214 results on '"Toelen J"'
Search Results
2. Minimal modulation of the host immune response to SIS matrix implants by mesenchymal stem cells from the amniotic fluid
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Lesage, F., Pranpanus, S., Bosisio, F. M., Jacobs, M., Ospitalieri, S., Toelen, J., and Deprest, J.
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- 2017
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3. Moderate and severe hyperoxia in preterm rabbits: airway reactivity, forced expiration and forced oscillation outcomes
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Regin, Y, primary, Gie, A, additional, Valenzuela, I, additional, Greyling, M, additional, Lenders, V, additional, Vanoirbeek, J, additional, and Toelen, J, additional
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- 2022
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4. The addition of idarucizumab to plasma samples containing dabigatran allows the use of routine coagulation assays for the diagnosis of hemostasis disorders
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JACQUEMIN, M., TOELEN, J., SCHOETERS, J., VAN HORENBEECK, I., VANLINTHOUT, I., DEBASSE, M., PEETERMANS, M., VANASSCHE, T., PEERLINCK, K., VAN RYN, J., and VERHAMME, P.
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- 2015
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5. The phalangeal microgeodic syndrome in childhood: awareness leads to diagnosis
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Van Ackere, T., Eykens, A., Wouters, C., and Toelen, J.
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- 2013
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6. Evaluation of the specificity and sensitivity of ferritin as an MRI reporter gene in the mouse brain using lentiviral and adeno-associated viral vectors
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Vande Velde, G, Rangarajan, J R, Toelen, J, Dresselaers, T, Ibrahimi, A, Krylychkina, O, Vreys, R, Van der Linden, A, Maes, F, Debyser, Z, Himmelreich, U, and Baekelandt, V
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- 2011
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7. Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9
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Van der Perren, A, Toelen, J, Carlon, M, Van den Haute, C, Coun, F, Heeman, B, Reumers, V, Vandenberghe, L H, Wilson, J M, Debyser, Z, and Baekelandt, V
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- 2011
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8. Practical and cost-effective measurement of B-domain deleted and full-length recombinant FVIII in the routine haemostasis laboratory
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Cauchie, M., Toelen, J., Peerlinck, K., and Jacquemin, M.
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- 2013
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9. Reactie
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Toelen, J.
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- 2013
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10. The adsorption of dabigatran is as efficient as addition of idarucizumab to neutralize the drug in routine coagulation assays
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Jacquemin, M., primary, Toelen, J., additional, Feyen, L., additional, Schoeters, J., additional, Van Horenbeeck, I., additional, Vanlinthout, I., additional, Debasse, M., additional, Vanassche, T., additional, Peerlinck, K., additional, and Verhamme, P., additional
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- 2018
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11. Extrauterine fetale Inkubation durch künstliche Perfusion der Plazenta: ein neues Modell zur Erforschung der Plazentafunktion im 2. Trimenon
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Engels, A, additional, Nöe, G, additional, Toelen, J, additional, and Deprest, J, additional
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- 2017
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12. The fetal patient – ethical aspects of fetal therapy
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Jan Deprest, Toelen J, Debyser Z, Rodrigues C, Devlieger R, De Catte L, Lewi L, Van Mieghem T, Naulaers G, Vandevelde M, Claus F, and Dierickx K
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Fetal therapy ,fetal surgery ,Viewpoint ,prenatal diagnosis ,informed consent ,termination of pregnancy ,fetoscopy ,trial - Abstract
The pregnant patient is a vulnerable subject, and even more so when a serious fetal condition is diagnosed. (Invasive) fetal therapy should only be offered when there is a good chance that the life of the fetus will be saved, or irreversible damage by the disease or disability is prevented. Following diagnosis of a potentially treatable condition, the patient needs to be referred to a center with sufficient expertise in diagnosis and all therapeutic options. Preferences of the physician towards one or another antenatal intervention is not at stake prior to that moment. When fetal therapy is justified--, it should be offered with full respect for maternal choice and individual assessment and perception of potential-- risks, and should be at the location where there is sufficient expertise. For therapies of unproven benefit, the absence of evidence must be disclosed, and therapy should only be undertaken with full voluntary consent of the mother. These ought to be undertaken within well designed and approved trials and only by experts in the treatment modality. Potential risks and eventual morbidities in case of therapeutic failure should be part of the counselling, neither-- should fetal therapy be presented as an alternative to termination of pregnancy.
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- 2011
13. Lung size and liver herniation predict need for extracorporeal membrane oxygenation but not pulmonary hypertension in isolated congenital diaphragmatic hernia: systematic review and meta-analysis
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Russo, F. M., primary, Eastwood, M. P., additional, Keijzer, R., additional, Al-Maary, J., additional, Toelen, J., additional, Van Mieghem, T., additional, and Deprest, J. A., additional
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- 2017
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14. The amplitude of coagulation curves from thrombin time tests allows dysfibrinogenemia caused by the common mutation FGG-Arg301 to be distinguished from hypofibrinogenemia
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Jacquemin, M., primary, Vanlinthout, I., additional, Van Horenbeeck, I., additional, Debasse, M., additional, Toelen, J., additional, Schoeters, J., additional, Lavend'homme, R., additional, Freson, K., additional, and Peerlinck, K., additional
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- 2017
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15. Measurement of B-domain-deleted ReFacto AF activity with a product-specific standard is affected by choice of reagent and patient-specific factors
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Jacquemin, M., primary, Vodolazkaia, A., additional, Toelen, J., additional, Schoeters, J., additional, Van Horenbeeck, I., additional, Vanlinthout, I., additional, Debasse, M., additional, and Peerlinck, K., additional
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- 2017
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16. Whole transcriptome sequencing (RNA-Seq) der Lunge nach fetaler Trachealokklusion im Kaninchen-Model für angeborene Zwerchfellhernien
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Engels, A, primary, Brady, P, additional, Kammoun, M, additional, Ferreiro, J, additional, Dekoninck, P, additional, Endo, M, additional, Toelen, J, additional, Vermeesch, J, additional, and Deprest, J, additional
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- 2015
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17. The adsorption of dabigatran is as efficient as addition of idarucizumab to neutralize the drug in routine coagulation assays.
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Feyen, L., Jacquemin, M., Vanassche, T., Peerlinck, K., Verhamme, P., Toelen, J., Schoeters, J., Van Horenbeeck, I., Vanlinthout, I., and Debasse, M.
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DIAGNOSIS of blood diseases ,THERAPEUTIC use of monoclonal antibodies ,ADSORPTION (Chemistry) ,BENZIMIDAZOLES ,PYRIDINE - Abstract
Abstract: Introduction: The direct thrombin inhibitor dabigatran interferes with thrombophilia screening and with the diagnosis of hemostasis disorders that develop during treatment with the anticoagulant. In vitro addition of idarucizumab, a humanized antibody fragment that binds dabigatran, to plasma samples containing dabigatran fully neutralizes the drug. This study was carried out to determine whether binding of dabigatran on selected insoluble commercial adsorbent material, DOAC‐STOP
R , was as efficient as idarucizumab to neutralize the anticoagulant activity of the drug in vitro. Methods: Coagulation assays sensitive to dabigatran were carried out with patient and control plasma samples spiked with dabigatran and supplemented with idarucizumab or incubated with adsorbent material. Results: In samples containing upto 10 000 ng/mL dabigatran, the adsorption procedure was at least as efficient as the addition of idarucizumab to neutralize the activity of the anticoagulant drug. Neither the adsorption procedure nor the addition of idarucizumab did impair routine coagulation assays carried out with plasma devoid of dabigatran, such as the activated partial thromboplastin time, prothrombin time, fibrinogen Clauss, and the thrombophilia screening assays used to detect antiphospholipid antibodies or activated protein C resistance. In addition, the adsorption procedure did not interfere with the detection of lupus anticoagulant samples. Conclusions: Adsorption of dabigatran in plasma samples containing the drug neutralizes its activity as efficiently as the addition of idarucizumab. This method allows the evaluation of thrombophilia markers without interruption of anticoagulation therapy or the detection of hemostasis disorders in patients treated with the drug. [ABSTRACT FROM AUTHOR]- Published
- 2018
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18. Measurement of B‐domain‐deleted ReFacto AF activity with a product‐specific standard is affected by choice of reagent and patient‐specific factors.
