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1. Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients

Author

A.J.J. Lammers, R.M. Brohet, R.E.P. Theunissen, C. Koster, R. Rood, D.W.M. Verhagen, K. Brinkman, R.J. Hassing, A. Dofferhoff, R. el Moussaoui, G. Hermanides, J. Ellerbroek, N. Bokhizzou, H. Visser, M. van den Berge, H. Bax, D.F. Postma, and P.H.P. Groeneveld

Subjects
COVID-19, Hydroxychloroquine, Chloroquine, Azithromycin, Clinical course, Infectious and parasitic diseases, RC109-216
Abstract

Background: The global push for the use of hydroxychloroquine (HCQ) and chloroquine (CQ) against COVID-19 has resulted in an ongoing discussion about the effectivity and toxicity of these drugs. Recent studies report no effect of (H)CQ on 28-day mortality. We investigated the effect of HCQ and CQ in hospitalized patients on the non-ICU COVID-ward. Methods: A nationwide, observational cohort study was performed in The Netherlands. Hospitals were given the opportunity to decide independently on the use of three different COVID-19 treatment strategies: HCQ, CQ, or no treatment. We compared the outcomes between these groups. The primary outcomes were 1) death on the COVID-19 ward, and 2) transfer to the intensive care unit (ICU). Results: The analysis included 1064 patients from 14 hospitals: 566 patients received treatment with either HCQ (n = 189) or CQ (n = 377), and 498 patients received no treatment. In a multivariate propensity-matched weighted competing regression analysis, there was no significant effect of (H)CQ on mortality on the COVID ward. However, HCQ was associated with a significantly decreased risk of transfer to the ICU (hazard ratio (HR) = 0.47, 95% CI = 0.27–0.82, p = 0.008) when compared with controls. This effect was not found in the CQ group (HR = 0.80, 95% CI = 0.55–1.15, p = 0.207), and remained significant after competing risk analysis. Conclusion: The results of this observational study demonstrate a lack of effect of (H)CQ on non-ICU mortality. However, we show that the use of HCQ — but not CQ — is associated with a 53% reduction in risk of transfer of COVID-19 patients from the regular ward to the ICU. Recent prospective studies have reported on 28-day, all-cause mortality only; therefore, additional prospective data on the early effects of HCQ in preventing transfer to the ICU are still needed.

Published
2020
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2. Response to correspondence concerning: 'Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients'

Author

A.J.J. Lammers, R.M. Brohet, R.E.P. Theunissen, C. Koster, R. Rood, D.W.M. Verhagen, K. Brinkman, R.J. Hassing, A. Dofferhoff, R. el Moussaoui, G. Hermanides, J. Ellerbroek, N. Bokhizzou, H. Visser, M. van den Berge, H. Bax, D.F. Postma, and P.H.P. Groeneveld

Subjects
Infectious and parasitic diseases, RC109-216
Published
2021
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3. External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Author

