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3. Artificial intelligence for predictive biomarker discovery in immuno-oncology: a systematic review

Author

Prelaj, A., Miskovic, V., Zanitti, M., Trovo, F., Genova, C., Viscardi, G., Rebuzzi, S.E., Mazzeo, L., Provenzano, L., Kosta, S., Favali, M., Spagnoletti, A., Castelo-Branco, L., Dolezal, J., Pearson, A.T., Lo Russo, G., Proto, C., Ganzinelli, M., Giani, C., Ambrosini, E., Turajlic, S., Au, L., Koopman, M., Delaloge, S., Kather, J.N., de Braud, F., Garassino, M.C., Pentheroudakis, G., Spencer, C., and Pedrocchi, A.L.G.

Published
2024
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4. ESMO Guidance for Reporting Oncology real-World evidence (GROW)

Author

Castelo-Branco, L., Pellat, A., Martins-Branco, D., Valachis, A., Derksen, J.W.G., Suijkerbuijk, K.P.M., Dafni, U., Dellaporta, T., Vogel, A., Prelaj, A., Groenwold, R.H.H., Martins, H., Stahel, R., Bliss, J., Kather, J., Ribelles, N., Perrone, F., Hall, P.S., Dienstmann, R., Booth, C.M., Pentheroudakis, G., Delaloge, S., and Koopman, M.

Published
2023
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5. COVID-19 in cancer patients: update from the joint analysis of the ESMO-CoCARE, BSMO, and PSMO international databases

Author

Martin, P., Tsourti, Z., Ribeiro, J., Castelo-Branco, L., de Azambuja, E., Gennatas, S., Rogado, J., Sekacheva, M., Šušnjar, S., Viñal, D., Lee, R., Khallaf, S., Dimopoulou, G., Pradervand, S., Whisenant, J., Choueiri, T.K., Arnold, D., Harrington, K., Punie, K., Oliveira, J., Michielin, O., Dafni, U., Peters, S., Pentheroudakis, G., and Romano, E.

Published
2023
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9. COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE)

Author

Castelo-Branco, L., Tsourti, Z., Gennatas, S., Rogado, J., Sekacheva, M., Viñal, D., Lee, R., Croitoru, A., Vitorino, M., Khallaf, S., Šušnjar, S., Soewoto, W., Cardeña, A., Djerouni, M., Rossi, M., Alonso-Gordoa, T., Ngelangel, C., Whisenant, J.G., Choueiri, T.K., Dimopoulou, G., Pradervand, S., Arnold, D., Harrington, K., Michielin, O., Dafni, U., Pentheroudakis, G., Peters, S., and Romano, E.

Published
2022
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10. Learning lessons from the COVID-19 pandemic for real-world evidence research in oncology—shared perspectives from international consortia

Author

Castelo-Branco, L., primary, Lee, R., additional, Brandão, M., additional, Cortellini, A., additional, Freitas, A., additional, Garassino, M., additional, Geukens, T., additional, Grivas, P., additional, Halabi, S., additional, Oliveira, J., additional, Pinato, D.J., additional, Ribeiro, J., additional, Peters, S., additional, Pentheroudakis, G., additional, Warner, J.L., additional, and Romano, E., additional

Published
2023
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12. Comprehensive mapping review of real-world evidence publications focusing on targeted therapies in solid tumors : A collaborative work from ESMO real-world data and Digital Health Working Group

Author

Pellat, A., Grinda, T., Prelaj, A., Cresta, P., Valachis, A, Zerdes, I., Branco, D. Martins, Provenzano, L., Spagnoletti, A., Marta, G. Nader, Wilson, B., Montemurro, F., Castelo-Branco, L., Pentheroudakis, G., Delaloge, S., Koopman, M., Pellat, A., Grinda, T., Prelaj, A., Cresta, P., Valachis, A, Zerdes, I., Branco, D. Martins, Provenzano, L., Spagnoletti, A., Marta, G. Nader, Wilson, B., Montemurro, F., Castelo-Branco, L., Pentheroudakis, G., Delaloge, S., and Koopman, M.

Abstract

Background: A growing body of real-world evidence (RWE) aims to better reflect outcomes of cancer patients treated in real-world settings. We aimed to conduct a first comprehensive mapping review of the RWE produced over the past 3 years in terms of tumor type, treatment strategies, setting, and data sources, focusing on targeted therapies (TT) in solid tumors. Methods: We conducted a systematic review in PubMed of RWE studies published between 01/2020 and 12/2022. We identified non-interventional studies using observational data, focusing on solid tumors exposure to targeted therapies, excluding immunotherapies. Abstract and full-text screening were performed by 11 independent reviewers. Results: A total of 7,774 publications were retrieved with 1,251 considered eligible and extracted. The number of publications per year progressively increased during this period (328 in 2020; 421 in 2021; 502 in 2022). Most studies (50%) were performed in Asia, followed by Europe (25%) and North America (17%). Only 8% of studies had patients treated in more than one country. Treatment effectiveness and safety were assessed in 71% and 42% of studies respectively. Main data sources were medical records. Conclusions: RWE publications on TT for solid tumors are heterogeneous and mostly rely on retrospective data such as medical records. Population-based and international studies are rare. Collaborative efforts towards international representativeness and the use of routinely collected and/or standardized data sources must be encouraged to increase the relevance and future quality of publications and their potential impact on oncology practice.

Published
2023
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13. Real-world evidence contributions to European medicines agency's safety and efficacy evaluations of oncology targeted therapies between 2018-2022

Author

Derksen, J. W. G., Branco, D. Martins, Pellat, A., Van Nassau, S. C. M. W., Valachis, A., Aggarwal, A., Koopman, M., Pentheroudakis, G., Castelo-Branco, L., Delaloge, S., Derksen, J. W. G., Branco, D. Martins, Pellat, A., Van Nassau, S. C. M. W., Valachis, A., Aggarwal, A., Koopman, M., Pentheroudakis, G., Castelo-Branco, L., and Delaloge, S.

Abstract

Background: While Real-world Evidence (RWE) has documented value for safety monitoring and disease epidemiology, its objective contribution to safety and efficacy evaluations for regulatory purposes is still unclear. Here, we aim to describe the prevalence and type of RWE considered by European Medicines Agency (EMA) as contribution to efficacy and safety-related evidence generation among approved oncology targeted therapies... Methods: On March 10, 2023, we screened the medicines listing of EMA to identify all anti-cancer targeted therapies for solid malignancies with a decision date (initial marketing authorizations and extension of indications) between 2018-2022. We screened the European public assessment reports (EPARs) using a standardized approach to collect data on RWE. When generated pre-authorization, the RWE contribution to the final regulatory decision was classified as definitive, supportive, or non-supportive. For... Results: Out of a total of 1976 medicines, we identified 55 oncology targeted therapies, corresponding to 75 EPARs (indications), which are described in the table. The use of RWE in regulatory deliberations occurred in 24/75 (32%) EPARs, increasing from 30% in 2018-2020, to 34% in 2021-2022. Pre-authorization RWE was described in 20/24 (83%) EPARs, among which none were definitive, 8 RWE studies (in 7 EPARs) non-supportive, and 20 RWE studies (in 15 EPARs) were supportive of the decision. Published RWE... Conclusions: Over the past 5 years, RWE involvement in the approval of oncology targeted therapies in Europe tends to increase, with the majority being supportive for EMA regulatory decision making complementary to traditional clinical trials...

Published
2023
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14. ESMO Guidance for Reporting Oncology real-World evidence (GROW)

Author

Epi Kanker Team B, Cancer, MS Medische Oncologie, Infection & Immunity, Castelo-Branco, L, Pellat, A, Martins-Branco, D, Valachis, A, Derksen, J W G, Suijkerbuijk, K P M, Dafni, U, Dellaporta, T, Vogel, A, Prelaj, A, Groenwold, R H H, Martins, H, Stahel, R, Bliss, J, Kather, J, Ribelles, N, Perrone, F, Hall, P S, Dienstmann, R, Booth, C M, Pentheroudakis, G, Delaloge, S, Koopman, M, Epi Kanker Team B, Cancer, MS Medische Oncologie, Infection & Immunity, Castelo-Branco, L, Pellat, A, Martins-Branco, D, Valachis, A, Derksen, J W G, Suijkerbuijk, K P M, Dafni, U, Dellaporta, T, Vogel, A, Prelaj, A, Groenwold, R H H, Martins, H, Stahel, R, Bliss, J, Kather, J, Ribelles, N, Perrone, F, Hall, P S, Dienstmann, R, Booth, C M, Pentheroudakis, G, Delaloge, S, and Koopman, M

Published
2023

15. 237P Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: A joint analysis of OnCovid and ESMO-CoCARE registries

Author

Cortellini, A., primary, Dettorre, G., additional, Dafni, U., additional, Aguilar Company, J., additional, Castelo-Branco, L., additional, Lambertini, M., additional, Gennatas, S., additional, Rogado, J., additional, Vinal Lozano, D., additional, Harrington, K.J., additional, Tsourti, Z., additional, Michielin, O.A., additional, Pommeret, F., additional, Brunet Vidal, J.M., additional, Tabernero, J., additional, Pentheroudakis, G., additional, Gennari, A., additional, Peters, S., additional, Romano, E., additional, and Pinato, D.J., additional

Published
2022
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16. LBA70 COVID-19 in cancer patients: Update from the joint analysis of ESMO-CoCARE, BSMO, PSMO international databases

Author

Romano, E., primary, Castelo-Branco, L., additional, Tsourti, Z., additional, de Azambuja, E., additional, Gennatas, S., additional, Oliveira, J., additional, Rogado, J., additional, Sekacheva, M., additional, Susnjar, S., additional, Lozano, D. Vinal, additional, Lee, R., additional, Khallaf, S.M., additional, Dimopoulou, G., additional, Pradervand, S., additional, Arnold, D., additional, Harrington, K.J., additional, Michielin, O.A., additional, Dafni, U., additional, Pentheroudakis, G., additional, and Peters, S., additional

Published
2022
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17. COVID-19 in patients with cancer: first report of the ESMO international, registry-based, cohort study (ESMO-CoCARE)

Author

Castelo-Branco, L. Tsourti, Z. Gennatas, S. Rogado, J. Sekacheva, M. Viñal, D. Lee, R. Croitoru, A. Vitorino, M. Khallaf, S. Šušnjar, S. Soewoto, W. Cardeña, A. Djerouni, M. Rossi, M. Alonso-Gordoa, T. Ngelangel, C. Whisenant, J.G. Choueiri, T.K. Dimopoulou, G. Pradervand, S. Arnold, D. Harrington, K. Michielin, O. Dafni, U. Pentheroudakis, G. Peters, S. Romano, E.

Abstract

Background: ESMO COVID-19 and CAncer REgistry (ESMO-CoCARE) is an international collaborative registry-based, cohort study gathering real-world data from Europe, Asia/Oceania and Africa on the natural history, management and outcomes of patients with cancer infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Patients and methods: ESMO-CoCARE captures information on patients with solid/haematological malignancies, diagnosed with coronavirus disease 2019 (COVID-19). Data collected since June 2020 include demographics, comorbidities, laboratory measurements, cancer characteristics, COVID-19 clinical features, management and outcome. Parameters influencing COVID-19 severity/recovery were investigated as well as factors associated with overall survival (OS) upon SARS-CoV-2 infection. Results: This analysis includes 1626 patients from 20 countries (87% from 24 European, 7% from 5 North African, 6% from 8 Asian/Oceanian centres), with COVID-19 diagnosis from January 2020 to May 2021. Median age was 64 years, with 52% of female, 57% of cancer stage III/IV and 65% receiving active cancer treatment. Nearly 64% patients required hospitalization due to COVID-19 diagnosis, with 11% receiving intensive care. In multivariable analysis, male sex, older age, Eastern Cooperative Oncology Group (ECOG) performance status ≥2, body mass index (BMI)

Published
2022

18. The Economic Burden of Localized Prostate Cancer and Insights Derived from Cost-Effectiveness Studies of the Different Treatments

Author

Cantarero-Prieto D, Lera J, Lanza-Leon P, Barreda-Gutierrez M, Guillem-Porta V, Castelo-Branco L, and Martin-Moreno J

Subjects
localized prostate cancer, economic burden, cost of illness, cost-effectiveness analysis
Abstract

Simple Summary Prostate cancer is one of the most frequent and impacting malignant neoplasms for men. In particular, localized prostate cancer has a notably high incidence and prevalence, despite which a solid consensus on treatment and procedure of care has not yet been reached. This article aims to shed light on this challenge by characterizing the economic burden and cost-effectiveness of different treatment strategies for localized prostate cancer after analyzing published comparable data from studies conducted in OECD countries. Prostate cancer has huge health and societal impacts, and there is no clear consensus on the most effective and efficient treatment strategy for this disease, particularly for localized prostate cancer. We have reviewed the scientific literature describing the economic burden and cost-effectiveness of different treatment strategies for localized prostate cancer in OECD countries. We initially identified 315 articles, studying 13 of them in depth (those that met the inclusion criteria), comparing the social perspectives of cost, time period, geographical area, and severity. The economic burden arising from prostate cancer due to losses in productivity and increased caregiver load is noticeable, but clinical decision-making is carried out with more subjective variability than would be advisable. The direct cost of the intervention was the main driver for the treatment of less severe cases of prostate cancer, whereas for more severe cases, the most important determinant was the loss in productivity. Newer, more affordable radiotherapy strategies may play a crucial role in the future treatment of early prostate cancer. The interpretation of our results depends on conducting thorough sensitivity analyses. This approach may help better understand parameter uncertainty and the methodological choices discussed in health economics studies. Future results of ongoing clinical trials that are considering genetic characteristics in assessing treatment response of patients with localized prostate cancer may shed new light on important clinical and pharmacoeconomic decisions.

Published
2022

19. Beyond the lessons learned from the COVID-19 pandemic: opportunities to optimize clinical trial implementation in oncology

Author

Castelo-Branco, L., primary, Awada, A., additional, Pentheroudakis, G., additional, Perez-Gracia, J.L., additional, Mateo, J., additional, Curigliano, G., additional, Banerjee, S., additional, Giuliani, R., additional, Lordick, F., additional, Cervantes, A., additional, Tabernero, J., additional, and Peters, S., additional

Published
2021
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20. 1567MO COVID-19 and cancer: First report of the ESMO international, registry-based, cohort study (ESMO CoCARE)

Author

Romano, E., primary, Gennatas, S., additional, Rogado, J., additional, Sekacheva, M., additional, Viñal, D., additional, Lee, R., additional, Croitoru, A-E., additional, Vitorino, M., additional, Khallaf, S.M., additional, Susnjar, S., additional, Widyanti, S., additional, Cardeña, A., additional, Djerouni, M., additional, Rossi, M., additional, Arnold, D., additional, Castelo-Branco, L., additional, Harrington, K.J., additional, Michielin, O.A., additional, Pentheroudakis, G., additional, and Peters, S., additional

Published
2021
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21. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Author

