Author Contributions: Dr Lundell had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Drs Galmiche and Hatlebakk contributed equally to the article's content.
Study concept and design: Galmiche, Hatlebakk, Attwood, Fiocca, Eklund, Lind, Lundell.
Acquisition of data: Galmiche, Hatlebakk, Attwood, Ell, Eklund, Lundell.
Analysis and interpretation of data: Galmiche, Hatlebakk, Attwood, Ell, Fiocca, Eklund, Långström, Lind, Lundell.
Drafting of the manuscript: Galmiche, Hatlebakk, Attwood, Ell, Eklund, Långström, Lind, Lundell.
Critical revision of the manuscript for important intellectual content: Galmiche, Hatlebakk, Attwood, Ell, Fiocca, Eklund, Långström, Lind, Lundell.
Statistical analysis: Långström.
Obtained funding: Galmiche, Hatlebakk, Lundell.
Administrative, technical, or material support: Galmiche, Hatlebakk, Attwood, Ell, Fiocca, Långström, Lind, Lundell.
Study supervision: Galmiche, Hatlebakk, Attwood, Lind, Lundell.
Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Galmiche reported that he is a consultant for several biomedical companies (AstraZeneca, Janssen-Cilag, Given Imaging, Xenoport, and Norgine) and that his institution receives grants for research from AstraZeneca, Given Imaging, and Mauna Kea Technology. He has prepared educational presentations for Shire Movetis. Dr Attwood reported that he has received honoraria for speaking at meetings sponsored by AstraZeneca. Dr Ell reported that he receives grants for research from several biomedical companies (AstraZeneca, Fujinon, Erbe, and Hitachi). Dr Fiocca reported that he has received travel and related expenses for attending study-associated meetings and his institution received a grant from AstraZeneca for central histological analyses. Drs Eklund, Långström, and Lind reported that they are employees of AstraZeneca. Dr Lundell reported that he receives consultancy and lecture fees from several biomedical companies including AstraZeneca and that his institution (Karolinska University Hospital) receives grants for research on his behalf.
LOTUS Trial Collaborators:Austria: Johannes Miholic (country coordinator), Univ Klinik für Chirurgie, Vienna; Rainer Hubmann, Jan Danis (country coordinator), Krankenhaus, Linz; Belgium: Jan Tack, Toni Lerut (country coordinator), UZ Gasthuisberg, Leuven; Hubert Piessevaux, UCL St-Luc, Jacques Devière, Clinique Universitaire Bruxelles Hôpital Erasme, Michel Buset, Centre Hospitalier Universitaire St-Pierre, and Cristiano Chioccioli, Clinique St-Jean, Brussels; Danny De Looze, UZ Gent, Gent; Jean-Claude Demoulin, Cliniques St-Joseph, and Edouard Louis, Centre Hospitalier Universitaire Sart Tilman, Liège; Jean-Michel Ghilain, Jean-Marc Maisin, CH Jolimont-Lobbes (Jolimont), Haine-Saint-Paul; Denmark: Peter Funch-Jensen (country coordinator), Århus Universitetshospital, Århus; Jørn Nielsen, Regionshospitalet Viborg, Viborg; Lars Christensen, Regionshospitalet Herning, Herning; Henning Antonsen, Kolding Sygehus, Kolding; Karsten Lauritsen, Odense Universitetshospital, Odense; Per Jess, Hillerød Hospital, Hillerød; Lene Wallin, Glostrup Hospital, Glostrup; Lars Naver, Hvidovre Hospital, Hvidovre; France: Jean-Paul Galmiche (country coordinator), Eric Letessier, CHU de Nantes–Hôtel Dieu, Nantes; Frank Zerbib, Groupe Hospitalier Saint André, Bordeaux; Bruno Bonaz, Richard Bost, CHU de Grenoble, Grenoble; Jean-Charles Delchier, Hôpital Henri Mondor, Creteil; Germany: Martin Fein, Jörn Maroske, Würzburg, Universitätsklinikum, Würzburg; Christian Ell, Dr Horst Schmidt Kliniken GmbH, Wiesbaden; Arnulf Hölscher, Uniklinik und Poliklinik für Visceral