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6. Using random forest to identify longitudinal predictors of health in a 30 year cohort study

Author

Loef, B, Wong, A, Jansen, NAH, Strak, M, Hoekstra, J, Picavet, HSJ, Boshuizen, HC, Verschuren, WMM, and Herber, GCM

Abstract

Due to the wealth of exposome data from longitudinal cohort studies that is currently available, the need for methods to adequately analyze these data is growing. We propose an approach in which machine learning is used to identify longitudinal exposome-related predictors of health, and illustrate its potential through an application. Our application involves studying the relation between exposome and self-perceived health based on the 30-year running Doetinchem Cohort Study. Random Forest (RF) was used to identify the strongest predictors due to its favorable prediction performance in prior research. The relation between predictors and outcome was visualized with partial dependence and accumulated local effects plots. To facilitate interpretation, exposures were summarized by expressing them as the average exposure and average trend over time. The RF model’s ability to discriminate poor from good self-perceived health was acceptable (Area-Under-the-Curve = 0.707). Nine exposures from different exposome-related domains were largely responsible for the model’s performance, while 87 exposures seemed to contribute little to the performance. Our approach demonstrates that ML can be interpreted more than widely believed, and can be applied to identify important longitudinal predictors of health over the life course in studies with repeated measures of exposure. The approach is context-independent and broadly applicable.

Published
2021

9. Shift work

Author

Loef, B., van der Beek, Allard Johan, Proper, Karin, van Baarle, D., Public and occupational health, APH - Societal Participation & Health, van der Beek, A.J., and Proper, K.I.

Published
2020

11. De effectiviteit van 'Individuele plaatsing en steun' (IPS) op gezondheid en participatie : Een literatuuroverzicht

Author

Loef, B, van Oostrom, S, and Proper, K

Subjects
RIVM rapport 2020-0182
Abstract

Individuele plaatsing en steun (IPS) maakt deel uit van een behandeling voor personen met ernstige psychische aandoeningen waar werk een onderdeel van is. Voorbeelden van deze aandoeningen zijn psychosen, bipolaire stoornissen, en ernstige depressies. Het doel van IPS is dat mensen snel een reguliere baan krijgen volgens het first place then train-principe. Dit betekent dat ze hulp voor hun aandoening blijven krijgen nadat ze met een baan zijn begonnen. Bij andere initiatieven houdt die hulp dan op. Er is nog weinig onderzoek gedaan naar de gezondheidseffecten van IPS. Het beschikbare onderzoek laat geen duidelijk positief of negatief effect zien op de kwaliteit van leven, het functioneren, en de mentale gezondheid van de mensen. De maatregel heeft wel een duidelijk positief effect als naar de arbeidsparticipatie wordt gekeken, zoals betaald werk vinden en behouden. Het bewijs of mensen die aan IPS deelnemen ook op lange termijn hun werk behouden is alleen nog heel beperkt. Dit blijkt uit een literatuurstudie van het RIVM naar de effecten van IPS op gezondheid en participatie van mensen met psychische aandoeningen. De literatuurstudie is uitgevoerd in opdracht van de werkgroep Inclusieve samenleving van de Brede Maatschappelijke Heroverwegingen (BMH). De BMH wilde weten wat de effecten van IPS zijn op gezondheid en participatie.

Published
2020
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12. ICONIC study-conservative versus conventional oxygenation targets in intensive care patients: study protocol for a randomized clinical trial.

Author

Grim, C. C. A., van der Wal, L. I., Helmerhorst, H. J. F., van Westerloo, D. J., Pelosi, P., Schultz, M. J., de Jonge, E., for the ICONIC Investigators and PROVE Network, del Prado, M. R., Wigbers, J., Sigtermans, M. J., Dawson, L., van der Heijden, P. L. J., den Berg, E. Y. Schriel-van, Loef, B. G., Reidinga, A. C., de Vreede, E., Qualm, J., Boerma, E. C., and Rijnhart-de Jong, H.

Subjects
RESEARCH protocols, INTENSIVE care patients, OXYGEN in the blood, OXYGEN therapy, LENGTH of stay in hospitals
Abstract

Background: Oxygen therapy is a widely used intervention in acutely ill patients in the intensive care unit (ICU). It is established that not only hypoxia, but also prolonged hyperoxia is associated with poor patient-centered outcomes. Nevertheless, a fundamental knowledge gap remains regarding optimal oxygenation for critically ill patients. In this randomized clinical trial, we aim to compare ventilation that uses conservative oxygenation targets with ventilation that uses conventional oxygen targets with respect to mortality in ICU patients.Methods: The "ConservatIve versus CONventional oxygenation targets in Intensive Care patients" trial (ICONIC) is an investigator-initiated, international, multicenter, randomized clinical two-arm trial in ventilated adult ICU patients. The ICONIC trial will run in multiple ICUs in The Netherlands and Italy to enroll 1512 ventilated patients. ICU patients with an expected mechanical ventilation time of more than 24 h are randomized to a ventilation strategy that uses conservative (PaO2 55-80 mmHg (7.3-10.7 kPa)) or conventional (PaO2 110-150 mmHg (14.7-20 kPa)) oxygenation targets. The primary endpoint is 28-day mortality. Secondary endpoints are ventilator-free days at day 28, ICU mortality, in-hospital mortality, 90-day mortality, ICU- and hospital length of stay, ischemic events, quality of life, and patient opinion of research and consent in the emergency setting.Discussion: The ICONIC trial is expected to provide evidence on the effects of conservative versus conventional oxygenation targets in the ICU population. This study may guide targeted oxygen therapy in the future.Trial Registration: Trialregister.nl NTR7376 . Registered on 20 July, 2018. [ABSTRACT FROM AUTHOR]

Published
2022
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22. Klokwerk plus study protocol: An observational study to the effects of night-shift work on body weight and infection susceptibility and the mechanisms underlying these health effects:Bmc Public Health

Author

Loef, B., van Baarle, D., van der Beek, A. J., van Kerkhof, L.W., van de Langenberg, D., Proper, K. I., Public and occupational health, and EMGO - Lifestyle, overweight and diabetes

Abstract

Background: Night-shift work may cause severe disturbances in the worker's circadian rhythm, which has been associated with the onset of health problems and diseases. As a substantial part of the workforce is exposed to night-shift work, harmful aspects of night-shift work should not be overlooked. The aim of the Klokwerk + study is to study the effects of night-shift work on body weight and infection susceptibility and the mechanisms underlying these health effects. First, we will study the relation between night-shift work exposure and body weight and between night-shift work exposure and infection susceptibility. Second, we will examine the mechanisms linking night-shift work exposure to body weight and infection susceptibility, with a specific focus on sleep, physical activity, diet, light exposure, vitamin D level, and immunological factors. Lastly, we will focus on the identification of biomarkers for chronic circadian disturbance associated with night-shift work. Methods/design: The design of this study is a prospective observational cohort study consisting of 1,960 health care workers aged 18-65 years. The study population will consist of a group of night-shift workers and an equally sized group of non-night-shift workers. During the study, there will be two measurement periods. As one of the main outcomes of this study is infection susceptibility, the measurement periods will take place at approximately the first (September/October) (T0) and the last month (April/May) (T1, after 6 months) of the flu season. The measurements will consist of questionnaires, anthropometric measurements, a smartphone application to determine infection susceptibility, food diaries, actigraphy, light sensors, and blood sample analyses. Discussion: The Klokwerk + study will contribute to the current need for high-quality data on the health effects of night-shift work and its underlying behavioral and physiological mechanisms. The findings can be the starting point for the development of interventions that prevent negative health effects caused by night-shift work. In addition, the identification of biomarkers indicative of loss of homeostasis due to circadian disturbance may be an important asset in monitoring the effects of such interventions.

Published
2016

23. HEPB

Author

Glas, G J, Muller, J, Binnekade, J M, Cleffken, B, Colpaert, K, Dixon, B, Juffermans, N P, Knape, P, Levi, M M, Loef, B G, Mackie, D P, Malbrain, M, Schultz, M J, van der Sluijs, K F, Faculty of Physical Education and Physical Therapy, Supporting clinical sciences, and Intensive Care

Subjects
safety, medicine, Time Factors, diagnosis, administration & dosage, artificial, recovery of function, administration, lung, methods, Belgium, Clinical Protocols, Double-Blind Method, Anesthesiology, Smoke, Humans, intensive care, Netherlands, Medicine(all), inhalation, therapy, research, Heparin, Nebulizers and Vaporizers, ventilation, Anticoagulants, Smoke Inhalation Injury, Intratracheal, Treatment Outcome, RESPIRATION, Research Design, drug effects, adverse effects, INJURIES, pathology, physiopathology, Intubation, Laboratories, Ventilator Weaning
Abstract

BACKGROUND: Pulmonary coagulopathy is a hallmark of lung injury following inhalation trauma. Locally applied heparin attenuates lung injury in animal models of smoke inhalation. Whether local treatment with heparin benefits patients with inhalation trauma is uncertain. The present trial aims at comparing a strategy using frequent nebulizations of heparin with standard care in intubated and ventilated burn patients with bronchoscopically confirmed inhalation trauma. METHODS: The Randomized Controlled Trial Investigating the Efficacy and Safety of Nebulized HEParin versus Placebo in BURN Patients with Inhalation Trauma (HEPBURN) is an international multi-center, double-blind, placebo-controlled, two-arm study. One hundred and sixteen intubated and ventilated burn patients with confirmed inhalation trauma are randomized to nebulizations of heparin (the nebulized heparin strategy) or nebulizations of normal saline (the control strategy) every four hours for 14 days or until extubation, whichever comes first. The primary endpoint is the number of ventilator-free days, defined as days alive and breathing without assistance during the first 28 days, if the period of unassisted breathing lasts for at least 24 consecutive hours. DISCUSSION: As far as the authors know, HEPBURN is the first randomized, placebo-controlled trial, powered to investigate whether local treatment with heparin shortens duration of ventilation of intubated and ventilated burn patients with inhalation trauma. TRIAL REGISTRATION: NCT01773083 (http://www.clinicaltrials.gov), registered on 16 January 2013.Recruiting. Randomisation commenced on 1 January 2014

Published
2014

33. Implementation and evaluation of a nurse-centered computerized potassium regulation protocol in the intensive care unit - a before and after analysis

Author

van der Horst Iwan CC, Loef Bert G, Janse Marcel, Drost José T, Vogelzang Mathijs, Hoekstra Miriam, Zijlstra Felix, and Nijsten Maarten WN

Subjects
Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Potassium disorders can cause major complications and must be avoided in critically ill patients. Regulation of potassium in the intensive care unit (ICU) requires potassium administration with frequent blood potassium measurements and subsequent adjustments of the amount of potassium administrated. The use of a potassium replacement protocol can improve potassium regulation. For safety and efficiency, computerized protocols appear to be superior over paper protocols. The aim of this study was to evaluate if a computerized potassium regulation protocol in the ICU improved potassium regulation. Methods In our surgical ICU (12 beds) and cardiothoracic ICU (14 beds) at a tertiary academic center, we implemented a nurse-centered computerized potassium protocol integrated with the pre-existent glucose control program called GRIP (Glucose Regulation in Intensive Care patients). Before implementation of the computerized protocol, potassium replacement was physician-driven. Potassium was delivered continuously either by central venous catheter or by gastric, duodenal or jejunal tube. After every potassium measurement, nurses received a recommendation for the potassium administration rate and the time to the next measurement. In this before-after study we evaluated potassium regulation with GRIP. The attitude of the nursing staff towards potassium regulation with computer support was measured with questionnaires. Results The patient cohort consisted of 775 patients before and 1435 after the implementation of computerized potassium control. The number of patients with hypokalemia (5.0 mmol/L) were recorded, as well as the time course of potassium levels after ICU admission. The incidence of hypokalemia and hyperkalemia was calculated. Median potassium-levels were similar in both study periods, but the level of potassium control improved: the incidence of hypokalemia decreased from 2.4% to 1.7% (P < 0.001) and hyperkalemia from 7.4% to 4.8% (P < 0.001). Nurses indicated that they considered computerized potassium control an improvement over previous practice. Conclusions Computerized potassium control, integrated with the nurse-centered GRIP program for glucose regulation, is effective and reduces the prevalence of hypo- and hyperkalemia in the ICU compared with physician-driven potassium regulation.

Published
2010
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34. The impact of a reduced dose of dexamethasone on glucose control after coronary artery bypass surgery

Author

Boonstra Piet W, van der Horst Iwan CC, Janse Marcel, Drost José T, Hoekstra Miriam, Vogelzang Mathijs, Zijlstra Felix, Loef Bert G, and Nijsten Maarten WN

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Intensive insulin therapy to maintain normoglycemia after cardiac surgery reduces morbidity and mortality. We investigated the magnitude and duration of hyperglycemia caused by dexamethasone administered after cardiopulmonary bypass. Methods A single-center before-after cohort study was performed. All consecutive patients undergoing coronary artery bypass grafting with cardiopulmonary bypass during a 6-month period were included. Insulin administration was guided by a sliding scale protocol. Halfway the observation period, the dexamethasone protocol was changed. The single dose (1D) group received a pre-operative dose of dexamethasone of 1 mg/kg. The double dose group (2D) received an additional dose of 0.5 mg/kg of dexamethasone post-operatively at ICU admission. Results We included 116 patients in the 1D group and 158 patients in the 2D group. There were no significant baseline differences between the groups. Median Euroscore was 5. In univariable analysis, the glucose level was different between groups 1D and 2D at 4, 6, 9, 12 and 24 hours after ICU admission (all p < 0.001). Insulin infusion was higher in the 1D group. Corrected for insulin dose in multivariable linear analysis, the difference in glucose between the 1D and 2D groups was 1.5 mmol/L (95% confidence interval 1.0–2.0, p < 0.001) 12 hours after ICU admission. Conclusion Dexamethasone exerts a hyperglycemic effect in cardiac surgery patients. Patients receiving high-dose corticosteroid therapy should be monitored and treated more intensively for hyperglycemic episodes.

