newsletter 202 EUROTRANSPLANT Introduction CONTENTS August 2005 ISSN Dear Reader of the Eurotransplant Newsletter,

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1 EUROTRANSPLANT newsletter 202 August 2005 ISSN CONTENTS 1 Introduction 2 Calendar of Events 3 Introduction of the new Eurotransplant management 5 DELEGATES OF THE EURO- TRANSPLANT ASSEMBLY News from the Eurotransplant Duty / Allocation Office 8 Abstract Eurotransplant Newsletter is a publication of the Eurotransplant International Foundation. The editor welcomes articles pertaining to organ donation, allocation and transplantation. If there are issues not discussed in the Eurotransplant Newsletter, that you would like to see, please contact the editor. Send copy preferably via Dr. B. Cohen, editor, Eurotransplant, P.O. Box 2304, 2301 CH Leiden, the Netherlands bcohen@eurotransplant.nl Introduction Dear Reader of the Eurotransplant Newsletter, This Newsletter will be my last one. Of course, there will be plenty of opportunity to say goodbye and thank you, either at the special symposium Organ donation, procurement, allocation and transplantation in a globalized world lessons from different cultures, which is organized by Dr. Bruno Meiser, President-elect and Prof. Dr. Ferdinand Mühlbacher, Vice-President, in Munich on September 9, 2005 or at the annual Eurotransplant meeting, which will be held in beautiful Noordwijk, the Netherlands on October 6 and 7, At the end of my career at Eurotransplant after more than 30 years and almost 190 editions of the Eurotransplant Newsletter it gives me the opportunity to put down a few things in writing. As you can read on the next pages in this Newsletter, the Board of Eurotransplant has been able to find three excellent new Directors to take over the tasks of Guido G. Persijn, Medical Director and myself. Guido and I are confident that these new directors are very capable to guarantee continued quality of services to the Eurotransplant community. We would like to wish them lots of success and a great time with a unique organisation. In having said this, I would like to underline that indeed the Eurotransplant organisation which includes both the users in the transplant centers as well as the people at the ET office represents a unique institute. Even though many changes have taken place over all these 30 years, it has been possible to preserve much of the old ET family spirit. This is certainly due to the willingness of individuals from within Eurotransplant, e.g. members of the Board and the Advisory Committees, as well as from the office many co-workers work in Leiden for more than years to spend their energy and creativity on this organisation. It has also been the reason why Eurotransplant has been able to survive some crises which, were sometimes even threatening its mere existence. Despite some of these events, Eurotransplant continues to serve as a successful example one of the few unfortunately of a truly European organisation, where clinicians from six very different countries work together on a daily basis, trusting each other in matters of life and death to save the lives of their patients. To have served such an organisation is something to be very grateful for. Working with so many individuals who are willing to commit their time and much more to Eurotransplant has been one of the most rewarding aspects of continuing working with this unique institute during such a long time! This last Newsletter truly has provided me an opportunity to communicate with you. The Newsletter has created a platform to exchange ideas, publish results and keep you updated on new developments from within Eurotransplant. I would like to express my sincere thanks to all of you and wish each of you a great future. Bernard Cohen

2 Calendar of Events Calendar of Events 2 Calendar of Events 8 TH INTERNATIONAL XENOTRANSPLANTATION COESS 2ND INTERNATIONAL SYMPOSIUM ON ABO INCOMPATIBILITY IN TRANSPLANTATION September 10 14, 2005 Göteborg, Sweden For information: Inspiro Event Kastellgatan Göteborg Sweden tel.: fax: ixa2005@inspiroevent.se website: 9 TH INTERNATIONAL WORKSHOP ON LANGERHANS CELLS September 15-18, 2005 Funchal/Madeira, Portugal For information: Vienna Academy of Postgraduate Medical Education and Research Alser Strasse 4, A Vienna, Austria tel.: fax: lc2005@medacad.org website: 14 TH JAHRESTAGUNG DER DEUTSCHEN TRANSPLANTATIONSGESELLSCHAFT September 22-24, 2005 Rostock, Germany For information: K.I.T. Congress