International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.


Journal

JAMA dermatology
ISSN: 2168-6084
Titre abrégé: JAMA Dermatol
Pays: United States
ID NLM: 101589530

Informations de publication

Date de publication:
01 05 2022
Historique:
pubmed: 31 3 2022
medline: 21 5 2022
entrez: 30 3 2022
Statut: ppublish

Résumé

A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.

Identifiants

pubmed: 35353175
pii: 2790347
doi: 10.1001/jamadermatol.2022.0434
doi:

Substances chimiques

Folic Acid 935E97BOY8
Methotrexate YL5FZ2Y5U1

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

561-572

Subventions

Organisme : Medical Research Council
ID : MR/T02383X/1
Pays : United Kingdom

Auteurs

Astrid M van Huizen (AM)

Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands.

Stef P Menting (SP)

Department of Dermatology, OLVG, Amsterdam, the Netherlands.

Rolland Gyulai (R)

Department of Dermatology, University of Pécs, Medical School, Venerology and Oncodermatology, Pécs, Hungary.

Lars Iversen (L)

Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.

Gayle E van der Kraaij (GE)

Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands.

Maritza A Middelkamp-Hup (MA)

Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands.

Richard B Warren (RB)

The Dermatology Centre, Salford Royal NHS Foundation Trust, The Manchester NIHR Biomedical Research Centre, United Kingdom.

Phyllis I Spuls (PI)

Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands.

Adrián A Schejtman (AA)

Centro Dermatológico Schejtman, Provincia de Buenos Aires, Argentina.

Alexander Egeberg (A)

Department of Dermatology, Bispebjerg Hospital, Copenhagen, Denmark.

Alireza Firooz (A)

Center for Research and Training in Skin Diseases and Leprosy, Tehran University of Medical Sciences, Tehran, Iran.

Alur S Kumar (AS)

Apollo Hospital, Secunderabad, Telangana, India.

Amanda Oakley (A)

Waikato District Health Board, University of Auckland, Auckland, New Zealand.

Amy Foulkes (A)

The Dermatology Centre, Salford Royal NHS Foundation Trust, The Manchester NIHR Biomedical Research Centre, United Kingdom.

Andrea Machado Coelho Ramos (AMC)

Hospital das Clínicas da Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

Anne-Claire Fougerousse (AC)

Military Teaching Hospital Begin, Saint Mandé, France.

Antoanela Carija (A)

School of Medicine, University of Split, University Hospital Centre Split, Croatia.

Ayse Akman-Karakas (A)

Department of Dermatology and Venerology, Akdeniz University School of Medicine, Antalya, Turkey.

Barbara Horváth (B)

Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Béata Fábos (B)

Department of Dermatology, Teaching Hospital Kaposvar, Kaposvar, Hungary.

Benjamin Hidalgo Matlock (BH)

University of Costa Rica/Hospital Nacional de Niños, San Pedro Montes de Oca, San Jose Province, Costa Rica.

Birgitta Wilson Claréus (BW)

Psoriasis Treatment Wards, Stockholm, Sweden.

Carla Castro (C)

Dermatologist Hospital Universitario Austral, Buenos Aires, Argentina.

Carlos Ferrándiz (C)

Department of Dermatology, Hospital universitario Germans Trias i Pujol, Universidad Autónoma de Barcelona, Barcelona, Spain.

Carolina Cortés Correa (CC)

Dermatology Service of La Samaritana University Hospital, Bogotá, Colombia.
Pontificia Universidad Javeriana/National University of Colombia, Bogotá, Colombia.

Carolina Marchesi (C)

Proderma, Clínica de la piel, San Juan, Argentina.

Catherine Goujon (C)

Department of Immunology and Clinical Allergology, Lyon sud Hospital, Saint-Genis-Laval, France.

Cesar Gonzalez (C)

Private practice, Bogotá, Colombia.

César Maldonado-García (C)

Centro Dermatologico "Dr. Ladislao de la Pascua," Mexico City, Mexico.

Chih-Ho Hong (CH)

Department of Dermatology and Skin Science, University of British Columbia, Vancouver, British Columbia, Canada.

