil Steen, Kjær, Maj-Brit Nørregaard, Lange, Theis, Ebdrup, Bjørn H., Collet, Marie Oxenbøll, Andreasen, Anne Sofie, Bestle, Morten Heiberg, Uslu, Bülent, Pedersen, Helle Scharling, Nielsen, Louise Gramstrup, Hästbacka, Johanna, Jensen, Troels Bek, Damgaard, Kjeld, Sommer, Trine, Morgen, Matthew, Dey, Nilanjan, Citerio, Giuseppe, Estrup, Stine, Egerod, Ingrid, Samuelson, Karin, Perner, Anders, and Mathiesen, Ole

Abstract

Purpose: We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. Methods: We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by Euroqol (EQ) 5-dimension 5-level questionnaire (EQ-5D-5L) index values and EQ visual analogue scale (EQ VAS) (deceased patients were assigned the numeric value zero). Outcomes were analysed using logistic and linear regressions with bootstrapping and G-computation, all with adjustment for the stratification variables (site and delirium motor subtype) and multiple imputations for missing HRQoL values. Results: At 1-year follow-up, we obtained vital status for 96.2% and HRQoL data for 83.3% of the 1000 randomised patients. One-year mortality was 224/501 (44.7%) in the haloperidol group versus 251/486 (51.6%) in the placebo group, with an adjusted absolute risk difference of − 6.4%-points (95% confidence interval [CI] − 12.8%-points to − 0.2%-points; P = 0.045). These results were largely consistent across the secondary analyses. For HRQoL, the adjusted mean differences were 0.04 (95% CI − 0.03 to 0.11; P = 0.091) for EQ-5D-5L-5L index values, and 3.3 (95% CI − 9.3 to 17.5; P = 0.142) for EQ VAS. Conclusions: In acutely admitted adult ICU patients with delirium, haloperidol treatment reduced mortality at 1-year follow-up, but did not statistically significantly improve HRQoL.

Published
2024

4. The intrafollicular concentrations of biologically active cortisol in women rise abruptly shortly before ovulation and follicular rupture

Author

Johannsen, M. L., Poulsen, L. C., Mamsen, L. S., Grøndahl, M. L., Englund, A. L. M., Lauritsen, N. L., Carstensen, E. C., Styrishave, B., Andersen, C. Yding, Johannsen, M. L., Poulsen, L. C., Mamsen, L. S., Grøndahl, M. L., Englund, A. L. M., Lauritsen, N. L., Carstensen, E. C., Styrishave, B., and Andersen, C. Yding

Abstract

STUDY QUESTION: What is the temporal activity and the concentration in follicular fluid (FF) of the anti-inflammatory steroid cortisol during the ovulatory process in humans? SUMMARY ANSWER: Intrafollicular concentrations of cortisol become massively upregulated close to ovulation concomitant with an exceptionally high biological activity securing a timely and efficient termination of inflammatory processes. WHAT IS KNOWN ALREADY: Ovulation has been described as a local, controlled inflammatory process resulting in the degeneration of the follicle wall which facilitate oocyte extrusion. Ovulation also affects the glucocorticoid metabolism of granulosa cells (GCs) and although de novo synthesis of cortisol only occurs in the adrenal cortex, the mid-cycle surge has been shown to induce a change from high expression of HSD11B2, inactivating cortisol to cortisone, to high expression of HSD11B1 which reversibly catalyses cortisol production from cortisone. Furthermore, high concentrations of progesterone and 17OH-proges-terone within follicles may cause dislodging of cortisol from cortisol binding protein (CBP) thereby activating the biological activity of cortisol. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 50 women undergoing fertility treatment according to a standard antagonist protocol at a university hospital-affiliated fertility clinic in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women donated FF and GCs from one follicle for research purpose aspirated at one of four time points during the process of final maturation of follicles: T ¼ 0 h, T ¼ 12 h, T ¼ 17 h, T ¼ 32 h. A second sample was collected at oocyte pick up at T ¼ 36 h. The concentration of cortisol and cortisone together with a range of sex steroids was measured by LC-MS/MS in FF collected at the five time points mentioned above. Whole genome microarray data, validated by q-PCR analysis, was used to evaluate gene expression of CYP11B1, CYP21A2, HSD11B1, HSD11B2, and

Published
2024

5. The intrafollicular concentrations of biologically active cortisol in women rise abruptly shortly before ovulation and follicular rupture.

Author

Johannsen, M L, Poulsen, L C, Mamsen, L S, Grøndahl, M L, Englund, A L M, Lauritsen, N L, Carstensen, E C, Styrishave, B, and Andersen, C Yding

Subjects
*OVULATION, *HYDROCORTISONE, *INDUCED ovulation, *GRANULOSA cells, *ADRENAL cortex
Abstract

STUDY QUESTION What is the temporal activity and the concentration in follicular fluid (FF) of the anti-inflammatory steroid cortisol during the ovulatory process in humans? SUMMARY ANSWER Intrafollicular concentrations of cortisol become massively upregulated close to ovulation concomitant with an exceptionally high biological activity securing a timely and efficient termination of inflammatory processes. WHAT IS KNOWN ALREADY Ovulation has been described as a local, controlled inflammatory process resulting in the degeneration of the follicle wall which facilitate oocyte extrusion. Ovulation also affects the glucocorticoid metabolism of granulosa cells (GCs) and although de novo synthesis of cortisol only occurs in the adrenal cortex, the mid-cycle surge has been shown to induce a change from high expression of HSD11B2, inactivating cortisol to cortisone, to high expression of HSD11B1 which reversibly catalyses cortisol production from cortisone. Furthermore, high concentrations of progesterone and 17OH-progesterone within follicles may cause dislodging of cortisol from cortisol binding protein (CBP) thereby activating the biological activity of cortisol. STUDY DESIGN, SIZE, DURATION This prospective cohort study included 50 women undergoing fertility treatment according to a standard antagonist protocol at a university hospital-affiliated fertility clinic in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS Women donated FF and GCs from one follicle for research purpose aspirated at one of four time points during the process of final maturation of follicles: T  = 0 h, T  = 12 h, T  = 17 h, T  = 32 h. A second sample was collected at oocyte pick up at T  = 36 h. The concentration of cortisol and cortisone together with a range of sex steroids was measured by LC-MS/MS in FF collected at the five time points mentioned above. Whole genome microarray data, validated by q-PCR analysis, was used to evaluate gene expression of CYP11B1 , CYP21A2 , HSD11B1 , HSD11B2 , and NR3C1 in GCs at the same time points. MAIN RESULTS AND THE ROLE OF CHANCE The concentration of cortisol was significantly increased from a few nM at 0 h to around 100–140 nM (P  ≤ 0.0001) at 32–36 h, whilst cortisone was almost constant from 0 to 17 h at a concentration of between 90 and 100 nM being significantly reduced to 25–40 nM (P  ≤ 0.0001) at 32–36 h. This was paralleled by a 690-fold upregulation of HSD11B1 from 0 to 12 h increasing to a more than 20.000-fold change at 36 h. HSD11B2 was quickly downregulated 15- to 20-fold after ovulation induction. Concentrations of progesterone and 17OH-progesterone increased during the ovulatory process to high levels which in essence displaces cortisol from its binding protein CBP due to similar binding affinities. Furthermore, a significant decrease in 11-deoxycortisol expression was seen, but CYP11B1 expression was below detection limit in GCs. LIMITATIONS, REASONS FOR CAUTION The study included women undergoing ovarian stimulation and results may differ from the natural cycle. More observations at each specific time point may have strengthened the conclusions. Furthermore, we have not been able to measure the actual active biological concentration of cortisol. WIDER IMPLICATIONS OF THE FINDINGS For the first time, this study collectively evaluated the temporal pattern of cortisol and cortisone concentrations during human ovulation, rendering a physiological framework for understanding potential dysregulations in the inflammatory reaction of ovulation. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the University Hospital of Copenhagen, Rigshospitalet, and Novo Nordisk Foundation grant number NNF21OC00700556. Interreg V ÔKS through ReproUnion (www.reprounion.eu); Region Zealand Research Foundation. The funders had no role in study design, collection of data, analyses, writing of the article, or the decision to submit it for publication. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Cardiovascular events following vascular endothelial growth factor inhibitor therapy with sunitinib or pazopanib in patients with renal cell carcinoma - a nationwide registry-based follow-up study

