Transplant Network: Despite the continuing and dramatic advances in medicine and health technology, the demand for organs for transplantation drastically exceeds the number of donors. To help this situation, US Congress passed the National Organ Transplant Act in 1984, establishing the Organ Procurement and Transplantation Network (OPTN) to match organ donors to patients with organ needs. Even with all this organizational technology and service in place, there are nearly 94,000 transplant candidates in the US waiting for an organ transplant and this number is predicted to exceed 100,000 very soon. The average wait time exceeds three years--double that in some areas, such as large cities. Organs for transplant are obtained either from a cadaver queue or from living donors. The keys for the effective use of the cadaver queue are cooperation and good communication throughout the network. The good news is that the system is functioning and more and more donors (alive and deceased) are identified and used each year with record numbers of transplants taking place every month. The bad news is that the candidate list grows longer and longer. Some people think that the current system with both regional and national aspects is headed for collapse with consequential failures for some of the neediest patients. Moreover, fundamental questions remain: Can this network be improved and how do we improve the effectiveness of a complex network like OPTN? Different countries have different processes and policies, which of these work best? What is the future status of the current system? 

 

Task 1: For a beginning reference, read the OPTN Website (http://www.optn.org) with its policy descriptions and data banks (http://www.optn.org/data and http://www.optn.org/latestData/viewDataReports.asp). Build a mathematical model for the generic US transplant network(s). This model must be able to give insight into the following: Where are the potential bottlenecks for efficient organ matching? If more resources were available for improving the efficiency of the donor-matching process, where and how could they be used? Would this network function better if it was divided into smaller networks (for instance at the state level)? And finally, can you make the system more effective by saving and prolonging more lives? If so, suggest policy changes and modify your model to reflect these improvements. 

 

Task 2: Investigate the transplantation policies used in a country other than the US. By modifying your model from Task 1, determine if the US policy be would improved by implementing the procedures used in the other country. As members of an expert analysis team (knowledge of public health issues and network science) hired by Congress to perform a study of these questions, write a one-page report to Congress addressing the questions and issues of Task 1 and the information and possible improvements you have discovered from your research of the different country's policies. Be sure to reference how you used your models from Task 1 to help address the issues. 

 

Focusing on Kidney Exchange: Kidneys filter blood, remove waste, make hormones, and produce urine. Kidney failure can be caused by many different diseases and conditions. People with end-stage kidney disease face death, dialysis (at over $60,000/yr), or the hope for a kidney transplant. A transplant can come from the cadavers of an individual who agreed to donate organs after death or from a live donor. In the US, about 68,000 patients are waiting for a kidney from a deceased donor, while each year only 10,000 are transplanted from cadavers and 6,000 from living individuals (usually relatives of the patients). Hence the median wait for a matching kidney is three years--unfortunately, some needy patients do not survive long enough to receive a kidney. 

 

There are many issues involved in kidney transplantation--the overall physical and mental health of the recipient, the financial situation of the recipient (insurance for transplant and post-operation medication), and donor availability (is there a living donor willing to provide a kidney). The transplanted kidney must be of a compatible ABO blood type. The 5-year survival of the transplant is enhanced by minimizing the number of mismatches on six HLA markers in the blood. At least 2,000 would-be-donor/recipient pairs are thwarted each year because of blood-type incompatibility or poor HLA match. Other sources indicate that over 6,000 people on the current waiting list have a willing but incompatible donor. This is a significant loss to the donor population and worthy of consideration when making new policies and procedures. 

 

An idea that originated in Korea is that of a kidney exchange system, which can take place either with a living donor or with the cadaver queue. One exchange is paired-kidney donation, where each of two patients has a willing donor who is incompatible, but each donor is compatible with the other patient; each donor donates to the other patient, usually in the same hospital on the same day. Another idea is list paired donation, in which a willing donor, on behalf of a particular patient, donates to another person waiting for a cadaver kidney; in return, the patient of the donor-patient pair receives higher priority for a compatible kidney from the cadaver queue. Yet a third idea is to expand the paired-kidney donation to 3-way, 4-way, or a circle (n-paired) in which each donor gives to the next patient around the circle. On November 20, 2006, 12 surgeons performed the firstever 5-way kidney swap at Johns Hopkins Medical Facility. None of the intended donor-recipient transplants were possible because of incompatibilities between the donor and the originally intended recipient. At any given time, there are many patient-donor pairs (perhaps as many as 6,000) with varying blood types and HLA markers. Meanwhile, the cadaver queue receives kidneys daily and is emptied daily as the assignments are made and the transplants performed. 

 

Task 3: Devise a procedure to maximize the number and quality of exchanges, taking into account the medical and psychological dynamics of the situation. Justify in what way your procedure achieves a maximum. Estimate how many more annual transplants your procedure will generate, and the resulting effect on the waiting list. 