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Jacquemin, M., Vodolazkaia, A., Toelen, J., Schoeters, J., Van Horenbeeck, I., Vanlinthout, I., Debasse, M., and Peerlinck, K.
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HEMOSTASIS ,BLOOD coagulation factors ,CHROMOGENIC compounds ,BLOOD coagulants ,VON Willebrand factor - Abstract
Introduction: Postinfusion ReFacto AF levels can be difficult to measure accurately due to discrepancies between one‐stage and chromogenic FVIII assays. To overcome this, the use of the ReFacto AF laboratory standard (RAFLS) is recommended, but there are discordant reports regarding its usefulness. Aim: We investigated whether calibration with RAFLS and measurement of ReFacto AF levels are influenced by the choice of reagents and patient‐specific factors in one‐stage FVIII assays. Methods: Calibration curves were generated with both the RAFLS and a plasma standard using different F8DPs and one‐stage FVIII assay reagents. This selection of reagents was then used to determine FVIII levels in the plasma of patients repeatedly treated with ReFacto AF. Results were compared with those obtained with a chromogenic assay. Results: F8DP devoid of von Willebrand factor (VWF) falsely increased the values of RAFLS pro‐coagulant activity generated using the APTT reagent. The resulting RAFLS calibration curve underestimated ReFacto AF levels to be half of their true concentration. The use of RAFLS with F8DP containing VWF reduced the discrepancy observed between the one‐stage and chromogenic FVIII assays. However, the mean difference between the two assays still varied up to 50% depending on the patient. Conclusions: The RAFLS is a suitable calibrator for one‐stage FVIII assays carried out with F8DP containing VWF. However, calibration with the RAFLS does not avoid the effect of patient‐specific variables that contribute to discrepancies between the measurements of ReFacto AF levels with one‐stage and chromogenic FVIII assays. [ABSTRACT FROM AUTHOR]
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- 2018
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19. Alteration of Cardiac Progenitor Cell Potency in GRMD Dogs
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Cassano, M., primary, Berardi, E., additional, Crippa, S., additional, Toelen, J., additional, Barthelemy, I., additional, Micheletti, R., additional, Chuah, M., additional, Vandendriessche, T., additional, Debyser, Z., additional, Blot, S., additional, and Sampaolesi, M., additional
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- 2012
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20. Modulation of Intratumoral Galectin-1 Expression To Improve Efficacy of DC-Mediated Immunotherapy For Malignant Glioma
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Verschuere, T., primary, Toelen, J., additional, Boon, L., additional, Lefranc, F., additional, Kiss, R., additional, Ceuppens, J., additional, Van Gool, S., additional, and De Vleeschouwer, S., additional
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- 2012
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21. Granulomatous inflammation in cartilage-hair hypoplasia: risks and benefits of anti-TNF alpha monoclonal antibodies
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Moshous, D, primary, Meyts, I, additional, Fraitag, S, additional, Janssen, C, additional, Debré, M, additional, Suarez, F, additional, Toelen, J, additional, De Boeck, K, additional, Roskams, T, additional, Deschildre, A, additional, Picard, C, additional, Bodemer, C, additional, Wouters, C, additional, and Fischer, A, additional
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- 2011
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22. Phalangeal microgeodic syndrome, a case series
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Toelen, J, primary, Van Ackere, T, additional, Brijs, S, additional, Brijs, A, additional, Eykens, A, additional, Maroteaux, P, additional, and Wouters, C, additional
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- 2011
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23. Albumin als Zusatz zur Trachealokklusion bei fetalen Ratten mit Nitrofen-induzierter Zwerchfellhernie – eine placebokontrollierte Studie
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Klaritsch, P, primary, Mayer, S, additional, Sbragia, L, additional, Toelen, J, additional, Roubliova, X, additional, Lewi, P, additional, Lang, U, additional, and Deprest, J, additional
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- 2009
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24. OP02.04: Prenatal intervention in fetuses with severe congenital diaphragmatic hernia and congenital cystic adenomatoid malformation
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Klaritsch, P., primary, Sbragia, L., additional, Done, E., additional, Gucciardo, L., additional, Debeer, A., additional, Toelen, J., additional, Cannie, M., additional, van Schoubroeck, D., additional, Jani, J., additional, and Deprest, J., additional
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- 2007
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25. OP02.01: Long term pulmonary gene therapy with a lentiviral vector in a fetal rat model
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Toelen, J., primary, Gijsbers, R., additional, Sbragia, L., additional, Deroose, C., additional, Debyser, Z., additional, and Deprest, J., additional
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- 2007
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26. Activity of recombinant HIV-1 integrase on mini-HIV DNA
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Cherepanov, P., primary, Surratt, D., additional, Toelen, J., additional, Pluymers, W., additional, Griffith, J., additional, De Clercq, E., additional, and Debyser, Z., additional
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- 1999
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27. The phalangeal microgeodic syndrome in childhood: awareness leads to diagnosis.
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Ackere, T., Eykens, A., Wouters, C., and Toelen, J.
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FINGER abnormalities ,JUVENILE diseases ,MAROTEAUX-Lamy syndrome ,SYMPTOMS ,RADIOLOGICAL research ,MAGNETIC resonance imaging ,OSTEOSARCOMA ,PHALANGES - Abstract
Phalangeal microgeodic syndrome is a rare but benign disorder that affects the fingers of children. This condition was originally described by Maroteaux in 1970. We present two patients who consulted a pediatrician with swelling of the digits of one or both hands. Both lacked additional clinical or biochemical signs. Radiological examination showed multiple small osteolytic areas with sclerotic lining and periostal reactions in the phalanges of the affected hands. These cases were treated with a conservative approach and spontaneous resolution occurred within weeks to months. As it is a rare disease, the clinical presentation can be misinterpreted as an infectious, inflammatory, or even malignant condition and prompts clinicians to expand the diagnostic process with radiological or nuclear imaging and even biopsy. In these patients, a timely clinical diagnosis by a physician who is aware of the disease prevented further investigations. [ABSTRACT FROM AUTHOR]
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- 2013
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28. Serum procalcitonin is not an early marker of pulmonary exacerbation in children with cystic fibrosis.