Christopher E M Griffiths (CEM)

The Dermatology Centre, Salford Royal NHS Foundation Trust, The Manchester NIHR Biomedical Research Centre, United Kingdom.

Christian Vestergaard (C)

Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.

Christina Mariela Echeverría (CM)

Instituto de Rehabilitación Psicofísica, IREP, Buenos Aires, Argentina.

Claudia de la Cruz (C)

Clinica Dermacross, Santiago, Chile.

Curdin Conrad (C)

Department of Dermatology, Lausanne University Hospital CHUV, Lausanne, Switzerland.

Dániel Törocsik (D)

Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Daniela Ledic Drvar (DL)

Department of Dermatology and Venereology, University Hospital Centre Zagreb, School of Medicine University of Zagreb, Croatia.

Deepak Balak (D)

Department of Dermatology, Ghent University Hospital, Ghent, Belgium.

Denis Jullien (D)

Hospices Civils de Lyon, Hôpital E. Herriot, Service de Dermatologie, Lyon, France.

Diebrecht Appelen (D)

Radboud University Medical Center, Nijmegen, the Netherlands.

Dong Hyun Kim (DH)

Department of Dermatology, CHA Bundang Medical Center, CHA University College of Medicine, Seongnam, Republic of Korea.

Elke M G J de Jong (EMGJ)

Radboud University Medical Center, Nijmegen, the Netherlands.

Emad El Gamal (E)

Damietta Faculty of Medicine, Al-Azhar University, Cairo, Egypt.

Emmanuel Laffitte (E)

Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland.

Emmanuel Mahé (E)

Service de Dermatologie, Hôpital Victor Dupouy, Argenteuil, France.

Enikö Sonkoly (E)

Department of Medical Sciences, Uppsala University, Uppsala, Sweden.

Erika Páez Colombo (EP)

Hospital Vargas de Caracas, Venezuela.

Eva Vilarrasa (E)

Dermatology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.

Fabienne Willaert (F)

Hôpital ERASME, Université Libre de Bruxelles, Anderlecht, Belgium.

Farah D Novoa (FD)

Private practice, Santiago de Surco, Peru.

Farhad Handjani (F)

Molecular Dermatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Fernando Valenzuela (F)

Department of Dermatology University of Chile and Centro Internacional de Estudios Clinicos, Probity Medical Research, Santiago, Chile.

Francisco Vílchez-Márquez (F)

Department of Dermatology, Hospital Universitario Virgen de las Nieves, Granada, Spain.

Gabriela Otero Gonzalez (GO)

Hospital de Clínicas. Universidad de la República Montevideo, Uruguay.

Gáspár Krisztián (G)

Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Giovanni Damiani (G)

Department of Clinical Dermatology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy.
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy.

Gordana Krnjevic-Pezic (G)

NAFTALAN, Special Hospital for Medical Rehabilitation, Zagreb, Croatia.

Graciela Pellerano (G)

SOARPSO, Argentina.

Gregorio Carretero (G)

Servicio de Dermatología, Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas de Gran Canaria, Spain.

Hamish J A Hunter (HJA)

The Dermatology Centre, Salford Royal NHS Foundation Trust, The Manchester NIHR Biomedical Research Centre, United Kingdom.

Hassan Riad (H)

Hamad Medical Corporation, Qatar.

Hazel H Oon (HH)

National Skin Centre, Singapore.

Hugo P J Boonen (HPJ)

Heilig Hartziekenhuis, Leuven, Belgium.

Iftin Osman Moussa (IO)

Service de Dermatologie, Hôpital Cheiko, Djibouti.

Ignacio García-Doval (I)

Dermatology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain.

Ildíko Csányi (I)

Department of Dermatology and Allergology, Albert Szent-Györgyi Health Center, Department of Dermatology and Allergology, Szeged, Hungary.

Ines Brajac (I)

Department of Dermatovenerology, University Hospital Clinic Rijeka, Croatia.

Irina Turchin (I)

Brunswick Dermatology Center, Fredericton, New Brunswick, Canada.
Dalhousie University, Halifax, Nova Scotia, Canada.
Probity Medical Research, Waterloo, Ontario, Canada.

