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2. Gender differences in the use of cardiovascular interventions in HIV‐positive persons; the D:A:D Study
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Hatleberg, Camilla I., Ryom, Lene, El?Sadr, Wafaa, Mocroft, Amanda, Reiss, Peter, De Wit, Stephane, Dabis, Francois, Pradier, Christian, Monforte, Antonella D'Arminio, Kovari, Helen, Law, Matthew, Lundgren, Jens D., Sabin, Caroline A., Calvo, G, Bonnet, F, Kirk, O, Morfeldt, L, Weber, R, Lind?Thomsen, A, Brandt, R Salbøl, Hillebreght, M, Zaheri, S, Wit, Fwnm, Scherrer, A, Schöni?Affolter, F, Rickenbach, M, Tavelli, A, Fanti, I, Leleux, O, Mourali, J, Le Marec, F, Boerg, E, Thulin, E, Sundström, A, Bartsch, G, Thompsen, G, Necsoi, C, Delforge, M, Fontas, E, Caissotti, C, Mateu, S, Torres, F, Petoumenos, K, Blance, A, Huang, R, Puhr, R, Laut, K, Kristensen, D, Phillips, An, Kamara, Da, Smith, Cj, Brandt, Rs, Raben, D, Matthews, C, Bojesen, A, Grevsen, Al, Powderly, B, Shortman, N, Moecklinghoff, C, Reilly, G, Franquet, X, Smit, C, Ross, M, Fux, Ca, Morlat, P, Friis?Møller, N, Kowalska, J, Bohlius, J, Bower, M, Fätkenheuer, G, Grulich, A, Sjøl, A, Meidahl, P, Iversen, Js, Hillebregt, M, Prins, Jm, Kuijpers, Tw, Scherpbier, Hj, Meer, Jtm, Godfried, Mh, Poll, T, Nellen, Fjb, Geerlings, Se, Vugt, M, Pajkrt, D, Bos, Jc, Wiersinga, Wj, Valk, M, Goorhuis, A, Hovius, Jw, Eden, J, Henderiks, A, Hes, Amh, Mutschelknauss, M, Nobel, He, Pijnappel, Fjj, Jurriaans, S, Back, Nkt, Zaaijer, Hl, Berkhout, B, Cornelissen, Mte, Schinkel, Cj, Thomas, Xv, Ziekenhuis, A De Ruyter, Berge, M, Stegeman, A, Baas, S, De Looff, L Hage, Ziekenhuis, C, Pronk, Mjh, Ammerlaan, Hsm, Munnik, E, Tjhie, J, Wegdam, Mca, Deiman, B, Scharnhorst, V, Weijsenfeld, Am, Ende, Me, Gorp, Ecm, Schurink, Cam, Nouwen, Jl, Verbon, A, Rijnders, Bja, Bax, Hi, Feltz, M, Bassant, N, Beek, Jea, Vriesde, M, Zonneveld, Lm, Oude?Lubbers, A, Berg?Cameron, Hj, Bruinsma?Broekman, Fb, Groot, J, Man, M Zeeuw?De, Boucher, Cab, Koopmans, Mpg, Kampen, Jja, Pas, Sd, Driessen, Gja, Rossum, Amc, Knaap, Lc, Flevoziekenhuis, E, Branger, J, Rijkeboer?Mes, A, Schippers, Ef, Ijperen, Jm, Geilings, J, Hut, G, Franck, Pfh, Eeden, A, Brokking, W, Groot, M, Elsenburg, Ljm, Damen, M, Isala, Is, Groeneveld, Php, Bouwhuis, Jw, Berg, Jf, Hulzen, Agw, Bliek, Gl, Bor, Pcj, Bloembergen, P, Wolfhagen, Mjhm, Ruijs, Gjhm, Kroon, Fp, Boer, Mgj, Bauer, Mp, Jolink, H, Vollaard, Am, Dorama, W, Holten, N, Claas, Ecj, Wessels, E, Den Hollander, Jg, Pogany, K, Roukens, A, Kastelijns, M, Smit, Jv, Smit, E, Struik?Kalkman, D, Tearno, C, Bezemer, M, Niekerk, T, Pontesilli, O, Lowe, Sh, Lashof, Aml Oude, Posthouwer, D, Ackens, Rp, Schippers, J, Vergoossen, R, Weijenberg?Maes, B, Loo, Ihm, Havenith, Tra, Leyten, Ems, Gelinck, Lbs, Hartingsveld, A, Meerkerk, C, Wildenbeest, Gs, Mutsaers, Jaem, Jansen, Cl, Mulder, Jw, Vrouenraets, Sme, Lauw, Fn, Broekhuizen, Mc, Paap, H, Vlasblom, Dj, Smits, Phm, Weijer, S, Moussaoui, R El, Bosma, As, Vonderen, Mga, Houte, Dpf, Kampschreur, Lm, Dijkstra, K, Faber, S, Weel, J, Kootstra, Gj, Delsing, Ce, De Plas, M Burg?Van, Heins, H, Lucas, E, Kortmann, W, Twillert¤, G, Stuart, Jwt Cohen, Diederen, Bmw, Pronk, D, Truijen?Oud, Fa, Reijden, Wa, Jansen, R, Brinkman¤, K, Berk, Gel, Blok, Wl, Frissen, Phj, Lettinga, Kd, Schouten, Wem, Veenstra, J, Brouwer, Cj, Geerders, Gf, Hoeksema, K, Kleene, Mj, Meché, Ib, Spelbrink, M, Sulman, H, Toonen, Ajm, Wijnands, S, Kwa, D, Witte, E, Koopmans, Pp, Keuter, M, Ven, Ajam, Hofstede, Hjm, Dofferhoff, Asm, Crevel, R, Albers, M, Bosch, Mew, Grintjes?Huisman, Kjt, Zomer, Bj, Stelma, Ff, Rahamat?Langendoen, J, Burger, D, Richter, C, Gisolf, Eh, Hassing, Rj, Beest, G, Van Bentum, Phm, Langebeek, N, Tiemessen, R, Swanink, Cma, Lelyveld, Sfl, Soetekouw, R, Hulshoff, N, Prijt, Lmm, Swaluw, J, Bermon, N, Herpers, Bl, Veenendaal, D, Verhagen, Dwm, Wijk, M, Brouwer, Ae, Kuipers, M, Santegoets, Rmwj, Ven, B, Marcelis, Jh, Buiting, Agm, Kabel, Pj, Bierman, Wfw, Scholvinck, H, Wilting, Kr, Stienstra, Y, Meulen, Pa, Weerd, Da, Ludwig?Roukema, J, Niesters, Hgm, Riezebos?Brilman, A, Leer?Buter, Cc, Knoester, M, Hoepelman, Aim, Mudrikova, T, Ellerbroek, Pm, Oosterheert, Jj, Arends, Je, Barth, Re, Wassenberg, Mwm, Schadd, Em, Elst?Laurijssen, Dhm, Oers?Hazelzet, Eeb, Vervoort, S, Berkel, M, Schuurman, R, Verduyn?Lunel, F, Wensing, Amj, Peters, Ejg, Agtmael, Ma, Bomers, M, Vocht, J, Heitmuller, M, Laan, Lm, Pettersson, Am, Ang, Cw, Geelen, Spm, Wolfs, Tfw, Bont, Lj, Bezemer, Do, Sighem, Ai, Boender, Ts, Jong, A, Bergsma, D, Hoekstra, P, Lang, A, Grivell, S, Jansen, A, Rademaker, Mj, Raethke, M, Meijering, R, Schnörr, S, Groot, L, Akker, M, Bakker, Y, Claessen, E, Berkaoui, A El, Koops, J, Kruijne, E, Lodewijk, C, Munjishvili, L, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Rutkens, T, Sande, L, Schoorl, M, Timmerman, A, Tuijn, E, Veenenberg, L, Vliet, S, Wisse, A, Woudstra, T, Tuk, B, Dupon, M, Gaborieau, V, Lacoste, D, Malvy, D, Mercié, P, Neau, D, Pellegrin, Jl, Tchamgoué, S, Lazaro, E, Cazanave, C, Vandenhende, M, Vareil, Mo, Gérard, Y, Blanco, P, Bouchet, S, Breilh, D, Fleury, H, Pellegrin, I, Chêne, G, Thiébaut, R, Wittkop, L, Lawson?Ayayi, S, Gimbert, A, Desjardin, S, Lacaze?Buzy, L, Petrov?Sanchez, V, André, K, Bernard, N, Caubet, O, Caunegre, L, Chossat, I, Courtault, C, Dauchy, Fa, Dondia, D, Duffau, P, Dutronc, H, Farbos, S, Faure, I, Ferrand, H, Gerard, Y, Greib, C, Hessamfar, M, Imbert, Y, Lataste, P, Marie, J, Mechain, M, Monlun, E, Ochoa, A, Pistone, T, Raymond, I, Receveur, Mc, Rispal, P, Sorin, L, Valette, C, Vandenhende, Ma, Viallard, Jf, Wille, H, Wirth, G, Lafon, Me, Trimoulet, P, Bellecave, P, Tumiotto, C, Haramburu, F, Miremeont?Salamé, G, Blaizeau, Mj, Decoin, M, Hannapier, C, Pougetoux, E Lenaud Et A., Delveaux, S, D' Ivernois, C, Diarra, F, Uwamaliya?Nziyumvira, B, Palmer, G, Conte, V, Sapparrart, V, Moore, R, Edwards, S, Hoy, J, Watson, K, Roth, N, Lau, H, Bloch, M, Baker, D, Carr, A, Cooper, D, O'Sullivan, M, Nolan, D, Guelfi, G, Domingo, P, Sambeat, Ma, Gatell, J, Del Cacho, E, Cadafalch, J, Fuster, M, Codina, C, Sirera, G, Vaqué, A, Clumeck, N, Gennotte, Af, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Payen, Mc, Semaille, P, Laethem, Y, Neaton, J, Krum, E, Thompson, G, Luskin?Hawk, R, Telzak, E, Abrams, Di, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, Lr, Sampson, J, Baxter, J, Gazzard, B, Horban, A, Karpov, I, Losso, M, Pedersen, C, Ristola, M, Phillips, A, Rockstroh, J, Peters, L, Fischer, Ah, Laut, K Grønborg, Larsen, Jf, Podlekareva, D, Cozzi?Lepri, A, Shepherd, L, Schultze, A, Amele, S, Kundro, M, Schmied, B, Vassilenko, A, Mitsura, Vm, Paduto, D, Florence, E, Vandekerckhove, L, Hadziosmanovic, V, Begovac, J, Machala, L, Jilich, D, Kronborg, G, Benfield, T, Gerstoft, J, Katzenstein, T, Møller, Nf, Ostergaard, L, Wiese, L, Nielsen, Ln, Zilmer, K, Aho, I, Viard, J?P, Girard, P?M, Duvivier, C, Degen, O, Stellbrink, Hj, Stefan, C, Bogner, J, Chkhartishvili, N, Gargalianos, P, Szlávik, J, Gottfredsson, M, Mulcahy, F, Yust, I, Turner, D, Burke, M, Shahar, E, Hassoun, G, Elinav, H, Haouzi, M, Elbirt, D, Sthoeger, Zm, Esposito, R, Mazeu, I, Mussini, C, Mazzotta, F, Gabbuti, A, Vullo, V, Lichtner, M, Zaccarelli, M, Antinori, A, Acinapura, R, Plazzi, M, Lazzarin, A, Castagna, A, Gianotti, N, Galli, M, Ridolfo, A, Rozentale, B, Uzdaviniene, V, Staub, T, Ormaasen, V, Maeland, A, Bruun, J, Knysz, B, Gasiorowski, J, Inglot, M, Bakowska, E, Flisiak, R, Grzeszczuk, A, Parczewski, M, Maciejewska, K, Aksak?Was, B, Beniowski, M, Mularska, E, Smiatacz, T, Gensing, M, Jablonowska, E, Malolepsza, E, Wojcik, K, Mozer?Lisewska, I, Caldeira, L, Radoi, R, Panteleev, A, Yakovlev, A, Trofimora, T, Khromova, I, Kuzovatova, E, Borodulina, E, Vdoushkina, E, Jevtovic, D, Tomazic, J, Gatell, Jm, Miró, Jm, Moreno, S, Rodriguez, Jm, Clotet, B, Jou, A, Paredes, R, Tural, C, Puig, J, Bravo, I, Gutierrez, M, Mateo, G, Laporte, Jm, Falconer, K, Thalme, A, Sonnerborg, A, Blaxhult, A, Flamholc, L, Cavassini, M, Calmy, A, Furrer, H, Schmid, P, Kuznetsova, A, Kyselyova, G, Sluzhynska, M, Johnson, Am, Simons, E, Johnson, Ma, Orkin, C, Weber, J, Scullard, G, Clarke, A, Leen, C, Thulin, G, Åkerlund, B, Koppel, K, Karlsson, A, Håkangård, C, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Marchetti, Gc, Perno, Cf, Schloesser, F, Viale, P, Ceccherini?Silberstein, F, Girardi, E, Lo Caputo, S, Puoti, M, Andreoni, M, Ammassari, A, Balotta, C, Bandera, A, Bonfanti, P, Bonora, S, Borderi, M, Calcagno, A, Calza, L, Capobianchi, Mr, Cingolani, A, Cinque, P, De Luca, A, Di Biagio, A, Gori, A, Guaraldi, G, Lapadula, G, Madeddu, G, Maggiolo, F, Marchetti, G, Marcotullio, S, Monno, L, Nozza, S, Roldan, E Quiros, Rossotti, R, Rusconi, S, Santoro, Mm, Saracino, A, Galli, L, Lorenzini, P, Rodano, A, Shanyinde, M, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petrone, F, Prota, G, Quartu, S, Truffa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Santoro, C, Suardi, C, Donati, V, Verucchi, G, Minardi, C, Quirino, T, Abeli, C, Manconi, Pe, Piano, P, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolfi, L, Segala, D, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Mastroianni, C, Belvisi, V, Caramma, I, Chiodera, A, Milini, P, Rizzardini, G, Moioli, Mc, Piolini, R, Ridolfo, Al, Salpietro, S, Tincati, C, Puzzolante, C, Abrescia, N, Chirianni, A, Borgia, G, Orlando, R, Bonadies, G, Di Martino, F, Gentile, I, Maddaloni, L, Cattelan, Am, Marinello, S, Cascio, A, Colomba, C, Baldelli, F, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, Ma, Cristaudo, A, Baldin, G, Capozzi, M, Cicalini, S, Sulekova, L Fontanelli, Iaiani, G, Latini, A, Mastrorosa, I, Plazzi, Mm, Savinelli, S, Vergori, A, Cecchetto, M, Viviani, F, Bagella, P, Rossetti, B, Franco, A, Del Vecchio, R Fontana, Francisci, D, Di Giuli, C, Caramello, P, Orofino, Gc, Sciandra, M, Bassetti, M, Londero, A, Pellizzer, G, Manfrin, V, Starnini, G, Ialungo, A, Dollet, K, Dellamonica, P, Bernard, E, Courjon, J, Cua, E, De Salvador?Guillouet, F, Durant, J, Etienne, C, Ferrando, S, Mondain?Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost?Keller, B, Pugliese, P, Rio, V, Risso, K, Roger, Pm, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, Dl, Bucher, Hc, Ciuffi, A, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Günthard, Hf, Haerry, D, Hasse, B, Hirsch, Hh, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, Rd, Ledergerber, B, Martinetti, G, De Tejada, B Martinez, Marzolini, C, Metzner, Kj, Müller, N, Nicca, D, Pantaleo, G, Paioni, P, Rauch, A, Rudin, C, Scherrer, Au, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Wandeler, G, and Yerly, S
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Medical care -- Utilization ,Cardiovascular system -- Surgery ,Sex factors in disease -- Analysis ,HIV patients -- Statistics -- Care and treatment -- Demographic aspects ,Health - Abstract
: Introduction: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV‐positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study. Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid‐lowering drugs (LLDs), angiotensin‐converting enzyme inhibitors (ACEIs), anti‐hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders. Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti‐hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow‐up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti‐hypertensives (1.17 [1.10, 1.25]). Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV‐positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions., Introduction HIV‐positive individuals are known to be at increased risk of cardiovascular disease (CVD) compared to the general population, partly due to an increased prevalence of some CVD risk factors, [...]