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Louw JJ, Toelen J, Proesmans M, Vermeulen F, Billen J, de Boeck K, Louw, Jacoba Johanna, Toelen, Jaan, Proesmans, Marijke, Vermeulen, François, Billen, Jaak, and de Boeck, Kris
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Unlabelled: Serum procalcitonin (PCT) has been proposed as a marker to identify bacterial infection in children. For optimal management of cystic fibrosis (CF) patients, early recognition of pulmonary exacerbations is necessary, but sensitive biomarkers to do so are lacking. Our study was done to establish baseline values for PCT in children with CF and to compare these to values at onset of a pulmonary exacerbation. Serum PCT values were determined in CF children during an outpatient clinic visit and at onset of treatment with intravenous (IV) antibiotics for a pulmonary exacerbation. Serum PCT was measured using a quantitative immunoassay (BRAHMS Kryptor PCTsensitive, Henningsdorf, Germany). In 92 outpatients (mean age 10.0 years, SD 4.8 years; mean forced expiratory volume in 1 s 91%, SD 18; 9 chronically colonized with Pseudomonas aeruginosa), mean baseline PCT was 0.05 ng/ml (SD 0.07). Mean PCT on admission for IV treatment of pulmonary exacerbation was 0.07 ng/ml (SD 0.06) (n = 22) and not different from the baseline value. PCT values were markedly higher in two CF patients with an acute nonrespiratory infection (central venous catheter-associated bloodstream infection, acute gastroenteritis), demonstrating that they can mount a PCT response.Conclusion: PCT values in CF children are not different from values reported in healthy children. In CF children, PCT values do not rise significantly at the onset of a respiratory exacerbation and thus hold no promise as an early marker to identify a pulmonary exacerbation. [ABSTRACT FROM AUTHOR]- Published
- 2012
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29. Closing schools for SARS-CoV-2: A pragmatic rapid Recommendation
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Alexandra Seghers, Tinne Lernout, Elke Wollants, Lode Sweldens, Lise Rans, Jaan Toelen, Nore Milissen, Sigrid Aertgeerts, Ignaas Devisch, Pedro De Bruyckere, Geert Molenberghs, Marc Raes, Patrik Vankrunkelsven, Sofie Crommen, Annelies Pascal, Bert Aertgeerts, Guido Vanham, Katrien Masschalck, Geertruida E Bekkering, Jeroen Vandenbussche, Nicolas Delvaux, Oscar Plomteux, Seghers, A, Lernout , T, Sweldens, L, Delvaux, N, MOLENBERGHS, Geert, Masschalck, K, RAES, Marc, Devisch, I, Rans, L, Aertgeerts, B, Vandenbussche, Jeroen, Milissen, N, Plomteux, O, Toelen, J, Wollants, E, Vanham, G, CROMMEN, Sofie, Aertgeerts, S, Pascal, A, Vankrunkelsven, P, Bekkering, G, and De Bruyckere, P
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Child abuse ,medicine.medical_specialty ,International studies ,media_common.quotation_subject ,Population ,education ,schools ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Evidence Based Medicine ,medicine ,Humans ,030212 general & internal medicine ,media_common ,education.field_of_study ,child ,SARS-CoV-2 ,practice guideline ,Closing (real estate) ,COVID-19 ,Guideline ,adolescent health ,Mental health ,Family medicine ,adolescent ,Pediatrics, Perinatology and Child Health ,Communicable Disease Control ,Position (finance) ,Educational Personnel ,epidemiology ,Psychology ,Adolescent health - Abstract
In Belgium schools closed during the first lockdown in March 2020, with a partial re-opening in May. They fully re-opened in September. During the summer, infections started to increase in the general population, speeding up in September. Some measures were taken to limit social contacts but those were insufficient to mitigate the exponential rise of infections in October. Children were still receiving all lessons at school at that time and it was questioned whether this position was tenable. We systematically compared the benefits and harms of closing primary and secondary schools and developed a recommendation. A multidisciplinary panel, including school pupils and teachers, educational experts, clinicians and researchers produced this recommendation in compliance with the standards for trustworthy rapid guidelines. The recommendation is based on data collected through national surveillance or studies from Belgium, and supported by a rapid literature review. Closing schools during the first lockdown probably resulted in a large learning delay and possibly led to more cases of child abuse. We are uncertain about the effect of the school closure on the infection rate, hospitalisations, and transmission rates, mental health of children, teachers, and parents. The panel concluded that the balance of benefits and harms of closing schools clearly shifts against closing schools. Detrimental effects are even worse for vulnerable children. This recommendation is affected by the local virus circulation. The guideline panel issues a strong recommendation against closing schools when the virus circulation is low to moderate, and a weak recommendation against closing schools when the virus circulation is high. It does not apply when the school system cannot function due to lack of teachers, too many children who are at home, or a shortage of support services. As the results of international studies are consistent with Belgian study results, this recommendation may also be relevant internationally. Keywords: COVID-19; practice guideline; schools; child; adolescent NOTE: This research was presented byBekkering G.E. (Academic Centre of General Parctice, KU Leuven, Belgium) at 2nd World Pediatrics Congress held on June 08-09, 2021. For more details visit:https://www.pediatrics-conference.com/
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- 2021
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30. Towards new therapies for bronchopulmonary dysplasia. : Op weg naar nieuwe behandelingen voor bronchopulmonale dysplasie
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Salaets, T, Deprest, J, Allegaert, K, and Toelen, J
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Despite advances in neonatology, bronchopulmonary dysplasia (BPD) remains a frequent and important consequence of preterm birth. Innovative therapeutic approaches are needed to improve the respiratory outcome of survivors of preterm birth. The drug discovery pipeline has not been particularly successful for BPD. Currently, budesonide mixed with surfactant, mesenchymal stem cells and IGF1 are promising candidates for further research, but many treatment candidates failed. In this thesis we aimed to search for novel treatment strategies for BPD and improve the research methods necessary to develop new therapies along different phases of the drug development pathway. In a first set of chapters we aimed to improve the methods for explorative and preclinical research on BPD. Animals models remain the cornerstone of BPD research, however many research results in the past were not translatable to humans. We hypothesize that the lack of prematurity in many models plays a role in this difficult translation. In chapter 1 we demonstrated that prematurity alone, in the absence of hyperoxia, results in altered lung function and structure in preterm rabbit pups, in comparison to term control animals. Focusing more on the effect and mechanisms by which preterm birth disrupts normal lung development, instead of focusing on hyperoxia and mechanical ventilation could advance the search for new therapies. A second reason for the difficult translation of positive findings from animal studies could be insufficient use of measures to avoid bias. A classic read-out in BPD research is the mean linear intercept, a read-out for alveolar structure, which is often obtained in a suboptimal way, prone to bias. In chapter 2 we developed and validated a semi-automatic method for rapid and reproducible assessment of mean linear intercept. In a second set of chapters we used a previously described preterm rabbit model, in which prematurity in combination with exposure hyperoxia results in a lung functional, structural and vascular phenotype reminiscent of BPD, to search for novel therapeutic strategies. We started with target identification, by transcriptome analysis, in chapter 3. 