Published
2007
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35. Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Author

Labeau, Sonia O, Afonso, Elsa, Benbenishty, Julie, Blackwood, Bronagh, Boulanger, Carole, Brett, Stephen J, Calvino-Gunther, Silvia, Chaboyer, Wendy, Coyer, Fiona, Deschepper, Mieke, François, Guy, Honore, Patrick M, Jankovic, Radmilo, Khanna, Ashish K, Llaurado-Serra, Mireia, Lin, Frances, Rose, Louise, Rubulotta, Francesca, Saager, Leif, Williams, Ged, Blot, Stijn I, Dritan, Muzha, Antoni Margarit Ribas, Fernando, Lipovesty, Cecilia, Loudet, Fiona, Coyer, Philipp, Eller, Nafseen, Mostafa, Patrick, M Honoré, Vanesa Mercado Telleria, Jasmina, Smajic, Paula Cristina Nogueira, Khalid Mahmood Khan Nafees, Romuald, Hentchoya, Louise, Rose, Javiera, Soledad, Frances, Lin, Yenny, Cardenas, Amylkar Garay Reyes, Alan, Sustic, Meropi, Mpouzika, Tamas, Vymazal, Hanne Irene Jensen, Hernan, Aguirre-Bermeo, Liivi, Maddison, Maija, Valta, Silvia, Calvino-Gunther, Frank, Bloos, Faustina Excel Adipa, Vasilios, Koulouras, Judy, Enamorado, Zsuzsann, Ágoston, Hrönn, Birgisdóttir, Amit, Gupta, Mohan, Gurjar, Bram, Kilapong, Seyed Mohammadreza Hashemian, Ignacio, Martin-Loeches, Julie, Benbenishty, Andrea, Cortegiani, Kelly, Fletcher, Yoshiro, Hayashi, Wangari, Waweru-Siika, Khalid, Abidi, Sang-Min, Lee, Burhan, Hadri, Mihails, Dolgusevs, Fayez François Abillama, Tomas, Jovaisa, Cyril, Thix, Muhammed, Elhadi, Basri Mat Nor, Shanti, Ratnam, Mohd Zulfakar Mazlan, Sundaresan, Maiyalagan, Luis, Sánchez-Hurtado, Adrian, Belii, Mendsaikhan, Naranpurev, Prabha, Gautam, Dylan De Lange, Rachael, Parke, Rose Ekama Ilesanmi, Mirjana, Shosholcheva, Antonija, Petosic, Ranveig, Lind, Madiha Hashmi Ffarcsi, Javier, Bogarin, Aaron Mark Hernandez, Malgorzata, Mikaszewska-Sokolewicz, Bruno, Sousa, Dana, Tomescu, Dorel, Sandesc, Theogene, Twagirumugabe, Vitaly, Gusarov, Maie, Ebaid, Radmilo, Jankovic, Gari, Slobodianiuk, Andrea, Martonova, Rihard, Knafelj, Mervyn, Mer, Emilio, Maseda, Bernardo, Panka, Joerg, C Schefold, Eva, Joelsson-Alm, Konlawij, Trongtrakul, Lorna, Merritt-Charles, Lamia Ouanes Besbes, Yalım, Dikmen, Lesia, Zgrzheblovska, Mark, Fielding, Francesca, Rubulotta, Ashish, K Khanna, Leif, Saager, Ingrid von der Osten, Alban, Greca, Alma, Cani, Nordian, Xhindi, Genci, Hyska, Antonio Margarit Ribas, Susana, Pinto, Paulo, Alves, Romina, Esposito, Emanuel, Valgolio, John Thomas Sanchez Minope, Antonio, Abdala, Maria, Ayala, Silvina, Bravo, Ana, Bantar, Patricia, Delgado, Gustavo, Badariotti, Fernando, Lipovestky, Ana, Diaz, Pablo, Saul, Mariano, Setten, Alejandra, Aucapina, Ysica, Acosta, Victor, Gonzalez, Luis, Camputaro, Fernando, Baccaro, Robert, Villa, Marcela, Mastantuono, Emiliano, Dean, Oscar Fernández Rostello, Patricia, Brizuela, Julio Ricardo Bartoli, Matias, Guereschi, Cristian, Quiroga, Sofia, Putruele, Paula, Villegas, Veronica, Curilen, Ruben, Fernandez, Mariangeles Gabriela Nocheretti, Rosana Gabriela Escalante, Cecilia Inés Loudet, Silvia, Fernandez, Ana Laura Gonzalez, Gustavo Andres Alvarez, Federico, Iglesias, Silvia, Chaparro, Graciela, Zakalik, Gonzalo, Pagella, Matías, Baini, Pierina Arias Campos, Ignacio, Sabbag, Armando, Schmukler, Imelda Perdomo Fonseca, Gonzalo Martín Alvarez, Mario, Ramirez, Fernando, Tapia, Carlos Alejandro Bascary, Graciela Del Valle Gimenez, Fernando Pablo Bertoletti, Esteban, Milioto, Pablo Julio Maldonaldo Bonsignore, Maria Alejandra Fernandez, Julie, Smith, Tim, Chimunda, Lorraine, Thompson, Teena, Maguire, Wendy, Chaboyer, Stacey, Watts, Marion, Mitchell, Madeleine, Powell, India, Lye, Leanne, Parsons, Nerilee, Baker, Claire, Reynolds, Amy, Thompson, Kristy, Masters, Kellie, Sosnowski, Lynette, Morrison, Gavin, D Leslie, Ramanathan, Lakshmanan, Alexis, Tabah, Wendy, Brown, Sharon, McDowell-Skaines, Andrea, Mclucas, Chris, Smith, Mandy, Tallot, Sarah, Jones, Michelle, Barakat-Johnson, Thomas, Leong, Rand, Butcher, Kerrie, Martin, Philipp, Douschan, Dirk von Lewinski, René, Schmutz, Uta, Kolussi, Fatema, Salman, Zainab, Ateya, Koen De Decker, Niels Van Regenmortel, Anita, Jans, Patricia, Wijnands, Stefano, Coremans, Patrick, M Honore, David De Bels, Tanja, Depuydt, Caroline, Paillet, Luc-Marie, Jacquet, Walter, Swinnen, Francis, Hannes, Matthia, Mergeay, Stijn Van de Velde, Silvie, Allaert, Pieter, Hoste, Christophe, Borin, Sandrine, Balon, Vincent, Fraipont, Patrick, Biston, Nicolas De Schryver, Thierry, Dugernier, Ilse Van Cotthem, Angelica Olivetto de Almeida, Silvia Angelica Jorge, Delmiro, Becker, Raysa Cristina Schmidt, Evellyn, Oliveira, Aline, Ramalho, Eliane, Mazocoli, Audrey, Fioretti, Elaine, Barros, Leticia, Serpa, Suzana, Bianchini, Ticiane, Campanili, Taís, Pantaleao, Paulo Carlos Garcia, Ana Lucia Vitti Ronchini, Rayanne, Santos, Nurulhuda Binti, A Manap, Sean, Bagshaw, Dominic, Carney, Jon, Davidow, Ella, Rokosh, Andréa Maria Laizner, Samantha, Smith, Megan, Mcquirter, Betty Star Kampayana, René, Favre, Martin, Sills, Julie, Dallaire, Cathy, Becker, Sherissa, Microys, Bonnie, Bowes, Jennifer, Lajeunesse, Rishi, Ghosh, Jacqueline, Baptiste-Savoie, Rose, Raizman, Gabriel, Suen, Noushin, Taghavi, Orla, Smith, Clare, Fielding, Julieta, Canales, Pia, Molina, Javiera, Chaparro, Maria Idalia Sepulveda, Matias Jesús Flamm Zamorano, Pamela, Rocha, Ximena, Villanueva, Paola, Araya, Meneses, Dayan, Fernando, Avalos, Xiaohan, Li, Liu, Yu, Xinxia, Li, Xiaoyan, Chen, Zhixia, Jiang, Jing, Yang, Jingfang, Chen, Lei, Yang, Kefang, Wang, Jie, Gao, Xiuhua, Fang, Ronghua, Zhao, Xinhua, Xia, Hongmei, Liu, Jing, Li, Haiyan, Wang, Gen, Meng, Yanhong, Di, Damei, Wang, Rong Hua Zhao, Li Ping Hu, Peipei, Xu, Qing Feng Jiao, Hai Yun Wang, Chun Jie Xia, Yan, Liu, Mei, Ye, Yan, Wan, Wenmei, Wang, Yajun, Ding, Aiua, Ren, Yan, Gao, Qi, Li, Guifang, Du, Yanling, Shen, Yanming, Ding, Ning, Li, Cui, Yuan, Lei, Tan, Qiang, Lin, Hailing, Guo, Howe, Yan, Xiao, Xu, Wei, Zhang, Jinxian, Liang, Libing, Zhang, Eryun, Tian, Qian, Zhao, Lin, Insu, Jingwen, Dong, Yanmei, Gu, Ying, Liu, Lina, Zhao, Wei, Wang, Hongmei, Qiao, Lili, Tuo, Mengmeng, Lv, Jin Yu Zhu, Jifen, Zhu, Ying, Wei, Man, Liu, Yin, He, Jiyin, Cheng, Jin, Liu, Jia, Na, Dongfang, Wei, Qing, Li, Xiaoying, Wu, Huan, Duan, Dongliang, Lin, Qiong, Liang, Xiaofang, Luo, Yunfeng, Xiong, Rong Fen Huang, Jing, Fu, Tao, Zan, Man, Ye, Zeya, Shi, Yanfei, Long, Yang, Lei, Xiaodi, Liu, Chen, Yumei, Lingling, Wang, Yali, Zhang, Yan, Xu, Cheng, Wang, Zhijuan, Chengxia, Sun, Jinhui, Song, Yingli, Wang, Xiumei, Liu, Yupeng, Liu, Yuxia, Yuan, Qingping, Huang, Fengling, Yang, Yun, Wu, Xianping, Luo, Xiaowu, Bai, Hong, Zheng, Min, Song, Yue, Sun, Zhangshuangzi, Li, Feifei, Luo, Miao, Liu, Li Chuntang Li, Xinjian, Li, Guiping, Zhang, Lina, Xiao, Tingting, Yu, Guangyuan, Gao, Wei, Wei, Fanglan, Wang, Ting, Han, Tingting, Li, Zeng, Qi, Jing Mei Zeng, Yan, Long, Fuqun, Pan, Jing, Wang, Guoxue, He, Haiyan, Chen, Feifei, Zhang, Chao, Yu, Gao, Chunhua, Xiuying, Yao, Dongmei, Bai, Liu, Lu, Xuelian, Xu, Yan, Wang, Xuejuan, Liang, Zhang, Na, Aizhi, Zhang, Xiaochun, Hu, Hui, Zhang, Ruixia, Wang, Poon Shing Tak, Sung Wai Ho, Qun Xia Jiang, Xinran, Ding, Liu, Hong, Limei, Miao, Zhaoxia, Feng, Liping, Huang, Juan, Wu, Yuping, Wang, Jiye, Guo, Baoke, Zhang, Chaoqun, Ma, Han, Yu, Congcong, Liu, Min, Ding, Linlin, Luan, Jing, Zheng, Shanshan, Lv, Shumin, Jiang, Wenzhen, Cao, Xiujuan, Xue, Guangyan, Liu, Xiyan, Wei, Youru, Jiang, Zhiru, Yao, Gao, Li, Jinhua, Li, Wenwen, Zhao, Mei, Jiang, Junping, Hao, Jing, Zhang, Caiju, Song, Feifei, Chen, Shuhui, Wang, Lili, Hu, Deyan, Cao, Jianhong, Wan, Xiaomin, Wang, Hongyan, Shao, Zhenxia, Zhang, Xia, Cui, Jingyu, Liu, Lijuan, Zhao, Xingguo, Li, Limei, Fan, Ling, Zhang, Min, Yu, Biyan, Li, Chunxia, Li, Ling, Liu, Xuelian, Liu, Wenmin, Chen, Yan, Li, Zhang, Zhigang, Yuchen, Wu, Chenghau, Mu, Guoyan, Zhu, Fan, Yang, Qi, Bo, Ling, Li, Meili, Chen, Jing Hua Jiang, Hai, Yin, Xuelian, Pang, Yue Ying Gong, Shunzhu, Yang, Xiaoli, Yan, Xianhong, Zheng, Dehong, Lei, Lei, Lei, Yinhua, Guo, Lihong, Liu, Jing, Yu, Wei, Sun, Aiping, Bi, Weiwei, Li, Yang, Wu, Ji, Li, Dongshu, Ni, Zijing, Wu, Bing, Song, Qin, Fei, Yang, Xiaoyan, Qiong, Ran, Xixi, Li, Xueping, Jiao, Hua, Ji, Sun, Zhiping, Hong, Ma, Jianhong, Mu, Yanhua, Hao, Yin, Li, Ying, Wang, Caihong, Hui, Wenjie, Ju, Yuxia, Huo, Yuxia, Wang, Lei, Chen, Yan, Yan, Qingli, Zhao, Hongjuan, Chen, Guijun, Bao, Ying, Cao, Hong, Li, Hong, Zhang, Ying, Zhang, Lina, Xu, Jia, Guixiang, Ying, Li, Hui Min Zhao, Xia, Huang, Zhaoxing, Dai, Yanman, Jian, Hongsu, Zhang, Zhixia, Tian, Zu Qing Cao, Miao, Li, Yang, Liu, Fei, Ouyang, Fuying, Ma, Wangyan, Jin, Liuyan, Ge, Shifen, Wu, Weilian, Yuan, Tianfei, Chen, Guanxiu, Shi, Zhihong, Chen, Kewei, Liu, Xue, Lin, Yuemen, Ly, Sun, Lijuan, Xiao Fang Tian, Shuo, Wang, Zhangxia, Feng, Xiaozhe, Liu, Yunchun, Dong, Jundi, Zhang, Nie, Bocui, Guoxian, Wang, Yingjuan, Zhao, Xiaojun, Wu, Qiao, Yang, Rongjun Ling Hu, Xue Qin Li, Zhu Jun Yu, Yanlan, Yao, Xiaoqiong, Deng, Yan, Xiao, Yan, Xie, Yanping, Yang, Huai, Yang, Yuming, Zhou, Zhuqing, Li, Min, Xiao, Yongxia, Yang, Yani, Tian, Luz Marina Silva Gama, Juan Sebastian Hernandez, Nestor, Caicedo, Jorge, Marin, Maria-Elena, Ochoa, Monica, Gomez, José, Rojas-Suarez, Jeniffer, Gonzalez, Amylkar José Garay Reyes, Edwin, Chapeta, Estefania, Orozco, Ina, Filipović-Grčić, Anita, Vuković, Suzana, Pečenković, Aleksandar, Šuput, Gordana, Zivanovic-Posilovic, Armanda, Bozena, Nikolina, Udiljak, Morena, Milic, Renata Curic Radivojevic, Slobodan, Mihaljevic, Marijana, Matas, Dinko, Tonkovic, Hemena, Čuljak, Ivana, Herceg, Gordana, Pavlisa, Milena, Dobric, Tatjana, Beker, Višnja Nesek Adam, Tanja, Goranovic, Chrysanthos, Markoulias, Mina, Mathaios, Maria, Mylordou, Eleni, Achilleos, Pavlina, Kleanthous, Veronika, Kotanidi, Maria, Foka, Iwy, Charalabous, Anna, Alexandrou, Marios, Georgiou, Artemis, Patsalos, Sofia, Zepoy, Constantina, Constantinou, Petr, Piza, Tomas, Vymazal, Elisabeth, Wiborg, Louise, Bruhn, Karin, Kaasby, Karin Rehnholt Pedersen, Sanne, Mikkelsen, Marie, Collet, Anne, Langvad, Hanne, Andresen, Susanne, Fischer, Inger Ebbesen Kjærgård, Britta, Jepsen, Birthe, Husted, Morten, Bestle, Anne Marie Kodal, Tina Charlotte Bitsch Hansen, Anne Sofie Bomholt Pedersen, Tina Damgaar Thomsen, Anisette, Hoegenhaven, Mette, From, Tine Melgaard Frandsen, Grit, Henning, Anja, Hansen, Inger Abildgaard Bliksted, Luis Mario Tamayo, Pedro, Mogrovejo, Carolina, Palaez, Diego Rolando Morocho Tutillo, Cintia Valencia Hurtado, Maria Fernanda García, Diana, Alvarez, Fausto, Guerrero, Alexandra, Vasquez, Martin, Kütimets, Kadri, Tamme, Eneli, Anvelt, Lomangisi, Dlamini-Sserumaga, Carita, Löfqvist, Virpi, Lusenius, Outi, Kauppi, Jenni-Katarina, Sakki, Tarja, Tervo-Heikkinen, Ulla, Kesti, Merja, Merilainen, Elina, Karjula, Minna, Peltomaa, Auli, Palmu, Maarit, Ahtiala, Maija