Incentives GmbH Dresden Münzgasse Dresden tel.: fax: herrmann@kitdresden.de website: IX COESS OF THE MEXICAN SOCIETY OF TRANSPLANT XIX COESS OF THE LATIN AMERICAN AND CARIBBEAN SOCIETY OF TRANSPLANT October 11 15, 2005 Cancún, Mexico For information: Sociedad Latinoamérica y del Caribe de Trasplantes tel.: fax: slact@aol.com website: 12 TH COESS OF THE EUROPEAN SOCIETY FOR ORGAN TRANSPLANTATION (ESOT) 14TH COESS OF THE EUROPEAN TRANSPLANT COORDINATORS ORGANIZATION (ETCO) October 15-19, 2005 Geneva, Switzerland For information: MCI Congress Rue de Lyon 75 PO Box Geneva 13 Switzerland tel.: fax: esot2005@mci-group.com website: 8 TH COESS OF THE ISODP (INTERNATIONAL SOCIETY FOR ORGAN DONATION AND PROCUREMENT) 5TH COESS OF THE ITCS (INTERNATIONAL TRANSPLANT COORDINATORS SOCIETY) December 3 7, 2005 Gramado, RS, Brazil For information: Congress secretariat VJS Rua Vieira de Castro, 150 / 501 CEP Santana Porto Alegre RS Brazil tel.: fax: isodp2005@vjs.com.br website: 7 TH INTERNATIONAL CONFERENCE ON NEW TRENDS IN IMMUNOSUPPRESSION AND IMMUNOTHERAPY February 16-19, 2006 Berlin, Germany For information: Kenes International (conference secretariat) 17 rue de Cendrier P.O. Box 1725, CH 1211 Geneva 1, Switzerland tel.: fax: immuno@kenes.com website: The Eurotransplant Duty Office can be reached 24 hours per day at Please note that all phone calls to the Duty Office and the Medical Staff are logged and recorded. Recording of these conversations is in accordance with Dutch Law.

3 Introduction of the new Eurotransplant management Arie Oosterlee - General Director From the first of September onwards I have been appointed as general director of the Eurotransplant International Foundation. Let me give you a short introduction of myself. I am Arie Oosterlee and 46 years old. For the past six years I have been Director Medical Affairs of the Leiden University Medical Centre in the Netherlands. Starting my career in 1987 as an Assistant Surgeon, I developed an interest in transplant medicine and the transplant community in my next job as Transplant Coordinator of the Academic Medical Centre of the Municipal University of Amsterdam. Realising that my real interest was in health care administration I followed an MBA, which I was able to bring into practice as a management consultant to the board of directors of the Medical Centre of the Free University of Amsterdam. To see what it was like to work in a commercial environment I joined an insurance company as a Risk manager where I was responsible for the development and implementation of risk management systems aimed at improving patient safety. While in this job I was offered my last position as Director Medical Affairs by the Leiden Medical Centre. My wife and I have a son (11) and a daughter (9). Whenever I can spare time I am a keen cyclist and ice-skater. Wim van Zwet - Director Finance & IT My name is Wim van Zwet and as from September 1, 2005 I have been appointed by the Board as Director Finance & IT. Despite of the fact that some of you will probably know me since I have been working for Eurotransplant for the last 10 years, I have been asked to write a small introduction of myself. I was born in The Hague on May 11, 1960 and have lived, studied and worked in the The Hague / Leiden area ever since. My educational background is in Business Economics, Accountancy and Business Administration. Prior to my professional career with Eurotransplant I have been working for 5 years in the audit practice of an international audit firm (Arthur Andersen, now Deloitte & Touche) and for 9 years as financial controller for a small American oil company. On July 1, 1995 I was appointed as controller for Eurotransplant with the responsibility for the operational financial matters of the Foundation. Since the year 2000, I have also been heading Eurotransplant s IT department. I am happily married to Anne and we have 4 children (3 daughters and 1 son). We live in Voorschoten a small suburb in the vicinity of Leiden. My hobbies are tennis, music, reading and classic Alfa Romeo s. Axel Rahmel - Medical Director I am Axel Rahmel and I will be joining Eurotransplant as the new medical director on October 1st. Born in 1962 I grew up in the small village of Uslar located south of Hannover. After graduating from the University of Goettingen medical school I became a research fellow at the Max Planck Institute for Experimental Medicine. When analysing the mechanisms of cardiopulmonary adaptation to exercise