Bernard Surial, Adrià Ramírez Mena, Marie Roumet, Andreas Limacher, Colette Smit, Olivier Leleux, Amanda Mocroft, Marc van der Valk, Fabrice Bonnet, Lars Peters, Jürgen K. Rockstroh, Huldrych F. Günthard, Annalisa Berzigotti, Andri Rauch, Gilles Wandeler, I. Abela, K. Aebi-Popp, A. Anagnostopoulos, M. Battegay, E. Bernasconi, D.L. Braun, H.C. Bucher, A. Calmy, M. Cavassini, A. Ciuffi, G. Dollenmaier, M. Egger, L. Elzi, J. Fehr, J. Fellay, H. Furrer, C.A. Fux, H.F. Günthard, A. Hachfeld, D. Haerry, B. Hasse, H.H. Hirsch, M. Hoffmann, I. Hösli, M. Huber, D. Jackson-Perry, C.R. Kahlert, L. Kaiser, O. Keiser, T. Klimkait, R.D. Kouyos, H. Kovari, K. Kusejko, N. Labhardt, K. Leuzinger, Martinez de Tejada B, C. Marzolini, K.J. Metzner, N. Müller, J. Nemeth, D. Nicca, J. Notter, P. Paioni, G. Pantaleo, M. Perreau, A. Rauch, L. Salazar-Vizcaya, P. Schmid, R. Speck, M. Stöckle, P. Tarr, A. Trkola, G. Wandeler, M. Weisser, S. Yerly, M. van der Valk, S.E. Geerlings, A. Goorhuis, V.C. Harris, J.W. Hovius, B. Lempkes, F.J.B. Nellen, T. van der Poll, J.M. Prins, V. Spoorenberg, M. van Vugt, W.J. Wiersinga, F.W.M.N. Wit, C. Bruins, J. van Eden, I.J. Hylkema-van den Bout, A.M.H. van Hes, F.J.J. Pijnappel, S.Y. Smalhout, A.M. Weijsenfeld, N.K.T. Back, B. Berkhout, M.T.E. Cornelissen, R. van Houdt, M. Jonges, S. Jurriaans, C.J. Schinkel, K.C. Wolthers, H.L. Zaaijer, E.J.G. Peters, M.A. van Agtmael, R.S. Autar, M. Bomers, K.C.E. Sigaloff, M. Heitmuller, L.M. Laan, M. van den Berge, A. Stegeman, S. Baas, L. Hage de Looff, A. van Arkel, J. Stohr, B. Wintermans, M.J.H. Pronk, H.S.M. Ammerlaan, E.S. de Munnik, B. Deiman, A.R. Jansz, V. Scharnhorst, J. Tjhie, M.C.A. Wegdam, A. van Eeden, E. Hoornenborg, J. Nellen, W. Alers, L.J.M. Elsenburg, H. Nobel, M.E.E. van Kasteren, M.A.H. Berrevoets, A.E. Brouwer, B.A.F.M. de Kruijf-van de Wiel, A. Adams, M. Pawels-van Rijkevoorsel, A.G.M. Buiting, J.L. Murck, C. Rokx, A.A. Anas, H.I. Bax, E.C.M. van Gorp, M. de Mendonça Melo, E. van Nood, J.L. Nouwen, B.J.A. Rijnders, C.A.M. Schurink, L. Slobbe, T.E.M.S. de Vries-Sluijs, N. Bassant, J.E.A. van Beek, M. Vriesde, L.M. van Zonneveld, J. de Groot, J.J.A. van Kampen, M.P.G. Koopmans, J.C. Rahamat-Langendoen, J. Branger, R.A. Douma, A.S. Cents-Bosma, C.J.H.M. Duijf-van de Ven, E.F. Schippers, C. van Nieuwkoop, J. Geilings, S. van Winden, G. van der Hut, N.D. van Burgel, E.M.S. Leyten, L.B.S. Gelinck, F. Mollema, G.S. Wildenbeest, T. Nguyen, P.H.P. Groeneveld, J.W. Bouwhuis, A.J.J. Lammers, A.G.W. van Hulzen, S. Kraan, M.S.M. Kruiper, G.L. van der Bliek, P.C.J. Bor, S.B. Debast, G.H.J. Wagenvoort, A.H.E. Roukens, M.G.J. de Boer, H. Jolink, M.M.C. Lambregts, H. Scheper, W. Dorama, N. van Holten, E.C.J. Claas, E. Wessels, J.G. den Hollander, R. El Moussaoui, K. Pogany, C.J. Brouwer, D. Heida-Peters, E. Mulder, J.V. Smit, D. Struik-Kalkman, T. van Niekerk, O. Pontesilli, C. van Tienen, S.H. Lowe, A.M.L. Oude Lashof, D. Posthouwer, M.E. van Wolfswinkel, R.P. Ackens, K. Burgers, M. Elasri, J. Schippers, T.R.A. Havenith, M. van Loo, M.G.A. van Vonderen, L.M. Kampschreur, M.C. van Broekhuizen, null S, null Faber, A. Al Moujahid, G.J. Kootstra, C.E. Delsing, M. van der Burg-van de Plas, L. Scheiberlich, W. Kortmann, G. van Twillert, R. Renckens, J. Wagenaar, D. Ruiter-Pronk, F.A. van Truijen-Oud, J.W.T. Cohen Stuart, M. Hoogewerf, W. Rozemeijer, J.C. Sinnige, K. Brinkman, G.E.L. van den Berk, K.D. Lettinga, M. de Regt, W.E.M. Schouten, J.E. Stalenhoef, J. Veenstra, S.M.E. Vrouenraets, H. Blaauw, G.F. Geerders, M.J. Kleene, M. Knapen, M. Kok, I.B. van der Meché, A.J.M. Toonen, S. Wijnands, E. Wttewaal, D. Kwa, T.J.W. van de Laar, R. van Crevel, K. van Aerde, A.S.M. Dofferhoff, S.S.V. Henriet, H.J.M. ter Hofstede, J. Hoogerwerf, O. Richel, M. Albers, K.J.T. Grintjes-Huisman, M. de Haan, M. Marneef, M. McCall, D. Burger, E.H. Gisolf, M. Claassen, R.J. Hassing, G. ter Beest, P.H.M. van Bentum, M. Gelling, Y. Neijland, C.M.A. Swanink, M. Klein Velderman, S.F.L. van Lelyveld, R. Soetekouw, L.M.M. van der Prijt, J. van der Swaluw, J.S. Kalpoe, A. Wagemakers, A. Vahidnia, F.N. Lauw, D.W.M. Verhagen, M. van Wijk, W.F.W. Bierman, M. Bakker, R.A. van Bentum, M.A. van den