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3. A cellular reporter system to evaluate endogenous fetal hemoglobin induction and screen for therapeutic compounds

Author

Thijs C. J. Verheul, Nynke Gillemans, Kerstin Putzker, Rezin Majied, Tingyue Li, Memnia Vasiliou, Bert Eussen, Annelies deKlein, Wilfred F. J. vanIJcken, Emile van denAkker, Marieke vonLindern, Joe Lewis, Ulrike Uhrig, Yukio Nakamura, Thamar vanDijk, and Sjaak Philipsen

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Abstract Reactivation of fetal hemoglobin expression alleviates the symptoms associated with β‐globinopathies, severe hereditary diseases with significant global health implications due to their high morbidity and mortality rates. The symptoms emerge following the postnatal transition from fetal‐to‐adult hemoglobin expression. Extensive research has focused on inducing the expression of the fetal γ‐globin subunit to reverse this switch and ameliorate these symptoms. Despite decades of research, only one compound, hydroxyurea, found its way to the clinic as an inducer of fetal hemoglobin. Unfortunately, its efficacy varies among patients, highlighting the need for more effective treatments. Erythroid cell lines have been instrumental in the pursuit of both pharmacological and genetic ways to reverse the postnatal hemoglobin switch. Here, we describe the first endogenously tagged fetal hemoglobin reporter cell line based on the adult erythroid progenitor cell line HUDEP2. Utilizing CRISPR‐Cas9‐mediated knock‐in, a bioluminescent tag was integrated at the HBG1 gene. Subsequent extensive characterization confirmed that the resulting reporter cell line closely mirrors the HUDEP2 characteristics and that the cells report fetal hemoglobin induction with high sensitivity and specificity. This novel reporter cell line is therefore highly suitable for evaluating genetic and pharmacologic strategies to induce fetal hemoglobin. Furthermore, it provides an assay compatible with high‐throughput drug screening, exemplified by the identification of a cluster of known fetal hemoglobin inducers in a pilot study. This new tool is made available to the research community, with the aspiration that it will accelerate the search for safer and more effective strategies to reverse the hemoglobin switch.

Published
2024
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4. A pragmatic approach to estimating average treatment effects from EHR data: the effect of prone positioning on mechanically ventilated COVID-19 patients

Author

Izdebski, Adam, Thoral, Patrick J., Lalisang, Robbert C. A., McHugh, Dean M., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., Rigter, Sander, Wils, Evert-Jan, Frenzel, Tim, Dongelmans, Dave A., de Jong, Remko, Peters, Marco A. A., Kamps, Marlijn J. A, Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G. C. A., de Ruijter, Wouter, Urlings-Strop, Louise C., Smit, Ellen G. M., Mehagnoul-Schipper, D. Jannet, Dormans, Tom, de Jager, Cornelis P. C., Hendriks, Stefaan H. A., Achterberg, Sefanja, Oostdijk, Evelien, Reidinga, Auke C., Festen-Spanjer, Barbara, Brunnekreef, Gert B., Cornet, Alexander D., Tempel, Walter van den, Boelens, Age D., Koetsier, Peter, Lens, Judith, Faber, Harald J., Karakus, A., Entjes, Robert, de Jong, Paul, Rettig, Thijs C. D., Arbous, Sesmu, Fleuren, Lucas M., Dam, Tariq A., Tonutti, Michele, de Bruin, Daan P., Elbers, Paul W. G., and Cinà, Giovanni

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence
Abstract

Despite the recent progress in the field of causal inference, to date there is no agreed upon methodology to glean treatment effect estimation from observational data. The consequence on clinical practice is that, when lacking results from a randomized trial, medical personnel is left without guidance on what seems to be effective in a real-world scenario. This article proposes a pragmatic methodology to obtain preliminary but robust estimation of treatment effect from observational studies, to provide front-line clinicians with a degree of confidence in their treatment strategy. Our study design is applied to an open problem, the estimation of treatment effect of the proning maneuver on COVID-19 Intensive Care patients.

Published
2021

5. Sprays from droplets impacting a mesh

Author

Kooij, Stefan, Moqaddam, Ali Mazloomi, de Goede, Thijs C., Derome, Dominique, Carmeliet, Jan, Shahidzadeh, Noushine, and Bonn, Daniel

Subjects
Physics - Fluid Dynamics
Abstract

In liquid spray applications, the sprays are often created by the formation and destabilization of a liquid sheet or jet. The disadvantage of such atomization processes is that the breakup is often highly irregular, causing a broad distribution of droplet sizes. As these sizes are controlled by the ligament corrugation and size, a monodisperse spray should consist of ligaments that are both smooth and of equal size. A straightforward way of creating smooth and equally sized ligaments is by droplet impact on a mesh. In this work we show that this approach does however not produce monodisperse droplets, but instead the droplet size distribution is very broad, with a large number of small satellite drops. We demonstrate that the fragmentation is controlled by a jet instability, where initial perturbations caused by the injection process result in long-wavelength disturbances that determine the final ligament breakup. During destabilization the crests of these disturbances are connected by thin ligaments which are the leading cause of the large number of small droplets. A secondary coalescence process, due to small relative velocities between droplets, partly masks this effect by reducing the amount of small droplets. Of the many parameters in this system, we describe the effect of varying the mesh size, mesh rigidity, impact velocity, wetting properties, keeping the liquid properties the same by focusing on water droplets only. We further perform Lattice Boltzmann modeling of the impact process that reproduces key features seen in the experimental data., Comment: 11 pages, 12 figures, 6 supplemental movies (not included)

Published
2018
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6. Predicting responders to prone positioning in mechanically ventilated patients with COVID-19 using machine learning

Author

Tariq A. Dam, Luca F. Roggeveen, Fuda van Diggelen, Lucas M. Fleuren, Ameet R. Jagesar, Martijn Otten, Heder J. de Vries, Diederik Gommers, Olaf L. Cremer, Rob J. Bosman, Sander Rigter, Evert-Jan Wils, Tim Frenzel, Dave A. Dongelmans, Remko de Jong, Marco A. A. Peters, Marlijn J. A. Kamps, Dharmanand Ramnarain, Ralph Nowitzky, Fleur G. C. A. Nooteboom, Wouter de Ruijter, Louise C. Urlings-Strop, Ellen G. M. Smit, D. Jannet Mehagnoul-Schipper, Tom Dormans, Cornelis P. C. de Jager, Stefaan H. A. Hendriks, Sefanja Achterberg, Evelien Oostdijk, Auke C. Reidinga, Barbara Festen-Spanjer, Gert B. Brunnekreef, Alexander D. Cornet, Walter van den Tempel, Age D. Boelens, Peter Koetsier, Judith Lens, Harald J. Faber, A. Karakus, Robert Entjes, Paul de Jong, Thijs C. D. Rettig, Sesmu Arbous, Sebastiaan J. J. Vonk, Tomas Machado, Willem E. Herter, Harm-Jan de Grooth, Patrick J. Thoral, Armand R. J. Girbes, Mark Hoogendoorn, Paul W. G. Elbers, and The Dutch ICU Data Sharing Against COVID-19 Collaborators

Subjects
COVID-19, Mechanical ventilation, Acute respiratory distress syndrome, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background For mechanically ventilated critically ill COVID-19 patients, prone positioning has quickly become an important treatment strategy, however, prone positioning is labor intensive and comes with potential adverse effects. Therefore, identifying which critically ill intubated COVID-19 patients will benefit may help allocate labor resources. Methods From the multi-center Dutch Data Warehouse of COVID-19 ICU patients from 25 hospitals, we selected all 3619 episodes of prone positioning in 1142 invasively mechanically ventilated patients. We excluded episodes longer than 24 h. Berlin ARDS criteria were not formally documented. We used supervised machine learning algorithms Logistic Regression, Random Forest, Naive Bayes, K-Nearest Neighbors, Support Vector Machine and Extreme Gradient Boosting on readily available and clinically relevant features to predict success of prone positioning after 4 h (window of 1 to 7 h) based on various possible outcomes. These outcomes were defined as improvements of at least 10% in PaO2/FiO2 ratio, ventilatory ratio, respiratory system compliance, or mechanical power. Separate models were created for each of these outcomes. Re-supination within 4 h after pronation was labeled as failure. We also developed models using a 20 mmHg improvement cut-off for PaO2/FiO2 ratio and using a combined outcome parameter. For all models, we evaluated feature importance expressed as contribution to predictive performance based on their relative ranking. Results The median duration of prone episodes was 17 h (11–20, median and IQR, N = 2632). Despite extensive modeling using a plethora of machine learning techniques and a large number of potentially clinically relevant features, discrimination between responders and non-responders remained poor with an area under the receiver operator characteristic curve of 0.62 for PaO2/FiO2 ratio using Logistic Regression, Random Forest and XGBoost. Feature importance was inconsistent between models for different outcomes. Notably, not even being a previous responder to prone positioning, or PEEP-levels before prone positioning, provided any meaningful contribution to predicting a successful next proning episode. Conclusions In mechanically ventilated COVID-19 patients, predicting the success of prone positioning using clinically relevant and readily available parameters from electronic health records is currently not feasible. Given the current evidence base, a liberal approach to proning in all patients with severe COVID-19 ARDS is therefore justified and in particular regardless of previous results of proning.