in heart and lung transplant recipients I had my first contacts with the field of transplantation. During residency training in internal medicine at the Department of Cardiology and Angiology at the University Hospital of Muenster I was predominantly involved in the management and care of heart failure and heart transplant patients. Since 1997, I have been in charge as a cardiologist of the heart failure and heart and lung transplant program at the University of Leipzig Heart Center. In addition to my clinical activities I participated in several committees dealing with different clinical and organizational aspects in the field of organ transplantation. In 2002, I was elected secretary of the Committee for Heart and Lung Transplantation of the German Transplant Society. I joined Prof. Dr. med. R. Hetzer (Chair, German Heart Center Berlin) to act as representative for all German thoracic transplant centers in the Standing Committee on Organ Transplantation of the German Medical Association. This included the development of new guidelines concerning a wide range of issues in clinical organ transplantation. As an external consultant, I also participated in meetings of the Thoracic Advisory Committee to closely coordinate all activities with Eurotransplant. I am extremely excited to join Eurotransplant and I am also very much looking forward to living and working in the Netherlands. In my spare time I enjoy playing the piano and reading. Biking, sailing and playing basketball are leisure time activities I enjoy with my wife and our two 7 and 11 years old daughters. Introduction of the new Eurotransplant management 3 Introduction of the new Eurotransplant management

4 Introduction of the new Eurotransplant management 4 Past and future presidents and directors meet in Noordwijk. Introduction of the new Eurotransplant management

5 Elections During the Assembly meeting on Thursday, October 6, 2005, the delegates of the kidney, liver and thoracic sections will have to elect four Board members A. Furthermore, all delegates will have to elect a new chairman of the Assembly. If no delegate for a transplant program is known, participation in the voting procedure is not possible. Transplant programs are now offered the last opportunity to nominate a delegate If no delegate has been nominated yet and you want to participate in the voting procedure, please contact Verena Diepeveen at the Eurotransplant office (phone or verena@eurotransplant.nl) AGA AIB AOE AOL AWG BBJ BLE GAK GAU GBB GBC GBE GBM GBO GDR GDU GES GFD GFM GFR GGI GGO GHA GHB GHG GHM AGA AIB AWG GBC GBO GES GFM GGO GHB GHG GHO GHS H. Holzer C. Bösmüller H-K. Stummvoll G. Biesenbach F. Mühlbacher D. Ysebaert J. Sennesael K. Wissing P. Peeters J-P. Squifflet R. Van Damme- Lombaerts A. Deroover Y. Vanrenterghem KIDNEY section A. Homburg H. Weihprecht R. Viebahn U. Frei / H. Neumayer G. Offermann K. Dreikorn H-U. Klehr J. Passauer K. Ivens O. Witzke R. Werner E. Scheuermann P. Pisarski E. Feuring F. Schulze A. Hamza J. Schmidt X. Rogiers V. Kliem LUNG section AIB G. Laufer AWG W. Klepetko / A. Zuckermann F. Iberer R. Steininger D. Ysebaert R. Troisi J. Lerut O. Detry J. Pirenne S. Jonas M. Wolff M. Malagó / A. Paul W. Bechstein T. Lorf J. Schmidt X. Rogiers Th. Becker O. Kollmar P. Van Schil M. Estenne M. Antoine G. Verleden GBD R. Hetzer GDR S. Tugtekin GES M. Kamler GFM H-G. Fieguth GFR GGI C. Fegbeutel LIVER section GHO GHS GJE GKI GKLM GKS GLP GLU GMA GMH GML GMN GMR GMZ GNB GRB GRO GST GTU GUL GWZ LLX NAW NLB NMS NNY NRD NRS NUT NUW SLO GJE GKI GKL GLP GMB GMH GML GMN GMZ GNB GRB GRO GTU GWZ NLB NRD SLO M. Neipp M. Girndt U. Ott F. Fändrich W. Arns T. Rath J. Fangmann L. Fricke P. Schnülle S. Thorban K-W. Jauch C. Krieglstein J. Hoyer E. Wandel B. Krämer H. Seiter / Nachfolger C. Olbricht W. Steurer J. Mayer K. Lopau P. Duhoux S. Surachno J. Homan van der Heide J. de Fijter J. van Hooff A. Hoitsma W. Weimar K. Cransberg R. Hené M. Lilien D. Kova c GHG F. Wagner GHO M. Strüber GHS H. Lausberg GJE Th. Wittwer GKI S. Hirt GLP H. Bittner GML B. Meiser GMN C. Schmid GMZ W. Kasper-König NRD NUT U. Settmacher A. Müller T. Beckurts J. Hauss H. Lippert V. Schulte-Frohlinde K-W. Jauch C. Krieglstein J. Thies T. Meyer A. Obed E. Klar W. Steurer D. Meyer M. Slooff B. van Hoek / J. Ringers H. Tilanus S. Markovi c M. Erasmus J. Bekkers AGA A. Wasler AIB G. Laufer AWG A. Zuckermann BAS AGA AIB AWG GBB GBC GBO GES GFM GFR GGI GHB GHG I. Rodrigus M. Walravens M. Antoine