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28 results on '"Fortunato, Lea"'

1. Intradermal substance P as a challenge agent in healthy individuals

Author

ten Voorde, Wouter, primary, Akinseye, Chika, additional, Abdisalaam, Ismahaan, additional, Wind, Selinde, additional, Klarenbeek, Naomi, additional, Bergmans, Menthe, additional, van Doorn, Martijn, additional, Rissmann, Robert, additional, Kaur, Rejbinder, additional, Hotee, Sarah, additional, Foster, Katie, additional, Nair, Arati, additional, Fortunato, Lea, additional, Macphee, Colin, additional, Mole, Sarah, additional, Baumann, Katrine, additional, and Brigandi, Richard, additional

Published
2023
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2. Intradermal substance P as a challenge agent in healthy individuals

Author

ten Voorde, Wouter, Akinseye, Chika, Abdisalaam, Ismahaan, Wind, Selinde, Klarenbeek, Naomi, Bergmans, Menthe, van Doorn, Martijn, Rissmann, Robert, Kaur, Rejbinder, Hotee, Sarah, Foster, Katie, Nair, Arati, Fortunato, Lea, Macphee, Colin, Mole, Sarah, Baumann, Katrine, Brigandi, Richard, ten Voorde, Wouter, Akinseye, Chika, Abdisalaam, Ismahaan, Wind, Selinde, Klarenbeek, Naomi, Bergmans, Menthe, van Doorn, Martijn, Rissmann, Robert, Kaur, Rejbinder, Hotee, Sarah, Foster, Katie, Nair, Arati, Fortunato, Lea, Macphee, Colin, Mole, Sarah, Baumann, Katrine, and Brigandi, Richard

Abstract

Pharmacological challenge models are deployed to evaluate drug effects during clinical development. Intradermal injection of Substance P (SP) neuropeptide, a potential challenge agent for investigating local mediators, is associated with wheal and flare response mediated by the MRGPRX2 receptor. Although dose-dependent data on SP effects exist, full characterization and information on potential carryover effect after repeated challenge are lacking. This open-label, two-part, prospective enabling study of SP intradermal challenge in healthy participants aimed to understand and distinguish between wheal and flare responses following various SP doses. Part 1 included one challenge visit to determine optimum SP dose range for evaluation in part 2, which determined variability in 20 participants and used intradermal microdialysis (IDM) for SP-challenged skin sampling. At 5, 15, 50, and 150 pmol doses, respectively, posterior median area under the curve (AUC; AUC0–2h) was 4090.4, 5881.2, 8846.8, and 9212.8 mm2/min, for wheal response, and 12020.9, 38154.3, 65470.6, and 67404.4 mm2/min for flare response (SP-challenge visit 2). When the challenge was repeated ~2 weeks later, no carryover effect was observed. IDM histamine levels were relatively low, resulting in low confidence in the data to define temporal characteristics for histamine release following SP challenge. No safety concerns were identified using SP. Wheal and flare responses following intradermal SP challenge were dose-dependent and different. The results indicate that this challenge model is fit-for-purpose in future first-in-human studies and further assessment of novel drugs targeting dermal inflammatory disease responses, such as chronic spontaneous urticaria, chronic inducible urticaria, and pseudo-allergic reactions.

Published
2023

6. 678 - Patient-reported outcomes for GSK1070806, an anti-IL-18 monoclonal antibody: a phase 1b, randomised, double-blind, parallel-group placebo-controlled study of patients with atopic dermatitis.

Author

Ghafoori, Parima, Fortunato, Lea, Patel, Dharm S, Ellis, Joanne, Wong, Gabriel, Kelly, John B, Birch, Helen, Chen, Wen-Hung, and Uings, Iain

Subjects
*SLEEP interruptions, *SLEEP duration, *ATOPIC dermatitis, *PATIENT reported outcome measures, *FATIGUE (Physiology)
Abstract

Introduction/Background Administration of GSK1070806, an anti–IL-18 monoclonal antibody, in patients with atopic dermatitis (AD) resulted in significant clinical improvements versus placebo after 12 weeks. Objectives Assessment of patient-reported outcomes (PROs) for patients with AD receiving GSK1070806. Methods In this multicentre, randomised, double-blind, parallel-group study (NCT04975438), adults (≥18 years) with confirmed AD diagnosis for ≥6 months and moderate-to-severe disease (Eczema Area and Severity Index ≥16; Investigator's Global Assessment score ≥3) received 2 mg/kg GSK1070806 or placebo (single one-hour intravenous infusion). PRO measures included Peak Pruritis Numerical Rating Scale (PP-NRS), Dermatology Life Quality Index (DLQI), Patient-Reported Outcomes Measurement Information System Sleep Disturbance Short Form 8b (PROMIS-SD 8b), Brief Fatigue Inventory Item 3 (BFI-Item 3), and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). PROs were assessed at baseline and either daily (PP-NRS and BFI-Item 3) or a combination of weekly (up to Week 4) and biweekly (after Week 4) (PROMIS-SD, DLQI and FACIT-F) for up to 24 weeks. Changes from baseline (CFB) in PP-NRS and DLQI scores at Week 12 were analysed using a Bayesian repeated measures model with all other PROs analysed descriptively. Results Of 34 enrolled patients (53% female, mean [standard deviation] age 44.8 [16.9] years), 23 received GSK1070806 and 11 received placebo. Posterior median of difference (95% credible interval) CFB at Week 12 in PP-NRS were -4.6 (-5.5, -3.7; GSK1070806) and -0.5 (-1.7, 0.7; placebo), and for DLQI were -6.1 (-8.8, -3.4; GSK1070806) and -0.01 (-4.3, 4.1; placebo). Observed mean PROMIS-SD 8b, BFI-Item 3 and FACIT-F scores also indicated improvements among patients who received GSK1070806 versus placebo. Conclusions Patients with moderate-to-severe AD who received GSK1070806 experienced positive improvements across all PROs versus placebo. These results provide further evidence of GSK1070806 benefit in patients with moderate-to-severe AD. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study

Author

Ellis, Joanne, Van Maurik, Andre, Fortunato, Lea, Gisbert, Sophie, Chen, Keguan, Schwartz, Ann, McHugh, Simon, Want, Andrew, Santos Franco, Sara, Oliveira, Joao-Joaquim, Price, Jeffrey, Coles, Alasdair, Brown, Kim, Su, Donggang, Craigen, Jenny L, Yang, Jiansong, Brett, Sara, Davis, Bill, Cheriyan, Joseph, Kousin-Ezewu, Onajite, Gray, Frank, Thompson, Paul W, Fernando, Disala, Coles, Alasdair [0000-0003-4738-0760], Cheriyan, Joseph [0000-0001-6921-1592], and Apollo - University of Cambridge Repository

Subjects
immunology, drug safety, pharmacodynamics, monoclonal antibodies, pharmacokinetics
Abstract