Author

Shanmuganathan, J, primary, Morten Schou, M S, additional, Jawad Haider Butt, J H B, additional, Christian Torp-Pedersen, C T P, additional, Laurids Ostergaard Poulsen, L O P, additional, Manan Pareek, M P, additional, Gunnar Gislason, G G, additional, Lars Kober, L K, additional, Dorte Nielsen, D N, additional, Tarec Christoffer El-Galaly, T C E, additional, Peter Soegaard, P S, additional, Mamas A Mamas, M A M, additional, Phillip Freeman, P F, additional, and Kristian Hay Kragholm, K H K, additional

Published
2023
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7. Risk of myocardial infarction following capecitabine treatment in patients with gastrointestinal cancer - a nationwide registry-based study

Author

Shanmuganathan, J, primary, Kristian Hay Kragholm, K H K, additional, Morten Schou, M S, additional, Christian Torp-Pedersen, C T P, additional, Laurids Ostergaard Poulsen, L O P, additional, Manan Pareek, M P, additional, Gunnar Gislason, G G, additional, Lars Kober, L K, additional, Dorte Nielsen, D N, additional, Tarec Christoffer El-Galaly, T C E, additional, Peter Soegaard, P S, additional, Mamas A Mamas, M A M, additional, and Phillip Freeman, P F, additional

Published
2023
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8. PD-0805 Inter-observer variation for national Danish contouring atlas on organs at risk in the pelvis

Author

Poulsen, L., primary, Søndergaard, J., additional, Lorenzen, E., additional, Bahij, R., additional, Bentzen, L., additional, Dysager, L., additional, Grønbech, M., additional, Havelund, B.M., additional, Holst, S., additional, Klüver-Kristensen, M., additional, Knudsen, A.Ø., additional, Kronborg, C., additional, Lindberg, H., additional, Madsen, C.V., additional, Mouritsen, L.S., additional, Nyborg, C., additional, Nøttrup, T.J., additional, Petersen, S.E., additional, Serup-Hansen, E., additional, Weber, B., additional, Wind, K., additional, and Hansen, C.R., additional

Published
2023
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9. Haloperidol vs. placebo for the treatment of delirium in ICU patients: a pre-planned, secondary Bayesian analysis of the AID-ICU trial

Author

Andersen-Ranberg, N, Poulsen, L, Perner, A, Hästbacka, J, Morgan, M, Citerio, G, Collet, M, Weber, S, Andreasen, A, Bestle, M, Uslu, B, Pedersen, H, Nielsen, L, Damgaard, K, Jensen, T, Sommer, T, Dey, N, Mathiesen, O, Granholm, A, Andersen-Ranberg, Nina C, Poulsen, Lone Musaeus, Perner, Anders, Hästbacka, Johanna, Morgan, Matthew, Citerio, Giuseppe, Collet, Marie Oxenbøll, Weber, Sven-Olaf, Andreasen, Anne Sofie, Bestle, Morten, Uslu, Bülent, Pedersen, Helle Scharling, Nielsen, Louise Gramstrup, Damgaard, Kjeld, Jensen, Troels Bek, Sommer, Trine, Dey, Nilanjan, Mathiesen, Ole, Granholm, Anders, Andersen-Ranberg, N, Poulsen, L, Perner, A, Hästbacka, J, Morgan, M, Citerio, G, Collet, M, Weber, S, Andreasen, A, Bestle, M, Uslu, B, Pedersen, H, Nielsen, L, Damgaard, K, Jensen, T, Sommer, T, Dey, N, Mathiesen, O, Granholm, A, Andersen-Ranberg, Nina C, Poulsen, Lone Musaeus, Perner, Anders, Hästbacka, Johanna, Morgan, Matthew, Citerio, Giuseppe, Collet, Marie Oxenbøll, Weber, Sven-Olaf, Andreasen, Anne Sofie, Bestle, Morten, Uslu, Bülent, Pedersen, Helle Scharling, Nielsen, Louise Gramstrup, Damgaard, Kjeld, Jensen, Troels Bek, Sommer, Trine, Dey, Nilanjan, Mathiesen, Ole, and Granholm, Anders

Abstract

Purpose: The AID–ICU trial was a randomised, blinded, placebo-controlled trial investigating effects of haloperidol versus placebo in acutely admitted, adult patients admitted in intensive care unit (ICU) with delirium. This pre-planned Bayesian analysis facilitates probabilistic interpretation of the AID–ICU trial results. Methods: We used adjusted Bayesian linear and logistic regression models with weakly informative priors to analyse all primary and secondary outcomes reported up to day 90, and with sensitivity analyses using other priors. The probabilities for any benefit/harm, clinically important benefit/harm, and no clinically important differences with haloperidol treatment according to pre-defined thresholds are presented for all outcomes. Results: The mean difference for days alive and out of hospital to day 90 (primary outcome) was 2.9 days (95% credible interval (CrI) − 1.1 to 6.9) with probabilities of 92% for any benefit and 82% for clinically important benefit. The risk difference for mortality was − 6.8 percentage points (95% CrI − 12.8 to − 0.8) with probabilities of 99% for any benefit and 94% for clinically important benefit. The adjusted risk difference for serious adverse reactions was 0.3 percentage points (95% CrI − 1.3 to 1.9) with 98% probability of no clinically important difference. Results were consistent across sensitivity analyses using different priors, with more than 83% probability of benefit and less than 17% probability of harm with haloperidol treatment. Conclusions: We found high probabilities of benefits and low probabilities of harm with haloperidol treatment compared with placebo in acutely admitted, adult ICU patients with delirium for the primary and most secondary outcomes.

Published
2023

16. Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products

Author

Bonertz, A., Roberts, G. C., Hoefnagel, M., Timon, M., Slater, J. E., Rabin, R. L., Bridgewater, J., Pini, C., Pfaar, O., Akdis, C., Goldstein, J., Poulsen, L. K., van Ree, R., Rhyner, C., Barber, D., Palomares, O., Sheikh, A., Pawankar, R., Hamerlijnk, D., Klimek, L., Agache, I., Angier, E., Casale, T., Fernandez‐Rivas, M., Halken, S., Jutel, M., Lau, S., Pajno, G., Sturm, G., Varga, E. M., Gerth van Wijk, R., Bonini, S., Muraro, A., and Vieths, S.

Published
2018
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19. Mortality and HRQoL in ICU patients with delirium: Protocol for 1-year follow-up of AID-ICU trial

Author

Mortensen, C, Poulsen, L, Andersen-Ranberg, N, Perner, A, Lange, T, Estrup S, S, Ebdrup, B, Egerod, I, Rasmussen, B, Hastbacka, J, Caballero, J, Citerio, G, Morgan, M, Samuelson, K, Mathiesen, O, Mortensen C. B., Poulsen L. M., Andersen-Ranberg N. C., Perner A., Lange T., Estrup S S., Ebdrup B. H., Egerod I., Rasmussen B. S., Hastbacka J., Caballero J., Citerio G., Morgan M. P. G., Samuelson K., Mathiesen O., Mortensen, C, Poulsen, L, Andersen-Ranberg, N, Perner, A, Lange, T, Estrup S, S, Ebdrup, B, Egerod, I, Rasmussen, B, Hastbacka, J, Caballero, J, Citerio, G, Morgan, M, Samuelson, K, Mathiesen, O, Mortensen C. B., Poulsen L. M., Andersen-Ranberg N. C., Perner A., Lange T., Estrup S S., Ebdrup B. H., Egerod I., Rasmussen B. S., Hastbacka J., Caballero J., Citerio G., Morgan M. P. G., Samuelson K., and Mathiesen O.

Abstract

Background: Intensive care unit (ICU)-acquired delirium is frequent and associated with poor short- and long-term outcomes for patients in ICUs. It therefore constitutes a major healthcare problem. Despite limited evidence, haloperidol is the most frequently used pharmacological intervention against ICU-acquired delirium. Agents intervening against Delirium in the ICU (AID-ICU) is an international, multicentre, randomised, blinded, placebo-controlled trial investigates benefits and harms of treatment with haloperidol in patients with ICU-acquired delirium. The current pre-planned one-year follow-up study of the AID-ICU trial population aims to explore the effects of haloperidol on one-year mortality and health related quality of life (HRQoL). Methods : The AID-ICU trial will include 1000 participants. One-year mortality will be obtained from the trial sites; we will validate the vital status of Danish participants using the Danish National Health Data Registers. Mortality will be analysed by Cox-regression and visualized by Kaplan-Meier curves tested for significance using the log-rank test. We will obtain HRQoL data using the EQ-5D instrument. HRQoL analysis will be performed using a general linear model adjusted for stratification variables. Deceased participants will be designated the worst possible value. Results: We expect to publish results of this study in 2022. Conclusion: We expect that this one-year follow-up study of participants with ICU-acquired delirium allocated to haloperidol vs. placebo will provide important information on the long-term consequences of delirium including the effects of haloperidol. We expect that our results will improve the care of this vulnerable patient group.