Kirmeier, E, Eriksson, L, Lewald, H, Jonsson Fagerlund, M, Hoeft, A, Hollmann, M, Meistelman, C, Hunter, J, Ulm, K, Blobner, M, Abad Gurumeta, A, Abernethy, C, Abigail, P, Achaibar, K, Adam, E, Afshari, A, Agudelo Montoya, M, Akgun, F, Aletti, G, Alkis, N, Allan, K, Allan, A, Allaouchiche, B, Allcock, C, Almasy, E, Amey, I, Amigoni, M, Andersen, E, Andersson, P, Anipchenko, N, Antunes, P, Armstrong, E, Aslam, T, Aslin, B, Assuncao, J, Ausserer, J, Avvai, M, Awad, N, Ayas Montero, B, Ayuso, M, Azevedo, P, Badarau, V, Badescu, R, Baiardo Redaelli, M, Baird, C, Baird, Y, Baker, T, Balaji, P, Balan, C, Balandin, A, Balescu-Arion, C, Baliuliene, V, Baltasar Isabel, J, Baluch, S, Bandrabur, D, Bankewitz, C, Barber, K, Barbera, F, Barcraft-Barnes, H, Barletti, V, Barnett, G, Baron, K, Barros, A, Barsan, V, Bartlett, P, Batistaki, C, Baumgarten, G, Baytas, V, Beauchamp, N, Becerra Cayetano, I, Bell, S, Bellandi, M, Belletti, A, Belmonte Cuenca, J, Benitez-Cano, A, Beretta, L, Berger, M, Bergmann, N, Bergmark, K, Bermudez Lopez, M, Bernotaite, M, Beurskens, C, Bidd, H, Bifulco, F, Bignami, E, Bilic, A, Bilskiene, D, Bischoff, P, Bishop, L, Bjonness, T, Blaylock, H, Blethyn, K, Blincoe, T, Blokhin, I, Blunt, N, Boer, C, Bois, G, Bonicolini, E, Booth, J, Borecka-Kedzierska, M, Borstnar, K, Borys, M, Boselli, E, Bouvet, L, Bouwman, A, Bowen, L, Bowrey, S, Boxall, L, Bozic, T, Bradley, T, Branco, T, Brazzi, L, Brazzoni, M, Brear, T, Brogly, N, Brohi, F, Broms, J, Bubliauskas, A, Bucolo, G, Buerkle, H, Buggy, D, Buhre, W, Bukauskas, T, Butturini, F, Byttner, A, Cabrera Diaz, I, Calderon, A, Calhau, R, Callejo, A, Cammu, G, Campesato, M, Can, O, Candeias, M, Cantor, A, Carise, E, Carmona, C, Carreteiro, J, Carrieri, C, Carter, A, Casal, M, Casanova, I, Cascella, M, Casero, L, Casiraghi, G, Castelo-Branco, L, Castro Arranz, C, Cernea, D, Cervantes, J, Chandler, B, Charnock, R, Chatzimicali, A, Chinery, E, Chishti, A, Chondhury, P, Christie, E, Christodoudiles, G, Ciardo, S, Cimpeanu, L, Cindea, I, Cinnella, G, Clark, S, Clayton, M, Cocu, S, Collyer, T, Colvin, C, Cope, S, Copeta, F, Copotoiu, S, Correia de Barros, F, Corso, R, Cortegiani, A, Costa, G, Cowton, A, Cox, N, Craig, J, Cricca, V, Cronin, J, Cunha, M, Cuomo, A, Curley, K, Czuczwar, M, Dabrowska, D, Damster, S, Danguy des Deserts, M, Daniliuc, A, Danninger, T, Darwish, I, Dascalu, C, Davies, K, Davies, S, De Boer, H, De Flaviis, A, De Selincourt, G, Deana, C, Debaene, B, Debreceni, G, Dedhia, J, Delgado Garcia, I, Della Rocca, G, Delroy-Buelles, L, Desai, T, Dhillon, P, Di Giacinto, I, Di Mauro, P, Diaz Gomez, T, Dimitrovski, A, Dinic, V, Dirzu, D, Divander, M, Dolinar, J, Domingues, S, Doolan, J, Downes, C, Dragoescu, N, Droc, G, Dum, E, Dumitrescu, A, Duncan, L, Dzurnakova, P, Eberl, S, Edwards, J, Edwards, M, Ekelund, K, Ekengren, P, Elghouty, E, Ellerkmann, R, Ellis, H, Elme, A, Ernst, T, Errando, C, Estenes, S, Ewaldsson, C, Farid, N, Featherstone, J, Febres, D, Fedorov, S, Feggeler, J, Feijten, P, Fellmann, T, Fernandez Candil, J, Fernandez Castineira, A, Fernandez Castineira, J, Fernando, A, Ferrando, C, Ferreira, L, Ferreira, P, Feyling, A, Filipescu, D, Fleischer, A, Floris, L, Foerster, U, Fox, B, Franke, U, Frasca, D, Frey, C, Frost, V, Fullin, G, Fumagalli, J, Furneval, J, Fusari, M, Gallacher, S, Galushka, S, Gambale, G, Gambino, I, Garcia-Perez, M, Garg, S, Garlak, J, Gavranovic, Z, Gavrilov, R, Gaynor, L, Gecaj Gashi, A, Georghiou, M, Gerjevic, B, Gferer, G, Giarratano, A, Gibson, A, Gievski, V, Giles, J, Gillberg, L, Gilowska, K, Gilsanz Rodriguez, F, Gioia, A, Giovannoni, C, Girotra, V, Gkinas, D, Gkiokas, G, Godoroja, D, Goebel, U, Goel, V, Gonzalez, M, Goranovic, T, Gornik-Wlaszczuk, E, Gosavi, S, Gottfridsson, P, Gottschalk, A, Granell, M, Granstrom, A, Grassetto, A, Greenwood, A, Grigoras, I, Grintescu, I, Gritsan, A, Gritsan, G, Grynyuk, A, Guadagnin, G, Guarnieri, M, Guclu, C, Guerrero Diez, M, Gunenc, F, Gunther, U, Gupta, P, Guttenthaler, V, Hack, Y, Hafisayena, A, Hagau, N, Haldar, J, Hales, D, Hanci, V, Hanna-Jumma, S, Harazim, H, Harlet, P, Harper, D, Harris, B, Harvey, O, Hashimi, M, Hawkins, L, Hayes, C, Heaton, J, Heier, T, Helliwell, L, Hemmes, S, Henderson, K, Hermanides, J, Hermanns, H, Herrera Hueso, B, Hestenes, S, Hettiarachchi, R, Highgate, J, Hodgson, K, Hoelbling, D, Holland, J, Horhota, L, Hormis, A, Hribar, R, Hua, A, Humphreys, S, Humphries, R, Humplikova, S, Hunt, J, Husnain, A, Hussein, A, Hyams, B, Iannuccelli, F, Ilette, K, Ilyas, C, Inan, T, India, I, Ionitav, V, Irwin, F, Jain, V, Janez, B, Jankovic, R, Jenkins, S, Jenko, M, Jimenez, R, Jimenez Gomez, B, Joachim, S, Joelsson-Alm, E, John, J, Jonikaite, L, Jovic, M, Jungwirth, B, Junke, E, Kabakov, B, Kadaoui, S, Kanski, A, Karadag, S, Karbonskiene, A, Karjagin, J, Kasnik, D, Katanolli, F, Katsika, E, Kaufmann, K, Keane, H, Kelly, M, Kent, M, Keraitiene, G, Khudhur, A, Khuenl-Brady, K, Kidd, L, King, S, Kirchgassner, K, Klancir, T, Klucniks, A, Knotzer, J, Knowlden, P, Koers, L, Kompan, J, Koneti, K, Kooij, F, Koolen, E, Koopman - van Gemert, A, Kopp, K, Korfiotis, D, Korolkov, O, Kosinova, M, Kostenberger, M, Kotzinger, O, Kovacevic, M, Kranke, P, Kranke, E, Kraus, C, Kraus, S, Kubitzek, C, Kucharski, R, Kucukguclu, S, Kudrashou, A, Kumar, V, Kummen, L, Kunit, C, Kushakovsky, V, Kuvaki, B, Kuzmanovska, B, Kyttari, A, Landoni, G, Lau, G, Lazarev, K, Legett, S, Legrottaglie, A, Leonardi, S, Leong, M, Lercher, H, Leuvrey, M, Leva, B, Levstek, M, Limb, J, Lindholm, E, Linton, F, Liperi, C, Lipski, F, Lirk, P, Lisi, A, Liskova, K, Lluch Oltra, A, Loganathan, V, Lombardi, S, Lopez, E, Lopez Rodriguez, M, Lorenzini, L, Lowicka, M, Lugovoy, A, Luippold, M, Lumb, A, Macas, A, Macgregor, M, Machado, H, Maciariello, M, Madeira, I, Maitan, S, Majewski, J, Maldini, B, Malewski, G, Manfredini, L, Manner, O, Marchand, B, Marcu, A, Margalef, J, Margarson, M, Marinheiro, L, Markic, A, Markovic Bozic, J, Marrazzo, F, Martin, J, Martin Ayuso, M, Martinez, E, Martino, E, Martinson, V, Marusic-Gaser, K, Mascarenhas, C, Mathis, C, Matsota, P, Mavrommati, E, Mazul Sunko, B, Mccourt, K, Mcgill, N, Mckee, R, Meco, B, Meier, S, Melbourne, S, Melbybrathen, G, Meli, A, Melia, A, Melotti, R, Menga, M, Mercer, P, Merotra, S, Mescolini, S, Metterlein, T, Michalov, M, Michlig, S, Midgley, S, Milic, M, Milojevic, M, Minana, A, Minto, G, Mirabella, L, Mirea, L, Mittelstadt, L, Moeglen, A, Moise, A, Mokini, Z, Molin, A, Molto, L, Monea, M, Montalto, F, Montgomery, J, Montgomery, C, Montillo, G, Moore, S, Moore, F, Moreira, Z, Moreno, T, Moreno, R, Moret, E, Moreton, S, Morgan, M, Moro Velasco, C, Morri, D, Moull, A, Moura, F, Mraz, P, Mrozek, K, Mukhtar, K, Muniyappa, S, Murray, H, Murthy, B, Mushambi, M, Nadolski, M, Nardelli, P, Nardin, G, Navarro Perez, R, Naveiro, A, Negri, M, Nesek Adam, V, Neskovic, V, Neuwersch, S, Neves, M, Nguyen, B, Ni Eochagain, A, Nicholas, C, Nightingale, J, Norrie, K, Novak-Jankovic, V, Novakova, A, Novillo, M, Numan, S, Oduro-Dominah, L, Oldner, A, Oliveira, I, Ologoiu, D, Oloktsidou, I, O'Reilly, R, Orlando, A, Ovezov, A, Ozbilgin, S, Paal, P, Padin Barreiro, L, Palugniok, R, Papaioannou, A, Papapostolou, K, Paranthaman, P, Pardey Bracho, G, Parente, S, Parfeni, A, Pasin, L, Passey, S, Pastor, E, Patch, S, Patil, A, Paunescu, M, Pehboeck, D, Pereira, M, Pereira, C, Perez Caballero, P, Perez Garcia, A, Perez Soto, A, Perez Tejero, G, Perez-Cerda, F, Pesenti, A, Petta, R, Philippe, S, Pickering, D, Pico Veloso, J, Pina, P, Pinho-Oliveira, V, Pinol, S, Pinto, R, Pistidda, L, Pitterle, M, Piwowarczyk, P, Plotnikova, O, Pohl, H, Poldermann, J, Polkovicova, L, Pompei, L, Popescu, M, Popovic, R, Pota, V, Potocnik, M, Potrec, B, Potter, A, Pramod, N, Prchalova, M, Preckel, B, Pugh, R, Pulletz, M, Radoeshki, A, Rafi, A, Ragazzi, R, Raineri Santi, M, Rajamanickam, T, Rajput, Z, Ramachandran, R, Ramasamy, R, Ramessur, S, Rao, R, Rasmussen, A, Rato, A, Razaque, U, Real Navacerrada, M, Reavley, C, Reid, J, 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Smith, N, Smith, T, Smitz, C, Smole, D, Sojcic, N, Soler Pedrola, M, Somanath, S, Sonksen, J, Sorella, M, Sormus, A, Soro, M, Soto, C, Spada, A, Spadaro, S, Spaeth, J, Sparr, H, Spielmann, A, Spindler-Vesel, A, Stamelos, M, Stancombe L, L, Stanculescu, A, Standl, T, Standley, T, Stanek, O, Stanisavljevic, S, Starczewska, M, Stauble, C, Steen, J, Stefan, O, Stell, E, Stera, C, Stevens, M, Stoerckel, M, Stosic, B, Stourac, P, Stroumpoulis, K, Struck, R, Suarez de la Rica, A, Sultanpori, A, Sundara Rajan, R, Suying, O, Svensen, C, Swan, L, Syrogianni, P, Sysiak, J, Szederjesi, J, Taddei, S, Tan Hao, E, Tanou, V, Tarabova, K, Tardaguila Sancho, P, Tarroso, M, Tartaglione, M, Taylor, E, Tbaily, L, Telford, R, Terenzoni, M, Theodoraki, K, Thornley, H, Tiganiuc, L, Toim, H, Tomescu, D, Tommasino, C, Toni, J, Toninelli, A, Toretti, I, Townley, S, Trepenaitis, D, Trethowan, B, Tsaousi, G, Tsiftsi, A, Tudor, A, Turan, G, Turhan, S, Unic-Stojanovic, D, Unterbuchner, C, Unzueta, C, Uranjek, J, 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M, Zuleika, M, Zupaneie, D, Kirmeier E., Eriksson L. I., Lewald H., Jonsson Fagerlund M., Hoeft A., Hollmann M., Meistelman C., Hunter J. M., Ulm K., Blobner M., Abad Gurumeta A., Abernethy C., Abigail P., Achaibar K., Adam E., Afshari A., Agudelo Montoya M. E., Akgun F. N., Aletti G., Alkis N., Allan K., Allan A., Allaouchiche B., Allcock C., Almasy E., Amey I., Amigoni M., Andersen E., Andersson P., Anipchenko N., Antunes P., Armstrong E., Aslam T. N., Aslin B., Assuncao J. P., Ausserer J., Avvai M., Awad N., Ayas Montero B., Ayuso M., Azevedo P., Badarau V., Badescu R., Baiardo Redaelli M., Baird C., Baird Y., Baker T., Balaji P., Balan C., Balandin A., Balescu-Arion C., Baliuliene V., Baltasar Isabel J., Baluch S. N., Bandrabur D., Bankewitz C., Barber K., Barbera F., Barcraft-Barnes H., Barletti V., Barnett G., Baron K., Barros A., Barsan V., Bartlett P., Batistaki C., Baumgarten G., Baytas V., Beauchamp N., Becerra Cayetano I. A., Bell S., Bellandi M., Belletti A., Belmonte Cuenca J., Benitez-Cano A., Beretta L., Berger M., Bergmann N., Bergmark K., Bermudez Lopez M., Bernotaite M., Beurskens C., Bidd H., Bifulco F., Bignami E., Bilic A., Bilskiene D., Bischoff P., Bishop L., Bjonness T., Blaylock H., Blethyn K., Blincoe T., Blokhin I., Blunt N., Boer C., Bois G., Bonicolini E., Booth J., Borecka-Kedzierska M., Borstnar K., Borys M., Boselli E., Bouvet L., Bouwman A., Bowen L., Bowrey S., Boxall L., Bozic T., Bradley T., Branco T., Brazzi L., Brazzoni M., Brear T., Brogly N., Brohi F., Broms J., Bubliauskas A., Bucolo G. E., Buerkle H., Buggy D., Buhre W., Bukauskas T., Butturini F., Byttner A., Cabrera Diaz I., Calderon A., Calhau R., Callejo A., Cammu G., Campesato M., Can O. S., Candeias M., Cantor A., Carise E., Carmona C., Carreteiro J., Carrieri C., Carter A., Casal M., Casanova I., Cascella M., Casero L. M., Casiraghi G. M., Castelo-Branco L., Castro Arranz C., Cernea D. D., Cervantes J., Chandler B., Charnock R., Chatzimicali A., Chinery E., Chishti A., Chondhury P., Christie E., Christodoudiles G., Ciardo S., Cimpeanu L., Cindea I., Cinnella G., Clark S., Clayton M., Cocu S., Collyer T., Colvin C., Cope S., Copeta F., Copotoiu S. -M., Correia de Barros F., Corso R. M., Cortegiani A., Costa G., Cowton A., Cox N., Craig J., Cricca V., Cronin J., Cunha M., Cuomo A., Curley K., Czuczwar M., Dabrowska D., Damster S., Danguy des Deserts M., Daniliuc A., Danninger T., Darwish I., Dascalu C., Davies K., Davies S., De Boer H., De Flaviis A., De Selincourt G., Deana C., Debaene B., Debreceni G., Dedhia J., Delgado Garcia I., Della Rocca G., Delroy-Buelles L., Desai T., Dhillon P., Di Giacinto I., Di Mauro P., Diaz Gomez T. V., Dimitrovski A., Dinic V., Dirzu D. -S., Divander M. B., Dolinar J., Domingues S., Doolan J., Downes C., Dragoescu N. A., Droc G., Dum E., Dumitrescu A., Duncan L., Dzurnakova P., Eberl S., Edwards J., Edwards M., Ekelund K., Ekengren P., Elghouty E., Ellerkmann R., Ellis H., Elme A., Ernst T., Errando C. L., Estenes S., Ewaldsson C., Farid N., Featherstone J., Febres D., Fedorov S., Feggeler J., Feijten P., Fellmann T., Fernandez Candil J., Fernandez Castineira A., Fernandez Castineira J., Fernando A., Ferrando C., Ferreira L., Ferreira P., Feyling A., Filipescu D., Fleischer A., Floris L., Foerster U., Fox B., Franke U., Frasca D., Frey C., Frost V., Fullin G., Fumagalli J., Furneval J., Fusari M., Gallacher S., Galushka S., Gambale G., Gambino I., Garcia-Perez M. L., Garg S., Garlak J., Gavranovic Z., Gavrilov R., Gaynor L., Gecaj Gashi A., Georghiou M., Gerjevic B., Gferer G., Giarratano A., Gibson A., Gievski V., Giles J., Gillberg L., Gilowska K., Gilsanz Rodriguez F., Gioia A., Giovannoni C., Girotra V., Gkinas D., Gkiokas G., Godoroja D., Goebel U., Goel V., Gonzalez M., Goranovic T., Gornik-Wlaszczuk E., Gosavi S., Gottfridsson P., Gottschalk A., Granell M., Granstrom A., Grassetto A., Greenwood A., Grigoras I., Grintescu I., Gritsan A., Gritsan G., Grynyuk A., Guadagnin G. M., Guarnieri M., Guclu C., Guerrero Diez M., Gunenc F., Gunther U., Gupta P., Guttenthaler V., Hack Y., Hafisayena A., Hagau N., Haldar J., Hales D., Hanci V., Hanna-Jumma S., Harazim H., Harlet P., Harper D., Harris B., Harvey O., Hashimi M., Hawkins L., Hayes C., Heaton J., Heier T., Helliwell L., Hemmes S., Henderson K., Hermanides J., Hermanns H., Herrera Hueso B., Hestenes S., Hettiarachchi R., Highgate J., Hodgson K., Hoelbling D., Holland J., Horhota L., Hormis A., Hribar R., Hua A., Humphreys S., Humphries R., Humplikova S., Hunt J., Husnain A., Hussein A., Hyams B., Iannuccelli F., Ilette K., Ilyas C., Inan T., India I., Ionitav V., Irwin F., Jain V., Janez B., Jankovic R., Jenkins S., Jenko M., Jimenez R., Jimenez Gomez B., Joachim S., Joelsson-Alm E., John J., Jonikaite L., Jovic M., Jungwirth B., Junke E., Kabakov B., Kadaoui S. -D., Kanski A., Karadag S., Karbonskiene A., Karjagin J., Kasnik D., Katanolli F., Katsika E., Kaufmann K., Keane H., Kelly M., Kent M., Keraitiene G., Khudhur A., Khuenl-Brady K., Kidd L., King S., Kirchgassner K., Klancir T., Klucniks A., Knotzer J., Knowlden P., Koers L., Kompan J., Koneti K. K., Kooij F., Koolen E., Koopman - van Gemert A. W. M. M., Kopp K., Korfiotis D., Korolkov O., Kosinova M., Kostenberger M., Kotzinger O., Kovacevic M., Kranke P., Kranke E., Kraus C., Kraus S., Kubitzek C., Kucharski R., Kucukguclu S., Kudrashou A., Kumar V., Kummen L., Kunit C., Kushakovsky V., Kuvaki B., Kuzmanovska B., Kyttari A., Landoni G., Lau G., Lazarev K., Legett S., Legrottaglie A. M., Leonardi S., Leong M., Lercher H., Leuvrey M., Leva B., Levstek M., Limb J., Lindholm E., Linton F., Liperi C., Lipski F., Lirk P., Lisi A., Liskova K., Lluch Oltra A., Loganathan V., Lombardi S., Lopez E., Lopez Rodriguez M., Lorenzini L., Lowicka M., Lugovoy A., Luippold M., Lumb A., Macas A., Macgregor M., Machado H., Maciariello M., Madeira I., Maitan S., Majewski J., Maldini B., Malewski G., Manfredini L., Manner O., Marchand B., Marcu A., Margalef J., Margarson M., Marinheiro L., Markic A., Markovic Bozic J., Marrazzo F., Martin J., Martin Ayuso M., Martinez E., Martino E. A., Martinson V., Marusic-Gaser K., Mascarenhas C., Mathis C., Matsota P., Mavrommati E., Mazul Sunko B., McCourt K., McGill N., McKee R., Meco B. C., Meier S., Melbourne S., Melbybrathen G., Meli A., Melia A., Melotti R. M., Menga M. R., Mercer P., Merotra S., Mescolini S., Metterlein T., Michalov M., Michlig S., Midgley S., Milic M., Milojevic M., Minana A., Minto G., Mirabella L., Mirea L., Mittelstadt L., Moeglen A., Moise A., Mokini Z., Molin A., Molto L., Monea M. C., Montalto F., Montgomery J., Montgomery C., Montillo G., Moore S., Moore F., Moreira Z., Moreno T., Moreno R., Moret E., Moreton S., Morgan M., Moro Velasco C., Morri D., Moull A., Moura F., Mraz P., Mrozek K., Mukhtar K., Muniyappa S., Murray H., Murthy B. V., Mushambi M., Nadolski M., Nardelli P., Nardin G., Navarro Perez R., Naveiro A., Negri M., Nesek Adam V., Neskovic V., Neuwersch S., Neves M., Nguyen B., Ni Eochagain A., Nicholas C., Nightingale J., Norrie K., Novak-Jankovic V., Novakova A., Novillo M., Numan S., Oduro-Dominah L., Oldner A., Oliveira I., Ologoiu D., Oloktsidou I., O'Reilly R., Orlando A., Ovezov A., Ozbilgin S., Paal P., Padin Barreiro L., Palugniok R., Papaioannou A., Papapostolou K., Paranthaman P., Pardey Bracho G., Parente S., Parfeni A., Pasin L., Passey S., Pastor E., Patch S., Patil A., Paunescu M. -A., Pehboeck D., Pereira M., Pereira C., Perez Caballero P., Perez Garcia A., Perez Soto A., Perez Tejero G., Perez-Cerda F., Pesenti A., Petta R., Philippe S., Pickering D., Pico Veloso J., Pina P., Pinho-Oliveira V., Pinol S., Pinto R., Pistidda L., Pitterle M., Piwowarczyk P., Plotnikova O., Pohl H., Poldermann J., Polkovicova L., Pompei L., Popescu M., Popovic R., Pota V., Potocnik M., Potrec B., Potter A., Pramod N., Prchalova M., Preckel B., Pugh R., Pulletz M., Radoeshki A., Rafi A., Ragazzi R., Raineri Santi M., Rajamanickam T., Rajput Z., Ramachandran R., Ramasamy R., Ramessur S., Rao R., Rasmussen A., Rato A., Razaque U., Real Navacerrada M. I., Reavley C., Reid J., Reschreiter H., Rial E., Ribas Carrasco P., Ribeiro S., Rich N., Richardson L., Rimaitis K., Rimaitis M., Ringvold E. -M., Ripke F., Ristescu I., Ritchie K., Rodenas F., Rodrigues P., Rogers E., Rogerson D., Romagnoli S., Romero E., Rondovic G., Rose B. O., Roth W., Rotter M. -T., Rousseau G., Rudjord A., Rueffert H., Rundgren M., Rupprecht K., Rushton A., Russotto V., Rypulak E., Ryszka M., Sa J., Sa Couto P., Saby S., Sagic J., Saleh O., Sales G., Sanchez Sanchez Y., Sanghera S., Sanli Karip C., Santiveri Papiol F. J., Santos S., Sarno S., Saul D., Saunders D., Savic N., Scalco L., Scanlon D., Schaller S., Schax C., Scheffer G. J., Schening A., Schiavone V., Schmidt-Ehrenberg F., Schmidt-Mutter C., Schonberg C., Schopflin C., Schreiber J. -U., Schultz M., Schurig M., Scott C., Sebestian S., Sehgal S., Sem V., Semenas E., Serafini E., Serchan P., Shields M., Shobha R., Shosholcheva M., Siamansour T., Siddaiah N., Siddiqi K., Sinclair R., Singh P., Singh R., Sinha A., Skinner A., Smee E., Smekalova O., Smith N., Smith T., Smitz C., Smole D., Sojcic N., Soler Pedrola M., Somanath S., Sonksen J., Sorella M. C., Sormus A., Soro M., Soto C., Spada A., Spadaro S., Spaeth J., Sparr H., Spielmann A., Spindler-Vesel A., Stamelos M., Stancombe L L., Stanculescu A., Standl T., Standley T., Stanek O., Stanisavljevic S., Starczewska M., Stauble C., Steen J., Stefan O. M., Stell E., Stera C., Stevens M., Stoerckel M., Stosic B., Stourac P., Stroumpoulis K., Struck R., Suarez de la Rica A., Sultanpori A., Sundara Rajan R., Suying O., Svensen C., Swan L., Syrogianni P., Sysiak J., Szederjesi J., Taddei S., Tan Hao E., Tanou V., Tarabova K., Tardaguila Sancho P., Tarroso M., Tartaglione M., Taylor E., Tbaily L., Telford R., Terenzoni M., Theodoraki K., Thornley H., Tiganiuc L., Toim H., Tomescu D., Tommasino C., Toni J., Toninelli A., Toretti I., Townley S., Trepenaitis D., Trethowan B., Tsaousi G., Tsiftsi A., Tudor A., Turan G., Turhan S. C., Unic-Stojanovic D., Unterbuchner C., Unzueta C., Uranjek J., Ursic T., Vaida S., Valldeperas Ferrer S., Valldeperas Hernandez M. I., Valsamidis D., Van Beek R., Van dasselaer N., Van Der Beek T., Van Duivenvoorde Y., van Klei W. A., Van Poorter F., Van Zaane B., Van Zundert T., Van Zyl R., Vargas Munoz A. M., Varsani N., Vasconcelos P., Vassilakis G., Vecchiatini T., Vecera L., Vercauteren M., Verdouw B., Verheyen V., Verri M., Vicari Sottosanti L. G., Vico M., Vidal Mitjans P., Vilardi A., Vissicchio D., Vitale G., Vitkovic B., Vizcaychipi M. P., Voicu A., Voje M., Volfova I., Volta C. A., Von Lutterotti T., von Tiesenhausen A., Vrecic-Slabe S., Vukcevic D., Vukovic R., Vullo P. A., Wade A., Wallberg H., Wallden J., Wallner J., Walther Sturesson L., Watson D., Weber S., Wegiel Leskiewiq A., Weller D., Wensing C., Werkmann M., Westberg H., Wikstrom E., Williams B., Wilson R., Wirth S., Wittmann M., Wood L., Wright S., Zachoval C., Zambon M., Zampieri S., Zampone S., Zangrillo A., Zani G., Zavackiene A., Zieglerder R., Zonneveldt H., Zsisku L., Zucker T. -P., Zukowski M., Zuleika M., Zupaneie D., Kirmeier, E, Eriksson, L, Lewald, H, Jonsson Fagerlund, M, Hoeft, A, Hollmann, M, Meistelman, C, Hunter, J, Ulm, K, Blobner, M, Abad Gurumeta, A, Abernethy, C, Abigail, P, Achaibar, K, Adam, E, Afshari, A, Agudelo Montoya, M, Akgun, F, Aletti, G, Alkis, N, Allan, K, Allan, A, Allaouchiche, B, Allcock, C, Almasy, E, Amey, I, Amigoni, M, Andersen, E, Andersson, P, Anipchenko, N, Antunes, P, Armstrong, E, Aslam, T, Aslin, B, Assuncao, J, Ausserer, J, Avvai, M, Awad, N, Ayas Montero, B, Ayuso, M, Azevedo, P, Badarau, V, Badescu, R, Baiardo Redaelli, M, Baird, C, Baird, Y, 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V., Mushambi M., Nadolski M., Nardelli P., Nardin G., Navarro Perez R., Naveiro A., Negri M., Nesek Adam V., Neskovic V., Neuwersch S., Neves M., Nguyen B., Ni Eochagain A., Nicholas C., Nightingale J., Norrie K., Novak-Jankovic V., Novakova A., Novillo M., Numan S., Oduro-Dominah L., Oldner A., Oliveira I., Ologoiu D., Oloktsidou I., O'Reilly R., Orlando A., Ovezov A., Ozbilgin S., Paal P., Padin Barreiro L., Palugniok R., Papaioannou A., Papapostolou K., Paranthaman P., Pardey Bracho G., Parente S., Parfeni A., Pasin L., Passey S., Pastor E., Patch S., Patil A., Paunescu M. -A., Pehboeck D., Pereira M., Pereira C., Perez Caballero P., Perez Garcia A., Perez Soto A., Perez Tejero G., Perez-Cerda F., Pesenti A., Petta R., Philippe S., Pickering D., Pico Veloso J., Pina P., Pinho-Oliveira V., Pinol S., Pinto R., Pistidda L., Pitterle M., Piwowarczyk P., Plotnikova O., Pohl H., Poldermann J., Polkovicova L., Pompei L., Popescu M., Popovic R., Pota V., Potocnik M., Potrec B., Potter A., Pramod N., Prchalova M., Preckel B., Pugh R., Pulletz M., Radoeshki A., Rafi A., Ragazzi R., Raineri Santi M., Rajamanickam T., Rajput Z., Ramachandran R., Ramasamy R., Ramessur S., Rao R., Rasmussen A., Rato A., Razaque U., Real Navacerrada M. I., Reavley C., Reid J., Reschreiter H., Rial E., Ribas Carrasco P., Ribeiro S., Rich N., Richardson L., Rimaitis K., Rimaitis M., Ringvold E. -M., Ripke F., Ristescu I., Ritchie K., Rodenas F., Rodrigues P., Rogers E., Rogerson D., Romagnoli S., Romero E., Rondovic G., Rose B. O., Roth W., Rotter M. -T., Rousseau G., Rudjord A., Rueffert H., Rundgren M., Rupprecht K., Rushton A., Russotto V., Rypulak E., Ryszka M., Sa J., Sa Couto P., Saby S., Sagic J., Saleh O., Sales G., Sanchez Sanchez Y., Sanghera S., Sanli Karip C., Santiveri Papiol F. J., Santos S., Sarno S., Saul D., Saunders D., Savic N., Scalco L., Scanlon D., Schaller S., Schax C., Scheffer G. J., Schening A., Schiavone V., Schmidt-Ehrenberg F., Schmidt-Mutter C., Schonberg C., Schopflin C., Schreiber J. -U., Schultz M., Schurig M., Scott C., Sebestian S., Sehgal S., Sem V., Semenas E., Serafini E., Serchan P., Shields M., Shobha R., Shosholcheva M., Siamansour T., Siddaiah N., Siddiqi K., Sinclair R., Singh P., Singh R., Sinha A., Skinner A., Smee E., Smekalova O., Smith N., Smith T., Smitz C., Smole D., Sojcic N., Soler Pedrola M., Somanath S., Sonksen J., Sorella M. C., Sormus A., Soro M., Soto C., Spada A., Spadaro S., Spaeth J., Sparr H., Spielmann A., Spindler-Vesel A., Stamelos M., Stancombe L L., Stanculescu A., Standl T., Standley T., Stanek O., Stanisavljevic S., Starczewska M., Stauble C., Steen J., Stefan O. M., Stell E., Stera C., Stevens M., Stoerckel M., Stosic B., Stourac P., Stroumpoulis K., Struck R., Suarez de la Rica A., Sultanpori A., Sundara Rajan R., Suying O., Svensen C., Swan L., Syrogianni P., Sysiak J., Szederjesi J., Taddei S., Tan Hao E., Tanou V., Tarabova K., Tardaguila Sancho P., Tarroso M., Tartaglione M., Taylor E., Tbaily L., Telford R., Terenzoni M., Theodoraki K., Thornley H., Tiganiuc L., Toim H., Tomescu D., Tommasino C., Toni J., Toninelli A., Toretti I., Townley S., Trepenaitis D., Trethowan B., Tsaousi G., Tsiftsi A., Tudor A., Turan G., Turhan S. C., Unic-Stojanovic D., Unterbuchner C., Unzueta C., Uranjek J., Ursic T., Vaida S., Valldeperas Ferrer S., Valldeperas Hernandez M. I., Valsamidis D., Van Beek R., Van dasselaer N., Van Der Beek T., Van Duivenvoorde Y., van Klei W. A., Van Poorter F., Van Zaane B., Van Zundert T., Van Zyl R., Vargas Munoz A. M., Varsani N., Vasconcelos P., Vassilakis G., Vecchiatini T., Vecera L., Vercauteren M., Verdouw B., Verheyen V., Verri M., Vicari Sottosanti L. G., Vico M., Vidal Mitjans P., Vilardi A., Vissicchio D., Vitale G., Vitkovic B., Vizcaychipi M. P., Voicu A., Voje M., Volfova I., Volta C. A., Von Lutterotti T., von Tiesenhausen A., Vrecic-Slabe S., Vukcevic D., Vukovic R., Vullo P. A., Wade A., Wallberg H., Wallden J., Wallner J., Walther Sturesson L., Watson D., Weber S., Wegiel Leskiewiq A., Weller D., Wensing C., Werkmann M., Westberg H., Wikstrom E., Williams B., Wilson R., Wirth S., Wittmann M., Wood L., Wright S., Zachoval C., Zambon M., Zampieri S., Zampone S., Zangrillo A., Zani G., Zavackiene A., Zieglerder R., Zonneveldt H., Zsisku L., Zucker T. -P., Zukowski M., Zuleika M., and Zupaneie D.