AIM: Interleukin (IL)-7 signalling modulates T cell activity and is implicated in numerous autoimmune diseases. The present study investigated the safety, pharmacokinetics, target engagement, pharmacodynamics and immunogenicity of GSK2618960, an IL-7 receptor-α subunit (CD127) monoclonal antibody. METHODS: A double-blind (sponsor-unblind) study of a single intravenous infusion of either GSK2618960 (0.6 mg kg-1 or 2.0 mg kg-1 ) or placebo was carried out in 18 healthy subjects over 24 weeks. RESULTS: GSK2618960 was well tolerated; there were no serious or significant adverse events. The observed half-life was 5 (±1) days (2.0 mg kg-1 ), with nonlinear pharmacokinetics. Full receptor occupancy (>95%) was observed until day 8 (0.6 mg kg-1 ) and day 22 (2.0 mg kg-1 ). Maximal inhibition of IL-7-mediated signal transducer and activator of transcription 5 (STAT5) phosphorylation was observed in 5/6 subjects until day 22 (2.0 mg kg-1 ). Mean circulating IL-7 and soluble receptor (CD127) levels were increased above baseline during days 2 and 15 (0.6 mg kg-1 ) and days 2 and 22 (2.0 mg kg-1 ). No meaningful changes were observed in absolute numbers or proportions of immune cell populations or inflammatory cytokine profiles (IL-6, tumour necrosis factor-α, interferon-γ, IL-2). Persistent antidrug antibodies (ADAs) were detected in 5/6 subjects administered a dose of 0.6 mg kg-1 (neutralizing in 2/6) and in 6/6 subjects administered 2.0 mg kg-1 (neutralizing in 5/6). CONCLUSION: GSK2618960 was well tolerated and blocked IL-7 receptor signalling upon full target engagement. Although there was no discernible impact on peripheral T cell subsets in healthy subjects, GSK2618960 may effectively modulate the autoinflammatory activity of pathogenic T cells in diseased tissue. A relatively short half-life is likely the result of target-mediated rather than ADA-mediated clearance., GSK

Published
2019
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9. Anti‐IL‐7 receptor α monoclonal antibody (GSK2618960) in healthy subjects – a randomized, double‐blind, placebo‐controlled study

Author

Ellis, Joanne, primary, Maurik, Andre, additional, Fortunato, Lea, additional, Gisbert, Sophie, additional, Chen, Keguan, additional, Schwartz, Ann, additional, McHugh, Simon, additional, Want, Andrew, additional, Santos Franco, Sara, additional, Oliveira, Joao‐Joaquim, additional, Price, Jeffrey, additional, Coles, Alasdair, additional, Brown, Kim, additional, Su, Donggang, additional, Craigen, Jenny L., additional, Yang, Jiansong, additional, Brett, Sara, additional, Davis, Bill, additional, Cheriyan, Joseph, additional, Kousin‐Ezewu, Onajite, additional, Gray, Frank, additional, Thompson, Paul W., additional, and Fernando, Disala, additional

Published
2018
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10. A century of trends in adult human height

Author

Bentham, James, Di Cesare, Mariachiara, Stevens, Gretchen A., Zhou, Bin, Bixby, Honor, Cowan, Melanie, Fortunato, Lea, Bennett, James E., Danaei, Goodarz, Hajifathalian, Kaveh, Lu, Yuan, Riley, Leanne M., Laxmaiah, Avula, Kontis, Vasillis, Paciorek, Christopher J., Riboli, Elio, Ezzati, Majid, and NCD Risk Factor Collaboration, (NCD-RisC)

Abstract

Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

Published
2016

11. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19·2 million participants

Author

Di Cesare, Mariachiara, Bentham, James, Stevens, Gretchen A., Zhou, Bin, Danaei, Goodarz, Lu, Yuan, Bixby, Honor, Cowan, Melanie J., Riley, Leanne M., Hajifathalian, Kaveh, Fortunato, Lea, Taddei, Cristina, Bennett, James E., Ikeda, Nayu, Khang, Young-Ho, Kyobutungi, Catherine, Laxmaiah, Avula, Li, Yanping, Lin, Hsien-Ho, Miranda, J. Jaime, Mostafa, Aya, Turley, Maria L., Paciorek, Christopher J., Gunter, Marc, Ezzati, Majid, NCD Risk Factor Collaboration, (NCD-RisC), and NCD-RisC Group

Abstract

Background: Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries.\ud \ud Methods: We analysed, with use of a consistent protocol, population based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (

Published
2016

12. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants

Author

Cesare, Mariachiara Di, Bentham, James, Stevens, Gretchen A., Zhou, Bin, Danaei, Goodarz, Lu, Yuan, Bixby, Honor, Cowan, Melanie J., Riley, Leanne M., Hajifathalian, Kaveh, Fortunato, Lea, Taddei, C., Bennett, James E., Ikeda, Nayu, Khang, Young-Ho, Kyobutungi, Catherine, Laxmaiah, Avula, Li, Yanping, Lin, Hsien-Ho, Miranda, J. Jaime, Mostafa, Aya, Turley, Maria L., Paciorek, Christopher J., Gunter, Marc, Ezzati, Majid, Abdeen, Ziad A., Hamid, Zargar Abdul, Abu-Rmeileh, Niveen M., Acosta-Cazares, Benjamin, Adams, Robert, Aekplakorn, Wichai, Aguilar-Salinas, Carlos A., Agyemang, Charles, Ahrens, Wolfgang, Ali, Farhan, Alkerwi, Ala'a, Alvarez-Pedrerol, Mar, Aly, Eman, Amouyel, Philippe, Amuzu, Antoinette, Andersen, Lars Bo, Anderssen, Sigmund A., Andrade, Dolores S., Anjana, Ranjit Mohan, Aounallah-Skhiri, Hajer, Ariansen, Inger, Aris, Tahir, Arlappa, Nimmathota, Arveiler, Dominique, Assah, Felix K., Avdicova, Maria, Azizi, Fereidoun, Babu, Bontha V., Balakrishna, Nagalla, Bandosz, Piotr, Banegas, Jose R., Barbagallo, Carlo M., Barcelo, Alberto, Barkat, Amina, Barros, Mauro V., Bata, Iqbal, Batieha, Anwar M., Batista, Rosangela L., Baur, Louise A., Beaglehole, Robert, Romdhane, H. B., Benet, Mikhail, Bernabe-Ortiz, Antonio, Bernotine, Gailute, Bettiol, Heloisa, Bhagyalaxmi, Aroor, Bharadwaj, Sumit, Bhargava, Santosh K., Bhatti, Zaid, Bhutta, Zulfiqar A., Bi, HongSheng, Bi, Yufang, Bjerregaard, Peter, Bjertness, Espen, Bjertness, Marius B., Bjorkelund, Cecilia, Blake, Margaret, Blokstra, Anneke, Bo, Simona, Bobak, Martin, Boddy, Lynne M., Boehm, Bernhard O., Boeing, Heiner, Boissonnet, Carlos P., Bongard, Vanina, Bovet, Pascal, Bradbury, Mark, Bragt, Marjolijn C. E., Brajkovich, Imperia, Branca, Francesco, Breckenkamp, Juergen, Brenner, Hermann, Brewster, Lizzy M., Brian, Garry R., Bruno, Graziella, Bueno-de-Mesquita, H. B., Bugge, Anna, Burns, C., Leon, Antonio Cabrera de, Cacciottolo, Joseph, Cama, Tilema, Cameron, Christine, Camolas, Jose, Can, Gunay, Candido, Ana Paula C., Capuano, Vincenzo, Cardoso, Viviane C., Carvalho, Maria J., Casanueva, Felipe F., Casas, Juan-Pablo, Caserta, Carmelo A., Castetbon, Katia, Chamukuttan, Snehalatha, Chan, Angelique W., Chan, Queenie, Chaturvedi, Himanshu K., Chaturvedi, Nishi, Chen, Chien-Jen, Chen, Fangfang, Chen, Shuohua, Chen, Y. Z., Cheng, Ching-Yu, Chetrit, Angela, Chiolero, Arnaud, Chiou, Shu-Ti, Chirita-Emandi, Adela, Cho, Yumi, Christensen, Kaare, Chudek, Jerzy, Cifkova, Renata, Claessens, Frank, Clays, Els, Concin, Hans, Cooper, Cyrus, Cooper, Rachel, Coppinger, Tara C., Costanzo, Simona, Cottel, Dominique, Cowell, Chris, Craig, Cora L., Crujeiras, Ana B., D'Arrigo, Graziella, d'Orsi, Eleonora, Dallongeville, Jean, Damasceno, Albertino, Damsgaard, Camilla T., Dankner, Rachel, Dauchet, Luc, Backer, Guy De, Bacquer, Dirk De, Gaetano, Giovanni de, Hanauw, Stefaan De, Smedt, Delphine De, Deepa, Mohan, Deev, Alexander D., Dehghan, Abbas, Delisle, Helene, Delpeuch, Francis, Dhana, Klodian, Castelnuovo, Augusto F. Di, Dias-da-Costa, Juvenal Soares, Diaz, Alejandro, Djalalinia, Shirin, Do, Ha T. P., Dobson, Annette J., Donfrancesco, Chiara, Döring, A., Doua, Kouamelan, Drygas, Wojciech, Egbagbe, Eruke E., Eggertsen, Robert, Ekelund, Ulf, Ati, Jalila El, Elliott, Paul, Engle-Stone, Reina, Erasmus, Rajiv T., Erem, Cihangir, Eriksen, Louise, Peña, J. E. De La, Evans, Alun, Faeh, David, Fall, Caroline H., Farzadfar, Farshad, Felix-Redondo, Francisco J., Ferguson, Trevor S., Fernandez-Berges, Daniel, Ferrante, Daniel, Ferrari, Marika, Ferreccio, Catterina, Ferrieres, Jean, Finn, Joseph D., Fischer, Krista, Flores, E. M., Foeger, Bernhard, Foo, Leng Huat, Forslund, Ann-Sofie, Fortmann, Stephen P., Fouad, Heba M., Francis, Damian K., Franco, M. Do Carmo, Franco, Oscar H., Frontera, Guillermo, Fuchs, Flavio D., Fuchs, Sandra C., Fujita, Yuki, Furusawa, Takuro, Gaciong, Zbigniew, Gafencu, Mihai, Gareta, Dickman, Garnett, Sarah P., Gaspoz, Jean-Michel, Gasull, Magda, Gates, Louise, Geleijnse, Johanna M., Ghasemian, Anoosheh, Giampaoli, Simona, Gianfagna, Francesco, Giovannelli, Jonathan, Giwercman, Aleksander, Goldsmith, Rebecca A., Gross, M. G., Rivas, J. P. G., Gorbea, M. B., Gottrand, Frederic, Graff-Iversen, Sidsel, Grafnetter, Dusan, Grajda, Aneta, Grammatikopoulou, Maria G., Gregor, Ronald D., Grodzicki, Tomasz, Grontved, Anders, Gruden, Grabriella, Grujic, Vera, Gu, Dongfeng, Guan, Ong Peng, Gudnason, Vilmundur, Guerrero, Ramiro, Guessous, Idris, Guimaraes, Andre L., Gulliford, Martin C., Gunnlaugsdottir, Johanna, Guo, Xiu H., Guo, Yin, Gupta, Prakash C., Gureje, Oye, Gurzkowska, Beata, Gutierrez, Laura, Gutzwiller, Felix, Halkjaer, Jytte, Hardy, Rebecca, Kumar, Rachakulla Hari, Hayes, Alison J., He, Jiang, Hendriks, Marleen Elisabeth, Cadena, L. H., Heshmat, Ramin, Hihtaniemi, Ilpo Tapani, Ho, Sai Yin, Ho, Suzanne C., Hobbs, Michael, Hofman, Albert, Hormiga, Claudia M., Horta, Bernardo L., Houti, Leila, Htay, Thein Thein, Htet, Aung Soe, Htike, Maung Maung Than, Hu, Yonghua, Hussieni, Abdullatif S., Huu, C. N., Huybrechts, Inge, Hwalla, Nahla, Iacoviello, Licia, Iannone, Anna G., Ibrahim, Mohsen M., Ikram, M. Arfan, Irazola, Vilma E., Islam, Muhammad, Iwasaki, Masanori, Jackson, Rod T., Jacobs, Jeremy M., Jafar, Tazeen, Jamil, Kazi M., Jamrozik, Konrad, Jasienska, Grazyna, Jiang, Chao Qiang, Joffres, Michel, Johansson, Mattias, Jonas, Jost B., Jorgensen, Torben, Joshi, Pradeep, Juolevi, Anne, Jurak, Gregor, Juresa, Vesna, Kaaks, Rudolf, Kafatos, Anthony, Kalter-Leibovici, Ofra, Kapantais, Efthymios, Kasaeian, Amir, Katz, Joanne, Kaur, Prabhdeep, Kavousi, Maryam, Keil, Ulrich, Boker, Lital Keinan, Kelishadi, Roya, Kemper, Han C. G., Kengne, Andre Pascal, Kersting, Mathilde, Key, Timothy, Khader, Yousef Saleh, Khalili, Davood, Khaw, Kay-Tee H., Khouw, Ilse M. S. L., Kiechl, Stefan, Killewo, Japhet, Kim, Jeongseon, Kiyohara, Yutaka, Klimont, Jeannette, Kolle, Elin, Kolsteren, Patrick, Korrovits, Paul, Koskinen, Seppo, Kouda, Katsuyasu, Koziel, Slawomir, Kratzer, Wolfgang, Krokstad, Steinar, Kromhout, Daan, Kruger, Herculina S., Kula, Krzysztof, Kulaga, Zbigniew, Kumar, R. Krishna, Kusuma, Yadlapalli S., Kuulasmaa, Kari, Laamiri, Fatima Zahra, Laatikainen, Tiina, Lachat, Carl, Laid, Youcef, Lam, Tai Hing, Landrove, Orlando, Lanska, Vera, Lappas, Georg, Laugsand, Lars E., Bao, K. Le Nguyen, Le, Tuyen D., Leclercq, Catherine, Lee, Jeannette, Lehtimaki, Terho, Lekhraj, Rampal, Leon-Munoz, Luz M., Lim, Wei-Yen, Lima-Costa, M. F., Lin, Xu, Linneberg, Allan, Lissner, Lauren, Litwin, Mieczyslaw, Liu, Jing, Lorbeer, Roberto, Lotufo, Paulo A., Lozano, J. E., Luksiene, Dalia, Lundqvist, Annamari, Lunet, Nuno, Lytsy, Per, Ma, Guansheng, Machi, Suka, Maggi, Stefania, Magliano, Dianna J., Makdisse, Marcia, Malekzadeh, Reza, Malhotra, Rahul, Rao, Kodavanti