Published
2022
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7. Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta‐analysis of European, North American and Australian cohorts

Author

Santos, S, Voerman, E, Amiano, P, Barros, H, Beilin, LJ, Bergström, A, Charles, M‐A, Chatzi, L, Chevrier, C, Chrousos, GP, Corpeleijn, E, Costa, O, Costet, N, Crozier, S, Devereux, G, Doyon, M, Eggesbø, M, Fantini, MP, Farchi, S, Forastiere, F, Georgiu, V, Godfrey, KM, Gori, D, Grote, V, Hanke, W, Hertz‐Picciotto, I, Heude, B, Hivert, M‐F, Hryhorczuk, D, Huang, R‐C, Inskip, H, Karvonen, AM, Kenny, LC, Koletzko, B, Küpers, LK, Lagström, H, Lehmann, I, Magnus, P, Majewska, R, Mäkelä, J, Manios, Y, McAuliffe, FM, McDonald, SW, Mehegan, J, Melén, E, Mommers, M, Morgen, CS, Moschonis, G, Murray, D, Chaoimh, C Ní, Nohr, EA, Andersen, A‐M Nybo, Oken, E, Oostvogels, AJJM, Pac, A, Papadopoulou, E, Pekkanen, J, Pizzi, C, Polanska, K, Porta, D, Richiardi, L, Rifas‐Shiman, SL, Roeleveld, N, Ronfani, L, Santos, AC, Standl, M, Stigum, H, Stoltenberg, C, Thiering, E, Thijs, C, Torrent, M, Tough, SC, Trnovec, T, Turner, S, Gelder, MMHJ, Rossem, L, Berg, A, Vrijheid, M, Vrijkotte, TGM, West, J, Wijga, AH, Wright, J, Zvinchuk, O, Sørensen, TIA, Lawlor, DA, Gaillard, R, and Jaddoe, VWV

Subjects
Obesity, Contraception/Reproduction, Diabetes, Preterm, Low Birth Weight and Health of the Newborn, Infant Mortality, Cardiovascular, Clinical Research, Perinatal Period - Conditions Originating in Perinatal Period, Prevention, Nutrition, Pediatric, Aetiology, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, 2.1 Biological and endogenous factors, Prevention of disease and conditions, and promotion of well-being, Metabolic and endocrine, Reproductive health and childbirth, Good Health and Well Being, Adult, Australia, Birth Weight, Body Mass Index, Cohort Studies, Europe, Female, Gestational Age, Gestational Weight Gain, Humans, Infant, Newborn, North America, Odds Ratio, Overweight, Pregnancy, Pregnancy Complications, Risk Factors, Birthweight, body mass index, pregnancy complications, preterm birth, weight gain, Medical and Health Sciences, Obstetrics & Reproductive Medicine
Abstract

ObjectiveTo assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact.DesignIndividual participant data meta-analysis of 39 cohorts.SettingEurope, North America, and Oceania.Population265 270 births.MethodsInformation on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used.Main outcome measuresGestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth.ResultsHigher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31- 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain.ConclusionsMaternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity.Tweetable abstractPromoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Published
2019

8. Mental health symptoms in family members of COVID-19 ICU survivors 3 and 12 months after ICU admission: a multicentre prospective cohort study

Author

Heesakkers, Hidde, van der Hoeven, Johannes G., Corsten, Stijn, Janssen, Inge, Ewalds, Esther, Burgers-Bonthuis, Dominique, and Rettig, Thijs C. D.

Subjects
Mental health, Depression, Mental -- Risk factors, Post-traumatic stress disorder -- Risk factors, Hospital patients, Coronaviruses, Health care industry
Abstract

Purpose Long-term mental outcomes in family members of coronavirus disease 2019 (COVID-19) intensive care unit (ICU) survivors are unknown. Therefore, we assessed the prevalence of mental health symptoms, including associated risk factors, and quality of life (QoL) in family members of COVID-19 ICU survivors 3 and 12 months post-ICU. Methods A prospective multicentre cohort study in ICUs of ten Dutch hospitals, including adult family members of COVID-19 ICU survivors admitted between March 1, and July 1, 2020. Symptom prevalence rates of anxiety, depression (Hospital Anxiety and Depression Scale) and Post-Traumatic Stress Disorder (Impact of Event Scale-6), and QoL (Short Form-12) before ICU admission (baseline), and after 3 and 12 months were measured. Additionally, associations between family and patient characteristics and mental health symptoms were calculated. Results A total of 166 out of 197 (84.3%) included family members completed the 12-month follow-up of whom 46.1% and 38.3% had mental health symptoms 3 and 12 months post-ICU, respectively; both higher compared to baseline (22.4%) (p < 0.001). The mental component summary score of the SF-12 was lower at 12-month follow-up compared with baseline [mean difference mental component score: - 5.5 (95% confidence interval (CI) - 7.4 to - 3.6)]. Furthermore, 27.9% experienced work-related problems. Symptoms of anxiety (odds ratio (OR) 9.23; 95% CI 2.296-37.24; p = 0.002) and depression (OR 5.96; 95% CI 1.29-27.42; p = 0.02) prior to ICU admission were identified as risk factors for mental health symptoms after 12 months. Conclusion A considerable proportion of family members of COVID-19 survivors reported mental health symptoms 3 and 12 months after ICU admission, disrupting QoL and creating work-related problems., Author(s): Hidde Heesakkers [sup.1], Johannes G. van der Hoeven [sup.1], Stijn Corsten [sup.2], Inge Janssen [sup.3], Esther Ewalds [sup.4], Dominique Burgers-Bonthuis [sup.5], Thijs C. D. Rettig [sup.6], Crétien Jacobs [sup.7], [...]

Published
2022
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9. Predicting responders to prone positioning in mechanically ventilated patients with COVID-19 using machine learning

Author

Dam, Tariq A., Roggeveen, Luca F., van Diggelen, Fuda, Fleuren, Lucas M., Jagesar, Ameet R., Otten, Martijn, de Vries, Heder J., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., Rigter, Sander, Wils, Evert-Jan, Frenzel, Tim, Dongelmans, Dave A., de Jong, Remko, Peters, Marco A. A., Kamps, Marlijn J. A., Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G. C. A., de Ruijter, Wouter, Urlings-Strop, Louise C., Smit, Ellen G. M., Mehagnoul-Schipper, D. Jannet, Dormans, Tom, de Jager, Cornelis P. C., Hendriks, Stefaan H. A., Achterberg, Sefanja, Oostdijk, Evelien, Reidinga, Auke C., Festen-Spanjer, Barbara, Brunnekreef, Gert B., Cornet, Alexander D., van den Tempel, Walter, Boelens, Age D., Koetsier, Peter, Lens, Judith, Faber, Harald J., Karakus, A., Entjes, Robert, de Jong, Paul, Rettig, Thijs C. D., Arbous, Sesmu, Vonk, Sebastiaan J. J., Machado, Tomas, Herter, Willem E., de Grooth, Harm-Jan, Thoral, Patrick J., Girbes, Armand R. J., Hoogendoorn, Mark, and Elbers, Paul W. G.

Published
2022
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10. Predictors for extubation failure in COVID-19 patients using a machine learning approach

Author

Lucas M. Fleuren, Tariq A. Dam, Michele Tonutti, Daan P. de Bruin, Robbert C. A. Lalisang, Diederik Gommers, Olaf L. Cremer, Rob J. Bosman, Sander Rigter, Evert-Jan Wils, Tim Frenzel, Dave A. Dongelmans, Remko de Jong, Marco Peters, Marlijn J. A. Kamps, Dharmanand Ramnarain, Ralph Nowitzky, Fleur G. C. A. Nooteboom, Wouter de Ruijter, Louise C. Urlings-Strop, Ellen G. M. Smit, D. Jannet Mehagnoul-Schipper, Tom Dormans, Cornelis P. C. de Jager, Stefaan H. A. Hendriks, Sefanja Achterberg, Evelien Oostdijk, Auke C. Reidinga, Barbara Festen-Spanjer, Gert B. Brunnekreef, Alexander D. Cornet, Walter van den Tempel, Age D. Boelens, Peter Koetsier, Judith Lens, Harald J. Faber, A. Karakus, Robert Entjes, Paul de Jong, Thijs C. D. Rettig, Sesmu Arbous, Sebastiaan J. J. Vonk, Mattia Fornasa, Tomas Machado, Taco Houwert, Hidde Hovenkamp, Roberto Noorduijn Londono, Davide Quintarelli, Martijn G. Scholtemeijer, Aletta A. de Beer, Giovanni Cinà, Adam Kantorik, Tom de Ruijter, Willem E. Herter, Martijn Beudel, Armand R. J. Girbes, Mark Hoogendoorn, Patrick J. Thoral, Paul W. G. Elbers, and the Dutch ICU Data Sharing Against Covid-19 Collaborators