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- 2018
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3. Identification of regulatory variants associated with genetic susceptibility to meningococcal disease
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Borghini, Lisa, Png, Eileen, Binder, Alexander, Wright, Victoria J, Pinnock, Ellie, de Groot, Ronald, Hazelzet, Jan, Emonts, Marieke, Van der Flier, Michiel, Schlapbach, Luregn J, Anderson, Suzanne, Secka, Fatou, Salas, Antonio, Fink, Colin, Carrol, Enitan D, Pollard, Andrew J, Coin, Lachlan J, Kuijpers, Taco W, Martinon-Torres, Federico, Zenz, Werner, Levin, Michael, Hibberd, Martin L, Davila, Sonia, Gormley, Stuart, Hamilton, Shea, Herberg, Jethro, Hourmat, Bernardo, Hoggart, Clive, Kaforou, Myrsini, Sancho-Shimizu, Vanessa, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Bellos, Evangelos, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stefanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Thakker, Clare, Bokhandi, S, Power, Sue, Barham, Heather, Pathan, N, Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, S, Patel, S, McCorkell, Jenni, Davies, P, Cratev, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, R, Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Willis, Louise, Young, Zoe, Royad, C, White, Sonia, Fortune, PM, Hudnott, Phil, Alvez Gonzalez, Fernando, Barral-Arca, Ruth, Cebey-Lopez, Miriam, Jose Curras-Tuala, Maria, Garcia, Natalia, Garcia Vicente, Luisa, Gomez-Carballa, Alberto, Gomez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leborans Iglesias, Pilar, Martinez Santos, Alba Elena, Martinon-Torres, Nazareth, Martinon Sanchez, Jose Maria, Mosquera Perez, Belen, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, Rivero Calle, Irene, Rodriguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Seren Fernandez, Sonia, Porto Silva, Maria del Sol, Vega, Ana, Beatriz Reyes, Susana, Leon Leon, Maria Cruz, Navarro Mingorance, Alvaro, Gabaldo Barrios, Xavier, Onate Vergara, Eider, Concha Torre, Andres, Vivanco, Ana, Fernandez, Reyes, Gimenez Sanchez, Francisco, Sanchez Forte, Miguel, Rojo, Pablo, Ruiz Contreras, J, Palacios, Alba, Navarro, Marisa, Alvarez Alvarez, Cristina, Jose Lozano, Maria, Carreras, Eduardo, Brio Sanagustin, Sonia, Neth, Olaf, Martinez Padilla, Ma del Carmen, Prieto Tato, Luis Manuel, Guillen, Sara, Fernandez Silveira, Laura, Moreno, David, van Furth, AM Tutu, van der Flier, M, Boeddha, NP, Driessen, GJA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, Philipp, Aebi, Christoph, Berger, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M, Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Paulus, Stephane, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Agbeko, Rachel, Bojang, Kalifa, Sarr, Isatou, Kebbeh, Ngane, Sey, Gibbi, Saidykhan, Momodou, Cole, Fatoumatta, Thomas, Gilleh, Antonio, Martin, Walcher, Wolfgang, Geishofer, Gotho, Klobassa, Daniela, Martin, Mueller, Pfurtscheller, Klaus, Reiter, Karl, Roedl, Siegfried, Zobel, Gerfried, Zoehrer, Bettina, Toepke, Baerbel, Fucik, Peter, Gabriel, Markwart, Penzien, Johann M, Diab, Gedeon, Miething, Robert, Deeg, KH, Hammer, Jurg, Varnholt, Verena, Schmidt, Andreas, Bindl, Lutz, Sillaber, Ursula, Huemer, Christian, Meier, Primrose, Simic-Schleicher, G, Markart, Markus, Pfau, Eberhard, Broede, Hans, Ausserer, Bernd, Kalhoff, Hermann, Arpe, Volker, Schweitzer-Krantz, Susanne, Kasper, Johannes-Martin, Loranth, Kathrin, Bittrich, Hans J, Simma, Burkhard, Klinge, Jens, Fedlmaier, Michael, Weigand, Nicola, Herting, Egbert, Grube, Regina, Fusch, Christoph, Gruber, Alois, Schimmel, Ulf, Knaufer-Schiefer, Suzanne, Laessig, Wolfgang, Hennenberger, Axel, von der Wense, Axel, Tillmann, Roland, Schwarick, Juergen, Sitzmann, Friedrich C, Streif, Werner, Mueller, Herbert, Kurnik, Peter, Groneck, Peter, Weiss, Ute, Groeblacher-Roth, Helene, Bensch, Juergen, Moser, Reinhard, Schwarz, Rudolf, Lenz, Kurt, Hofmann, Thomas, Goepel, Wolfgang, Schulz, Dietrich, Berger, Thomas, Hauser, Erwin, Foerster, Kai Martin, Peters, Jochen, Nicolai, T Homas, Kumlien, Bjoern, Beckmann, Regina, Seitz, Christiane, Hueseman, D, Schuermann, Roland, Ta, Van Hop, Weikmann, Eckart, Evert, W, Hautz, Juergen, Seidenberg, Juergen, Wocko, Lucia, Luigs, Petra, Reiter, Hans-Ludwig, Quietzach, J, Koenig, Michael, Herrmann, Johanna, Mitter, Horst, Seidler, Ekkehard, Maak, Bernhard, Sperl, Wolfgang, Zwiauer, Karl, Meissl, Manfred, Koch, Reinhard, Cremer, Manfred, Breuer, HA, Goerke, W, Nossal, Robert, Pernice, Walter, Brangenberg, Ralf, Salzer, Hans R, Koch, Hartmut, Schaller, Gerhard, Paky, Franz, Strasser, Friedrich, Eitelberger, Franz, Sontheimer, D, Lischka, Andreas, Kronberger, Martina, Dilch, Alfred, Scheibenpflug, Christian, Bruckner, Robert, Mahler, Klaus, Runge, Klaus, Kunze, Wolfgang, Schermann, Peter, Consortium, EUCLIDS, European Commission, Meningitis Research Foundation, National Institute for Health Research (UK), Newcastle Biomedical Research Centre, Newcastle University, Newcastle upon Tyne Hospitals NHS Foundation Trust, Instituto de Salud Carlos III, Xunta de Galicia, Wyeth Farma, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela, Novartis, Swiss National Science Foundation, Swiss Society of Intensive Care Medicine, Gottfried und Julia Bangerter-Rhyner-Stiftung, Vinetum and Borer Foundation, Foundation for the Health of Children and Adolescents, Austrian National Bank, University of Zurich, Borghini, Lisa, Universidade de Santiago de Compostela. Departamento de Ciencias Forenses, Anatomía Patolóxica, Xinecoloxía e Obstetricia, e Pediatría, Png, Eileen [0000-0001-5586-6395], Wright, Victoria J [0000-0001-7826-1516], Schlapbach, Luregn J [0000-0003-2281-2598], Salas, Antonio [0000-0002-2336-702X], Martinon-Torres, Federico [0000-0002-9023-581X], Apollo - University of Cambridge Repository, ARD - Amsterdam Reproduction and Development, AII - Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Neurology, ANS - Neuroinfection & -inflammation, Medical Microbiology and Infection Prevention, Pediatrics, Public Health, Posfay Barbe, Klara, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), APH - Aging & Later Life, Amsterdam Reproduction & Development (AR&D), and Pediatric surgery
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0301 basic medicine ,Candidate gene ,Hypopharyngeal Neoplasms / microbiology ,Meningococcal Infections / microbiology ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,MathematicsofComputing_GENERAL ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,lcsh:Medicine ,Neisseria meningitidis ,Regulatory Sequences, Nucleic Acid ,Cohort Studies ,0302 clinical medicine ,ComputingMethodologies_SYMBOLICANDALGEBRAICMANIPULATION ,Hypopharyngeal Neoplasms / pathology ,BINDING ,Tumor Cells, Cultured ,lcsh:Science ,Genetics ,Multidisciplinary ,ddc:618 ,Cultured ,TheoryofComputation_GENERAL ,High-Throughput Nucleotide Sequencing ,Genomics ,Phenotype ,3. Good health ,ddc ,Tumor Cells ,Multidisciplinary Sciences ,GENOME ,Science & Technology - Other Topics ,Neisseria meningitidis / isolation & purification ,Single-nucleotide polymorphism ,610 Medicine & health ,KAPPA-B ,Biology ,Hypopharyngeal Neoplasms / genetics ,Polymorphism, Single Nucleotide ,Article ,Meningococcal Infections / epidemiology ,03 medical and health sciences ,SEQUENCE VARIATION ,Genetic predisposition ,Journal Article ,Humans ,Meningitis ,Meningococcal Infections / genetics ,Genetic Predisposition to Disease ,Nucleic Acid ,Polymorphism ,General ,Gene ,Genotyping ,Neisseria meningitidis / genetics ,Genetic Association Studies ,Genetic association ,Genetic association study ,1000 Multidisciplinary ,Science & Technology ,Hypopharyngeal Neoplasms ,genetic variants ,meningococcal disease ,lcsh:R ,Single Nucleotide ,EUCLIDS consortium ,Gene regulation ,Meningococcal Infections ,030104 developmental biology ,10036 Medical Clinic ,Case-Control Studies ,lcsh:Q ,Software_PROGRAMMINGLANGUAGES ,Regulatory Sequences ,030217 neurology & neurosurgery - Abstract
EUCLIDS consortium., Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA – a NF-kB subunit, master regulator of the response to infection – under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes., This work has been partially funded by the European Seventh Framework Programme for Research and Technological Development (FP7) under EUCLIDS Grant Agreement No. 279185. The UK meningococcal cohort was established with support from Meningitis Research Foundation through grants to Imperial College London. The Research from Newcastle partners was supported by the National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The ESIGEM Research group activities were supported by grants from Instituto de Salud Carlos III (Proyecto de Investigación en Salud, Acción Estratégica en Salud: proyecto GePEM PI16/01478) (A.S.); Consellería de Sanidade, Xunta de Galicia (RHI07/2-intensificación actividad investigadora, PS09749 and 10PXIB918184PR), Instituto de Salud Carlos III (Intensificación de la actividad investigadora 2007–2016), Convenio de colaboración de investigación (Wyeth España-Fundación IDICHUS 2007–2011), Convenio de colaboración de investigación (Novartis España-Fundación IDICHUS 2010–2011), Fondo de Investigación Sanitaria (FIS; PI070069/PI1000540) del plan nacional de I + D + I and ‘fondos FEDER’ (F.M.T.). The Swiss Pediatric Sepsis study was funded by grants from the Swiss National Science Foundation (342730_153158/1), the Swiss Society of Intensive Care, the Bangerter Foundation, the Vinetum and Borer Foundation, and the Foundation for the Health of Children and Adolescents. The Western Europe Meningococcal Study was supported by grants no 8842, 10112 and 12710 of the Oesterreichische Nationalbank (Austria), grants A3-16.K-8/2008-11 and A3-16.K-8/2006–9 of the Department for Science and Research of the Styrian federal government (Austria) and the non for profit association ‘In Vita’, Graz (Austria).