2217 gene transcripts were significantly dysregulated in the lungs of preterm rabbit pups exposed to hyperoxia for 7 days. We identified clusters of dysregulated genes around functions as inflammation, lung development, vascular development and metabolism of reactive oxygen species. Furthermore we identified novel therapeutic approaches by upstream regulator analysis. One of these approaches was the use of simvastatin. In chapter 4, we evaluated the efficacy of simvastatin therapy on lung disease in preterm rabbits exposed to hyperoxia. We noticed a beneficial effect on lung function and vascular remodeling, which makes it a promising approach for further research. More knowledge on the exact working mechanism is needed, as we were unable to confirm the gene transcription changes predicted by the upstream regulator analysis. Furthermore, control pups treated with simvastatin depicted an unexpectedly high mortality which warrants caution. A recent clinical trial showed beneficial effects of a repetitively administered surfactant plus budesonide mixture. The important dysregulation of many inflammatory mediators in the transcriptome analysis suggested that the preterm rabbit model is appropriate to investigate this strategy. In chapter 5, we demonstrated that the preterm rabbit model can be used for studies evaluating the effect of intratracheally administered BPD drugs, something that was previously only possible in preterm lambs and baboons. We demonstrated a good distribution of labeled surfactant or saline after intratracheal injection in spontaneously breathing rabbit pups. In chapter 6 we then assessed the efficacy of a mixture of surfactant plus budesonide. We could show that a single dose of 0,25mg/kg budesonide in surfactant was as (and even more) effective than a daily repetitive dosing regimen. This suggests future clinical trials should assess the efficacy of lower cumulative doses (or a single doses) of budesonide in surfactant. In final set of chapters, we focused on improving the methods for clinical trials in newborns. Any promising therapy for BPD should undergo evaluation in clinical trials. While a difficult task in any population, clinical trials have additional specific challenges in neonates. Also for the availability of research tools, neonates remain an "orphan population". While neonates experience relatively more adverse events, there is a lack of tools to standardize safety reporting in this population. In chapter 7 we developed, with the input of broad field of stakeholders, a consensus adverse event severity scale, that can make safety information more comparable across trials and centers. Finally, clinical trials in neonates are ethically difficult. There is paucity of empirical data on the parental perspectives on neonatal clinical trial participation, which we assessed in chapter 8. We showed, with a well-designed survey, that parents are overall contented with their participation. Almost no parents reported anxiety, stress or guilt when looking back at trial participation. A relevant minority was not aware of typical trial characteristics such as equipoise, the possibility of side effects, the presence of a control group, randomization and blinding. Contentment with follow-up was furthermore low. Research teams should ensure effective communication on trial characteristics and follow-up during consent procedures. In conclusion, we advanced the ongoing search for novel therapies for BPD in several ways. Along several phases of the drug development process, we developed new methods and new hypotheses to boost future research that will help to improve the respiratory outcome of survivors of extremely preterm birth. status: published
- Published
- 2019
31. Transplacental sildenafil rescues lung abnormalities in the rabbit model of diaphragmatic hernia
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Andre Hadyme Miyague, Greetje Vande Velde, Jaan Toelen, Francesca Russo, M Patrice Eastwood, Uwe Himmelreich, Philip DeKoninck, Patrizia Vergani, Jan Deprest, Julio Jimenez, Karel Allegaert, Russo, F, Toelen, J, Eastwood, M, Jimenez, J, Miyague, A, Vande Velde, G, Dekoninck, P, Himmelreich, U, Vergani, P, Allegaert, K, and Deprest, J
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Sildenafil ,Rare lung diseases ,Sildenafil Citrate ,Paediatric Lung Disaese ,Random Allocation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pregnancy ,030225 pediatrics ,Internal medicine ,medicine.artery ,medicine ,Animals ,Diaphragmatic hernia ,Lung ,Fetus ,030219 obstetrics & reproductive medicine ,business.industry ,Congenital diaphragmatic hernia ,Ultrasonography, Doppler ,X-Ray Microtomography ,medicine.disease ,Pulmonary hypertension ,respiratory tract diseases ,Disease Models, Animal ,medicine.anatomical_structure ,chemistry ,Anesthesia ,Pulmonary artery ,Respiratory Mechanics ,cardiovascular system ,Cardiology ,Vascular resistance ,Female ,Vascular Resistance ,Rabbits ,Hernias, Diaphragmatic, Congenital ,business - Abstract
Introduction The management of congenital diaphragmatic hernia (DH) would benefit from an antenatal medical therapy, which addresses both lung hypoplasia and persistent pulmonary hypertension. We aimed at evaluating the pulmonary effects of sildenafil in the fetal rabbit model for DH. Methods We performed a dose-finding study to achieve therapeutic fetal plasmatic concentrations without toxicity following maternal sildenafil administration. Subsequently, DH fetuses were randomly exposed to transplacental placebo or sildenafil 10 mg/kg/day from gestational day 24 until examination at term (day 30). Efficacy measures were ipsilateral pulmonary vascular and airway morphometry, micro-CT-based branching analysis, Doppler flow in the main pulmonary artery and postnatal lung mechanics. Results Fetal sildenafil plasmatic concentration was above the minimal therapeutic level for at least 22 h/day without maternal and fetal side effects. The placebo-exposed DH fetuses had increased wall thickness in peripheral pulmonary vessels and significantly less fifth-order vessels compared with controls (CTR). Sildenafil-exposed DH fetuses, instead, had a medial and adventitial thickness in peripheral pulmonary vessels in the normal range and normal vascular branching. Fetal pulmonary artery Doppler showed a reduction of pulmonary vascular resistances both in DH and in CTR fetuses treated by sildenafil compared with the placebo-treated ones. Sildenafil also reversed the mean terminal bronchiolar density to normal and improved lung mechanics, yet without measurable impact on lung-to-bodyweight ratio. Conclusions In the rabbit model for DH, antenatal sildenafil rescues vascular branching and architecture, reduces pulmonary vascular resistances and also improves airway morphometry and respiratory mechanics.
- Published
- 2016
32. Cardiac niche influences the direct reprogramming of canine fibroblasts into cariomyocyte-like cells
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Marco Cassano, Giacomo Palazzolo, Rik Gijsbers, Guido Tettamenti, Inès Barthélémy, Mattia Quattrocelli, Roberto Dominici, Luigi Anastasia, Maurilio Sampaolesi, Jaan Toelen, Stéphane Blot, Palazzolo, G., Quattrocelli, M., Toelen, J., Dominici, R., Anastasia, L., Tettamanti, G., Barthelemy, I., Blot, S., Gijsbers, R., Cassano, M., and Sampaolesi, M.