Mallikharjuna, Manios, Yannis, Mann, Jim I., Manzato, Enzo, Margozzini, Paula, Markey, Oonagh, Marques-Vidal, Pedro, Marrugat, Jaume, Martin-Prevel, Yves, Martorell, Reynaldo, Masoodi, Shariq R., Matsha, Tandi E., Mazur, Artur, Mbanya, Jean Claude N., McFarlane, Shelly R., McGarvey, Stephen T., McKee, Martin, McLachlan, Stela, McLean, Rachael M., McNulty, Breige A., Yusof, S. Md, Mediene-Benchekor, Sounnia, Meirhaeghe, Aline, Meisinger, Christa, Mendes, Larissa L., Menezes, Ana Maria B., Mensink, Gert B. M., Meshram, Indrapal I., Metspalu, Andres, Mi, Jie, Michaelsen, Kim F., Mikkel, Kairit, Miller, Jody C., Miquel, J. F., Misigoj-Durakovic, Marjeta, Mohamed, Mostafa K., Mohammad, Kazem, Mohammadifard, Noushin, Mohan, Viswanathan, Yusoff, Muhammad Fadhli Mohd, Molbo, Drude, Moller, Niels C., Molnar, Denes, Mondo, Charles K., Monterrubio, Eric A., Monyeki, Kotsedi Daniel K., Moreira, Leila B., Morejon, Alain, Moreno, Luis A., Morgan, Karen, Mortensen, Erik Lykke, Moschonis, George, Mossakowska, Malgorzata, Mota, Jorge, Motlagh, Mohammad Esmaeel, Motta, Jorge, Mu, Thet Thet, Muiesan, Maria Lorenza, Mueller-Nurasyid, Martina, Murphy, Neil, Mursu, Jaakko, Murtagh, Elaine M., Musa, Kamarul Imran, Musil, Vera, Nagel, Gabriele, Nakamura, Harunobu, Namesna, Jana, Nang, E. E. K., Nangia, Vinay B., Nankap, Martin, Narake, Sameer, Navarrete-Muñoz, E. M., Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Neuhauser, Hannelore K., Nguyen, Nguyen D., Nieto-Martinez, Ramfis E., Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Norat, Teresa, Noto, Davide, Nsour, Mohannad Al, O'Reilly, Dermot, Ochoa-Avilés, A. M., Oh, Kyungwon, Olayan, Iman H., Olinto, M. T. A., Oltarzewski, Maciej, Omar, Mohd A., Onat, Altan, Ordunez, Pedro, Ortiz, Ana P., Osler, Merete, Osmond, Clive, Ostojic, Sergej M., Otero, Johanna A., Overvad, Kim, Paccaud, Fred Michel, Padez, Cristina, Pajak, Andrzej, Palli, Domenico, Palloni, Alberto, Palmieri, Luigi, Panda-Jonas, Songhomitra, Panza, Francesco, Parnell, Winsome R., Parsaeian, Mahboubeh, Pednekar, Mangesh S., Peeters, Petra H., Peixoto, Sergio Viana, Pereira, Alexandre C., Perez, Cynthia M., Peters, Annette, Peykari, Niloofar, Pham, S. T., Pigeot, Iris, Pikhart, Hynek, Pilav, Aida, Pilotto, Lorenza, Pistelli, Francesco, Pitakaka, Freda, Piwonska, Aleksandra, Piwonski, J., Plans-Rubio, Pedro, Poh, Bee Koon, Porta, Miquel, Portegies, Marileen L. P., Poulimeneas, Dimitrios, Pradeepa, Rajendra, Prashant, Mathur, Price, Jacqueline F., Puiu, Maria, Punab, Margus, Qasrawi, Radwan F., Qorbani, Mostafa, Bao, T. Q., Radic, Ivana, Radisauskas, Ricardas, Rahman, Mahmudur, Raitakari, Olli, Raj, Manu, Rao, Sudha Ramachandra, Ramachandran, Ambady, Ramke, Jacqueline, Ramos, Rafel, Rampal, Sanjay, Rasmussen, Finn, Redon, Josep, Reganit, Paul Ferdinand M., Ribeiro, Robespierre, Riboli, Elio, Rigo, Fernando, Wit, Tobias Floris Rinke de, Ritti-Dias, Raphael M., Rivera, Juan A., Robinson, Sian M., Robitaille, Cynthia, Rodriguez-Artalejo, Fernando, Rodriguez-Perez, Maria del Cristo, Rodriguez-Villamizar, Laura A., Rojas-Martinez, Rosalba, Rojroongwasinkul, Nipa, Romaguera, Dora, Ronkainen, Kimmo, Rosengren, Annika, Rouse, Ian, Rubinstein, Adolfo, Ruhli, Frank J., Rui, Ornelas, Ruiz-Betancourt, B. S., Horimoto, Andrea R. V. Russo, Rutkowski, Marcin, Sabanayagam, Charumathi, Sachdev, Harshpal S., Saidi, Olfa, Salanave, Benoit, Martinez, E. S., Salomaa, Veikko, Salonen, Jukka T., Salvetti, Massimo, Sanchez-Abanto, Jose, Sandjaja, Sans, Susana, Santos, Diana A., Santos, Osvaldo, Santos, Renata Nunes dos, Santos, Rute, Sardinha, Luis B., Sarrafzadegan, Nizal, Saum, Kai-Uwe, Savva, Savvas C., Scazufca, Marcia, Rosario, Angelika Schaffrath, Schargrodsky, Herman, Schienkiewitz, Anja, Schmidt, Ida Maria, Schneider, Ione J., Schultsz, Constance, Schutte, Aletta E., Sein, Aye Aye, Sen, Abhijit, Senbanjo, Idowu O., Sepanlou, Sadaf G., Shalnova, Svetlana A., Shaw, Jonathan E., Shibuya, Kenji, Shin, Youchan, Shiri, Rahman, Siantar, Rosalynn, Sibai, Abla M., Silva, Antonio M., Silva, D. A. S., Simon, Mary, Simons, Judith, Simons, Leon A., Sjostrom, Michael, Slowikowska-Hilczer, Jolanta, Slusarczyk, Przemyslaw, Smeeth, Liam, Smith, Margaret C., Snijder, Marieke B., So, Hung-Kwan, Sobngwi, Eugene, Soderberg, Stefan, Soekatri, Moesijanti Y. E., Solfrizzi, Vincenzo, Sonestedt, Emily, Sorensen, Thorkild I. A., Soric, Maroje, Jerome, Charles Sossa, Soumare, Aicha, Staessen, Jan A., Starc, Gregor, Stathopoulou, Maria G., Staub, Kaspar, Stavreski, Bill, Steene-Johannessen, Jostein, Stehle, Peter, Stein, Aryeh D., Stergiou, George S., Stessman, Jochanan, Stieber, Jutta, Stöckl, D., Stocks, Tanja, Stokwiszewski, Jakub, Stratton, Gareth, Strufaldi, Maria Wany, Sun, C. A., Sundstroem, Johan, Sung, Y. T., Sunyer, Jordi, Suriyawongpaisal, Paibul, Swinburn, Boyd A., Sy, Rody G., Szponar, Lucjan, Tai, E. Shyong, Tammesoo, Mari-Liis, Tamosiunas, Abdonas, Tang, Line, Tang, Xun, Tanser, Frank, Tao, Yong, Tarawneh, Mohammed Rasoul, Tarp, Jakob, Tarqui-Mamani, Carolina B., Taylor, Anne, Tchibindat, Felicite, Thijs, Lutgarde, Thuesen, Betina H., Tjonneland, Anne, Tolonen, Hanna K., Tolstrup, Janne S., Topbas, Murat, Topor-Madry, Roman, Torrent, Maties, Traissac, Pierre, Trichopoulou, Antonia, Trichopoulos, Dimitrios, Trinh, Oanh T. 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Goya, Wareham, Nicholas, Weerasekera, Deepa, Whincup, Peter H., Widhalm, Kurt, Widyahening, Indah S., Wiecek, Andrzej, Wilks, Rainford J., Willeit, Johann, Wojtyniak, Bogdan, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C., Wu, Jianfeng, Wu, Shou Ling, Xu, Haiquan, Xu, Liang, Yamborisut, Uruwan, Yan, Weili, Yang, Xiaoguang, Yardim, Nazan, Ye, Xingwang, Yiallouros, Panayiotis K., Yoshihara, Akihiro, You, Qi Sheng, Younger-Coleman, Novie O., Yusoff, Ahmad F., Zainuddin, Ahmad A., Zambon, Sabina, Zdrojewski, Tomasz, Zeng, Yi, Zhao, Dong, Zhao, Wenhua, Zheng, Yingfeng, Zhou, Maigeng, Zhu, Dan, Zimmermann, Esther, Cisneros, Julio Zuniga, NCD Risk Factor Collaboration (NCD-RisC), Di Cesare, M., Bentham, J., Stevens, G.A., Zhou, B., Danaei, G., Lu, Y., Bixby, H., Cowan, M.J., Riley, L.M., Hajifathalian, K., Fortunato, L., Taddei, C., Bennett, J.E., Ikeda, N., Khang, Y.H., Kyobutungi, C., Laxmaiah, A., Li, Y., Lin, H.H., Miranda, J.J., Mostafa, A., Turley, M.L., 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TC, Costanzo C, Cottel D, Cowell C, Craig CL, Crujeiras AB, D'Arrigo G, d'Orsi E, Dallongeville J, Damasceno A, Damsgaard CT, Dankner R, Luc Dauchet L, De Backer G, De Bacquer D, de Gaetano G, De Henauw S, De Smedt D, Deepa M, Deev AD, Dehghan A, Delisle H, Delpeuch F, Dhana K, Di Castelnuovo AF, Dias-da-Costa JS, Diaz A, Djalalinia S, Do HTP, Dobson AJ, Donfrancesco C, Döring A, Doua K, Drygas W, Egbagbe EE, Eggertsen R, Ekelund U, El Ati J, Elliott P, Engle-Stone R, Erasmus RT, Erem C, Eriksen L, Escobedo-de la Peña