und Gefäßchirurgie, Köln; Carsten Zornig, Israelitisches Krankenhaus Hamburg, Hamburg; Joachim Helmut Schneider, Klinikum der Eberhard Karls Universität, Tübingen; Thomas Hüttl, München, Ludwig Maximilians Universität LMU, Chirurgie Poliklinikum, München; Markus Büchler, Universitätsklinikum Heidelberg, Heidelberg; Ursula Wehrmann, Universitätsklinikum Carl-Gustav-Carus an der TU Dresden, Dresden; Matthias Kemen, Herne, Ev Kkh, Chirurgie, Herne; Peter Layer, Hamburg Israelitisches Krankenhaus, Hamburg; Karl-Hermann Fuchs (country coordinator), St Markus Krankenhaus, Allgemeine Chirurgie Frankfurt/Main, Frankfurt; Solveig Kemen, Schwerpunktpraxis Gastroenterologie Praxis Kemen & Schmidt-Heinevetter, Bochum; Dieterich Hüppe, Internistische Praxisgemeinschaft, Herne; Iceland: Margrét Oddsdóttir (country coordinator), Bjarni Thjodleifsson (country coordinator), Landspitali, University Hospital, Reykjavik; Italy: Luigi Bonavina (country coordinator), Policlinico S Donato, San Donato Milanese; Ermanno Ancona, Policlinico Universitario di Padova, Padova; Mario Morino, Ospedale Le Molinette, Torino; Giusto Pignata, Alessandro Giurissa, Ospedale di Monfalcone, Monfalcone; Mauro Rossi, Ospedale S Chiara, Pisa; Riccardo Rosati, Istituto Clinico Humanitas, Rozzano; Renzo Cestari, Spedali Civili di Brescia, Brescia; Netherlands: Hein Gooszen (country coordinator), Universitair Medisch Centrum Utrecht, Utrecht; Norway: Jan Hatlebakk (country coordinator), Helse Bergen HF Haukeland Universitetssykehus, and Solomon Tefera, Haraldsplass Diakonale Sykehus AS, Bergen; Gjermund Johnsen, St Olav's Hospital HF, Trondheim; Jørgen Jahnsen, Aker Universitetssykehus HF, and Olav Sandstad, Ullevål Universitetssykehus HF, Oslo; Asbjørn Stallemo, Sørlandet Sykehus HF, Kristiansand; Jon Florholmen, Universitetssykehuset Nord-Norge HF, Tromsø; Geir Tollåli, Nordlandssykehuset HF, Bodø; Sweden: Cecilia Engström, Bengt Liedman, Lars Lundell (country coordinator), SU/Sahlgrenska Universitetssjukhus, Göteborg; United Kingdom: Chris Babbs, Stephen Attwood (country coordinator), Hope Hospital, Salford.
Funding/Support: The study was funded in total by AstraZeneca Research and Development, Mölndal, Sweden.
Role of the Sponsor: AstraZeneca contributed to the design of the study; collection, management, analysis, and interpretation of the data; and preparation, review, and approval of the manuscript, in full collaboration with the independent statistician and the study steering committee. Madeline Frame, BSc, PhD, a medical scientist affiliated with AstraZeneca, provided medical writing support to the principal author in terms of drafting the methods and results and incorporating edits from all authors. All writing was done in close collaboration with the first author and the steering committee and they gave major input to the introduction, interpretation, and discussion sections.
Independent Statistical Analysis: Hans Wedel, PhD, emeritus professor in Epidemiology and Biostatistics at the Nordic School of Public Health, Gothenburg, Sweden, undertook an independent statistical analysis, of the data on behalf of AstraZeneca, for which he was reimbursed at standard rates. The results of his analyses are included in this article. His position as an academic faculty member working independent of AstraZeneca has been verified by the dean of the faculty, Anders Foldspang.
Additional Contributions: We thank all study site personnel who contributed to the study. This article is dedicated to Ola Junghard, PhD, our colleague and statistician for many years, who passed away in November 2009.