Ivan Grozdev (I)

Department of Dermatology, Brugmann University Hospital, Brussels, Belgium.

Jeffrey M Weinberg (JM)

Icahn School of Medicine at Mount Sinai, New York, New York.

Jenny Nicolopoulos (J)

Department of Dermatology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Jillian Wells (J)

University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.

Jo L W Lambert (JLW)

Department of Dermatology, Ghent University Hospital, Ghent, Belgium.

John R Ingram (JR)

Department of Dermatology, Division of Infection & Immunity, Cardiff University, Cardiff, Wales.

Jörg Christoph Prinz (JC)

Department of Dermatology and Allergy, University Hospital, LMU Munich, Munich, Germany.

José Alexandre de Souza Sittart (JA)

Hospital do Servidor Publico Estadual de Sao Paulo, Brazil.

Jose Luis Sanchez (JL)

Department of Dermatology, General Hospital Valencia, Valencia, Spain.

Josephine Pa-Fan Hsiao (JP)

Department of Dermatology, MacKay Memorial Hospital, Taipei City, Taiwan.

Juan Raul Castro-Ayarza (JR)

Universidad Militar, Colpsor, Colombia.

Julia-Tatjana Maul (JT)

Department of Dermatology, University Hospital of Zürich, Zürich, Switzerland.

Juul M P A van den Reek (JMPA)

Department of Dermatology, Radboudumc, Nijmegen, the Netherlands.

Katarina Trcko (K)

Department of Dermatology and Venereal Diseases, University Medical Centre Maribor, Maribor, Slovenia.

Kirk Barber (K)

University of Calgary, Calgary, Alberta, Canada.

Kristian Reich (K)

Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Germany.

Kurt Aaron Gebauer (KA)

Fremantle Dermatology, Western Australia, Australia.

Kuzma Khobzei (K)

Kyiv Medical University, Medical Centre Khobzei Clinic, Kyiv, Ukraine.

Lara V Maul (LV)

Department of Dermatology, University Hospital of Basel, Basel, Switzerland.

Larisa Prpic Massari (LP)

Department of Dermatovenerology, Clinical Hospital Center Rijeka, Medical Faculty University of Rijeka, Rijeka, Croatia.

Laurence Fardet (L)

Department of dermatology, Hôpital Henri Mondor, Creteil, France.

Laurence le Cleach (L)

University Paris Est Créteil, Créteil, France.
Department of Dermatology, Hôpitaux universitaires Henri Mondor, UPEC, Créteil, France.

Laurent Misery (L)

Department of Dermatology, University Hospital of Brest, Department of Dermatology, Brest, France.

Laxmisha Chandrashekar (L)

Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India.

Lidia Irinel Muresanu (LI)

European Academy of Dermatology and Venereology member, Romania.

Lidian Lecluse (L)

Bergman Clinics, Dermatology, Haarlem and Amsterdam.

Lone Skov (L)

Department of Dermatology and Allergy, Copenhagen University Hospital-Herlev and Gentofte, Copenhagen, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Ma Lorna Frez (ML)

University of the Philippines College of Medicine, Philippine General Hospital, Manila, Philippines.

Lucija Tomic Babic (LT)

Special Hospital for Medical Rehabilitation, Naftalan, Azerbaijan.

Lluís Puig (L)

Department of Dermatology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona School of Medicine, Barcelona, Spain.

Luis Castro Gomez (LC)

Hospital Militar Central Universidad Militar Nueva Granada, Bogota, Colombia.

M Ramam (M)

All India Institute of Medical Sciences, New Delhi, India.

Maha Dutil (M)

University of Toronto, Toronto, Ontario, Canada.

Mahira Hamdy El-Sayed (MH)

Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Malgorzata Olszewska (M)

Department of Dermatology, Medical Unversity of Warsaw, Warsaw, Poland.

Mandy Elvira Schram (ME)

ZBC Multicare, Hilversum, the Netherlands.

Manuel Dario Franco (MD)

Universidad El Bosque, Bogotá, Colombia.

Mar Llamas-Velasco (M)

Dermatology Department, Hospital Universitario de la Princesa, Madrid, Spain.