Anniina Valta, Hervé, Mentec, Gaëtan, Plantefève, Guillaume, Besch, Sébastien, Pili-Floury, Stanislas, Ledochowski, Marc Danguy des Déserts, Christophe, Giacardi, Cédric, Daubin, Audrey, Massard, Yann Le Guen, Agnès, Blanc, Simon, Mandaroux, Silvia Calvino Günther, Prune, Avogadro, Anthony, Radavidson, Jean, Turc, Sébastien, Jochmans, Hervé, Quintard, Laetitia, Boyer, Cédric, Bruel, François, Philippart, Philippe, Montravers, Enora, Atchade, Nadine, Flessel, Benoît, Chinardet, Léa, Soulisse, Cindy, Pillard, Delphine, Ngo, Benjamin, Bongiorno, Nathalie, Heitzler, Virginie, Souppart, Nathalie, Gautheret, Jean-Francois, Timsit, Fatiha, Essardy, Muriel, Fartoukh, Daisy, Mehay, Fabienne, Etourneau, Jean-Christophe, Farkas, Pascal, Beuret, Gabriel, Preda, Etienne De Montmollin, Vincent, Castelain, Ulrich, Jaschinski, Monika, Rothenfusser, Detlef, Kindgen-Milles, Thomas, Dimski, Christine, Fiedler, Tobias, Heinicke, Patrick, Meybohm, Tobias, Schulze, Marc, Bota, Sabrina, Pelz, Tobias, Odenthal, Martin, Christ, Kathrin, Bösl, Achilleas, Chovas, Sebastian, Stehr, Philipp, Simon, Sarah, Grotheer, Sebastian, Schüppel, Stefan, Schaller, Lea, Albrecht, Andeas, Stübner, Stephan, Graeser, Nina, Kolbe, Martina, Lausch, Anja, Diers, Ulf, Guenther, Reimer, Riessen, Martin, Roller, Irene Pearl Osei, Anita-Chrysolyte, Kusi-Appiah, Yakubu, H Yakubu, Belinda, Guadi-Gosh, Christos, Dragoumanis, Christos, Christofis, Nikolaos, Kazakos, Styliani, Bastani, Charalampos, Martinos, Vasileios, Bekos, Metaxia, Papanikolaou, Theonymfi, Papavasilopoulou, Anna, Efthymiou, Vasiliki, Chantziara, Anna, Kyriakoudi, Nikolaos, Kakaras, Chrisi, Diakaki, Aikaterini, Flevari, Charikleia, Nikolaou, Kounougeri, Katerina, Lamprini, Avramopoulou, Kyriaki, Tsikritsaki, Georgios, Gkiokas, Eirini, Pantiora, Chrysostomos, Katsenos, Eirini-Chysovalanto, Patsiou, Paraskevi, Alexandropoulou, Ioannis, Koutsodimitropoulos, Epaminontas, Farmakis, Konstantina, Nestora, Marinos, Chatzis, Eumorfia, Kondili, Stella, Soundoulounaki, Ourania, Mousafiri, Dimitra, Lepida, Antonia, Liarmakopoulou, Georgios, Papathanakos, Mrina, Oikonomou, Panagiotis, Ioannides, Dimitrios, Papadopoulos, Ioannis, Staikos, Maria, Stafylaraki, Bogdan, Raitsiou, Konstantinos, Mandis, Ifigenia, Ravani, Styliani, Kourelea, Aikaterini, Efthimiou, Giannoula, Thoma, Apostolos, Bakas, Konstantinos, Psarulis, Souzana, Anisoglou, Eirini, Papageorgiou, Evangelia, Michailidou, Thomai, Tholioti, Athena, Lavrentieva, Evdokia, Sourla, Anastasia, Spyropoulou, Nikolaos, Pantelas, Kristina Mariana Matei Stalika, Ioannis, Georgakas, Antigoni, Karathanou, Syragoula, Tsikriki, Aikaterini, Dimoula, Sofia, Kanakaki, Aristeidis, Vakalos, Konstantinos, Pagioulas, Judy Enamorado Enamorado, Gabor, Nardai, Fatime, Hawchar, Asbjorn, Blondal, Brynja, Rygvadottir, Rannveig, J Jonasdottir, Hrönn, Birgisdottir, Bhagyesh, Shah, Shuchi, Kaushik, Swagata, Tripathy, Mukta, Singh, Sonika, Agarwal, Manish, Gupta, Meraj, Ahmad, Kishore, Mangal, Vaibhav, Bhargava, Vilas, Kushare, Simant, Jha, Lakshay, Bhakhtiani, Manoj, Kamal, Arvind, Baronia, Ade, Susanti, Mayang Indah Lestari, Zulkifli, Zulkifli, Windu, Baskoro, Farid, Zand, Fatemeh, Zarei, Ata, Mahmoodpoor, Farshad, Heidari, Fateme, Jafaraghaee, Aidan, O'Shea, Fiona, O'Shea, Caroline, O'Donnell, Geraldine, Craig, Gerry, Fitzpatrick, Lisa, Dunne, Jennifer, Hastings, Brian, Marsh, Caitriona, Cody, Elizabeth, Campbell, Deirdre, Doyle, Michelle, Pacturanan, Christine, Sheehan, Annette, Carey, Charlotte, Carter, Regina, Mulvey, Damien O'Connell Rosemary Finn, Catherine, Motherway, Amy, Walsh, Jennifer, Kehoe, Shella, Delossantos, Jennifer, Lalor, Siobhan, O'Nuallain, Helena, Behan, Sandra, Mcpherson, Ailesh, Corcoran, Patricia, Gordon, Glenda, Rooney, Dassy, Levy, Mazal, Azencot, Vladimir, Gurevich, Alinoy, Lavy, Valentina, Bendelari, Romina, Marconi, Antonio, Barone, Chiara, Gatti, Andrea, Giampaoletti, Cinzia, Borgognoni, Davide Massimo Ghioldi, Arena, Raimondo, Giacomo, Castiglione, Anna Vita Bruno, Giorgia, Rubulotta, Antonella, Mo, Amalia, Corso, Salvatore, Girianni, Andrea, Bruni, Eugenio, Garofalo, Salvatore Maurizio Maggiore, Alessandro Di Risio, Italo, Calamai, Rosario, Spina, Savino, Spadaro, Carlo Alberto Volta, Antonella, Cotoia, Lucia, Mirabella, Laura, Maulicino, Giancarlo, Abregal, Maria, Donvito, Paolo, D'Ambrosio, Filipo, Binda, Ileana, Adamina, Alessandro, Galazzi, Alessandra, Negro, Rosanna, Vaschetto, Fabio, Capuzzi, Margherita, Boschetto, Lucia, Stivanello, Luciano, Bonaccorso, Chiara, Megna, Pasquale, Iozzo, Antonino, Rizzo, Giovanni, Scire, Maria Rosa Taibi, Francesca Paola Tranello, Antonio, Manzo, Lidia, Traina, Beatrice, Pastore, Attilio, Quaini, Gian Domenico Giusti, Gloria, Montaldi, Federica, Piergentili, Federica, Mancini, Simona, Casaioli, Francesco, Uccelli, Fabio, Guarracino, Adriana, Onelli, Valentina Di Gravio, Maria, Cossu, Oliva, Matrona, Monica, Rocco, Daniela, Alampi, Federica, Dellafiore, Flavia, Ranalli, Matteo, Bossolasco, Elisabetta, Brizio, Pina, Migliorino, Paolo, Cortellazi, Moris, Rosati, Francesco, D'Ambrosio, Catia, Quagliotto, Erik, Roman-Pognuz, Alberto, Peratoner, De Rosa, Silvia, Marina Alessandra Martin, Francesca De Sanctis, Paolo, Ciorba, Patrick, Toppin, Hyacinth, Harding-Goldson, Shunsuke, Taito, Nobuaki, Shime, Ryohey, Yamamoto, Fumiya, Kanda, Akemi, Hirao, Moritoki, Egi, Ayako, Noguchi, Satoru, Hashimoto, Umeda, Aya, Hideaki, Sakuramoto, Akira, Ohuchi, Jun, Kataoka, Kumi, Maruyama, Izumi, Nakayama, Yoshimasa, Nishime, Koji, Fujimoto, Kenji, Takahashi, Mayumi, Tsujimoto, Masako, Shimizu, Eunice, Tole, Malcolm, C Correia, Je Hyeong Kim, Sunghoon, Park, Kyung Chan Kim, Jonghyun, Baek, Jung-Min, Bae, So Young Park, Tai Sun Park, Heung Bum Lee, Seung Yong Park, Jisoo, Park, Lee, Yeon-Joo, Cho, Young-Jae, Sang-Miin, Lee, Kyeongman, Jeon, Seok Chan Kim, Jongmin, Lee, Hyun Keun Chee, Jin Won Huh, Yun Su Sim, Junghyun, Kim, Youjin, Chang, Jong-Joon, Ahn, Byung Ju Kang, Won-Yeon, Lee, Seok Jeong Lee, Nehat, Baftiu, Ivasr, Krastins, Sonia, Stiban, Michel El Feghaly, Elie, Gharios, Marie, Merheb, Mohamed, Benlamin, Ala, Khaled, Wesal Ali Belkhair, Majd, Tabib, Firas, Ashour, Ahmed, Elhadi, Osama Wanees Emhemid Tababa, Taha, Khaled, Soad Imhmed, R Alkhumsi, Abdualhamid, I Alshrif, Ahmed Ali Aboufray, Aya, Alabuzidi, Ahmed Ramadan Triki, Mala, Elgammudi, Hajer Ben Zahra, Enas, Soula, Maram Milud Said Al-Alawi, Hazem, Ahmed, Mohamed Abdurazzag Ali Ghula, Saulius, Vosylius, Lucie, Mouton, Touraj, Rastegar, Claude, Sertznig, Gilles, Martin, Christian, Theisen, Christian, Ferretti, Fränk, Gils, Marc, Gallion, Asmah, Zainudin, Laila Kamaliah Kamalul Bahrin, Shanti Rudra Deva, Azmin Huda Abdul Rahim, Sherliza, Wahab, W Nazaruddin, W Hassan, Wan Nasrudin Wan Ismail, Mohd Nazri Ali, Tien Meng Khoo, Noryani Mohd Samat, Jenny May Geok Tong, Nik Azman Nik Adib, Mohd Basri Mat Nor, Shanthi, Ratnam, Nahla, Ismail, Siti Rohayah Sulaiman, Kit Weng Foong, Anita, Alias, Ngu Pei Hua, Jorge Macias Zermeno, Daniel, Blanco, Karely, Duran, Claudia Lizbeth Lopez Nava, San Juan Roman Nandyelly, Luis Alejandro Sanchez-Hurtado, Brigitte, Tejeda-Huezo, Mario Del Moral Armengol, Luis Pedro Ambriz Nava, Jorge Guerra Herrera, Gilberto Felipe Vazquez de Anda, Humberto, Gallegos-Perez, Nancy, Hernandez-Sanchez, Lucia, Hernandez-Ponce, Luis, Gorordo-Delsol, Marcos, Hernandez-Romero, Saira, Gomez, Fernando, Molinar, Silvio, A Ñamendys-Silva, Juan, P Romero-Gonzalez, Daira, Gonzalez, Antonio, Landaverde, Miguel Ángel Sosa, Berenice, Navarro, José Ivan Rodriguez de Molina Serrano, Sergio Reyes Iburrigarro, Alejandro, Ibarra, Joaquin, Aguirre, Mayra, Martinez-Gonzalez, Nayeli Rocio Cañas Padilla, Ana Alícia Velarde Pineda, Missael Vladimir Espinoza Villafuerte, María Ocotlan Gonzalez Herrera, Battsetseg, Baasanjav, Abdelhamid, Hachimi, Mina, Elkhayari, Tarek, Dendane, Nisha Bhandari Subedi, Sabina Dhakal Pathak, Meena, Manandhar, Laura Van Gulik, Mark Van Den Brink, Peter Van Vliet, Benjamin, Gerretsen, Lettie Van Den Berg, Marina De Haan, Binny, Tuinstra, Paul, Kuijpers, Jennifer, Reijntjens, Jan Wytze Vermeijden, Martin, Rinket, Margijske, Vanroest, Auke, Reidinga, Bert, Loef, Willem, Dieperink, Marisa, Onrust, Tom, Dormans, Laura, Bormans, 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Guillén, Josep Trenado Alvarez, Mercedes Del Cotillo, Jesus Emilio Barrueco-Francioni, Belen Burgos Conde, Maria Pilar Sogues Blanco, Maria Luisa Blasco, Ana Isabel Clement, Clara, Hurtado, Luz Coronado Sanz, David, Perez-Torres, Estefanía, Prol-Silva, Jorge, Pereira, Iván Areán González, Anastasio Espejo Cano, Cesar Rodriguez Nuñez, Inmaculada Lorenzo Fernadez, Alejandra Azahara Marguello Fernandez, Rosa Del Bosque Diez, Badiola, Hilario, Begoña, Zalba-Etayo, Ana, Pascual-Bielsa, Preveen, Banwarie, Dick, Nahar, Alisha van Axel, Naraindath, N Boedjawan, Erika Backlund Jansson, Ann-Sofie, Malvemyr, Lotta, Johansson, Ulla, Sandberg, Catarina, Tingsvik, Gunilla, Mattsson, Gun, Löf, Martin, Spångfors, Mona, Ringdal, Sebastian, Geijer, Lotti, Orvelius, Mia, Hylen, Caroline, Lagerhäll, Eva, Åkerman, Viveca Hamback Hellkvist, Ulrica, Mickelsson, Ewa, Wahlbom, Ing-Marie, Larsson, Ewa, Wallin, Filippo, Boroli, Solenne, Ory, Margaret Lynn Jong, Alexander, Dullenkopf, Martin, Lang, Yvan, Fleury, 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Polgarova, Shaly, George, Ritoo, Kapoor, Ceri, Lynch, Nathalie, Fox, Karen, Cranmer, Natalie, Fox, Thomas, Llewellym, Kelly, Matthews, Louise, Maltby, Jowena, Ibao, Karen, Boulton, Rachel, Jarman, Karen, Baxter, Ashok Sundai Raj, Arif, Moghal, Joanne, White, Suzanne, Barrowcliffe, Mark, Pulletz, Vaarisan, Ganeshalingam, Rosaleen, Baruah, Carole, Boulanger, Helen, Baker, Justin, Woods, Poe Poe Ei, Vongayi, Ogbeide, Paul, Hayden, Jennifer, Hughes, Madhu, Balasubramanian, Armorel, Salberg, Rajnish, Saha, Dagmar, Holmquist, Claire, Derbyshire, Neil, Smith, Elizabeth, Stones, Jane, Ademokun, Monica, Popescu, Maria Schofield Legorburo, Samantha, North, Carole, Brett, Helen, Jaundoo, Jayne, Craig, Simon, Whiteley, Clare, Howcroft, Liz, Wilby, Peter, Delve, David, Shaw, Karen, Williams, Ingeborg, D Welters, Jane, Mcmullen, Stephen, Brett, Leah, Flores, Treiza, Trueman-Dawkins, Mae, Templeton, John, Adams, Catherine, Smith, John, Prowle, Heather, Byers, Andrea, Mcdonnell, Bernd Oliver Rose, Rosie, Reece-Anthony, Luis, Mendes, Marcela, Vizcaychipi, Rhian, Bull, Grace, Lacaden, Eleanor, Santiago, Carlos Castro