 

Strategies: Patients can face agonizing choices. For example, suppose a barely compatible--in terms of HLA mismatches--kidney becomes available from the cadaver queue. Should they take it or wait for a better match from the cadaver queue or from an exchange? In particular, a cadaver kidney has a shorter half-life than a live donor kidney. 

 

Task 4: Devise a strategy for a patient to decide whether to take an offered kidney, or to even participate in a kidney exchange. Consider the risks, alternatives, and probabilities in your analysis. 

 

Ethical Concerns: Transplantation is a controversial issue with both technical and political issues that involve balancing what is best for society with what is best for the individual. Criteria have been developed very carefully to try to ensure that people on the waiting list are treated fairly, and several of the policies try to address the ethical concerns of who should go on to the list or who should come off. Criteria involved for getting on or coming off the list can include diagnosis of a malignant disease, HIV infection or AIDS, severe cardiovascular disease, a history of non-compliance with prior treatment, or poorly controlled psychosis. Criteria used in determining placement priority include: time on the waiting list, the quality of the match between donor and recipient, and the physical distance between the donor and the recipient. As a result of recent changes in policy, children under 18 years of age receive priority on the waiting list and often receive a transplant within weeks or months of being placed on the list. The United Network for Organ Sharing Website recently (Oct 27, 2006) showed the age of waiting patients as: 

 

  Under 18: 748

  18 to 34: 8,033

  35 to 49: 20,553

  50 to 64: 28,530

  65 and over: 10,628

One ethical issue of continual concern is the amount of emphasis and priority on age to increase overall living time saved through donations. From a statistical standpoint, since age appears to be the most important factor in predicting length of survival, some believe kidneys are being squandered on older recipients. 

 

Political issues: Regionalization of the transplant system has produced political ramifications (e.g., someone may desperately need a kidney and is quite high on the queue, but his or her deceased neighbor's kidney still can go to an alcoholic drug dealer 500 miles away in a big city). Doctors living in small communities, who want to do a good job in transplants, need continuing experience by doing a minimum number of transplants per year. However, the kidneys from these small communities frequently go to the hospitals in the big city and, therefore, the local doctors cannot maintain their proficiency. This raises the question, should transplants be performed only in a few large centers, by a few expert and experienced surgeons? Would that be a fair system and would it add or detract from system efficiency? 

 

Many other ethical and political issues are being debated. Some of the current policies can be found at http://www.unos.org/policiesandbylaws/policies.asp?resources=true For example, recent laws have been passed in the US that forbid the selling or mandating the donation of organs, yet there are many agencies advocating for donors to receive financial compensation for their organ. The state of Illinois has a new policy that assumes everyone desires to be an organ donor (presumed consent) and people must opt out if they do not. The Department of Health and Human Services Advisory Committee on Organ Transplantation is expected to recommend that all states adopt policies of presumed consent for organ donation. The final decision on new national policies rests with the Health Resources and Services Administration within the US Department of Health and Human Services. 

 

Task 5: Based on your analysis, do you recommend any changes to these criteria and policies? Discuss the ethical dimensions of your recommended exchange procedure and your recommended patient strategy (Tasks 3 and 4). Rank order the criteria you would use for priority and placement, as above, with rationale as to why you placed each where you did. Would you consider allowing people to sell organs for transplantation? Write a onepage paper to the Director of the US Health Resources and Services Administration with your recommendations. 

 

Task 6: From the potential donor's perspective, the risks in volunteering involve assessing the probability of success for the recipient, the probability of survival of the donor, the probability of future health problems for the donor, the probability of future health risks (such as failure of the one remaining kidney), and the postoperative pain and recovery. How do these risks and others affect the decision of the donor? How do perceived risks and personal issues (phobias, irrational fears, misinformation, previous experiences with surgery, level of altruism, and level of trust) influence the decision to donate? If entering a list paired network rather than a direct transplant to the relative or friend, does the size n of the n-paired network have any effect on the decision of the potential donor? Can your models be modified to reflect and analyze any of these issues? Finally, suggest ways to develop and recruit more altruistic donors. 