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0301 basic medicine ,lcsh:Internal medicine ,Pathology ,medicine.medical_specialty ,Article Subject ,health care facilities, manpower, and services ,education ,Cardiomyopathy ,DOG-MODEL ,THERAPY ,DUCHENNE MUSCULAR-DYSTROPHY ,03 medical and health sciences ,Cell & Tissue Engineering ,cell biology ,medicine ,MOUSE FIBROBLASTS ,Myocyte ,molecular biology ,MEF2C ,cardiac niche ,lcsh:RC31-1245 ,Molecular Biology ,health care economics and organizations ,Science & Technology ,biology ,GATA4 ,Myogenesis ,business.industry ,INDUCTION ,Skeletal muscle ,IN-VITRO ,Cell Biology ,medicine.disease ,GENE ,Cell biology ,TRANSCRIPTION FACTORS ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,HEART ,DEFINED FACTORS ,HAND2 ,business ,Life Sciences & Biomedicine ,Reprogramming ,Research Article - Abstract
The Duchenne and Becker muscular dystrophies are caused by mutation of dystrophin gene and primarily affect skeletal and cardiac muscles. Cardiac involvement in dystrophic GRMD dogs has been demonstrated by electrocardiographic studies with the onset of a progressive cardiomyopathy similar to the cardiac disease in DMD patients. In this respect, GRMD is a useful model to explore cardiac and skeletal muscle pathogenesis and for developing new therapeutic protocols. Here we describe a protocol to convert GRMD canine fibroblasts isolated from heart and skin into induced cardiac-like myocytes (ciCLMs). We used a mix of transcription factors (GATA4, HAND2, TBX5, and MEF2C), known to be able to differentiate mouse and human somatic cells into ciCLMs. Exogenous gene expression was obtained using four lentiviral vectors carrying transcription factor genes and different resistance genes. Our data demonstrate a direct switch from fibroblast into ciCLMs with no activation of early cardiac genes. ciCLMs were unable to contract spontaneously, suggesting, differently from mouse and human cells, an incomplete differentiation process. However, when transplanted in neonatal hearts of SCID/Beige mice, ciCLMs participate in cardiac myogenesis. ispartof: Stem Cells International vol:2016 pages:4969430- ispartof: location:United States status: published
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- 2016
33. miR669a and miR669q prevent skeletal muscle differentiation in postnatal cardiac progenitors
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Claudia Altomare, Marco Cassano, Tomaz Curk, Jaan Toelen, Rik Gijsbers, Giulio Cossu, Maurilio Sampaolesi, Stefania Crippa, Graziella Messina, Antonio Zaza, Beatriz G. Gálvez, Daniela Galli, Blaz Zupan, Flavio Lorenzo Ronzoni, Stefan Janssens, Zeger Debyser, Crippa, S, Cassano, M, Messina, G, Galli, D, Galvez, B, Curk, T, Altomare, C, Ronzoni, F, Toelen, J, Gijsbers, R, Debyser, Z, Janssens, S, Zupan, B, Zaza, A, Cossu, G, and Sampaolesi, M
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medicine.medical_specialty ,Cardiac progenitors ,Cardiomyopathy ,Cellular differentiation ,Down-Regulation ,Biology ,MyoD ,Muscle Development ,Article ,Gene and cell therapy ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Muscular dystrophy ,miRNAs ,Stem Cell ,Internal medicine ,Sarcoglycans ,medicine ,Myocyte ,Animals ,Regeneration ,Myocytes, Cardiac ,Progenitor cell ,Sarcoglycan ,Muscle, Skeletal ,Research Articles ,030304 developmental biology ,0303 health sciences ,Models, Genetic ,Myogenesis ,Animal ,Stem Cells ,Skeletal muscle ,MicroRNA ,Cell Differentiation ,Cell Biology ,musculoskeletal system ,3. Good health ,Cell biology ,MicroRNAs ,medicine.anatomical_structure ,Endocrinology ,030220 oncology & carcinogenesis ,Myogenic regulatory factors ,Stem cell - Abstract
miR669a and miR669q inhibit postnatal cardiac progenitor differentiation by directly targeting the 3′UTR of MyoD., Postnatal heart stem and progenitor cells are a potential therapeutic tool for cardiomyopathies, but little is known about the mechanisms that control cardiac differentiation. Recent work has highlighted an important role for microribonucleic acids (miRNAs) as regulators of cardiac and skeletal myogenesis. In this paper, we isolated cardiac progenitors from neonatal β-sarcoglycan (Sgcb)–null mouse hearts affected by dilated cardiomyopathy. Unexpectedly, Sgcb-null cardiac progenitors spontaneously differentiated into skeletal muscle fibers both in vitro and when transplanted into regenerating muscles or infarcted hearts. Differentiation potential correlated with the absence of expression of a novel miRNA, miR669q, and with down-regulation of miR669a. Other miRNAs are known to promote myogenesis, but only miR669a and miR669q act upstream of myogenic regulatory factors to prevent myogenesis by directly targeting the MyoD 3′ untranslated region. This finding reveals an added level of complexity in the mechanism of the fate choice of mesoderm progenitors and suggests that using endogenous cardiac stem cells therapeutically will require specially tailored procedures for certain genetic diseases.
34. Effectiveness of safety netting approaches for acutely ill children: a network meta-analysis.
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Burvenich R, Bos DA, Lowie L, Peeters K, Toelen J, Wynants L, and Verbakel JY
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Background: Safety netting advice (SNA) can help in the management of acutely ill children., Aim: Assess the effectiveness of different SNA methods for acutely ill children on antibiotic prescription and consumption., Design and Setting: Systematic review and network meta-analysis of randomised controlled trials, non-randomised trials of interventions, and controlled before-after studies in ambulatory care., Method: We searched MEDLINE, Embase, Web-Of-Science Core Collection, and Cochrane Central Register of Controlled Trials (22 January 2024). We assessed the risk of bias (RoB) with the Cochrane Tool 2, Revised Cochrane Tool for Cluster-Randomised Trials, and ROBINS-I tool. Certainty of evidence was assessed using the CINeMA approach. We performed sensitivity analyses and network meta-regression., Results: We included 30 studies (20 interventions). Compared to usual care, paper SNA may reduce antibiotic prescribing (OR=0.66 (95%CI: 0.53-0.85), I²=92%, very low certainty; 3 studies, 35,988 participants), especially when combined with oral SNA (OR=0.40 (95%CI: 0.08-2.00), P-score: 0.86), antibiotic consumption (OR=0.39 (95%CI: 0.27-0.58), low RoB; 1 study, 509 participants), and return visits (OR=0.74 , 95%CI 0.63-0.87). Paper SNA without antibiotics may reduce antibiotic consumption compared to paper SNA and delayed antibiotics (OR=0.27 (95%CI: 0.15-0.51, some RoB; 1 study, 206 participants). Video SNA, oral SNA, read-only websites, and web-based modules may increase parental knowledge (ORs 2.23-4.52). Video SNA and web-based modules may improve parental satisfaction (ORs 1.64-4.08)., Conclusion: Paper SNA (with oral SNA) may reduce antibiotic use and return visits. Video, oral, and online SNA, may improve parental knowledge while video SNA and web-based modules may increase parental satisfaction., (Copyright © 2024, The Authors.)
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- 2024
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35. Cycle safe or cycle cool? Adolescents' views on bicycle helmet use and injury prevention campaigns in Belgium.
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Verlinde L, Verlinde F, Van Doren S, De Coninck D, and Toelen J
- Abstract
Objectives: Although cycling is a healthy, ecological and practical way of transportation, it is not without risk. The effect of bicycle helmets to prevent head injuries on crashing has been extensively investigated. Nonetheless, the overall use of helmets by adolescents remains low. While various interventions to increase helmet use have been adopted, adolescents' perspectives on these interventions have not been extensively explored. In our study, we aim to understand the facilitators and barriers to bicycle helmet use by adolescents and their perspectives on injury prevention campaigns., Methods: A qualitative methodology was selected. A convenience sample of three schools in Belgium was selected for participation. 12 focus groups were conducted with a total of 84 adolescents aged 12-17 years in the second, third or fourth year of secondary school., Results: Four key themes regarding adolescents' views on safe cycling practices emerged from the analysis: external motivation, internal motivation, factors specific to the helmet and the cycling environment. The main barriers to bicycle helmet use identified by adolescents were peer pressure, appearance and discomfort. The perceived risks of cycling without a helmet among adolescents were low. Mandatory bicycle helmet laws and non-legislative programmes were considered to be an effective strategy by the study participants. Parental strategies, including strict parental rules and parental helmet use, further contributed to wear a bicycle helmet., Conclusion: The results of this qualitative study add to the literature by expanding the understanding of motivation for bicycle helmet use and should be considered when designing interventions to promote bicycle helmet use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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36. The Association of Social Media Use and Eating Behaviour of Belgian Adolescent Girls Diagnosed with Anorexia Nervosa-A Qualitative Approach.