Subjects
Extubation, Prediction, Risk factors, Extubation failure, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Introduction Determining the optimal timing for extubation can be challenging in the intensive care. In this study, we aim to identify predictors for extubation failure in critically ill patients with COVID-19. Methods We used highly granular data from 3464 adult critically ill COVID patients in the multicenter Dutch Data Warehouse, including demographics, clinical observations, medications, fluid balance, laboratory values, vital signs, and data from life support devices. All intubated patients with at least one extubation attempt were eligible for analysis. Transferred patients, patients admitted for less than 24 h, and patients still admitted at the time of data extraction were excluded. Potential predictors were selected by a team of intensive care physicians. The primary and secondary outcomes were extubation without reintubation or death within the next 7 days and within 48 h, respectively. We trained and validated multiple machine learning algorithms using fivefold nested cross-validation. Predictor importance was estimated using Shapley additive explanations, while cutoff values for the relative probability of failed extubation were estimated through partial dependence plots. Results A total of 883 patients were included in the model derivation. The reintubation rate was 13.4% within 48 h and 18.9% at day 7, with a mortality rate of 0.6% and 1.0% respectively. The grandient-boost model performed best (area under the curve of 0.70) and was used to calculate predictor importance. Ventilatory characteristics and settings were the most important predictors. More specifically, a controlled mode duration longer than 4 days, a last fraction of inspired oxygen higher than 35%, a mean tidal volume per kg ideal body weight above 8 ml/kg in the day before extubation, and a shorter duration in assisted mode (

Published
2021
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11. Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial

Author

Sander Rozemeijer, Harm-Jan de Grooth, Paul W. G. Elbers, Armand R. J. Girbes, Corstiaan A. den Uil, Eric A. Dubois, Evert-Jan Wils, Thijs C. D. Rettig, Arthur R. H. van Zanten, Roel Vink, Bas van den Bogaard, Rob J. Bosman, Heleen M. Oudemans-van Straaten, and Angélique M. E. de Man

Subjects
Out-of-hospital cardiac arrest, Ischemia/reperfusion injury, Post-cardiac arrest syndrome, Cardiac arrest, Free radicals, Reactive oxygen species, Medicine (General), R5-920
Abstract

Abstract Background High-dose intravenous vitamin C directly scavenges and decreases the production of harmful reactive oxygen species (ROS) generated during ischemia/reperfusion after a cardiac arrest. The aim of this study is to investigate whether short-term treatment with a supplementary or very high-dose intravenous vitamin C reduces organ failure in post-cardiac arrest patients. Methods This is a double-blind, multi-center, randomized placebo-controlled trial conducted in 7 intensive care units (ICUs) in The Netherlands. A total of 270 patients with cardiac arrest and return of spontaneous circulation will be randomly assigned to three groups of 90 patients (1:1:1 ratio, stratified by site and age). Patients will intravenously receive a placebo, a supplementation dose of 3 g of vitamin C or a pharmacological dose of 10 g of vitamin C per day for 96 h. The primary endpoint is organ failure at 96 h as measured by the Resuscitation-Sequential Organ Failure Assessment (R-SOFA) score at 96 h minus the baseline score (delta R-SOFA). Secondary endpoints are a neurological outcome, mortality, length of ICU and hospital stay, myocardial injury, vasopressor support, lung injury score, ventilator-free days, renal function, ICU-acquired weakness, delirium, oxidative stress parameters, and plasma vitamin C concentrations. Discussion Vitamin C supplementation is safe and preclinical studies have shown beneficial effects of high-dose IV vitamin C in cardiac arrest models. This is the first RCT to assess the clinical effect of intravenous vitamin C on organ dysfunction in critically ill patients after cardiac arrest. Trial registration ClinicalTrials.gov NCT03509662. Registered on April 26, 2018. https://clinicaltrials.gov/ct2/show/NCT03509662 European Clinical Trials Database (EudraCT): 2017-004318-25. Registered on June 8, 2018. https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-004318-25/NL

Published
2021
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12. The Dutch Data Warehouse, a multicenter and full-admission electronic health records database for critically ill COVID-19 patients

Author

Lucas M. Fleuren, Tariq A. Dam, Michele Tonutti, Daan P. de Bruin, Robbert C. A. Lalisang, Diederik Gommers, Olaf L. Cremer, Rob J. Bosman, Sander Rigter, Evert-Jan Wils, Tim Frenzel, Dave A. Dongelmans, Remko de Jong, Marco Peters, Marlijn J. A. Kamps, Dharmanand Ramnarain, Ralph Nowitzky, Fleur G. C. A. Nooteboom, Wouter de Ruijter, Louise C. Urlings-Strop, Ellen G. M. Smit, D. Jannet Mehagnoul-Schipper, Tom Dormans, Cornelis P. C. de Jager, Stefaan H. A. Hendriks, Sefanja Achterberg, Evelien Oostdijk, Auke C. Reidinga, Barbara Festen-Spanjer, Gert B. Brunnekreef, Alexander D. Cornet, Walter van den Tempel, Age D. Boelens, Peter Koetsier, Judith Lens, Harald J. Faber, A. Karakus, Robert Entjes, Paul de Jong, Thijs C. D. Rettig, Sesmu Arbous, Sebastiaan J. J. Vonk, Mattia Fornasa, Tomas Machado, Taco Houwert, Hidde Hovenkamp, Roberto Noorduijn-Londono, Davide Quintarelli, Martijn G. Scholtemeijer, Aletta A. de Beer, Giovanni Cina, Martijn Beudel, Willem E. Herter, Armand R. J. Girbes, Mark Hoogendoorn, Patrick J. Thoral, and Paul W. G. Elbers

Subjects
Database, Big data, COVID-19, Data sharing, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background The Coronavirus disease 2019 (COVID-19) pandemic has underlined the urgent need for reliable, multicenter, and full-admission intensive care data to advance our understanding of the course of the disease and investigate potential treatment strategies. In this study, we present the Dutch Data Warehouse (DDW), the first multicenter electronic health record (EHR) database with full-admission data from critically ill COVID-19 patients. Methods A nation-wide data sharing collaboration was launched at the beginning of the pandemic in March 2020. All hospitals in the Netherlands were asked to participate and share pseudonymized EHR data from adult critically ill COVID-19 patients. Data included patient demographics, clinical observations, administered medication, laboratory determinations, and data from vital sign monitors and life support devices. Data sharing agreements were signed with participating hospitals before any data transfers took place. Data were extracted from the local EHRs with prespecified queries and combined into a staging dataset through an extract–transform–load (ETL) pipeline. In the consecutive processing pipeline, data were mapped to a common concept vocabulary and enriched with derived concepts. Data validation was a continuous process throughout the project. All participating hospitals have access to the DDW. Within legal and ethical boundaries, data are available to clinicians and researchers. Results Out of the 81 intensive care units in the Netherlands, 66 participated in the collaboration, 47 have signed the data sharing agreement, and 35 have shared their data. Data from 25 hospitals have passed through the ETL and processing pipeline. Currently, 3464 patients are included in the DDW, both from wave 1 and wave 2 in the Netherlands. More than 200 million clinical data points are available. Overall ICU mortality was 24.4%. Respiratory and hemodynamic parameters were most frequently measured throughout a patient's stay. For each patient, all administered medication and their daily fluid balance were available. Missing data are reported for each descriptive. Conclusions In this study, we show that EHR data from critically ill COVID-19 patients may be lawfully collected and can be combined into a data warehouse. These initiatives are indispensable to advance medical data science in the field of intensive care medicine.

Published
2021
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13. One-year outcomes in COVID-19 and non-COVID-19 intensive care unit survivors

Author

AIOS Psychiatrie, Brain, Heesakkers, Hidde, van der Hoeven, Johannes G, Corsten, Stijn, Janssen, Inge, Ewalds, Esther, Simons, Koen S, de Blauw, Maaike, Rettig, Thijs C D, Jacobs, Crétien, van Santen, Susanne, Slooter, Arjen J C, van der Woude, Margaretha C E, Zegers, Marieke, van den Boogaard, Mark, AIOS Psychiatrie, Brain, Heesakkers, Hidde, van der Hoeven, Johannes G, Corsten, Stijn, Janssen, Inge, Ewalds, Esther, Simons, Koen S, de Blauw, Maaike, Rettig, Thijs C D, Jacobs, Crétien, van Santen, Susanne, Slooter, Arjen J C, van der Woude, Margaretha C E, Zegers, Marieke, and van den Boogaard, Mark

Published
2024

14. Changes in quality of life 1 year after intensive care: a multicenter prospective cohort of ICU survivors

Author

AIOS Psychiatrie, Brain, Porter, Lucy L, Simons, Koen S, Corsten, Stijn, Westerhof, Brigitte, Rettig, Thijs C D, Ewalds, Esther, Janssen, Inge, Jacobs, Crétien, van Santen, Susanne, Slooter, Arjen J C, van der Woude, Margaretha C E, van der Hoeven, Johannes G, Zegers, Marieke, van den Boogaard, Mark, AIOS Psychiatrie, Brain, Porter, Lucy L, Simons, Koen S, Corsten, Stijn, Westerhof, Brigitte, Rettig, Thijs C D, Ewalds, Esther, Janssen, Inge, Jacobs, Crétien, van Santen, Susanne, Slooter, Arjen J C, van der Woude, Margaretha C E, van der Hoeven, Johannes G, Zegers, Marieke, and van den Boogaard, Mark

Published
2024

15. Improving access to healthcare for paediatric sickle cell disease patients: a qualitative study on healthcare professionals’ views

Author

Maite E. Houwing, Marit Buddenbaum, Thijs C. J. Verheul, Anne P. J. de Pagter, Jacobus N. J. Philipsen, Jan A. Hazelzet, and Marjon H. Cnossen

Subjects
Sickle cell disease, Access to health care, Accessibility of health services, Qualitative research, Health care professionals, Public aspects of medicine, RA1-1270
Abstract

