Joint management models of kidney exchange program and deceased donor waiting list

Tese de mestrado, Estatística e Investigação Operacional (Investigação Operacional) Universidade de Lisboa, Faculdade de Ciências, 2019Pacientes com problemas renais que levem a insuficiência renal têm de se submeter a hemodiálise, um tratamento que substitui a função do rim e filtra as substâncias tóxicas do sangue. É um tratamento que envolve bastante tempo e que tem de ser repetido várias vezes por semana e como tal, dá uma qualidade de vida baixa aos pacientes. Como alternativa a este tratamento os doentes podem fazer um transplante renal e para isso podem ser transplantados através de um dador vivo ou cadáver. Um dador vivo é alguém que geralmente conhece o paciente e quer doar um dos seus dois rins saudáveis enquanto o dador cadáver é alguém que quando falece pode ser considerado um potencial dador de órgãos, de-pendendo das circunstancias da sua morte. A lista de espera para transplantação através de dadores ca-dáver normalmente é bastante longa e demorada, por isso aconselha-se sempre o paciente a tentar arran-jar um dador vivo compatível. Como por vezes é bastante difícil arranjar alguém compatível, criou-se o programa de doação renal cruzada. Este programa permite criar trocas entre pares de pacientes-dadores incompatíveis de forma a ar-ranjar compatibilidades. Assim, o dador de um par pode doar um rim a um paciente de outro, desde que o seu paciente receba um transplante de um dador de outro par. Desta forma criam-se ciclos onde se pretendem maximizar o número de transplantes. Ao longo dos anos foram-se criando várias variantes deste programa de doação renal e foram efe-tuados diversos estudos que pretendem aumentar o número de transplantes e ao mesmo tempo reduzir o tempo de espera dos pacientes, reduzindo assim o tamanho da lista de espera, mas este trabalho foca-se nos modelos propostos por Haynes et al. (2017). Estes três modelos misturam o conceito de troca entre pares incompatíveis e transplantes de dadores cadáveres. Desta forma podem-se criar cadeias iniciadas por dadores cadáveres onde o rim destes é transplantado para um paciente que se encontrava no programa com o seu dador incompatível. De se-guida o seu dador doa para o paciente de outro par e assim sucessivamente até que o dador do último par doa de volta para a lista de espera, para um paciente que não tinha um dador vivo e que portanto não estava no programa. Os modelos diferem principalmente quanto à prioridade que se dá aos pacientes e pela ordem com que se efetuam os transplantes. O simulador criado por Santos et al. (2018) foi adaptado para simular a utilização destes modelos numa população também criada pelo simulador e foram analisados e comparados de acordo com a per-centagem de transplantes feita e com o tempo de espera médio e máximo para pacientes de acordo com o seu tipo de sangue e PRA (Panel-active antibody). As maiores conclusões que se retiraram são que existe um benefício enorme em ter um dador vivo disponível para doar um rim e que, na maior parte dos casos, estes três modelos são mais vantajosos do que usar um modelo que separa a gestão do pro-grama de doação renal cruzada e a lista de espera de dadores cadáveres.Patients with kidney diseases leading to kidney failure have to undergo hemodialysis, a treatment that replaces kidney function and filters out toxic blood substances. It is a treatment that involves a lot of time and that must be repeated several times a week and as such, gives a low quality of life to patients. As an alternative to this treatment, patients can have a kidney transplant and can be transplanted through a living donor or a deceased one. A living donor is someone who usually knows the patient and wants to donate one of his two healthy kidneys while a deceased donor is someone who, when dies, can be considered a potential organ donor, depending on the circumstances of his/her death. The waitlist for transplantation by deceased donors can usually be quite long in terms of patients and waiting time, so it is always advisable for the patient to try to find a compatible living donor. As it is sometimes quite difficult to find a match, a kidney exchange program (KEP) was created. This program allows to create exchanges between incompatible patient-donor pairs in order to achieve compatibilities. Thus, the donor of one pair can donate a kidney to a patient of another, as long as his/her patient receives a transplant from a donor of another pair. This creates cycles where the num-ber of transplants aims to be maximized. Over the years, several variants of the KEP have been created and several studies have been con-ducted to increase the number of transplants and at the same time reduce the patients’ waiting time, thus reducing the size of the waiting list, but this work focuses on the models proposed by Haynes et al. (2017). These three models mix the concepts of incompatible pair exchange and deceased donor transplan-tation. Therefore, chains initiated by deceased donors can be created where the kidney is transplanted to a patient who was in the program with the incompatible donor. Then the incompatible donor donates to the patient of another pair and so on until the donor of the last pair donates back to the waitlist, to a patient who did not have a living donor and consequently was not in the program. The models differ mainly in the priority given to the patients and in the order in which the transplants are performed. The simulator created by Santos et al. (2018) was adapted to simulate the use of these models in a population also created by the simulator, being analyzed and compared according to the percentage of transplants performed and the mean and maximum waiting time for patients according to their blood type and PRA (Panel-active antibody). The main conclusions drawn were that there is an enormous benefit in having a living donor available to donate a kidney and that, in most cases, these three models are more advantageous than using a model that separates the management of the KEP and the deceased donors waitlist