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- 2019
4. Plasma lipid profiles discriminate bacterial from viral infection in febrile children
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Wang, Xinzhu, Nijman, Ruud, Camuzeaux, Stephane, Sands, Caroline, Jackson, Heather, Kaforou, Myrsini, Emonts, Marieke, Herberg, Jethro A, Maconochie, Ian, Carrol, Enitan D, Paulus, Stephane C, Zenz, Werner, Van der Flier, Michiel, de Groot, Ronald, Martinon-Torres, Federico, Schlapbach, Luregn J, Pollard, Andrew J, Fink, Colin, Kuijpers, Taco T, Anderson, Suzanne, Lewis, Matthew R, Levin, Michael, McClure, Myra, Gormley, Stuart, Hamilton, Shea, Hourmat, Bernardo, Hoggart, Clive, Sancho-Shimizu, Vanessa, Wright, Victoria, Abdulla, Amina, Agapow, Paul, Bartlett, Maeve, Bellos, Evangelos, Eleftherohorinou, Hariklia, Galassini, Rachel, Inwald, David, Mashbat, Meg, Menikou, Stefanie, Mustafa, Sobia, Nadel, Simon, Rahman, Rahmeen, Thakker, Clare, Coin, Lachlan MJ, Bokhand, S, Power, Sue, Barham, Heather, Pathan, N, Ridout, Jenna, White, Deborah, Thurston, Sarah, Faust, S, Patel, S, McCorkell, Jenni, Davies, P, Crate, Lindsey, Navarra, Helen, Carter, Stephanie, Ramaiah, R, Patel, Rekha, Tuffrey, Catherine, Gribbin, Andrew, McCready, Sharon, Peters, Mark, Hardy, Katie, Standing, Fran, O'Neill, Lauren, Abelake, Eugenia, Deep, Akash, Nsirim, Eniola, Willis, Louise, Young, Zoe, Royad, C, White, Sonia, Fortune, PM, Hudnott, Phil, Alvez Gonzalez, Fernando, Barral-Arca, Ruth, Cebey-Lopez, Miriam, Jose Curras-Tuala, Maria, Garcia, Natalia, Garcia Vicente, Luisa, Gomez-Carballa, Alberto, Gomez Rial, Jose, Grela Beiroa, Andrea, Justicia Grande, Antonio, Leborans Iglesias, Pilar, Martinez Santos, Alba Elena, MartinonTorres, Nazareth, Martinon Sanchez, Jose Maria, Morillo Gutierrez, Beatriz, Mosquera Perez, Belen, Obando Pacheco, Pablo, Pardo-Seco, Jacobo, Pischedda, Sara, RiveroCalle, Irene, Rodriguez-Tenreiro, Carmen, Redondo-Collazo, Lorenzo, Salas Ellacuriagal, Antonio, Seren Fernandez, Sonia, Porto Silva, Maria del Sol, Vega, Ana, Vilanova Trillo, Lucia, Salas, Antonio, Beatriz Reyes, Susana, Leon Leon, Maria Cruz, Navarro Mingorance, Alvaro, Gabaldo Barrios, Xavier, Onate Vergara, Eider, Concha Torre, Andres, Vivanco, Ana, Fernandez, Reyes, Gimenez Sanchez, Francisco, Sanchez Forte, Miguel, Rojo, Pablo, Ruiz Contreras, J, Palacios, Alba, Epalza Ibarrondo, Cristina, Fernandez Cooke, Elizabeth, Navarro, Marisa, Alvarez Alvarez, Cristina, Jose Lozano, Maria, Carreras, Eduardo, Brio Sanagustin, Sonia, Neth, Olaf, Martinez Padilla, Ma del Carmen, Prieto Tato, Luis Manuel, Guillen, Sara, Fernandez Silveira, Laura, Moreno, David, van Furth, AM Tutu, Boeddha, NP, Driessen, GJA, Emonts, M, Hazelzet, JA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, Philipp, Aebi, Christoph, Berger, Christoph, Giannoni, Eric, Stocker, Martin, Posfay-Barbe, Klara M, Heininger, Ulrich, Bernhard-Stirnemann, Sara, Niederer-Loher, Anita, Kahlert, Christian, Hasters, Paul, Relly, Christa, Baer, Walter, Frederick, Hannah, Jennings, Rebecca, Johnston, Joanne, Kenwright, Rhian, Pinnock, Elli, Agbeko, Rachel, Secka, Fatou, Bojang, Kalifa, Sarr, Isatou, Kebbeh, Ngange, Sey, Gibbi, Momodou, Saidy Khan, Cole, Fatoumata, Thomas, Gilleh, Antonio, Martin, Klobassa, Daniela S, Binder, Alexander, Schweintzger, Nina A, Sagmeister, Manfred, Baumgart, Hinrich, Baumgartner, Markus, Behrends, Uta, Biebl, Ariane, Birnbacher, Robert, Blanke, Jan-Gerd, Boelke, Carsten, Breuling, Kai, Brunner, Juergen, Buller, Maria, Dahlem, Peter, Dietrich, Beate, Eber, Ernst, Elias, Johannes, Emhofer, Josef, Etschmaier, Rosa, Farr, Sebastian, Girtler, Ylenia, Grigorow, Irina, Heimann, Konrad, Ihm, Ulrike, Jaros, Zdenek, Kalhoff, Hermann, Kaulfersch, Wilhelm, Kemen, Christoph, Klocker, Nina, Koester, Bernhard, Kohlmaier, Benno, Komini, Eleni, Kramer, Lydia, Neubert, Antje, Ortner, Daniel, Pescollderungg, Lydia, Pfurtscheller, Klaus, Reiter, Karl, Ristic, Goran, Roedl, Siegfried, Sellner, Andrea, Sonnleitner, Astrid, Sperl, Matthias, Stelzl, Wolfgang, Till, Holger, Trobisch, Andreas, Vierzig, Anne, Vogel, Ulrich, Weingarten, Christina, Welke, Stefanie, Wimmer, Andreas, Wintergerst, Uwe, Wueller, Daniel, Zaunschirm, Andrew, Ziuraite, Ieva, Zukovskaja, Veslava, Consortium, EUCLIDS, Sands, Caroline [0000-0002-3749-7941], Jackson, Heather [0000-0002-1054-9983], Kaforou, Myrsini [0000-0001-9878-4007], Paulus, Stephane C [0000-0002-0703-9114], Martinon-Torres, Federico [0000-0002-9023-581X], Apollo - University of Cambridge Repository, Pediatric surgery, AII - Infectious diseases, Internal medicine, Pathology, Psychiatry, Amsterdam Reproduction & Development (AR&D), Posfay Barbe, Klara, European Commission, National Institute for Health Research (UK), NIHR Biomedical Research Centre (UK), Medical Research Council (UK), Wellcome Trust, Pediatrics, Public Health, Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Neurology, Medical Microbiology and Infection Prevention, and Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE)
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Male ,0301 basic medicine ,ACCURACY ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,MENINGITIS ,Antibiotics ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,MathematicsofComputing_GENERAL ,lcsh:Medicine ,0601 Biochemistry and Cell Biology ,chemistry.chemical_compound ,0302 clinical medicine ,ComputingMethodologies_SYMBOLICANDALGEBRAICMANIPULATION ,Blood plasma ,030212 general & internal medicine ,Child ,lcsh:Science ,ddc:618 ,Multidisciplinary ,music.instrument ,TheoryofComputation_GENERAL ,Bacterial Infections ,Lipidome ,ddc ,Sphingomyelins ,3. Good health ,Cholesterol ,Virus Diseases ,Child, Preschool ,Female ,Adolescent ,medicine.drug_class ,Bilirubin ,Inositol Phosphates ,0299 Other Physical Sciences ,610 Medicine & health ,DIAGNOSIS ,Fever of Unknown Origin ,Article ,Virus ,Diagnosis, Differential ,03 medical and health sciences ,Lactosylceramide ,Journal Article ,medicine ,Metabolomics ,Humans ,General ,music ,business.industry ,lcsh:R ,Infant ,Lysophosphatidylcholines ,Diagnostic markers ,Omics ,EUCLIDS consortium ,030104 developmental biology ,chemistry ,Immunology ,lcsh:Q ,Software_PROGRAMMINGLANGUAGES ,business ,ddc:600 ,Biomarkers - Abstract
EUCLIDS consortium., Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The ‘omics’ approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics., This work was partially supported by the European Seventh Framework Programme for Research and Technological Development (FP7) under EUCLIDS Grant Agreement no. 279185. ICED: The Research was supported by the National Institute for Health Research Biomedical Research Centre based at Imperial College. This work was further supported by the Medical Research Council and National Institute for Health Research [grant number MC_PC_12025] through funding for the MRC-NIHR National Phenome Centre, infrastructure support was provided by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at Imperial NHS Healthcare Trust. MK acknowledges funding from the Wellcome Trust (Sir Henry Wellcome Fellowship grant 206508/Z/17/Z).
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- 2019
5. Identification of regulatory variants associated with genetic susceptibility to meningococcal disease
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Borghini, L, Png, E, Binder, A, Wright, VJ, Pinnock, E, de Groot, R, Hazelzet, J, Emonts, M, Van der Flier, M, Schlapbach, LJ, Anderson, S, Secka, F, Salas, A, Fink, C, Carrol, ED, Pollard, AJ, Coin, LJ, Kuijpers, TW, Martinon-Torres, F, Zenz, W, Levin, M, Hibberd, ML, Davila, S, Gormley, S, Hamilton, S, Herberg, J, Hourmat, B, Hoggart, C, Kaforou, M, Sancho-Shimizu, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Bokhandi, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Cratev, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, Martinon-Torres, N, Martinon Sanchez, JM, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, Rivero Calle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, van der Flier, M, Boeddha, NP, Driessen, GJA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Paulus, S, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Agbeko, R, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Saidykhan, M, Cole, F, Thomas, G, Antonio, M, Walcher, W, Geishofer, G, Klobassa, D, Martin, M, Pfurtscheller, K, Reiter, K, Roedl, S, Zobel, G, Zoehrer, B, Toepke, B, Fucik, P, Gabriel, M, Penzien, JM, Diab, G, Miething, R, Deeg, KH, Hammer, J, Varnholt, V, Schmidt, A, Bindl, L, Sillaber, U, Huemer, C, Meier, P, Simic-Schleicher, G, Markart, M, Pfau, E, Broede, H, Ausserer, B, Kalhoff, H, Arpe, V, Schweitzer-Krantz, S, Kasper, J-M, Loranth, K, Bittrich, HJ, Simma, B, Klinge, J, Fedlmaier, M, Weigand, N, Herting, E, Grube, R, Fusch, C, Gruber, A, Schimmel, U, Knaufer-Schiefer, S, Laessig, W, Hennenberger, A, von der Wense, A, Tillmann, R, Schwarick, J, Sitzmann, FC, Streif, W, Mueller, H, Kurnik, P, Groneck, P, Weiss, U, Groeblacher-Roth, H, Bensch, J, Moser, R, Schwarz, R, Lenz, K, Hofmann, T, Goepel, W, Schulz, D, Berger, T, Hauser, E, Foerster, KM, Peters, J, Nicolai, TH, Kumlien, B, Beckmann, R, Seitz, C, Hueseman, D, Schuermann, R, Ta, VH, Weikmann, E, Evert, W, Hautz, J, Seidenberg, J, Wocko, L, Luigs, P, Reiter, H-L, Quietzach, J, Koenig, M, Herrmann, J, Mitter, H, Seidler, E, Maak, B, Sperl, W, Zwiauer, K, Meissl, M, Koch, R, Cremer, M, Breuer, HA, Goerke, W, Nossal, R, Pernice, W, Brangenberg, R, Salzer, HR, Koch, H, Schaller, G, Paky, F, Strasser, F, Eitelberger, F, Sontheimer, D, Lischka, A, Kronberger, M, Dilch, A, Scheibenpflug, C, Bruckner, R, Mahler, K, Runge, K, Kunze, W, Schermann, P, Borghini, L, Png, E, Binder, A, Wright, VJ, Pinnock, E, de Groot, R, Hazelzet, J, Emonts, M, Van der Flier, M, Schlapbach, LJ, Anderson, S, Secka, F, Salas, A, Fink, C, Carrol, ED, Pollard, AJ, Coin, LJ, Kuijpers, TW, Martinon-Torres, F, Zenz, W, Levin, M, Hibberd, ML, Davila, S, Gormley, S, Hamilton, S, Herberg, J, Hourmat, B, Hoggart, C, Kaforou, M, Sancho-Shimizu, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Bokhandi, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Cratev, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, Martinon-Torres, N, Martinon Sanchez, JM, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, Rivero Calle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, van der Flier, M, Boeddha, NP, Driessen, GJA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Paulus, S, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Agbeko, R, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Saidykhan, M, Cole, F, Thomas, G, Antonio, M, Walcher, W, Geishofer, G, Klobassa, D, Martin, M, Pfurtscheller, K, Reiter, K, Roedl, S, Zobel, G, Zoehrer, B, Toepke, B, Fucik, P, Gabriel, M, Penzien, JM, Diab, G, Miething, R, Deeg, KH, Hammer, J, Varnholt, V, Schmidt, A, Bindl, L, Sillaber, U, Huemer, C, Meier, P, Simic-Schleicher, G, Markart, M, Pfau, E, Broede, H, Ausserer, B, Kalhoff, H, Arpe, V, Schweitzer-Krantz, S, Kasper, J-M, Loranth, K, Bittrich, HJ, Simma, B, Klinge, J, Fedlmaier, M, Weigand, N, Herting, E, Grube, R, Fusch, C, Gruber, A, Schimmel, U, Knaufer-Schiefer, S, Laessig, W, Hennenberger, A, von der Wense, A, Tillmann, R, Schwarick, J, Sitzmann, FC, Streif, W, Mueller, H, Kurnik, P, Groneck, P, Weiss, U, Groeblacher-Roth, H, Bensch, J, Moser, R, Schwarz, R, Lenz, K, Hofmann, T, Goepel, W, Schulz, D, Berger, T, Hauser, E, Foerster, KM, Peters, J, Nicolai, TH, Kumlien, B, Beckmann, R, Seitz, C, Hueseman, D, Schuermann, R, Ta, VH, Weikmann, E, Evert, W, Hautz, J, Seidenberg, J, Wocko, L, Luigs, P, Reiter, H-L, Quietzach, J, Koenig, M, Herrmann, J, Mitter, H, Seidler, E, Maak, B, Sperl, W, Zwiauer, K, Meissl, M, Koch, R, Cremer, M, Breuer, HA, Goerke, W, Nossal, R, Pernice, W, Brangenberg, R, Salzer, HR, Koch, H, Schaller, G, Paky, F, Strasser, F, Eitelberger, F, Sontheimer, D, Lischka, A, Kronberger, M, Dilch, A, Scheibenpflug, C, Bruckner, R, Mahler, K, Runge, K, Kunze, W, and Schermann, P
- Abstract
Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.