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Praet N, Stevens J, Casteels K, and Toelen J
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Background: Social media have become integral in adolescents' lives, presenting both opportunities and risks, especially concerning psychiatric issues like eating disorders, prevalent in this vulnerable age group., Methods: This qualitative study employed semi-structured interviews with seven adolescent girls (aged 15-17) diagnosed with eating disorders. Interviews covered seven predefined topics, recorded and transcribed for thematic analysis., Results: Participants identified four key themes: exposure to selective content, biased interpretation, behavioural adaptation, and evolving perspectives during recovery. They highlighted social media's role in exacerbating body dissatisfaction and altering behaviours related to eating disorders., Conclusions: This research underscores the critical need for awareness and guidance in adolescents' social media use to mitigate negative impacts, emphasizing the potential link between exposure to specific content and cognitive-behavioural changes in those with eating disorders. Further investigation is warranted to deepen our comprehension of these dynamics.
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- 2024
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37. Shared decision-making in adolescent healthcare: a literature review of ethical considerations.
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Sobode OR, Jegan R, Toelen J, and Dierickx K
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- Humans, Adolescent, Adolescent Health Services ethics, Parents psychology, Adolescent Health ethics, Patient Participation, Decision Making, Shared
- Abstract
Purpose: Adolescence is a period of growing independence and maturity, within the period of legal minority. As parents or guardians are socially and legally responsible for adolescents' medical decisions, shared decision-making in adolescent healthcare could be ethically challenging. This review aims to identify and map the ethical tensions in shared decision-making in adolescent healthcare., Methods: We systematically searched the literature following the PRISMA guidelines to identify relevant articles, which were analyzed using the review of reasons methodology Strech and Sofaer (J Med Ethics 38(2):121-6, 2012)., Results: We included 38 articles which involved adolescents, healthcare professionals and parents as being the main stakeholders. Shared decision-making was influenced not only by individual stakeholders' characteristics, but by tensions between stakeholder dyads. Most studies supported the involvement of the adolescent in decision-making, depending on their life experience, decision-making capacity and clinical condition., Conclusions: Shared decision-making in adolescent health is receiving increasing attention. However, questions remain on what this concept entails, the roles and involvement of stakeholders and its practical implementation., What Is Known: • Although adolescents wish to be involved in health decisions, shared decision-making in adolescents is underexplored • Adolescent shared decision-making is different from pediatric and adult shared decision-making, and is ethically complex due to the adolescent's growing autonomy What is new: • Adolescent SDM involves three-way interactions between the adolescent, healthcare professional and parents • In adolescent shared decision-making, involving or excluding a stakeholder and sharing or withholding information are ethically value-laden steps • Research is needed to further understand the roles of adolescents' personal value systems, extended or reconstituted families and decision aids in shared decision-making., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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38. Temporal trends in antibiotic prescribing and serious and nonserious infections in children presenting to general practice: a registry-based longitudinal cohort study of 162 507 individuals.
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Burvenich R, De Boodt S, Lowie L, Janssens A, Beerten SG, Vaes B, Toelen J, and Verbakel JY
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- Humans, Child, Child, Preschool, Infant, Female, Male, Retrospective Studies, Longitudinal Studies, Infant, Newborn, Incidence, Belgium epidemiology, Practice Patterns, Physicians' trends, Practice Patterns, Physicians' statistics & numerical data, Registries, Respiratory Tract Infections drug therapy, Respiratory Tract Infections epidemiology, Drug Prescriptions statistics & numerical data, Otitis Media drug therapy, Otitis Media epidemiology, Anti-Bacterial Agents therapeutic use, General Practice statistics & numerical data, General Practice trends
- Abstract
Background: It is crucial to understand the trends in paediatric antibiotic prescribing and serious and nonserious infections to improve antibiotic prescribing practices for children in ambulatory care., Objectives: Assessing trends in paediatric antibiotic prescribing and infection incidence in general practice from 2002 to 2022., Methods: In this retrospective cohort study using INTEGO network data from 162 507 patients in Flanders (Belgium), we calculated antibiotic prescribing rates and proportions alongside incidence rates of serious and nonserious infections, stratified by age (0-1, 2-6, 7-12 years) and municipality. We performed autoregressive moving average time-series analyses and seasonality analyses., Results: From 2002 to 2022, antibiotic prescribing rate decreased significantly: 584/1000 person-years (PY) (95% CI 571-597) to 484/1000PY (95% CI 478-491); so did antibiotic overall prescribing proportion: 46.3% (95% CI 45.1-47.6) to 23.3% (95% CI 22.9-23.7) (59.3% amoxicillin and 17.8% broad spectrum). Prescribing proportions dropped significantly for nonserious (45.6% to 20.9%) and increased for serious infections (64.1% to 69.8%). Proportions significantly dropped for acute suppurative otitis media (74.7% to 64.1%), upper respiratory tract infections (44.9% to 16.6%), bronchitis/bronchiolitis (73.6% to 44.1%) and acute tonsillopharyngitis (59.5% to 21.7%), while significantly increasing for pneumonia (65.2% to 80.2%). Nonserious and serious infection incidence rates increased from 785/1000PY and 34.2/1000PY to 1223/1000PY and 64.1/1000PY, respectively. Blood and CRP testing proportions increased significantly., Conclusions: Antibiotic prescribing in general practice for children declined from 2002 to 2022. Further targeted antibiotic stewardship initiatives are needed to reduce the use of broad-spectrum antibiotics and antibiotic prescribing for conditions such as otitis media and bronchitis/bronchiolitis., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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39. Empowering young voices: navigating the complexities of minors in healthcare decisions.
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de Winter JP, Toelen J, and Milani GP
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- Humans, Adolescent, Child, Patient Participation, Decision Making, Minors psychology
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- 2024
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40. Parenting dimensions and views on adolescent decision making in health care: A cross-national study of Belgian and Dutch parents.
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De Coninck D, Devillé C, Van Bavel J, de Winter P, Toelen J, and Van Leeuwen K
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Background: The aim of this study was to investigate the link between parenting and parents' perspectives on health-related decision making for adolescents. During adolescence, there is a gradual increase in responsibility and autonomy, which influences parenting behavior and child development. Understanding how parenting is associated with parents' views on medical decision making is crucial in the context of the parent-child-physician triad. This study was the first to explore parenting and parents' views on adolescent health care decision making. We compare Belgian and Dutch parents-two countries selected for their different legal frameworks on medical adolescent decision making., Method: An online questionnaire surveyed 984 Belgian and 992 Dutch parents (ages 35-55) with at least one child. Analytical methods included t tests, structural equation modeling, and latent profile analysis., Results: Parents considered adolescents to be competent decision makers at 16.7 years old. Dutch parents granted autonomy at younger ages than Belgian parents. Parents with high behavioral expectations granted autonomy to adolescents at higher ages, while those high in autonomy support and punishment granted autonomy at lower ages. When classifying parents into profiles, we distinguished four types: highly permissive, moderately permissive, moderately restrictive, and highly restrictive groups. The majority of the sample was classified into moderately and highly restrictive profiles., Conclusion: The study highlighted the importance of providing parents with education and support on adolescent development and autonomy. Parenting practices that encourage autonomy and support open communication between parents and adolescents may contribute to a more trusting and supportive parent-child context for adolescent medical decision making. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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- 2024
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41. Vitamin D Status in Belgian Children: A Regional Study.