Abstract

Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary

Published
2019

24. Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

Author

Ekhtiari, H. (Hamed), Tavakoli, H. (Hosna), Addolorato, G. (Giovanni), Baeken, C. (Chris), Bonci, A. (Antonello), Campanella, S. (Salvatore), Castelo-Branco, L. (Luis), Challet-Bouju, G. (Gaëlle), Clark, V.P., Claus, E. (Eric), Dannon, P.N. (Pinhas N.), Del Felice, A. (Alessandra), den Uyl, T. (Tess), Diana, M. (Marco), di Giannantonio, M. (Massimo), Fedota, J.R. (John R.), Fitzgerald, P. (Paul), Gallimberti, L. (Luigi), Grall-Bronnec, M. (Marie), Herremans, S.C. (Sarah C.), Herrmann, M.J. (Martin J.), Jamil, A. (Asif), Khedr, E. (Eman), Kouimtsidis, C. (Christos), Kozak, K. (Karolina), Krupitsky, E. (Evgeny), Lamm, C. (Claus), Lechner, W.V. (William V.), Madeo, G. (Graziella), Malmir, N. (Nastaran), Martinotti, G. (Giovanni), McDonald, W.M. (William M.), Montemitro, C. (Chiara), Nakamura-Palacios, E.M. (Ester M.), Nasehi, M. (Mohammad), Noël, X. (Xavier), Nosratabadi, M. (Masoud), Paulus, M. (Martin), Pettorruso, M. (Mauro), Pradhan, B. (Basant), Praharaj, S.K. (Samir K.), Rafferty, H. (Haley), Sahlem, G. (Gregory), Salmeron, B.J. (Betty jo), Sauvaget, A. (Anne), Schluter, R.S. (Renée S.), Sergiou, C.S. (Carmen), Shahbabaie, A. (Alireza), Sheffer, C. (Christine), Spagnolo, P.A. (Primavera A.), Steele, V.R. (Vaughn R.), Yuan, T.-F. (Ti-fei), Dongen, J.D.M. (Josanne) van, Van Waes, V. (Vincent), Venkatasubramanian, G. (Ganesan), Verdejo-García, A. (Antonio), Verveer, I. (Ilse), Welsh, J.W. (Justine W.), Wesley, M.J. (Michael J.), Witkiewitz, K. (Katie), Yavari, F. (Fateme), Zarrindast, M.-R. (Mohammad-Reza), Zawertailo, L. (Laurie), Zhang, X. (Xiaochu), Cha, Y.-H. (Yoon-Hee), George, T.P. (Tony P.), Frohlich, F. (Flavio), Goudriaan, A.E. (Anna), Fecteau, S. (Shirley), Daughters, S.B. (Stacey B.), Stein, E.A. (Elliot A.), Fregni, F. (Felipe), Nitsche, M.A. (Michael A.), Zangen, A. (Abraham), Bikson, M. (Marom), Hanlon, C.A. (Colleen A.), Ekhtiari, H. (Hamed), Tavakoli, H. (Hosna), Addolorato, G. (Giovanni), Baeken, C. (Chris), Bonci, A. (Antonello), Campanella, S. (Salvatore), Castelo-Branco, L. (Luis), Challet-Bouju, G. (Gaëlle), Clark, V.P., Claus, E. (Eric), Dannon, P.N. (Pinhas N.), Del Felice, A. (Alessandra), den Uyl, T. (Tess), Diana, M. (Marco), di Giannantonio, M. (Massimo), Fedota, J.R. (John R.), Fitzgerald, P. (Paul), Gallimberti, L. (Luigi), Grall-Bronnec, M. (Marie), Herremans, S.C. (Sarah C.), Herrmann, M.J. (Martin J.), Jamil, A. (Asif), Khedr, E. (Eman), Kouimtsidis, C. (Christos), Kozak, K. (Karolina), Krupitsky, E. (Evgeny), Lamm, C. (Claus), Lechner, W.V. (William V.), Madeo, G. (Graziella), Malmir, N. (Nastaran), Martinotti, G. (Giovanni), McDonald, W.M. (William M.), Montemitro, C. (Chiara), Nakamura-Palacios, E.M. (Ester M.), Nasehi, M. (Mohammad), Noël, X. (Xavier), Nosratabadi, M. (Masoud), Paulus, M. (Martin), Pettorruso, M. (Mauro), Pradhan, B. (Basant), Praharaj, S.K. (Samir K.), Rafferty, H. (Haley), Sahlem, G. (Gregory), Salmeron, B.J. (Betty jo), Sauvaget, A. (Anne), Schluter, R.S. (Renée S.), Sergiou, C.S. (Carmen), Shahbabaie, A. (Alireza), Sheffer, C. (Christine), Spagnolo, P.A. (Primavera A.), Steele, V.R. (Vaughn R.), Yuan, T.-F. (Ti-fei), Dongen, J.D.M. (Josanne) van, Van Waes, V. (Vincent), Venkatasubramanian, G. (Ganesan), Verdejo-García, A. (Antonio), Verveer, I. (Ilse), Welsh, J.W. (Justine W.), Wesley, M.J. (Michael J.), Witkiewitz, K. (Katie), Yavari, F. (Fateme), Zarrindast, M.-R. (Mohammad-Reza), Zawertailo, L. (Laurie), Zhang, X. (Xiaochu), Cha, Y.-H. (Yoon-Hee), George, T.P. (Tony P.), Frohlich, F. (Flavio), Goudriaan, A.E. (Anna), Fecteau, S. (Shirley), Daughters, S.B. (Stacey B.), Stein, E.A. (Elliot A.), Fregni, F. (Felipe), Nitsche, M.A. (Michael A.), Zangen, A. (Abraham), Bikson, M. (Marom), and Hanlon, C.A. (Colleen A.)