- Published
- 2019
6. Plasma lipid profiles discriminate bacterial from viral infection in febrile children
- Author
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Wang, X, Nijman, R, Camuzeaux, S, Sands, C, Jackson, H, Kaforou, M, Emonts, M, Herberg, JA, Maconochie, I, Carrol, ED, Paulus, SC, Zenz, W, Van der Flier, M, de Groot, R, Martinon-Torres, F, Schlapbach, LJ, Pollard, AJ, Fink, C, Kuijpers, TT, Anderson, S, Lewis, MR, Levin, M, McClure, M, Gormley, S, Hamilton, S, Hourmat, B, Hoggart, C, Sancho-Shimizu, V, Wright, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Coin, LMJ, Bokhand, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Crate, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, MartinonTorres, N, Martinon Sanchez, JM, Morillo Gutierrez, B, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, RiveroCalle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Salas Ellacuriagal, A, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Vilanova Trillo, L, Salas, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Epalza Ibarrondo, C, Fernandez Cooke, E, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, Boeddha, NP, Driessen, GJA, Hazelzet, JA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Pinnock, E, Agbeko, R, Secka, F, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Momodou, SK, Cole, F, Thomas, G, Antonio, M, Klobassa, DS, Binder, A, Schweintzger, NA, Sagmeister, M, Baumgart, H, Baumgartner, M, Behrends, U, Biebl, A, Birnbacher, R, Blanke, J-G, Boelke, C, Breuling, K, Brunner, J, Buller, M, Dahlem, P, Dietrich, B, Eber, E, Elias, J, Emhofer, J, Etschmaier, R, Farr, S, Girtler, Y, Grigorow, I, Heimann, K, Ihm, U, Jaros, Z, Kalhoff, H, Kaulfersch, W, Kemen, C, Klocker, N, Koester, B, Kohlmaier, B, Komini, E, Kramer, L, Neubert, A, Ortner, D, Pescollderungg, L, Pfurtscheller, K, Reiter, K, Ristic, G, Roedl, S, Sellner, A, Sonnleitner, A, Sperl, M, Stelzl, W, Till, H, Trobisch, A, Vierzig, A, Vogel, U, Weingarten, C, Welke, S, Wimmer, A, Wintergerst, U, Wueller, D, Zaunschirm, A, Ziuraite, I, Zukovskaja, V, Wang, X, Nijman, R, Camuzeaux, S, Sands, C, Jackson, H, Kaforou, M, Emonts, M, Herberg, JA, Maconochie, I, Carrol, ED, Paulus, SC, Zenz, W, Van der Flier, M, de Groot, R, Martinon-Torres, F, Schlapbach, LJ, Pollard, AJ, Fink, C, Kuijpers, TT, Anderson, S, Lewis, MR, Levin, M, McClure, M, Gormley, S, Hamilton, S, Hourmat, B, Hoggart, C, Sancho-Shimizu, V, Wright, V, Abdulla, A, Agapow, P, Bartlett, M, Bellos, E, Eleftherohorinou, H, Galassini, R, Inwald, D, Mashbat, M, Menikou, S, Mustafa, S, Nadel, S, Rahman, R, Thakker, C, Coin, LMJ, Bokhand, S, Power, S, Barham, H, Pathan, N, Ridout, J, White, D, Thurston, S, Faust, S, Patel, S, McCorkell, J, Davies, P, Crate, L, Navarra, H, Carter, S, Ramaiah, R, Patel, R, Tuffrey, C, Gribbin, A, McCready, S, Peters, M, Hardy, K, Standing, F, O'Neill, L, Abelake, E, Deep, A, Nsirim, E, Willis, L, Young, Z, Royad, C, White, S, Fortune, PM, Hudnott, P, Alvez Gonzalez, F, Barral-Arca, R, Cebey-Lopez, M, Jose Curras-Tuala, M, Garcia, N, Garcia Vicente, L, Gomez-Carballa, A, Gomez Rial, J, Grela Beiroa, A, Justicia Grande, A, Leborans Iglesias, P, Martinez Santos, AE, MartinonTorres, N, Martinon Sanchez, JM, Morillo Gutierrez, B, Mosquera Perez, B, Obando Pacheco, P, Pardo-Seco, J, Pischedda, S, RiveroCalle, I, Rodriguez-Tenreiro, C, Redondo-Collazo, L, Salas Ellacuriagal, A, Seren Fernandez, S, Porto Silva, MDS, Vega, A, Vilanova Trillo, L, Salas, A, Beatriz Reyes, S, Leon Leon, MC, Navarro Mingorance, A, Gabaldo Barrios, X, Onate Vergara, E, Concha Torre, A, Vivanco, A, Fernandez, R, Gimenez Sanchez, F, Sanchez Forte, M, Rojo, P, Ruiz Contreras, J, Palacios, A, Epalza Ibarrondo, C, Fernandez Cooke, E, Navarro, M, Alvarez Alvarez, C, Jose Lozano, M, Carreras, E, Brio Sanagustin, S, Neth, O, Martinez Padilla, MDC, Prieto Tato, LM, Guillen, S, Fernandez Silveira, L, Moreno, D, van Furth, AMT, Boeddha, NP, Driessen, GJA, Hazelzet, JA, Pajkrt, D, Sanders, EAM, van de Beek, D, van der Ende, A, Philipsen, HLA, Adeel, AOA, Breukels, MA, Brinkman, DMC, de Korte, CCMM, de Vries, E, de Waal, WJ, Dekkers, R, Dings-Lammertink, A, Doedens, RA, Donker, AE, Dousma, M, Faber, TE, Gerrits, GPJM, Gerver, JAM, Heidema, J, Homan-van der Veen, J, Jacobs, MAM, Jansen, NJG, Kawczynski, P, Klucovska, K, Kneyber, MCJ, Koopman-Keemink, Y, Langenhorst, VJ, Leusink, J, Loza, BF, Merth, IT, Miedema, CJ, Neeleman, C, Noordzij, JG, Obihara, CC, van Overbeek-van Gils, ALT, Poortman, GH, Potgieter, ST, Potjewijd, J, Rosias, PPR, Sprong, T, ten Tussher, GW, Thio, BJ, Tramper-Stranders, GA, van Deuren, M, van der Meer, H, van Kuppevelt, AJM, van Wermeskerken, AM, Verwijs, WA, Wolfs, TFW, Agyeman, P, Aebi, C, Berger, C, Giannoni, E, Stocker, M, Posfay-Barbe, KM, Heininger, U, Bernhard-Stirnemann, S, Niederer-Loher, A, Kahlert, C, Hasters, P, Relly, C, Baer, W, Frederick, H, Jennings, R, Johnston, J, Kenwright, R, Pinnock, E, Agbeko, R, Secka, F, Bojang, K, Sarr, I, Kebbeh, N, Sey, G, Momodou, SK, Cole, F, Thomas, G, Antonio, M, Klobassa, DS, Binder, A, Schweintzger, NA, Sagmeister, M, Baumgart, H, Baumgartner, M, Behrends, U, Biebl, A, Birnbacher, R, Blanke, J-G, Boelke, C, Breuling, K, Brunner, J, Buller, M, Dahlem, P, Dietrich, B, Eber, E, Elias, J, Emhofer, J, Etschmaier, R, Farr, S, Girtler, Y, Grigorow, I, Heimann, K, Ihm, U, Jaros, Z, Kalhoff, H, Kaulfersch, W, Kemen, C, Klocker, N, Koester, B, Kohlmaier, B, Komini, E, Kramer, L, Neubert, A, Ortner, D, Pescollderungg, L, Pfurtscheller, K, Reiter, K, Ristic, G, Roedl, S, Sellner, A, Sonnleitner, A, Sperl, M, Stelzl, W, Till, H, Trobisch, A, Vierzig, A, Vogel, U, Weingarten, C, Welke, S, Wimmer, A, Wintergerst, U, Wueller, D, Zaunschirm, A, Ziuraite, I, and Zukovskaja, V
- Abstract
Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics.
- Published
- 2019
7. HIV Monitoring Report 2018 : Chapter 5: Distinct populations: Children living with HIV in the Netherlands
- Author
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Smit, Colette, Wolfs, TFW, and van Rossum, Annemarie M. C.
- Published
- 2018
8. HIV Monitoring Report 2018 : Chapter 5: Distinct populations: Children living with HIV in the Netherlands
- Author
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Ebeling, Sally H., Smit, Colette, Wolfs, TFW, van Rossum, Annemarie M. C., Ebeling, Sally H., Smit, Colette, Wolfs, TFW, and van Rossum, Annemarie M. C.
- Published
- 2018
9. HIV Monitoring Report 2018: Chapter 5: Distinct populations: Children living with HIV in the Netherlands
- Author
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Infectieziekten patientenzorg, Child Health, Infection & Immunity, Ebeling, Sally H., Smit, Colette, Wolfs, TFW, van Rossum, Annemarie M. C., Infectieziekten patientenzorg, Child Health, Infection & Immunity, Ebeling, Sally H., Smit, Colette, Wolfs, TFW, and van Rossum, Annemarie M. C.
- Published
- 2018
10. Ontwikkelingen op adoptiegebied in Nederland
- Author
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Wolfs, TFW and Pelleboer, Rolf A.A.
- Subjects
special needs-kinderen ,adoptie ,medische evaluatie buitenlandsadoptiekind - Abstract
Het adopteren van een buitenlands kind is een zorgvuldige, langdurige en kostbare procedure waarbij veel instanties zijn betrokken. Het aanbod van adoptiekinderen is de afgelopen jaren aanzienlijk afgenomen. Bovendien heeft een steeds groter deel van de adoptiekinderen een extra zorgbehoefte (special needs). In 2015 was dit zelfs 85%. Medische evaluatie van adoptiekinderen blijft noodzakelijk, waarbij rekening moet worden gehouden met het land van herkomst.
- Published
- 2017
11. HIV Monitoring Report : Human immunodeficiency virus (HIV) infection in the Netherlands
- Author
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Smit, Colette, Wolfs, TFW, Rossum, Annemarie van, Smit, Colette, Wolfs, TFW, and Rossum, Annemarie van
- Published
- 2017
12. HIV Monitoring Report: Human immunodeficiency virus (HIV) infection in the Netherlands
- Author
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Infectieziekten patientenzorg, Child Health, Infection & Immunity, Smit, Colette, Wolfs, TFW, Rossum, Annemarie van, Infectieziekten patientenzorg, Child Health, Infection & Immunity, Smit, Colette, Wolfs, TFW, and Rossum, Annemarie van
- Published
- 2017
13. Ontwikkelingen op adoptiegebied in Nederland
- Author
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Infectieziekten patientenzorg, Child Health, Infection & Immunity, Wolfs, TFW, Pelleboer, Rolf A.A., Infectieziekten patientenzorg, Child Health, Infection & Immunity, Wolfs, TFW, and Pelleboer, Rolf A.A.
- Published
- 2017
14. Infecties van de onderste luchtwegen en tuberculose
- Author
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Verbon, Annelies, Wolfs, TFW, Prins, JM, Hoepelman, AIM, Kroes, ACM, Sauerwein, RW, Verbrugh, HA, Nouwen, JL, and Medical Microbiology & Infectious Diseases
- Published
- 2016
15. Impact of treatment reduction for childhood acute lymphoblastic leukemia on serum immunoglobulins ans antibodies against vaccine-preventable diseases
- Author
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van Tilburg, CM, Bierings, MB (Marc), Berbers, GAM, Wolfs, TFW, Pieters, Rob, Bloem, AC, Sanders, EAM, Clinical Chemistry, and Pediatrics
- Subjects
SDG 3 - Good Health and Well-being - Published
- 2012
16. Impact of reduced chemotherapy treatment for good ristk childhood acute lymphoblastic leukaemia on infectious morbidity
- Author
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van Tilburg, CM, Sanders, EAM, Nibbelke, EE, Pieters, Rob, Revesz, T, Westers, P, Wolfs, TFW, Bierings, M, and Pediatrics
- Published
- 2011
17. Infectieziekten
- Author
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Hartwig, Nico, Wolfs, TFW, and Pediatrics
- Published
- 2011
18. Maag-darmstelsel en buikholte
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Wolfs, TFW, de Laat, P.C.J., van Furth, A.M., Hartwig, N.G., and Pediatrics
- Published
- 2008
19. Bacteremic complications of intravascular catheters colonized with Staphylococcus aureus
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Ekkelenkamp, MB, van der Bruggen, T, van de Vijver, David, Wolfs, TFW, Bonten, MJM, and Virology
- Subjects
bacterial infections and mycoses - Abstract
Patients with Staphylococcus aureus colonization of an intravascular catheter but without demonstrated bacteremia within 24 h after intravascular catheter removal had a 24% (12 of 49 patients) chance of subsequent S. aureus bacteremia if they did not receive immediate antistaphylococcal antibiotics. Treatment within 24 h after intravascular catheter removal led to a 83% reduction in the incidence of subsequent bacteremia.
- Published
- 2008
20. Advies ten aanzien van de behandeling met dexamethason bij kinderen met verdenking op bacteriële meningitis
- Author
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van Furth, AM, Wolfs, TFW, Hartwig, Nico, and Pediatrics
- Published
- 2005
21. PO-0557 Neuro-imaging In Infants With Congenital Cytomegalovirus Infection: Relation With Time Of Onset Of Infection During Pregnancy
- Author
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Oosterom, N, primary, Nijman, J, additional, Gunkel, J, additional, Wolfs, TFW, additional, Groenendaal, F, additional, Verboon-Maciolek, MA, additional, and de Vries, LS, additional
- Published
- 2014
- Full Text
- View/download PDF
22. Pneumococcal immune adherence to human erythrocytes
- Author
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Hament, JM, van Dijk, H, Fleer, A, Aerts, PC, Schoenmakers, M, de Snoo, MW, Dekker, BHAT, Kimpen, JLL, Wolfs, TFW, Molecular and Computational Toxicology, AIMMS, and University of Groningen
- Subjects
CLEARANCE ,RECEPTOR ,INVIVO ,bacterial sepsis ,CIRCULATION ,chemical and pharmacologic phenomena ,immune adherence ,PRIMATES ,CHIMPANZEES ,factor I ,Streptococcus pneumoniae ,BINDING ,COMPLEXES ,ASSAY ,complement ,mannose-binding lectin ,adherence ,pneumococcus - Abstract
Background Human red blood cells bind various C3b-coated microorganisms via their C3b/CR1 receptor, a phenomenon referred to as immune adherence. The aim of the present study was to measure pneumococcal adherence to human red blood cells by flow cytometry and to study kinetic aspects of this binding. Materials and methods We quantified pneumococcal adherence to human erythrocytes by FACS analysis and tested the involvement of antibodies and complement activation in this process. Results Pneumococci are able to bind to human red blood cells in the presence of human serum. Coating with C3b/C4b appeared obligatory for pneumococcal adherence to red blood cells. The ligand on erythrocytes was confirmed to be complement receptor 1. Kinetic studies showed that innate (mannose-binding lectin) and specific immune factors (IgG antibodies) contributed to the binding of C3b-coated pneumococci to human erythrocytes. After initial binding, serum-derived factor I was found to induce bacterial detachment from the erythrocyte. Conclusions Pneumococci are able to adhere to red blood cells. Both the classical and lectin complement pathways are important for optimal C3b-coating of pneumococci for immune adherence. Bound pneumococci are detached from red blood cells by factor I. These findings are in line with the hypothesis of immune adherence in which human erythrocytes are able to bind pneumococci and target the bacteria to the reticulo-endothelial system in the spleen.