Performance evaluation of national and international kidney exchange programmes with the ENCKEP simulator

In this paper we present simulations for international kidney exchange programmes (KEPs). KEPs are organised in more than ten countries in Europe to facilitate the exchanges of immunologically incompatible donors. The matching runs are typically conducted in every three months for finding optimal exchanges using hierarchical optimisation with integer programming techniques. In recent years several European countries started to organise international exchanges using different collaboration policies. In this paper we conduct simulations for estimating the benefits of such collaborations with a simulator developed by the team of the ENCKEP COST Action. We conduct our simulations on generated datasets mimicking the practice of the three largest KEPs in Europe, the UK, Spanish and the Dutch programmes. Our main performance measure is the number of transplants compared to the number of registrations to the KEP pools over a 5-year period, however, as a novelty we also analyse how the optimisation criteria play a role in the lexicographic and weighted optimisation policies for these countries. Besides analysing the performances on a single instance, we also conduct large number of simulations to obtain robust findings on the performance of specific national programmes and on the possible benefits of international collaborations

IP Solutions for International Kidney Exchange Programmes

In kidney exchange programmes patients with end-stage renal failure may exchange their willing, but incompatible living donors among each other. National kidney exchange programmes are in operation in ten European countries, and some of them have already conducted international exchanges through regulated collaborations. The exchanges are selected by conducting regular matching runs (typically every three months) according to well-defined constraints and optimisation criteria, which may differ across countries. In this work we give integer programming formulations for solving international kidney exchange problems, where the optimisation goals and constraints may be different in the participating countries and various feasibility criteria may apply for the international cycles and chains. We also conduct simulations showing the long-run effects of international collaborations for different pools and under various national restrictions and objectives. We compute the expected gains of the cooperation between two countries with different pool sizes and different restrictions on the cycle-length. For instance, if country A allows 3-way cycles and country B allows 2-way cycles only, whilst the pool size of country A is four times larger than the pool size of country B (which is a realistic case for the relation of Spain and France, respectively), then the increase in the number of transplants will be about 2% for country A and about 37% for country B

Otimização da doação renal cruzada com dessensibilização

Trabalho de projecto de mestrado, Matemática Aplicada à Economia e Gestão, Universidade de Lisboa, Faculdade de Ciências, 2015O transplante representa uma desejável alternativa de tratamento à hemodiálise para pacientes com doenças crónicas graves dos rins, melhorando consideravelmente a sua qualidade de vida e reduzindo custos a longo prazo para o Sistema Nacional de Saúde. Um rim para transplante pode vir de um dador cadáver ou de um dador vivo, porém, questões de compatibilidade continuam a ser uma barreira significativa ao acesso ao transplante, em particular para pacientes mais sensibilizados (PRA elevado), para quem é mais difícil encontrar um dador compatível. A taxa de transplante desses pacientes, tanto pela lista de espera de dador cadáver, como em programas KEP, continua a ser baixa, e o tempo de espera é habitualmente superior. A dessensibilização, um tratamento médico que diminui a quantidade de anticorpos que reagem contra tecido transplantado, melhora as hipóteses do paciente tratado encontrar um dador compatível através da lista de espera ou do KEP, no entanto o alto custo do tratamento impede que ele seja amplamente difundido. Neste trabalho propõe-se um novo método – uma conjugação do KEP e da dessensibilização – com o objectivo de aumentar a taxa de transplante e ao mesmo tempo melhorar a probabilidade de um paciente sensibilizado encontrar um dador compatível. Este método permite a pacientes que tenham um dador vivo, com quem sejam incompatíveis, participar no KEP com outros pares paciente-dador incompatíveis, recorrendo à dessensibilização, quando necessário, para aumentar o número de emparelhamentos no conjunto de pares. A dessensibilização permite também incluir mais pares com pacientes mais sensibilizados nesses emparelhamentos. Adaptando o modelo de otimização de programação inteira subjacente ao problema do KEP para incluir a dessensibilização, recorreu-se a simulações computacionais para comparar o novo modelo com 3 outras conjugações da dessensibilização com o KEP. Mostra-se que o novo método melhora a taxa de transplante para todos os pacientes da simulação, em particular para os pacientes mais sensibilizados, mantendo baixo o número de dessensibilizações empregues.Kidney transplants are a desirable treatment alternative to haemodialysis for patients with end-stage renal disease, allowing for a considerable improvement in life-quality for the patients and reducing long-term costs for the National Health System (SNS). A kidney for a transplant may come from a live or deceased donor, but both types of donors are subject to compatibility issues which remain a significant barrier to transplantation, especially for highly sensitized (high PRA) patients, for whom it is more difficult to find a compatible donor. The match rates for these patients, both on the deceased donor list and in Kidney Exchange Programs and are notoriously low, while waiting times are usually longer. Desensitization, a medical treatment that diminishes the amount of antibodies that react against transplanted tissue, improves these patients’ chances for being matched with a compatible donor through the waiting list or through KEO, but the procedure’s high cost prevents its widespread use in sensitized patients. A new method is proposed in this dissertation – a combination of KEP and desensitization – aiming to improve overall match rates while also improving the match rate for hard-to-match patients. This new method allows patients with an incompatible live donor to participate in a KEP with other incompatible patient-donor pairs, resorting to desensitization, when necessary, to achieve a larger number of matches. Desensitization also allows more pairs whose patients are more sensitizes to be included in these matches. The underlying integer programming optimization model was adapted to include desensitization and computational simulations were used to compare the new model to 3 other combinations of desensitization and KEP based on their results when applied to computer generated sets of incompatible pairs