Abstract Background In well-resourced countries, comprehensive care programs have increased life expectancy of patients with sickle cell disease, with almost all infants surviving into adulthood. However, families affected by sickle cell disease are more likely to be economically disenfranchised because of their racial or ethnic minority status. As every individual child has the right to the highest attainable standard of health under the United Nations Convention on the Rights of the Child, it is essential to identify both barriers and facilitators with regard to the delivery of adequate healthcare. Optimal healthcare accessibility will improve healthcare outcomes for children with sickle cell disease and their families. Healthcare professionals in the field of sickle cell care have first-hand experience of the barriers that patients encounter when it comes to effective care. We therefore hypothesised that these medical professionals have a clear picture of what is necessary to overcome these barriers and which facilitators will be most feasible. Therefore, this study aims to map best practises and lessons learnt in order to attain more optimal healthcare accessibility for paediatric patients with sickle cell disease and their families. Methods Healthcare professionals working with young patients with sickle cell disease were recruited for semi-structured interviews. An interview guide was used to ensure the four healthcare accessibility dimensions were covered. The interviews were transcribed and coded. Based on field notes, initial codes were generated, to collate data (both barriers and solutions) to main themes (such as “transportation”, or “telecommunication”). Through ongoing thematic analysis, definitive themes were formulated and best practices were reported as recommendations. Quotations were selected to highlight or illustrate the themes and link the reported results to the empirical data. Results In 2019, 22 healthcare professionals from five different university hospitals in the Netherlands were interviewed. Participants included (paediatric) haematologists, nurses and allied health professionals. Six themes emerged, all associated with best practices on topics related to the improvement of healthcare accessibility for children with sickle cell disease and their families. Firstly, the full reimbursement of invisible costs made by caregivers. Secondly, clustering of healthcare appointments on the same day to help patients seeing all required specialists without having to visit the hospital frequently. Thirdly, organisation of care according to shared care principles to deliver specialised services as close as possible to the patient’s home without compromising quality. Fourthly, optimising verbal and written communication methods with special consideration for families with language barriers, low literacy skills, or both. Fifthly, improving the use of eHealth services tailored to users’ health literacy skills, including accessible mobile telephone contact between healthcare professionals and caregivers of children with sickle cell disease. Finally, increasing knowledge and interest in sickle cell disease among key stakeholders and the public to ensure that preventive and acute healthcare measures are understood and safeguarded in all settings. Conclusion This qualitative study describes the views of healthcare professionals on overcoming barriers of healthcare accessibility that arise from the intersecting vulnerabilities faced by patients with sickle cell disease and their families. The recommendations gathered in this report provide high-income countries with a practical resource to meet their obligations towards individual children under the United Nations Convention on the Rights of the Child.

Published
2021
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17. Changes in quality of life 1 year after intensive care: a multicenter prospective cohort of ICU survivors.

Author

Porter, Lucy L., Simons, Koen S., Corsten, Stijn, Westerhof, Brigitte, Rettig, Thijs C. D., Ewalds, Esther, Janssen, Inge, Jacobs, Crétien, van Santen, Susanne, Slooter, Arjen J. C., van der Woude, Margaretha C. E., van der Hoeven, Johannes G., Zegers, Marieke, and van den Boogaard, Mark

Abstract

Background: With survival rates of critical illness increasing, quality of life measures are becoming an important outcome of ICU treatment. Therefore, to study the impact of critical illness on quality of life, we explored quality of life before and 1 year after ICU admission in different subgroups of ICU survivors. Methods: Data from an ongoing prospective multicenter cohort study, the MONITOR-IC, were used. Patients admitted to the ICU in one of eleven participating hospitals between July 2016 and June 2021 were included. Outcome was defined as change in quality of life, measured using the EuroQol five-dimensional (EQ-5D-5L) questionnaire, and calculated by subtracting the EQ-5D-5L score 1 day before hospital admission from the EQ-5D-5L score 1 year post-ICU. Based on the minimal clinically important difference, a change in quality of life was defined as a change in EQ-5D-5L score of ≥ 0.08. Subgroups of patients were based on admission diagnosis. Results: A total of 3913 (50.6%) included patients completed both baseline and follow-up questionnaires. 1 year post-ICU, patients admitted after a cerebrovascular accident, intracerebral hemorrhage, or (neuro)trauma, on average experienced a significant decrease in quality of life. Conversely, 11 other subgroups of ICU survivors reported improvements in quality of life. The largest average increase in quality of life was seen in patients admitted due to respiratory disease (mean 0.17, SD 0.38), whereas the largest average decrease was observed in trauma patients (mean -0.13, SD 0.28). However, in each of the studied 22 subgroups there were survivors who reported a significant increase in QoL and survivors who reported a significant decrease in QoL. Conclusions: This large prospective multicenter cohort study demonstrated the diversity in long-term quality of life between, and even within, subgroups of ICU survivors. These findings emphasize the need for personalized information and post-ICU care. Trial registration: The MONITOR-IC study was registered at ClinicalTrials.gov: NCT03246334 on August 2nd 2017. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Prediction of Long-Term Physical, Mental, and Cognitive Problems Following Critical Illness: Development and External Validation of the PROSPECT Prediction Model*

Author

van Sleeuwen, Dries, primary, Zegers, Marieke, additional, Ramjith, Jordache, additional, Cruijsberg, Juliette K., additional, Simons, Koen S., additional, van Bommel, Daniëlle, additional, Burgers-Bonthuis, Dominique, additional, Koeter, Julia, additional, Bisschops, Laurens L. A., additional, Janssen, Inge, additional, Rettig, Thijs C. D., additional, van der Hoeven, Johannes G., additional, van de Laar, Floris A., additional, and van den Boogaard, Mark, additional

Published
2023
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19. Predictors for extubation failure in COVID-19 patients using a machine learning approach

Author

Fleuren, Lucas M., Dam, Tariq A., Tonutti, Michele, de Bruin, Daan P., Lalisang, Robbert C. A., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., Rigter, Sander, Wils, Evert-Jan, Frenzel, Tim, Dongelmans, Dave A., de Jong, Remko, Peters, Marco, Kamps, Marlijn J. A., Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G. C. A., de Ruijter, Wouter, Urlings-Strop, Louise C., Smit, Ellen G. M., Mehagnoul-Schipper, D. Jannet, Dormans, Tom, de Jager, Cornelis P. C., Hendriks, Stefaan H. A., Achterberg, Sefanja, Oostdijk, Evelien, Reidinga, Auke C., Festen-Spanjer, Barbara, Brunnekreef, Gert B., Cornet, Alexander D., van den Tempel, Walter, Boelens, Age D., Koetsier, Peter, Lens, Judith, Faber, Harald J., Karakus, A., Entjes, Robert, de Jong, Paul, Rettig, Thijs C. D., Arbous, Sesmu, Vonk, Sebastiaan J. J., Fornasa, Mattia, Machado, Tomas, Houwert, Taco, Hovenkamp, Hidde, Noorduijn Londono, Roberto, Quintarelli, Davide, Scholtemeijer, Martijn G., de Beer, Aletta A., Cinà, Giovanni, Kantorik, Adam, de Ruijter, Tom, Herter, Willem E., Beudel, Martijn, Girbes, Armand R. J., Hoogendoorn, Mark, Thoral, Patrick J., and Elbers, Paul W. G.

Published
2021
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20. The Dutch Data Warehouse, a multicenter and full-admission electronic health records database for critically ill COVID-19 patients

Author

Fleuren, Lucas M., Dam, Tariq A., Tonutti, Michele, de Bruin, Daan P., Lalisang, Robbert C. A., Gommers, Diederik, Cremer, Olaf L., Bosman, Rob J., Rigter, Sander, Wils, Evert-Jan, Frenzel, Tim, Dongelmans, Dave A., de Jong, Remko, Peters, Marco, Kamps, Marlijn J. A., Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G. C. A., de Ruijter, Wouter, Urlings-Strop, Louise C., Smit, Ellen G. M., Mehagnoul-Schipper, D. Jannet, Dormans, Tom, de Jager, Cornelis P. C., Hendriks, Stefaan H. A., Achterberg, Sefanja, Oostdijk, Evelien, Reidinga, Auke C., Festen-Spanjer, Barbara, Brunnekreef, Gert B., Cornet, Alexander D., van den Tempel, Walter, Boelens, Age D., Koetsier, Peter, Lens, Judith, Faber, Harald J., Karakus, A., Entjes, Robert, de Jong, Paul, Rettig, Thijs C. D., Arbous, Sesmu, Vonk, Sebastiaan J. J., Fornasa, Mattia, Machado, Tomas, Houwert, Taco, Hovenkamp, Hidde, Noorduijn-Londono, Roberto, Quintarelli, Davide, Scholtemeijer, Martijn G., de Beer, Aletta A., Cina, Giovanni, Beudel, Martijn, Herter, Willem E., Girbes, Armand R. J., Hoogendoorn, Mark, Thoral, Patrick J., and Elbers, Paul W. G.