Delgado, Sarah, Farnell-Ward, Elaine, Thorpe, Justine, Somerville, Anne, Williams, Donna, Cummings, Helen, Derrick, Sarah, Brumwell, Claire, Randell, Nicola, Mccann, Emma, Aves, Gillian, Berry, Tamas, Szakmany, Una, Gunter, Paul, Pulak, Nikki, Sarkar, Kerry, Wright, Vitor, Gomes, Jones, Jo, Ruth, Palfrey, Julie, Camsooksai, Abby, Lewis, Antony, Eneas, Ascanio, Tridente, Louise, Barr, Beverley, Thomas, Emma, Parkin, Daniel, Horner, Christian, Frey, Suzanne, Bench, Rachel, Baumber, Phil, Broadhurst, Matthew, Jackson, Lynne, Williams, Michele, Clark, Jonathan, Paddle, Sarah, Bean, Sarah, Buckley, Christopher, Palfreeman, Sophie, Liu, Nicola, Allison, Ben, Attwood, Penny, Parsons, Victoria, Houghton, Sarah Jane Turner, David, Higgins, Egidija, Bielskute, Nicola, Horrigan, Reni, Jacob, Karen, Habgood, Ahmed, Zaki, Amy, Collins, Jenny, Lord, Charalice, Ramiro, Agnieszka, 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European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, Muzha, D., Ribas, A.M., Lipovesty, F., Loudet, C., Coyer, F., Eller, P., Mostafa, N., Honoré, P.M., Telleria, V.M., Smajic, J., Nogueira, P.C., Nafees, KMK, Hentchoya, R., Rose, L., Soledad, J., Lin, F., Cardenas, Y., Reyes, A.G., Sustic, A., Mpouzika, M., Vymazal, T., Jensen, H.I., Aguirre-Bermeo, H., Maddison, L., Valta, M., Calvino-Gunther, S., Bloos, F., Adipa, F.E., Koulouras, V., Enamorado, J., Ágoston, Z., Birgisdóttir, H., Gupta, A., Gurjar, M., Kilapong, B., Hashemian, S.M., Martin-Loeches, I., Benbenishty, J., Cortegiani, A., Fletcher, K., Hayashi, Y., Waweru-Siika, W., Abidi, K., Lee, S.M., Hadri, B., Dolgusevs, M., Abillama, F.F., Jovaisa, T., Thix, C., Elhadi, M., Nor, B.M., Ratnam, S., Mazlan, M.Z., Maiyalagan, S., Sánchez-Hurtado, L., Belii, A., Naranpurev, M., Gautam, P., De Lange, D., Parke, R., Ilesanmi, R.E., Shosholcheva, M., Petosic, A., Lind, R., Ffarcsi, M.H., Bogarin, J., Hernandez, A.M., Mikaszewska-Sokolewicz, M., Sousa, B., Tomescu, D., Sandesc, D., Twagirumugabe, T., Gusarov, V., Ebaid, M., Jankovic, R., Slobodianiuk, G., Martonova, A., Knafelj, R., Mer, M., Maseda, E., Panka, B., Schefold, J.C., Joelsson-Alm, E., Trongtrakul, K., Merritt-Charles, L., Besbes, L.O., Dikmen, Y., Zgrzheblovska, L., Fielding, M., Rubulotta, F., Khanna, A.K., Saager, L., von der Osten, I., Greca, A., Cani, A., Xhindi, N., Hyska, G., Pinto, S., Alves, P., Esposito, R., Valgolio, E., Minope, JTS, Abdala, A., Ayala, M., Bravo, S., Bantar, A., Delgado, P., Badariotti, G., Lipovestky, F., Diaz, A., Saul, P., Setten, M., Aucapina, A., Acosta, Y., Gonzalez, V., Camputaro, L., Baccaro, F., Villa, R., Mastantuono, M., Dean, E., Rostello, O.F., Brizuela, P., Bartoli, J.R., Guereschi, M., Quiroga, C., Putruele, S., Villegas, P., Curilen, V., Fernandez, R., Nocheretti, M.G., Escalante, R.G., Loudet, C.I., Fernandez, S., Gonzalez, A.L., Alvarez, G.A., Iglesias, F., Chaparro, S., Zakalik, G., Pagella, G., Baini, M., Campos, P.A., Sabbag, I., Schmukler, A., Fonseca, I.P., Alvarez, G.M., Ramirez, M., Tapia, F., Bascary, C.A., Del Valle Gimenez, G., Bertoletti, F.P., Milioto, E., Bonsignore, PJM, Fernandez, M.A., Smith, J., Chimunda, T., Thompson, L., Maguire, T., Chaboyer, W., Watts, S., Mitchell, M., Powell, M., Lye, I., Parsons, L., Baker, N., Reynolds, C., Thompson, A., Masters, K., Sosnowski, K., Morrison, L., Leslie, G.D., Lakshmanan, R., Tabah, A., Brown, W., McDowell-Skaines, S., McLucas, A., Smith, C., Tallot, M., Jones, S., Barakat-Johnson, M., Leong, T., Butcher, R., Martin, K., Douschan, P., von Lewinski, D., Schmutz, R., Kolussi, U., Salman, F., Ateya, Z., De Decker, K., Van Regenmortel, N., Jans, A., Wijnands, P., Coremans, S., Honore, P.M., De Bels, D., Depuydt, T., Paillet, C., Jacquet, L.M., Swinnen, W., Hannes, F., Mergeay, M., Van de Velde, S., Allaert, S., Hoste, P., Borin, C., Balon, S., Fraipont, V., Biston, P., De Schryver, N., Dugernier, T., Van 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Yuan, C., Tan, L., Lin, Q., Guo, H., Yan, H., Xu, X., Zhang, W., Liang, J., Zhang, L., Tian, E., Zhao, Q., InSu, L., Dong, J., Gu, Y., Zhao, L., Qiao, H., Tuo, L., Lv, M., Zhu, J.Y., Zhu, J., Wei, Y., Liu, M., He, Y., Cheng, J., Liu, J., Jia, N., Wei, D., Wu, X., Duan, H., Lin, D., Liang, Q., Luo, X., Xiong, Y., Huang, R.F., Fu, J., Zan, T., Shi, Z., Long, Y., Lei, Y., Liu, X., Yumei, C., Wang, L., Zhang, Y., Xu, Y., Cheng, X., Zhijuan, W., Sun, C., Song, J., Wang, Y., Yuan, Y., Huang, Q., Yang, F., Wu, Y., Bai, X., Zheng, H., Song, M., Sun, Y., Li, Z., Luo, F., Li, L.C., Zhang, G., Xiao, L., Yu, T., Gao, G., Wei, W., Wang, F., Han, T., Li, T., Zeng, Q., Zeng, J.M., Pan, F., Wang, J., He, G., Chen, H., Zhang, F., Chao, Y., Chunhua, G., Yao, X., Bai, D., Liu, L., Liang, X., Zhang, N., Zhang, A., Hu, X., Zhang, H., Wang, R., Tak, P.S., Ho, S.W., Jiang, Q.X., Ding, X., Hong, L., Miao, L., Feng, Z., Huang, L., Wu, J., Guo, J., Zhang, B., Ma, C., Han, Y., Liu, C., Ding, M., Luan, L., Zheng, J., Lv, S., Jiang, S., Cao, W., Xue, X., Liu, G., Wei, X., Jiang, Y., Yao, Z., Gao, L., Zhao, W., Jiang, M., Hao, J., Zhang, J., Song, C., Chen, F., Wang, S., Hu, L., Cao, D., Wan, J., Wang, X., Shao, H., Zhang, Z., Cui, X., Fan, L., Yu, M., Li, B., Li, C., Chen, W., Li, Y., Zhigang, Z., Yuchen, W., Mu, C., Zhu, G., Bo, Q., Li, L., Chen, M., Jiang, J.H., Yin, H., Pang, X., Gong, Y.Y., Yang, S., Yan, X., Zheng, X., Lei, D., Lei, L., Guo, Y., Yu, J., Sun, W., Bi, A., Li, W., Ni, D., Wu, Z., Song, B., Fei, Q., Xiaoyan, Y., Ran, Q., Xixi, L., Jiao, X., Ji, H., Zhiping, S., Hong, M., Jianhong, M., Hao, Y., Yin, L., Hui, C., Ju, W., Huo, Y., Chen, L., Yan, Y., Bao, G., Cao, Y., Xu, L., Guixiang, J., Zhao, H.M., Huang, X., Dai, Z., Jian, Y., Tian, Z., Cao, Z.Q., Li, M., Ouyang, F., Ma, F., Jin, W., Ge, L., Wu, S., Yuan, W., Chen, T., Shi, G., Chen, Z., Liu, K., Lin, X., Yuemen, L., Lijuan, S., Tian, X.F., Dong, Y., Bocui, N., Wang, G., Zhao, Y., Yang, Q., Hu, R.L., Li, X.Q., Yu, Z.J., Yao, 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D'Ambrosio, F., Quagliotto, C., Roman-Pognuz, E., Peratoner, A., De Rosa, S., Martin, M.A., De Sanctis, F., Ciorba, P., Toppin, P., Harding-Goldson, H., Taito, S., Shime, N., Yamamoto, R., Kanda, F., Hirao, A., Egi, M., Noguchi, A., Hashimoto, S., Aya, U., Sakuramoto, H., Ohuchi, A., Kataoka, J., Maruyama, K., Nakayama, I., Nishime, Y., Fujimoto, K., Takahashi, K., Tsujimoto, M., Shimizu, M., Tole, E., Correia, M.C., Kim, J.H., Park, S., Kim, K.C., Baek, J., Bae, J.M., Park, S.Y., Park, T.S., Lee, H.B., Park, J., Yeon-Joo, L., Young-Jae, C., Jeon, K., Kim, S.C., Lee, J., Chee, H.K., Huh, J.W., Sim, Y.S., Kim, J., Chang, Y., Ahn, J.J., Kang, B.J., Lee, W.Y., Lee, S.J., Baftiu, N., Krastins, I., Stiban, S., Feghaly, M.E., Gharios, E., Merheb, M., Benlamin, M., Khaled, A., Belkhair, W.A., Tabib, M., Ashour, F., Elhadi, A., Tababa, OWE, Khaled, T., Alkhumsi, SIR, Alshrif, A.I., Aboufray, A.A., Alabuzidi, A., Triki, A.R., Elgammudi, M., Zahra, H.B., Soula, E., Al-Alawi, MMS, Ahmed, H., Ghula, MAA, Vosylius, S., Mouton, L., Rastegar, T., Sertznig, C., Martin, G., Theisen, C., Ferretti, C., Gils, F., Gallion, M., Zainudin, A., Bahrin, LKK, Deva, S.R., Rahim, AHA, Wahab, S., Hassan, WNW, Ismail, WNW, Ali, M.N., Khoo, T.M., Samat, N.M., Tong, JMG, Adib, NAN, Nor, MBM, Ismail, N., Sulaiman, S.R., Foong, K.W., Alias, A., Hua, N.P., Zermeno, J.M., Blanco, D., Duran, K., Nava, CLL, Nandyelly, SJR, Sanchez-Hurtado, L.A., Tejeda-Huezo, B., Del Moral Armengol, M., Nava, LPA, Herrera, J.G., de Anda, GFV, Gallegos-Perez, H., Hernandez-Sanchez, N., Hernandez-Ponce, L., Gorordo-Delsol, L., Hernandez-Romero, M., Gomez, S., Molinar, F., Ñamendys-Silva, S.A., Romero-Gonzalez, J.P., Gonzalez, D., Landaverde, A., Sosa, M.Á., Navarro, B., de Molina Serrano, JIR, Iburrigarro, S.R., Ibarra, A., Aguirre, J., Martinez-Gonzalez, M., Padilla, NRC, Pineda, AAV, Villafuerte, MVE, Herrera, MOG, Baasanjav, B., Hachimi, A., Elkhayari, M., Dendane, T., Subedi, N.B., Pathak, S.D., Manandhar, M., Van 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A.S., Goller, S., Afonso, E., Larina, E., Labeau, Sonia O. 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Lee S.J., Baftiu N., Krastins I., Stiban S., Feghaly M.E., Gharios E., Merheb M., Benlamin M., Khaled A., Belkhair W.A., Tabib M., Ashour F., Elhadi A., Tababa O.W.E., Khaled T., Alkhumsi S.I.R., Alshrif A.I., Aboufray A.A., Alabuzidi A., Triki A.R., Elgammudi M., Zahra H.B., Soula E., Al-Alawi M.M.S., Ahmed H., Ghula M.A.A., Vosylius S., Mouton L., Rastegar T., Sertznig C., Martin G., Theisen C., Ferretti C., Gils F., Gallion M., Zainudin A., Bahrin L.K.K., Deva S.R., Rahim A.H.A., Wahab S., Hassan W.N.W., Ismail W.N.W., Ali M.N., Khoo T.M., Samat N.M., Tong J.M.G., Adib N.A.N., Nor M.B.M., Ismail N., Sulaiman S.R., Foong K.W., Alias A., Hua N.P., Zermeno J.M., Blanco D., Duran K., Nava C.L.L., Nandyelly S.J.R., Sanchez-Hurtado L.A., Tejeda-Huezo B., Del Moral Armengol M., Nava L.P.A., Herrera J.G., de Anda G.F.V., Gallegos-Perez H., Hernandez-Sanchez N., Hernandez-Ponce L., Gorordo-Delsol L., Hernandez-Romero M., Gomez S., Molinar F., Namendys-Silva S.A., Romero-Gonzalez J.P., Gonzalez D., Landaverde A., Sosa M.A., Navarro B., de Molina Serrano J.I.R., Iburrigarro S.R., Ibarra A., Aguirre J., Martinez-Gonzalez M., Padilla N.R.C., Pineda A.A.V., Villafuerte M.V.E., Herrera M.O.G., Baasanjav B., Hachimi A., Elkhayari M., Dendane T., Subedi N.B., Pathak S.D., Manandhar M., Van Gulik L., Van Den Brink M., Van Vliet P., Gerretsen B., Van Den Berg L., De Haan M., Tuinstra B., Kuijpers P., Reijntjens J., Vermeijden J.W., Rinket M., Vanroest M., Reidinga A., Loef B., Dieperink W., Onrust M., Dormans T., Bormans L., Koopmans M., Gerritsen R.T., Van Den Elst A., Evers M., Oiting O., Wilting R., Ramaker B., van der Kuil M., Fijen J.