Boomgaard, J. Kleinnijenhuis, E. Kloeze, A. Middel, D.F. Postma, H.M. Schenk, Y. Stienstra, M. Wouthuyzen-Bakker, A. Boonstra, H. de Jonge, M.M.M. Maerman, D.A. de Weerd, K.J. van Eije, M. Knoester, C.C. van Leer-Buter, H.G.M. Niesters, null T.Mudrikova, R.E. Barth, A.H.W. Bruns, P.M. Ellerbroek, M.P.M. Hensgens, J.J. Oosterheert, E.M. Schadd, A. Verbon, B.J. van Welzen, H. Berends, B.M.G. Griffioen-van Santen, I. de Kroon, F.M. Verduyn Lunel, A.M.J. Wensing, S. Zaheri, A.C. Boyd, D.O. Bezemer, A.I. van Sighem, C. Smit, M.M.J. Hillebregt, T.J. Woudstra, T. Rutkens, D. Bergsma, N.M. Brétin, K.J. Lelivelt, L. van de Sande, K.M. Visser.S.T. van der Vliet, F. Paling, L.G.M. de Groot-Berndsen, M. van den Akker, R. Alexander, Y. Bakker, A. El Berkaoui, M. Bezemer-Goedhart, E.A. Djoechro, M. Groters, L.E. Koster, C.R.E. Lodewijk, E.G.A. Lucas, L. Munjishvili, B.M. Peeck, C.M.J. Ree, R. Regtop, A.F. van Rijk, Y.M.C. Ruijs-Tiggelman, P.P. Schnörr, M.J.C. Schoorl, E.M. Tuijn, D.P. Veenenberg, E.C.M. Witte, I. Karpov, M. Losso, J. Lundgren, J. Rockstroh, I. Aho, L.D. Rasmussen, P. Novak, C. Pradier, N. Chkhartishvili, R. Matulionyte, C. Oprea, J.D. Kowalska, J. Begovac, J.M. Miró, G. Guaraldi, R. Paredes, L. Peters, J.F. Larsen, B. Neesgaard, N. Jaschinski, O. Fursa, D. Raben, D. Kristensen, A.H. Fischer, S.K. Jensen, T.W. Elsing, M. Gardizi, A. Mocroft, A. Phillips, J. Reekie, A. Cozzi-Lepri, A. Pelchen-Matthews, A. Roen, E.S. Tusch, W. Bannister, P. Bellecave, P. Blanco, F. Bonnet, S. Bouchet, D. Breilh, C. Cazanave, S. Desjardin, V. Gaborieau, A. Gimbert, M. Hessamfar, L. Lacaze-Buzy, D. Lacoste, M.E. Lafon, E. Lazaro, O. Leleux, F. Le Marec, G. Le Moal, D. Malvy, L. Marchand, P. Mercié, D. Neau, I. Pellegrin, A. Perrier, V. Petrov-Sanchez, M.O. Vareil, L. Wittkop, N. Bernard, D. Bronnimann H. Chaussade, D. Dondia, P. Duffau, I. Faure, P. Morlat, E. Mériglier, F. Paccalin, E. Riebero, C. Rivoisy, M.A. Vandenhende, L. Barthod, F.A. Dauchy, A. Desclaux, M. Ducours, H. Dutronc, A. Duvignaud, J. Leitao, M. Lescure, D. Nguyen, T. Pistone, M. Puges, G. Wirth, C. Courtault, F. Camou, C. Greib, J.L. Pellegrin, E. Rivière, J.F. Viallard, Y. Imbert, M. Thierry-Mieg, P. Rispal, O. Caubet, H. Ferrand, S. Tchamgoué, S. Farbos, H. Wille, K. Andre, L. Caunegre, Y. Gerard, F. Osorio-Perez, I. Chossat, G. Iles, M. Labasse-Depis, F. Lacassin, A. Barret, B. Castan, J. Koffi, N. Rouanes, A. Saunier, J.B. Zabbe, G. Dumondin, G. Beraud, M. Catroux, M. Garcia, V. Giraud, J.P. Martellosio, F. Roblot, T. Pasdeloup, A. Riché, M. Grosset, S. Males, C. Ngo Bell, C. Carpentier, Virology P. Bellecave, C. Tumiotto, G. Miremeont-Salamé, D. Arma, G. Arnou, M.J. Blaizeau, P. Camps, M. Decoin, S. Delveaux, F. Diarra, L. Gabrea, S. Lawson-Ayayi, E. Lenaud, D. Plainchamps, A. Pougetoux, B. Uwamaliya, K. Zara, V. Conte, M. Gapillout, Internal medicine, VU University medical center, Medical Microbiology and Infection Prevention, AII - Infectious diseases, CCA - Cancer biology and immunology, AII - Inflammatory diseases, AMS - Rehabilitation & Development, APH - Quality of Care, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Ethics, Law & Medical humanities, APH - Methodology, Midwifery Science, Amsterdam Reproduction & Development (AR&D), Infectious diseases, APH - Digital Health, APH - Personalized Medicine, APH - Aging & Later Life, APH - Global Health, Global Health, APH - Health Behaviors & Chronic Diseases, Center of Experimental and Molecular Medicine, General Internal Medicine, AII - Cancer immunology, Landsteiner Laboratory, Cardiology, ACS - Heart failure & arrhythmias, Obstetrics and Gynaecology, ARD - Amsterdam Reproduction and Development, Microbes in Health and Disease (MHD), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Global Health in the Global South (GHiGS), Institut de Recherche pour le Développement (IRD)- Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Hepatitis B virus, model validation, Hepatology, liver neoplasms, risk prediction models, liver cirrhosis, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], risk assessment, 610 Medicine & health, hepatocellular carcinoma, HIV infection, tenofovir, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 610 Medizin und Gesundheit
Abstract