Published
2020

21. Is diet partly responsible for differences in COVID-19 death rates between and within countries?

Author

Bousquet J., Anto J. M., Iaccarino G., Czarlewski W., Haahtela T., Anto A., Akdis C. A., Blain H., Canonica G. W., Cardona V., Cruz A. A., Illario M., Ivancevich J. C., Jutel M., Klimek L., Kuna P., Laune D., Larenas-Linnemann D., Mullol J., Papadopoulos N. G., Pfaar O., Samolinski B., Valiulis A., Yorgancioglu A., Zuberbier T., Abdul Latiff A. H., Abdullah B., Aberer W., Abusada N., Adcock I., Afani A., Agache I., Aggelidis X., Agustin J., Akdis C., Akdis M., Al-Ahmad M., Al-Zahab Bassam A., Aldrey-Palacios O., Alvarez Cuesta E., Alzaabi A., Amad S., Ambrocio G., Annesi-Maesano I., Ansotegui I., Anto J., Arshad H., Artesani M. C., Asayag E., Avolio F., Azhari K., Baiardini I., Bajrovic N., Bakakos P., Bakeyala Mongono S., Balotro-Torres C., Barba S., Barbara C., Barbosa E., Barreto B., Bartra J., Bateman E. D., Battur L., Bedbrook A., Bedolla Barajas M., Beghe B., Bel E., Ben Kheder A., Benson M., Berghea C., Bergmann K. -C., Bernstein D., Bewick M., Bialek S., Bialoszewski A., Bieber T., Billo N., Bilo M. B., Bindslev-Jensen C., Bjermer L., Bochenska Marciniak M., Bond C., Boner A., Bonini M., Bonini S., Bosnic-Anticevich S., Bosse I., Botskariova S., Bouchard J., Boulet L. -P., Bourret R., Bousquet P., Braido F., Briggs A., Brightling C., Brozek J., Buhl R., Bumbacea R., Burguete Cabanas M. T., Bush A., Busse W. W., Buters J., Caballero-Fonseca F., Calderon M. A., Calvo M., Camargos P., Camuzat T., Cano A., Capriles-Hulett A., Caraballo L., Carlsen K. -H., Caro J., Carr W., Carreon-Asuncion F., Carriazo A. M., Casale T., Castor M. A., Castro E., Cecchi L., Cepeda Sarabia A., Chandrasekharan R., Chang Y. -S., Chato-Andeza V., Chatzi L., Chatzidaki C., Chavannes N. H., Chen Y., Cheng L., Chivato T., Chkhartishvili E., Christoff G., Chrystyn H., Chu D. K., Chua A., Chuchalin A., Chung K. F., Ciceran A., Cingi C., Ciprandi G., Cirule I., Coelho A. C., Constantinidis J., Correia De Sousa J., Costa E., Costa D., Costa Dominguez M. D. C., Coste A., Cox L., Cullen J., Custovic A., Cvetkovski B., D'Amato G., Da Silva J., Dahl R., Dahlen S. -E., Daniilidis V., Darjazini Nahhas L., Darsow U., De Blay F., De Guia E., De Los Santos C., De Manuel Keenoy E., De Vries G., Deleanu D., Demoly P., Denburg J., Devillier P., Didier A., Dimou M., Dinh-Xuan A. T., Djukanovic R., Dokic D., Dominguez Silva M. G., Douagui H., Douladiris N., Doulaptsi M., Dray G., Dubakiene R., Durham S., Dykewicz M., Ebo D., Edelbaher N., Eklund P., El-Gamal Y., El-Sayed Z. A., El-Sayed S. S., El-Seify M., Emuzyte R., Enecilla L., Espinoza H., Espinoza Contreras J. G., Farrell J., Fernandez L., Fink Wagner A., Fiocchi A., Fokkens W. J., Fontaine J. -F., Forastiere F., Fuentes Perez J. M., Gaerlan-Resureccion E., Gaga M., Galvez Romero J. L., Gamkrelidze A., Garcia A., Garcia Cobas C. Y., Garcia Cruz M. D. L. L. H., Gayraud J., Gemicioglu B., Genova S., Gereda J., Gerth Van Wijk R., Gomez M., Gonzalez Diaz S., Gotua M., Grigoreas C., Grisle I., Guidacci M., Guldemond N., Gutter Z., Guzman A., Halloum R., Hamelmann E., Hammadi S., Harvey R., Heinrich J., Hejjaoui A., Hellquist-Dahl B., Hernandez Velazquez L., Hew M., Hossny E., Howarth P., Hrubisko M., Huerta Villalobos Y. R., Humbert M., Hyland M., Ibrahim M., Ilyina N., Irani C., Ispayeva Z., Jares E., Jarvis D., Jassem E., Jenko K., Jimeneracruz Uscanga R. D., Johnston S., Joos G., Jost M., Julge K., Jung K. -S., Just J., Kaidashev I., Kalayci O., Kalyoncu F., Kapsali J., Kardas P., Karjalainen J., Kasala C. A., Katotomichelakis M., Kazi B., Keil T., Keith P., Khaitov M., Khaltaev N., Kim Y. -Y., Kleine-Tebbe J., Koffi N'Goran B., Kompoti E., Kopac P., Koppelman G., Koren Jeverica A., Kosnik M., Kostov K. V., Kowalski M. L., Kralimarkova T., Kramer Vrscaj K., Kraxner H., Kreft S., Kritikos V., Kudlay D., Kull I., Kupczyk M., Kvedariene V., Kyriakakou M., Lalek N., Lane S., Latiff A., Lau S., Lavrut J., Le L., Lessa M., Levin M., Li J., Lieberman P., Liotta G., Lipworth B., Liu X., Lobo R., Lodrup Carlsen K. C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J. A., Madjar B., Magnan A., Mahboub B., Mair A., Mais Y., Maitland Van Der Zee A. -H., Makela M., Makris M., Malling H. -J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marshall G., Martinsmartins P., Masjedi M. R., Maspero J. F., Matta Campos J. J., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melo-Gomes E., Meltzer E. O., Menditto E., Menzies-Gow A., Merk H., Michel J. -P., Miculinic N., Midao L., Mihaltan F., Mikael K., Mikos N., Milenkovic B., Mitsias D., Moalla B., Moda G., Mogica Martinez M. D., Mohammad Y., Moin M., Molimard M., Momas I., Monaco A., Montefort S., Mora D., Morais-Almeida M., Mosges R., Mostafa B. E., Munter L., Muraro A., Murray R., Mustakov T., Naclerio R., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nicod L., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'Hehir R., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G. L., Orru M. P., Ouedraogo S., Ouoba K., Paggiaro P. L., Pagkalos A., Palaniappan S. P., Pali-Scholl I., Palkonen S., Palmer S., Panaitescu Bunu C., Panzner P., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H. S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pereira A., Perez T., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Pitsios K., Plavec D., Poethig D., Pohl W., Poplas Susic A., Popov T. A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puy R., Rabe K., Raciborski F., Ramos J., Recto M. T., Reda S. M., Regateiro F., Reider N., Reitsma S., Repka-Ramirez S., Rimmer J., Rivero Yeverino D., Rizzo J. A., Robalo-Cordeiro C., Roberts G., Roche N., Rodriguez Gonzalez M., Rodriguez Zagal E., Rolland C., Roller-Wirnsberger R., Roman Rodriguez M., Romano A., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rottem M., Rouadi P., Rovina N., Rozman Sinur I., Ruiz M., Ruiz Segura L. T., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Salina H., Samitas K., Sanchez Coronel M. G., Sanchez-Borges M., Sanchez-Lopez J., Sarafoleanu C., Sarquis Serpa F., Sastre-Dominguez J., Scadding G., Scheire S., Schmid-Grendelmeier P., Schuhl J. F., Schunemann H., Schvalbova M., Scichilone N., Sepulveda C., Serrano E., Sheikh A., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E. F., Sisul J. 