-W., Haas L., De Lange D., Haringman J., Newby L., Gilder E., Hacking D., Dagooc R., Song R., Waibel H., Dawn F., Rapley J., Chadwick L., Chapman C., Crone P., Albrett J., Marko P., Goodson J., Browne T., Whitticase R., Davidson C., Judd H., Owens D., Onyeka T., Ugwu I., Ilesanmi R., Adejumo P.O., Owojuyigbe A., Adenekan A., Uba S., Chime C., Jibrin D., Sankey B.J., Adekola O., Olanipekun S., Shosolcheva M., Gievski V., Kartalov A., Naumovski F., Kuzmanovska B., Trposak A., Bogoevska-Miteva Z., Rosalia R., Olsen B.F., Sjobo B., Jensen K.D., Sykehus D., Johansen B.F., Straede E., Johansen E., Finnstrom I.J., Toellefsen A., Ostenjo H., Bjorgen H., Bratsberg B., Kristoffersen E., Skorstad E.M., Hansen S., Vullum S., Lunde G.A., Arntsen W., Lund M., Akselsen G.R., Monstad K.R., Stenset A., Haugom H., Monsen B., Hogvall L., Trudvang S., Galaaen B., Malmin S.K., Andersen M.H., Hargott R.F., Andersen Y., Steffenak E., Nyhus M., Meland B., Hashmi M., Rivas N., Maidana E., de Jesus Ortiz A., Cabral D.M.B., Simi M., Aponte C., Rivas J.C., Gill S., Garcia A., Alvarenga G., Cespedes L., Perez H., Moreira M.L., Canete F., Gonzalez R., Monges N., Coman M., Pederzani M., Franco N., Aganon F., Martinez R., Noblezada-Uy D., Ellazar C.G., Cerezo F.D., Palo J.E., Aperocho C.A.J., Isanan M., Tubacka M., Jasiewicz P., Czuczwar M., Borys M., Gutysz-Wojnicka A., Glinka L., Gawda R., Bilawicz J., Cabrita P., Vieira J., Figueiredo M.F., Pinheiro C.M., Antunes N., Pedro L., Ferreira F., Parente I., Varela M., Fernandes F., Martins C., Viveiros A., Cavaco R., Rita C.S., Dias S., Feranandes A.M., Silva P., Nunes C., Cabral J., Pires F., Ferreira H., Santos J., Pinto V.M.V., Bispo B.M., Ferreira A., Molinos E., Lafuente E., Gregorio R., Costa H., Lima A., Ferreira S., Seromenho V., Luis E., Valerio I., Cesar H., Tavares A., Alsheikhly A.S., Mahmood S., Guran C.T., Moise A., Filipescu D.C., Luchian M., Popescu M., Scutariu M.A., Petrisor C., Hagau N., Grigoras I., Patrichi T., Gusarev V., Pivkina A., Kulakov V., Ignatenko O., Kovaleva J., Zhivotneva T., Zhedaeva M., Matiushkov N., Ershova O., Egorova N., Khoronenko V., Baskakov D., Sergeev D., Piradov M., Grishina L., Magomedov M., Zuev E., Gorokhovatsky U., Leonova A., Fadeeva L., Belskiy V., Galishevskiy D., Zubareva N., Tribulev M., Zueva O., Kiselev A., Kamenshchikov N., Tokareva E., Petrushin M., Starchenko I., Nshimyumuremyi I., Muhizi J., Buregeya E., Nzarora J., Assiri A., Ebaid M.S., Almekhlafi G., Mandourah Y., Velickovic J., Velickovic D., Jovanovic B., Hadzibegovic A., Stefanovic B., Misic V., Bumbasirevic V., Rajkovic M., Stojanovic M., Gavrilovic S., Stanojevic M., Yaghi A., Turcan A., Firment P., Rabarova D., Lancaricova D., Vlaovic J., Groznik M., Lukic M., Perme J., Sostaric M., Umek N., Mirkovic T., Dolenc S., Fister M., Zorko N., Markota A., Yeni N.P., Jali P., Schmollgruber S., Syed M.R., Parag N., Wise R., Galiana M., Navarro J.A., De Pablo A.M., Albert P., Martinez P., Mendiara Y., Garcia B., Llinas A.A., Riveiro M., Gallart E., Riera A., Sanz M., Salo S., Lajara M.A.G., Nieto M.V., Garcia R., Pena J.M.G., Gorgolas M.C., Isasi M.A., Sierra R., Gordo F., Conejo I., Salva-Costa V., Garzon-Tovar C., Lospitao S., Gutierrez P., Girona M., Adamuz J., Olivares P.G., de Ceballos J.P.G., Tirado C., De Wit I., Polo A.B.C., del Mar Diaz Salcedo M., Ripolles-Melchor J., Martinez-Hurtado E., Alvarez J.D., Arcas M.L.B., Gonzalez J.I.T., de la Ventana A.B.S., Calleja P.L.-A., Alvarez R.G., Zamora P.S., Guerrero A.O., Cosano R., Perez-Vacas J., Campos-Perez M., Barreiro E.M., Sanchez L.C., Diaz M.G., Jimenez R., Del Rio Cabajo L., Muriel D.S., Alonso H.F., Fernandez A.W., Pinan I.S., Albaiceta G.M., Fernandez M.C.I., Abos F.J.S., Monedero P., Chueca R.M., Aguirre L.G., Manosa S.C., Luque C.P., Calpe N., Losilla M.R., Fores M.T., Farre O., Fernandez O., del Rosario Villar Redondo M., Arteta Arteta D.S., Sanchez M.A.H., Espinosa C.P., Reyes L.M., Domenech L.C., Guillen C.V., Alvarez J.T., del Cotillo M., Barrueco-Francioni J.E., Conde B.B., Blanco M.P.S., Blasco M.L., Clement A.I., Hurtado C., Sanz L.C., Perez-Torres D., Prol-Silva E., Pereira J., Gonzalez I.A., Cano A.E., Nunez C.R., Fernadez I.L., Fernandez A.A.M., Del Bosque Diez R., Hilario B., Zalba-Etayo B., Pascual-Bielsa A., Banwarie P., Nahar D., van Axel A., Boedjawan N.N., Jansson E.B., Malvemyr A.-S., Johansson L., Sandberg U., Tingsvik C., Mattsson G., Lof G., Spangfors M., Ringdal M., Geijer S., Orvelius L., Hylen M., Lagerhall C., Akerman E., Hellkvist V.H., Mickelsson U., Wahlbom E., Larsson I.-M., Wallin E., Boroli F., Ory S., Jong M.L., Dullenkopf A., Lang M., Fleury Y., Maus M., Ben-Hamouda N., Fishman A., Hsu M.Y., Chang S.C., Trongtratul K., Sawawiboon C., Morakul S., Khwannimit B., Singh K., Ventour D., Figaro-Barclay D., Sankar-Maharaj S., Mebazaa M.S., Kamoun S., Elatrous S., Besbes L., Abroug F., Naija W., Elhechmi Y.Z., Sellami W., Hajjej Z., Merhabene T., Talik I., Kuscu O.O., Dilek O., Zerman A., Dal H.C., Turan S., Aydemir S., Yilmaz H., Calili D.K., Izdes S., Cengiz M., Gumus A., Tasdemir B., Kagnici A., Ay M., Ay S.A., Caliskan G., Akbas T., Balbay A.O., Efe S., Inal V., Elay G., Karabacak P., Ozserezli B., Senturk E., Demirkiran O., Bozbay S., Erdogan E., Akker M., Peker N., Ozgultekin A., Serin S.O., Turan C., Karaoren G., Goksu S., Karakurt S., Arikan H., Gul F., Cinel I., Kara I., Undar H.N., Bayraktar Y.S., Celik J.B., Tokur M.E., Aydin D.T., Yildiz I., Ozcan B., Erdivanli B., Eroglu A., Akdag D., Unlu N., Dungca A., Ali A., Thankamma B., Reyes P.E., John S., Rajendran A., Ahmad F.K.E., Smiley K.A., Hojden S., Miller M.T., Das Sasidharan Nair V., Antonio M.G.S., Qawasmeh K.A., Shawish S.A., Twiggs H., Rosado I., Babych V., Morren F., Young C., Vaughan-Jones N., Harris S., Burns K., Georgiev C., Shayamano R., Kerslake I., Creber P., Vochin A., O'Brien C., Caddell P., Hagan S., Hughes M., Torlinski T., Sherwin J., Kannan S., Markham A., Lebon R., Cupitt J., Cranshaw J., White N., Marriott V., Milner W., Groba C.B., Azoia J., Polgarova P., George S., Kapoor R., Lynch C., Fox N., Cranmer K., Llewellym T., Matthews K., Maltby L., Ibao J., Boulton K., Jarman R., Baxter K., Raj A.S., Moghal A., White J., Barrowcliffe S., Pulletz M., Ganeshalingam V., Baruah R., Baker H., Woods J., Ei P.P., Ogbeide V., Hayden P., Hughes J., Balasubramanian M., Salberg A., Saha R., Holmquist D., Derbyshire C., Smith N., Stones E., Ademokun J., Legorburo M.S., North S., Brett C., Jaundoo H., Craig J., Whiteley S., Howcroft C., Wilby L., Delve P., Shaw D., Williams K., Welters I.D., McMullen J., Brett S., Flores L., Trueman-Dawkins T., Templeton M., Adams J., Prowle J., Byers H., McDonnell A., Rose B.O., Reece-Anthony R., Mendes L., Vizcaychipi M., Bull R., Lacaden G., Santiago E., Delgado C.C., Farnell-Ward S., Thorpe E., Somerville J., Williams A., Cummings D., Derrick H., Brumwell S., Randell C., McCann N., Aves E., Berry G., Szakmany T., Gunter U., Pulak P., Sarkar N., Wright K., Gomes V., Jones J., Palfrey R., Camsooksai J., Lewis A., Eneas A., Tridente A., Barr L., Thomas B., Parkin E., Horner D., Frey C., Bench S., Baumber R., Broadhurst P., Jackson M., Williams L., Clark M., Paddle J., Bean S., Buckley S., Palfreeman C., Liu S., Allison N., Attwood B., Parsons P., Houghton V., Turner S.J., Higgins D., Bielskute E., Horrigan N., Jacob R., Habgood K., Zaki A., Collins A., Lord J., Ramiro C., Kubisz-Pudelko A., Kotze M., Williams H., Iovenko I., Tsarev A., Briva A., Mendez G., Napolitano L., Teig M., Rodriguez G.E., Ben-Jacob T., Potestio C., Eng T., Mahanes D., Khanna A., Duggal A., Nananmori M., Lois M., Karamchandani K., Bealer C., Barefield C., Terry D., Fivecoat P., Idowu O., Cata J., Clesi T., Peterson J., Hatton K., Dhaliwal J., Mueller D., Tao J., Eltorai A.S., Pastores S.M., Remor N., Salazar J., Barkas D., Joffe A., Barnes C., Sona C., Schallom M., Short J., Lorenzo J., Von Der Osten I., Borkowska M., Demarre L., Pleitinckx V., Xing C., Debue A.-S., Goller S., Larina E., Labeau, S. O., Blackwood, B., Brett, S. J., Deschepper, M., Francois, G., Honore, P. M., Khanna, A. K., Williams, G., Blot, S. I., Ribas, A. M., Telleria, V. M., Nogueira, P. C., Nafees, K. M. K., Reyes, A. G., Jensen, H. I., Adipa, F. E., Agoston, Z., Hashemian, S. M., Lee, S. -M., Abillama, F. F., Nor, B. M., Mazlan, M. Z., Sanchez-Hurtado, L., De lange, D., Ilesanmi, R. E., Ffarcsi, M. H., Hernandez, A. M., Schefold, J. C., Besbes, L. O., Minope, J. T. S., Rostello, O. F., Bartoli, J. R., Nocheretti, M. G., Escalante, R. G., Loudet, C. I., Gonzalez, A. L., Alvarez, G. A., Campos, P. A., Fonseca, I. P., Alvarez, G. M., Bascary, C. A., del Valle Gimenez, G., Bertoletti, F. P., Bonsignore, P. J. M., Fernandez, M. A., Leslie, G. D., Mclucas, A., Jacquet, L. -M., de Almeida, A. O., Jorge, S. A., Schmidt, R. C., Garcia, P. C., Ronchini, A. L. V., Manap, N. B. A., Laizner, A. M., Mcquirter, M., Kampayana, B. S., Sepulveda, M. I., Zamorano, M. J. F., Zhao, R. H., Hu, L. P., Jiao, Q. F., Wang, H. 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V., Namendys-Silva, S. A., Romero-Gonzalez, J. P., Sosa, M. A., de Molina Serrano, J. I. R., Iburrigarro, S. R., Padilla, N. R. C., Pineda, A. A. V., Villafuerte, M. V. E., Herrera, M. O. G., Subedi, N. B., Pathak, S. D., Vermeijden, J. W., Gerritsen, R. T., Fijen, J. -W., Adejumo, P. O., Sankey, B. J., Olsen, B. F., Jensen, K. D., Johansen, B. F., Finnstrom, I. J., Skorstad, E. M., Lunde, G. A., Akselsen, G. R., Monstad, K. R., Hogvall, L., Malmin, S. K., Andersen, M. H., Hargott, R. F., de Jesus Ortiz, A., Cabral, D. M. B., Rivas, J. C., Moreira, M. L., Ellazar, C. G., Cerezo, F. D., Palo, J. E., Aperocho, C. A. J., Figueiredo, M. F., Pinheiro, C. M., Rita, C. S., Feranandes, A. M., Pinto, V. M. V., Bispo, B. M., Lima, A., Alsheikhly, A. S., Guran, C. T., Filipescu, D. C., Scutariu, M. A., Ebaid, M. S., Velickovic, D., Rajkovic, M., Stanojevic, M., Turcan, A., Lancaricova, D., Yeni, N. P., Syed, M. R., Navarro, J. A., De Pablo, A. M., Llinas, A. A., Lajara, M. A. G., Nieto, M. V., Pena, J. M. G., Gorgolas, M. C., Isasi, M. A., Salva-Costa, V., Garzon-Tovar, C., Olivares, P. G., de Ceballos, J. P. G., Polo, A. B. C., del Mar Diaz Salcedo, M., Alvarez, J. D., Arcas, M. L. B., Gonzalez, J. I. T., de la Ventana, A. B. S., Calleja, P. L. -A., Alvarez, R. G., Zamora, P. S., Guerrero, A. O., Barreiro, E. M., Sanchez, L. C., Diaz, M. G., Muriel, D. S., Alonso, H. F., Fernandez, A. W., Pinan, I. S., Albaiceta, G. M., Fernandez, M. C. I., Abos, F. J. S., Chueca, R. M., Aguirre, L. G., Manosa, S. C., Luque, C. P., Losilla, M. R., Fores, M. T., del Rosario Villar Redondo, M., Arteta Arteta, D. S., Sanchez, M. A. H., Espinosa, C. P., Reyes, L. M., Domenech, L. C., Guillen, C. V., Alvarez, J. T., del Cotillo, M., Barrueco-Francioni, J. E., Conde, B. B., Blanco, M. P. S., Blasco, M. L., Clement, A. I., Sanz, L. C., Gonzalez, I. A., Cano, A. E., Nunez, C. R., Fernadez, I. L., Fernandez, A. A. M., Boedjawan, N. N., Jansson, E. B., Malvemyr, A. -S., Lof, G., Spangfors, M., Lagerhall, C., Akerman, E., Hellkvist, V. H., Larsson, I. -M., Jong, M. L., Hsu, M. Y., Chang, S. C., Mebazaa, M. S., Elhechmi, Y. Z., Kuscu, O. O., Dal, H. C., Calili, D. K., Izdes, S., Gumus, A., Tasdemir, B., Kagnici, A., Ay, S. A., Balbay, A. O., Ozserezli, B., Senturk, E., Serin, S. O., Gul, F., Cinel, I., Undar, H. N., Bayraktar, Y. S., Celik, J. B., Tokur, M. E., Aydin, D. T., Yildiz, I., Ozcan, B., Akdag, D., Unlu, N., Reyes, P. E., Ahmad, F. K. E., Smiley, K. A., Miller, M. T., Antonio, M. G. S., Qawasmeh, K. A., Shawish, S. A., Groba, C. B., Raj, A. S., Ei, P. P., Legorburo, M. S., Welters, I. D., Mcmullen, J., Mcdonnell, A., Rose, B. O., Delgado, C. C., Mccann, N., Turner, S. J., Rodriguez, G. E., Eltorai, A. S., Pastores, S. M., Demarre, L., and Debue, A. -S.