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection.Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves.Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and implications: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of

Published
2023

4. Immunogenicity and reactogenicity of booster vaccinations after Ad26.COV2.S priming

Author

D.F. Postma, P.H.M. van der Kuy, Daryl Geers, D. van Baarle, Wim J R Rietdijk, Melvin Lafeber, M.P.G. Koopmans, R. de Vries, Corine H. GeurtsvanKessel, Abraham Goorhuis, Katharina S. Schmitz, H.M. Garcia Garrido, Leo G. Visser, Neeltje A. Kootstra, Anke Huckriede, Virgil A. S. H. Dalm, and Roos S G Sablerolles

Subjects
Reactogenicity, Booster (rocketry), business.industry, Immunogenicity, Heterologous, law.invention, Vaccination, Regimen, Immunization, Randomized controlled trial, law, Immunology, Medicine, business
Abstract

BackgroundIn face of the developing COVID-19 pandemic with a need for rapid and practical vaccination strategies, Ad26.COV2.S was approved as single shot immunization regimen. While effective against severe COVID-19, Ad26.COV2.S vaccination induces lower SARS-CoV-2-specific antibody levels compared to its mRNA-based counterparts. To support decision making on the need for booster vaccinations in Ad26.COV2.S-primed individuals, we assessed the immunogenicity and reactogenicity of homologous and heterologous booster vaccinations in Ad26.COV2.S-primed health care workers (HCWs).MethodsThe SWITCH trial is a single-(participant)-blinded, multi-center, randomized controlled trial among 434 HCWs who received a single Ad26.COV2.S vaccination. HCWs were randomized to no boost, Ad26.COV2.S boost, mRNA-1273 boost, or BNT162b2 boost. We assessed the level of SARS-CoV-2-specific binding antibodies, neutralizing antibodies against infectious virus, SARS-CoV-2-specific T-cell responses, and reactogenicity.ResultsHomologous and heterologous booster vaccinations resulted in an increase in SARS-CoV-2-specific binding antibodies, neutralizing antibodies and T-cell responses when compared to single Ad26.COV.2.S vaccination. In comparison with the homologous boost, the increase was significantly larger in heterologous regimens with the mRNA-based vaccines. mRNA-1273 boosting was most immunogenic, associated with higher reactogenicity. Only mild to moderate local and systemic reactions were observed on the first two days following booster.ConclusionsBoosting of Ad26.COV2.S-primed HCWs was well-tolerated and immunogenic. Strongest responses were detected after boosting with mRNA-based vaccines. Based on our data, efficacy on infection and transmission of boosters is expected. In addition to efficacy, decision making on boost vaccinations should include timing, target population, level of SARS CoV-2 circulation, and the global inequity in vaccine access.Trial registrationFunded by ZonMW (10430072110001);ClinicalTrials.govnumber,NCT04927936.