J, Evans A, Faeh D, Fall CH, Farshad Farzadfar F, Felix-Redondo FJ, Ferguson TS, Fernández-Bergés D, Ferrante D, Ferrari M, Ferreccio C, Ferrieres J, Finn JD, Fischer K, Monterubio Flores E, Föger B, Foo LH, Forslund A-S, Fortmann SP, Fouad HM, Francis DK, Franco MdC, Franco OH, Guillermo Frontera G, Fuchs FH, Fuchs SC, Fujita Y, Furusawa T, Gaciong Z, Gafencu M, Gareta D, Garnett SP, Gaspoz J-M, GasulL M, Gates L, Geleijnse JM, Ghasemian A, Giampaoli S, GianfagnA F, Giovannelli J, Giwercman A, Goldsmith RA, Gonzalez Gross M, González Rivas JP, Gorbea MB, Gottrand F, Graff-Iversen S, Grafnetter D, Grajda A, Grammatikopoulou MG, Gregor RD, Grodzicki T, Grøntved A, Gruden G, Grujic V, Gu D, Guan OP, Gudnason V, Guerrero R, Guessous I, Guimaraes AL, Gulliford MC, Gunnlaugsdottir J, Guo XK, Guo Y, Gupta PC, Gureje O, Gurzkowska B, Gutierrez L, Gutzwiller F, Halkjær J, Hardy R, Kumar RH, Hayes AJ, He J, Hendriks ME, Hernandez Cadena L, Heshmat R, Hihtaniemi IP, Sai SY, Ho SC, Hobbs M, Hofman A, Hormiga CM, Horta BH, Houti L, Htay TT, Htet AS, Htike MMT, Hu Y, Hussieni HS, Huu CN, Huybrechts I, Hwalla N, Iacoviello L, Iannone AG, Ibrahim MM, Ikram MA, Irazola VE, Islam M, Iwasaki M, Jackson RT, Jacobs JM, Tazeen Jafar T, Jamil KM, Jamrozi K, Jasienska G, Jiang CQ, Joffres M, Johansson M, Jonas JB, Jørgensen T, Joshi P, Juolevi A, Jurak G, Vesna Jureša V, Kaaks R, Kafatos A, Kalter-Leibovici O, Kapantais E, Kasaeian A, Katz J, Kaur P, Kavousi M, Keil U, Keinan Boker L, Kelishadi R, Kemper HHCG, Kengne AP, Kersting M, Key T, Khader YS, Khalili D, Khang Y-H, Kay-Tee H Khaw K-TH, Khouw LMSL, Kiechl S, Killewo J, Kim J, Kiyohara Y, Klimont J, Kolle E, Kolsteren P, Korrovits P, Koskinen S, Kouda K, Koziel S, Kratzer W, Krokstad S, Kromhout D, Kruger HS, Kula K, Kulaga Z, Kumar RK, Kusuma YS, Kuulasmaa K, Laamiri FZ, Laatikainen T, Lachat C, Laid Y, Lam TH, Landrove O, Lanska V, Lappas G, Laugsand LE, Nguyen Bao KL, Le TD, Leclercq C, Lee J, Jeonghee Lee J, Lehtimäki T, Lekhraj R, León-Muñoz LM, Lim W-Y, M Fernanda Lima-Costa MF, Lin H-H, Lin X, Linneberg A, Lissner L, Litwin M, Liu J, Lorbeer R, Lotufo PA, Lozano JE, Luksiene D, Lundqvist A, Lunet N, Lytsy P, Ma G, Machi S, Maggi S, Magliano DJ, Makdisse M, Malekzadeh R, Malhotra R, Mallikharjuna Rao K, Manios Y, Mann JI, Manzato E, Margozzini P, Markey O, Marques-Vidal P, Marrugat P, Martin-Prevel Y, Martorell R, Masoodi SR, Matsha TE, Mazur A, Mbanya JCN, McFarlane SR, McGarvey ST, McKee M, McLachlan S, McLean RM, McNulty BA, Md Yusof S, Mediene-Benchekor S, Meirhaeghe A, Meisinger A, Mendes LL, Menezes AMB, Mensink GBM, Meshram II, Metspalu A, Mi JM, Michaelsen KF, Miller JC, Miquel JF, Mišigoj-Duraković M, Mohamed MK, Mohammad K, Mohammadifard N, Mohan V, Mohd Yusoff MF, Molbo D, Møller NC, Molnár D, Mondo CK, Monterrubio EA, Monyeki KDK, Leila B Moreira LB, Morejon A, Moreno LA, Morgan K, Mortensen EL, Moschonis G, Mossakowska M, Mota J, Motlagh ME, Motta J, Mu TT, Muiesan ML, Müller-Nurasyid M, Murphy N, Mursu J, Murtagh EM, Musa KI, Musil V, Nagel G, Nakamura H, Námešná J, Nang EEK, Nangia VB, Nankap M, Narake S, Navarrete-Muñoz EM, Nenko I, Neovius M, Nervi F, Neuhauser HK, Nguyen ND, Ngoc Nguyen Q, Nieto-Martínez RE, Ning G, Ninomiya T, Nishtar S, Noale M, Norat T, Noto D, Al Nsour M, O'Reilly D, Ochoa-Avilés AM, Oh K, Olayan IH, Olinto MTA, Oltarzewski M, Omar MA, Onat A, Ordunez P, Ortiz AP, Osler M, Osmond C, Ostojic AM, Otero JA, Overvad K, Paccaud F, Padez C, Pajak A, Palli D, Palloni A, Palmieri L, Panda-Jonas S, Panza F, Parnell WR, Parsaeian M, Pednekar MS, Peeters PH, Peixoto SV, Pereira AC, Pérez CM, Peters A, Peykari N, Pham ST, Pigeot I, Pikhart H, Pilav A, Pilotto L, Pistelli F, Pitakaka F, Piwonska A, Piwonski J, Pedro Plans-Rubió P, Poh BK, Porta M, Portegies MLP, Poulimeneas D, Pradeepa R, Prashant M, Price JF, Puiu M, Punab M, Qasrawi RF, Qorbani M, Quoc Bao T, Radic I, Ricardas Radisauskas R, Rahman M, Raitakari O, Raj M, Ramachandra Rao S, Ramachandran A, Ramke J, Ramos R, Rampal S, Rasmussen F, Redon J, Reganit PFM, Robespierre Ribeiro R, Riboli E, Rigo F, Rinke de Wit TF, Ritti-Dias RM, Juan A Rivera JA, Robinson SM, Robitaille C, Rodríguez-Artalejo F, Rodriguez-Perez MdC, Rodríguez-Villamizar LA, Rojas-Martinez R, Rojroongwasinkul N, Romaguera D, Ronkainen K, Rosengren A, Rouse I, Rubinstein A, Rühli FJ, Rui O, Ruiz-Betancourt BS, Russo Horimoto ARV, Rutkowski M, Sabanayagam C, Sachdev HS, Saidi O, Salanave B, Salazar Martinez E, Salomaa V, Salonen JT, Salvetti M, Sánchez-Abanto J, Sandjaja A, Sans S, Santos DA, Santos O, dos Santos RN, Santos R, Sardinha LB, Sarrafzadegan N, Saum K-U, Savva SC, Scazufca M, Schaffrath Rosario A, Schargrodsky H, Schienkiewitz A, Schmidt IM, Schneider IJ, Schultsz C, Schutte AE, Sein AA, Sen A, Senbanjo IO, Sepanlou SG, Shalnova SA, Shaw JE, Shibuya K, Shin Y, Shiri R, Siantar R, Sibai AM, Silva AM, Simon M, Simons J, Simons LA, Sjostrom M, Slowikowska-Hilczer J, Slusarczyk P, Smeeth L, Smith MC, Snijder MB, So H-K, Sobngwi E, Söderberg S, Soekatri MYE, Solfrizzi V, Sonestedt E, Sørensen TIA, Sorić M, Sossa Jérome C, Soumare A, Staessen JA, Starc G, Stathopoulou MG, Staub K, Stavreski B, Steene-Johannessen J, Stehle P, Stein AD, Stergiou GS, Stessman J, Stieber J, Stöckl D, Stocks T, Stokwiszewski J, Stratton G, Strufaldi MW, Chien-An Sun C-A, Sundström J, Sung Y-T, Sunyer J, Suriyawongpaisal P, Swinburn BA, Sy RG, Szponar L, E Shyong Tai E, Tammesoo M-L, Tamosiunas A, Tang L, Tang X, Tanser F, Tao Y, Tarawneh M, Jakob Tarp J, Tarqui-Mamani CB, Taylor A, Félicité Tchibindat F, Thijs L, Thuesen BH, Tjonneland A, Tolonen HK, Janne S Tolstrup JS, Topbas M, Topór-Madry R, Torrent M, Traissac P, Trichopoulos D, Trinh OTH, Trivedi A, Tshepo L, Tulloch-Reid MK, Tuomainen T-P, Tuomilehto J, Tynelius P, Tzotzas T, Tzourio C, Ueda P, Ukoli FAM, Ulmer H, Unal B, Valdivia G, Susana Va S, Valvi D, van der Schouw YT, Van Herck K, Van Minh H, van Valkengoed IGM, Vanderschueren D, Vanuzzo D, Vatten L, Vega T, Velasquez-Melendez G, Veronesi G, Verschuren WMM, Viegi G, Viet L, Viikari-Juntura E, Vineis P, Vioque P, Virtanen JK, Visvikis-Siest S, Viswanathan B, Vollenweider P, Voutilainen S, Vrijheid M, Wade AN, Wagner A, Walton J, Wan Mohamud WN, Wang M-D, Wang Q, Wang YX, Wannamethee SG, Wareham N, Deepa Weerasekera D, Whincup PH, Widhalm K, Widyahening IS, Wiecek A, Wilks RJ, Willeit J, Wojtyniak B, Wong, Wong TY, Woo J, Woodward M, Wu FC, JianFeng Wu JF, Wu SL, Xu H, Xu L, Yamborisut U, Yan W, Yang X, Yardim N, Ye X, Yiallouros PK, Yoshihara A, Qi Sheng You QS, Younger-Coleman NO, Yusoff AF, Ahmad A Zainuddin AA, Zambon S, Zdrojewski T, Zeng Y, Zhao D, Zhao W, Zheng Y, Zhou M, Zhu D, Zimmermann E, Zuñiga Cisneros J, General Internal Medicine, AII - Amsterdam institute for Infection and Immunity, Public and occupational health, Global Health, and APH - Amsterdam Public Health