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Y., Waserman S., Wickman M., Williams S., Williams D., Wilson N., Woo K., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y. Y., Yawn B., Yiallouros P., Yoshihara S., Young I., Yusuf O. 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Carlsen K.C., Lombardi C., Louis R., Loukidis S., Lourenco O., Luna Pech J.A., Madjar B., Magnan A., Mahboub B., Mair A., Mais Y., van der Zee A.-H.M., Makela M., Makris M., Malling H.-J., Mandajieva M., Manning P., Manousakis M., Maragoudakis P., Marshall G., Martins P., Reza Masjedi M., Maspero J.F., Campos J.J.M., Maurer M., Mavale-Manuel S., Meco C., Melen E., Melo-Gomes E., Meltzer E.O., Menditto E., Menzies-Gow A., Merk H., Michel J.-P., Miculinic N., Midao L., Mihaltan F., Mikael K., Mikos N., Milenkovic B., Mitsias D., Moalla B., Moda G., Martinez M.D.M., Mohammad Y., Moin M., Molimard M., Momas I., Monaco A., Montefort S., Mora D., Morais-Almeida M., Mosges R., Mostafa B.E., Munter L., Muraro A., Murray R., Mustakov T., Naclerio R., Nadif R., Nakonechna A., Namazova-Baranova L., Navarro-Locsin G., Neffen H., Nekam K., Neou A., Nicod L., Niederberger-Leppin V., Niedoszytko M., Nieto A., Novellino E., Nunes E., Nyembue D., O'hehir R., Odjakova C., Ohta K., Okamoto Y., Okubo K., Oliver B., Onorato G.L., Orru M.P., Ouedraogo S., Ouoba K., Paggiaro P.L., Pagkalos A., Palaniappan S.P., Pali-Scholl I., Palkonen S., Palmer S., Bunu C.P., Panzner P., Papanikolaou V., Papi A., Paralchev B., Paraskevopoulos G., Park H.S., Passalacqua G., Patella V., Pavord I., Pawankar R., Pedersen S., Peleve S., Pereira A., Perez T., Pham-Thi N., Pigearias B., Pin I., Piskou K., Pitsios C., Pitsios K., Plavec D., Poethig D., Pohl W., Susic A.P., Popov T.A., Portejoie F., Potter P., Poulsen L., Prados-Torres A., Prarros F., Price D., Prokopakis E., Puy R., Rabe K., Raciborski F., Ramos J., Recto M.T., Reda S.M., Regateiro F., Reider N., Reitsma S., Repka-Ramirez S., Rimmer J., Yeverino D.R., Rizzo J.A., Robalo-Cordeiro C., Roberts G., Roche N., Gonzalez M.R., Zagal E.R., Rolland C., Roller-Wirns-berger R., Rodriguez M.R., Romano A., Rombaux P., Romualdez J., Rosado-Pinto J., Rosario N., Rosenwasser L., Rottem M., Rouadi P., Rovina N., Sinur I.R., Ruiz M., Segura L.T.R., Ryan D., Sagara H., Sakai D., Sakurai D., Saleh W., Salimaki J., Salina H., Samitas K.-N., Coronel M.G.S., Sanchez-Borges M., Sanchez-Lopez J., Sarafoleanu C., Serpa F.S., Sastre-Dominguez J., Scadding G., Scheire S., Schmid-Grendelmeier P., Schuhl J.F., Schunemann H., Schvalbova M., Scichilone N., Sepulveda C., Serrano E., Sheikh A., Shields M., Shishkov V., Siafakas N., Simeonov A., Simons E.F., Sisul J.C., Sitkauskiene B., Skrindo I., Kosak T.S., Sole D., Sooronbaev T., Soto-Martinez M., Sova M., Spertini F., Spranger O., Stamataki S., Stefanaki L., Stellato C., Stelmach R., Sterk P., Strandberg T., Stute P., Subramaniam A., Suppli Ulrik C., Sutherland M., Sylvestre S., Syrigou A., Barata L.T., Takovska N., Tan R., Tan F., Tan V., Tang I.P., Taniguchi M., Tannert L., Tattersall J., Teixeira M.D.C., Thijs C., Thomas M., To T., Todo-Bom A.M., Togias A., Tomazic P.-V., Toppila-Salmi S., Toskala E., Triggiani M., Triller N., Triller K., Tsiligianni I., Ulmeanu R., Urbancic J., Pereira M.U., Vachova M., Valdes F., Valenta R., Rostan M.V., Valero A., Vallianatou M., Valovirta E., Eerd M.V., Ganse E.V., Hage M., Vandenplas O., Vasankari T., Vassileva D., Ventura T., Vera-Munoz C., Vicheva D., Vichyanond P., Vidgren P., Viegi G., Vogelmeier C., Hertzen L.V., Vontetsianos T., Vourdas D., Wagenmann M., Walker S., Wallace D., Wang D.Y., Waserman S., Wickman M., Williams S., Williams D., Wilson N., Woo K., Wright J., Wroczynski P., Xepapadaki P., Yakovliev P., Yamaguchi M., Yan K., Yap Y.Y., Yawn B., Yiallouros P., Yoshihara S., Young I., Yusuf O.B., Zaidi A., Zaitoun F., Zar H., Zernotti M., Zhang L., Zhong N., Zidarn M., Zubrinich C., Dubakienė, Rūta, Ėmužytė, Regina, Kvedarienė, Violeta, Bousquet, J., Anto, J. M., Iaccarino, G., Czarlewski, W., Haahtela, T., Anto, A., Akdis, C. A., Blain, H., Canonica, G. W., Cardona, V., Cruz, A. A., Illario, M., Ivancevich, J. C., Jutel, M., Klimek, L., Kuna, P., Laune, D., Larenas-Linnemann, D., Mullol, J., Papadopoulos, N. G., Pfaar, O., Samolinski, B., Valiulis, A., Yorgancioglu, A., Zuberbier, T., Abdul Latiff, A. H., Abdullah, B., Aberer, W., Abusada, N., Adcock, I., Afani, A., Agache, I., Aggelidis, X., Agustin, J., Akdis, C., Akdis, M., Al-Ahmad, M., Al-Zahab Bassam, A., Aldrey-Palacios, O., Alvarez Cuesta, E., Alzaabi, A., Amad, S., Ambrocio, G., Annesi-Maesano, I., Ansotegui, I., Anto, J., Arshad, H., Artesani, M. C., Asayag, E., Avolio, F., Azhari, K., Baiardini, I., Bajrovic, N., Bakakos, P., Bakeyala Mongono, S., Balotro-Torres, C., Barba, S., Barbara, C., Barbosa, E., Barreto, B., Bartra, J., Bateman, E. D., Battur, L., Bedbrook, A., Bedolla Barajas, M., Beghe, B., Bel, E., Ben Kheder, A., Benson, M., Berghea, C., Bergmann, K. -C., Bernstein, D., Bewick, M., Bialek, S., Bialoszewski, A., Bieber, T., Billo, N., Bilo, M. B., Bindslev-Jensen, C., Bjermer, L., Bochenska