Published
2021

5. HCV micro-elimination in individuals with HIV in the Netherlands 4 years after universal access to direct-acting antivirals

Author

Colette Smit, Anders Boyd, Bart J A Rijnders, Thijs J W van de Laar, Eliane M Leyten, Wouter F Bierman, Kees Brinkman, Mark A A Claassen, Jan den Hollander, Anne Boerekamps, Astrid M Newsum, Janke Schinkel, Maria Prins, Joop E Arends, Eline L M Op de Coul, Marc van der Valk, Peter Reiss, M. van der Valk, S.E. Geerlings, A. Goorhuis, J.W. Hovius, B. Lempkes, F.J.B. Nellen, T. van der Poll, J.M. Prins, M. van Vugt, W.J. Wiersinga, F.W.M.N. Wit, M. van Duinen, J. van Eden, A. Hazenberg, A.M.H. van Hes, F.J.J. Pijnappel, S.Y. Smalhout, A.M. Weijsenfeld, S. Jurriaans, N.K.T. Back, H.L. Zaaijer, B. Berkhout, M.T.E. Cornelissen, C.J. Schinkel, K.C. Wolthers, E.J.G. Peters, M.A. van Agtmael, R.S. Autar, M. Bomers, K.C.E. Sigaloff, M. Heitmuller, L.M. Laan, C.W. Ang, R. van Houdt, M. Jonges, M. van den Berge, A. Stegeman, S. Baas, L. Hage de Looff, A. Buiting, A. Reuwer, J. Veenemans, B. Wintermans, M.J.H. Pronk, H.S.M. Ammerlaan, D.N.J. van den Bersselaar, E.S. de Munnik, B. Deiman, A.R. Jansz, V. Scharnhorst, J. Tjhie, M.C.A. Wegdam, A. van Eeden, J. Nellen, W. Brokking, L.J.M. Elsenburg, H. Nobel, M.E.E. van Kasteren, M.A.H. Berrevoets, A.E. Brouwer, A. Adams, R. van Erve, B.A.F.M. de Kruijf-van de Wiel, S. Keelan-Phaf, B. van de Ven, A.G.M. Buiting, J.L. Murck, T.E.M.S. de Vries-Sluijs, H.I. Bax, E.C.M. van Gorp, N.C. de Jong-Peltenburg, M. de Mendonça Melo, E. van Nood, J.L. Nouwen, B.J.A. Rijnders, C. Rokx, C.A.M. Schurink, L. Slobbe, A. Verbon, N. Bassant, J.E.A. van Beek, M. Vriesde, L.M. van Zonneveld, J. de Groot, C.A.B. Boucher, M.P.G. Koopmans, J.J.A. van Kampen, J. Branger, R.A. Douma, A.S. Cents-Bosma, C.J.H.M. Duijf-van de Ven, E.F. Schippers, C. van Nieuwkoop, J.M. van IJperen, J. Geilings, N.D. van Burgel, E.M.S. Leyten, G. van der Hut, L.B.S. Gelinck, F. Mollema, S. Davids-Veldhuis, C. Tearno, G.S. Wildenbeest, E. Heikens, P.H.P. Groeneveld, J.W. Bouwhuis, A.J.J. Lammers, S. Kraan, A.G.W. van Hulzen, M.S.M. Kruiper, G.L. van der Bliek, P.C.J. Bor, S.B. Debast, G.H.J. Wagenvoort, F.P. Kroon, M.G.J. de Boer, H. Jolink, M.M.C. Lambregts, A.H.E. Roukens, H. Scheper, W. Dorama, N. van Holten, E.C.J. Claas, E. Wessels, J.G. den Hollander, C.J. Brouwer, J.V. Smit, D. Struik-Kalkman, T. van Niekerk, R. El Moussaoui, K. Pogany, O. Pontesilli, S.H. Lowe, A.M.L. Oude Lashof, D. Posthouwer, M.E. van Wolfswinkel, R.P. Ackens, K. Burgers, J. Schippers, B. Weijenberg-Maes, I.H.M. van Loo, T.R.A. Havenith, M.G.A. van Vonderen, L.M. Kampschreur, S. Faber, R. Steeman-Bouma, A. Al Moujahid, G.J. Kootstra, C.E. Delsing, M. van