Margarida Gonçalo (M)

Department of Dermatology, Coimbra University Hospital and Faculty of Medicine, University of Coimbra, Coimbra, Portugal.

Margarita M Velásquez-Lopera (MM)

Universidad de Antioquia, Centro de Investigaciones Dermatológicas CIDERM, Medellín, Colombia.

Maria Eugenia Abad (ME)

Hospital Aleman and Hospital Ramos Mejia, Buenos Aires, Argentina.

Maria de Fátima Santos Paim de Oliveira (MFSP)

Federal University of Bahia, Brazil.

Marieke M B Seyger (MMB)

Department of Dermatology, Radboud University Medical Centre, Nijmegen, the Netherlands.

Marija Kaštelan (M)

Department of Dermatovenergology, Referral Center for Psoriasis, CHC Rijeka, University of Rijeka, Rijeka, Croatia.

Marius Rademaker (M)

Waikato Clinical School, School of Medicine, University of Auckland, Auckland, New Zealand.

Mariusz Sikora (M)

National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.

Mark Lebwohl (M)

Icahn School of Medicine at Mount Sinai, New York, New York.

Marni C Wiseman (MC)

Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

Marta Ferran (M)

Department of Dermatology, Hospital del Mar, Barcelona, Spain.

Martijn van Doorn (M)

Department of Dermatology, Erasmus Medical Center, Rotterdam, the Netherlands.

Maryam Danespazhooh (M)

Department of Dermatology, Tehran University of Medical Sciences, Tehran, Iran.

Matilda Bylaite-Bucinskiene (M)

Clinic of Infectious Diseases and Dermatovenereology, Centre of Dermatovenereology, Vilnius University, Vilnius, Lithuania.

Melinda J Gooderham (MJ)

SKiN Centre for Dermatology and Probity Medical Research, Queen's University, Peterborough, Ontario, Canada.

Melita Vukšic Polic (MV)

Osijek University Hospital, Faculty of Medicine, Osijek, Croatia.

Menno A de Rie (MA)

Department of Dermatology, Amsterdam UMC, University of Amsterdam, Amsterdam Public Health, Infection and Immunity, Amsterdam, the Netherlands.

Min Zheng (M)

School of Medicine, the Second Affiliated Hospital of Zhejiang University, Hangzhou, China.

Minerva Gómez-Flores (M)

Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Mexico.

Montse Salleras I Redonnet (M)

Department of Dermatology, Hospital Sagrat Cor, Barcelona, Spain.

Nanette B Silverberg (NB)

Icahn School of Medicine at Mount Sinai, New York, New York.

Nejib Doss (N)

Golden Towers Médical Centre, Tunis, Tunisia.

Nikhil Yawalkar (N)

Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Olivier Chosidow (O)

Universités de Tours et Nantes, Créteil, France.

Omid Zargari (O)

Skin Research Center, Tehran, Iran.

Pablo de la Cueva (P)

Dermatology Department, Hospital Unuversitario Infanta Leonor, Madrid, Spain.

Pablo Fernandez-Peñas (P)

Department of Dermatology, University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia.

Paola J Cárdenas Rojas (PJ)

National University of Colombia, Bogata, Colombia.

Paolo Gisondi (P)

Section of Dermatology and Venereology, University of Verona, Verona, Italy.

Parbeer Grewal (P)

University of Alberta, Edmonton, Alberta, Canada.

Paul Sator (P)

Department of Dermatology, Clinic Hietzing, Vienna, Austria.

Paula Carolina Luna (PC)

Hospital Aleman, Buenos Aires, Argentina.

Paulo Antonio Oldani Félix (PAO)

Departament of Dermatology, Hospital Federal dos Servidores do Estado, Rio de Janeiro, Brazil.

Paulo Varela (P)

Dermatology Department, Centro Hospitalar VN Gaia, Portugal.

Péter Holló (P)

Department of Dermatology, Venereology, and Dermatooncology, Semmelweis University, Budapest, Hungary.

Petra Cetkovska (P)

Department of Dermatovenereology, Faculty of Medicine, Charles University, Prague, Czech Republic.