Subjects
Male, Original, medicine.medical_treatment, artificial, Critical Care and Intensive Care Medicine, Medical and Health Sciences, Pressure ulcer, law.invention, Decubitus epidemiology, ICU, Morbidity, Mortality, Outcome, Pressure injury, Risk factors, Adult, Aged, Hospital Mortality, Humans, Patient Discharge, Prevalence, Risk Factors, Intensive Care Units, Respiration, Artificial, 0302 clinical medicine, decubitus epidemiology, pressure injury, pressure ulcer, outcome, risk factors, morbidity, mortality, law, Medicine and Health Sciences, adults, Medicine, Simplified Acute Physiology Score, icu, ziekenhuissterfte, Immunodeficiency, intensive care, European Society of Intensive Care Medicine (ESICM) Trials Group Collaborators, mannen, volwassenen, COST, Intensive care unit, STATE, ULCERS, Underweight, medicine.symptom, Life Sciences & Biomedicine, Human, medicine.medical_specialty, risicofactoren, Decubitus epidemiology, ICU, Pressure injury, Pressure ulcer, Outcome, Risk factors, Morbidity, Mortality, pressure injuries, Intensive Care Unit, prevalentie, NO, 1117 Public Health and Health Services, DecubICUs Study Team, 03 medical and health sciences, Critical Care Medicine, Anesthesiology, General & Internal Medicine, Health Sciences, ouderen, Mechanical ventilation, Science & Technology, business.industry, decubitus, Risk Factor, 030208 emergency & critical care medicine, 1103 Clinical Sciences, Odds ratio, medicine.disease, Emergency & Critical Care Medicine, Confidence interval, 030228 respiratory system, Emergency medicine, kunstmatige ademhaling, RISK-FACTORS, business, respiration
Abstract