der Burg-van de Plas, L. Scheiberlich, W. Kortmann, G. van Twillert, R. Renckens, D. Ruiter-Pronk, F.A. van Truijen-Oud, J.W.T. Cohen Stuart, E.R. Jansen, M. Hoogewerf, W. Rozemeijer, W.A. van der Reijden, J.C. Sinnige, K. Brinkman, G.E.L. van den Berk, W.L. Blok, K.D. Lettinga, M. de Regt, W.E.M. Schouten, J.E. Stalenhoef, J. Veenstra, S.M.E. Vrouenraets, H. Blaauw, G.F. Geerders, M.J. Kleene, M. Kok, M. Knapen, I.B. van der Meché, E. Mulder-Seeleman, A.J.M. Toonen, S. Wijnands, E. Wttewaal, D. Kwa, R. van Crevel, A.S.M. Dofferhoff, H.J.M. ter Hofstede, J. Hoogerwerf, M. Keuter, O. Richel, M. Albers, K.J.T. Grintjes-Huisman, M. de Haan, M. Marneef, R. Strik-Albers, J. Rahamat-Langendoen, F.F. Stelma, D. Burger, E.H. Gisolf, R.J. Hassing, M. Claassen, G. ter Beest, P.H.M. van Bentum, N. Langebeek, R. Tiemessen, C.M.A. Swanink, S.F.L. van Lelyveld, R. Soetekouw, L.M.M. van der Prijt, J. van der Swaluw, N. Bermon, R. Jansen, B.L. Herpers, D. Veenendaal, D.W.M. Verhagen, F.N. Lauw, M.C. van Broekhuizen, M. van Wijk, W.F.W. Bierman, M. Bakker, J. Kleinnijenhuis, E. Kloeze, A. Middel, D.F. Postma, Y. Stienstra, M. Wouthuyzen-Bakker, A. Boonstra, H. de Groot-de Jonge, P.A. van der Meulen, D.A. de Weerd, H.G.M. Niesters, C.C. van Leer-Buter, M. Knoester, A.I.M. Hoepelman, J.E. Arends, R.E. Barth, A.H.W. Bruns, P.M. Ellerbroek, T. Mudrikova, J.J. Oosterheert, E.M. Schadd, B.J. van Welzen, K. Aarsman, B.M.G. Griffioen-van Santen, I. de Kroon, M. van Berkel, C.S.A.M. van Rooijen, R. Schuurman, F. Verduyn-Lunel, A.M.J. Wensing, P. Reiss, S. Zaheri, A.C. Boyd, D.O. Bezemer, A.I. van Sighem, C. Smit, M. Hillebregt, A. de Jong, T. Woudstra, D. Bergsma, R. Meijering, L. van de Sande, T. Rutkens, S. van der Vliet, L. de Groot, M. van den Akker, Y. Bakker, A. El Berkaoui, M. Bezemer, N. Brétin, E. Djoechro, M. Groters, E. Kruijne, K.J. Lelivelt, C. Lodewijk, E. Lucas, L. Munjishvili, F. Paling, B. Peeck, C. Ree, R. Regtop, Y. Ruijs, M. Schoorl, P. Schnörr, A. Scheigrond, E. Tuijn, L. Veenenberg, K.M. Visser, E.C. Witte, Infectious diseases, Medical Microbiology and Infection Prevention, AII - Infectious diseases, APH - Global Health, Global Health, APH - Aging & Later Life, APH - Quality of Care, Center of Experimental and Molecular Medicine, Landsteiner Laboratory, AII - Inflammatory diseases, Obstetrics and Gynaecology, ARD - Amsterdam Reproduction and Development, Gastroenterology and Hepatology, APH - Health Behaviors & Chronic Diseases, APH - Methodology, APH - Digital Health, APH - Personalized Medicine, Internal medicine, ACS - Diabetes & metabolism, General practice, Internal Medicine, and Medical Microbiology & Infectious Diseases