Published
2021
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22. Early high-dose vitamin C in post-cardiac arrest syndrome (VITaCCA): study protocol for a randomized, double-blind, multi-center, placebo-controlled trial

Author

Rozemeijer, Sander, de Grooth, Harm-Jan, Elbers, Paul W. G., Girbes, Armand R. J., den Uil, Corstiaan A., Dubois, Eric A., Wils, Evert-Jan, Rettig, Thijs C. D., van Zanten, Arthur R. H., Vink, Roel, van den Bogaard, Bas, Bosman, Rob J., Oudemans-van Straaten, Heleen M., and de Man, Angélique M. E.

Published
2021
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23. Some Patients Are More Equal Than Others: Variation in Ventilator Settings for Coronavirus Disease 2019 Acute Respiratory Distress Syndrome

Author

Tariq A. Dam, MD, Harm-Jan de Grooth, MD, PhD, Thomas Klausch, PhD, Lucas M. Fleuren, MD, Daan P. de Bruin, MSc, Robert Entjes, MD, Thijs C. D. Rettig, MD, PhD, Dave A. Dongelmans, MD, PhD, Age D. Boelens, MD, Sander Rigter, MD, Stefaan H. A. Hendriks, MD, Remko de Jong, MD, Marlijn J. A Kamps, MD, Marco Peters, MD, A. Karakus, MD, Diederik Gommers, MD, PhD, Dharmanand Ramnarain, MD, Evert-Jan Wils, MD, PhD, Sefanja Achterberg, MD, PhD, Ralph Nowitzky, MD, Walter van den Tempel, MD, Cornelis P. C. de Jager, MD, PhD, Fleur G. C. A. Nooteboom, MD, Evelien Oostdijk, MD, PhD, Peter Koetsier, MD, Alexander D. Cornet, MD, PhD, FRCP, Auke C. Reidinga, MD, Wouter de Ruijter, MD, PhD, Rob J. Bosman, MD, Tim Frenzel, MD, PhD, Louise C. Urlings-Strop, MD, PhD, Paul de Jong, MD, Ellen G. M. Smit, MD, Olaf L. Cremer, MD, PhD, D. Jannet Mehagnoul-Schipper, MD, PhD, Harald J. Faber, MD, Judith Lens, MD, Gert B. Brunnekreef, MD, Barbara Festen-Spanjer, MD, Tom Dormans, MD, PhD, Annemieke Dijkstra, MD, Bram Simons, MD, A. A. Rijkeboer, MD, Sesmu Arbous, MD, PhD, Marcel Aries, MD, PhD, Menno Beukema, MD, Daniël Pretorius, MD, Rutger van Raalte, MD, Martijn van Tellingen, MD, EDIC, Niels C. Gritters van den Oever, MD, Robbert C. A. Lalisang, MD, Michele Tonutti, MRes, Armand R. J. Girbes, MD, PhD, EDIC, Mark Hoogendoorn, PhD, Patrick J. Thoral, MD, EDIC, Paul W. G. Elbers, MD, PhD, EDIC, on behalf of the Dutch ICU Data Sharing Against COVID-19 Collaborators, Remko van den Akker, Tom A. Rijpstra, M. C. Reuland, Klaas Sierk Arnold, Arend Jan Meinders, Nicolas Schroten, Laura van Manen, Leon Montenij, Julia Koeter, J. W. Fijen, Jasper van Bommel, Roy van den Berg, Martha de Bruin, Roger van Rietschote, Ellen van Geest, Koen S. Simons, Anisa Hana, Joost Labout, Michael Kuiper, Albertus Beishuizen, Bart van de Gaauw, Roos Renckens, B. van den Bogaard, Peter Pickkers, Pim van der Heiden, Dennis Geutjes, Claudia (C. W.) van Gemeren, Emma Rademaker, Frits H. M. van Osch, Johan Lutisan, Jacomar J. M. van Koesveld, Bart P. Grady, Martijn de Kruif, Martin E. Haan, Luca Roggeveen, Dagmar M. Ouweneel, Ronald Driessen, Jan Peppink, G. J. Zijlstra, A. J. van Tienhoven, Evelien van der Heiden, Jan Jaap Spijkstra, Hans van der Spoel, Angelique de Man, Heder J. de Vries, Fuda van Diggelen, Ali el Hassouni, David Romero Guzman, Sandjai Bhulai, Sebastiaan J. J. Vonk, Mattia Fornasa, Tomas Machado, Adam Izdebski, Taco Houwert, Hidde Hovenkamp, Roberto Noorduijn Londono, Davide Quintarelli, Martijn G. Scholtemeijer, Aletta A. de Beer, Giovanni Cinà, Willem E. Herter, Michael de Neree tot Babberich, Olivier Thijssens, Lot Wagemakers, Hilde G. A. van der Pol, Tom Hendriks, Julie Berend, Virginia Ceni Silva, Robert F. J. Kullberg, Leo Heunks, Nicole Juffermans, Arjen J. C. Slooter, Martijn Beudel, and Nicolet F. de Keizer

Subjects
Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

OBJECTIVES:. As coronavirus disease 2019 is a novel disease, treatment strategies continue to be debated. This provides the intensive care community with a unique opportunity as the population of coronavirus disease 2019 patients requiring invasive mechanical ventilation is relatively homogeneous compared with other ICU populations. We hypothesize that the novelty of coronavirus disease 2019 and the uncertainty over its similarity with noncoronavirus disease 2019 acute respiratory distress syndrome resulted in substantial practice variation between hospitals during the first and second waves of coronavirus disease 2019 patients. DESIGN:. Multicenter retrospective cohort study. SETTING:. Twenty-five hospitals in the Netherlands from February 2020 to July 2020, and 14 hospitals from August 2020 to December 2020. PATIENTS:. One thousand two hundred ninety-four critically ill intubated adult ICU patients with coronavirus disease 2019 were selected from the Dutch Data Warehouse. Patients intubated for less than 24 hours, transferred patients, and patients still admitted at the time of data extraction were excluded. MEASUREMENTS AND MAIN RESULTS:. We aimed to estimate between-ICU practice variation in selected ventilation parameters (positive end-expiratory pressure, Fio2, set respiratory rate, tidal volume, minute volume, and percentage of time spent in a prone position) on days 1, 2, 3, and 7 of intubation, adjusted for patient characteristics as well as severity of illness based on Pao2/Fio2 ratio, pH, ventilatory ratio, and dynamic respiratory system compliance during controlled ventilation. Using multilevel linear mixed-effects modeling, we found significant (p ≤ 0.001) variation between ICUs in all ventilation parameters on days 1, 2, 3, and 7 of intubation for both waves. CONCLUSIONS:. This is the first study to clearly demonstrate significant practice variation between ICUs related to mechanical ventilation parameters that are under direct control by intensivists. Their effect on clinical outcomes for both coronavirus disease 2019 and other critically ill mechanically ventilated patients could have widespread implications for the practice of intensive care medicine and should be investigated further by causal inference models and clinical trials.

Published
2021
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24. Some Patients Are More Equal Than Others: Variation in Ventilator Settings for Coronavirus Disease 2019 Acute Respiratory Distress Syndrome

Author

Dam, Tariq A., de Grooth, Harm-Jan, Klausch, Thomas, Fleuren, Lucas M., de Bruin, Daan P., Entjes, Robert, Rettig, Thijs C. D., Dongelmans, Dave A., Boelens, Age D., Rigter, Sander, Hendriks, Stefaan H. A., de Jong, Remko, Kamps, Marlijn J. A, Peters, Marco, Karakus, A., Gommers, Diederik, Ramnarain, Dharmanand, Wils, Evert-Jan, Achterberg, Sefanja, Nowitzky, Ralph, van den Tempel, Walter, de Jager, Cornelis P. C., Nooteboom, Fleur G. C. A., Oostdijk, Evelien, Koetsier, Peter, Cornet, Alexander D., Reidinga, Auke C., de Ruijter, Wouter, Bosman, Rob J., Frenzel, Tim, Urlings-Strop, Louise C., de Jong, Paul, Smit, Ellen G. M., Cremer, Olaf L., Mehagnoul-Schipper, D. Jannet, Faber, Harald J., Lens, Judith, Brunnekreef, Gert B., Festen-Spanjer, Barbara, Dormans, Tom, Dijkstra, Annemieke, Simons, Bram, Rijkeboer, A. A., Arbous, Sesmu, Aries, Marcel, Beukema, Menno, Pretorius, Daniël, van Raalte, Rutger, van Tellingen, Martijn, Gritters van den Oever, Niels C., Lalisang, Robbert C. A., Tonutti, Michele, Girbes, Armand R. J., Hoogendoorn, Mark, Thoral, Patrick J., and Elbers, Paul W. G.