- Published
- 2003
23. Pharmacokinetics of nelfinavir in children: influencing factors and dose implications
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Bergshoeff, AS, Fraaij, PLA, van Rossum, AMC, Wolfs, TFW, Geelen, SPM, de Groot, R, Burger, DM, and Pediatrics
- Subjects
VIROLOGICAL RESPONSE ,TRIPLE THERAPY ,EFAVIRENZ ,PLASMA-CONCENTRATIONS ,INFECTED CHILDREN ,ANTIRETROVIRAL THERAPY ,virus diseases ,P-GLYCOPROTEIN ,HIV-PROTEASE INHIBITORS ,IMMUNODEFICIENCY-VIRUS TYPE-1 ,REVERSE-TRANSCRIPTASE INHIBITORS - Abstract
Objectives: The study describes the pharmacokineties (PK) of the protease inhibitor nelfinavir and its active metabolite M8 in children and evaluates the influence of patient-related factors on nelfinavir plasma levels. Methods: HIV-1-infected children treated with nelfinavir every 8 h (q8h) were eligible for inclusion in this retrospective study. 0-8 h intensive plasma pharmacokinetics (PK) sampling was performed at steady state. Nelfinavir maximum concentration (C-max), area under the plasma concentration-time curve in 0-8 h (AUC(0-8)), trough level at the 8 h time point (C-8) and relative apparent oral clearance (Cl*F/kg) were calculated. Results: Twenty-four children (median age: 4.5 years, median nelfinavir dose: 28 mg/kg q8h) were included. Nelfinavir PK were highly variable: 10/24 children had an AUC(0-8) below the value of 12.5 mg/l*h, which has previously been associated with an increased virological failure rate in children. With children aged 0.69 mg/l predicted an AUC(0-8) >12.5 mg/l*h with 71% sensitivity and 80% specificity. Dose of nelfinavir per body surface area was a better predictor of AUC(0-8) than dose per body weight. Conclusion: Nelfinavir PK show high interindividual variability in children. Children
- Published
- 2003
24. Rat-to-human transmission of cowpox infection
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Wolfs, TFW, Wagenaar, JA, Niesters, HGM, Osterhaus, Ab, and Virology
- Published
- 2002
25. Reductie van verticale transmissie door perinatale profylaxe bij aan HIV-1 geëxposeerde in Nederland geboren kinderen in de periode van 1995-1999
- Author
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van Rossum, Annemarie, Kuiper, IE, Rodrigues Pereira, R, Scherpbier, HJ, Wolfs, TFW, Groot, Ronald, Pediatrics, and Erasmus MC other
- Subjects
SDG 3 - Good Health and Well-being - Published
- 2002
26. Respiratory viral infection predisposing for bacterial disease: a concise review
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Hament, JM, Kimpen, JLL, Fleer, A, Wolfs, TFW, and University of Groningen
- Subjects
ACUTE OTITIS-MEDIA ,viruses ,SYNCYTIAL VIRUS ,bacterial superinfection ,STREPTOCOCCUS-PNEUMONIAE ,viral glycoprotein ,HAEMOPHILUS-INFLUENZAE ,INFLUENZA-A VIRUS ,virus-induced receptor ,NEISSERIA-MENINGITIDIS ,ADHERENCE ,INFANT-DEATH-SYNDROME ,bacterial adhesin ,bacterial adherence ,HUMAN EPITHELIAL-CELLS ,STAPHYLOCOCCUS-AUREUS - Abstract
Although bacterial superinfection in viral respiratory disease is a clinically well documented phenomenon, the pathogenic mechanisms are still poorly understood. Recent studies have revealed some of the mechanisms involved. Physical damage to respiratory cells as a result of viral infection may lead to opportunistic adherence of bacteria. Enhanced bacterial adherence by specific mechanisms has been documented for respiratory cells infected With influenza A virus, respiratory syncytial virus and adenovirus in both in vitro and in vivo models. To date, results of various experimental studies indicate that different mechanisms for increased bacterial adherence induced by viruses are operating for specific viral-bacterial combinations. In the present review, a number of key findings obtained during the past two decades is presented and discussed. (C) 1999 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.
- Published
- 1999
27. Randomised double blind placebo controlled trial of prednisolone in children admitted to hospital with respiratory syncytial virus bronchiolitis
- Author
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van Woensel, JBM, Wolfs, TFW, vanAalderen, WMC, Brand, PLP, Kimpen, JLL, Faculteit Medische Wetenschappen/UMCG, and Groningen Research Institute for Asthma and COPD (GRIAC)
- Subjects
INTERFERON ,treatment ,respiratory syncytial virus ,INFECTION ,INFANTS ,ASTHMA ,bronchiolitis ,EMERGENCY ,corticosteroids ,TRACT - Abstract
Background - Experimental and clinical evidence suggests that respiratory syncytial virus (RSV) bronchiolitis is an immune mediated disease. Corticosteroids might therefore be effective in the treatment of RSV bronchiolitis. Methods - A randomised double blind trial was conducted in children up to two years of age admitted to hospital with RSV bronchiolitis to compare prednisolone (1 mg/kg/day orally for seven days) with placebo. Variables used for the efficacy analysis were a daily symptom score and the length of time in hospital in the non-ventilated patients, and the duration of mechanical ventilation and the length of time in hospital in the ventilated patients. Results - Fifty four patients were included in the trial, 40 of whom were non-ventilated (20 in each group) and 14 were ventilated (seven in each group). During the first three days of treatment the symptom score decreased significantly faster in the prednisolone group than in the placebo group (mean (SE) decrease -1.2 (0.2) points/day versus -0.6 (0,2) points/day; mean (95% confidence interval (CI)) for difference = -0.6 (-0.1 to -1.2); p = 0.02). The mean duration of hospital stay of all 40 non-ventilated patients was not significantly different between the two groups. In the ventilated patients the duration of mechanical ventilation was not significantly different, but the length of time in hospital was six days shorter in the prednisolone group than in the placebo group (mean (SE) 11.0 (0.7) versus 17.0 (2.0) days; mean (95% CI) difference = 7.0 (1.8 to 10.2) days; p
- Published
- 1997
28. Treatment with highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children is associated with a sustained effect on growth
- Author
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Verweel, Gwenda, van Rossum, Annemarie, Hartwig, Nico, Wolfs, TFW, Scherpbier, HJ, Groot, Ronald, Verweel, Gwenda, van Rossum, Annemarie, Hartwig, Nico, Wolfs, TFW, Scherpbier, HJ, and Groot, Ronald
- Published
- 2002
29. Prevalence and impact of respiratory viral infections in young children with cystic fibrosis: prospective cohort study.
- Author
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van Ewijk BE, van der Zalm MM, Wolfs TFW, Fleer A, Kimpen JLL, Wilbrink B, and van der Ent CK
- Published
- 2008
- Full Text
- View/download PDF
30. Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America
- Author
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Costagliola, D., Dabis, F., Monforte, Ad, Wolf, F., Egger, M., Fatkenheuer, G., Gill, J., Hogg, R., Justice, A., Ledergerber, B., Lundgren, J., May, M., Phillips, A., Reiss, P., Sabin, C., Staszewski, S., Sterne, J., Weller, I., Beckthold, B., Yip, B., Dauer, B., Fusco, J., Grabar, S., Lanoy, E., Junghans, C., Lavignolle, V., Leth, F., Pereira, E., Pezzotti, P., Schmeisser, N., Billaud, E., Boue, F., Duval, X., Duvivier, C., Enel, P., Fournier, S., Gasnault, J., Gaud, C., Gilquin, J., Khuong, Ma, Lang, Jm, Mary-Krause, M., Matheron, S., Meyohas, Mc, Pialoux, G., Poizot-Martin, I., Pradier, C., Rouveix, E., Salmon-Ceron, D., Sobel, A., Tattevin, P., Tissot-Dupont, H., Yasdanpanah, Y., Aronica, E., Tirard-Fleury, V., Tortay, I., Abgrall, S., Guiguet, M., Leneman, H., Lievre, L., Potard, V., Saidi, S., Vilde, Jl, Leport, C., Yeni, P., Bouvet, E., Gaudebout, C., Crickx, B., Picard-Dahan, C., Weiss, L., Tisne-Dessus, D., Sicard, D., Salmon, D., Auperin, I., Viard, Jp, Roudiere, L., Delfraissy, Jf, Goujard, C., Lesprit, P., Jung, C., Meynard, Jl, Picard, O., Desplanque, N., Cadranel, J., Mayaud, C., Rozenbaum, W., Bricaire, F., Katlama, C., Herson, S., Simon, A., Decazes, Jm, Molina, Jm, Clauvel, Jp, Gerard, L., Widal, Ghlf, Sellier, P., Diemer, M., Dupont, C., Berthe, H., Saiag, P., Mortier, L., Mortier, E., Chandemerle, C., Truchis, P., Bentata, M., Honore, P., Tassi, S., Jeantils, V., Mechali, D., Taverne, B., Laurichesse, H., Gourdon, F., Lucht, F., Fresard, A., Faller, Jp, Eglinger, P., Bazin, C., Verdon, R., Peyramond, D., Boibieux, A., Touraine, Jl, Livrozet, Jm, Trepo, C., Cotte, L., Ravaux, I., Delmont, Jp, Moreau, J., Gastaut, Ja, Soubeyrand, J., Retornaz, F., Blanc, Pa, Allegre, T., Galinier, A., Ruiz, Jm, Lepeu, G., Granet-Brunello, P., Pelissier, L., Esterni, Jp, Nezri, M., Cohen-Valensi, R., Laffeuillade, A., Chadapaud, S., Reynes, J., May, T., Rabaud, C., Raffi, F., Pugliese, P., Michelet, C., Arvieux, C., Caron, F., Borsa-Lebas, F., Fraisse, P., Massip, P., Cuzin, L., Arlet-Suau, E., Legrand, Mft, Sobesky, M., Pradinaud, R., Guyon, F., Contant, M., Montroni, M., Scalise, G., Braschi, Mc, Aviano, Ar, Tirelli, U., Cinelli, R., Pastore, G., Ladisa, N., Minafra, G., Suter, F., Arici, C., Chiodo, F., Colangeli, V., Fiorini, C., Coronado, O., Carosi, G., Cadeo, Gp, Torti, C., Minardi, C., Bertelli, D., Rizzardini, G., Melzi, S., Manconi, Pe, Catanzaro, Pp, Cosco, L., Scerbo, A., Vecchiet, J., D Alessandro, M., Santoro, D., Pusterla, L., Carnevale, G., Citterio, P., Vigano, P., Mena, M., Ghinelli, F., Sighinolfi, L., Leoncini, F., Mazzotta, F., Pozzi, M., Lo Caputo, S., Angarano, G., Grisorio, B., Saracino, A., Ferrara, S., Grima, P., Tundo, P., Pagano, G., Cassola, G., Alessandrini, A., Piscopo, R., Toti, M., Chigiotti, S., Soscia, F., Tacconi, L., Orani, A., Perini, P., Scasso, A., Vincenti, A., Chiodera, F., Castelli, P., Scalzini, A., Palvarini, L., Moroni, M., Lazzarin, A., Cargnel, A., Vigevani, Gm, Caggese, L., Repetto, D., Galli, A., Merli, S., Pastecchia, C., Moioli, Mc, Esposito, R., Mussini, C., Abrescia, N., Chirianni, A., Izzo, Cm, Piazza, M., Marco, M., Viglietti, R., Manzillo, E., Nappa, S., Colomba, A., Abbadessa, V., Prestileo, T., Mancuso, S., Ferrari, C., Pizzaferri, P., Filice, G., Minoli, L., Bruno, R., Novati, S., Baldelli, F., Tinca, M., Petrelli, E., Cioppi, A., Alberici, F., Ruggieri, A., Menichetti, F., Martinelli, C., Stefano, C., La Gala, A., Ballardini, G., Rizzo, E., Magnani, G., Ursitti, Ma, Arlotti, M., Ortolani, P., Cauda, R., Dianzani, F., Ippolito, G., Antinori, A., Antonucci, G., D Elia, S., Narciso, P., Petrosillo, N., Vullo, V., Luca, A., Bacarelli, A., Zaccarelli, M., Acinapura, R., Longis, P., Brandi, A., Trotta, Mp, Noto, P., Lichtner, M., Capobianchi, MR, Carletti, F., Girardi, E., Rezza, G., Mura, Ms, Mannazzu, M., Caramello, P., Di Perri, G., Soranzo, Ml, Orofino, Gc, Arnaudo, I., Bonasso, M., Grossi, Pa, Basilico, C., Poggio, A., Bottari, G., Raise, E., Ebo, F., Lalla, F., Tositti, G., Resta, F., Loso, K., Lepri, Ac, Battegay, M., Bernasconi, E., Boni, J., Bucher, H., Burgisser, P., Cattacin, S., Cavassini, M., Dubs, R., Elzi, L., Erb, P., Fantelli, K., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Gorgievski, M., Hirschel, B., Kaiser, L., Kind, C., Klimkait, T., Lauper, U., Opravil, M., Paccaud, F., Pantaleo, G., Perrin, L., Piffaretti, Jc, Rickenbach, M., Rudin, C., Schmid, P., Schupbach, J., Speck, R., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Bronsveld, W., Hillebrand-Haverkort, Me, Prins, Jm, Bos, Jc, Schattenkerk, Jkme, Geerlings, Se, Godfried, Mh, Lange, Jma, Leth, Fc, Lowe, Sh, Meer, Jtm, Nellen, Fjb, Pogany, K., Poll, T., Ruys, Ta, Sankatsing, S., Steingrover, R., Twillert, G., Valk, M., Vonderen, Mga, Vrouenraets, Sme, Vugt, M., Wit, Fwmn, Kuijpers, Tw, Pajkrt, D., Scherpbier, Hj, Eeden, A., Ten Veen, Jh, Dam, Ps, Roos, Jc, Brinkman, K., Frissen, Phj, Weigel, Hm, Mulder, Jw, Gorp, Ecm, Meenhorst, Pl, Mairuhu, Ata, Ziekenhuis, S., Veenstra, J., Danner, Sa, Agtmael, Ma, Claessen, Fap, Perenboom, Rm, Rijkeboer, A., Vonderen, M., Richter, C., Berg, J., Leusen, R., Vriesendorp, R., Jeurissen, Fjf, Kauffmann, Rh, Koger, Elw, Bravenboer, B., Ten Napel, Chh, Kootstra, Gj, Sprenger, Hg, Miesen, Wmaj, Doedens, R., Scholvinck, Eh, Ten Kate, Rw, Houte, Dpf, Polee, M., Kroon, Fp, van den Broek, Dissel, Jt, Schippers, Ef, Schreij, G., Geest, Sv, Verbon, A., Koopmans, Pp, Keuter, M., Post, F., Ven, Ajam, Ende, Me, Gyssens, Ic, Feltz, M., Den