Subjects
0301 basic medicine, Adult, Male, Epidemiology, Immunology, HIV Infections, Hepacivirus, Antiviral Agents, Men who have sex with men, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Virology, Medicine, Humans, 030212 general & internal medicine, Homosexuality, Male, Substance Abuse, Intravenous, Netherlands, Retrospective Studies, Proportional hazards model, business.industry, Coinfection, Incidence (epidemiology), Incidence, Retrospective cohort study, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, 030112 virology, Chronic infection, Infectious Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Cohort, HIV-1, Female, business, Demography
Abstract

Contains fulltext : 232443.pdf (Publisher’s version ) (Closed access) BACKGROUND: In the Netherlands, access to direct-acting antivirals (DAAs) against hepatitis C virus (HCV) has been unrestricted for chronic infection since 2015. We evaluated whether the nationwide incidence of HCV infections in individuals with HIV has changed since 2015. METHODS: In this retrospective cohort study, data from the ATHENA cohort of people with HIV aged 18 years or older attending any of the 24 HIV treatment centres in the Netherlands between 2000 and 2019 were assessed. We used parametric proportional hazards models with a piecewise exponential survival function to model HCV primary infection and reinfection incidence per 1000 person-years. FINDINGS: Of the 23 590 individuals without previous HCV infection, 1269 cases of HCV primary infection were documented (incidence 5·2 per 1000 person-years [95% CI 5·0-5·5]). The highest incidence was observed in men who have sex with men (MSM; 7·7 per 1000 person-years [7·3-8·2]) and was lower in people who inject drugs (PWID; 1·7 per 1000 person-years [0·7-4·1]) and other key populations (1·0 per 1000 person-years [0·8-1·2]). In MSM, incidence increased in 2007 to 14·3 per 1000 person-years and fluctuated between 8·7 and 13·0 per 1000 person-years from 2008 to 2015. In 2016, incidence declined to 6·1 cases per 1000 person-years and remained steady between 4·1 and 4·9 per 1000 person-years from 2017 to 2019. Of the 1866 individuals with a previous HCV infection, 274 reinfections were documented (incidence 26·9 per 1000 person-years [95% CI 23·9-30·3]). The highest incidence rate was observed in MSM (38·5 per 1000 person-years [33·9-43·7]) and was lower in PWID (10·9 per 1000 person-years [3·5-33·8]) and other key populations (8·9 per 1000 person-years [6·3-12·5]). In MSM, reinfection incidence fluctuated between 38·0 and 88·9 per 1000 person-years from 2006 to 2015, reaching 55·6 per 1000 person-years in 2015. In 2016, reinfection incidence declined to 41·4 per 1000 person-years, followed by further decreases to 24·4 per 1000 person-years in 2017 and 11·4 per 1000 person-years in 2019. INTERPRETATION: The sharp decline in HCV incidence in MSM with HIV shortly after restrictions on DAAs were lifted suggests a treatment-as-prevention effect. HCV incidence was already low in PWID and other groups before unrestricted access. Ongoing HCV transmission is occurring in MSM, as illustrated by a declining but high rate of reinfection, stressing the need for additional preventive measures. FUNDING: Dutch Ministry of Health, Welfare, and Sport.

Published
2021

6. Response to correspondence concerning: 'Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients'

Author

D. W. M. Verhagen, Paul H. P. Groeneveld, N. Bokhizzou, C. Koster, G. Hermanides, R. E.P. Theunissen, R. M. Brohet, R. el Moussaoui, Anton S M Dofferhoff, H. Visser, R. Rood, Hannelore I. Bax, A. J.J. Lammers, Robert Jan Hassing, J. Ellerbroek, Kees Brinkman, D.F. Postma, M. van den Berge, and Internal Medicine

Subjects
Microbiology (medical), 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, COVID-19/drug therapy, lcsh:Infectious and parasitic diseases, SDG 3 - Good Health and Well-being, Chloroquine, Internal medicine, medicine, Humans, lcsh:RC109-216, Letter to the Editor, SARS-CoV-2, business.industry, Hydroxychloroquine, General Medicine, Icu admission, Intensive Care Units, Infectious Diseases, Hydroxychloroquine/therapeutic use, Chloroquine/therapeutic use, business, medicine.drug
Published
2021
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7. Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients

Author

R. M. Brohet, R. E.P. Theunissen, K. Brinkman, A. J.J. Lammers, D.F. Postma, D. W. M. Verhagen, N. Bokhizzou, M. van den Berge, H. Visser, Anton S M Dofferhoff, G. Hermanides, Paul H. P. Groeneveld, Hannelore I. Bax, Robert-Jan Hassing, R. Rood, J. Ellerbroek, C. Koster, R. el Moussaoui, Internal Medicine, and Medical Microbiology & Infectious Diseases

Subjects
0301 basic medicine, Male, Azithromycin, law.invention, AZM, azithromycin, 0302 clinical medicine, Patient Admission, Clinical course, Chloroquine, law, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Letter to the Editor, Netherlands, Aged, 80 and over, Hazard ratio, Cq, chloroquine, General Medicine, Middle Aged, ICU, intensive care unit, Intensive care unit, Hospitalization, Intensive Care Units, Infectious Diseases, Treatment Outcome, ED, emergency department, Female, medicine.drug, Cohort study, Hydroxychloroquine, Microbiology (medical), Adult, medicine.medical_specialty, 030106 microbiology, Antiviral Agents, Article, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Internal medicine, medicine, Humans, lcsh:RC109-216, Aged, business.industry, SARS-CoV-2, COVID-19, HCQ, hydroxychloroquine, COVID-19 Drug Treatment, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Observational study, business
Abstract