Published
2021
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25. A novel method to standardise serum IgA measurements shows an increased prevalence of IgA deficiency in young children with recurrent respiratory tract infections

Author

Mischa H Koenen, Madeleen Bosma, Udo A Roorda, Fabiënne MY Wopereis, Anja Roos, Erhard vander Vries, Debby Bogaert, Elisabeth AM Sanders, Marianne Boes, Jojanneke Heidema, Joris M vanMontfrans, Walter AF Balemans, Thijs C vanHolten, and Lilly M Verhagen

Subjects
case–control study, IgA deficiency, immunoglobulin A, reference values, respiratory tract infections, Immunologic diseases. Allergy, RC581-607
Abstract

Abstract Objectives While physicians are often confronted with immunoglobulin A (IgA) deficiency in children with recurrent infections, the clinical relevance of this finding is unclear. Large‐scale studies examining the significance of IgA deficiency in children are hampered by differences in techniques for measuring IgA and the physiological increase of IgA with age. Both result in a variety of reference values used for diagnosing IgA deficiency. We propose a new laboratory‐independent method to accurately compare IgA measurements in children of varying ages. Methods We present a method to standardise IgA values for age and laboratory differences. We applied this method to a multicentre case–control study of children under the age of seven suffering from recurrent respiratory tract infections (rRTI, cases) and children who had IgA measured as part of coeliac disease screening (controls). We defined IgA deficiency as serum IgA measurements

Published
2021
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27. The Why of YY1: Mechanisms of Transcriptional Regulation by Yin Yang 1

Author

Thijs C. J. Verheul, Levi van Hijfte, Elena Perenthaler, and Tahsin Stefan Barakat

Subjects
YY1, neurodevelopment, gene regulation, non-coding genome, enhancer, non-coding regulatory element, Biology (General), QH301-705.5
Abstract

First described in 1991, Yin Yang 1 (YY1) is a transcription factor that is ubiquitously expressed throughout mammalian cells. It regulates both transcriptional activation and repression, in a seemingly context-dependent manner. YY1 has a well-established role in the development of the central nervous system, where it is involved in neurogenesis and maintenance of homeostasis in the developing brain. In neurodevelopmental and neurodegenerative disease, the crucial role of YY1 in cellular processes in the central nervous system is further underscored. In this mini-review, we discuss the various mechanisms leading to the transcriptional activating and repressing roles of YY1, including its role as a traditional transcription factor, its interactions with cofactors and chromatin modifiers, the role of YY1 in the non-coding genome and 3D chromatin organization and the possible implications of the phase-separation mechanism on YY1 function. We provide examples on how these processes can be involved in normal development and how alterations can lead to various diseases.

Published
2020
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29. Prediction of Long-Term Physical, Mental, and Cognitive Problems Following Critical Illness: Development and External Validation of the PROSPECT Prediction Model.

Author

van Sleeuwen, Dries, Zegers, Marieke, Ramjith, Jordache, Cruijsberg, Juliette K., Simons, Koen S., van Bommel, Daniëlle, Burgers-Bonthuis, Dominique, Koeter, Julia, Bisschops, Laurens L. A., Janssen, Inge, Rettig, Thijs C. D., van der Hoeven, Johannes G., van de Laar, Floris A., and van den Boogaard, Mark

Published
2024
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31. The effect of P2Y12 inhibition on platelet activation assessed with aggregation- and flow cytometry-based assays

Author

Tesse C. Leunissen, Peter Paul Wisman, Thijs C. van Holten, Philip G. de Groot, Suzanne J. Korporaal, Arnold C. Koekman, Frans L. Moll, Martin Teraa, Marianne C. Verhaar, Gert Jan de Borst, Rolf T. Urbanus, and Mark Roest

Subjects
platelet aggregation, platelet aggregation inhibitor, platelet function test, platelet membrane glycoprotein iib, p-selectin, Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Patients on P2Y12 inhibitors may still develop thrombosis or bleeding complications. Tailored antiplatelet therapy, based on platelet reactivity testing, might reduce these complications. Several tests have been used, but failed to show a benefit of tailored antiplatelet therapy. This could be due to the narrowness of current platelet reactivity tests, which are limited to analysis of platelet aggregation after stimulation of the adenosine diphosphate (ADP)-pathway. However, the response to ADP does not necessarily reflect the effect of P2Y12 inhibition on platelet function in vivo. Therefore, we investigated whether measuring platelet reactivity toward other physiologically relevant agonists could provide more insight in the efficacy of P2Y12 inhibitors. The effect of in vitro and in vivo P2Y12 inhibition on αIIbβ3-activation, P-selectin and CD63-expression, aggregate formation, release of alpha, and dense granules content was assessed after stimulation of different platelet activation pathways. Platelet reactivity measured with flow cytometry in 72 patients on P2Y12 inhibitors was compared to VerifyNow results. P2Y12 inhibitors caused strongly attenuated platelet fibrinogen binding after stimulation with peptide agonists for protease activated receptor (PAR)-1 and -4, or glycoprotein VI ligand crosslinked collagen-related peptide (CRP-xl), while aggregation was normal at high agonist concentration. P2Y12 inhibitors decreased PAR-agonist and CRP-induced dense granule secretion, but not alpha granule secretion. A proportion of P2Y12-inhibitor responsive patients according to VerifyNow, displayed normal fibrinogen binding assessed with flow cytometry after stimulation with PAR-agonists or CRP despite full inhibition of the response to ADP, indicating suboptimal platelet inhibition. Concluding, measurement of platelet fibrinogen binding with flow cytometry after stimulation of thrombin- or collagen receptors in addition to ADP response identifies different patients as nonresponders to P2Y12 inhibitors, compared to only ADP-induced aggregation-based assays. Future studies should investigate the value of both assays for monitoring on-treatment platelet reactivity.

Published
2017
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33. Human milk oligosaccharides, antimicrobial drugs, and the gut microbiota of term neonates : observations from the KOALA birth cohort study

Author

Barnett, D.J.M., Endika, M.F., Klostermann, C.E., Gu, F., Thijs, C., Nauta, A., Schols, H.A., Smidt, H., Arts, I.C.W., Penders, J., Barnett, D.J.M., Endika, M.F., Klostermann, C.E., Gu, F., Thijs, C., Nauta, A., Schols, H.A., Smidt, H., Arts, I.C.W., and Penders, J.

Abstract

The infant gut microbiota affects childhood health. This pioneer microbiota may be vulnerable to antibiotic exposures, but could be supported by prebiotic oligosaccharides found in breast milk and some infant formulas. We sought to characterize the effects of several exposures on the neonatal gut microbiota, including human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), and infant/maternal antimicrobial exposures. We profiled the stool microbiota of 1023 one-month-old infants from the KOALA Birth Cohort using 16S rRNA gene amplicon sequencing. We quantified 15 HMOs in breast milk from the mothers of 220 infants, using high-performance liquid chromatography-mass spectrometry. Both breastfeeding and antibiotic exposure decreased gut microbial diversity, but each was associated with contrasting shifts in microbiota composition. Other factors associated with microbiota composition included C-section, homebirth, siblings, and exposure to animals. Neither infant exposure to oral antifungals nor maternal exposure to antibiotics during pregnancy were associated with infant microbiota composition. Four distinct groups of breast milk HMO compositions were evident, corresponding to maternal Secretor status and Lewis group combinations defined by the presence/absence of certain fucosylated HMOs. However, we found the strongest evidence for microbiota associations between two non-fucosylated HMOs: 6'-sialyllactose (6'-SL) and lacto-N-hexaose (LNH), which were associated with lower and higher relative abundances of Bifidobacterium, respectively. Among 111 exclusively formula-fed infants, the GOS-supplemented formula was associated with a lower relative abundance of Clostridium perfringens. In conclusion, the gut microbiota is sensitive to some prebiotic and antibiotic exposures during early infancy and understanding their effects could inform future strategies for safeguarding a health-promoting infant gut microbiota.

Published
2023

34. First-in-Human Robot-Assisted Subretinal Drug Delivery Under Local Anesthesia

Author

Robert E MacLaren, Maarten Beelen, Thijs C. M. Meenink, Thomas L Edwards, Kanmin Xue, Gerrit Naus, Jasmina Cehajic-Kapetanovic, and Marc D. de Smet

Subjects
medicine.medical_specialty, Visual acuity, business.industry, medicine.medical_treatment, Retinal Hemorrhage, Microtrauma, Vitrectomy, Robotics, Macular degeneration, medicine.disease, Cannula, Surgery, Clinical trial, Ophthalmology, Fibrinolytic Agents, Pharmaceutical Preparations, Tolerability, Tissue Plasminogen Activator, Inclusion and exclusion criteria, medicine, Humans, medicine.symptom, business, Anesthesia, Local
Abstract

Purpose To report the results of a first-in-human study using a robotic device to assist subretinal drug delivery in patients undergoing vitreoretinal surgery for macular haemorrhage. Design Double armed, randomized controlled surgical trial (ClinicalTrials.gov identifier: NCT03052881). Methods Setting Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom. Participants In total, 12 participants were recruited: 6 in the robot-assisted and 6 in the control manual surgery arm according to the pre-specified inclusion and exclusion criteria. All subjects presented with acute loss of vision due to a sub-foveal haemorrhage secondary to neovascular age-related macular degeneration. Intervention After standard vitrectomy, intraoperative OCT-guided subretinal injection of tissue plasminogen activator (TPA) was performed either by robot-assisted or conventional manual technique under local anaesthesia. The robotic part of the procedure involved advancement of a cannula through the retina and stabilizing it during foot-controlled injection of up to 100µl of TPA solution. Main Outcome Measures We assessed surgical success, duration of surgery, adverse events, and tolerability of surgery under local anaesthesia. Results The procedure was well tolerated by all participants and safely performed in all cases. Total duration of surgery, time taken to complete the injection and retinal microtrauma were similar between the groups and not clinically significant. Subretinal haemorrhage was successfully displaced at 1-month post-intervention, except for one control subject, and the median gain in visual acuity was similar in both arms. Conclusions This first-in-human study demonstrates the feasibility and safety of high precision robot-assisted subretinal drug delivery as part of the surgical management of sub-macular haemorrhage, simulating its potential future application in gene or cell therapy.