F. Caes A. Poncelet J. Defraigne J. Vanhaecke GAK A. Moza GBA G. Tenderich GBD R. Hetzer GDR S. Tugtekin GES M. Kamler GFM H-G. Fieguth GFR J. Martin GGI J. Bauer GGO M. Voß GHA I. Friedrich F. Iberer F. Mühlbacher D. Ysebaert A. Hoang J. de Roose J-P. Squifflet A. Deroover W. Coosemans R. Viebahn A. Kahl M. Wolff A. Paul W. Bechstein P. Pisarski D. Winter J. Schmidt X. Rogiers AGA U. Posch AIB H. Schennach AOL C. Gabriel AOW R. Loizenbauer AWG W. Mayr BBJ A. Vanhonsebrouck C. Demanet M. Andrien I. Van Haute D. Latinne G. Maggipinto M-P. Emonds GBC C. Schönemann GBE V. Mannsmann GDU R. Wassmuth GER B. Spriewald GES F. Heinemann GFM C. Seidl GFR GGI S. Immenschuh GGO H. Neumeyer GHA W. Altermann HEART section GHB F-U. Sack GHG F. Wagner GHO M. Strüber GHS H. Lausberg GJE Th. Wittwer GKI S. Hirt GKL F. Kuhn-Régnier GLP J. Gummert GMD A. Schütz GML B. Meiser GMN C. Schmid GMZ W. Kasper-König GNB R. Tandler GRB L. Rupprecht NRD NUT SLO PANCREAS section GHO GJE GKI GKL GLP GMH GML GMN GMR GMZ GNB GRB GRO GTU GUL GWZ NLB A. Maat R. Blumauer R. Lück M. Hommann F. Fändrich T. Beckurts H. Witzigmann M. Stangl H. Arbogast C. Krieglstein E. Dominguez J. Thies T. Meyer E. Klar W. Steurer J. Mayer D. Meyer R. Ploeg J. Ringers TISSUE TYPING section GHB S. Scherer GHG T. Binder GHO M. Hallensleben GKI S. Jenisch GKM G. Brand GKS GLU S. Görg GML M. Spannagl GMZ W. Hitzler GRO V. Kiefel GTU D. Wernet GUL J. Mytilineos LLX F. Hentges NAW N. Lardy S. Lems NLB G. Schreuder NMS P. van den Berg-Loonen NNY W. Allebes NUT H. Otten SLO B. Vidan-Jeras open places mean: no delegate appointed by transplant / tissue typing program in italics = representative DELEGATES OF THE EUROTRANSPLANT ASSEMBLY DELEGATES OF THE EUROTRANSPLANT ASSEMBLY

6 News from the Eurotransplant Duty / Allocation Office News from the Eurotransplant Duty / Allocation xxxxxxxxxxxxx Office News xxxxxxxxxx from the Eurotransplant Duty / Allocation Office 6 Important message regarding german blood group rules In order to comply with the current German regulations regarding post-mortem liver allocation (Richtlinien zur Organtransplantation gemäß 16 TPG, Vermittlung Leber; available at programming for blood group rules for combinations of German donors and patients has been temporarily changed. As of September 1, 2005, all German post-mortem organs will be matched for German patients blood group compatible, i.e. AB0-0 only to AB0-0 recipients. This rule applies to all donor types (pediatric/adult), recipient age groups (pediatric/adult), urgencies (HU, ACO, T2-T4) and graft types (whole/split). As of December 7, 2005, the German blood group rules will be changed in the Richtlinien according to the rules applied in Eurotransplant until August 31, Allocation of post-mortem livers will then revert back to the situation as of August 31, Please check the website frequently for future updates. Response time after organ offer Recently it occurred that some transplant centers needed too much time to decide about acceptance of an organ offer. This can cause problems with allocation and implies the risk that organs can get lost. In order to be able to allocate the organs within a reasonable time frame, a maximum response time of 30 minutes is given (in case of kidney-only allocation the response time is set to 60 minutes). When no decision is made within this time, the offer will be withdrawn by the ET duty officers without prior notice. Only in exceptional cases a delay may be granted by the Eurotransplant Medical Staff. Information More information can be found in the Eurotransplant manual on the member site of If you have any further questions after consulting the manual, please contact the Eurotransplant Duty Office ( ) or mail to Klasien Dijkstra (k.dijkstra@eurotransplant.nl). Rescue Allocation for post-mortem livers By Dr. T. Gerling One of the most controversial topics in the current ET Liver Allocation System (ELAS) is the so-called rescue allocation. When is rescue allocation indicated? Rescue allocation is indicated whenever a post-mortem organ might be lost in the regular, patient-oriented allocation. The decision to switch from regular allocation to rescue allocation is taken exclusively by the ET medical officer on call. The following two scenarios are common: a) Liver is first offered in a regularly procedure A post-mortem liver is initially offered in a patientoriented fashion according to the matchlist created in ENIS. In the course of the regular allocation, the