Piergiacomo Calzavara-Pinton (P)

University of Brescia, Brescia, Italy.

Pierre-Dominique Ghislain (PD)

Department of Dermatology UCL St-Luc, Brussels, Belgium.

Raquel Ruiz Araujo (RR)

University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.

Ricardo Romiti (R)

Department of Dermatology, Hospital das Clínicas, University of São Paulo, São Paulo, Brazil.

Róbert Kui (R)

Department of Dermatology and AllergologyAlbert Szent-Györgyi Medical School, University of Szeged, Szeged, Hungary.

Romana Ceovic (R)

Department of Dermatology and Venereology, University Hospital Center Zagreb, School of Medicine, University of Zagreb, Zagreb, Croatia.

Ronald Vender (R)

Dermatrials Research Inc, Hamilton, Ontario, Canada.

Rosario Fátima Lafuente-Urrez (RF)

Hospital Reina Sofia, Tudela, Spain.

Rubén Del-Río (R)

Hospital L´Esperit Sant, Santa Coloma de Gramenet, Spain.

Sandra J Gulin (SJ)

Department of Dermatology, Ryhov County Hospital, Jonkoping, Sweden.

Sanjeev Handa (S)

Department of Dermatology, Venereology & Leprology, Chandigarh, India.

Satveer K Mahil (SK)

St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust and King's College London, London, England.

Seetharam A Kolalapudi (SA)

GSL Medical College, Rajahmundry, Andhra Pradesh, India.

Servando E Marrón (SE)

Dermatology Department, University Hospital Miguel Servet, Zaragoza, Spain.
Aragon Psychodermatology Research Group, Zaragoza, Spain.

Seyyede Zeinab Azimi (SZ)

Center for Research and Training in Skin Diseases and Leprosy, Tehran, Iran.

Sherief R Janmohamed (SR)

Department of Dermatology, Unit Pediatric Dermatology, SKIN Research Group, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.

Sidney Augusto da Cruz Costa (SA)

Secretaria Municipal de Saúde de Natal, Brazil.

Siew Eng Choon (SE)

Clinical School Johor Bahru, Monash University Malaysia, Subang Jaya, Malaysia.

Slavomir Urbancek (S)

Department of Dermatology, F.D. Roosevelt Hospital, Banska Bystrica, Slovakia.

Olusola Ayanlowo (O)

Dermatology Unit, Department of Medicine, Faculty of Clinical Sciences, University of Lagos, Lagos, Nigeria.

Susana M Margasin (SM)

Consultorios Integrados Rosio, Hospital I Carrasco Rosario, Argentina.

Tak-Wah Wong (TW)

Departments of Dermatology, Biochemistry & Molecular Biology, Center of Applied Nanomedicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.

Tarja Mälkönen (T)

Helsinki University Hospital, Skin and Allergy Hospital, Helsinki, Finland.

Tatiana Hurtová (T)

Jessenius Faculty of Medicine, Martin, Comenius University, Bratislava, Slovakia.

Tatiana Riveros Reciné (TR)

Faculty of Medicine, Universidad del Desarrollo Santiago de Chile, Santiago, Chile.

Theis Huldt-Nystrøm (T)

Hudpoliklinikken i Namsos, Norway.

Tiago Torres (T)

Department of Dermatology, Centro Hospitalar Universitário do Porto, Porto, Portugal.

Tong-Yun Liu (TY)

First Affiliated Hospital of Kunming Medical University, Kunming, China.

Tsira Leonidze (T)

Akad.N.Kipshidze Central University Clinic, Tbilisi, Georgia.

Vinod Kumar Sharma (VK)

School of Medical Sciences and Research, Sharda University, Uttar Pradesh, India.

Warren Weightman (W)

Queen Elizabeth Hospital, Woodville, South Australia, Australia.

Wayne Gulliver (W)

Faculty of Medicine, Memorial University of Newfoundland and Labrador, St. John's, Newfoundland and Labrador, Canada.

Wendelien Veldkamp (W)

Department of Dermatology, Radboudumc Nijmegen, Nijmegen, the Netherlands.

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