Abstract

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Published
2019
Full Text
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25. Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

Author

Ekhtiari, H., Tavakoli, H., Addolorato, Giovanni, Baeken, C., Bonci, Antonello, Campanella, Salvatore, Castelo-Branco, L., Challet-Bouju, G., Clark, V. P., Claus, E., Dannon, P. N., Del Felice, A., den Uyl, T., Diana, Maria Letizia, Di Giannantonio, Massimo, Fedota, J. R., Fitzgerald, P., Gallimberti, L., Grall-Bronnec, M., Herremans, S. C., Herrmann, M. J., Jamil, A., Khedr, E., Kouimtsidis, C., Kozak, K., Krupitsky, E., Lamm, C., Lechner, W. V., Madeo, G., Malmir, N., Martinotti, Giovanni, Mcdonald, W. M., Montemitro, C., Nakamura-Palacios, E. M., Nasehi, M., Noel, X., Nosratabadi, M., Paulus, M., Pettorruso, Mauro, Pradhan, B., Praharaj, S. K., Rafferty, H., Sahlem, G., Salmeron, B. J., Sauvaget, A., Schluter, R. S., Sergiou, C., Shahbabaie, A., Sheffer, C., Spagnolo, P. A., Steele, V. R., Yuan, T. -F., van Dongen, J. D. M., Van Waes, V., Venkatasubramanian, G., Verdejo-Garcia, A., Verveer, I., Welsh, J. W., Wesley, M. J., Witkiewitz, K., Yavari, F., Zarrindast, M. -R., Zawertailo, L., Zhang, X., Cha, Y. -H., George, T. P., Frohlich, F., Goudriaan, A. E., Fecteau, S., Daughters, S. B., Stein, E. A., Fregni, F., Nitsche, M. A., Zangen, A., Bikson, M., Hanlon, C. A., Addolorato G. (ORCID:0000-0002-1522-9946), Bonci A., Campanella S., Diana M., di Giannantonio M., Martinotti G., Pettorruso M., Ekhtiari, H., Tavakoli, H., Addolorato, Giovanni, Baeken, C., Bonci, Antonello, Campanella, Salvatore, Castelo-Branco, L., Challet-Bouju, G., Clark, V. P., Claus, E., Dannon, P. N., Del Felice, A., den Uyl, T., Diana, Maria Letizia, Di Giannantonio, Massimo, Fedota, J. R., Fitzgerald, P., Gallimberti, L., Grall-Bronnec, M., Herremans, S. C., Herrmann, M. J., Jamil, A., Khedr, E., Kouimtsidis, C., Kozak, K., Krupitsky, E., Lamm, C., Lechner, W. V., Madeo, G., Malmir, N., Martinotti, Giovanni, Mcdonald, W. M., Montemitro, C., Nakamura-Palacios, E. M., Nasehi, M., Noel, X., Nosratabadi, M., Paulus, M., Pettorruso, Mauro, Pradhan, B., Praharaj, S. K., Rafferty, H., Sahlem, G., Salmeron, B. J., Sauvaget, A., Schluter, R. S., Sergiou, C., Shahbabaie, A., Sheffer, C., Spagnolo, P. A., Steele, V. R., Yuan, T. -F., van Dongen, J. D. M., Van Waes, V., Venkatasubramanian, G., Verdejo-Garcia, A., Verveer, I., Welsh, J. W., Wesley, M. J., Witkiewitz, K., Yavari, F., Zarrindast, M. -R., Zawertailo, L., Zhang, X., Cha, Y. -H., George, T. P., Frohlich, F., Goudriaan, A. E., Fecteau, S., Daughters, S. B., Stein, E. A., Fregni, F., Nitsche, M. A., Zangen, A., Bikson, M., Hanlon, C. A., Addolorato G. (ORCID:0000-0002-1522-9946), Bonci A., Campanella S., Diana M., di Giannantonio M., Martinotti G., and Pettorruso M.

Abstract

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Published
2019

26. Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries

Author

Alessio Cortellini, Gino M Dettorre, Urania Dafni, Juan Aguilar-Company, Luis Castelo-Branco, Matteo Lambertini, Spyridon Gennatas, Vasileios Angelis, Ailsa Sita-Lumsden, Jacobo Rogado, Paolo Pedrazzoli, David Viñal, Aleix Prat, Maura Rossi, Rossana Berardi, Teresa Alonso-Gordoa, Salvatore Grisanti, Georgia Dimopoulou, Paola Queirolo, Sylvain Pradervand, Alexia Bertuzzi, Mark Bower, Dirk Arnold, Ramon Salazar, Marco Tucci, Kevin J Harrington, Francesca Mazzoni, Uma Mukherjee, Zoi Tsourti, Olivier Michielin, Fanny Pommeret, Joan Brunet, Bruno Vincenzi, Giuseppe Tonini, Andrea Patriarca, Federica Biello, Marco Krengli, Josep Tabernero, George Pentheroudakis, Alessandra Gennari, Solange Peters, Emanuela Romano, David J Pinato, Institut Català de la Salut, [Cortellini A] Department of Surgery & Cancer, Hammersmith Hospital Campus, Imperial College London, London, UK. Medical Oncology, Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Italy. [Dettorre GM] Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA. [Dafni U] Laboratory of Biostatistics, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece. [Aguilar-Company J] Servei d’Oncologia Mèdica, Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Castelo-Branco L] Scientific and Medical Division, ESMO (European Society for Medical Oncology), Lugano, Switzerland. NOVA National School of Publich Health, NOVA University, Lisbon, Portugal. [Lambertini M] Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genoa, Genova, Italy. Medical Oncology Department, U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy, Vall d'Hebron Barcelona Hospital Campus, and Wellcome Trust

Subjects
Cytotoxicity, Immunologic, Cancer Research, Immunology, Immunoteràpia, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Immunotheraphy, Vacunes, Other subheadings::Other subheadings::/drug therapy [Other subheadings], Medical Oncology, COVID-19 (Malaltia), Cell-mediated cytotoxicity, neoplasias [ENFERMEDADES], Immunitat cel·lular, Immunogenicity, Vaccine, COVID-19 Testing, Neoplasms, Immunogenetics, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Immunology and Allergy, Humans, Immunologia, Vacunació, Registries, Immune Checkpoint Inhibitors, Pharmacology, Vaccines, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], SARS-CoV-2, Càncer - Tractament, terapéutica::terapia biológica::inmunomodulación::inmunoterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Vaccination, COVID-19, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Cancer patients, Cellular immunity, Citotoxicitat per mediació cel·lular, Neoplasms [DISEASES], Malalts de càncer, Oncology, Molecular Medicine, Immunotherapy, Immunogenètica
Abstract

BackgroundAs management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.MethodsIn a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.FindingsThe study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30(4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, pOverall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13–48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30(10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.0098).ConclusionAnti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2.

Published
2022

27. Beyond the lessons learned from the COVID-19 pandemic: opportunities to optimize clinical trial implementation in oncology

Author

L. Castelo-Branco, Florian Lordick, Susana Banerjee, Andrés Cervantes, Ahmad Awada, Solange Peters, Joaquin Mateo, Josep Tabernero, Jose Luis Perez-Gracia, G. Pentheroudakis, R. Giuliani, Giuseppe Curigliano, Institut Català de la Salut, [Castelo-Branco L, Pentheroudakis G] Scientific and Medical Division, European Society for Medical Oncology (ESMO), Lugano, Switzerland. [Awada A] Head of the Oncology Medicine Department, Institut Jules Bordet, Université libre de Bruxelles, Belgium. [Perez-Gracia JL] Department of Oncology, Clinica Universidad de Navarra, Pamplona, Spain. [Mateo J] Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Curigliano G] Istituto Europeo di Oncologia, IRCCS and University of Milano, Milano, Italy. [Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. UVic-UCC, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Oncology, Cancer Research, Telemedicine, medicine.medical_specialty, Oncologia, media_common.quotation_subject, Medical Oncology, profesiones sanitarias::medicina::medicina interna::oncología médica [DISCIPLINAS Y OCUPACIONES], Quality of life (healthcare), características del estudio::estudio clínico::ensayo clínico [CARACTERÍSTICAS DE PUBLICACIONES], Study Characteristics::Clinical Study::Clinical Trial [PUBLICATION CHARACTERISTICS], Internal medicine, Pandemic, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], medicine, Pandèmia de COVID-19, 2020, Humans, Quality (business), Health Occupations::Medicine::Internal Medicine::Medical Oncology [DISCIPLINES AND OCCUPATIONS], Pandemics, media_common, COVID-19, Pandemics/prevention & control, SARS-CoV-2, Surrogate endpoint, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], World population, Clinical trial, Editorial, Good clinical practice, Business, Assaigs clínics
Abstract

The COVID-19 pandemic affected millions of people globally with lasting effects on society, patients, investigators and health institutions. Clinical trials, our best tool to improve cancer treatment for patients through testing the clinical value of a new treatment, have been affected by the pandemic. The pandemic footprint represents both a risk of compromising development of new therapies and an opportunity to elicit discussion over a portfolio of broader reforms, applicable irrespective of pandemics, in order to improve the design and implementation of clinical trials in oncology. The administrative load should be reduced, without affecting the quality of research and principles of good clinical practice. Cancer centres are encouraged to adapt their research/operational structures to the requirements of molecular oncology and embrace novel trial designs. Technological and methodological leaps in telemedicine can convert physical to virtual visits while routine examinations may be performed in local institutions (co-research centres), maintaining adherence to good clinical and research practices. The adoption of broader inclusion criteria and clinically significant endpoints (survival, quality of life) should be promoted, co-existing with pathways for fast-track “conditional” drug approvals in areas of unmet need, based on surrogate endpoints that are linked to strict post-approval validation requirements. The utility of Real World Data as part of these validation requirements should be actively investigated. Lessons learnt from the SARS Cov2 pandemic can be developed in order to expand equitable access to clinical trials of a real world population, in a simplified and methodologically robust modus operandi, for the benefit of all our patients.

Published
2021

28. Post-anaesthesia pulmonary complications after use of muscle relaxants (POPULAR): a multicentre, prospective observational study