Highlights • After the global push for the use of Hydroxychloroquine and Chloroquine there is ongoing discussion about the effectivity of these drugs. • Findings of this observational study provide crucial data on a potential protective effect of Hydroxychloroquine in non-ICU, hospitalized COVID-19 patients. • Early treatment with HCQ on the first day of admission is associated with a reduced risk of 53% in transfer to the ICU for mechanical ventilation. • This protective effect was not observed for Chloroquine, therefore these drugs cannot be regarded as interchangeable., Background The global push for the use of hydroxychloroquine (HCQ) and chloroquine (CQ) against COVID-19 resulted in an ongoing discussion about the effectivity and toxicity of these drugs. Recent studies report no effect of (H)CQ on 28 day-mortality. We investigated the effect of HCQ and CQ in hospitalized patients on the non-ICU COVID-ward. Methods A nationwide, observational cohort study was performed in The Netherlands. Hospitals were given the opportunity to decide independently on the use of three different COVID-19 treatment strategies: HCQ or CQ, or no treatment. We compared the outcome between these groups. The primary outcomes were 1) death on the COVID-19 ward, and 2) transfer to the Intensive Care Unit (ICU). Results The analysis contained 1064 patients from 14 hospitals: 566 patients received treatment with either HCQ (n = 189) or CQ (n = 377), and 498 patients received no treatment. In a multivariate propensity matched weighted competing regression analysis, there was no significant effect of (H)CQ on mortality on the COVID-ward. HCQ however was associated with a significant decreased risk of transfer to the ICU (Hazard ratio (HR) = 0.47, 95%CI = 0.27–0.82, p = 0.008), when compared to controls. This effect was not found in the CQ group (HR = 0.80; 95%CI = 0.55–1.15, p = 0.207), and remained significant after competing risk analysis. Conclusion The results of this observational study demonstrate a lack of effect of (H)CQ on non-ICU mortality. However, we show that the use of HCQ - but not CQ - is associated with 53% decreased risk of transfer of COVID-19 patients from the regular ward to the ICU. Recent prospective studies have reported on 28 days all-cause mortality only, therefore additional prospective data on the early effect of HCQ in preventing transfer to the ICU is still needed.

Published
2020

8. Identification of patients at high risk for Clostridium difficile infection: development and validation of a risk prediction model in hospitalized patients treated with antibiotics

Author

Steven F. T. Thijsen, Jan Jelrik Oosterheert, R.J.A. Diepersloot, C.H. van Werkhoven, J. van der Tempel, D.F. Postma, Marc J. M. Bonten, and R. Jajou

Subjects
Adult, Male, Microbiology (medical), medicine.medical_specialty, Adolescent, Logistic regression, Risk Assessment, Decision Support Techniques, law.invention, Young Adult, Antibiotics, law, Internal medicine, Journal Article, medicine, Humans, Validation Studies, Aged, Retrospective Studies, Aged, 80 and over, Primary prevention, Framingham Risk Score, Receiver operating characteristic, Clostridioides difficile, Enterocolitis, business.industry, Retrospective cohort study, Clostridium difficile, General Medicine, Middle Aged, Intensive care unit, Risk prediction, Confidence interval, Anti-Bacterial Agents, Surgery, Hospitalization, Infectious Diseases, ROC Curve, Clostridium Infections, Female, Antibiotic-associated diarrhoea, business, Risk assessment, Hospital infection control
Abstract

To develop and validate a prediction model for Clostridium difficile infection (CDI) in hospitalized patients treated with systemic antibiotics, we performed a case–cohort study in a tertiary (derivation) and secondary care hospital (validation). Cases had a positive Clostridium test and were treated with systemic antibiotics before suspicion of CDI. Controls were randomly selected from hospitalized patients treated with systemic antibiotics. Potential predictors were selected from the literature. Logistic regression was used to derive the model. Discrimination and calibration of the model were tested in internal and external validation. A total of 180 cases and 330 controls were included for derivation. Age >65 years, recent hospitalization, CDI history, malignancy, chronic renal failure, use of immunosuppressants, receipt of antibiotics before admission, nonsurgical admission, admission to the intensive care unit, gastric tube feeding, treatment with cephalosporins and presence of an underlying infection were independent predictors of CDI. The area under the receiver operating characteristic curve of the model in the derivation cohort was 0.84 (95% confidence interval 0.80–0.87), and was reduced to 0.81 after internal validation. In external validation, consisting of 97 cases and 417 controls, the model area under the curve was 0.81 (95% confidence interval 0.77–0.85) and model calibration was adequate (Brier score 0.004). A simplified risk score was derived. Using a cutoff of 7 points, the positive predictive value, sensitivity and specificity were 1.0%, 72% and 73%, respectively. In conclusion, a risk prediction model was developed and validated, with good discrimination and calibration, that can be used to target preventive interventions in patients with increased risk of CDI.

Published
2015

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