responses from centers may indicate that the quality of the donor organ is compromised. The ET duty desk officers are instructed to contact the ET medical officer after three different centers have rejected the organ offer on medical grounds in the donor. The ET medical officer will then decide whether to continue the regular allocation or whether rescue allocation should be considered. He will take into consideration whether there is still time until procurement, whether procurement is already in progress or if the liver has already been procured (duration of cold ischemia time (CIT)). If the officer decides to switch to rescue allocation, then he will determine the centers to be contacted, preferably in the region where the organ is at that moment. Please note, that centers are not necessarily those from the donor region, but could be those close to the transplant center that already received a procured liver. The resulting organ offers to these centers are then by definition center offers, i.e. the center can choose a patient from its own waiting list. b) Liver is immediately allocated through rescue allocation A transplant coordinator (TC), after evaluation of the donor, can contact the ET duty desk upon reporting the donor to discuss with the ET medical officer the indication for an initial rescue allocation. Reasons to offer a post-mortem liver immediately through rescue allocation can be: unstable donor, compromised organ quality, logistical aspects, other medical reasons, e.g. donor virology, AB0-blood group (e.g. AB0-AB), donor age (e.g. very young/very old).

7 The decision to offer such organs immediately through rescue allocation is, in close contact with the TC, again taken exclusively by the ET medical officer (see a). Rescue allocation has become a point of interest due to several reasons. One is the change in the donor population, as donors have become increasingly older, thus an increased chance of age-related co-morbidity. Organs from these older donors are likely to be refused more frequently in the regular allocation when offered to HU and/or T2 recipients, i.e. patients in need of a good organ. A second reason may be that centers are under the pressure of long waiting lists and a stagnant number of donors. This forced more and more transplant centers, over the course of the last years, to push the limits by accepting organs that had before been regarded as not transplantable. A third reason could be that for some patients, e.g. in status T4 or T3 with no or little chance to Figure 1 Number of post-mortem whole liver transplantations in ET, stratified by decision code (regular/rescue/violation) Rescue allocation of post-mortem livers Number of post-mortem whole liver transplantations, by organ offer code (regular/rescue/violation) % N=584 N=668 N= regular rescue violation Table 1 Age of post-mortem donors whose liver was transplanted in ET, stratified by donor age group and year progress to T2 (e.g. HCC), and the need for a transplantation within a reasonable amount of time, compromised organs have become an accepted alternative. The change in strategy regarding this category of donor livers can be demonstrated in figure 1. When analyzing the number of post-mortem whole livers transplanted between 2002 and 2004, stratified for the decision code, a clear tendency can be demonstrated. One of the sources for post-mortem donor livers with increased co-morbidity is the older donor (table 1). The increased number of reported and transplanted livers from older donors is almost exclusively present in Belgium and Germany. In 2004, the number of transplanted livers from donors 66 years of age or older in these two countries was 18 (10%) and 85 (11.7%), respectively. What do we ask of the transplant coordinators? If you are asked to evaluate older donors be aware of the fact that these livers are being used more often than only a few years ago. So if, during the evaluation, the liver shows good or acceptable function, you might want to consider reporting the liver to ET. Even if this donor would not be accepted in your own country, there are many centers in ET that have indicated to be willing to accept them. What do we ask of you in the transplant centers? You might, during regular allocation, receive a patientspecific offer from a donor that you refuse because the donor organ is not acceptable for this patient. Nonetheless, if you think that this organ could be accepted for a patient lower on the match list in case of a rescue allocation later on, please inform our duty desk officers accordingly. ET will take your information into consideration once the decision to switch to rescue allocation is taken. Year 0-15 % % % % Total yrs yrs yrs yrs 55 yrs yrs 65 yrs 75 yrs yrs yrs % % % % 3 0.3% % % % % 6 0.6% % % % % 7 0.7% % % % % % % % % % % * % % % % % 773 Total % % % % % 6316 News from the Eurotransplant Duty / Allocation Office 7 News from the Eurotransplant Duty / Allocation Office * until July 31, 2005