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347, Funder: Flemish Society for Critical Care Nurses, Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score < 19, ICU stay > 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat.

Published
2021
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36. Effectiveness of workplace interventions with digital elements to reduce sedentary behaviours in office employees: a systematic review and meta-analysis.

Author

Parés-Salomón I, Señé-Mir AM, Martín-Bozas F, Loef B, Coffey A, Dowd KP, Jabardo-Camprubí G, Proper KI, Puig-Ribera A, and Bort-Roig J

Subjects
Humans, Sitting Position, Occupational Health, Randomized Controlled Trials as Topic, Sedentary Behavior, Workplace, Health Promotion methods
Abstract

Background: Digital interventions are potential tools for reducing and limiting occupational sedentary behaviour (SB) in sedentary desk-based jobs. Given the harmful effects of sitting too much and sitting for too long while working, the aim of this systematic review and meta-analysis was to examine the effectiveness of workplace interventions, that incorporated digital elements, to reduce the time spent in SB in office workers., Methods: Randomised control trials that evaluated the implementation of workplace interventions that incorporated digital elements for breaking and limiting SB among desk-based jobs were identified by literature searches in six electronic databases (PubMed, Web of Science, Scopus, CINAHL, PsycINFO and PEDro) published up to 2023. Studies were included if total and/or occupational SB were assessed. Only studies that reported pre- and postintervention mean differences and standard deviations or standard errors for both intervention arms were used for the meta-analysis. The meta-analysis was conducted using Review Manager 5 (RevMan 5; Cochrane Collaboration, Oxford, UK). Risk of bias was assessed using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields QUALSYST tool., Results: Nineteen studies were included in the systematic review. The most employed digital elements were information delivery and mediated organisational support and social influences. Multicomponent, information, and counselling interventions measuring total and/or occupational/nonoccupational SB time by self-report or via device-based measures were reported. Multicomponent interventions were the most represented. Eleven studies were included in the meta-analysis, which presented a reduction of 29.9 (95% CI: -45.2, -14.5) min/8 h workday in SB (overall effect: Z = 3.81)., Conclusions: Multicomponent interventions, using a wide range of digital features, have demonstrated effectiveness in reducing time spent in SB at the workplace among desk-based employees. However, due to hybrid work (i.e., work in the office and home) being a customary mode of work for many employees, it is important for future studies to assess the feasibility and effectiveness of these interventions in the evolving work landscape., Trial Registration: The review protocol was registered in the Prospero database (CRD42022377366)., (© 2024. The Author(s).)

Published
2024
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37. Sleep quality, sleep duration, and sleep disturbances among hospital night workers: a prospective cohort study.

Author

van Elk F, Loef B, Proper KI, Burdorf A, Robroek SJW, and Oude Hengel KM

Subjects
Humans, Sleep Duration, Prospective Studies, Sleep, Hospitals, Sleep Quality, Sleep Initiation and Maintenance Disorders
Abstract

Purpose: This study aimed to assess among hospital night workers (i) to what extent sleep quality, sleep duration and sleep disturbances overlap, and (ii) associations between sociodemographic factors, lifestyle factors and work characteristics and sleep components., Methods: Data were used from 467 hospital night workers participating in the Klokwerk + study, a prospective cohort study with two measurements. Sleep quality was measured by the Pittsburgh Sleep Quality Index, sleep duration and sleep disturbances were measured by the Medical Outcomes Study Sleep Scale. The overlap between the three sleep measures was visualized with a Venn diagram and the proportions of overlap was calculated. Associations between independent variables (sociodemographic factors, lifestyle factors and work characteristics) and the three sleep outcomes were estimated using between-within Poisson regression models., Results: About 50% of the hospital night workers had at least one poor sleep outcome. Overlap in poor sleep outcomes was apparent for 36.8% of these workers, while the majority had a poor outcome in one of the sleep components only (63.1%). Former smoking had a significant association with poor sleep quality. For most independent variables no associations with poor sleep outcomes were observed., Conclusion: Our findings suggest that sleep quality, sleep duration and sleep disturbances are separate entities and should be studied separately. Lifestyle factors and work characteristics were generally not associated with poor sleep. Since these factors can have an acute effect on sleep, future research should consider ecological momentary assessment to examine how exposure and outcomes (co)vary within-persons, over time, and across contexts. Trial registration Netherlands Trial Register trial number NL56022.041.16., (© 2023. The Author(s).)

Published
2024
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38. Past or Present; Which Exposures Predict Metabolomic Aging Better? The Doetinchem Cohort Study.

Author

Smit AP, Herber GM, Kuiper LM, Loef B, Picavet HSJ, and Verschuren WMM

Subjects
Male, Humans, Female, Cohort Studies, Cross-Sectional Studies, Smoking, Aging, Metabolomics
Abstract

People age differently. Differences in aging might be reflected by metabolites, also known as metabolomic aging. Predicting metabolomic aging is of interest in public health research. However, the added value of longitudinal over cross-sectional predictors of metabolomic aging is unknown. We studied exposome-related exposures as potential predictors of metabolomic aging, both cross-sectionally and longitudinally in men and women. We used data from 4 459 participants, aged 36-75 of Round 4 (2003-2008) of the long-running Doetinchem Cohort Study (DCS). Metabolomic age was calculated with the MetaboHealth algorithm. Cross-sectional exposures were demographic, biological, lifestyle, and environmental at Round 4. Longitudinal exposures were based on the average exposure over 15 years (Round 1 [1987-1991] to 4), and trend in these exposure over time. Random Forest was performed to identify model performance and important predictors. Prediction performances were similar for cross-sectional and longitudinal exposures in both men (R2 6.8 and 5.8, respectively) and women (R2 14.8 and 14.4, respectively). Biological and diet exposures were most predictive for metabolomic aging in both men and women. Other important predictors were smoking behavior for men and contraceptive use and menopausal status for women. Taking into account history of exposure levels (longitudinal) had no added value over cross-sectionally measured exposures in predicting metabolomic aging in the current study. However, the prediction performances of both models were rather low. The most important predictors for metabolomic aging were from the biological and lifestyle domain and differed slightly between men and women., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Published
2024
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39. Mental health of healthcare workers during the first year of the COVID-19 pandemic in the Netherlands: a longitudinal study.

Author

van der Noordt M, Proper KI, Loef B, Boot CRL, Kroese FM, de Bruin M, and van Oostrom SH

Subjects
Humans, Longitudinal Studies, Netherlands epidemiology, Pandemics, Health Personnel, Mental Health, COVID-19 epidemiology
Abstract

Purpose: In March 2020, the WHO declared COVID-19 a pandemic. Previous virus outbreaks, such as the SARS outbreak in 2003, appeared to have a great impact on the mental health of healthcare workers. The aim of this study is to examine to what extent mental health of healthcare workers differed from non-healthcare workers during the first year of the COVID-19 pandemic., Methods: We used data from a large-scale longitudinal online survey conducted by the Corona Behavioral Unit in the Netherlands. Eleven measurement rounds were analyzed, from April 2020 to March 2021 ( N  = 16,615; number of observations = 64,206). Mental health, as measured by the 5-item Mental Health Inventory, was compared between healthcare workers and non-healthcare workers over time, by performing linear GEE-analyses., Results: Mental health scores were higher among healthcare workers compared to non-healthcare workers during the first year of the pandemic (1.29 on a 0-100 scale, 95%-CI = 0.75-1.84). During peak periods of the pandemic, with over 100 hospital admissions or over 25 ICU admissions per day and subsequently more restrictive measures, mental health scores were observed to be lower in both healthcare workers and non-healthcare workers., Conclusion: During the first year of the COVID-19 pandemic, we observed no relevant difference in mental health between healthcare workers and non-healthcare workers in the Netherlands. To be better prepared for another pandemic, future research should investigate which factors hinder and which factors support healthcare workers to maintain a good mental health., 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 © 2023 van der Noordt, Proper, Loef, Boot, Kroese, de Bruin and van Oostrom.)

Published
2023
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40. Perimenopause: Symptoms, work ability and health among 4010 Dutch workers.

Author

Oude Hengel KM, Soeter M, In der Maur M, van Oostrom SH, Loef B, and Hooftman WE

Subjects
Female, Humans, Cross-Sectional Studies, Work Capacity Evaluation, Surveys and Questionnaires, Perimenopause psychology, Menopause psychology
Abstract

Objective: In this study we examined the associations between menopausal symptoms and work ability and health among a general population of Dutch female workers., Study Design: This nationwide cross-sectional study was a follow-up of the Netherlands Working Conditions Survey 2020. In 2021, 4010 Dutch female employees aged 40-67 years completed an online survey on a variety of topics, including menopausal symptoms, work ability and health., Methods: Linear and logistic regression analyses were performed to investigate the association between the degree of menopausal symptoms with work ability, self-rated health and emotional exhaustion, after adjustment for potential confounders., Results: Almost one-fifth of participants were in the perimenopause (n = 743). Of these women, 80 % experienced menopausal symptoms: 27.5 % 'often' and 52.5 % 'sometimes'. Experiencing menopausal symptoms was associated with lower work ability, poorer self-rated health, and more emotional exhaustion. These associations were most pronounced among perimenopausal women 'often' experiencing symptoms., Conclusions: Menopausal symptoms threaten the sustainable employability of female workers. Interventions and guidelines are needed to support women, employers and (occupational) health professionals., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2023
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41. Estimating healthcare expenditures after becoming divorced or widowed using propensity score matching.

Author

Meulman I, Loef B, Stadhouders N, Moger TA, Wong A, Polder JJ, and Uiters E

Subjects
Female, Humans, Health Expenditures, Propensity Score, Marital Status, Divorce, Widowhood
Abstract

Becoming divorced or widowed are stressful life events experienced by a substantial part of the population. While marital status is a significant predictor in many studies on healthcare expenditures, effects of a change in marital status, specifically becoming divorced or widowed, are less investigated. This study combines individual health claims data and registered sociodemographic characteristics from all Dutch inhabitants (about 17 million) to estimate the differences in healthcare expenditure for individuals whose marital status changed (n = 469,901) compared to individuals who remained married, using propensity score matching and generalized linear models. We found that individuals who were (long-term) divorced or widowed had 12-27% higher healthcare expenditures (RR = 1.12, 95% CI 1.11-1.14; RR = 1.27, 95% CI 1.26-1.29) than individuals who remained married. Foremost, this could be attributed to higher spending on mental healthcare and home care. Higher healthcare expenditures are observed for both divorced and widowed individuals, both recently and long-term divorced/widowed individuals, and across all age groups, income levels and educational levels., (© 2022. The Author(s).)

Published
2023
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42. Predicting self-perceived general health status using machine learning: an external exposome study.

Author

Hoekstra J, Lenssen ES, Wong A, Loef B, Herber GM, Boshuizen HC, Strak M, Verschuren WMM, and Janssen NAH

Subjects
Humans, Emotions, Loneliness, Health Status, Machine Learning, Exposome
Abstract

Background: Self-perceived general health (SPGH) is a general health indicator commonly used in epidemiological research and is associated with a wide range of exposures from different domains. However, most studies on SPGH only investigated a limited set of exposures and did not take the entire external exposome into account. We aimed to develop predictive models for SPGH based on exposome datasets using machine learning techniques and identify the most important predictors of poor SPGH status., Methods: Random forest (RF) was used on two datasets based on personal characteristics from the 2012 and 2016 editions of the Dutch national health survey, enriched with environmental and neighborhood characteristics. Model performance was determined using the area under the curve (AUC) score. The most important predictors were identified using a variable importance procedure and individual effects of exposures using partial dependence and accumulated local effect plots. The final 2012 dataset contained information on 199,840 individuals and 81 variables, whereas the final 2016 dataset had 244,557 individuals with 91 variables., Results: Our RF models had overall good predictive performance (2012: AUC = 0.864 (CI: 0.852-0.876); 2016: AUC = 0.890 (CI: 0.883-0.896)) and the most important predictors were "Control of own life", "Physical activity", "Loneliness" and "Making ends meet". Subjects who felt insufficiently in control of their own life, scored high on the De Jong-Gierveld loneliness scale or had difficulty in making ends meet were more likely to have poor SPGH status, whereas increased physical activity per week reduced the probability of poor SPGH. We observed associations between some neighborhood and environmental characteristics, but these variables did not contribute to the overall predictive strength of the models., Conclusions: This study identified that within an external exposome dataset, the most important predictors for SPGH status are related to mental wellbeing, physical exercise, loneliness, and financial status., (© 2023. The Author(s).)

Published
2023
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43. The longitudinal association between working from home and musculoskeletal pain during the COVID-19 pandemic.

Author

Bosma E, Loef B, van Oostrom SH, and Proper KI

Subjects
Humans, Pandemics, Surveys and Questionnaires, Shoulder, Musculoskeletal Pain epidemiology, Musculoskeletal Pain etiology, COVID-19 epidemiology
Abstract

Objective: This study investigates the associations between working from home and the presence of MSP during the COVID-19 pandemic. Working from home often involves a lot of sedentary computer screen work and the home working environment might not be optimally equipped, which can lead to health problems, including musculoskeletal pain (MSP)., Methods: Longitudinal data from 16 questionnaire rounds of the Lifelines COVID-19 cohort during the first year of the COVID-19 pandemic (March 2020-February 2021) were used. In total, 40,702 Dutch workers were included. In every round, participants reported whether they worked on location, from home, or hybrid. Logistic Generalized Estimating Equations were used to study the association of work situation with the presence of MSP and the presence of severe MSP., Results: Working from home was associated with higher risks of having MSP in the lower back (OR: 1.05, 95% CI 1.02-1.08), in the upper back (OR: 1.24, 95% CI 1.18-1.31), and in the neck, shoulder(s) and/or arm(s) (OR: 1.18, 95% CI 1.13-1.22). Hybrid working was associated with higher risks of having pain in the upper back (OR: 1.09, 95% CI 1.02-1.17) and in the neck, shoulder(s) and/or arm(s) (OR: 1.14, 95% CI 1.09-1.20). Both home and hybrid workers had higher risks of severe MSP in the different body areas., Conclusion: Home workers, and to a smaller extent hybrid workers, had higher risks of having MSP than location workers during the first year of the COVID-19 pandemic. The results indicate the importance of measures to prevent MSP in future policies involving working from home., (© 2022. The Author(s).)