Subjects
Male, Obesidad, CHILDREN, Salud, Review, países desarrollados, Global Health, Body Mass Index, Body mass index, population study, 0302 clinical medicine, Models, Factores de riesgo cardiovascular, Medicine, body mass index, underweight, overweight, obesity, Young adult, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, General Medicine, ASSOCIATION, 11 Medical And Health Sciences, adulto, predicción, adulto joven, CARDIOVASCULAR-DISEASE, thinness/epidemiology, NONCOMMUNICABLE DISEASES, NCD Risk Factor Collaboration (NCD-RisC), Enfermedades cardiovasculares, Developed country, teorema de Bayes, Medical sciences, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Thinness, Humans, education, Developing Countries, obesidad, VLAG, Science & Technology, Models, Statistical, CAUSE-SPECIFIC MORTALITY, Bayes Theorem, medicine.disease, QP, Obesity, adult body-mass, Indice de masa corporal (IMC), RISK-FACTORS, Adolescent, Adult, Developed Countries, Female, Forecasting, Obesity/epidemiology, Prevalence, Thinness/epidemiology, Young Adult, RA, Body mass index, Demography, Meta-Analysis, Gerontology, Settore MED/09 - Medicina Interna, Nutrition and Disease, humanos, adolescente, Overweight, países en desarrollo, Voeding en Ziekte, Medicine and Health Sciences, Global health, 030212 general & internal medicine, Non-U.S. Gov't, Medicine (all), Research Support, Non-U.S. Gov't, prevalencia, Public Health, Global Health, Social Medicine and Epidemiology, Statistical, Underweight, medicine.symptom, pooled analysis, Life Sciences & Biomedicine, obesity/*epidemiology, Population, 030209 endocrinology & metabolism, Research Support, Medicine, General & Internal, EPIDEMIC, General & Internal Medicine, Journal Article, Life Science, ddc:610, Obesidad morbida, OBESITY PREVENTION, OVERWEIGHT, business.industry, índice de masa corporal, COHORTS, purl.org/pe-repo/ocde/ford#3.02.00 [https], Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Ciencias socio biomédicas, business, delgadez
Abstract