 

器官移植: 肾交换问题(美国竞赛2007年C题) 

 

移植网络：尽管有医学和健康技术的持续不断和引人注目的进展，对移植用的器官的需求大大超过了捐赠者的数目。为帮助改善这种情况，美国国会在1984年通过了全国器官移植法案，建立了器官获得和移植网络(OPTN)来匹配器官捐赠者和需要器官的病人。即使所有这些有组织的技术和服务都到位，在美国仍然有近94000个移植申请人在等待器官移植而且预计申请人的数目很快就会超过100000人。平均的等待时间超过3年--是诸如大城市那样的地区的2倍。移植用的器官是从尸体队列或活着的捐献者那里得到的。有效的利用尸体队列是通过网络来进行配合并进行很好的交流。好消息是该系统正在起作用而且今年有越来越多的捐赠者(活着的和故去的)认可并利用该系统，这是和每个月创记录的移植数目相一致的。坏消息是等待移植的候补表列变得越来越长。有人认为由于对最需要移植的病人的重要失败，就当地以及全国而言，目前的系统面临着崩溃。此外，基本问题仍然存在：能否改进该网络以及如何改进像OPTN 那样的复杂网络的有效性？不同的国家有不同的处理过程和政策，哪个做起来最好呢？什么是目前这个系统将来的处境呢？ 

 

任务1 作为一开始的参考资料，请阅读OPTN网址(http://www.optn.org)上有关其政策的描述以及数据库(http://www.optn.org/data和http://www.optn.org/latestData/viewDataReports.asp).试对普通的美国移植网络建立一个数学模型。该模型必须对以下问题给出洞察：什么环节是有效的器官匹配的潜在的瓶颈？如果有更多的资源可用来改进捐赠者-匹配过程的有效性，什么环节以及怎样来利用这些资源？如果把该网络分为若干较小的(例如州一级的)网络，该网络的功能会更好些吗？最后，你们能够通过挽救和延长更多的生命来使该系统更为有效吗？如果可以的话，提出政策改变的建议并修改你们的模型来反映这些改进。 

 

任务2 调研不同于美国的另一个国家的移植政策。修改你们在任务1中的模型来确定通过在另一个国家所采用的步骤看美国的政策是否可以得到改进。作为受雇于国会的(有关公共卫生事务和网络科学方面)专家分析小组的成员，请完成对这些问题的研究，并向国会写一个一页纸的报告，提出任务1中要回答的问题和有争议的问题以及你们对不同国家的政策的研究中发现的信息以及可能的改进措施。务必说明怎样参考任务1中你们的模型来帮助回答这些问题。把注意力集中于肾交换：肾过滤血液、排除废物、制造荷尔蒙以及生产尿液。不同的疾病和条件会造成肾功能的衰退。末期肾病患者要面对死亡、透析(每年超过6 万美元的费用)或者寄希望于肾移植。移植的肾可能来自同意在死后捐赠器官的个人的尸体或活着的捐赠者。在美国，大约有686000人正等待着已经死亡的捐赠者的肾，每年只有10000人是从来自尸体的肾移植的，而6000人是从来自活人(通常是病人的亲戚)的肾移植的。因此等待一个匹配好的肾平均时间为3年--遗憾的是有些贫困的病人没能活到那么长的时间来接受一个肾移植。有许多与肾移植有关的问题--接受肾移植的个体(受体)总的身体健康和精神健康的情况、受体的经济状况(移植和术后医疗保险)以及捐赠者的可得性(有活的捐赠者愿意捐赠一个肾)。捐赠的肾必须是相容的ABO血型。通过使血液中6个HLA1制造者不匹配的数目极小的方法来提高接受移植者5年的存活时间。每年至少有2000自以为是捐赠者-受体对因为血型不相容或者很差的HLA匹配而受阻。其他一些信息来源表明在当前的等待表列中超过6000人有排除不相容捐赠者的意愿。对于捐赠者群体来说这是一种巨大的损失并且是制定新政策和步骤时值得考虑的问题。来自韩国的一种会发生在活的捐赠者或者尸体队列的有关肾交换系统的方法。一种交换就是成对-肾的捐赠，两个病人中的每一个人都有一个不相容的捐赠者，但是每一个捐赠者和另一个病人是相容的；每一个捐赠者通常是在同一个医院同一天捐赠给另一个病人。另一种方法是表列配对捐赠，一位心甘情愿的捐赠者代表一个特定的病人捐赠给正等待尸体肾另一个病人；作为回报，该捐赠者-病人对的病人得到来自尸体队列的相容肾的更高的优先权。还有第三种方法，即把配对-肾的捐赠扩大到三方、四方或者(n-对)的圈，每个捐赠者给圈中的下一个人。2006 年11月20日在JohnsHopkins Medical Facility(约翰霍浦金斯大学医疗诊所)12 位外科医生完成了第一次全五方的肾交换手术。因为捐赠者和原先计划好的受体之间的不相容性，所以不可能有预先计划好的捐赠者-受体的移植。在任何给定的时刻，有许多(也许有6000人之多的)具有不同的血型和HLA 制造者的病人-捐赠者对。眼下，每天尸体队列都得到肾而且当作出指派和完成移植时这些肾也就用完了。 

 