Hollander, Jg, Marie, S., Nouwen, Jl, Rijnders, Bja, Vries, Tems, Driessen, G., Groot, R., Hartwig, N., Juttmann, Jr, Heul, C., Kasteren, Mee, Schneider, Mme, Bonten, Mjm, Borleffs, Jcc, Ellerbroek, Pm, Hoepelman, Im, Jaspers, Cajj, Schouten, I., Schurink, Cam, Geelen, Spm, Wolfs, Tfw, Blok, Wl, Tanis, Aa, Groeneveld, Php, Klinieken-Zwolle, I., Back, Nkt, Bakker, Meg, Berkhout, B., Jurriaans, S., Cuijpers, T., Rietra, Pjgm, Roozendaal, Kj, Pauw, W., Zanten, Ap, Blomberg, Bme, Savelkoul, P., Swanink, Cma, Franck, Pfh, Lampe, As, Hendriks, R., Schirm, J., Veenendaal, D., Storm, H., Weel, J., Zeijl, H., Kroes, Acm, Claas, Hcj, Bruggeman, Camva, Goossens, Vj, Galama, Jmd, Melchers, Wjg, Poort, Yag, Doornum, Gjj, Niesters, Mg, Osterhaus, Adme, Schutten, M., Buiting, Agm, Swaans, Cam, Boucher, Cab, Boel, E., Jansz, Af, Losso, M., Duran, A., Vetter, N., Karpov, I., Vassilenko, A., Clumeck, N., Wit, S., Poll, B., Colebunders, R., Machala, L., Rozsypal, H., Dalibor Sedlacek, Nielsen, J., Benfield, T., Kirk, O., Gerstoft, J., Katzenstein, T., Hansen, Abe, Skinhoj, P., Pedersen, C., Zilmer, K., Girard, Pm, Saint-Marc, T., Vanhems, P., Dietrich, M., Manegold, C., Lunzen, J., Stellbrink, Hj, Bickel, M., Goebel, Fd, Rockstroh, J., Schmidt, R., Kosmidis, J., Gargalianos, P., Sambatakou, H., Perdios, J., Panos, G., Filandras, A., Karabatsaki, E., Banhegyi, D., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., Hassoun, G., Sthoeger, Z., Maayan, S., Chiesi, A., Borghi, R., Pristera, R., Gabbuti, A., Montesarchio, E., Iacomi, F., Finazzi, R., Viksna, L., Chaplinskas, S., Hemmer, R., Staub, T., Bruun, J., Maeland, A., Ormaasen, V., Knysz, B., Gasiorowski, J., Horban, A., Prokopowicz, D., Wiercinska-Drapalo, A., Boron-Kaczmarska, A., Pynka, M., Beniowski, M., Mularska, E., Trocha, H., Antunes, F., Valadas, E., Mansinho, K., Matez, F., Duiculescu, D., Babes, V., Streinu-Cercel, A., Vinogradova, E., Rakhmanova, A., Jevtovic, D., Mokras, M., Stanekova, D., Gonzalez-Lahoz, J., Sanchez-Conde, M., Garcia-Benayas, T., Martin-Carbonero, L., Soriano, V., Clotet, B., Jou, A., Conejero, J., Tural, C., Gatell, Jm, Miro, Jm, Blaxhult, A., Karlsson, A., Pehrson, P., Soravia-Dunand, V., Kravchenko, E., Chentsova, N., Barton, S., Johnson, Am, Mercey, D., Johnson, Ma, Mocroft, A., Murphy, M., Weber, J., Scullard, G., Fisher, M., Brettle, R., Loveday, C., Gatell, J., Johnson, A., Vella, S., Gjorup, I., Friis-Moeller, N., Cozzi-Lepri, A., Bannister, W., Mollerup, D., Podlevkareva, D., Olsen, Ch, Kjaer, J., Raffanti, S., Dieterch, D., Becker, S., Scarsella, A., Fusco, G., Most, B., Balu, R., Rana, R., Beckerman, R., Ising, T., Irek, R., Johnson, B., Hirani, A., Dejesus, E., Pierone, G., Lackey, P., Irek, C., Burdick, J., Leon, S., Arch, J., Helm, Eb, Carlebach, A., Muller, A., Haberl, A., Nisius, G., Lennemann, T., Rottmann, C., Wolf, T., Stephan, C., Mosch, M., Gute, P., Locher, L., Lutz, T., Klauke, S., Knecht, G., Doerr, Hw, Sturmer, M., Hentig, N., Jennings, B., Beylot, J., Chene, G., Dupon, M., Longy-Boursier, M., Pellegrin, Jl, Ragnaud, Jm, Salamon, R., Thiebaut, R., Lewden, C., Lawson-Ayayi, S., Mercie, P., Moreau, Jf, Moriat, P., Bernard, N., Lacoste, D., Malvy, D., Neau, D., Blaizeau, Mj, Decoin, M., Delveaux, S., Hannapier, C., Labarrere, S., Lavignolle-Aurillac, V., Uwamaliya-Nziyumvira, B., Palmer, G., Touchard, D., Balestre, E., Alioum, A., Jacqmin-Gadda, H., Morlat, P., Bonarek, M., Bonnet, F., Coadou, B., Gellie, P., Nouts, C., Bocquentin, F., Dutronc, H., Lafarie, S., Aslan, A., Pistonne, T., Thibaut, P., Vatan, R., Chambon, D., La Taille, C., Cazorla, C., Ocho, A., Castera, L., Fleury, H., Lafon, Me, Masquelier, B., Pellegrin, I., Breilh, D., Blanco, P., Loste, P., Caunegre, L., Bonnal, F., Farbos, S., Ferrand, M., Ceccaldi, J., Tchamgoue, S., Witte, S., Buy, E., Alexander, C., Barrios, R., Braitstein, P., Brumme, Z., Chan, K., Cote, H., Gataric, N., Geller, J., Guillemi, S., Harrigan, Harris, M., Joy, R., Levy, A., Montaner, J., Montessori, V., Palepu, A., Phillips, E., Phillips, P., Press, N., Tyndall, M., Wood, E., Ballinger, J., Bhagani, S., Breen, R., Byrne, P., Carroll, A., Cropley, I., Cuthbertson, Z., Drinkwater, T., Fernandez, T., Geretti, Am, Murphy, G., Ivens, D., Johnson, M., Kinloch-De Loes, S., Lipman, M., Madge, S., Prinz, B., Bell, Dr, Shah, S., Swaden, L., Tyrer, M., Youle, M., Chaloner, C., Gumley, H., Holloway, J., Puradiredja, D., Sweeney, J., Tsintas, R., Bansi, L., Fox, Z., Lampe, F., Smith, C., Amoah, E., Clewley, G., Dann, L., Gregory, B., Jani, I., Janossy, G., Kahan, M., Thomas, M., Gill, Mj, Read, R., Schmeisser, V., Voigt, K., Wasmuth, Jc, Wohrmann, A., and Antiretroviral Therapy Cohort Coll
31. Central Venous Catheter-related Bloodstream Infections Caused by Enterobacterales in Pediatric Oncology Patients: Catheter Salvage or Removal.
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van den Bosch CH, Kops AL, Loeffen YGT, van der Steeg AFW, van de Wetering MD, Fiocco MF, Ekkelenkamp MB, and Wolfs TFW
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- Child, Humans, Retrospective Studies, Anti-Bacterial Agents therapeutic use, Central Venous Catheters adverse effects, Catheterization, Central Venous adverse effects, Sepsis epidemiology, Neoplasms complications, Neoplasms therapy, Catheter-Related Infections drug therapy, Catheter-Related Infections epidemiology, Catheter-Related Infections complications
- Abstract
Background: The aim was to determine whether salvage treatment with systemic antibiotics is a safe and effective strategy for Enterobacterales bloodstream infections (BSI) in pediatric oncology patients with a central venous catheter (CVC)., Methods: A retrospective study was performed on oncology and stem cell recipient patients with a CVC and blood culture with Enterobacterales , at the Princess Máxima Centre for Pediatric Oncology, Utrecht, the Netherlands. Analyses were performed for all BSI and for episodes meeting central line-associated bloodstream infection (CLABSI) criteria. The cumulative incidence of an event (ie, removal, intensive care admission or death) was estimated after blood culture collection for episodes primarily treated with antibiotics. The effect of prognostic factors on the hazard of the event of interest was assessed by estimating a Cox proportional hazard regression model., Results: In total, 95 CVC-related Enterobacterales BSIs in 82 patients were included; 12 (13%) BSIs required immediate CVC removal and for 83 (87%) BSIs CVC salvage was attempted. The cumulative incidence of events at 60 days was 53.0% [95% confidence interval (CI): 41.7-63.1] for BSIs (n = 83), and 64.4% (95% CI: 48.3-76.7) for CLABSIs (n = 45). The events occurred after a median of 6 (Q1-Q3: 2-15) and 6 (Q1-Q3: 2-20) days for BSIs and CLABSIs, respectively. Intensive care admission after salvage treatment was required in 16% of the BSIs and CLABSIs, resulting in death in 5% and 2% of cases, respectively. No significant association between risk factors and events was found., Conclusions: The cumulative incidence of an event at 60 days after salvage treatment for Enterobacterales CLABSIs and BSIs in pediatric oncology patients is high. Immediate CVC removal appears recommendable for this patient group., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2024
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32. Micafungin twice-a-week for prophylaxis of invasive Aspergillus infections in children with acute lymphoblastic leukaemia: A controlled cohort study.
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Bury D, Wolfs TFW, Muilwijk EW, Fiocco M, Pieters R, Brüggemann RJ, and Tissing WJE
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- Humans, Child, Infant, Child, Preschool, Adolescent, Micafungin therapeutic use, Antifungal Agents pharmacology, Echinocandins adverse effects, Cohort Studies, Lipopeptides therapeutic use, Lipopeptides pharmacology, Aspergillosis drug therapy, Aspergillosis prevention & control, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma chemically induced
- Abstract
Objectives: Invasive Aspergillus infections during the early phase of childhood acute lymphoblastic leukemia (ALL) treatment come with morbidity and mortality. The interaction with vincristine hampers first-line azole prophylaxis. We describe the efficacy of an alternative twice-a-week micafungin regimen for Aspergillus prophylaxis., Methods: Newly diagnosed paediatric patients with ALL treated according to the ALL-11 protocol received micafungin twice-a-week (9 mg/kg/dose [max. 300 mg]) during the induction course (first 35 days of treatment) as part of routine care. A historical control cohort without Aspergillus prophylaxis was used. During the first consolidation course (day 36-79), standard itraconazole prophylaxis was used in both groups. The percentage of proven/probable Aspergillus infections during the induction/first consolidation course was compared between the cohorts. The cumulative incidence of proven/probable Aspergillus infections was estimated using a competing risk model. For safety evaluation, liver laboratory chemistry values were analysed., Results: A total of 169 and 643 paediatric patients with ALL were treated in the micafungin cohort (median age: 4 years [range 1-17]) and historical cohort (median age: 5 years [range 1-17]). The percentage of proven/probable Aspergillus infections was 1·2% (2/169) in the micafungin cohort versus 5·8% (37/643) in the historical cohort (p=0.013; Fisher's exact test). The differences in estimated cumulative incidence were assessed (p=0·014; Gray's test). Although significantly higher ALT/AST values were reported in the micafungin cohort, no clinically relevant side effects were observed., Conclusions: Twice-a-week micafungin prophylaxis during the induction course significantly reduced the occurrence of proven/probable Aspergillus infections in the early phase of childhood ALL treatment., (Copyright © 2023. Published by Elsevier Ltd.)
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- 2024
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33. Pharmacokinetic investigations of isavuconazole in paediatric cancer patients show reduced exposure of isavuconazole after opening capsules for administration via a nasogastric tube.
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Bury D, Wolfs TFW, Ter Heine R, Muilwijk EW, van der Elst KCM, Tissing WJE, and Brüggemann RJM
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- Adult, Humans, Child, Infant, Child, Preschool, Adolescent, Prospective Studies, Pyridines, Nitriles, Neoplasms
- Abstract
Objectives: To study the isavuconazole pharmacokinetics in a real-life paediatric cohort and confirm whether the isavuconazole exposures are within the adult exposure range. Furthermore, we are the first to describe unbound isavuconazole pharmacokinetics., Methods: In this prospective, observational study, the isavuconazole dosing regimen was as follows (IV/oral/nasogastric tube): 5.4 mg/kg isavuconazole (maximum 200 mg/dose) three times daily on Days 1 and 2, followed by 5.4 mg/kg isavuconazole (maximum 200 mg/dose) once daily. At least one pharmacokinetic curve was assessed. Non-linear mixed effects modelling was used for analysis. Monte Carlo simulations were performed with the above mentioned maintenance dose for IV administrations and a weight band dosing regimen for oral/nasogastric tube administrations: I) <18 kg (100 mg daily); II) 18-37 kg (150 mg daily); III)>37 kg (200 mg daily)., Results: Seventeen paediatric patients with a median age of 9 years (range 1-17) and median weight of 26.0 kg (range 8.4-78.5) were evaluated. A two-compartment model describing linear pharmacokinetics of the unbound concentrations and saturable protein binding fitted the isavuconazole concentrations best. The absolute bioavailability of isavuconazole was 41.0% (95% CI: 32.4%-50.8%). The median (IQR) simulated exposures (AUC0-24h, SS) of the total isavuconazole concentrations after IV and oral/nasogastric tube administration were 87.7 mg·h/L (70.5-105.1) and 50.3 mg·h/L (39.0-62.4), respectively. The unbound isavuconazole fraction (unbound/total) ranged from 0.5% to 2.3%., Conclusions: This study revealed low bioavailability after nasogastric tube administration with opened capsules. Isavuconazole exposures were in the expected range following IV administration. Total and unbound isavuconazole pharmacokinetics were reported with a 5-fold range in the unbound fraction., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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34. Through the Looking Glass: A Child With Arthralgia, Malaise and Weight Loss.