Marciniak, M., Bond, C., Boner, A., Bonini, M., Bonini, S., Bosnic-Anticevich, S., Bosse, I., Botskariova, S., Bouchard, J., Boulet, L. -P., Bourret, R., Bousquet, P., Braido, F., Briggs, A., Brightling, C., Brozek, J., Buhl, R., Bumbacea, R., Burguete Cabanas, M. T., Bush, A., Busse, W. W., Buters, J., Caballero-Fonseca, F., Calderon, M. A., Calvo, M., Camargos, P., Camuzat, T., Cano, A., Capriles-Hulett, A., Caraballo, L., Carlsen, K. -H., Caro, J., Carr, W., Carreon-Asuncion, F., Carriazo, A. M., Casale, T., Castor, M. A., Castro, E., Cecchi, L., Cepeda Sarabia, A., Chandrasekharan, R., Chang, Y. -S., Chato-Andeza, V., Chatzi, L., Chatzidaki, C., Chavannes, N. H., Chen, Y., Cheng, L., Chivato, T., Chkhartishvili, E., Christoff, G., Chrystyn, H., Chu, D. K., Chua, A., Chuchalin, A., Chung, K. F., Ciceran, A., Cingi, C., Ciprandi, G., Cirule, I., Coelho, A. C., Constantinidis, J., Correia De Sousa, J., Costa, E., Costa, D., Costa Dominguez, M. D. C., Coste, A., Cox, L., Cullen, J., Custovic, A., Cvetkovski, B., D'Amato, G., Da Silva, J., Dahl, R., Dahlen, S. -E., Daniilidis, V., Darjazini Nahhas, L., Darsow, U., De Blay, F., De Guia, E., De Los Santos, C., De Manuel Keenoy, E., De Vries, G., Deleanu, D., Demoly, P., Denburg, J., Devillier, P., Didier, A., Dimou, M., Dinh-Xuan, A. T., Djukanovic, R., Dokic, D., Dominguez Silva, M. G., Douagui, H., Douladiris, N., Doulaptsi, M., Dray, G., Dubakiene, R., Durham, S., Dykewicz, M., Ebo, D., Edelbaher, N., Eklund, P., El-Gamal, Y., El-Sayed, Z. A., El-Sayed, S. S., El-Seify, M., Emuzyte, R., Enecilla, L., Espinoza, H., Espinoza Contreras, J. G., Farrell, J., Fernandez, L., Fink Wagner, A., Fiocchi, A., Fokkens, W. J., Fontaine, J. -F., Forastiere, F., Fuentes Perez, J. M., Gaerlan-Resureccion, E., Gaga, M., Galvez Romero, J. L., Gamkrelidze, A., Garcia, A., Garcia Cobas, C. Y., Garcia Cruz, M. D. L. L. H., Gayraud, J., Gemicioglu, B., Genova, S., Gereda, J., Gerth Van Wijk, R., Gomez, M., Gonzalez Diaz, S., Gotua, M., Grigoreas, C., Grisle, I., Guidacci, M., Guldemond, N., Gutter, Z., Guzman, A., Halloum, R., Hamelmann, E., Hammadi, S., Harvey, R., Heinrich, J., Hejjaoui, A., Hellquist-Dahl, B., Hernandez Velazquez, L., Hew, M., Hossny, E., Howarth, P., Hrubisko, M., Huerta Villalobos, Y. R., Humbert, M., Hyland, M., Ibrahim, M., Ilyina, N., Irani, C., Ispayeva, Z., Jares, E., Jarvis, D., Jassem, E., Jenko, K., Jimeneracruz Uscanga, R. D., Johnston, S., Joos, G., Jost, M., Julge, K., Jung, K. -S., Just, J., Kaidashev, I., Kalayci, O., Kalyoncu, F., Kapsali, J., Kardas, P., Karjalainen, J., Kasala, C. 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G., Sanchez-Borges, M., Sanchez-Lopez, J., Sarafoleanu, C., Sarquis Serpa, F., Sastre-Dominguez, J., Scadding, G., Scheire, S., Schmid-Grendelmeier, P., Schuhl, J. F., Schunemann, H., Schvalbova, M., Scichilone, N., Sepulveda, C., Serrano, E., Sheikh, A., Shields, M., Shishkov, V., Siafakas, N., Simeonov, A., Simons, E. F., Sisul, J. C., Sitkauskiene, B., Skrindo, I., Soklic Kosak, T., Sole, D., Sooronbaev, T., Soto-Martinez, M., Sova, M., Spertini, F., Spranger, O., Stamataki, S., Stefanaki, L., Stellato, C., Stelmach, R., Sterk, P., Strandberg, T., Stute, P., Subramaniam, A., Suppli Ulrik, C., Sutherland, M., Sylvestre, S., Syrigou, A., Taborda Barata, L., Takovska, N., Tan, R., Tan, F., Tan, V., Tang, I. P., Taniguchi, M., Tannert, L., Tattersall, J., Teixeira, M. D. C., Thijs, C., Thomas, M., To, T., Todo-Bom, A. M., Togias, A., Tomazic, P. -V., Toppila-Salmi, S., Toskala, E., Triggiani, M., Triller, N., Triller, K., Tsiligianni, I., Ulmeanu, R., Urbancic, J., Urrutia Pereira, M., Vachova, M., Valdes, F., Valenta, R., Valentin Rostan, M., Valero, A., Vallianatou, M., Valovirta, E., Van Eerd, M., Van Ganse, E., Van Hage, M., Vandenplas, O., Vasankari, T., Vassileva, D., Ventura, M. T., Vera-Munoz, C., Vicheva, D., Vichyanond, P., Vidgren, P., Viegi, G., Vogelmeier, C., Von Hertzen, L., Vontetsianos, T., Vourdas, D., Wagenmann, M., Walker, S., Wallace, D., Wang, D. Y., Waserman, S., Wickman, M., Williams, S., Williams, D., Wilson, N., Woo, K., Wright, J., Wroczynski, P., Xepapadaki, P., Yakovliev, P., Yamaguchi, M., Yan, K., Yap, Y. Y., Yawn, B., Yiallouros, P., Yoshihara, S., Young, I., Yusuf, O. B., Zaidi, A., Zaitoun, F., Zar, H., Zernotti, M., Zhang, L., Zhong, N., Zidarn, M., Zubrinich, C., University of Zurich, Bousquet, Jean, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, IMIM-Hospital del Mar, Generalitat de Catalunya, Universitat Pompeu Fabra [Barcelona] (UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), 'Federico II' University of Naples Medical School, Medical Consulting Czarlewski, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Euromov (EuroMov), Université de Montpellier (UM), IRCCS Humanitas Research Hospital, 20089 Rozzano, Italy., Vall d'Hebron University Hospital [Barcelona], ProAR – Nucleo de Excelencia em Asma, Universidade Federal da Bahia (UFBA), Global Alliance Against Chronic Respiratory Diseases (GARD-WHO), Division for Health Innovation, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Wrocław Medical University, Center for Rhinology and Allergology Wiesbaden, University Hospital Mannheim, Barlicki University Hospital, KYomed INNOV [Montpellier], Hospital Medica Sur [Mexico City, Mexico], Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Royal Manchester Children's Hospital, University of Manchester [Manchester], General Children's Hospital of Athens P & A Kyriakou, Philipps Universität Marburg = Philipps University of Marburg, Medical University of Warsaw - Poland, Vilnius University [Vilnius], Manisa Celal Bayar University, and Salvy-Córdoba, Nathalie