Copyright © NCD Risk Factor Collaboration. Open Access article distributed under the terms of CC BY., Background: Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries. Methods: We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (, Wellcome Trust, Grand Challenges Canada

Published
2016

13. Occupational cancer in Britain

Author

Bevan, Ruth, Young, Charlotte, Holmes, Phillip, Fortunato, Lea, Slack, Rebecca, and Rushton, Lesley

Subjects
Male, Full Paper, oesophagus, liver, Risk Assessment, United Kingdom, Occupational Diseases, Risk Factors, Occupational Exposure, occupation, Carcinogens, Humans, Female, pancreas, stomach, Gastrointestinal Neoplasms
Published
2012

14. Occupational cancer in Britain

Author

Brown, Terry, Darnton, Andy, Fortunato, Lea, and Rushton, Lesley

Subjects
larynx, Male, Mesothelioma, Occupational Diseases, Lung Neoplasms, Full Paper, occupation, Humans, Female, Laryngeal Neoplasms, lung
Published
2012

16. Aircraft Noise and Cardiovascular Disease near Heathrow Airport in London

Author

Hansell*, Anna, primary, Blangiardo, Marta, additional, Fortunato, Lea, additional, Floud, Sarah, additional, de Hoogh, Kees, additional, Fecht, Daniela, additional, Ghosh, Rebecca, additional, Laszlo, Helga, additional, Pearson, Clare, additional, Beale, Linda, additional, Beevers, Sean, additional, Gulliver, John, additional, Best, Nicky, additional, Richardson, Sylvia, additional, and Elliott, Paul, additional

Published
2014
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18. THE ENVIRONMENT AND HEALTH ATLAS FOR ENGLAND AND WALES

Author

Ghosh, Rebecca, primary, Fortunato, Lea, additional, Fabbri, Federico, additional, McRobie, Ellen, additional, Laszlo, Helga, additional, Fecht, Daniela, additional, Robinson, Oliver, additional, Beale, Linda, additional, Järup, Lars, additional, Elliott, Paul, additional, and Hansell, Anna, additional

Published
2013
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22. Occupational cancer burden in Great Britain

Author

Rushton, Lesley, primary, Hutchings, Sally J, additional, Fortunato, Lea, additional, Young, Charlotte, additional, Evans, Gareth S, additional, Brown, Terry, additional, Bevan, Ruth, additional, Slack, Rebecca, additional, Holmes, Phillip, additional, Bagga, Sanjeev, additional, Cherrie, John W, additional, and Van Tongeren, Martie, additional

Published
2012
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26. Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.

Author

Ellis J, van Maurik A, Fortunato L, Gisbert S, Chen K, Schwartz A, McHugh S, Want A, Santos Franco S, Oliveira JJ, Price J, Coles A, Brown K, Su D, Craigen JL, Yang J, Brett S, Davis B, Cheriyan J, Kousin-Ezewu O, Gray F, Thompson PW, and Fernando D

Subjects
Adolescent, Adult, Aged, Antibodies, Monoclonal, Humanized adverse effects, Antibodies, Monoclonal, Humanized pharmacokinetics, Antibodies, Monoclonal, Humanized therapeutic use, Autoimmune Diseases drug therapy, Autoimmune Diseases immunology, Double-Blind Method, Female, Half-Life, Healthy Volunteers, Humans, Infusions, Intravenous, Interleukin-7 Receptor alpha Subunit immunology, Male, Middle Aged, Placebos administration & dosage, Placebos adverse effects, T-Lymphocytes immunology, T-Lymphocytes metabolism, Young Adult, Antibodies, Monoclonal, Humanized pharmacology, Interleukin-7 Receptor alpha Subunit antagonists & inhibitors, T-Lymphocytes drug effects
Abstract