任务3 设计一种考虑到医学和生理学动态情形的能够极大化肾交换数量和质量的步骤。证明以什么样的方式你的步骤可以取得最大的效益。估计你们的步骤每年将多产生多少移植，以及对等待表列所产生的效果。对策：病人可能面对非常痛苦的选择。假设从HLA 的不匹配来说，来自尸体队列的一个勉强相容的肾成为可利用的。病人应该用它，或者等待来自尸体队列或交换的比较好的匹配的肾呢？特别是，尸体肾的半有效期比活的捐赠者的肾的半有效期要短。 

 

任务4　为病人设计一种对策以决定是否要接受一个提供给你的肾，或者甚至去参与肾交换计划。考虑风险、可供选择的方案以及在你们的分析中可能有的后果。道德方面的忧虑：器官移植无论从技术还是从在什么是对社会最好和什么是对个人最好之间的平衡有关的政治问题而言都是有争议的问题。试图确保在等待表列上的人都能得到公平的处理的准则已经非常仔细地研制出来了，而某些政策试图处理有关谁应该留在表列上以及谁应该从表列上去掉的道德忧虑问题。与留在表列上或者从表列去掉的准则包括：癌病的诊断、HIV 感染或爱滋病、严重的心血管疾病、不遵从优先考虑的治疗的病史或者控制得不好的精神病。决定安排优先次序的准则包括：在等待表列上的时间、捐赠者和受体之间匹配的质量以及捐赠者和受体的身体差距。作为最近的政策改变的结果，18岁以下的儿童排在等待表列优先接受的位置而且常常能够在从放在表列上的几周或几个月内接受移植。器官共享统一网络(United Network for Organ Sharing)网站最近(2006年10月27日)展示的正在等候的病人的年龄为： 

 

 18岁以下：748

 18 – 34：8,033

 35 – 49：20,553

 50 – 64：28,530

 65及大于65岁：10,628

人们持续关心的一个道德问题是就通过捐赠的挽救来延长总的存活时间中强调并优先考虑年龄的总体效果有多大。从统计观点来看，因为在预测存活时间长度看来年龄是最重要的因素，有些人相信对老年受体而言，肾正在被浪费掉。政治问题：分区的移植系统已经产生了一些政治后果(例如，某人急需一个肾而且在表列上排在相当前面，但是他或她的患病的邻居的肾仍有可能供给500英里外的大城市的一个酒精中毒的毒贩子)。想要做好移植手术的居住在小社区的医生需要通过每年做最低限度次数的移植来获得重复的经验。然而，来自这些小社区的肾常常去了大城市的医院 ，所以当地的医生就不可能保持他们的水平。这就提出了问题：只应该在不多几个大医疗中心由少数几个专家和有经验的外科医生来做移植手术吗？这是一种公平的方法吗？以及这是提高或者降低了方法的有效性吗？许多其他的道德和政治问题正在辩论之中。某些当前的政策可以从网址 http://www.unos.org/policiesandbylaws/policies.asp?resources=true获得。例如，最近在美国已经通过了禁止贩卖或批准捐赠器官的法律，然而有许多中介主张捐赠者接受对他们的器官的经济上的补贴。Illinois州有一个新政策：假设每个人都愿意成为器官捐赠者(假设同意)，如果有人不同意，那就要提出退出。卫生和人事服务部的器官移植咨询委员会(The Department of Health and Human Services Advisory Committee on Organ Transplantation)预期会建议所有的州都采用器官捐赠的假设同意的政策。有关新的全国性政策的最后决定要有美国卫生和人事服务部属下的卫生资源和服务管理部(Health Resources and Services Administration)来作出裁决。 

 

任务5 基于你们的分析，你们会建议对这些准则和政策作任何改变吗？讨论你们所建议的交换步骤和病人的对策(任务3和4)的道德方面的特点。对前面你们用作优先性和布局的次序排个序，并说明为什么你们要安排在那里的理由。你们会考虑允许人们出售用作移植的器官吗？就你们的建议给美国卫生资源和服务管理部的主任写一页纸的短文。 

 

任务6 从潜在的捐赠者的前景来看，志愿捐赠的风险包括评估受体成功的概率、捐赠者存活的概率、捐赠者未来健康问题的概率、(诸如剩下的一个肾出问题那样的)未来健康风险的概率以及术后的病痛和康复的问题。这些以及其他的风险怎样影响着捐赠者的决定？已经认识到的风险和个人问题(恐惧症、不合情理的害怕、错误的信息、先前的外科手术的经验、无私的程度以及信任的程度)怎样影响捐赠的决定？如果是进入一个成对的网络表列而不是直接移植给亲戚或朋友，n-对网络的大小 n 会对潜在的捐赠者的决定产生任何影响吗？能否修改你们的模型来反映和分析这些问题吗？最后，对扩展和补充更多的无私的捐赠者的方法提出建议。