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Verhage AR, Nagtegaal ID, van der Feen C, and Wolfs TFW
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- Humans, Child, Arthralgia etiology, Weight Loss
- Abstract
Competing Interests: The authors have no funding or conflicts of interest to disclose.
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- 2023
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35. Adoption is not associated with immunological and virological outcomes in children with perinatally acquired HIV infection in the Netherlands.
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Van Den Hof M, Smit C, Rossum AMCV, Fraaij PLA, Wolfs TFW, Geelen SPM, Scherpbier HJ, Schölvinck EH, Aerde KV, Reiss P, Wit FWNM, and Pajkrt D
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- Humans, Child, Prospective Studies, Netherlands epidemiology, Antiretroviral Therapy, Highly Active, Viral Load, HIV Infections drug therapy, HIV Infections epidemiology, Anti-HIV Agents therapeutic use
- Abstract
Objectives: To provide an overview of the demographics, treatment characteristics and long-term outcomes of children with perinatal HIV-1 infection (PHIV) living in the Netherlands (NL) and to specifically investigate whether outcomes differ by children's adoption status., Design: A prospective population-based open cohort including children with PHIV in NL., Methods: We included children with PHIV who had entered HIV care in NL since 2007, in view of a sharp increase in the number of adopted children with PHIV since that year. We compared the proportion with virologic suppression and CD4+T-cell count over time between the following groups of children with PHIV: adopted and born outside NL, non-adopted born in NL, and non-adopted born outside NL, using generalized estimating equations and linear mixed effects models, respectively. To account for the variation in cohort inclusion, we analyzed data of children exposed to at least one year of antiretroviral therapy (ART)., Results: We included 148 children (827.5 person-years of follow-up, 72% adopted, age at start care in NL 2.4 (0.5-5.3)). Under-18 mortality was zero. Over the years, a boosted PI-based regimen was most often prescribed. The use of integrase inhibitors increased since 2015. Non-adopted children born in NL were less likely to achieve virological suppression compared to adopted children (OR 0.66, 95%CI 0.51-0.86, p = 0.001), which disappeared after excluding one child with suspected treatment nonadherence (OR 0.85, 95%CI 0.57-1.25, p = 0.400). CD4+T-cell Z-score trajectories were not significantly different between groups., Conclusions: Despite considerable and increasing diversity of the population of children with PHIV in NL, geographical origin and adoption status do not seem to pose important challenges in achieving good immunological and virological outcomes., Competing Interests: MH, CS, AvR, TW, SG, ES, KvA, FW and DP and reported no conflicts of interest. PF receives funding from PREPARE Europe (EU FP7 grant no 602525). HS received a small grant from Gilead. PR through his institution has received independent scientific grant support from Gilead Sciences, Janssen Pharmaceuticals Inc, Merck & Co and ViiV Healthcare, and has served on scientific advisory boards for Gilead Sciences, ViiV Healthcare, Merck & Co, Teva pharmaceutical industries, for which honoraria were all paid to his institution. None related to the current manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Van Den Hof et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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36. The Dutch Working Party on Antibiotic Policy (SWAB) Recommendations for the Diagnosis and Management of Febrile Neutropenia in Patients with Cancer.
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de la Court JR, Bruns AHW, Roukens AHE, Baas IO, van Steeg K, Toren-Wielema ML, Tersmette M, Blijlevens NMA, Huis In 't Veld RAG, Wolfs TFW, Tissing WJE, Kyuchukova Y, and Heijmans J
- Abstract
Introduction: This guideline was written by a multidisciplinary committee with mandated members of the Dutch Society for Infectious Diseases, Dutch Society for Hematology, Dutch Society for Medical Oncology, Dutch Association of Hospital Pharmacists, Dutch Society for Medical Microbiology, and Dutch Society for Pediatrics. The guideline is written for adults and pediatric patients., Method: The recommendations are based on the answers to nine questions formulated by the guideline committee. To provide evidence-based recommendations we used all relevant clinical guidelines published since 2010 as a source, supplemented with systematic searches and evaluation of the recent literature (2010-2020) and, where necessary, supplemented by expert-based advice., Results: For adults the guideline distinguishes between high- and standard-risk neutropenia based on expected duration of neutropenia (> 7 days versus ≤ 7 days). Where possible a distinction has been made between pediatric and adult patients., Conclusion: This guideline was written to aid diagnosis and management of patients with febrile neutropenia due to chemotherapy in the Netherlands. The guideline provides recommendation for children and adults. Adults patient are subdivided as having a standard- or high-risk neutropenic episode based on estimated duration of neutropenia. The most important recommendations are as follows. In adults with high-risk neutropenia (duration of neutropenia > 7 days) and in children with neutropenia, ceftazidime, cefepime, and piperacillin-tazobactam are all first-choice options for empirical antibiotic therapy in case of fever. In adults with standard-risk neutropenia (duration of neutropenia ≤ 7 days) the MASCC score can be used to assess the individual risk of infectious complications. For patients with a low risk of infectious complications (high MASCC score) oral antibiotic therapy in an outpatient setting is recommended. For patients with a high risk of infectious complications (low MASCC score) antibiotic therapy per protocol sepsis of unknown origin is recommended., (© 2022. The Author(s).)
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- 2022
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37. [Carbapenems: take it when needed but leave it if you can].
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de Stoppelaar SF, Ten Oever J, Wertheim HFL, van Hest RM, van Mens S, van Dijk K, van Agtmael MA, and Wolfs TFW
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- Humans, Netherlands, Carbapenems therapeutic use, Anti-Bacterial Agents therapeutic use
- Abstract
Surveillance data and literature have shown a worldwide increase in infections with resistant bacteria, which has led to increased prescriptions of carbapenems, which in turn has led to increased carbapenem resistance. There is also an increasing use of carbapenems in the Netherlands, a county usually very conservative in antibiotic use. Carbapenem sparing strategies are essential in an attempt to prevent further rise of infections caused by carbapenem resistant bacteria. This article discusses carbapenem sparing strategies with old forgotten antibiotics and novel antibiotics from a Dutch perspective.
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- 2022
38. Mucormycosis in Children With Hematologic Malignancies: A Case Series and Review of the Literature.
- Author
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Loeffen YGT, Scharloo F, Goemans BF, Heitink-Polle KMJ, Lindemans CA, van der Bruggen T, Hagen F, and Wolfs TFW
- Subjects
- Adolescent, Antifungal Agents therapeutic use, Child, Child, Preschool, Humans, Retrospective Studies, Hematologic Neoplasms complications, Hematologic Neoplasms therapy, Invasive Fungal Infections diagnosis, Invasive Fungal Infections drug therapy, Mucormycosis diagnosis, Mucormycosis epidemiology, Mucormycosis therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications
- Abstract
Background: Mucormycosis is classified as the third leading cause of invasive fungal disease in immunocompromised patients and is characterized by high morbidity and mortality (33%-56%). The aim of this study is to describe presentation, treatment and outcome of Dutch pediatric hemato-oncology patients recently diagnosed with mucormycosis and to review the literature to gain more insight specifically into contemporary outcome data., Methods: Ten cases were diagnosed in the Princess Máxima Center for Pediatric Oncology from 2018 to 2021 and were retrospectively reviewed. In addition, 9 case series (n = 148) were included from literature., Results: In our case series, 5 patients of 10 children (age 2-17 years) had disseminated invasive fungal disease. Four patients had localized pulmonary disease and 1 had a localized renal infection. One diagnosis was made postmortem. The underlying diseases were acute lymphoblastic leukemia (n = 6), acute myeloid leukemia (n = 2) and lymphoma (n=2). Seven patients received combination therapy comprising of a lipid amphotericin B formulation and a triazole, surgery was performed in 67%. All neutropenic patients received granulocyte transfusions and/or granulocyte colony-stimulating factor. Mucormycosis-related mortality was 20%. In the literature review, mucormycosis-related mortality was 36% for all patients and 66% for patients with disseminated disease. Survival rates were similar over the past 2 decades. The most common underlying disorder was acute lymphoblastic leukemia. Liposomal amphotericin B was the mainstay of treatment. Seventy percent of patients underwent surgery., Conclusions: Although survival of mucormycosis improved significantly overtime, it plateaued in the past decades. This series shows that with screening, early diagnostics and early antifungal and if possible surgical treatment, mortality is low and even disseminated disease is salvageable if approached aggressively with a combination of surgery and antifungal treatment. Further research focused on diagnostics, combination antifungal and adjunctive therapy is necessary to enhance the survival of mucormycosis in children., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
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- 2022
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39. Effect of Antibacterial Prophylaxis on Febrile Neutropenic Episodes and Bacterial Bloodstream Infections in Dutch Pediatric Patients with Acute Myeloid Leukemia: A Two-Center Retrospective Study.
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Van Weelderen RE, Klein K, Goemans BF, Tissing WJE, Wolfs TFW, and Kaspers GJL
- Abstract
Bloodstream infections (BSIs), especially those caused by Gram-negative rods (GNR) and viridans group streptococci (VGS), are common and potentially life-threatening complications of pediatric acute myeloid leukemia (AML) treatment. Limited literature is available on prophylactic regimens. We retrospectively evaluated the effect of different antibacterial prophylaxis regimens on the incidence of febrile neutropenic (FN) episodes and bacterial BSIs. Medical records of children (0−18 years) diagnosed with de novo AML and treated at two Dutch centers from May 1998 to March 2021 were studied. Data were analyzed per chemotherapy course and consecutive neutropenic period. A total of 82 patients had 316 evaluable courses: 92 were given with single-agent ciprofloxacin, 138 with penicillin plus ciprofloxacin, and 51 with teicoplanin plus ciprofloxacin. The remaining 35 courses with various other prophylaxis regimens were not statistically compared. During courses with teicoplanin plus ciprofloxacin, significantly fewer FN episodes (43 vs. 90% and 75%; p < 0.0001) and bacterial BSIs (4 vs. 63% and 33%; p < 0.0001) occurred than with single-agent ciprofloxacin and penicillin plus ciprofloxacin, respectively. GNR and VGS BSIs did not occur with teicoplanin plus ciprofloxacin and no bacterial BSI-related pediatric intensive care unit (PICU) admissions were required, whereas, with single-agent ciprofloxacin and penicillin plus ciprofloxacin, GNR BSIs occurred in 8 and 1% (p = 0.004), VGS BSIs in 24 and 14% (p = 0.0005), and BSI-related PICU admissions were required in 8 and 2% of the courses (p = 0.029), respectively. Teicoplanin plus ciprofloxacin as antibacterial prophylaxis is associated with a lower incidence of FN episodes and bacterial BSIs. This may be a good prophylactic regimen for pediatric AML patients during treatment.
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- 2022
- Full Text
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40. The diagnostic value of nasal microbiota and clinical parameters in a multi-parametric prediction model to differentiate bacterial versus viral infections in lower respiratory tract infections.
- Author
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Li Y, van Houten CB, Boers SA, Jansen R, Cohen A, Engelhard D, Kraaij R, Hiltemann SD, Ju J, Fernández D, Mankoc C, González E, de Waal WJ, de Winter-de Groot KM, Wolfs TFW, Meijers P, Luijk B, Oosterheert JJ, Sankatsing SUC, Bossink AWJ, Stein M, Klein A, Ashkar J, Bamberger E, Srugo I, Odeh M, Dotan Y, Boico O, Etshtein L, Paz M, Navon R, Friedman T, Simon E, Gottlieb TM, Pri-Or E, Kronenfeld G, Oved K, Eden E, Stubbs AP, Bont LJ, and Hays JP
- Subjects
- C-Reactive Protein metabolism, Humans, Nose microbiology, Bacterial Infections drug therapy, Microbiota, Respiratory Tract Infections drug therapy, Virus Diseases diagnosis
- Abstract
Background: The ability to accurately distinguish bacterial from viral infection would help clinicians better target antimicrobial therapy during suspected lower respiratory tract infections (LRTI). Although technological developments make it feasible to rapidly generate patient-specific microbiota profiles, evidence is required to show the clinical value of using microbiota data for infection diagnosis. In this study, we investigated whether adding nasal cavity microbiota profiles to readily available clinical information could improve machine learning classifiers to distinguish bacterial from viral infection in patients with LRTI., Results: Various multi-parametric Random Forests classifiers were evaluated on the clinical and microbiota data of 293 LRTI patients for their prediction accuracies to differentiate bacterial from viral infection. The most predictive variable was C-reactive protein (CRP). We observed a marginal prediction improvement when 7 most prevalent nasal microbiota genera were added to the CRP model. In contrast, adding three clinical variables, absolute neutrophil count, consolidation on X-ray, and age group to the CRP model significantly improved the prediction. The best model correctly predicted 85% of the 'bacterial' patients and 82% of the 'viral' patients using 13 clinical and 3 nasal cavity microbiota genera (Staphylococcus, Moraxella, and Streptococcus)., Conclusions: We developed high-accuracy multi-parametric machine learning classifiers to differentiate bacterial from viral infections in LRTI patients of various ages. We demonstrated the predictive value of four easy-to-collect clinical variables which facilitate personalized and accurate clinical decision-making. We observed that nasal cavity microbiota correlate with the clinical variables and thus may not add significant value to diagnostic algorithms that aim to differentiate bacterial from viral infections., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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41. Pharmacokinetic evaluation of twice-a-week micafungin for prophylaxis of invasive fungal disease in children with acute lymphoblastic leukaemia: a prospective observational cohort study.