Aim: Interleukin (IL)-7 signalling modulates T cell activity and is implicated in numerous autoimmune diseases. The present study investigated the safety, pharmacokinetics, target engagement, pharmacodynamics and immunogenicity of GSK2618960, an IL-7 receptor-α subunit (CD127) monoclonal antibody., Methods: A double-blind (sponsor-unblind) study of a single intravenous infusion of either GSK2618960 (0.6 mg kg -1 or 2.0 mg kg -1 ) or placebo was carried out in 18 healthy subjects over 24 weeks., Results: GSK2618960 was well tolerated; there were no serious or significant adverse events. The observed half-life was 5 (±1) days (2.0 mg kg -1 ), with nonlinear pharmacokinetics. Full receptor occupancy (>95%) was observed until day 8 (0.6 mg kg -1 ) and day 22 (2.0 mg kg -1 ). Maximal inhibition of IL-7-mediated signal transducer and activator of transcription 5 (STAT5) phosphorylation was observed in 5/6 subjects until day 22 (2.0 mg kg -1 ). Mean circulating IL-7 and soluble receptor (CD127) levels were increased above baseline during days 2 and 15 (0.6 mg kg -1 ) and days 2 and 22 (2.0 mg kg -1 ). No meaningful changes were observed in absolute numbers or proportions of immune cell populations or inflammatory cytokine profiles (IL-6, tumour necrosis factor-α, interferon-γ, IL-2). Persistent antidrug antibodies (ADAs) were detected in 5/6 subjects administered a dose of 0.6 mg kg -1 (neutralizing in 2/6) and in 6/6 subjects administered 2.0 mg kg -1 (neutralizing in 5/6)., Conclusion: GSK2618960 was well tolerated and blocked IL-7 receptor signalling upon full target engagement. Although there was no discernible impact on peripheral T cell subsets in healthy subjects, GSK2618960 may effectively modulate the autoinflammatory activity of pathogenic T cells in diseased tissue. A relatively short half-life is likely the result of target-mediated rather than ADA-mediated clearance., (© 2018 GlaxoSmithKline. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Published
2019
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27. Geographical and socioeconomic inequalities in women and children's nutritional status in Pakistan in 2011: an analysis of data from a nationally representative survey.

Author

Di Cesare M, Bhatti Z, Soofi SB, Fortunato L, Ezzati M, and Bhutta ZA

Subjects
Adult, Anthropometry, Bayes Theorem, Body Mass Index, Child, Preschool, Educational Status, Female, Food Supply, Growth Disorders epidemiology, Humans, Infant, Linear Models, Middle Aged, Pakistan epidemiology, Poverty, Prevalence, Socioeconomic Factors, Thinness epidemiology, Wasting Syndrome epidemiology, Young Adult, Health Status Disparities, Nutritional Status
Abstract

Background: Pakistan has one of the highest levels of child and maternal undernutrition worldwide, but little information about geographical and socioeconomic inequalities is available. We aimed to analyse anthropometric indicators for childhood and maternal nutrition at a district level in Pakistan and assess the association of nutritional status with food security and maternal and household socioeconomic factors., Methods: We used data from the 2011 Pakistan National Nutrition Survey, which included anthropometric measurements for 33 638 children younger than 5 years and 24 826 women of childbearing age. We estimated the prevalences of stunting, wasting, and underweight among children and of underweight, overweight, and obesity in women for all 143 districts of Pakistan using a Bayesian spatial technique. We used a mixed-effect linear model to analyse the association of nutritional status with individual and household sociodemographic factors and food security., Findings: Stunting prevalence in Pakistan's districts ranged between 22% (95% credible interval 19-26) and 76% (69-83); the lowest figures for wasting and underweight were both less than 2·5% and the highest were 42% (34-50) for wasting and 54% (49-59) for underweight. In 106 districts, more women were overweight than were underweight; in 49 of these districts more women were obese than were underweight. Children were better nourished if their mothers were taller or had higher weight, if they lived in wealthier households, and if their mothers had 10 or more years of education. Severe food insecurity was associated with worse nutritional outcomes for both children and women., Interpretation: We noted large social and geographical inequalities in child and maternal nutrition in Pakistan, masked by national and provincial averages. Pakistan is also beginning to face the concurrent challenge of high burden of childhood undernutrition and overweight and obesity among women of reproductive age. Planning, implementation, and evaluation of programmes for food and nutrition should be based on district-level needs and outcomes., Funding: Bill & Melinda Gates Foundation, Grand Challenges Canada, UK Medical Research Council., (Copyright © 2015 Di Cesare et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.)

Published
2015
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28. Aircraft noise and cardiovascular disease near Heathrow airport in London: small area study.

Author

Hansell AL, Blangiardo M, Fortunato L, Floud S, de Hoogh K, Fecht D, Ghosh RE, Laszlo HE, Pearson C, Beale L, Beevers S, Gulliver J, Best N, Richardson S, and Elliott P

Subjects
Aged, Cardiovascular Diseases etiology, Female, Humans, London epidemiology, Male, Middle Aged, Morbidity trends, Retrospective Studies, Risk Factors, Rural Population, Small-Area Analysis, Survival Rate trends, Time Factors, Aircraft, Airports, Cardiovascular Diseases epidemiology, Environmental Exposure adverse effects, Hospitalization statistics & numerical data, Noise, Transportation adverse effects, Risk Assessment methods
Abstract

Objective: To investigate the association of aircraft noise with risk of stroke, coronary heart disease, and cardiovascular disease in the general population., Design: Small area study., Setting: 12 London boroughs and nine districts west of London exposed to aircraft noise related to Heathrow airport in London., Population: About 3.6 million residents living near Heathrow airport. Risks for hospital admissions were assessed in 12 110 census output areas (average population about 300 inhabitants) and risks for mortality in 2378 super output areas (about 1500 inhabitants)., Main Outcome Measures: Risk of hospital admissions for, and mortality from, stroke, coronary heart disease, and cardiovascular disease, 2001-05., Results: Hospital admissions showed statistically significant linear trends (P<0.001 to P<0.05) of increasing risk with higher levels of both daytime (average A weighted equivalent noise 7 am to 11 pm, L(Aeq),16 h) and night time (11 pm to 7 am, Lnight) aircraft noise. When areas experiencing the highest levels of daytime aircraft noise were compared with those experiencing the lowest levels (>63 dB v ≤ 51 dB), the relative risk of hospital admissions for stroke was 1.24 (95% confidence interval 1.08 to 1.43), for coronary heart disease was 1.21 (1.12 to 1.31), and for cardiovascular disease was 1.14 (1.08 to 1.20) adjusted for age, sex, ethnicity, deprivation, and a smoking proxy (lung cancer mortality) using a Poisson regression model including a random effect term to account for residual heterogeneity. Corresponding relative risks for mortality were of similar magnitude, although with wider confidence limits. Admissions for coronary heart disease and cardiovascular disease were particularly affected by adjustment for South Asian ethnicity, which needs to be considered in interpretation. All results were robust to adjustment for particulate matter (PM10) air pollution, and road traffic noise, possible for London boroughs (population about 2.6 million). We could not distinguish between the effects of daytime or night time noise as these measures were highly correlated., Conclusion: High levels of aircraft noise were associated with increased risks of stroke, coronary heart disease, and cardiovascular disease for both hospital admissions and mortality in areas near Heathrow airport in London. As well as the possibility of causal associations, alternative explanations such as residual confounding and potential for ecological bias should be considered.

Published
2013
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