Subjects
BLOOD-PRESSURE, Review, Angiotensin-converting enzyme, Antioxidant, Coronavirus, Diet, Food, law.invention, Dietary interventions, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 10183 Swiss Institute of Allergy and Asthma Research, law, Medicine and Health Sciences, Immunology and Allergy, Medicine, 030212 general & internal medicine, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, education.field_of_study, Mortality rate, 3. Good health, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 2723 Immunology and Allergy, Angiotensin-converting enzyme, Antioxidant, Coronavirus, Diet, Food, Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Coronaviru, Immunology, Population, 610 Medicine & health, COVID-19, Settore MED/10 - Malattie Dell'Apparato Respiratorio, 03 medical and health sciences, Environmental health, population, angiotensin-converting enzyme, Quarantine, education, 2403 Immunology, ANTIHYPERTENSIVE PEPTIDES, business.industry, RC581-607, GENE, POLYMORPHISM, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030228 respiratory system, 2740 Pulmonary and Respiratory Medicine, Immunologic diseases. Allergy, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Regional differences, Coronavirus Infections
Abstract

Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.

Published
2020

22. Haloperidol for the Treatment of Delirium in ICU Patients

Author

Andersen-Ranberg, N, Poulsen, L, Perner, A, Wetterslev, J, Estrup, S, Hästbacka, J, Morgan, M, Citerio, G, Caballero, J, Lange, T, Kjær, M, Ebdrup, B, Engstrøm, J, Olsen, M, Oxenbøll Collet, M, Mortensen, C, Weber, S, Andreasen, A, Bestle, M, Uslu, B, Scharling Pedersen, H, Gramstrup Nielsen, L, Toft Boesen, H, Jensen, J, Nebrich, L, La Cour, K, Laigaard, J, Haurum, C, Olesen, M, Overgaard-Steensen, C, Westergaard, B, Brand, B, Kingo Vesterlund, G, Thornberg Kyhnauv, P, Mikkelsen, V, Hyttel-Sørensen, S, de Haas, I, Aagaard, S, Nielsen, L, Eriksen, A, Rasmussen, B, Brix, H, Hildebrandt, T, Schønemann-Lund, M, Fjeldsøe-Nielsen, H, Kuivalainen, A, Mathiesen, O, Andersen-Ranberg, Nina C, Poulsen, Lone M, Perner, Anders, Wetterslev, Jørn, Estrup, Stine, Hästbacka, Johanna, Morgan, Matt, Citerio, Giuseppe, Caballero, Jesus, Lange, Theis, Kjær, Maj-Brit N, Ebdrup, Bjørn H, Engstrøm, Janus, Olsen, Markus H, Oxenbøll Collet, Marie, Mortensen, Camilla B, Weber, Sven-Olaf, Andreasen, A Sofie, Bestle, Morten H, Uslu, Bülent, Scharling Pedersen, Helle, Gramstrup Nielsen, Louise, Toft Boesen, Hans C, Jensen, Jacob V, Nebrich, Lars, La Cour, Kirstine, Laigaard, Jens, Haurum, Cecilie, Olesen, Marie W, Overgaard-Steensen, Christian, Westergaard, Bo, Brand, Björn, Kingo Vesterlund, Gitte, Thornberg Kyhnauv, Pernille, Mikkelsen, Vibe S, Hyttel-Sørensen, Simon, de Haas, Inge, Aagaard, Søren R, Nielsen, Line O, Eriksen, Anne S, Rasmussen, Bodil S, Brix, Helene, Hildebrandt, Thomas, Schønemann-Lund, Martin, Fjeldsøe-Nielsen, Hans, Kuivalainen, Anna-Maria, Mathiesen, Ole, Andersen-Ranberg, N, Poulsen, L, Perner, A, Wetterslev, J, Estrup, S, Hästbacka, J, Morgan, M, Citerio, G, Caballero, J, Lange, T, Kjær, M, Ebdrup, B, Engstrøm, J, Olsen, M, Oxenbøll Collet, M, Mortensen, C, Weber, S, Andreasen, A, Bestle, M, Uslu, B, Scharling Pedersen, H, Gramstrup Nielsen, L, Toft Boesen, H, Jensen, J, Nebrich, L, La Cour, K, Laigaard, J, Haurum, C, Olesen, M, Overgaard-Steensen, C, Westergaard, B, Brand, B, Kingo Vesterlund, G, Thornberg Kyhnauv, P, Mikkelsen, V, Hyttel-Sørensen, S, de Haas, I, Aagaard, S, Nielsen, L, Eriksen, A, Rasmussen, B, Brix, H, Hildebrandt, T, Schønemann-Lund, M, Fjeldsøe-Nielsen, H, Kuivalainen, A, Mathiesen, O, Andersen-Ranberg, Nina C, Poulsen, Lone M, Perner, Anders, Wetterslev, Jørn, Estrup, Stine, Hästbacka, Johanna, Morgan, Matt, Citerio, Giuseppe, Caballero, Jesus, Lange, Theis, Kjær, Maj-Brit N, Ebdrup, Bjørn H, Engstrøm, Janus, Olsen, Markus H, Oxenbøll Collet, Marie, Mortensen, Camilla B, Weber, Sven-Olaf, Andreasen, A Sofie, Bestle, Morten H, Uslu, Bülent, Scharling Pedersen, Helle, Gramstrup Nielsen, Louise, Toft Boesen, Hans C, Jensen, Jacob V, Nebrich, Lars, La Cour, Kirstine, Laigaard, Jens, Haurum, Cecilie, Olesen, Marie W, Overgaard-Steensen, Christian, Westergaard, Bo, Brand, Björn, Kingo Vesterlund, Gitte, Thornberg Kyhnauv, Pernille, Mikkelsen, Vibe S, Hyttel-Sørensen, Simon, de Haas, Inge, Aagaard, Søren R, Nielsen, Line O, Eriksen, Anne S, Rasmussen, Bodil S, Brix, Helene, Hildebrandt, Thomas, Schønemann-Lund, Martin, Fjeldsøe-Nielsen, Hans, Kuivalainen, Anna-Maria, and Mathiesen, Ole

Abstract

Background Haloperidol is frequently used to treat delirium in patients in the intensive care unit (ICU), but evidence of its effect is limited. Methods In this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg) or placebo. Haloperidol or placebo was administered in the ICU for as long as delirium continued and as needed for recurrences. The primary outcome was the number of days alive and out of the hospital at 90 days after randomization. Results A total of 1000 patients underwent randomization; 510 were assigned to the haloperidol group and 490 to the placebo group. Among these patients, 987 (98.7%) were included in the final analyses (501 in the haloperidol group and 486 in the placebo group). Primary outcome data were available for 963 patients (97.6%). At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% confidence interval [CI], 32.9 to 38.6) in the haloperidol group and 32.9 (95% CI, 29.9 to 35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI, -1.2 to 7.0) (P=0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, -6.9 percentage points [95% CI, -13.0 to -0.6]). Serious adverse reactions occurred in 11 patients in the haloperidol group and in 9 patients in the placebo group. Conclusions Among patients in the ICU with delirium, treatment with haloperidol did not lead to a significantly greater number of days alive and out of the hospital at 90 days than placebo.

Published
2022

24. Impact of Food Matrices on Digestibility of Allergens and Poorly Allergenic Homologs

Author

Akkerdaas, J H, Cianferoni, A, Islamovic, E, Kough, J, Ladics, G S, McClain, S, Poulsen, L K, Silvanovich, A, Pereira Mouriès, L, van Ree, R, Akkerdaas, J H, Cianferoni, A, Islamovic, E, Kough, J, Ladics, G S, McClain, S, Poulsen, L K, Silvanovich, A, Pereira Mouriès, L, and van Ree, R

Abstract

Background: Protease resistance is considered a risk factor for allergenicity of proteins, although the correlation is low. It is nonetheless a part of the weight-of-evidence approach, proposed by Codex, for assessing the allergenicity risk of novel food proteins. Susceptibility of proteins to pepsin is commonly tested with purified protein in solution.Objective: Food proteins are rarely consumed in purified form. Our aim was to evaluate the impact of experimental and endogenous food matrices on protease susceptibility of homologous protein pairs with different degrees of allergenicity.Methods: Porcine and shrimp tropomyosin (ST) were subjected to sequential exposure to amylase, pepsin, and pancreatin in their respective endogenous matrix (pork tenderloin/boiled shrimp) and in three different experimental matrices (dessert mousse [DM], soy milk [SM], and chocolate bar [CB]). Digestion was monitored by immunoblotting using tropomyosin-specific antibodies. Recombinant peach and strawberry lipid transfer protein were biotinylated, spiked into both peach and strawberry fruit pulp, and subjected to the same sequential digestion protocol. Digestion was monitored by immunoblotting using streptavidin for detection.Results: Chocolate bar, and to a lesser extent SM, had a clear protective effect against pepsin digestion of porcine tropomyosin (PT) and to a lesser extent of ST. Increased resistance was associated with increased protein content. Spiking experiments with bovine serum albumin (BSA) confirmed the protective effect of a protein-rich matrix. The two tropomyosins were both highly resistant to pepsin in their protein-rich and lean native food matrix. Pancreatin digestion remained rapid and complete, independent of the matrix. The fat-rich environment did not transfer protection against pepsin digestion. Spiking of recombinant peach and strawberry lipid transfer proteins into peach and strawberry pulp did not reveal any differential protective e

Published
2022

25. Agents intervening against delirium in the intensive care unit (AID-ICU) trial-protocol for a secondary Bayesian analysis

Author

Andersen-Ranberg, N, Poulsen, L, Perner, A, Hästbacka, J, Morgan, M, Citerio, G, Collet, M, Weber, S, Andreasen, A, Bestle, M, Uslu, B, Pedersen, H, Nielsen, L, Damgaard, K, Jensen, T, Sommer, T, Dey, N, Mathiesen, O, Granholm, A, Andersen-Ranberg, Nina, Poulsen, Lone M, Perner, Anders, Hästbacka, Johanna, Morgan, Matthew P G, Citerio, Giuseppe, Collet, Marie Oxenbøll, Weber, Sven-Olaf, Andreasen, Anne Sofie, Bestle, Morten H, Uslu, Bülent, Pedersen, Helle B S, Nielsen, Louise G, Damgaard, Kjeld, Jensen, Troels B, Sommer, Trine, Dey, Nilanjan, Mathiesen, Ole, Granholm, Anders, Andersen-Ranberg, N, Poulsen, L, Perner, A, Hästbacka, J, Morgan, M, Citerio, G, Collet, M, Weber, S, Andreasen, A, Bestle, M, Uslu, B, Pedersen, H, Nielsen, L, Damgaard, K, Jensen, T, Sommer, T, Dey, N, Mathiesen, O, Granholm, A, Andersen-Ranberg, Nina, Poulsen, Lone M, Perner, Anders, Hästbacka, Johanna, Morgan, Matthew P G, Citerio, Giuseppe, Collet, Marie Oxenbøll, Weber, Sven-Olaf, Andreasen, Anne Sofie, Bestle, Morten H, Uslu, Bülent, Pedersen, Helle B S, Nielsen, Louise G, Damgaard, Kjeld, Jensen, Troels B, Sommer, Trine, Dey, Nilanjan, Mathiesen, Ole, and Granholm, Anders

Abstract

Background: Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID-ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients. Methods: This protocol describes the secondary, pre-planned Bayesian analyses of the primary and secondary outcomes up to day 90 of the AID-ICU trial. We will use Bayesian linear regression models for all count outcomes and Bayesian logistic regression models for all dichotomous outcomes. We will adjust for stratification variables (site and delirium subtype) and use weakly informative priors supplemented with sensitivity analyses using sceptical priors. We will present results as absolute differences (mean differences and risk differences) and relative differences (ratios of means and relative risks). Posteriors will be summarised using median values as point estimates and percentile-based 95% credibility intervals. Probabilities of any benefit/harm, clinically important benefit/harm and clinically unimportant differences will be presented for all outcomes. Discussion: The results of this secondary, pre-planned Bayesian analysis will complement the primary frequentist analysis of the AID-ICU trial and facilitate a nuanced and probabilistic interpretation of the trial results.