Published
2022

35. Development and External Validation of a Prediction Model for Quality of Life of ICU Survivors: A Subanalysis of the MONITOR-IC Prospective Cohort Study

Author

Porter, Lucy L., primary, Simons, Koen S., additional, Ramjith, Jordache, additional, Corsten, Stijn, additional, Westerhof, Brigitte, additional, Rettig, Thijs C. D., additional, Ewalds, Esther, additional, Janssen, Inge, additional, van der Hoeven, Johannes G., additional, van den Boogaard, Mark, additional, and Zegers, Marieke, additional

Published
2023
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36. Prediction model for appropriate routine ICU admission after pulmonary resection: multicentre study

Author

Detillon, Deniece D E M A, primary, Noordzij, Peter G, additional, Kortekaas, Bettina, additional, Kortekaas, Robert T J, additional, Hofman, Erik F N, additional, Kant, Merijn, additional, Rijpstra, Tom A, additional, Boonman-de Winter, Leandra J M, additional, Wils, Evert-Jan, additional, van Eijck, Casper H J, additional, Veen, Eelco J, additional, and Rettig, Thijs C D, additional

Published
2023
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38. Rapid Evaluation of Coronavirus Illness Severity (RECOILS) in intensive care

Author

Tim Frenzel, Nicolas Bennett, Tariq A Dam, Johan Mårtensson, Drago Plecko, Tom Dormans, Olaf L. Cremer, Gert B. Brunnekreef, Marco Peters, Judith Lens, Paul W. G. Elbers, Fleur G C A Nooteboom, Attila Karakus, Dharmanand Ramnarain, Sefanja Achterberg, Alexander D. Cornet, Evert-Jan Wils, Peter Koetsier, Patrick Thoral, Louise C Urlings-Strop, Robbert C. A. Lalisang, Paul de Jong, Barbara Festen-Spanjer, Stefaan H A Hendriks, Wouter de Ruijter, Daan P de Bruin, Thijs C D Rettig, Sebastiaan J J Vonk, Sander Rigter, Auke C Reidinga, Lucas M. Fleuren, Age D Boelens, Remko de Jong, Ellen G M Smit, Dave A Dongelmans, Cornelis P.C. de Jager, Harald J. Faber, Ralph Nowitzky, Walter van den Tempel, Rinaldo Bellomo, Rob J. Bosman, Martin E Haan, D Jannet Mehagnoul-Schipper, Marlijn J A Kamps, Evelien A. N. Oostdijk, Robert Entjes, Diederik Gommers, Intensive Care Medicine, AII - Infectious diseases, APH - Quality of Care, Intensive care medicine, VU University medical center, ACS - Microcirculation, ACS - Diabetes & metabolism, and Intensive Care

Subjects
Adult, Male, medicine.medical_specialty, Critical Care, medicine.medical_treatment, mechanical ventilation, COVID‐19, Intensive care, Internal medicine, medicine, Illness severity, Humans, Multicenter Studies as Topic, Hospital Mortality, corona virus, Blood urea nitrogen, Research Articles, Aged, Retrospective Studies, intensive care, Mechanical ventilation, business.industry, SARS-CoV-2, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Glasgow Coma Scale, Patient Acuity, respiratory failure, COVID-19, General Medicine, Prognosis, Intensive Care Units, Observational Studies as Topic, Anesthesiology and Pain Medicine, Respiratory failure, Cohort, Observational study, business, Research Article
Abstract

Background The prediction of in-hospital mortality for ICU patients with COVID-19 is fundamental to treatment and resource allocation. The main purpose was to develop an easily implemented score for such prediction. Methods This was an observational, multicenter, development, and validation study on a national critical care dataset of COVID-19 patients. A systematic literature review was performed to determine variables possibly important for COVID-19 mortality prediction. Using a logistic multivariable model with a LASSO penalty, we developed the Rapid Evaluation of Coronavirus Illness Severity (RECOILS) score and compared its performance against published scores. Results Our development (validation) cohort consisted of 1480 (937) adult patients from 14 (11) Dutch ICUs admitted between March 2020 and April 2021. Median age was 65 (65) years, 31% (26%) died in hospital, 74% (72%) were males, average length of ICU stay was 7.83 (10.25) days and average length of hospital stay was 15.90 (19.92) days. Age, platelets, PaO2/FiO2 ratio, pH, blood urea nitrogen, temperature, PaCO2, Glasgow Coma Scale (GCS) score measured within +/−24 h of ICU admission were used to develop the score. The AUROC of RECOILS score was 0.75 (CI 0.71–0.78) which was higher than that of any previously reported predictive scores (0.68 [CI 0.64–0.71], 0.61 [CI 0.58–0.66], 0.67 [CI 0.63–0.70], 0.70 [CI 0.67–0.74] for ISARIC 4C Mortality Score, SOFA, SAPS-III, and age, respectively). Conclusions Using a large dataset from multiple Dutch ICUs, we developed a predictive score for mortality of COVID-19 patients admitted to ICU, which outperformed other predictive scores reported so far., Acta Anaesthesiologica Scandinavica, 66 (1), ISSN:0001-5172, ISSN:1399-6576

Published
2022

39. Development and External Validation of a Prediction Model for Quality of Life of ICU Survivors: A Subanalysis of the MONITOR-IC Prospective Cohort Study

Author

Lucy L. Porter, Koen S. Simons, Jordache Ramjith, Stijn Corsten, Brigitte Westerhof, Thijs C. D. Rettig, Esther Ewalds, Inge Janssen, Johannes G. van der Hoeven, Mark van den Boogaard, and Marieke Zegers

Subjects
All institutes and research themes of the Radboud University Medical Center, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Critical Care and Intensive Care Medicine, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
Abstract

Item does not contain fulltext

Published
2023

43. Randomised controlled trial on robot-assisted versus manual surgery for pucker peeling

Author

Koorosh Faridpooya, Saskia H. M. van Romunde, Sonia S. Manning, Jan C. van Meurs, Gerrit J. L. Naus, Maarten J. Beelen, Thijs C. M. Meenink, Jorrit Smit, and Marc D. de Smet

Subjects
Ophthalmology, Treatment Outcome, Vitrectomy, Visual Acuity, Skin Abnormalities, Humans, Epiretinal Membrane, Robotics, Tomography, Optical Coherence, Retrospective Studies
Abstract

The aim was to explore the feasibility and safety of performing common surgical steps in epiretinal membrane (ERM) peeling using the Preceyes Surgical System (PSS).In a tertiary centre, 15 pseudophakic patients with an idiopathic ERM were randomised to robot-assistance or manual surgery in a 2:1 ratio. In the robot-assisted group, the following steps were performed using PSS: (1) staining the internal limiting membrane (ILM), (2) removal of the dye, (3) creating an ILM flap, (4) completing the peeling, (5) holding a light pipe and (6) fluid-air exchange. Primary outcome measures were feasibility and safety. Secondary outcome measures were duration, best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Moreover, the distance travelled by the instrument during peeling was assessed using motion tracking software.All steps performed with PSS were feasible with no clinical adverse events or complications. The surgical time was longer in the robot-assisted group (mean 56 min, SD = 12 vs. 24 min, SD = 5). During the study, the duration of robot-assisted surgeries decreased from 72 to 46 min. The distance travelled by the forceps was shorter in the robot-assisted group (mean 403 mm, SD = 186 vs. 550 mm, SD = 134). BCVA and CRT improved equally in both groups.This is the world's first randomised controlled trial on robotic surgery for ERM. Although more time-consuming, we found that several surgical steps were feasible with assistance of the PSS.

Published
2022

45. Mental health symptoms in family members of COVID-19 ICU survivors 3 and 12 months after ICU admission

Author

Hidde Heesakkers, Johannes G. van der Hoeven, Stijn Corsten, Inge Janssen, Esther Ewalds, Dominique Burgers-Bonthuis, Thijs C. D. Rettig, Crétien Jacobs, Susanne van Santen, Arjen J. C. Slooter, Margaretha C. E. van der Woude, Marieke Zegers, Mark van den Boogaard, Clinical sciences, Neuroprotection & Neuromodulation, MUMC+: MA Medische Staf IC (9), and RS: FHML non-thematic output

Subjects
Adult, Quality of life, OUTCOMES, CRITICALLY-ILL, Depression, SARS-CoV-2, Original, COVID-19, HOSPITAL ANXIETY, Anxiety, Critical Care and Intensive Care Medicine, EXPERIENCES, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Cohort Studies, Stress Disorders, Post-Traumatic, Intensive Care Units, Critical care, Mental Health, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Family members, Humans, Family, Prospective Studies, Survivors, CAREGIVERS
Abstract

Purpose Long-term mental outcomes in family members of coronavirus disease 2019 (COVID-19) intensive care unit (ICU) survivors are unknown. Therefore, we assessed the prevalence of mental health symptoms, including associated risk factors, and quality of life (QoL) in family members of COVID-19 ICU survivors 3 and 12 months post-ICU. Methods A prospective multicentre cohort study in ICUs of ten Dutch hospitals, including adult family members of COVID-19 ICU survivors admitted between March 1, and July 1, 2020. Symptom prevalence rates of anxiety, depression (Hospital Anxiety and Depression Scale) and Post-Traumatic Stress Disorder (Impact of Event Scale-6), and QoL (Short Form-12) before ICU admission (baseline), and after 3 and 12 months were measured. Additionally, associations between family and patient characteristics and mental health symptoms were calculated. Results A total of 166 out of 197 (84.3%) included family members completed the 12-month follow-up of whom 46.1% and 38.3% had mental health symptoms 3 and 12 months post-ICU, respectively; both higher compared to baseline (22.4%) (p