Author

Kirmeier E. a, Eriksson L. I. c, Lewald H. a, Jonsson Fagerlund, M. c Hoeft, A. f Hollmann, M. g Meistelman, C. e Hunter, J. M. d Ulm, K. b Blobner, M. aEmail Author, Abad Gurumeta, A. Abernethy, C. Abigail, P. Achaibar, K. Adam, E. Afshari, Agudelo Montoya, M. E. Akgün, F. N. Aletti, G. Alkış, N. Allan, K. Allan, A. Allaouchiche, B. Allcock, C. Almasy, E. Amey, I. Amigoni, M. Andersen, E. Andersson, P. Anipchenko, N. Antunes, P. Armstrong, E. Aslam, T. N. Aslin, B. Assunção, J. P. Ausserer, J. Avvai, M. Awad, Ayas Montero, B. Ayuso, M. Azevedo, P. Badarau, V. Badescu, Baiardo Redaelli, M. Baird, C. Baird, Y. Baker, T. Balaji, P. Bălan, C. Balandin, A. Balescu-Arion, C. Baliuliene, Baltasar Isabel, J. Baluch, S. N. Bandrabur, D. Bankewitz, C. Barber, K. Barbera, F. Barcraft-Barnes, H. Barletti, V. Barnett, G. Baron, K. Barros, A. Barsan, V. Bartlett, P. Batistaki, C. Baumgarten, G. Baytas, V. Beauchamp, Becerra Cayetano, I. A. Bell, S. Bellandi, M. Belletti, Belmonte Cuenca, J. Benitez-Cano, A. Beretta, L. Berger, M. Bergmann, N. Bergmark, Bermudez Lopez, M. Bernotaite, M. Beurskens, C. Bidd, H. Bifulco, F. Bignami, E. Bilic, A. Bilskiene, D. Bischoff, P. Bishop, L. Bjonness, T. Blaylock, H. Blethyn, K. Blincoe, T. Blokhin, I. Blunt, N. Boer, C. Bois, G. Bonicolini, E. Booth, J. Borecka-Kedzierska, M. Borstnar, K. Borys, M. Boselli, E. Bouvet, L. Bouwman, A. Bowen, L. Bowrey, S. Boxall, L. Božić, T. Bradley, T. Branco, T. Brazzi, L. Brazzoni, M. Brear, T. Brogly, N. Brohi, F. Broms, J. Bubliauskas, A. Bucolo, G. E. Buerkle, H. Buggy, D. Buhre, W. Bukauskas, T. Butturini, F. Byttner, Cabrera Díaz, I. Calderon, A. Calhau, R. Callejo, A. Cammu, G. Campesato, M. Can, Ö. S. Candeias, M. Cantor, A. Carise, E. Carmona, C. Carreteiro, J. Carrieri, C. Carter, A. Casal, M. Casanova, I. Cascella, M. Casero, L. M. Casiraghi, G. M. Castelo-Branco, Castro Arranz, C. Cernea, D. D. Cervantes, J. Chandler, B. Charnock, R. Chatzimicali, A. Chinery, E. Chishti, A. Chondhury, P. Christie, E. Christodoudiles, G. Ciardo, S. Cimpeanu, L. Cindea, I. Cinnella, G. Clark, S. Clayton, M. Cocu, S. Collyer, T. Colvin, C. Cope, S. Copeta, F. Copotoiu, S. -M., Correia de Barros, F. Corso, R. M. Cortegiani, A. Costa, G. Cowton, A. Cox, N. Craig, J. Cricca, V. Cronin, J. Cunha, M. Cuomo, A. Curley, K. Czuczwar, M. Dabrowska, D. Damster, Danguy des Déserts, M. Daniliuc, A. Danninger, T. Darwish, I. Dascalu, C. Davies, K. Davies, De Boer, De Flaviis, De Selincourt, G. Deana, C. Debaene, B. Debreceni, G. Dedhia, Delgado Garcia, Della Rocca, G. Delroy-Buelles, L. Desai, T. Dhillon, Di Giacinto, Di Mauro, Diaz Gomez, T. V. Dimitrovski, A. Dinic, V. Dîrzu, D. -S., Divander M. B., Dolinar J., Domingues S., Doolan J., Downes C., Dragoescu N. A., Droc G., Dum E., Dumitrescu A., Duncan L., Dzurňáková P., Eberl S., Edwards J., Edwards M., Ekelund K., Ekengren P., Elghouty E., Ellerkmann R., Ellis H., Elme A., Ernst T., Errando C. L., Estenes S., Ewaldsson C., Farid N., Featherstone J., Febres D., Fedorov S., Feggeler J., Feijten P., Fellmann T., Fernandez Candil, Fernandez Castineira, Fernández Castineira, J. Fernando, A. Ferrando, C. Ferreira, L. Ferreira, P. Feyling, A. Filipescu, D. Fleischer, A. Floris, L. Foerster, U. Fox, B. Franke, U. Frasca, D. Frey, C. Frost, V. Fullin, G. Fumagalli, J. Furneval, J. Fusari, M. Gallacher, S. Galushka, S. Gambale, G. Gambino, I. Garcia-Perez, M. L. Garg, S. Garlak, J. Gavranovic, Z. Gavrilov, R. Gaynor, Gecaj Gashi, A. Georghiou, M. Gerjevic, B. Gferer, G. Giarratano, A. Gibson, A. Gievski, V. Giles, J. Gillberg, L. Gilowska, Gilsanz Rodriguez, F. Gioia, A. Giovannoni, C. Girotra, V. Gkinas, D. Gkiokas, G. Godoroja, D. Goebel, U. Goel, V. Gonzalez, M. Goranovic, T. Gornik-Wlaszczuk, E. Gosavi, S. Gottfridsson, P. Gottschalk, A. Granell, M. Granstrom, A. Grassetto, A. Greenwood, A. Grigoras, I. Grintescu, I. Gritsan, A. Gritsan, G. Grynyuk, A. Guadagnin, G. M. Guarnieri, M. Güçlü, Guerrero Diez, M. Gunenc, F. Günther, U. Gupta, P. Guttenthaler, V. Hack, Y. Hafisayena, A. Hagau, N. Haldar, J. Hales, D. Hancı, V. Hanna-Jumma, S. Harazim, H. Harlet, P. Harper, D. Harris, B. Harvey, O. Hashimi, M. Hawkins, L. Hayes, C. Heaton, J. Heier, T. Helliwell, L. Hemmes, S. Henderson, K. Hermanides, J. Hermanns, Herrera Hueso, B. Hestenes, S. Hettiarachchi, R. Highgate, J. Hodgson, K. Hoelbling, D. Holland, J. Horhota, L. Hormis, A. Hribar, R. Hua, A. Humphreys, S. Humphries, R. Humpliková, S. Hunt, J. Husnain, A. Hussein, A. Hyams, B. Iannuccelli, F. Ilette, K. Ilyas, C. Inan, T. India, I. Ionițăv, V. Irwin, F. Jain, V. Janez, B. Jankovic, R. Jenkins, S. Jenko, M. Jimenez, Jiménez Gomez, B. Joachim, S. Joelsson-Alm, E. John, J. Jonikaite, L. Jovic, M. Jungwirth, B. Junke, E. Kabakov, B. Kadaoui, S. -D., Kanski A., Karadag S., Karbonskiene A., Karjagin J., Kasnik D., Katanolli F., Katsika E., Kaufmann K., Keane H., Kelly M., Kent M., Keraitiene G., Khudhur A., Khuenl-Brady K., Kidd L., King S., Kirchgäßner K., Klancir T., Klucniks A., Knotzer J., Knowlden P., Koers L., Kompan J., Koneti K. K., Kooij F., Koolen E., Koopman - van Gemert, A. W. M. M. Kopp, K. Korfiotis, D. Korolkov, O. Kosinová, M. Köstenberger, M. Kotzinger, O. Kovačević, M. Kranke, P. Kranke, E. Kraus, C. Kraus, S. Kubitzek, C. Kucharski, R. Kucukguclu, S. Kudrashou, A. Kumar, V. Kummen, L. Kunit, C. Kushakovsky, V. Kuvaki, B. Kuzmanovska, B. Kyttari, A. Landoni, G. Lau, G. Lazarev, K. Legett, S. Legrottaglie, A. M. Leonardi, S. Leong, M. Lercher, H. Leuvrey, M. Leva, B. Levstek, M. Limb, J. Lindholm, E. Linton, F. Liperi, C. Lipski, F. Lirk, P. Lisi, A. Lišková, Lluch Oltra, A. Loganathan, V. Lombardi, S. Lopez, Lopez Rodríguez, M. Lorenzini, L. Lowicka, M. Lugovoy, A. Luippold, M. Lumb, A. Macas, A. Macgregor, M. Machado, H. Maciariello, M. Madeira, I. Maitan, S. Majewski, J. Maldini, B. Malewski, G. Manfredini, L. Männer, O. Marchand, B. Marcu, A. Margalef, J. Margarson, M. Marinheiro, L. Markic, Markovic Bozic, J. Marrazzo, F. Martin, Martin Ayuso, M. Martinez, E. Martino, E. A. Martinson, V. Marusic-Gaser, K. Mascarenhas, C. Mathis, C. Matsota, P. Mavrommati, Mazul Sunko, B. McCourt, K. McGill, N. McKee, R. Meço, B. C. Meier, S. Melbourne, S. Melbybråthen, G. Meli, A. Melia, A. Melotti, R. M. Menga, M. R. Mercer, P. Merotra, S. Mescolini, S. Metterlein, T. Michalov, M. Michlig, S. Midgley, S. Milić, M. Milojevic, M. Miñana, A. Minto, G. Mirabella, L. Mirea, L. Mittelstädt, L. Moeglen, A. Moise, A. Mokini, Z. Molin, A. Moltó, L. Monea, M. C. Montalto, F. Montgomery, J. Montgomery, C. Montillo, G. Moore, S. Moore, F. Moreira, Z. Moreno, T. Moreno, R. Moret, E. Moreton, S. Morgan, Moro Velasco, C. Morri, D. Moull, A. Moura, F. Mráz, P. Mrozek, K. Mukhtar, K. Muniyappa, S. Murray, H. Murthy, B. V. Mushambi, M. Nadolski, M. Nardelli, P. Nardin, Navarro Pérez, R. Naveiro, A. Negri, Nesek Adam, V. Neskovic, V. Neuwersch, S. Neves, M. Nguyen, Ní Eochagáin, A. Nicholas, C. Nightingale, J. Norrie, K. Novak-Jankovic, V. Novakova, A. Novillo, M. Numan, S. Oduro-Dominah, L. Oldner, A. Oliveira, I. Ologoiu, D. Oloktsidou, I. O'Reilly, R. Orlando, A. Ovezov, A. Ozbilgin, S. Paal, Padin Barreiro, L. Palugniok, R. Papaioannou, A. Papapostolou, K. Paranthaman, Pardey Bracho, G. Parente, S. Parfeni, A. Pasin, L. Passey, S. Pastor, E. Patch, S. Patil, A. Paunescu, M. -A., Pehboeck D., Pereira M., Pereira C., Perez Caballero, Pérez García, Pérez Soto, Perez Tejero, G. Perez-Cerda, F. Pesenti, A. Petta, R. Philippe, S. Pickering, Pico Veloso, J. Pina, P. Pinho-Oliveira, V. Pinol, S. Pinto, R. Pistidda, L. Pitterle, M. Piwowarczyk, P. Plotnikova, O. Pohl, H. Poldermann, J. Polkovicová, L. Pompei, L. Popescu, M. Popović, Pota V, Potocnik M., Potręć B., Potter A., Pramod N., Prchalova M., Preckel B., Pugh R., Pulletz M., Radoeshki A., Rafi A., Ragazzi R., Raineri Santi, M. Rajamanickam, T. Rajput, Z. Ramachandran, R. Ramasamy, R. Ramessur, S. Rao, R. Rasmussen, A. Rato, A. Razaque, Real Navacerrada, M. I. Reavley, C. Reid, J. Reschreiter, H. Rial, Ribas Carrasco, P. Ribeiro, S. Rich, N. Richardson, L. Rimaitis, K. Rimaitis, M. Ringvold, E. -M., Ripke F., Ristescu I., Ritchie K., Ródenas F., Rodrigues P., Rogers E., Rogerson D., Romagnoli S., Romero E., Rondovic G., Rose B. O., Roth W., Rotter, M. -T., Rousseau G., Rudjord A., Rueffert H., Rundgren M., Rupprecht K., Rushton A., Russotto V., Rypulak E., Ryszka M., Sà J., Sà Couto, P. Saby, S. Sagic, J. Saleh, O. Sales, Sánchez Sánchez, Y. Sanghera, Şanli Karip, Santiveri Papiol, F. J. Santos, S. Sarno, S. Saul, D. Saunders, D. Savic, N. Scalco, L. Scanlon, D. Schaller, S. Schax, C. Scheffer, G. J. Schening, A. Schiavone, V. Schmidt-Ehrenberg, F. Schmidt-Mutter, C. Schönberg, C. Schopflin, C. Schreiber, J. -U., Schultz M., Schurig M., Scott C., Sebestian S., Sehgal S., Sem V., Semenas E., Serafini E., Serchan P., Shields M., Shobha R., Shosholcheva M., Siamansour T., Siddaiah N., Siddiqi K., Sinclair R., Singh P., Singh R., Sinha A., Skinner A., Smee E., Smekalova O., Smith N., Smith T., Smitz C., Smole D., Sojčić N., Soler Pedrola, M. Somanath, S. Sonksen, J. Sorella, M. C. Sörmus, A. Soro, M. Soto, C. Spada, A. Spadaro, S. Spaeth, J. Sparr, H. Spielmann, A. Spindler-Vesel, A. Stamelos, Stancombe L, L. Stanculescu, A. Standl, T. Standley, T. Stanek, O. Stanisavljević, S. Starczewska, M. Stäuble, C. Steen, J. Stefan, O. M. Stell, E. Stera, C. Stevens, M. Stoerckel, M. Stošić, B. Stourac, P. Stroumpoulis, K. Struck, Suarez de la Rica, A. Sultanpori, Sundara Rajan, R. Suying, O. Svensen, C. Swan, L. Syrogianni, P. Sysiak, J. Szederjesi, J. Taddei, Tan Hao, E. Tanou, V. Tarabová, Tardaguila Sancho, P. Tarroso, M. Tartaglione, M. Taylor, E. Tbaily, L. Telford, R. Terenzoni, M. Theodoraki, K. Thornley, H. Tiganiuc, L. Toim, H. Tomescu, D. Tommasino, C. Toni, J. Toninelli, A. Toretti, I. Townley, S. Trepenaitis, D. Trethowan, B. Tsaousi, G. Tsiftsi, A. Tudor, A. Turan, G. Turhan, S. Ç. Unic-Stojanovic, D. Unterbuchner, C. Unzueta, C. Uranjek, J. Ursic, T. Vaida, Valldeperas Ferrer, Valldeperas Hernandez, M. I. Valsamidis, Van Beek, Van dasselaer, Van Der Beek, Van Duivenvoorde, van Klei, W. A., Van Poorter, Van Zaane, Van Zundert, Van Zyl, Vargas Munoz, A. M. Varsani, N. Vasconcelos, P. Vassilakis, G. Vecchiatini, T. Vecera, L. Vercauteren, M. Verdouw, B. Verheyen, V. Verri, Vicari Sottosanti, L. G. Vico, Vidal Mitjans, P. Vilardi, A. Vissicchio, D. Vitale, G. Vitković, B. Vizcaychipi, M. P. Voicu, A. Voje, M. Volfová, I. Volta, C. A., Von Lutterotti, von Tiesenhausen, A. Vrecic-Slabe, S. Vukcevic, D. Vukovic, R. Vullo, P. A. Wade, A. Wallberg, H. Wallden, J. Wallner, Walther Sturesson, L. Watson, D. Weber, Wegiel Leskiewiq, A. Weller, D. Wensing, C. Werkmann, M. Westberg, H. Wikström, E. Williams, B. Wilson, R. Wirth, S. Wittmann, M. Wood, L. Wright, S. Zachoval, C. Zambon, M. Zampieri, S. Zampone, S. Zangrillo, A. Zani, G. Zavackiene, A. Zieglerder, R. Zonneveldt, H. Zsisku, L. Zucker, T. -P., Żukowski M., Zuleika M., Zupanĕiĕ D., Kirmeier, E. a., Eriksson, L. I. c., Lewald, H. a., Jonsson, Fagerlund, Hoeft, M. c., Hollmann, A. f., Meistelman, M. g., Hunter, C. e., Ulm, J. M. d., Blobner, K. b., M., aEmail Author, Abad, Gurumeta, A., Abernethy, C., Abigail, P., Achaibar, K., Adam, E., Afshari, Agudelo, Montoya, M. E., Akgün, F. N., Aletti, G., Alkış, N., Allan, K., Allan, A., Allaouchiche, B., Allcock, C., Almasy, E., Amey, I., Amigoni, M., Andersen, E., Andersson, P., Anipchenko, N., Antune, P., Armstrong, E., Aslam, T. N., Aslin, B., Assunção, J. P., Ausserer, J., Avvai, M., Awad, Ayas, Montero, B., Ayuso, M., Azevedo, P., Badarau, V., Badescu, Baiardo, Redaelli, M., Baird, C., Baird, Y., Baker, T., Balaji, P., Bălan, C., Balandin, A., Balescu-Arion, C., Baliuliene, Baltasar, Isabel, J., Baluch, S. N., Bandrabur, D., Bankewitz, C., Barber, K., Barbera, F., Barcraft-Barne, H., Barletti, V., Barnett, G., Baron, K., Barro, A., Barsan, V., Bartlett, P., Batistaki, C., Baumgarten, G., Bayta, V., Beauchamp, Becerra, Cayetano, I. A., Bell, S., Bellandi, M., Belletti, Belmonte, Cuenca, J., Benitez-Cano, A., Beretta, L., Berger, M., Bergmann, N., Bergmark, Bermudez, Lopez, M., Bernotaite, M., Beursken, C., Bidd, H., Bifulco, F., Bignami, E., Bilic, A., Bilskiene, D., Bischoff, P., Bishop, L., Bjonne, T., Blaylock, H., Blethyn, K., Blincoe, T., Blokhin, I., Blunt, N., Boer, C., Boi, G., Bonicolini, E., Booth, J., Borecka-Kedzierska, M., Borstnar, K., Bory, M., Boselli, E., Bouvet, L., Bouwman, A., Bowen, L., Bowrey, S., Boxall, L., Božić, T., Bradley, T., Branco, T., Brazzi, L., Brazzoni, M., Brear, T., Brogly, N., Brohi, F., Brom, J., Bubliauska, A., Bucolo, G. E., Buerkle, H., Buggy, D., Buhre, W., Bukauska, T., Butturini, F., Byttner, Cabrera, Díaz, I., Calderon, A., Calhau, R., Callejo, A., Cammu, G., Campesato, M., Can, Ö. S., Candeia, M., Cantor, A., Carise, E., Carmona, C., Carreteiro, J., Carrieri, C., Carter, A., Casal, M., Casanova, I., Cascella, M., Casero, L. M., Casiraghi, G. M., Castelo-Branco, Castro, Arranz, C., Cernea, D. D., Cervante, J., Chandler, B., Charnock, R., Chatzimicali, A., Chinery, E., Chishti, A., Chondhury, P., Christie, E., Christodoudile, G., Ciardo, S., Cimpeanu, L., Cindea, I., Cinnella, G., Clark, S., Clayton, M., Cocu, S., Collyer, T., Colvin, C., Cope, S., Copeta, F., Copotoiu, S., -M., Correia de, Barro, F., Corso, R. M., Cortegiani, A., Costa, G., Cowton, A., Cox, N., Craig, J., Cricca, V., Cronin, J., Cunha, M., Cuomo, A., Curley, K., Czuczwar, M., Dabrowska, D., Damster, Danguy des, Désert, M., Daniliuc, A., Danninger, T., Darwish, I., Dascalu, C., Davie, K., Davie, De, Boer, De, Flavii, De, Selincourt, G., Deana, C., Debaene, B., Debreceni, G., Dedhia, Delgado, Garcia, Della, Rocca, G., Delroy-Buelle, L., Desai, T., Dhillon, Di, Giacinto, Di, Mauro, Diaz, Gomez, T. V., Dimitrovski, A., Dinic, V., Dîrzu, D., -S., Divander, M. B., Dolinar, J., Domingues, S., Doolan, J., Downes, C., Dragoescu, N. A., Droc, G., Dum, E., Dumitrescu, A., Duncan, L., Dzurňáková, P., Eberl, S., Edwards, J., Edwards, M., Ekelund, K., Ekengren, P., Elghouty, E., Ellerkmann, R., Ellis, H., Elme, A., Ernst, T., Errando, C. L., Estenes, S., Ewaldsson, C., Farid, N., Featherstone, J., Febres, D., Fedorov, S., Feggeler, J., Feijten, P., Fellmann, T., Fernandez, Candil, Fernandez, Castineira, Fernández, Castineira, J., Fernando, A., Ferrando, C., Ferreira, L., Ferreira, P., Feyling, A., Filipescu, D., Fleischer, A., Flori, L., Foerster, U., Fox, B., Franke, U., Frasca, D., Frey, C., Frost, V., Fullin, G., Fumagalli, J., Furneval, J., Fusari, M., Gallacher, S., Galushka, S., Gambale, G., Gambino, I., Garcia-Perez, M. L., Garg, S., Garlak, J., Gavranovic, Z., Gavrilov, R., Gaynor, Gecaj, Gashi, A., Georghiou, M., Gerjevic, B., Gferer, G., Giarratano, A., Gibson, A., Gievski, V., Gile, J., Gillberg, L., Gilowska, Gilsanz, Rodriguez, F., Gioia, A., Giovannoni, C., Girotra, V., Gkina, D., Gkioka, G., Godoroja, D., Goebel, U., Goel, V., Gonzalez, M., Goranovic, T., Gornik-Wlaszczuk, E., Gosavi, S., Gottfridsson, P., Gottschalk, A., Granell, M., Granstrom, A., Grassetto, A., Greenwood, A., Grigora, I., Grintescu, I., Gritsan, A., Gritsan, G., Grynyuk, A., Guadagnin, G. M., Guarnieri, M., Güçlü, Guerrero, Diez, M., Gunenc, F., Günther, U., Gupta, P., Guttenthaler, V., Hack, Y., Hafisayena, A., Hagau, N., Haldar, J., Hale, D., Hancı, V., Hanna-Jumma, S., Harazim, H., Harlet, P., Harper, D., Harri, B., Harvey, O., Hashimi, M., Hawkin, L., Haye, C., Heaton, J., Heier, T., Helliwell, L., Hemme, S., Henderson, K., Hermanide, J., Hermann, Herrera, Hueso, B., Hestene, S., Hettiarachchi, R., Highgate, J., Hodgson, K., Hoelbling, D., Holland, J., Horhota, L., Hormi, A., Hribar, R., Hua, A., Humphrey, S., Humphrie, R., Humpliková, S., Hunt, J., Husnain, A., Hussein, A., Hyam, B., Iannuccelli, F., Ilette, K., Ilya, C., Inan, T., India, I., Ionițăv, V., Irwin, F., Jain, V., Janez, B., Jankovic, R., Jenkin, S., Jenko, M., Jimenez, Jiménez, Gomez, B., Joachim, S., Joelsson-Alm, E., John, J., Jonikaite, L., Jovic, M., Jungwirth, B., Junke, E., Kabakov, B., Kadaoui, S., -D., Kanski, A., Karadag, S., Karbonskiene, A., Karjagin, J., Kasnik, D., Katanolli, F., Katsika, E., Kaufmann, K., Keane, H., Kelly, M., Kent, M., Keraitiene, G., Khudhur, A., Khuenl-Brady, K., Kidd, L., King, S., Kirchgäßner, K., Klancir, T., Klucniks, A., Knotzer, J., Knowlden, P., Koers, L., Kompan, J., Koneti, K. K., Kooij, F., Koolen, E., Koopman, - van Gemert, A. W. M. M., Kopp, K., Korfioti, D., Korolkov, O., Kosinová, M., Köstenberger, M., Kotzinger, O., Kovačević, M., Kranke, P., Kranke, E., Krau, C., Krau, S., Kubitzek, C., Kucharski, R., Kucukguclu, S., Kudrashou, A., Kumar, V., Kummen, L., Kunit, C., Kushakovsky, V., Kuvaki, B., Kuzmanovska, B., Kyttari, A., Landoni, G., Lau, G., Lazarev, K., Legett, S., Legrottaglie, A. M., Leonardi, S., Leong, M., Lercher, H., Leuvrey, M., Leva, B., Levstek, M., Limb, J., Lindholm, E., Linton, F., Liperi, C., Lipski, F., Lirk, P., Lisi, A., Lišková, Lluch, Oltra, A., Loganathan, V., Lombardi, S., Lopez, Lopez, Rodríguez, M., Lorenzini, L., Lowicka, M., Lugovoy, A., Luippold, M., Lumb, A., Maca, A., Macgregor, M., Machado, H., Maciariello, M., Madeira, I., Maitan, S., Majewski, J., Maldini, B., Malewski, G., Manfredini, L., Männer, O., Marchand, B., Marcu, A., Margalef, J., Margarson, M., Marinheiro, L., Markic, Markovic, Bozic, J., Marrazzo, F., Martin, Martin, Ayuso, M., Martinez, E., Martino, E. A., Martinson, V., Marusic-Gaser, K., Mascarenha, C., Mathi, C., Matsota, P., Mavrommati, Mazul, Sunko, B., Mccourt, K., Mcgill, N., Mckee, R., Meço, B. C., Meier, S., Melbourne, S., Melbybråthen, G., Meli, A., Melia, A., Melotti, R. M., Menga, M. 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Elizabeth, Akgün, Fatma Nur, Aletti, Gabriele, Alkış, Neslihan, Allan, Katie, Allan, Ashley, Allaouchiche, Bernard, Allcock, Clare, Almasy, Emoke, Amey, Isobel, Amigoni, Maria, Andersen, Elin, Andersson, Peder, Anipchenko, Natalya, Antunes, Pedro, Armstrong, Earlene, Aslam, Tayyba Naz, Aslin, Bjorn, Assunção, José Pedro, Ausserer, Julia, Avvai, Mary, Awad, Nahla, Ayas Montero, Begoña, Ayuso, Mercede, Azevedo, Patricia, Badarau, Victoria, Badescu, Roxana, Baiardo Redaelli, Martina, Baird, Colin, Baird, Yolanda, Baker, Tim, Balaji, Packianathaswamy, Bălan, Cristina, Balandin, Alina, Balescu-Arion, Carmen, Baliuliene, Vilda, Baltasar Isabel, Jorge, Baluch, Saif Nasr, Bandrabur, Daniela, Bankewitz, Carla, Barber, Katrina, Barbera, Francesco, Barcraft-Barnes, Helena, Barletti, Valentina, Barnett, Gill, Baron, Kirsty, Barros, Ana, Barsan, Victoria, Bartlett, Pauline, Batistaki, Chrysanthi, Baumgarten, Georg, Baytas, Volkan, Beauchamp, Nigel, Becerra Cayetano, Isabel A., Bell, Stephanie, 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Ricardo, Callejo, Angel, Cammu, Guy, Campesato, Manuela, Can, Özlem S, Candeias, Margarida, Cantor, Andreea, Carise, Elsa, Carmona, Cristina, Carreteiro, Joana, Carrieri, Cosima, Carter, Anna, Casal, Manuela, Casanova, Irene, Cascella, Marco, Casero, Luis M., Casiraghi, Guiseppina Maria, Castelo-Branco, Laila, Castro Arranz, Carlo, Cernea, Daniela Denisa, Cervantes, Jesoporiol, Chandler, Ben, Charnock, Robert, Chatzimicali, Aikaterini, Chinery, Elane, Chishti, Ahmed, Chondhury, Priyakam, Christie, Emily, Christodoudiles, George, Ciardo, Stefano, Cimpeanu, Luminata, Cindea, Iulia, Cinnella, Gilda, Clark, Sebastian, Clayton, Matthew, Cocu, Simona, Collyer, Thoma, Colvin, Carie, Cope, Sean, Copeta, Filomena, Copotoiu, Sanda-Maria, Correia de Barros, Filinto, Corso, Ruggero Massimo, Cortegiani, Andrea, Costa, Gabriela, Cowton, Amanda, Cox, Nicola, Craig, Jame, Cricca, Valentina, Cronin, John, Cunha, Mariana, Cuomo, Arturo, Curley, Katherine, Czuczwar, Mirosław, Dabrowska, Domenika, Damster, Sabrine, Danguy des Déserts, Marc, Daniliuc, Aura, Danninger, Thoma, Darwish, Imad, Dascalu, Corina, Davies, Kirsty, Davies, Simon, De Boer, Han, De Flaviis, Adelisa, De Selincourt, Gabrielle, Deana, Cristian, Debaene, Bertrand, Debreceni, Gabor, Dedhia, Jatin, Delgado Garcia, Isabel, Della Rocca, Giorgio, Delroy-Buelles, Llana, Desai, Tejal, Dhillon, Parveen, Di Giacinto, Ida, Di Mauro, Piero, Diaz Gomez, Tamara V., Dimitrovski, Aleksandar, Dinic, Vesna, Dîrzu, Dan-Sebastian, Divander, Mona Britt, Dolinar, Janez, Domingues, Susana, Doolan, Jame, Downes, Charlotte, Dragoescu, Nicoleta Alice, Droc, Gabriela, Dum, Elisabeth, Dumitrescu, Alexandra, Duncan, Louise, Dzurňáková, Paul, Eberl, Susanne, Edwards, Jayne, Edwards, Mark, Ekelund, Kim, Ekengren, Patrik, Elghouty, Eyad, Ellerkmann, Richard, Ellis, Helen, Elme, Andrea, Ernst, Thoma, Errando, Carlos Lui, Estenes, Simao, Ewaldsson, Calli, Farid, Nahla, Featherstone, Jame, Febres, Daniela, Fedorov, Sergey, Feggeler, Johanna, Feijten, Prisca, Fellmann, Tobia, Fernandez Candil, Juan, Fernandez Castineira, Ana, Fernández Castineira, Juan, Fernando, Aruna, Ferrando, Carlo, Ferreira, Leonia, Ferreira, Patrick, Feyling, Ander, Filipescu, Daniela, Fleischer, Andrea, Floris, Leda, Foerster, Ur, Fox, Benjamin, Franke, Uwe, Frasca, Deni, Frey, Christian, Frost, Victoria, Fullin, Giorgio, Fumagalli, Jacopo, Furneval, Julie, Fusari, Maurizio, Gallacher, Stuart, Galushka, Svetlana, Gambale, Giorgio, Gambino, Irene, Garcia-Perez, Maria Luisa, Garg, Sanjeev, Garlak, Justyna, Gavranovic, Zeljka, Gavrilov, Roman, Gaynor, Lame, Gecaj Gashi, Agreta, Georghiou, Maria, Gerjevic, Bozena, Gferer, Gudrun, Giarratano, Antonino, Gibson, Andy, Gievski, Vanja, Giles, Julian, Gillberg, Lar, Gilowska, Katarzyna, Gilsanz Rodriguez, Fernando, Gioia, Antonio, Giovannoni, Cecilia, Girotra, Vandana, Gkinas, Dimitrio, Gkiokas, George, Godoroja, Daniela, Goebel, Ulrich, Goel, Vandana, Gonzalez, Matilde, Goranovic, Tatjana, Gornik-Wlaszczuk, Ewa, Gosavi, Smita, Gottfridsson, peter, Gottschalk, André, Granell, Manuel, Granstrom, Anna, Grassetto, Alberto, Greenwood, Anna, Grigoras, Ioana, Grintescu, Ioana, Gritsan, Alexey, Gritsan, Galina, Grynyuk, Andriy, Guadagnin, Giovanni Maria, Guarnieri, Marcello, Güçlü, Çiğdem, Guerrero Diez, Maria, Gunenc, Ferim, Günther, Ulf, Gupta, Pawan, Guttenthaler, Vera, Hack, Yvonne, Hafisayena, Ade, Hagau, Natalia, Haldar, Jagannath, Hales, Dawn, Hancı, Volkan, Hanna-Jumma, Sameer, Harazim, Hana, Harlet, Pierre, Harper, Daniel, Harris, Benjamin, Harvey, Orla, Hashimi, Medita, Hawkins, Lesley, Hayes, Conrad, Heaton, Jame, Heier, Tom, Helliwell, Laurence, Hemmes, Sabrine, Henderson, Kate, Hermanides, Jeroen, Hermanns, Henning, Herrera Hueso, Berta, Hestenes, Siv, Hettiarachchi, Roshane, Highgate, Judith, Hodgson, Keith, Hoelbling, Daniel, Holland, Jonathan, Horhota, Lucian, Hormis, Anil, Hribar, Renata, Hua, Alina, Humphreys, Sally, Humphries, Ryan, Humpliková, Simona, Hunt, Janez, Husnain, Ali, Hussein, Ahmed, Hyams, Benjamin, Iannuccelli, Fabrizio, Ilette, Katie, Ilyas, Carl, Inan, Turgay, India, Immaculada, Ionițăv, Victor, Irwin, Foo, Jain, Vipul, Janez, Benedikt, Jankovic, Radmilo, Jenkins, Sarah, Jenko, Matej, Jimenez, Raquel, Jiménez Gomez, Bárbara, Joachim, Sugganthi, Joelsson-Alm, Eva, John, John, Jonikaite, Lina, Jovic, Miomir, Jungwirth, Bettina, Junke, Etienne, Kabakov, Bory, Kadaoui, Salah-Din, Kanski, Andrzej, Karadag, Süheyla, Karbonskiene, Aurika, Karjagin, Juri, Kasnik, Darja, Katanolli, Fato, Katsika, Eleni, Kaufmann, Kai, Keane, Helen, Kelly, Martin, Kent, Melanie, Keraitiene, Grazina, Khudhur, Ahmed, Khuenl-Brady, Karin, Kidd, Laurie, King, Siobhan, Kirchgäßner, Katharina, Klancir, Tino, Klucniks, Andri, Knotzer, Johann, Knowlden, Peter, Koers, Lena, Kompan, Janez, Koneti, Kiran K, Kooij, Fabian, Koolen, Eric, Koopman - van Gemert, Anna Wilhelmina Margaretha Maria, Kopp, Kristen, Korfiotis, Dimitrio, Korolkov, Oleg, Kosinová, Martina, Köstenberger, Marku, Kotzinger, Oskar, Kovačević, Marko, Kranke, Peter, Kranke, Eva, Kraus, Christiane, Kraus, Stephanie, Kubitzek, Christiane, Kucharski, Rafal, Kucukguclu, Semih, Kudrashou, Allaksandr, Kumar, Vinayak, Kummen, Live, Kunit, Cornelia, Kushakovsky, Vlad, Kuvaki, Bahar, Kuzmanovska, Biljana, Kyttari, Aikaterina, Landoni, Giovanni, Lau, Gary, Lazarev, Konstantin, Legett, Samantha, Legrottaglie, Anna Maria, Leonardi, Silvia, Leong, Maria, Lercher, Helene, Leuvrey, Matthieu, Leva, Brigitte, Levstek, Meta, Limb, Jame, Lindholm, Espen, Linton, Fiona, Liperi, Corradero, Lipski, Fabian, Lirk, Philipp, Lisi, Alberto, Lišková, Katarina, Lluch Oltra, Aitana, Loganathan, Vinothan, Lombardi, Stefania, Lopez, Eloisa, Lopez Rodríguez, Maria, Lorenzini, Laura, Lowicka, Malgorzata, Lugovoy, Alexander, Luippold, Madeleine, Lumb, Andrew, Macas, Andriu, Macgregor, Mark, Machado, Humberto, Maciariello, Maria, Madeira, Isabel, Maitan, Stefan, Majewski, Jacek, Maldini, Branka, Malewski, Georgia, Manfredini, Livia, Männer, Olja, Marchand, Bahareh, Marcu, Alexandra, Margalef, Jordi, Margarson, Michael, Marinheiro, Lucia, Markic, Ana, Markovic Bozic, Jasmina, Marrazzo, Francesco, Martin, Jane, Martin Ayuso, Maria, Martinez, Esteher, Martino, Enrico Antonio, Martinson, Victoria, Marusic-Gaser, Katarina, Mascarenhas, Catia, Mathis, Cindy, Matsota, Paraskevi, Mavrommati, Eleni, Mazul Sunko, Branka, McCourt, Killian, McGill, Neil, McKee, Raymond, Meço, Başak Ceyda, Meier, Sonja, Melbourne, Susan, Melbybråthen, Grethe, Meli, Andrea, Melia, Aiden, Melotti, Rita Maria, Menga, Maria Rosaria, Mercer, Pauline, Merotra, Susan, Mescolini, Silvia, Metterlein, Thoma, Michalov, Martin, Michlig, Sam, Midgley, Susan, Milić, Morena, Milojevic, Milan, Miñana, Amanda, Minto, Gary, Mirabella, Lucia, Mirea, Liliana, Mittelstädt, Ludger, Moeglen, Aude, Moise, Alida, Mokini, Zhirajr, Molin, Anna, Moltó, Lui, Monea, Maria Concetta, Montalto, Francesca, Montgomery, Jane, Montgomery, Claire, Montillo, Gerardo, Moore, Sally, Moore, Faye, Moreira, Zelia, Moreno, Tania, Moreno, Ricardo, Moret, Enrique, Moreton, Sarah, Morgan, Marianne, Moro Velasco, Concepción, Morri, Davide, Moull, Alice, Moura, Fernando, Mráz, Peter, Mrozek, Katarzyna, Mukhtar, Karim, Muniyappa, Sudeshkumar, Murray, Heather, Murthy, Burra VS, Mushambi, Mary, Nadolski, Maria, Nardelli, Pasquale, Nardin, Giordano, Navarro Pérez, Rosalía, Naveiro, Andrea, Negri, Manuela, Nesek Adam, Visnja, Neskovic, Vojislava, Neuwersch, Stefan, Neves, Miriam, Nguyen, Bavinh, Ní Eochagáin, Aisling, Nicholas, Caroline, Nightingale, Jeremy, Norrie, Kylie, Novak-Jankovic, Vesna, Novakova, Andrea, Novillo, Marta, Numan, Sandra, Oduro-Dominah, Louise, Oldner, Ander, Oliveira, Isabel, Ologoiu, Daniela, Oloktsidou, Irini, O'Reilly, Rosalind, Orlando, Alessandro, Ovezov, Alexey, Ozbilgin, Sule, Paal, Peter, Padin Barreiro, Lidia, Palugniok, Ryszard, Papaioannou, Alexandra, Papapostolou, Konstantino, Paranthaman, Prabhakar, Pardey Bracho, Gilda, Parente, Suzana, Parfeni, Alexandru, Pasin, Laura, Passey, Samuel, Pastor, Ernesto, Patch, Sarah, Patil, Andan, Paunescu, Marilena-Alina, Pehboeck, Daniel, Pereira, Manuela, Pereira, Carla, Perez Caballero, Paula, Pérez García, Aníbal, Pérez Soto, Antonia, Perez Tejero, Gisela, Perez-Cerda, Francisco, Pesenti, Antonio, Petta, Rocco, Philippe, Simon, Pickering, David, Pico Veloso, Jandro, Pina, Pedro, Pinho-Oliveira, Vítor, Pinol, Santiago, Pinto, Rita, Pistidda, Laura, Pitterle, Manuela, Piwowarczyk, Paweł, Plotnikova, Olga, Pohl, Holger, Poldermann, Jorinde, Polkovicová, Lucia, Pompei, Livia, Popescu, Mihai, Popović, Radmila, Pota, Vincenzo, Potocnik, Miriam, Potręć, Beata, Potter, Alison, Pramod, Nalwaya, Prchalova, Martina, Preckel, Benedikt, Pugh, Richard, Pulletz, Mark, Radoeshki, Aleksandar, Rafi, Amir, Ragazzi, Riccardo, Raineri Santi, Maurizio, Rajamanickam, Tamiselvan, Rajput, Zahra, Ramachandran, Rajeskar, Ramasamy, Radhika, Ramessur, Suneil, Rao, Roshan, Rasmussen, Ander, Rato, André, Razaque, Usman, Real Navacerrada, M. Isabel, Reavley, Caroline, Reid, Jame, Reschreiter, Henrik, Rial, Erick, Ribas Carrasco, Patricia, Ribeiro, Sandy, Rich, Nathalie, Richardson, Lydia, Rimaitis, Kestuti, Rimaitis, Mariu, Ringvold, Else-Marie, Ripke, Fabian, Ristescu, Irina, Ritchie, Keith, Ródenas, Frederic, Rodrigues, Patrícia, Rogers, Emma, Rogerson, David, Romagnoli, Stefano, Romero, Esther, Rondovic, Goran, Rose, Bernd Oliver, Roth, Winfried, Rotter, Marie-Therese, Rousseau, Guy, Rudjord, Ander, Rueffert, Henrik, Rundgren, Malin, Rupprecht, Korbinian, Rushton, Andrew, Russotto, Vincenzo, Rypulak, Elżbieta, Ryszka, Maciej, Sà, Jacinta, Sà Couto, Paula, Saby, Sandrine, Sagic, Jelena, Saleh, Omar, Sales, Gabriele, Sánchez Sánchez, Yván, Sanghera, Sumayer, Şanli Karip, Ceren, Santiveri Papiol, Francisco Javier, Santos, Sofia, Sarno, Stephen, Saul, Daniel, Saunders, David, Savic, Nenad, Scalco, Loïc, Scanlon, Deborah, Schaller, Stefan, Schax, Christoph, Scheffer, Gert Jan, Schening, Anna, Schiavone, Vincenzo, Schmidt-Ehrenberg, Florian, Schmidt-Mutter, Catherine, Schönberg, Christina, Schopflin, Christian, Schreiber, Jan-Uwe, Schultz, Marcu, Schurig, Marlen, Scott, Carmen, Sebestian, Siby, Sehgal, Selena, Sem, Victoria, Semenas, Egidiju, Serafini, Elena, Serchan, Pashalitsa, Shields, Martin, Shobha, Ramakrishnan, Shosholcheva, Mirjana, Siamansour, Tanja, Siddaiah, Narendra, Siddiqi, Khalid, Sinclair, Rhona, Singh, Permendra, Singh, Rajendra, Sinha, Aneeta, Sinha, Ashok, Skinner, Amanda, Smee, Elizabeth, Smekalova, Olga, Smith, Neil, Smith, Thoma, Smitz, Carine, Smole, Daniel, Sojčić, Nataša, Soler Pedrola, Maria, Somanath, Sameer, Sonksen, Julian, Sorella, Maria Christina, Sörmus, Alar, Soro, Marina, Soto, Carmen, Spada, Anna, Spadaro, Savino, Spaeth, Johanne, Sparr, Harald, Spielmann, Annika, Spindler-Vesel, Alenka, Stamelos, Matthaio, Stancombe L, Liucia, Stanculescu, Andreea, Standl, Thoma, Standley, Tom, Stanek, Ondrej, Stanisavljević, Snežana, Starczewska, Malgorzata, Stäuble, Christiane, Steen, Julie, Stefan, Oana Maria, Stell, Elizabeth, Stera, Caterina, Stevens, Marku, Stoerckel, Marlène, Stošić, Biljana, Stourac, Petr, Stroumpoulis, Konstantino, Struck, Rafael, Suarez de la Rica, Alejandro, Sultanpori, Altaf, Sundara Rajan, Rajinikanth, Suying, Ong, Svensen, Christer, Swan, Louise, Syrogianni, Paulina, Sysiak, Justyna, Szederjesi, Jano, Taddei, Stefania, Tan Hao, Ern, Tanou, Virginia, Tarabová, Katarina, Tardaguila Sancho, Paula, Tarroso, Maria, Tartaglione, Marco, Taylor, Emma, Tbaily, Lee, Telford, Richard, Terenzoni, Massimo, Theodoraki, Kassiani, Thornley, Helen, Tiganiuc, Liviu, Toim, Hardo, Tomescu, Dana, Tommasino, Concezione, Toni, Jessica, Toninelli, Arturo, Toretti, Ilaria, Townley, Stephen, Trepenaitis, Dariu, Trethowan, Brian, Tsaousi, Georgia, Tsiftsi, Aikaterini, Tudor, Adrada, Turan, Güldem, Turhan, Sanem Çakar, Unic-Stojanovic, Dragana, Unterbuchner, Christoph, Unzueta, Carmen, Uranjek, Jasna, Ursic, Tomaz, Vaida, Simona, Valldeperas Ferrer, Silvia, Valldeperas Hernandez, Maria Inmaculada, Valsamidis, Dimitri, Van Beek, Rienk, Van dasselaer, Nick, Van Der Beek, Tim, Van Duivenvoorde, Yoni, van Klei, Wilton A., Van Poorter, Fran, Van Zaane, Ba, Van Zundert, Tom, Van Zyl, Rebekka, Vargas Munoz, Ana Milena, Varsani, Nimu, Vasconcelos, Pedro, Vassilakis, Georgio, Vecchiatini, Tommaso, Vecera, Lubomir, Vercauteren, Marcel, Verdouw, Ba, Verheyen, Veerle, Verri, Marco, Vicari Sottosanti, Luigi Giancarlo, Vico, Manuel, Vidal Mitjans, Patricia, Vilardi, Anna, Vissicchio, Daniela, Vitale, Giovanni, Vitković, Bibiana, Vizcaychipi, Marcela Paola, Voicu, Alexandra, Voje, Minca, Volfová, Ivana, Volta, Carlo Alberto, Von Lutterotti, Theresa, von Tiesenhausen, Anna, Vrecic-Slabe, Simona, Vukcevic, Dejan, Vukovic, Rade, Vullo, P. Agostina, Wade, Andrew, Wallberg, Hanna, Wallden, Jakob, Wallner, Johann, Walther Sturesson, Louise, Watson, Davina, Weber, Stefan, Wegiel Leskiewiq, Anna, Weller, Debbie, Wensing, Carine, Werkmann, Marku, Westberg, Henrik, Wikström, Erik, Williams, Benedict, Wilson, Robin, Wirth, Steffen, Wittmann, Maria, Wood, Laura, Wright, Stella, Zachoval, Christian, Zambon, Massimo, Zampieri, Silvia, Zampone, Salvatore, Zangrillo, Alberto, Zani, Gianluca, Zavackiene, Asta, Zieglerder, Raphael, Zonneveldt, Harry, Zsisku, Lajo, Zucker, Tom-Philipp, Żukowski, Maciej, Zuleika, Mehrun, and Zupanĕiĕ, Darja