Published
2022

28. Regulation of human oocyte maturation in vivo during the final maturation of follicles.

Author

Cadenas, J, Poulsen, L C, Nikiforov, D, Grøndahl, M L, Kumar, A, Bahnu, K, Englund, A L M, Malm, J, Marko-Varga, G, Pla, I, Sanchez, A, Pors, S E, and Andersen, C Yding

Subjects
*OVUM, *GROWTH differentiation factors, *OVARIAN follicle, *EPIDERMAL growth factor, *GRANULOSA cells
Abstract

STUDY QUESTION Which substances and signal transduction pathways are potentially active downstream to the effect of FSH and LH in the regulation of human oocyte maturation in vivo ? SUMMARY ANSWER The regulation of human oocyte maturation appears to be a multifactorial process in which several different signal transduction pathways are active. WHAT IS KNOWN ALREADY Many studies in animal species have provided insight into the mechanisms that govern the final maturation of oocytes. Currently, these studies have identified several different mechanisms downstream to the effects of FSH and LH. Some of the identified mechanisms include the regulation of cAMP/cGMP levels in oocytes involving C-type natriuretic peptide (CNP), effects of epidermal growth factor (EGF)-related peptides such as amphiregulin (AREG) and/or epiregulin (EREG), effect of TGF-β family members including growth differentiation factor 9 (GDF9) and morphogenetic protein 15 (BMP15), activins/inhibins, follicular fluid meiosis activating sterol (FF-MAS), the growth factor midkine (MDK), and several others. However, to what extent these pathways and mechanisms are active in humans in vivo is unknown. STUDY DESIGN, SIZE, DURATION This prospective cohort study included 50 women undergoing fertility treatment in a standard antagonist protocol at a university hospital affiliated fertility clinic in 2016–2018. PARTICIPANTS/MATERIALS, SETTING, METHODS We evaluated the substances and signalling pathways potentially affecting human oocyte maturation in follicular fluid (FF) and granulosa cells (GCs) collected at five time points during the final maturation of follicles. Using ELISA measurement and proteomic profiling of FF and whole genome gene expression in GC, the following substances and their signal transduction pathways were collectively evaluated: CNP, the EGF family, inhibin-A, inhibin-B, activins, FF-MAS, MDK, GDF9, and BMP15. MAIN RESULTS AND THE ROLE OF CHANCE All the evaluated substances and signal transduction pathways are potentially active in the regulation of human oocyte maturation in vivo except for GDF9/BMP15 signalling. In particular, AREG, inhibins, and MDK were significantly upregulated during the first 12–17 h after initiating the final maturation of follicles and were measured at significantly higher concentrations than previously reported. Additionally, the genes regulating FF-MAS synthesis and metabolism were significantly controlled in favour of accumulation during the first 12–17 h. In contrast, concentrations of CNP were low and did not change during the process of final maturation of follicles, and concentrations of GDF9 and BMP15 were much lower than reported in small antral follicles, suggesting a less pronounced influence from these substances. LARGE SCALE DATA None. LIMITATIONS, REASONS FOR CAUTION Although GC and cumulus cells have many similar features, it is a limitation of the current study that information for the corresponding cumulus cells is not available. However, we seldom recovered a cumulus–oocyte complex during the follicle aspiration from 0 to 32 h. WIDER IMPLICATIONS OF THE FINDINGS Delineating the mechanisms governing the regulation of human oocyte maturation in vivo advances the possibility of developing a platform for IVM that, as for most other mammalian species, results in healthy offspring with good efficacy. Mimicking the intrafollicular conditions during oocyte maturation in vivo in small culture droplets during IVM may enhance oocyte nuclear and cytoplasmic maturation. The primary outlook for such a method is, in the context of fertility preservation, to augment the chances of achieving biological children after a cancer treatment by subjecting oocytes from small antral follicles to IVM. Provided that aspiration of oocytes from small antral follicles in vivo can be developed with good efficacy, IVM may be applied to infertile patients on a larger scale and can provide a cheap alternative to conventional IVF treatment with ovarian stimulation. Successful IVM has the potential to change current established techniques for infertility treatment. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the University Hospital of Copenhagen, Rigshospitalet, the Independent Research Fund Denmark (grant number 0134-00448), and the Interregional EU-sponsored ReproUnion network. There are no conflicts of interest to be declared. [ABSTRACT FROM AUTHOR]

Published
2023
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32. ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

Author

Bousquet, J., Hellings, P. W., Agache, I., Bedbrook, A., Bachert, C., Bergmann, K. C., Bewick, M., Bindslev-Jensen, C., Bosnic-Anticevitch, S., Bucca, C., Caimmi, D. P., Camargos, P. A. M., Canonica, G. W., Casale, T., Chavannes, N. H., Cruz, A. A., De Carlo, G., Dahl, R., Demoly, P., Devillier, P., Fonseca, J., Fokkens, W. J., Guldemond, N. A., Haahtela, T., Illario, M., Just, J., Keil, T., Klimek, L., Kuna, P., Larenas-Linnemann, D., Morais-Almeida, M., Mullol, J., Murray, R., Naclerio, R., O’Hehir, R. E., Papadopoulos, N. G., Pawankar, R., Potter, P., Ryan, D., Samolinski, B., Schunemann, H. J., Sheikh, A., Simons, F. E. R., Stellato, C., Todo-Bom, A., Tomazic, P. V., Valiulis, A., Valovirta, E., Ventura, M. T., Wickman, M., Young, I., Yorgancioglu, A., Zuberbier, T., Aberer, W., Akdis, C. A., Akdis, M., Annesi-Maesano, I., Ankri, J., Ansotegui, I. J., Anto, J. M., Arnavielhe, S., Asarnoj, A., Arshad, H., Avolio, F., Baiardini, I., Barbara, C., Barbagallo, M., Bateman, E. D., Beghé, B., Bel, E. H., Bennoor, K. S., Benson, M., Białoszewski, A. Z., Bieber, T., Bjermer, L., Blain, H., Blasi, F., Boner, A. L., Bonini, M., Bonini, S., Bosse, I., Bouchard, J., Boulet, L. P., Bourret, R., Bousquet, P. J., Braido, F., Briggs, A. H., Brightling, C. E., Brozek, J., Buhl, R., Bunu, C., Burte, E., Bush, A., Caballero-Fonseca, F., Calderon, M. A., Camuzat, T., Cardona, V., Carreiro-Martins, P., Carriazo, A. M., Carlsen, K. H., Carr, W., Cepeda Sarabia, A. M., Cesari, M., Chatzi, L., Chiron, R., Chivato, T., Chkhartishvili, E., Chuchalin, A. G., Chung, K. F., Ciprandi, G., de Sousa, J. Correia, Cox, L., Crooks, G., Custovic, A., Dahlen, S. E., Darsow, U., Dedeu, T., Deleanu, D., Denburg, J. A., De Vries, G., Didier, A., Dinh-Xuan, A. T., Dokic, D., Douagui, H., Dray, G., Dubakiene, R., Durham, S. R., Du Toit, G., Dykewicz, M. S., Eklund, P., El-Gamal, Y., Ellers, E., Emuzyte, R., Farrell, J., Fink Wagner, A., Fiocchi, A., Fletcher, M., Forastiere, F., Gaga, M., Gamkrelidze, A., Gemicioğlu, B., Gereda, J. E., van Wick, R. Gerth, González Diaz, S., Grisle, I., Grouse, L., Gutter, Z., Guzmán, M. A., Hellquist-Dahl, B., Heinrich, J., Horak, F., Hourihane, J. O’. B., Humbert, M., Hyland, M., Iaccarino, G., Jares, E. J., Jeandel, C., Johnston, S. L., Joos, G., Jonquet, O., Jung, K. S., Jutel, M., Kaidashev, I., Khaitov, M., Kalayci, O., Kalyoncu, A. F., Kardas, P., Keith, P. K., Kerkhof, M., Kerstjens, H. A. M., Khaltaev, N., Kogevinas, M., Kolek, V., Koppelman, G. H., Kowalski, M. L., Kuitunen, M., Kull, I., Kvedariene, V., Lambrecht, B., Lau, S., Laune, D., Le, L. T. T., Lieberman, P., Lipworth, B., Li, J., Lodrup Carlsen, K. C., Louis, R., Lupinek, C., MacNee, W., Magar, Y., Magnan, A., Mahboub, B., Maier, D., Majer, I., Malva, J., Manning, P., De Manuel Keenoy, E., Marshall, G. D., Masjedi, M. R., Mathieu-Dupas, E., Maurer, M., Mavale-Manuel, S., Melén, E., Melo-Gomes, E., Meltzer, E. O., Mercier, J., Merk, H., Miculinic, N., Mihaltan, F., Milenkovic, B., Millot-Keurinck, J., Mohammad, Y., Momas, I., Mösges, R., Muraro, A., Namazova-Baranova, L., Nadif, R., Neffen, H., Nekam, K., Nieto, A., Niggemann, B., Nogueira-Silva, L., Nogues, M., Nyembue, T. D., Ohta, K., Okamoto, Y., Okubo, K., Olive-Elias, M., Ouedraogo, S., Paggiaro, P., Pali-Schöll, I., Palkonen, S., Panzner, P., Papi, A., Park, H. S., Passalacqua, G., Pedersen, S., Pereira, A. M., Pfaar, O., Picard, R., Pigearias, B., Pin, I., Plavec, D., Pohl, W., Popov, T. A., Portejoie, F., Postma, D., Poulsen, L. K., Price, D., Rabe, K. F., Raciborski, F., Roberts, G., Robalo-Cordeiro, C., Rodenas, F., Rodriguez-Mañas, L., Rolland, C., Roman Rodriguez, M., Romano, A., Rosado-Pinto, J., Rosario, N., Rottem, M., Sanchez-Borges, M., Sastre-Dominguez, J., Scadding, G. K., Scichilone, N., Schmid-Grendelmeier, P., Serrano, E., Shields, M., Siroux, V., Sisul, J. C., Skrindo, I., Smit, H. A., Solé, D., Sooronbaev, T., Spranger, O., Stelmach, R., Sterk, P. J., Strandberg, T., Sunyer, J., Thijs, C., Triggiani, M., Valenta, R., Valero, A., van Eerd, M., van Ganse, E., van Hague, M., Vandenplas, O., Varona, L. L., Vellas, B., Vezzani, G., Vazankari, T., Viegi, G., Vontetsianos, T., Wagenmann, M., Walker, S., Wang, D. Y., Wahn, U., Werfel, T., Whalley, B., Williams, D. M., Williams, S., Wilson, N., Wright, J., Yawn, B. P., Yiallouros, P. K., Yusuf, O. M., Zaidi, A., Zar, H. J., Zernotti, M. E., Zhang, L., Zhong, N., and Zidarn, M.