Published
2022

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

Author

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

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

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

Published
2020

47. Preoperative anaemia and outcome after elective cardiac surgery: a Dutch national registry analysis

Author

Medische staf Anesthesiologie, Other research (not in main researchprogram), Hazen, Yannick J J M, Noordzij, Peter G, Gerritse, Bastiaan M, Scohy, Thierry V, Houterman, Saskia, Bramer, Sander, Berendsen, Remco R, Bouwman, R Arthur, Eberl, Susanne, Haenen, Johannes S E, Hofland, Jan, Ter Horst, Maarten, Kingma, Marieke F, Van Klarenbosch, Jan, Klok, Toni, De Korte, Marcel P J, Van Der Maaten, Joost M A A, Spanjersberg, Alexander J, Wietsma, Nicobert E, van der Meer, Nardo J M, Rettig, Thijs C D, Cardiothoracic Surgery Registration Committee of the Netherlands Heart Registration, Medische staf Anesthesiologie, Other research (not in main researchprogram), Hazen, Yannick J J M, Noordzij, Peter G, Gerritse, Bastiaan M, Scohy, Thierry V, Houterman, Saskia, Bramer, Sander, Berendsen, Remco R, Bouwman, R Arthur, Eberl, Susanne, Haenen, Johannes S E, Hofland, Jan, Ter Horst, Maarten, Kingma, Marieke F, Van Klarenbosch, Jan, Klok, Toni, De Korte, Marcel P J, Van Der Maaten, Joost M A A, Spanjersberg, Alexander J, Wietsma, Nicobert E, van der Meer, Nardo J M, Rettig, Thijs C D, and Cardiothoracic Surgery Registration Committee of the Netherlands Heart Registration

Published
2022

48. Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children

Author

van Meel, E.R., Mensink-Bout, S.M., den Dekker, H.T., Ahluwalia, T.S., Annesi-Maesano, I., Arshad, S.H., Baïz, N., Barros, H., von Berg, A., Bisgaard, H., Bønnelykke, K., Carlsson, C.J., Casas, M., Chatzi, L., Chevrier, C., Dalmeijer, G., Dezateux, C., Duchen, K., Eggesbø, M., van der Ent, C., Fantini, M., Flexeder, C., Frey, U., Forastiere, F., Gehring, U., Gori, D., Granell, R., Griffiths, L.J., Inskip, H., Jerzynska, J., Karvonen, A.M., Keil, T., Kelleher, C., Kogevinas, M., Koppen, G., Kuehni, C.E., Lambrechts, N., Lau, S., Lehmann, Irina, Ludvigsson, J., Magnus, M.C., Mélen, E., Mehegan, J., Mommers, M., Nybo Andersen, A.-M., Nystad, W., Pedersen, E.S.L., Pekkanen, J., Peltola, V., Pike, K.C., Pinot de Moira, A., Pizzi, C., Polanska, K., Popovic, M., Porta, D., Roberts, G., Santos, A.C., Schultz, E.S., Standl, M., Sunyer, J., Thijs, C., Toivonen, L., Uphoff, E., Usemann, J., Vafeidi, M., Wright, J., de Jongste, J.C., Jaddoe, V.W.V., Duijts, L., van Meel, E.R., Mensink-Bout, S.M., den Dekker, H.T., Ahluwalia, T.S., Annesi-Maesano, I., Arshad, S.H., Baïz, N., Barros, H., von Berg, A., Bisgaard, H., Bønnelykke, K., Carlsson, C.J., Casas, M., Chatzi, L., Chevrier, C., Dalmeijer, G., Dezateux, C., Duchen, K., Eggesbø, M., van der Ent, C., Fantini, M., Flexeder, C., Frey, U., Forastiere, F., Gehring, U., Gori, D., Granell, R., Griffiths, L.J., Inskip, H., Jerzynska, J., Karvonen, A.M., Keil, T., Kelleher, C., Kogevinas, M., Koppen, G., Kuehni, C.E., Lambrechts, N., Lau, S., Lehmann, Irina, Ludvigsson, J., Magnus, M.C., Mélen, E., Mehegan, J., Mommers, M., Nybo Andersen, A.-M., Nystad, W., Pedersen, E.S.L., Pekkanen, J., Peltola, V., Pike, K.C., Pinot de Moira, A., Pizzi, C., Polanska, K., Popovic, M., Porta, D., Roberts, G., Santos, A.C., Schultz, E.S., Standl, M., Sunyer, J., Thijs, C., Toivonen, L., Uphoff, E., Usemann, J., Vafeidi, M., Wright, J., de Jongste, J.C., Jaddoe, V.W.V., and Duijts, L.

Abstract

Background Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age.Methods We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4–15) years.Results Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: −0.09 (95% CI −0.14– −0.04) to −0.30 (95% CI −0.36– −0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98–2.22) to 6.30 (95% CI 5.64–7.04) and 1.25 (95% CI 1.18–1.32) to 1.55 (95% CI 1.47–1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma.Conclusions Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Published
2022

49. Incidence, Risk Factors and Outcome of Suspected Central Venous Catheter-related Infections in Critically Ill COVID-19 Patients: A Multicenter Retrospective Cohort Study

Author

Medische Staf Intensive Care, Infection & Immunity, MMB Medische Staf, Exterkate, Lotte, van Tienhoven, Arne J, Haaksma, Mark E, Heldeweg, Micah L A, Fleuren, Lucas, Thoral, Patrick, Dam, Tariq A, Heunks, Leo M A, Gommers, Diederik, Cremer, Olaf L, Bosman, Rob J, Rigter, Sander, Wils, Evert-Jan, Frenzel, Tim, Vlaar, Alexander P, Dongelmans, Dave A, de Jong, Remko, Peters, Marco, Kamps, Marlijn J A, Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G C A, de Ruijter, Wouter, Urlings-Strop, Louise C, Smit, Ellen G M, Mehagnoul-Schipper, D Jannet, Dormans, Tom, de Jager, Cornelis P C, Hendriks, Stefaan H A, Achterberg, Sefanja, Oostdijk, Evelien, Reidinga, Auke C, Festen-Spanjer, Barbara, Brunnekreef, Gert B, Cornet, Alexander D, van den Tempel, Walter, Boelens, Age D, Koetsier, Peter, Lens, Judith, Faber, Harald J, Karakus, A, Entjes, Robert, de Jong, Paul, Rettig, Thijs C D, Arbous, Sesmu, Vonk, Bas, Machado, Tomas, Girbes, Armand R J, Sieswerda, Elske, Elbers, Paul W G, Tuinman, Pieter R, Medische Staf Intensive Care, Infection & Immunity, MMB Medische Staf, Exterkate, Lotte, van Tienhoven, Arne J, Haaksma, Mark E, Heldeweg, Micah L A, Fleuren, Lucas, Thoral, Patrick, Dam, Tariq A, Heunks, Leo M A, Gommers, Diederik, Cremer, Olaf L, Bosman, Rob J, Rigter, Sander, Wils, Evert-Jan, Frenzel, Tim, Vlaar, Alexander P, Dongelmans, Dave A, de Jong, Remko, Peters, Marco, Kamps, Marlijn J A, Ramnarain, Dharmanand, Nowitzky, Ralph, Nooteboom, Fleur G C A, de Ruijter, Wouter, Urlings-Strop, Louise C, Smit, Ellen G M, Mehagnoul-Schipper, D Jannet, Dormans, Tom, de Jager, Cornelis P C, Hendriks, Stefaan H A, Achterberg, Sefanja, Oostdijk, Evelien, Reidinga, Auke C, Festen-Spanjer, Barbara, Brunnekreef, Gert B, Cornet, Alexander D, van den Tempel, Walter, Boelens, Age D, Koetsier, Peter, Lens, Judith, Faber, Harald J, Karakus, A, Entjes, Robert, de Jong, Paul, Rettig, Thijs C D, Arbous, Sesmu, Vonk, Bas, Machado, Tomas, Girbes, Armand R J, Sieswerda, Elske, Elbers, Paul W G, and Tuinman, Pieter R

Published
2022

50. Postoperative anaemia and disability-free survival in older cardiac surgery patients

Author

Sepsis and Inflammation, Onderzoek, MS Geriatrie, Circulatory Health, Medische Staf Intensive Care, Infection & Immunity, Smoor, Rosa M, Rettig, Thijs C D, Vernooij, Lisette M, Huijsmans, Roel L N, Verwijmeren, Lisa, Emmelot-Vonk, Marielle H, van Dongen, Eric P A, Cremer, Olaf L, Noordzij, Peter G, Sepsis and Inflammation, Onderzoek, MS Geriatrie, Circulatory Health, Medische Staf Intensive Care, Infection & Immunity, Smoor, Rosa M, Rettig, Thijs C D, Vernooij, Lisette M, Huijsmans, Roel L N, Verwijmeren, Lisa, Emmelot-Vonk, Marielle H, van Dongen, Eric P A, Cremer, Olaf L, and Noordzij, Peter G

Published
2022

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