8 Abstract News from the Eurotransplant Duty / Allocation Office 8 What should we keep in mind for the future of rescue allocation? So far, no results are available regarding the short and long term results. Further analyses will have to show whether an increased initial poor function or even failure rate can be observed and what factors might be of importance. Furthermore, the influence of using this category of donor livers on waiting list mortality and/or incidence of (acute) re-transplantation should be investigated in the near future. The issue of registration of non-resident patients on the Eurotransplant waiting list By K. Dijkstra, MD Lately there have been questions about the Eurotransplant rules for registration of non-resident patients on the waiting lists. See below for a summary of these rules. Definition of non-resident patient A non-resident patient is a patient who has his permanent address outside and is treated outside the ET region. Standard exception The resident status is automatically assigned to a nonresident patient at the time of registration if he / she: - lives and is treated in either of the two Italian provinces Süd-Tirol or Alto- Adige, and is listed at the transplant center Innsbruck, Austria; - is registered for an organ retransplant in the same transplant center where previously the same post-mortem organ was transplanted. Liver and thoracic organs The number of non-resident registrations for patients (either first or repeat) for a thoracic or liver (re)transplant should not exceed 5% of the total number of post-mortem transplantations (either first or repeat) by this center in the preceding year (RThAC01.05/RLAC01.05). This so-called 5% rule is checked on a monthly basis by the Eurotransplant administration. Transplant centers approaching this 5% will receive a warning letter. When a center exceeds the number of 5% non-resident registrations, the Eurotransplant Board will be informed immediately and appropriate sanctions will be undertaken. Kidney and Pancreas Non-resident patients are not allowed to be registered for a post-mortem transplantation on the ET kidney and pancreas waiting list, respectively. Deviant Belgian regulation According to the Royal Decree regarding the procurement and allocation of human organs (November 24, 1997), registration of non-residents on any of the Belgian organspecific waiting lists is not allowed. A non-resident person is defined as a person who has a nationality different from the Belgian or one of the other ET-countries, and who has no permanent address in Belgium or one of the other ET-countries. Information More information can be found in the Eurotransplant manual on the member site of When there are questions left about the rules concerning the registration of non-residents on one of your waiting lists, please contact the Eurotransplant Duty Office ( ) or mail to Klasien Dijkstra (k.dijkstra@eurotransplant.nl). Abstract Growth in children after kidney transplantation with living related donor graft or cadaveric graft In The Lancet, Vol. 366, issue 9480, page 151 By L. Pape, J.H.H. Ehrich, M. Zivicnjak, G. Offner The extent to which growth after renal transplantation differs between children with a living related donor graft (LRD) and those with a cadaveric donor graft (CAD) is unclear. We retrospectively studied growth in the 5 years after transplantation in 30 boys who received LRD and 21 who received CAD. Height was similar in both groups after transplantation but was greater in LRD than in CAD recipients during follow-up. LRD recipients were taller at all ages, and had greater growth velocity in infancy and during puberty. Glomerular filtration rate (GFR) was higher immediately after transplantation in LRD than in CAD recipients, but did not differ between the groups during follow-up. GFR and other factors did not affect height 5 years after transplantation. These findings support use of LRD as the preferred option in children.