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Bury D, Wolfs TFW, Ter Heine R, Muilwijk EW, Tissing WJE, and Brüggemann RJ
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- Adolescent, Adult, Antifungal Agents, Child, Child, Preschool, Echinocandins, Humans, Infant, Lipopeptides, Micafungin pharmacokinetics, Prospective Studies, Invasive Fungal Infections drug therapy, Invasive Fungal Infections prevention & control, Precursor Cell Lymphoblastic Leukemia-Lymphoma complications, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy
- Abstract
Objectives: To determine the pharmacokinetics of twice-a-week micafungin prophylaxis in paediatric leukaemic patients to provide the rationale for this approach., Methods: Twice-a-week micafungin at a dose of 9 mg/kg (maximum 300 mg) was given during the leukaemic induction treatment with at least one pharmacokinetic assessment. Non-linear mixed-effects modelling was used for analysis. For model building, our paediatric data were strengthened with existing adult data. Monte Carlo simulations were performed with twice-a-week dosing regimens of 5, 7 and 9 mg/kg and flat dosing per weight band. Simulated paediatric exposures were compared with the exposure in adults after a once-daily 100 mg regimen., Results: Sixty-one paediatric patients were included with a median age and weight of 4.0 years (range 1.0-17) and 19.5 kg (range 8.60-182), respectively. A two-compartment model best fitted the data. CL and central Vd were lower (P < 0.01) in paediatric patients compared with adults. Predicted exposures (AUC0-168 h) for the 5, 7 and 9 mg/kg and flat dosing per weight band regimens exceeded the adult reference exposure., Conclusions: All twice-a-week regimens appeared to result in adequate exposure for Candida therapy, with simulated exposures well above the adult reference exposure. These findings provide the rationale for the pharmacokinetic equivalence of twice-a-week and once-daily micafungin regimens. The greater micafungin exposures seem to be caused by a slower-than-anticipated CL in our paediatric leukaemic patients. The generalizability of our results for Aspergillus prophylaxis cannot be provided without assumptions on target concentrations and within-class identical efficacy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
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- 2022
- Full Text
- View/download PDF
42. Clinical Pharmacokinetics of Triazoles in Pediatric Patients.
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Bury D, Tissing WJE, Muilwijk EW, Wolfs TFW, and Brüggemann RJ
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- Adult, Antifungal Agents therapeutic use, Child, Fluconazole, Humans, Itraconazole, Triazoles, Voriconazole, Mycoses drug therapy
- Abstract
Triazoles represent an important class of antifungal drugs in the prophylaxis and treatment of invasive fungal disease in pediatric patients. Understanding the pharmacokinetics of triazoles in children is crucial to providing optimal care for this vulnerable population. While the pharmacokinetics is extensively studied in adult populations, knowledge on pharmacokinetics of triazoles in children is limited. New data are still emerging despite drugs already going off patent. This review aims to provide readers with the most current knowledge on the pharmacokinetics of the triazoles: fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole. In addition, factors that have to be taken into account to select the optimal dose are summarized and knowledge gaps are identified that require further research. We hope it will provide clinicians guidance to optimally deploy these drugs in the setting of a life-threatening disease in pediatric patients., (© 2021. The Author(s).)
- Published
- 2021
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43. Allogenic Hematopoietic Stem Cell Transplantation Is Feasible in Pediatric Patients with an Active or Recently Diagnosed Invasive Fungal Infection.
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Rotte LGY, Loeffen YGT, Bierings MB, Wolfs TFW, and Lindemans CA
- Subjects
- Antifungal Agents therapeutic use, Child, Humans, Retrospective Studies, Treatment Outcome, Hematopoietic Stem Cell Transplantation adverse effects, Invasive Fungal Infections diagnosis
- Abstract
Data on the outcome of allogenic hematopoietic stem cell transplantation (HSCT) in pediatric patients with a history of invasive fungal infection (IFI) are limited. The aim of this study was to report on the feasibility and outcome of allogenic HSCT in pediatric patients with an active or recently diagnosed IFI. In this retrospective, single-center study, 317 children underwent an allogenic HSCT (January 2012 to June 2020), of whom 23 had an active or recent (<6 months before transplantation) diagnosis of a probable or proven IFI before HSCT. Medical records were reviewed for data collection. Descriptive statistics were performed. One-year survival was described with Kaplan-Meier analysis. Four proven and 19 probable IFIs were diagnosed. The lungs were the main site of infection (22 out of 23 patients); brain involvement was diagnosed in six patients (26.1%). Aspergillus spp. were the most frequently identified organisms. Of the four patients diagnosed with mucormycosis, three had mixed infections with Aspergillus spp. One patient was diagnosed with Alternaria sinusitis and one patient with an infection with Curvularia spp. with both pulmonary and cutaneous involvement. One year after HSCT, 18 of the 23 patients (78.3%) were alive. Four of the five patients who did not survive died of non-IFI-related causes. One patient died due to a newly developed IFI post-transplant. Three patients showed non-fatal progression of their original IFIs that required prolonged antifungal treatment. Survival of this cohort of high-risk pediatric patients who underwent allogenic HSCT with an active or recently diagnosed IFI was favorable. An active IFI or recent history of IFI should not be a contraindication for proceeding to allogenic HSCT., (Copyright © 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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44. Safety and efficacy of early vaccination with live attenuated measles vaccine for hematopoietic stem cell transplant recipients and solid organ transplant recipients.
- Author
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Groeneweg L, Loeffen YGT, Versluys AB, and Wolfs TFW
- Subjects
- Measles Vaccine, Transplant Recipients, Vaccination, Vaccines, Attenuated adverse effects, Hematopoietic Stem Cell Transplantation adverse effects, Organ Transplantation
- Abstract
Background and Objective: Vaccination with the live attenuated measles vaccine is currently recommended two years after hematopoietic stem cell transplantation (HSCT) and generally contraindicated after solid organ transplantation (SOT) due to safety concerns. However, in the last few years new data on the administration of the measles vaccine to HSCT recipients less two years post-transplantation and to SOT recipients have become available. This new data may change current guidelines and practices. The objective of this review is to provide an overview of the current data on the safety and efficacy of early measles vaccination for HSCT- and SOT recipients., Method: PubMed and EMBASE were searched from the earliest date available through October 2019 to identify all research that reported on the safety and efficacy of measles vaccination after SOT or less than two years after HSCT., Results: A total of ten studies was included in this review. In the six studies that evaluated the efficacy of measles vaccination after SOT, seroconversion rates ranged from 41 to 100% after one dose and 73 to 100% after two doses. In the four studies that evaluated the efficacy of measles vaccination less than two years after HSCT, seroconversion rates ranged from 33 to 100% after one dose and 100% after two doses. In all studies, the administration of the measles vaccine after transplantation was considered to be safe. There were no cases of infection with the attenuated vaccine strain, and there were no adverse events related to the vaccination., Conclusion: Data on the administration of the measles vaccine after SOT and less than two years after HSCT is scarce. However, the current data available suggest that it is efficacious and well tolerable. Therefore, early measles vaccination could be considered in selected groups of SOT- and HSCT recipients during increased measles transmission or an outbreak setting., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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45. Anterior uveitis in paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2.
- Author
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Wong Chung JERE, Engin Ö, Wolfs TFW, Renson TJC, and de Boer JH
- Subjects
- Anti-Inflammatory Agents therapeutic use, Child, Humans, Male, Ophthalmic Solutions, Prednisolone therapeutic use, SARS-CoV-2, Uveitis, Anterior diagnosis, Uveitis, Anterior drug therapy, COVID-19 complications, Systemic Inflammatory Response Syndrome complications, Uveitis, Anterior virology
- Abstract
Competing Interests: Declaration of interests We declare no competing interests.
- Published
- 2021
- Full Text
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46. Clinical Characteristics of Invasive Fungal Infections in Pediatric Oncology Patients With Solid Tumors.
- Author
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Ruijters VJ, Oosterom N, van der Perk MEM, Wolfs TFW, Meijer AJM, van den Heuvel-Eibrink MM, and van Grotel M
- Subjects
- Antifungal Agents therapeutic use, Antineoplastic Agents therapeutic use, Child, Child, Preschool, Female, Humans, Invasive Fungal Infections drug therapy, Invasive Fungal Infections pathology, Male, Neoplasms drug therapy, Neoplasms pathology, Neuroblastoma complications, Neuroblastoma drug therapy, Neuroblastoma pathology, Retrospective Studies, Wilms Tumor complications, Wilms Tumor drug therapy, Wilms Tumor pathology, Invasive Fungal Infections complications, Neoplasms complications
- Abstract
Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in children with cancer. Studies on the clinical characteristics of IFI in children with solid tumors are limited. This Dutch retrospective cohort study reviewed the medical records of 61 children with solid tumors to analyze the clinical characteristics during their full treatment period. Seven IFI episodes were reported in 6/61 patients (10%), all diagnosed with intermediate-risk or high-risk Wilms tumor or neuroblastoma. Larger studies are necessary to reveal the determinants of IFI in this group of patients and the value of fungal prophylaxis., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
- Full Text
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47. COVID-19 - Impact on Childhood Haematology Patients.
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Wolfs TFW, Attarbaschi A, Balduzzi A, Bernardo ME, Bomken S, Borkhardt A, Bourquin JP, Dufour C, Gennery A, Grainger J, Hasle H, Hrusak O, Izraeli S, Mechinaud F, Trka J, and Vormoor J
- Published
- 2020
- Full Text
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48. The needs for diagnostic imaging in cases of group A streptococcal meningitis in children: a case report and review of the literature.
- Author
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van Dijk L, Wolfs TFW, Debast SB, and Langenhorst VVJ
- Abstract
Group A streptococcus (GAS) is a rare cause of bacterial meningitis in children and is associated with a high cerebral complication rate. In this case report, we present a 9-year-old girl with GAS meningitis complicated with cerebritis. Clear guidelines about choice of treatment and indications of follow-up by imaging tests are lacking, making GAS meningitis unpredictable and difficult to treat. Eventually, we found 25 paediatric cases of GAS meningitis presented in the literature and reviewed their treatment choices, outcomes and follow-up by imaging tests. Penicillin and ceftriaxone are most preferred for the treatment of GAS meningitis and adding rifampicin to the antibiotic treatment could be of potential benefit. When considering the duration of antibiotic treatment and follow-up by imaging tests, no clear recommendations were found. We found that GAS meningitis is associated with higher mortality and cerebral complication rates compared to other, more common, bacterial causes of meningitis in children. This should alert the clinician to consider imaging tests routinely, even if the patient improves clinically. We advise clinicians to routinely evaluate for possible cerebral complications through magnetic resonance imaging (MRI) scans. When cerebral complications are found, antibiotic treatment should be prolonged and adding rifampicin to the antibiotic regime may be considered., Competing Interests: The authors declare that there are no conflicts of interest., (© 2019 The Authors.)
- Published
- 2019
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49. Expert panel diagnosis demonstrated high reproducibility as reference standard in infectious diseases.
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van Houten CB, Naaktgeboren CA, Ashkenazi-Hoffnung L, Ashkenazi S, Avis W, Chistyakov I, Corigliano T, Galetto A, Gangoiti I, Gervaix A, Glikman D, Ivaskeviciene I, Kuperman AA, Lacroix L, Loeffen Y, Luterbacher F, Meijssen CB, Mintegi S, Nasrallah B, Papan C, van Rossum AMC, Rudolph H, Stein M, Tal R, Tenenbaum T, Usonis V, de Waal W, Weichert S, Wildenbeest JG, de Winter-de Groot KM, Wolfs TFW, Mastboim N, Gottlieb TM, Cohen A, Oved K, Eden E, Feigin PD, Shani L, and Bont LJ
- Subjects
- Child, Preschool, Diagnosis, Differential, Diagnostic Tests, Routine, Expert Testimony methods, Expert Testimony standards, Female, Humans, Infant, Male, Reference Standards, Reproducibility of Results, Standard of Care, Clinical Decision-Making methods, Fever of Unknown Origin diagnosis, Pediatrics methods, Pediatrics standards, Respiratory Tract Infections diagnosis
- Abstract
Objective: If a gold standard is lacking in a diagnostic test accuracy study, expert diagnosis is frequently used as reference standard. However, interobserver and intraobserver agreements are imperfect. The aim of this study was to quantify the reproducibility of a panel diagnosis for pediatric infectious diseases., Study Design and Setting: Pediatricians from six countries adjudicated a diagnosis (i.e., bacterial infection, viral infection, or indeterminate) for febrile children. Diagnosis was reached when the majority of panel members came to the same diagnosis, leaving others inconclusive. We evaluated intraobserver and intrapanel agreement with 6 weeks and 3 years' time intervals. We calculated the proportion of inconclusive diagnosis for a three-, five-, and seven-expert panel., Results: For both time intervals (i.e., 6 weeks and 3 years), intrapanel agreement was higher (kappa 0.88, 95%CI: 0.81-0.94 and 0.80, 95%CI: NA) compared to intraobserver agreement (kappa 0.77, 95%CI: 0.71-0.83 and 0.65, 95%CI: 0.52-0.78). After expanding the three-expert panel to five or seven experts, the proportion of inconclusive diagnoses (11%) remained the same., Conclusion: A panel consisting of three experts provides more reproducible diagnoses than an individual expert in children with lower respiratory tract infection or fever without source. Increasing the size of a panel beyond three experts has no major advantage for diagnosis reproducibility., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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50. [An infant with a red and swollen eyelid].
- Author
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Meeuwes M and Wolfs TFW
- Subjects
- Corynebacterium Infections diagnosis, Eyelid Diseases diagnosis, Female, Humans, Infant, Corynebacterium isolation & purification, Corynebacterium Infections microbiology, Eyelid Diseases microbiology
- Abstract
An 8-month-old girl was admitted with fever and a red and swollen left eye with purulent discharge. A CT scan revealed no postseptal (orbital) involvement. Preseptal cellulitis was diagnosed. Pus culture showed that Corynebacterium bovis, normally only seen in bovine colonization. C. bovis had been transmitted by the family's pet dog.
- Published
- 2019
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