Subjects
Pulmonary and Respiratory Medicine, pulmonary complications, muscle relaxants, Post-anaesthesia complications, Neuromuscular Blockade, pulmonary complication, muscle relaxant, neuromuscular block, postoperative pulmonary complication, business.industry, Retrospective cohort study, post-operative pulmonary complications, Neuromuscular monitoring, Neuromuscular Blocking Agents, Sugammadex, NO, Anaesthesia, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Anesthesia, Medicine, General anaesthesia, Neuromuscular Agents, 030212 general & internal medicine, MED/41 - ANESTESIOLOGIA, Prospective cohort study, business, medicine.drug
Abstract

Background: Results from retrospective studies suggest that use of neuromuscular blocking agents during general anaesthesia might be linked to postoperative pulmonary complications. We therefore aimed to assess whether the use of neuromuscular blocking agents is associated with postoperative pulmonary complications. Methods: We did a multicentre, prospective observational cohort study. Patients were recruited from 211 hospitals in 28 European countries. We included patients (aged ≥18 years) who received general anaesthesia for any in-hospital procedure except cardiac surgery. Patient characteristics, surgical and anaesthetic details, and chart review at discharge were prospectively collected over 2 weeks. Additionally, each patient underwent postoperative physical examination within 3 days of surgery to check for adverse pulmonary events. The study outcome was the incidence of postoperative pulmonary complications from the end of surgery up to postoperative day 28. Logistic regression analyses were adjusted for surgical factors and patients' preoperative physical status, providing adjusted odds ratios (ORadj) and adjusted absolute risk reduction (ARRadj). This study is registered with ClinicalTrials.gov, number NCT01865513. Findings: Between June 16, 2014, and April 29, 2015, data from 22 803 patients were collected. The use of neuromuscular blocking agents was associated with an increased incidence of postoperative pulmonary complications in patients who had undergone general anaesthesia (1658 [7·6%] of 21 694); ORadj 1·86, 95% CI 1·53–2·26; ARRadj −4·4%, 95% CI −5·5 to −3·2). Only 2·3% of high-risk surgical patients and those with adverse respiratory profiles were anaesthetised without neuromuscular blocking agents. The use of neuromuscular monitoring (ORadj 1·31, 95% CI 1·15–1·49; ARRadj −2·6%, 95% CI −3·9 to −1·4) and the administration of reversal agents (1·23, 1·07–1·41; −1·9%, −3·2 to −0·7) were not associated with a decreased risk of postoperative pulmonary complications. Neither the choice of sugammadex instead of neostigmine for reversal (ORadj 1·03, 95% CI 0·85–1·25; ARRadj −0·3%, 95% CI −2·4 to 1·5) nor extubation at a train-of-four ratio of 0·9 or more (1·03, 0·82–1·31; −0·4%, −3·5 to 2·2) was associated with better pulmonary outcomes. Interpretation: We showed that the use of neuromuscular blocking drugs in general anaesthesia is associated with an increased risk of postoperative pulmonary complications. Anaesthetists must balance the potential benefits of neuromuscular blockade against the increased risk of postoperative pulmonary complications. Funding: European Society of Anaesthesiology.