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Van de Walle L, Vandenplas Y, Toelen J, and Raaijmakers A
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- Child, Adolescent, Humans, Belgium epidemiology, Cross-Sectional Studies, Vitamins, Prevalence, Seasons, Vitamin D, Vitamin D Deficiency
- Abstract
Background: Vitamin D deficiency is the most frequent cause of impaired skeletal growth, and can lead to the development of nutritional rickets. The aim of this study was to evaluate the vitamin D status in a large group of children aged 0-18 years. Methods: We collected laboratory data on vitamin D levels from children who underwent blood sampling between 2014 and 2021. Results: We included 14,887 samples. In this group, 17.7% were vitamin D severely deficient (<12 ng/mL), 25.2% were insufficient (12-20 ng/mL), and another large proportion (28.3%) was borderline (20-30 ng/mL). Sufficient levels (>30 ng/mL) were met in 28.8% of children. We observed no association between gender and vitamin D status ( p = 0.132). Adolescents aged 13-18 years ( n = 3342) had the highest prevalence of severe vitamin D deficiency (24.9%). Vitamin D levels were higher in summer/autumn compared to winter/spring. Conclusions: Vitamin D deficiency/insufficiency has a high prevalence in children, mostly in children above 7 years of age. Many of these children (over 80%) do not meet the 30 ng/mL sufficiency threshold. It is essential that Belgian Health Authorities are aware of this high prevalence, as the current Belgian recommendation suggests ceasing vitamin D supplementation at the age of six. Additional research is required to investigate the consequences of our findings, and what specific approach is needed to achieve normal vitamin D levels in children aged 0 to 18 years., Competing Interests: The authors declare no conflicts of interest.
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- 2024
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42. Towards an international consensus on safety netting advice for acutely ill children presenting to ambulatory care: a modified e-Delphi procedure.
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Burvenich R, Heytens S, De Sutter A, Struyf T, Toelen J, and Verbakel JY
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- Child, Humans, Consensus, Surveys and Questionnaires, Uncertainty, Delphi Technique, Ambulatory Care, Parents education
- Abstract
Objective: Develop a consensus on the content and form of safety netting advice (SNA) for parents of acutely ill children., Design: Four-round modified e-Delphi using online questionnaires and feedback among clinical and research experts., Setting: Ambulatory care in high-income countries., Participants: Forty-one experts from 13 countries: 3 emergency physicians, 15 general practitioners, 4 nurses and 19 paediatricians., Results: The experts defined the content of SNA as advice on the normal, expected disease course of the provisional diagnosis, diagnostic uncertainty, alarm signs that indicate the need for medical help and information on where and how to find such help. Regarding the form of the SNA, the experts agree that a reliable source should give SNA verbally with paper or digital written or video/image resources at every appropriate healthcare encounter in a short and simple empowering fashion, specific to the child's situation and seek confirmatory feedback from parents., Conclusions: SNA needs to contain advice on the expected disease course, alarm signs and where and how to find help. It should be given verbally with written resources by a reliable healthcare professional or digital platform. Short, simple and specific, SNA needs to empower the parent whose understanding of the advice should be checked. The effectiveness of SNA resources coproduced by parents and experts should be assessed in different settings and those providing SNA require up-to-date and reliable training., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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43. Knowledge Gaps and Bridges: The Relationship between the Awareness of General Patient Rights and the Awareness of Minors' Patient Rights in the Netherlands.
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Adu-Gallant C, Toelen J, Sluiter-Post J, De Coninck D, and de Winter P
- Abstract
The major focus of this research is the level of awareness among Dutch parents of general patient rights in relation to minors' patient rights. Moreover, this study is intended to highlight the most effective strategies to increase the awareness of general and minor patient rights in the Netherlands. A survey was conducted among 1010 Dutch parents aged between 35 and 55 years who had at least one child. In this study, we described the relationship between the knowledge among parents of general patient rights and their understanding of the patient rights of minors. A significant connection was found between the knowledge levels of general patient rights and the knowledge levels of the patient rights of minors ( p < 0.05 [95% CI: 0.019-0.183]). While age and sex (male/female) did not appear to be significant confounders in this association, the educational background of the participants may have played a role. This study provides comprehensive insights into the association between the knowledge of general patient rights and the patient rights of minors among Dutch parents. Furthermore, this study points out that there is a need for focused educational interventions to address specific areas of misunderstanding or uncertainty.
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- 2024
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44. Testing a Home Solution for Preparing Young Children for an Awake MRI: A Promising Smartphone Application.
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Geuens S, Lemiere J, Nijs J, Treunen M, Aertsen M, Toelen J, Pauwels G, Sauer K, Potoms M, Van Cauter S, Wouters L, Hohlbaum K, Sjölinder M, Ståhl O, Buyse G, Demaerel P, and Weyn B
- Abstract
Thanks to its non-invasive nature and high-resolution imaging capabilities, magnetic resonance imaging (MRI) is a valuable diagnostic tool for pediatric patients. However, the fear and anxiety experienced by young children during MRI scans often result in suboptimal image quality and the need for sedation/anesthesia. This study aimed to evaluate the effect of a smartphone application called COSMO@home to prepare children for MRI scans to reduce the need for sedation or general anesthesia. The COSMO@home app was developed incorporating mini-games and an engaging storyline to prepare children for learning goals related to the MRI procedure. A multicenter study was conducted involving four hospitals in Belgium. Eligible children aged 4-10 years were prepared with the COSMO@home app at home. Baseline, pre-scan, and post-scan questionnaires measured anxiety evolution in two age groups (4-6 years and 7-10 years). Eighty-two children participated in the study, with 95% obtaining high-quality MRI images. The app was well-received by children and parents, with minimal technical difficulties reported. In the 4-6-year-old group (N = 33), there was a significant difference between baseline and pre-scan parent-reported anxiety scores, indicating an increase in anxiety levels prior to the scan. In the 7-10-year-old group (N = 49), no significant differences were observed between baseline and pre-scan parent-reported anxiety scores. Overall, the COSMO@home app proved to be useful in preparing children for MRI scans, with high satisfaction rates and successful image outcomes across different hospitals. The app, combined with minimal face-to-face guidance on the day of the scan, showed the potential to replace or assist traditional face-to-face training methods. This innovative approach has the potential to reduce the need for sedation or general anesthesia during pediatric MRI scans and its associated risks and improve patient experience.
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- 2023
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45. Diagnosis of IRAK-4-deficiency by flow cytometric measurement of IκB-α degradation.
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Frans G, Michiels B, Picard C, Ampofo L, Raes M, Toelen J, Bucciol G, van der Werff Ten Bosch J, Moens L, Wuyts G, Dillaerts D, Casanova JL, Schrijvers R, Meyts I, and Bossuyt X
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- Humans, NF-KappaB Inhibitor alpha, Interleukin-1 Receptor-Associated Kinases metabolism, Primary Immunodeficiency Diseases
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- 2023
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46. Challenges of Antibiotic Formulations and Administration in the Treatment of Bloodstream Infections in Children Under Five Admitted to Kisantu Hospital, Democratic Republic of Congo.