Published
2016
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35. Haloperidol for the Treatment of Delirium in ICU Patients.

Author

Andersen-Ranberg, N. C., Poulsen, L. M., Perner, A., Wetterslev, J., Estrup, S., Hästbacka, J., Morgan, M., Citerio, G., Caballero, J., Lange, T., Kjær, M.-B. N., Ebdrup, B. H., Engstrøm, J., Olsen, M. H., Collet, M. Oxenbøll, Mortensen, C. B., Weber, S.-O., Andreasen, A. S., Bestle, M. H., and Uslu, B.

Subjects
*HALOPERIDOL, *INTENSIVE care patients, *DELIRIUM
Abstract

BACKGROUND Haloperidol is frequently used to treat deliriUm in patients in the intensive care deunit (ICU), but evidence of its effect is limited. METHODS In this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg) or placebo. Haloperidol or placebo was administered in the ICU for as long as delirium continued and as needed for recurrences. The primary outcome was the number of days alive and out of the hospital at 90 days after randomization. RESULTS A total of 1000 patients underwent randomization; 510 were assigned to the halo-peridol group and 490 to the placebo group. Among these patients, 987 (98.796) were included in the final analyses (501 in the haloperidol group and 486 in the placebo group). Primary outcome data were available for 963 patients (97.60). At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% confidence interval ICI], 32.9 to 38.6) in the haloperidol group and 32.9 (95°6 CI, 29.9 to 35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI, -1.2 to ZO) (P=0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, -6.9 percentage points [95% CI, -13.0 to -0.6]). Serious adverse reactions occurred in 11 patients in the haloperidol group and in 9 patients in the placebo group. CONCLUSIONS Among patients in the ICU with delirium, treatment with haloperidol did not lead to a significantly greater number of days alive and out of the hospital at 90 days than placebo. (Funded by Innovation Fund Denmark and others; AID-ICU ClinicalTrials.gov number, NCT03392376; EudraCT number, 2017-003829-15.). [ABSTRACT FROM AUTHOR]

Published
2022
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36. Agents intervening against delirium in the intensive care unit (AID-ICU) – Protocol for a randomised placebo-controlled trial of haloperidol in patients with delirium in the ICU

Author

Andersen-Ranberg, N, Poulsen, L, Perner, A, Wetterslev, J, Estrup, S, Lange, T, Ebdrup, B, Hästbacka, J, Morgan, M, Citerio, G, Zafrani, L, Caballero, J, Collet, M, Weber, S, Andreasen, A, Bestle, M, Pedersen, H, Hildebrandt, T, Thee, C, Jensen, T, Dey, N, Nielsen, L, Mathiesen, O, Poulsen, L M, Morgan, M P G, Collet, M O, Andreasen, A S, Pedersen, H B S, Jensen, T B, Nielsen, L G, Andersen-Ranberg, N, Poulsen, L, Perner, A, Wetterslev, J, Estrup, S, Lange, T, Ebdrup, B, Hästbacka, J, Morgan, M, Citerio, G, Zafrani, L, Caballero, J, Collet, M, Weber, S, Andreasen, A, Bestle, M, Pedersen, H, Hildebrandt, T, Thee, C, Jensen, T, Dey, N, Nielsen, L, Mathiesen, O, Poulsen, L M, Morgan, M P G, Collet, M O, Andreasen, A S, Pedersen, H B S, Jensen, T B, and Nielsen, L G

Abstract

Background: Delirium among patients in the intensive care unit (ICU) is a common condition associated with increased morbidity and mortality. Haloperidol is the most frequently used pharmacologic intervention, but its use is not supported by firm evidence. Therefore, we are conducting Agents Intervening against Delirium in the Intensive Care Unit (AID-ICU) trial to assess the benefits and harms of haloperidol for the treatment of ICU-acquired delirium. Methods: AID-ICU is an investigator-initiated, pragmatic, international, randomised, blinded, parallel-group, trial allocating adult ICU patients with manifest delirium 1:1 to haloperidol or placebo. Trial participants will receive intravenous 2.5 mg haloperidol three times daily or matching placebo (isotonic saline 0.9%) if they are delirious. If needed, a maximum of 20 mg/daily haloperidol/placebo is given. An escape protocol, not including haloperidol, is part of the trial protocol. The primary outcome is days alive out of the hospital within 90 days post-randomisation. Secondary outcomes are number of days without delirium or coma, serious adverse reactions to haloperidol, usage of escape medication, number of days alive without mechanical ventilation; mortality, health-related quality-of-life and cognitive function at 1-year follow-up. A sample size of 1000 patients is required to detect a 7-day improvement or worsening of the mean days alive out of the hospital, type 1 error risk of 5% and power 90%. Perspective: The AID-ICU trial is based on gold standard methodology applied to a large sample of clinically representative patients and will provide pivotal high-quality data on the benefits and harms of haloperidol for the treatment ICU-acquired delirium.

Published
2019

42. 538P Nadunolimab (CAN04), a first-in-class monoclonal antibody against IL1RAP, in combination with chemotherapy in subjects with pancreatic cancer (PDAC) and non-small cell lung cancer (NSCLC)

Author

Awada, A.H., primary, Zematis, M., additional, Ochsenreither, S., additional, Eefsen, R.L., additional, Arnold, D., additional, Cicenas, S., additional, Yachnin, J., additional, Pfeiffer, P., additional, Paz-Ares, L., additional, Jungels, C., additional, Greil, R., additional, Poulsen, L. Østergaard, additional, Van Cutsem, E., additional, Ribas, I. Garcia, additional, Thorsson, L., additional, and Collignon, J.J., additional

Published
2021
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47. Randomized multicentre feasibility trial of intermediate care versus standard ward care after emergency abdominal surgery (InCare trial)

Author

Vester-Andersen, M., Waldau, T., Wetterslev, J., Mller, M. H., Rosenberg, J., Jrgensen, L. N., Jakobsen, J. C., Mller, A. M., Gillesberg, I. E., Jakobsen, H. L., Hansen, E. G., Poulsen, L. M., Skovdal, J., Sgaard, E. K., Bestle, M., Vilandt, J., Rosenberg, I., Itenov, T. S., Pedersen, J., Madsen, M. R., Maschmann, C., Rasmussen, M., Jessen, C., and Bugge, L.

Published
2015
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