Published
2019
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29. The Emerging Predictive and Prognostic Role of Aggressive-Variant-Associated Tumor Suppressor Genes Across Prostate Cancer Stages.

Author

Pedrani M, Barizzi J, Salfi G, Nepote A, Testi I, Merler S, Castelo-Branco L, Mestre RP, Turco F, Tortola L, Theurillat JP, Gillessen S, and Vogl U

Subjects
Humans, Male, Prognosis, Genes, Tumor Suppressor, Neoplasm Staging, Tumor Suppressor Protein p53 genetics, Prostatic Neoplasms genetics, Prostatic Neoplasms pathology, Prostatic Neoplasms therapy, Prostatic Neoplasms diagnosis, Biomarkers, Tumor genetics, PTEN Phosphohydrolase genetics
Abstract

Aggressive variant prostate cancer (AVPC) is characterized by a molecular signature involving combined defects in TP53 , RB1 , and/or PTEN (AVPC-TSGs), identifiable through immunohistochemistry or genomic analysis. The reported prevalence of AVPC-TSG alterations varies widely, reflecting differences in assay sensitivity, treatment pressure, and disease stage evolution. Although robust clinical evidence is still emerging, the study of AVPC-TSG alterations in prostate cancer (PCa) is promising. Alterations in TP53 , RB1 , and PTEN , as well as the combined loss of AVPC-TSGs, may have significant implications for prognosis and treatment. These biomarkers might help predict responses to various therapies, including hormonal treatments, cytotoxic agents, radiotherapy, and targeted therapies. Understanding the impact of these molecular alterations in patients with PCa is crucial for personalized management. In this review, we provide a comprehensive overview of the emerging prognostic and predictive roles of AVPC-TSG alterations across PCa stages. Moreover, we discuss the implications of different methods used for detecting AVPC-TSG alterations and summarize factors influencing their prevalence. As our comprehension of the genomic landscape of PCa disease deepens, incorporating genomic profiling into clinical decision making will become increasingly important for improving patient outcomes.

Published
2025
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30. Drug resistance of Acinetobacter ssp. in patients with pneumonia in a Brazilian Pre-Amazon region during the pre-pandemic and pandemic periods of COVID-19.

Author

Costa MCC, Mesquita GP, Silva MA, Araújo LG, Vila Nova BG, Castelo Branco LCM, Silva RCS, Marques SG, and Abreu AG

Subjects
Humans, Brazil epidemiology, Male, Female, Middle Aged, Adult, Aged, Microbial Sensitivity Tests, SARS-CoV-2 drug effects, Acinetobacter Infections drug therapy, Acinetobacter Infections microbiology, Acinetobacter Infections epidemiology, Pandemics, Drug Resistance, Bacterial, Young Adult, Adolescent, COVID-19, Anti-Bacterial Agents pharmacology, Acinetobacter drug effects, Acinetobacter isolation & purification
Abstract

Antimicrobial resistance is a global public health threat that has been impacted by the COVID-19 pandemic. The aim of this study was to evaluate the resistance of Acinetobacter spp. isolated from patients with pneumonia in a Brazilian Pre-Amazon region during the pre-pandemic and pandemic periods of COVID-19. Bacterial strains were obtained from tracheal aspiration, sputum and bronchoalveolar lavage for diagnosis and phenotypic characterization. MALD-TOF was used to identify strains. The automated Phoenix and VITEK® 2 Compact system and the disc diffusion method were performed to determine the antimicrobial susceptibility profile. Were analyzed a total of 41,590 samples from patients admitted to hospitals of a Brazilian Pre-Amazon region, from January 2019 to December 2021. Of these, 162 isolates of Acinetobacter spp. were from the pre-pandemic period and 308 from the pandemic COVID-19. A. baumannii was the most prevalent species. Among the samples, 52% were male patients, aged over 60 years, hospitalized in intensive care units. Acinetobacter spp. showed higher rates of resistance to cefepime (79.1%), levofloxacin (77.8%), and ceftazidime (77%) in the pre-pandemic period and during the pandemic to piperacillin (72.4%), imipenem (71.6%) and ciprofloxacin (71.8%). Taken together, the data showed that A. baumannii was the most prevalent species among Acinetobacter spp., being more frequent among elderly patients admitted to the ICU. The strains presented high resistance to most antibiotics tested, mainly carbapenems. In addition, there was an increase in resistance to polymyxin B, which raises an alert since this is a therapeutic choice to treat infections caused by Acinetobacter spp. multidrug resistant.

Published
2024
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31. Treatment-related Hypertension as a Prognostic Factor for De Novo Metastatic Hormone-sensitive Prostate Cancer: A Retrospective Real-world Evidence Study.

Author

Salfi G, Pedrani M, Candan S, Urechie V, Merler S, Ruinelli L, Colombo A, Castelo-Branco L, Testi I, Turco F, Tortola L, Vogl U, Gabutti L, Gillessen S, and Pereira Mestre R

Abstract

Background and Objective: Hypertension (HTN) has been linked to an elevated risk of prostate cancer (PC) development and poorer prognosis in localized cases, and is a common side effect of hormonal PC treatments. However, its relationship with the prognosis of metastatic PC is still unclear. We assessed the prognostic role of treatment-related HTN in patients with de novo metastatic hormone-sensitive PC (mHSPC) undergoing androgen deprivation therapy (ADT) alone or in combination with docetaxel or androgen receptor pathway inhibitors (ARPIs)., Methods: Our retrospective analysis included 100 patients with de novo mHSPC treated with ADT, ADT + docetaxel, or ADT + ARPI between 2014 and 2021. Data on clinical variables, antihypertensive drugs, and blood pressure were collected from treatment initiation to 7 mo from ADT start. HTN development within 7 mo from hormonal treatment initiation was graded according to the Common Toxicity Criteria for Adverse Events version 5.0, and Cox analyses were performed for time to castration resistance (TTCR) and overall survival (OS)., Key Findings and Limitations: In the overall population, grade (G) 2-3 HTN development within 7 mo from hormonal treatment initiation was associated with improved TTCR and OS at both univariate (TTCR: 19.8 vs 7.9 mo, hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.20-0.63, p  < 0.001; OS: 42 vs 18.4 mo, HR: 0.48, 95% CI: 0.26-0.87, p  = 0.017) and multivariate (TTCR: HR: 0.41, 95% CI: 0.18-0.91, p  = 0.029; OS: HR: 0.42, 95% CI: 0.18-0.97, p  = 0.042) analyses. A subgroup analysis of the ADT + ARPI-treated population revealed 7-mo treatment-related G2-3 HTN to be an independent positive prognostic factor in terms of both TTCR and OS multivariate survival analyses (HR: 0.30, 95% CI: 0.09-0.95, p  = 0.040, and HR: 0.12, 95% CI: 0.02-0.57, p  = 0.008, respectively)., Conclusions and Clinical Implications: The early development or worsening of HTN under hormonal treatment may be associated with longer TTCR and OS in de novo mHSPC patients. Larger studies are needed to validate these findings and explore the potential underlying mechanisms., Patient Summary: In this report, we examined the outcomes of patients with metastatic hormone-sensitive prostate cancer and their correlation with hypertension toxicities. We found that patients who developed clinically significant blood pressure toxicity early in oncological treatment experienced longer survival., (© 2024 The Authors.)

Published
2024
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32. The role of symptoms severity, heart rate, and central sensitization for predicting sleep quality in patients with fibromyalgia.

Author

Lima D, Pacheco-Barrios K, Slawka E, Camargo L, Castelo-Branco L, Cardenas-Rojas A, Neto MS, and Fregni F

Subjects
Humans, Sleep Quality, Central Nervous System Sensitization, Cross-Sectional Studies, Heart Rate, Fatigue, Sleep, Surveys and Questionnaires, Fibromyalgia diagnosis, Sleep Initiation and Maintenance Disorders complications, Sleep Wake Disorders etiology, Sleep Wake Disorders complications
Abstract

Background: Clinical predictors of sleep quality in patients with fibromyalgia syndrome (FMS) are still unknown. By identifying these factors, we could raise new mechanistic hypotheses and guide management approaches. We aimed to describe the sleep quality of FMS patients and to explore the clinical and quantitative sensory testing (QST) predictors of poor sleep quality and its subcomponents., Methods: This study is a cross-sectional analysis of an ongoing clinical trial. We performed linear regression models between sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and demographic, clinical, and QST variables, controlling for age and gender. Predictors for the total PSQI score and its seven subcomponents were found using a sequential modeling approach., Results: We included 65 patients. The PSQI score was 12.78 ± 4.39, with 95.39% classified as poor sleepers. Sleep disturbance, use of sleep medications, and subjective sleep quality were the worst subdomains. We found poor PSQI scores were highly associated with symptom severity (FIQR score and PROMIS fatigue), pain severity, and higher depression levels, explaining up to 31% of the variance. Fatigue and depression scores also predicted the subjective sleep quality and daytime dysfunction subcomponents. Heart rate changes (surrogate of physical conditioning) predicted the sleep disturbance subcomponent. QST variables were not associated with sleep quality or its subcomponents., Conclusions: Symptom severity, fatigue, pain, and depression (but no central sensitization) are the main predictors of poor sleep quality. Heart rate changes independently predicted the sleep disturbance subdomain (the most affected one in our sample), suggesting an essential role of physical conditioning in modulating sleep quality in FMS patients. This underscores the need for multidimensional treatments targeting depression and physical activity to improve the sleep quality of FMS patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2023
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33. Functional and Neural Correlates Associated with Conditioned Pain Modulation in Patients with Chronic Knee Osteoarthritis Pain: A Cross-Sectional Study.

Author

Simis M, Pacheco-Barrios K, Vasquez-Avila K, Rebello-Sanchez I, Parente J, Castelo-Branco L, Marduy A, de Melo PS, Imamura M, Battistella L, and Fregni F

Abstract

Background: In this study, we aimed to assess the factors that predict a dysfunctional conditioned pain modulation (CPM) in chronic knee OA. Methods: This is a cross-sectional analysis of patients with chronic knee OA from a prospective cohort study in Brazil (n = 85). We performed linear and logistic multivariate regression models using the purposeful selection approach to test the relationship between the CPM in both knees (average) as a dependent variable and demographics, clinical, and neurophysiological as independent variables. Results: A significant negative association between WOMAC pain scores and CPM (β: -0.13) was found. This association was modified by the subjects' race, being stronger in the non-white subjects. In our logistic regression models, pain intensity indexed with the WOMAC pain scale remained a significant association with dichotomized CPM. Furthermore, a significant CPM association with balance, indexed with the Berg Balance score, was evidenced (β: 0.04). Neurophysiological variables showed a significant negative relationship with CPM, such as the relative power of delta oscillations in the frontal area (β: -3.11) and central area (β: -3.23). There was no significant relationship between CPM and the following domains: cognitive, emotion, sleep, opioid receptor polymorphisms, and intrinsic variables of OA disease. There was no association of CPM with TMS-indexed inhibitory markers. Conclusions: These results may indicate that less function of the pain descending inhibitory system in patients with OA is correlated with higher activity-related pain (WOMAC), less balance, and cortical plasticity especially with increased low-frequency (delta) brain oscillations. These associations seem modified by race.

Published
2023
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34. Antimicrobial resistance of Pseudomonas aeruginosa isolated from patients with pneumonia during the COVID-19 pandemic and pre-pandemic periods in Northeast Brazil.

Author

Mesquita GP, Costa MCC, Silva MA, Araújo LG, Vila Nova BG, Castro ÉJM, Castelo Branco LCM, Silva RCSD, Marques SG, and Abreu AG

Subjects
Male, Humans, Aged, Anti-Bacterial Agents pharmacology, Pseudomonas aeruginosa, Pandemics, Brazil epidemiology, Drug Resistance, Bacterial, Microbial Sensitivity Tests, COVID-19, Anti-Infective Agents
Abstract

Healthcare-related infections caused by resistant microorganisms are a severe public health problem and are becoming increasingly prevalent in the hospital environment, especially Pseudomonas aeruginosa. This work aimed to evaluate the resistance profile of Pseudomonas aeruginosa to antimicrobials before the COVID-19 pandemic and during the pandemic period. Bacteria strains were obtained from tracheal aspiration, sputum, and bronchoalveolar lavage for diagnosis and phenotypic characterization. Matrix assisted laser-desorption ionization-time of flight mass spectrometry (MALD-TOF MS) was used to identify strains. Automated Phoenix and VITEK® 2 Compact system and the disc diffusion method were performed to determine the antimicrobial susceptibility profile. A total of 41,000 medical reports from adult patients with pneumonia were analyzed. Of these, 951 patients were positive for P. aeruginosa, of which 373 were related to the pre-pandemic period and 578 to the pandemic period. Older men (≥60 years) were more prevalent in both periods. P. aeruginosa strains were resistant to imipenem in both periods: 38.8 and 42.5%, respectively, followed by meropenem (34.2 and 39.2%), ciprofloxacin (33.6 and 36.7%), and levofloxacin (34.9 and 43.5%). Intensive care units had the highest percentage of affected patients (62 and 65%) compared with other sectors, with a prevalence of 71% in the public network before COVID-19 and 59% during the pandemic. Our data showed a prevalence of P. aeruginosa in elderly patients in both the pre-pandemic and pandemic periods. In addition, an increase in P. aeruginosa resistance to beta-lactams, quinolones, carbapenems, and cephalosporins was observed during the COVID-19 pandemic compared with the period before the pandemic, especially in ICUs.

Published
2023
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35. Association of Mu opioid receptor (A118G) and BDNF (G196A) polymorphisms with rehabilitation-induced cortical inhibition and analgesic response in chronic osteoarthritis pain.

Author

Gonçalves FT, Pacheco-Barrios K, Rebello-Sanchez I, Castelo-Branco L, de Melo PS, Parente J, Cardenas-Rojas A, Firigato I, Pessotto AV, Imamura M, Simis M, Battistella L, and Fregni F

Abstract

Background/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates., Method: We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation., Results: Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship., Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population., Competing Interests: No conflict of interest to declare. This study was developed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Authors.)

Published
2023
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36. Transcutaneous auricular vagus nerve stimulation effects on inflammatory markers and clinical evolution of patients with COVID-19: a pilot randomized clinical trial.

Author

Uehara L, Corrêa JCF, Ritti R, Leite P, de Faria DRG, Pacheco-Barrios K, Castelo-Branco L, Fregni F, and Corrêa FI

Subjects
Humans, Pilot Projects, Hydrocortisone, Interleukin-6, Vagus Nerve, Vagus Nerve Stimulation, COVID-19 therapy, Transcutaneous Electric Nerve Stimulation
Abstract

Objective: To evaluate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammatory markers and clinical outcomes in patients with COVID-19., Methods: A randomized blinded pilot study was carried out with 21 individuals hospitalized with COVID-19 who received 14 sessions of active (a-taVNS) or sham taVNS (s-taVNS). The level of interleukin-6 (IL-6), interleukin-10 (IL-10), cortisol, and C-reactive protein (CRP) in plasma and clinical evolution pre- and post-intervention were evaluated. The memory and attention levels were evaluated 14 days after the end of the treatment., Results: After treatment, significant intragroup differences were found in the CRP (p = 0.01), IL-6 (p = 0.01), and cortisol (p = 0.01) levels; however, in the comparison between the groups, only the CRP level was statistically lower for the a-taVNS (p = 0.04). The impression of improvement in memory and attention was greater in the a-taVNS than in the s-taVNS (p = 0.01, p = 0.04, respectively). There was no difference between the other clinical outcomes., Conclusions: taVNS is a viable and safe intervention in the acute care of patients with COVID-19, which can modulate their inflammatory profile and improve cognitive symptoms. However, improvements in overall clinical outcomes were not detected. Larger sample sizes and longer follow-ups are needed to confirm the anti-inflammatory and clinical effects of taVNS in patients with COVID-19., Trials Registry: The Brazilian Registry of Clinical Trials (RBR-399t4g5).

Published
2022
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37. Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: a joint analysis of OnCovid and ESMO-CoCARE registries.