Published
2023
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44. Predictors of healthy physiological aging across generations in a 30-year population-based cohort study: the Doetinchem Cohort Study.

Author

Loef B, Herber GM, Wong A, Janssen NAH, Hoekstra J, Picavet HSJ, and Verschuren WMM

Subjects
Humans, Aged, Aged, 80 and over, Cohort Studies, Overweight, Aging physiology, Cholesterol, Body Mass Index, Risk Factors, Healthy Aging
Abstract

Background: Predicting healthy physiological aging is of major interest within public health research. However, longitudinal studies into predictors of healthy physiological aging that include numerous exposures from different domains (i.e. the exposome) are scarce. Our aim is to identify the most important exposome-related predictors of healthy physiological aging over the life course and across generations., Methods: Data were used from 2815 participants from four generations (generation 1960s/1950s/1940s/1930s aged respectively 20-29/30-39/40-49/50-59 years old at baseline, wave 1) of the Doetinchem Cohort Study who were measured every 5 years for 30 years. The Healthy Aging Index, a physiological aging index consisting of blood pressure, glucose, creatinine, lung function, and cognitive functioning, was measured at age 46-85 years (wave 6). The average exposure and trend of exposure over time of demographic, lifestyle, environmental, and biological exposures were included, resulting in 86 exposures. Random forest was used to identify important predictors., Results: The most important predictors of healthy physiological aging were overweight-related (BMI, waist circumference, waist/hip ratio) and cholesterol-related (using cholesterol lowering medication, HDL and total cholesterol) measures. Diet and educational level also ranked in the top of important exposures. No substantial differences were observed in the predictors of healthy physiological aging across generations. The final prediction model's performance was modest with an R 2 of 17%., Conclusions: Taken together, our findings suggest that longitudinal cardiometabolic exposures (i.e. overweight- and cholesterol-related measures) are most important in predicting healthy physiological aging. This finding was similar across generations. More work is needed to confirm our findings in other study populations., (© 2023. The Author(s).)

Published
2023
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45. The mediating role of physical activity and sedentary behavior in the association between working from home and musculoskeletal pain during the COVID-19 pandemic.

Author

Loef B, van Oostrom SH, Bosma E, and Proper KI

Subjects
Humans, Sedentary Behavior, Pandemics, Exercise, Musculoskeletal Pain epidemiology, COVID-19 epidemiology
Abstract

Introduction: Working from home during the COVID-19 pandemic has been associated both with physical inactivity and musculoskeletal pain. However, it has not been examined whether physical activity and sedentary behavior are underlying mechanisms in the association between working from home and musculoskeletal pain. Therefore, we examined their mediating role in this association., Methods: Data were used from 24 questionnaire rounds of the Lifelines COVID-19 cohort (March 2020-January 2022). Longitudinal information on work situation (location, home, hybrid), physical activity, sedentary behavior, and musculoskeletal pain was collected among 28,586 workers. Analysis of physical activity/sedentary behavior as mediators of the association between working from home and musculoskeletal pain was performed using multilevel structural equation modeling., Results: Home workers more often had pain in the upper back [odds ratio (OR) = 1.17, 95%-confidence interval (CI) = 1.02-1.34] and arm, neck, and/or shoulder (ANS) (OR = 1.32, 95%-CI = 1.19-1.47) than location workers. Furthermore, home workers were more often sedentary for >9 h per work day than location workers (OR = 2.82, 95%-CI = 2.56-3.09), and being more sedentary was associated with musculoskeletal pain (upper back: OR = 1.17, 95%-CI = 1.06-1.30; ANS: OR = 1.25, 95%-CI = 1.16-1.34). Corresponding indirect effects were OR = 1.18 (95%-CI = 1.04-1.33) and OR = 1.26 (95%-CI = 1.12-1.35). No indirect effect was found for physical activity. Similar indirect effects were observed for hybrid workers., Conclusion: Home and hybrid workers were more likely to have pain in the upper musculoskeletal system during the COVID-19 pandemic than location workers, which was partly mediated by increased sedentary behavior, but not by reduced physical activity. Measures to reduce sedentary time in home workers may contribute to preventing musculoskeletal pain., 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 Loef, van Oostrom, Bosma, Lifelines Corona Research Initiative and Proper.)

Published
2022
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46. GlycA, a Biomarker of Low-Grade Inflammation, Is Increased in Male Night Shift Workers.

Author

Bizzarri D, Dollé MET, Loef B, van den Akker EB, and van Kerkhof LWM

Abstract

Sustained night shift work is associated with various adverse health risks, including an increased risk of cardiovascular disease, type II diabetes, and susceptibility to infectious respiratory diseases. The extent of these adverse health effects, however, seems to greatly vary between night shift workers, yet the underlying reasons and the mechanisms underlying these interindividual differences remain poorly understood. Metabolomics assays in the blood have recently gained much attention as a minimally invasive biomarker platform capturing information predictive of metabolic and cardiovascular diseases. In this cross-sectional study, we explored and compared the metabolic profiles of 1010 night shift workers and 1010 age- and sex-matched day workers (non-shift workers) from the Lifelines Cohort Study. The metabolic profiles were determined using the 1 H-NMR Nightingale platform for the quantification of 250 parameters of metabolism, including routine lipids, extensive lipoprotein subclasses, fatty acid composition, and various low-molecular metabolites, including amino acids, ketone bodies, and gluconeogenesis-related metabolites. Night shift workers had an increased BMI (26.6 vs. 25.9 kg/m 2 ) compared with day workers (non-shift workers) in both sexes, were slightly more likely to be ever smokers (only in males) (54% vs. 46%), worked on average 5.9 ± 3.7 night shifts per month, and had been working in night shifts for 18.3 ± 10.5 years on average. We observed changes in several metabolic markers in male night shift workers compared with non-shift workers, but no changes were observed in women. In men, we observed higher levels of glycoprotein acetyls (GlycA), triglycerides, and fatty acids compared with non-shift workers. The changes were seen in the ratio of triglycerides and cholesterol(esters) to total lipids in different sizes of VLDL particles. Glycoprotein acetyls (GlycAs) are of particular interest as markers since they are known as biomarkers for low-grade chronic inflammation. When the analyses were adjusted for BMI, no significant associations were observed. Further studies are needed to better understand the relationship between night shift work and metabolic profiles, particularly with respect to the role of sex and BMI in this relationship.

Published
2022
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47. Night-shift work is associated with increased susceptibility to SARS-CoV-2 infection.

Author

Loef B, Dollé MET, Proper KI, van Baarle D, Initiative LCR, and van Kerkhof LW

Subjects
Circadian Rhythm, Humans, Prospective Studies, SARS-CoV-2, Work Schedule Tolerance, COVID-19, Shift Work Schedule
Abstract

Night-shift workers experience disturbances of their circadian rhythm and sleep, which may make them more susceptible to infectious diseases. Therefore, we studied whether night-shift workers are at higher risk of testing positive for SARS-CoV-2 infection than day workers. In this prospective study, data were used from 20 questionnaire rounds of the Dutch Lifelines COVID-19 cohort that was initiated in March 2020. In the different questionnaire rounds, 2285 night-shift workers and 23,766 day workers reported whether they had tested positive for SARS-CoV-2. Cox proportional hazards regression models adjusted for demographic, work, and health covariates were used to compare SARS-CoV-2 incidence between night-shift and day workers. From March 2020-January 2021, 3.4% of night-shift workers and 2.2% of day workers reported to have tested positive for SARS-CoV-2 (p < .001). After adjustment for covariates, night-shift workers had a 37% higher risk of testing positive for SARS-CoV-2 (hazard ratio: 1.37, 95% confidence interval: 1.05-1.77). In this study, we show that night-shift workers were more likely to test positive for SARS-CoV-2 than day workers, which adds to the growing evidence that night-shift work may influence the complex processes involved in infection susceptibility. Further mechanistic insight is needed to understand the relation between night-shift work and (SARS-CoV-2) infection susceptibility.

Published
2022
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48. Working from home during the COVID-19 pandemic and its longitudinal association with physical activity and sedentary behavior.

Author

Loef B, van Oostrom SH, van der Noordt M, and Proper KI

Subjects
Exercise, Humans, Pandemics, Sitting Position, COVID-19 epidemiology, Sedentary Behavior
Abstract

Objective: Working from home during the COVID-19 pandemic has affected many workers' daily life and possibly their physical activity behavior. We studied the longitudinal association of working from home during the pandemic with physical activity and sedentary behavior., Methods: Longitudinal data from 17 questionnaire rounds of the Lifelines COVID-19 cohort (March 2020-February 2021) were used. In total, 33 325 workers were included. In every round, participants reported their current work situation: location, home, or hybrid (working on location and from home). Physical activity levels and sedentary behavior before and during the pandemic were asked. Logistic generalized estimating equations adjusted for demographic/work/health covariates were used to study the association of work situation with physical activity and sedentary behavior., Results: Home workers were less likely to meet the recommended ≥150 minutes/week of moderate-to-vigorous-intensity activity during the pandemic than location workers [odds ratio (OR) 0.93, 95% confidence interval (CI) 0.90-0.96] and more likely to be less physically active than before the pandemic (OR 1.09, 95% CI 1.04-1.14). Furthermore, compared to location workers, home and hybrid workers were more likely to be more sedentary (sitting ≥8 hours/day) on workdays during than before the pandemic (OR 1.51, 95% CI 1.39-1.64/1.36-1.68, respectively)., Conclusions: Compared to location workers, home workers (and to a lesser extent hybrid workers) were more often physically inactive and sedentary during than before the COVID-19 pandemic. As a substantial part of the working population may continue to work (partly) from home after the pandemic, workers should be supported to increase activity and reduce sitting while working from home.

Published
2022
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49. Using random forest to identify longitudinal predictors of health in a 30-year cohort study.

Author

Loef B, Wong A, Janssen NAH, Strak M, Hoekstra J, Picavet HSJ, Boshuizen HCH, Verschuren WMM, and Herber GM

Subjects
Cohort Studies, Environmental Exposure, Humans, Longitudinal Studies, Machine Learning, Exposome
Abstract

Due to the wealth of exposome data from longitudinal cohort studies that is currently available, the need for methods to adequately analyze these data is growing. We propose an approach in which machine learning is used to identify longitudinal exposome-related predictors of health, and illustrate its potential through an application. Our application involves studying the relation between exposome and self-perceived health based on the 30-year running Doetinchem Cohort Study. Random Forest (RF) was used to identify the strongest predictors due to its favorable prediction performance in prior research. The relation between predictors and outcome was visualized with partial dependence and accumulated local effects plots. To facilitate interpretation, exposures were summarized by expressing them as the average exposure and average trend over time. The RF model's ability to discriminate poor from good self-perceived health was acceptable (Area-Under-the-Curve = 0.707). Nine exposures from different exposome-related domains were largely responsible for the model's performance, while 87 exposures seemed to contribute little to the performance. Our approach demonstrates that ML can be interpreted more than widely believed, and can be applied to identify important longitudinal predictors of health over the life course in studies with repeated measures of exposure. The approach is context-independent and broadly applicable., (© 2022. The Author(s).)

Published
2022
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50. Night shift work characteristics are associated with several elevated metabolic risk factors and immune cell counts in a cross-sectional study.

Author

Streng AA, Loef B, Dollé MET, van der Horst GTJ, Chaves I, Proper KI, and van Kerkhof LWM

Subjects
Body Mass Index, Cohort Studies, Cross-Sectional Studies, Risk Factors, Time Factors, Waist Circumference, Immunity, Cellular, Leukocyte Count, Occupational Health, Shift Work Schedule adverse effects, Work Schedule Tolerance physiology
Abstract

Night shift work is associated with increased health risks. Here we examined the association of metabolic risk factors and immune cell counts, with both night shift work and particular characteristics thereof: frequency, duration and consecutive night shifts. We performed a cross-sectional study using data from 10,201 non-shift workers and 1062 night shift workers of the Lifelines Cohort study. Linear regression analyses, adjusted for demographic, lifestyle and occupational factors, were used to study associations of night shift work characteristics with metabolic risk factors and immune cell counts. Night shift workers had an increased BMI, waist circumference and immune cell counts compared to non-shift workers. This was especially seen in night shift workers who had a higher frequency of night shifts per month (≥ 5: BMI: B = 0.81 kg/m 2 (95%-CI = 0.43-1.10); waist circumference: B = 1.58 cm (95%-Cl = 0.34-1.71; leukocytes: B = 0.19 × 10 9 cells/L (95%-CI = 0.04-0.34 × 10 9 )) and worked more consecutive night shifts (> 3: BMI: B = 0.92 kg/m 2 (95%-CI = 0.41-1.43); waist circumference: B = 1.85 cm (95%-Cl = 0.45-3.24); leukocytes: B = 0.32 × 10 9 cells/L (95%-CI = 0.09-0.55 × 10 9 )). This association was less pronounced in long-term night shift workers (≥ 20 years). Our findings provide evidence for the association between night shift work characteristics and BMI, waist circumference and leukocytes (including, monocytes, lymphocytes, and basophil granulocytes)., (© 2022. The Author(s).)

Published
2022
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