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Tack B, Vita D, Ntangu E, Ngina J, Mukoko P, Lutumba A, Vangeluwe D, Toelen J, Allegaert K, Lunguya O, Ravinetto R, and Jacobs J
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- Adult, Child, Humans, Cohort Studies, Prospective Studies, Democratic Republic of the Congo epidemiology, Hospitals, Anti-Bacterial Agents therapeutic use, Sepsis drug therapy
- Abstract
Severe bacterial infections in children need prompt, appropriate antibiotic treatment. We report challenges observed within a prospective, cohort study on antibiotic efficacy in non-typhi Salmonella bloodstream infection (NCT04850677) in Kisantu district hospital (Democratic Republic of Congo). Children (aged > 28 days to < 5 years) admitted with suspected bloodstream infection (August 1, 2021 through July 31, 2022) were enrolled and followed until day 3 or discharge for non-typhi Salmonella patients. Antibiotics were administered to 98.4% (1,838/1,867) of children, accounting for 2,296 antibiotic regimens (95.7% intravenous, 4.3% oral). Only 78.3% and 61.8% of children were, respectively, prescribed and administered antibiotics on the admission day. At least one dose was not administered in 3.6% of children, mostly because of mismatch of the four times daily cefotaxime schedule with the twice-daily administration rounds. Inappropriate intravenous administration practices included multidose use, air-venting, and direct injection instead of perfusion. There was inaccurate aliquoting in 18.0% (32/178) of intravenous ciprofloxacin regimens, and thus administered doses were > 16% below the intended dose. Dosing accuracy of oral suspensions was impaired by lack of instructions for reconstitution, volume indicators, and/or dosing devices. Adult-dose tablets were split without/beyond scoring lines in 84.4% (27/32) of tablets. Poor availability and affordability of age-appropriate oral formulations contributed to low proportions of intravenous-to-oral switch (33.3% (79/237) of non-typhi Salmonella patients). Other quality issues included poor packaging, nonhomogeneous suspensions, and unsafe water for reconstitution. In conclusion, poor antibiotic products (no age-appropriate formulations, poor quality and access), processes (delayed prescription/administration, missed doses), and practices (inaccurate doses, [bio]safety risks) must be urgently addressed to improve pediatric antibiotic treatment.
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- 2023
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47. Is blood thicker than water? Perceptions on the role of stepparents in medical decisions among minors.
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Willekens M, De Coninck D, de Winter P, Matthijs K, Lierman S, Boone I, and Toelen J
- Abstract
Alternative family configurations are becoming more prevalent, yet current legislative statutory does not support stepparents in medical decisions for their stepchildren. We investigate opinions of Belgian and Dutch adults regarding inclusion of stepparents in medical decision-making in minors. We make two observations. First, participants wanted stepparents to be involved in cases when medical information had to be shared or informed consent signed. Second, when stepparents object against previously approved medical interventions by a biological parent, respondents were less likely to support stepparents. Participants with stepchildren were likely to favour inclusion of stepparents in decision-making. Overall, our findings indicate that Belgian and Dutch adults view stepparents as potential executive actors in medical decision-making for minors, but not as primary decision-makers. This study is a first step in showing to what extent stepparents could be included in medical information and decision-making regarding stepchildren. We reflect on these findings in light of implications for medical practice and legislative shortcomings., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2023
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48. Knowledge of Child Abuse and Neglect among General Practitioners and Pediatricians in Training: A Survey.
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Jamaer M, Van den Eynde J, Aertgeerts B, and Toelen J
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Child abuse and neglect is a common, underreported, and worldwide problem. Health care providers play an important role in detecting and reporting this problem. This study examined the knowledge on the clinical signs and mimickers of child abuse among Belgian trainees in family medicine and pediatrics. Participants filled out an anonymous online survey of 15 fictional but realistic cases with either suspicious or non-suspicious signs of abuse or neglect in the context of primary or emergency care. The overall score on all cases, the number of correct answers per case, and the median score were calculated, and the association of the participant's demographic characteristics with their score was examined using regression analysis. A total of 70 participants completed the survey. The overall median score was 73.3% (IQR 20.0%). The suspicious cases were solved more correctly than the non-suspicious cases (median: 85.7% versus 62.5%, p < 0.001). Regression analysis could not reveal a significant association of type and level of education with the performance on the survey. Knowledge of the clinical signs of child maltreatment among pediatricians and general practitioners in training is good, but there is still room for improvement.
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- 2023
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49. Navigating the unknown: understanding and managing parental anxiety when a child is ill.
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Simoens E, Michiels L, Toelen J, and de Winter P
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- Child, Humans, Qualitative Research, Parents, Anxiety diagnosis, Fear, Physicians
- Abstract
Background: Parents are often confronted with a difficult decision when their child falls ill: should they go to the general practitioner (GP) or not? This study aims to describe this process comprehensively in order to allow clinicians to assess the extent to which parents can recognise clinical warning signs and act accordingly. The purpose of this study is to describe parents' decision-making processes when deciding whether or not to consult a GP for their sick child., Methods: We used a qualitative study design based on semistructured interviews to investigate the decision-making process of 25 parents. Four case scenarios describing a developing illness in a child were presented., Results: Parents' reasons for seeking medical attention could be divided into two main categories. First, non-specific fears lead parents to consult a doctor. Parents were alarmed by the persistence and progression of symptoms, the combination of symptoms or changes in their child's behaviour or they needed reassurance. Second, several specific fears were identified. Sometimes, parents fear a specific disease, while at other times, they are concerned about warning signs. Some parents, however, would not seek medical attention at any decision point even though their child could be in a potentially life-threatening situation., Conclusions: Although parents make carefully considered decisions on whether or not to consult a doctor, many appear to miss red flags, including more experienced parents. Conversely, some become overly concerned with certain specific symptoms such as fever, and few parents are familiar with self-management strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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50. Modulation of engineered nanomaterial interactions with organ barriers for enhanced drug transport.
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Lenders V, Koutsoumpou X, Phan P, Soenen SJ, Allegaert K, de Vleeschouwer S, Toelen J, Zhao Z, and Manshian BB
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- Pregnancy, Humans, Female, Drug Carriers therapeutic use, Tissue Distribution, Placenta pathology, Drug Delivery Systems, Nanoparticles, Neoplasms drug therapy
- Abstract
The biomedical use of nanoparticles (NPs) has been the focus of intense research for over a decade. As most NPs are explored as carriers to alter the biodistribution, pharmacokinetics and bioavailability of associated drugs, the delivery of these NPs to the tissues of interest remains an important topic. To date, the majority of NP delivery studies have used tumor models as their tool of interest, and the limitations concerning tumor targeting of systemically administered NPs have been well studied. In recent years, the focus has also shifted to other organs, each presenting their own unique delivery challenges to overcome. In this review, we discuss the recent advances in leveraging NPs to overcome four major biological barriers including the lung mucus, the gastrointestinal mucus, the placental barrier, and the blood-brain barrier. We define the specific properties of these biological barriers, discuss the challenges related to NP transport across them, and provide an overview of recent advances in the field. We discuss the strengths and shortcomings of different strategies to facilitate NP transport across the barriers and highlight some key findings that can stimulate further advances in this field.
- Published
- 2023
- Full Text
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