Author

Cortellini A, Dettorre GM, Dafni U, Aguilar-Company J, Castelo-Branco L, Lambertini M, Gennatas S, Angelis V, Sita-Lumsden A, Rogado J, Pedrazzoli P, Viñal D, Prat A, Rossi M, Berardi R, Alonso-Gordoa T, Grisanti S, Dimopoulou G, Queirolo P, Pradervand S, Bertuzzi A, Bower M, Arnold D, Salazar R, Tucci M, Harrington KJ, Mazzoni F, Mukherjee U, Tsourti Z, Michielin O, Pommeret F, Brunet J, Vincenzi B, Tonini G, Patriarca A, Biello F, Krengli M, Tabernero J, Pentheroudakis G, Gennari A, Peters S, Romano E, and Pinato DJ

Subjects
Humans, Immune Checkpoint Inhibitors therapeutic use, COVID-19 Testing, SARS-CoV-2, Medical Oncology, Registries, COVID-19, Neoplasms drug therapy, Neoplasms epidemiology
Abstract

Background: As management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer., Methods: In a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19., Findings: The study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR 30 ) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR 30 (4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, p<0.0001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.0030), COVID-19 complication rate (11.9% vs 34.6%, p=0.0040), with a reduced need for COVID-19-specific therapy (26.3% vs 57.9%, p=0.0004) compared with unvaccinated patients. Inverse probability of treatment weighting (IPTW)-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated patients experienced a decreased risk of death at 30 days (adjusted OR, aOR 0.08, 95% CI 0.01 to 0.69).Overall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR 30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 10 9  cells/L, p=0.0098)., Conclusion: Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2., Competing Interests: Competing interests: KJH declares research funding from AstraZeneca, Boehringer-Ingelheim, MSD, Replimune and advisory board fees/honoraria from Arch Oncology, AstraZeneca, BMS, Boehringer-Ingelheim, Codiak Biosciences, Inzen Therapeutics, Merck-Serono, MSD, Pfizer, Replimune. DA reports consultation/advisory role for AstraZeneca, Bristol Myers Squibb, Merck Sharp reports speaker’s engagement from AstraZeneca, Bristol Myers Squibb, Merck Sharp reports serving as local PI for Bristol Myers Squibb, Pierre Fabre Pharma and coordinating PI for OncoLytics; reports grant funding from AbbVie; reports being/been DSMB chair of Sanofi (Genzyme); reports being/been a steering committee member of Roche. Olivier Michielin reports personal fees from Bristol-Myers Squibb, MSD, Novartis, Roche, Amgen, NeraCare, outside the submitted work. JR received speaker or advisory fees from Roche, Astra Zeneca, Merck, Ferrer, Persan Farma, Teva Pharma, Leo Pharma, Fresenius kabi, MSD, BMS. Travel expenses support from BMS, MSD, RocheUrania Dafni reports honorarium as Member of the Tumor Agnostic Evidence Generation Working Group of Roche, outside the submitted work. GP reports grants from Amgen, Lilly; grants, personal fees and nonfinancial support from Merck; grants and non-financial support from AstraZeneca; grants and personal fees from Roche, Bristol Myers Squibb, MSD, Novartis, outside the submitted work. Solange Peters reports consultation/advisory role for AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Biocartis, Bio Invent, Blueprint Medicines, Boehringer Ingelheim, Bristol- Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, Elsevier, F Hoffmann-La Roche/Genentech, Foundation Medicine, Illumina, Incyte, IQVIA, Janssen, Medscape, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Pharma Mar, Phosplatin Therapeutics, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Vaccibody; talk in a company’s organized public event for AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, e-cancer, Eli Lilly, F. Hoffmann-La Roche/Genentech, Illumina, Medscape, Merck Sharp and Dohme, Novartis, PER, Pfizer, Prime, RTP, Sanofi, Takeda; receipt of grants/research supports from being a (sub)investigator in trials (institutional financial support for clinical trials) sponsored by Amgen, AstraZeneca, Biodesix, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis, F Hoffmann-La Roche/Genentech, GSK, Illumina, Lilly, Merck Sharp and Dohme, Merck Serono, Mirati, Novartis, and Pfizer, Phosplatin Therapeutics. Emanuela Rromano reports investigator-initiated trial (funds paid to the institution) supported by Astra-Zeneca, BMS; serves on the consultancy/advisory board for Astra-Zeneca, Merck, Roche, Pierre Fabre. ML acted as consultant for Roche, Novartis, Lilly, AstraZeneca, Exact Sciences, MSD, Pfizer, Seagen and received speaker honoraria from Roche, Novartis, Lilly, Pfizer, Takeda, Ipsen and Sandoz outside the submitted work.Alessandra Gennari has declared consulting/advisory role for Roche, MSD, Eli Lilly, Pierre Fabre, EISAI, and Daichii Sankyo; speakers bureau for Eisai, Novartis, Eli Lilly, Roche, Teva, Gentili, Pfizer, Astra Zeneca, Celgene, and Daichii Sankyo; research funds: EISAI, Eli Lilly, and Roche. CMV has received travel grants and other honoraria from BMS, MSD, Novartis and Roche. Joan Brunet has declared consulting/advisory role for MSD and Astra Zeneca. Aleix Prat has declared personal honoraria from Pfizer, Roche, MSD Oncology, Eli Lilly, and Daiichi Sankyo; travel, accommodations, and expenses paid by Daiichi Sankyo; research funding from Roche and Novartis; and consulting/advisory role for NanoString Technologies, Amgen, Roche, Novartis, Pfizer and Bristol-Myers Squibb. Mark Bower received speakers’ fee from EISAI pharma, Gilead Sciences, Merck and ViiV. JT reports consulting fees from Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F Hoffmann-La Roche, Genentech, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, and TheraMyc; speaker’s fees from Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource; and institutional research support from Amgen, Array Biopharma, AstraZeneca Pharmaceuticals, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International, F Hoffmann-La Roche, Genentech, HalioDX, Hutchison MediPharma International, Janssen-Cilag, MedImmune, Menarini, Merck Health, Merck Sharp and has had leadership roles in the European AIDS Clinical Society, UNAIDS, WHO, and The European Hematology Association/ European Society of Medical Oncology. DJP received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, EISAI, Falk Foundation, travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, DaVolterra and Astra Zeneca; research funding (to institution) from MSD and BMS. AC received consulting fees from MSD, BMS, AstraZeneca, Roche; speakers’ fee from AstraZeneca, MSD, Novartis and Eisai. All remaining authors have declared no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Published
2022
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38. An International Comparison of Presentation, Outcomes and CORONET Predictive Score Performance in Patients with Cancer Presenting with COVID-19 across Different Pandemic Waves.

Author

Wysocki O, Zhou C, Rogado J, Huddar P, Shotton R, Tivey A, Albiges L, Angelakas A, Arnold D, Aung T, Banfill K, Baxter M, Barlesi F, Bayle A, Besse B, Bhogal T, Boyce H, Britton F, Calles A, Castelo-Branco L, Copson E, Croitoru A, Dani SS, Dickens E, Eastlake L, Fitzpatrick P, Foulon S, Frederiksen H, Ganatra S, Gennatas S, Glenthøj A, Gomes F, Graham DM, Hague C, Harrington K, Harrison M, Horsley L, Hoskins R, Hudson Z, Jakobsen LH, Joharatnam-Hogan N, Khan S, Khan UT, Khan K, Lewis A, Massard C, Maynard A, McKenzie H, Michielin O, Mosenthal AC, Obispo B, Palmieri C, Patel R, Pentheroudakis G, Peters S, Rieger-Christ K, Robinson T, Romano E, Rowe M, Sekacheva M, Sheehan R, Stockdale A, Thomas A, Turtle L, Viñal D, Weaver J, Williams S, Wilson C, Dive C, Landers D, Cooksley T, Freitas A, Armstrong AC, Lee RJ, and On Behalf Of The Esmo Co-Care

Abstract

Patients with cancer have been shown to have increased risk of COVID-19 severity. We previously built and validated the COVID-19 Risk in Oncology Evaluation Tool (CORONET) to predict the likely severity of COVID-19 in patients with active cancer who present to hospital. We assessed the differences in presentation and outcomes of patients with cancer and COVID-19, depending on the wave of the pandemic. We examined differences in features at presentation and outcomes in patients worldwide, depending on the waves of the pandemic: wave 1 D614G (n = 1430), wave 2 Alpha (n = 475), and wave 4 Omicron variant (n = 63, UK and Spain only). The performance of CORONET was evaluated on 258, 48, and 54 patients for each wave, respectively. We found that mortality rates were reduced in subsequent waves. The majority of patients were vaccinated in wave 4, and 94% were treated with steroids if they required oxygen. The stages of cancer and the median ages of patients significantly differed, but features associated with worse COVID-19 outcomes remained predictive and did not differ between waves. The CORONET tool performed well in all waves, with scores in an area under the curve (AUC) of >0.72. We concluded that patients with cancer who present to hospital with COVID-19 have similar features of severity, which remain discriminatory despite differences in variants and vaccination status. Survival improved following the first wave of the pandemic, which may be associated with vaccination and the increased steroid use in those patients requiring oxygen. The CORONET model demonstrated good performance, independent of the SARS-CoV-2 variants.

Published
2022
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39. Temporal Summation in Fibromyalgia Patients: Comparing Phasic and Tonic Paradigms.

Author

Castelo-Branco L, Cardenas-Rojas A, Rebello-Sanchez I, Pacheco-Barrios K, de Melo PS, Gonzalez-Mego P, Marduy A, Vasquez-Avila K, Costa Cortez P, Parente J, Teixeira PEP, Rosa G, McInnis K, Caumo W, and Fregni F

Abstract

Introduction: Fibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables., Materials and Methods: In this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity., Results: Fifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, p = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = -0.5, p = 0.009)., Conclusion: Our results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Castelo-Branco, Cardenas-Rojas, Rebello-Sanchez, Pacheco-Barrios, de Melo, Gonzalez-Mego, Marduy, Vasquez-Avila, Costa Cortez, Parente, Teixeira, Rosa, McInnis, Caumo and Fregni.)

Published
2022
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40. Specific Electroencephalographic Signatures for Pain and Descending Pain Inhibitory System in Spinal Cord Injury.

Author

Simis M, Pacheco-Barrios K, Uygur-Kucukseymen E, Castelo-Branco L, Battistella LR, and Fregni F

Subjects
Cross-Sectional Studies, Humans, Pain complications, Pain Measurement, Electroencephalography methods, Spinal Cord Injuries complications
Abstract

Objectives: The pain related to spinal cord injury (SCI) is difficult to treat, and it is associated with significant morbidity. One aspect to improve therapeutics is to explore markers of pain and its correlates in SCI., Methods: In this cross-sectional neurophysiological analysis of a randomized, double-blind controlled trial, 39 patients with SCI were included. We analyzed conditioned pain modulation (CPM) efficiency as the index of the descending pain inhibitory system, EEG variables, and clinical pain levels as measured by the Visual Analogue Scale. Regression analyses were performed to assess the relationship among EEG variables, pain levels, and CPM., Results: We included 39 SCI patients, 74% reported SCI-related pain. We found that (1) less alpha and beta power are related to pain presence, (2) less alpha and beta power are associated with higher pain levels among patients with pain, (3) patients with pain have decreased peak alpha-theta frequency compared to no-pain group, (4) more relative theta power are related to the presence of low CPM efficiency, (5) higher relative theta power is associated with lower CPM efficiency., Conclusions: Our results confirm and provide additional data on the relationship between decreased alpha and beta frequencies and higher pain levels. One important finding, though, was a specific and different EEG signature for the descending inhibitory pain system, as we showed that increased theta EEG power is related to decreased CPM efficiency; suggesting that, although low CPM efficiency plays a major role in pain in these participants, it does seem to be associated with a specific oscillatory brain rhythm different from clinical pain. These findings have significant implications for future research on EEG-based biomarkers of pain in post-SCI and new interventions as neurofeedback to manage pain in this population., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2022
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41. Association Between Step Count Measured With a Smartphone App (Pain-Note) and Pain Level in Patients With Chronic Pain: Observational Study.

Author

Ogawa T, Castelo-Branco L, Hatta K, and Usui C

Abstract

Background: Chronic pain is the leading cause of disability, affecting between 20% and 50% of the global population. The key recommended treatment is physical activity, which can be measured in daily life using a pedometer. However, poor adherence to pedometer use can result in incorrect measurements. Furthermore, only a few studies have investigated a possible curvilinear association between physical activity and chronic pain., Objective: In this study, we developed the Pain-Note smartphone app to collect real-world data on step count, using the smartphone's built-in pedometer. The aims of our research are (1) to evaluate the association between daily step count and pain level among patients with chronic pain and (2) determine if the association between daily step count and pain level was curvilinear., Methods: We conducted a cross-sectional study based on step count data collected with the app and on the results of questionnaires, which measured the duration and intensity of pain, the widespread pain index, the symptom severity score, and the insomnia severity scale, including 7 questions for symptoms of depression. We analyzed the association between step count and pain level as a nonlinear relationship using a restricted cubic spline model. A prespecified subgroup analysis was also conducted based on fibromyalgia criteria., Results: Between June 1, 2018, and June 11, 2020, a total of 6138 records were identified, of which 1273 were analyzed. The mean age of the participants was 38.7 years, 81.9% (1043/1273) were female, and chronic pain was present for more than 5 years in 43.2% (550/1273) of participants. Participants in the third and fourth quartiles for step count (more than 3045 and 5668 steps a day, respectively) showed a significant positive association between higher step count and lower numerical pain rating scale (mean difference -0.43, 95% CI -0.78 to -0.08, P=.02; -0.45; 95% CI -0.8 to -0.1, P=.01, respectively) than those in the first quartile (less than or equal to 1199 steps a day). The restricted cubic spline model for the association between step count and pain scale displayed a steep decline followed by a moderate decrease as the step count increased; the inflection point was 5000 steps. However, this association was not observed among participants who met the fibromyalgia criteria (491/1273), who showed a steep positive increase below 2000 steps. Data were collected between June 1, 2018, and June 11, 2020, and were analyzed on November 18, 2021., Conclusions: Step count measured with the Pain-Note app showed a nonlinear association with pain level. Although participants with and without fibromyalgia showed a negative correlation between step count and pain level, participants who meet the criteria for fibromyalgia may present a different relationship between walking and pain perception compared to those in the general chronic pain population., (©Takahisa Ogawa, Luis Castelo-Branco, Kotaro Hatta, Chie Usui. Originally published in JMIR Formative Research (https://formative.jmir.org), 06.04.2022.)

Published
2022
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42. Recruitment characteristics and non-adherence associated factors of fibromyalgia patients in a randomized clinical trial: A retrospective survival analysis.

Author

Cardenas-Rojas A, Castelo-Branco L, Pacheco-Barrios K, Shaikh ES, Uygur-Kucukseymen E, Giannoni-Luza S, Vasconcelos Felippe L, Gonzalez-Mego P, Luna-Cuadros MA, Gianlorenco ACL, Teixeira PEP, Caumo W, and Fregni F

Abstract

Introduction: Fibromyalgia is a complex pain condition that affects mostly women. Given the disease's lack of understanding, patients report poor adherence to medication and mistrust of medical services. This study aims to describe the recruitment characteristics and non-adherence associated factors of fibromyalgia patients to an RCT., Methods: We performed a retrospective longitudinal analysis with data from our ongoing RCT. We investigated characteristics of subjects recruited, consented, and randomized. Adherence was studied using survival analysis techniques, and its associated factors were identified using Cox proportional hazards regression model., Results: 524 subjects were contacted, 269 were eligible, 61 consented and 40 subjects were randomized. Thirty-eight percent were non-adherent to the protocol with a median of visits of five. The recruitment survey reported that 90% would likely participate in RCTs, 52% had previous participation, and 19% were aware of RCTs by their physicians. Some barriers were investigator-related (staff's friendliness and receiving the results of their trial participation) and center-related (privacy-confidentiality issues and the institution's reputation), without difference between adherent and non-adherent participants. We report significant factors for non-adherence as VAS anxiety score of 5 or more (5.3 HR, p = 0.01), Body Mass Index (BMI) (0.91 HR, p = 0.041) and Quality of Life (QoL) - Personal development subdomain (0.89 HR, p = 0.046)., Conclusion: Recruitment and adherence of fibromyalgia patients is a challenge; however, they seem eager to participate in RCTs. We recommend creating a comfortable, friendly and trusting environment to increase the recruitment rate. Higher anxiety, lower BMI and lower quality of life were associated with a higher attrition rate., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Inc.)

Published
2021
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43. Barriers and facilitators for clinical trial participation of underrepresented and non-underrepresented fibromyalgia patients: A cross-sectional internet survey.

Author

Cardenas-Rojas A, Pacheco-Barrios K, Castelo-Branco L, Giannoni-Luza S, Balbuena-Pareja A, Luna-Cuadros MA, Vasconcelos Felippe L, Uygur-Kucukseymen E, Gonzalez-Mego P, Gunduz ME, Shaikh ES, Gianlorenco ACL, and Fregni F

Abstract

Background: There is a need of well-powered randomized clinical trials in fibromyalgia. However, challenges for recruitment are presented. This study aims to describe and assess the perception of barriers and facilitators and the associated factors for the participation of underrepresented and non-underrepresented fibromyalgia patients., Methods: We performed an online survey through REDCap (Research Electronic Data Capture) targeting fibromyalgia patients from April 7 to July 3, 2020 during the COVID-19 stay home mandate and it was restricted to the United States of America. We described and compared the survey characteristics between underrepresented and non-underrepresented participants, and we performed logistic regression models to assess the associated factors with clinical trial participation., Results: In total, 481 completed the survey including 168 underrepresented fibromyalgia patients. Only (1) 11.09 % reported previous participation in clinical trials and the significant perceived barriers were investigator-related (lack of friendliness of research staff and the opportunity to receive the results) and center-related (privacy and confidentiality policies, and the institution's reputation); (2) the participation rate and perceived barriers and facilitators were similar between underrepresented and non-underrepresented patients; and was positively associated with low income, higher age, and clinical trial awareness from their physician; and negatively associated with the perception of investigator-related barriers; and (4) for the underrepresented population, the presence of emotional support., Conclusion: Our findings suggest low rates of participation, regardless of underrepresented population status. Strategies as involving their physician as liaison to increase the awareness of clinical trials, as well as improving patient-researcher communication should be considered in this population., Competing Interests: The authors declare no conflict of interest., (© 2021 Published by Elsevier Ltd.)

Published
2021
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44. Therapeutic Approaches With Immune Checkpoint Inhibitors in Head and Neck Cancers and the Role of PD-L1 as a Biomarker.

Author

Oualla K, Castelo Branco L, Nouiyakh L, Amaadour L, Benbrahim Z, Arifi S, and Mellas N

Subjects
B7-H1 Antigen physiology, Biomarkers, Tumor physiology, Clinical Trials as Topic, Clinical Trials, Phase III as Topic, Humans, Head and Neck Neoplasms drug therapy, Immune Checkpoint Inhibitors therapeutic use, Squamous Cell Carcinoma of Head and Neck drug therapy
Abstract

Head and neck squamous cell carcinoma (HNSCC) is a potential curative disease at its localized stage, by the use of multimodal treatment including surgery, radiation, and chemotherapy. While the metastatic stage is considered incurable and is characterized by poor prognosis. Conventional cytotoxic chemotherapy in addition to cetuximab were the only available systemic treatment with limited efficacy and modest median overall survival barely crossing the 1 year limit. Immunotherapy with PD-1 and PD-L1 inhibitors has revolutionized the treatment of multiple cancers. Recently, Immunotherapy is being extensively explored in head and neck cancer and clinical trials have shown impressive results that allowed to immune check point inhibitors to be the new standard of care. In this article we tried to explain the rationale and mechanisms of targeting the immune system in head and neck carcinoma and to report the results from the phase III clinical trials that put the immunotherapy as a new standard of care for head and neck cancer.

Published
2021
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46. Optimised transcranial direct current stimulation (tDCS) for fibromyalgia-targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol.

Author

Castelo-Branco L, Uygur Kucukseymen E, Duarte D, El-Hagrassy MM, Bonin Pinto C, Gunduz ME, Cardenas-Rojas A, Pacheco-Barrios K, Yang Y, Gonzalez-Mego P, Estudillo-Guerra A, Candido-Santos L, Mesia-Toledo I, Rafferty H, Caumo W, and Fregni F

Subjects
Adult, Double-Blind Method, Exercise Therapy methods, Female, Humans, Male, Middle Aged, Prospective Studies, Randomized Controlled Trials as Topic, Young Adult, Fibromyalgia therapy, Pain Management methods, Transcranial Direct Current Stimulation methods
Abstract

Introduction: Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control., Methods and Analysis: A prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)-primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study-CPM and TSPS-and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables., Ethics and Dissemination: This study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications., Trial Registration Number: NCT03371225., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2019
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47. Promising Immuno-Oncology Treatments Beyond the 2018 Nobel Prize.

Author

Castelo-Branco L, Silva IP, Canhão H, and Awada A

Subjects
Antibodies, Monoclonal therapeutic use, Cancer Vaccines therapeutic use, Humans, Lymphocyte Activation, Melanoma therapy, Skin Neoplasms therapy, CTLA-4 Antigen antagonists & inhibitors, Immunotherapy, Adoptive methods, Neoplasms therapy, Nobel Prize, Programmed Cell Death 1 Receptor antagonists & inhibitors
Published
2019
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