Investigation of Matching Problems using Constraint Programming and Optimisation Methods

This thesis focuses on matching under ordinal preferences, i.e. problems where agents may be required to list other agents that they find acceptable in order of preference. In particular, we focus on two main cases: the popular matching and the kidney exchange problem. These problems are important in practice and in this thesis we develop novel algorithms and techniques to solve them as combinatorial optimisation problems. The first part of the thesis focuses on one-sided matching on a bipartite graph, specifically the popular matching. When the participants express their preferences in an ordinal order, one might want to guarantee that no two applicants are inclined to form a coalition in order to maximise their welfare, thus finding a stable matching is needed. Popularity is a concept that offers an attractive trade- off between these two notions. In particular, we examine the popular matching in the context of constraint programming using global constraints. We discuss the possibility to find a popular matching even for the instances that does not admit one. The second part of the thesis focuses on non-bipartite graphs, i.e. the kidney exchange problem. Kidney transplant is the most effective treatment to cure end-stage renal disease, affecting one in every thousand European citizen. Motivated by the observation that the kidney exchange is inherently a stochastic online problem, first, we give a stochastic online method, which provides an expected value estimation that is correct within the limit of sampling errors. Second, we show that by taking into consideration a probabilistic model of future arrivals and drop-offs, we can get reduce sampling scenarios, and we can even construct a sampling-free probabilistic model, called the Abstract Exchange Graph (AEG). A final contribution of this thesis is related to finding robust solutions when uncertainty occurs. Uncertainty is inherent to most real world problems

Políticas de Copyright de Publicações Científicas em Repositórios Institucionais: O Caso do INESC TEC

A progressiva transformação das práticas científicas, impulsionada pelo desenvolvimento das novas Tecnologias de Informação e Comunicação (TIC), têm possibilitado aumentar o acesso à informação, caminhando gradualmente para uma abertura do ciclo de pesquisa. Isto permitirá resolver a longo prazo uma adversidade que se tem colocado aos investigadores, que passa pela existência de barreiras que limitam as condições de acesso, sejam estas geográficas ou financeiras. Apesar da produção científica ser dominada, maioritariamente, por grandes editoras comerciais, estando sujeita às regras por estas impostas, o Movimento do Acesso Aberto cuja primeira declaração pública, a Declaração de Budapeste (BOAI), é de 2002, vem propor alterações significativas que beneficiam os autores e os leitores. Este Movimento vem a ganhar importância em Portugal desde 2003, com a constituição do primeiro repositório institucional a nível nacional. Os repositórios institucionais surgiram como uma ferramenta de divulgação da produção científica de uma instituição, com o intuito de permitir abrir aos resultados da investigação, quer antes da publicação e do próprio processo de arbitragem (preprint), quer depois (postprint), e, consequentemente, aumentar a visibilidade do trabalho desenvolvido por um investigador e a respetiva instituição. O estudo apresentado, que passou por uma análise das políticas de copyright das publicações científicas mais relevantes do INESC TEC, permitiu não só perceber que as editoras adotam cada vez mais políticas que possibilitam o auto-arquivo das publicações em repositórios institucionais, como também que existe todo um trabalho de sensibilização a percorrer, não só para os investigadores, como para a instituição e toda a sociedade. A produção de um conjunto de recomendações, que passam pela implementação de uma política institucional que incentive o auto-arquivo das publicações desenvolvidas no âmbito institucional no repositório, serve como mote para uma maior valorização da produção científica do INESC TEC.The progressive transformation of scientific practices, driven by the development of new Information and Communication Technologies (ICT), which made it possible to increase access to information, gradually moving towards an opening of the research cycle. This opening makes it possible to resolve, in the long term, the adversity that has been placed on researchers, which involves the existence of barriers that limit access conditions, whether geographical or financial. Although large commercial publishers predominantly dominate scientific production and subject it to the rules imposed by them, the Open Access movement whose first public declaration, the Budapest Declaration (BOAI), was in 2002, proposes significant changes that benefit the authors and the readers. This Movement has gained importance in Portugal since 2003, with the constitution of the first institutional repository at the national level. Institutional repositories have emerged as a tool for disseminating the scientific production of an institution to open the results of the research, both before publication and the preprint process and postprint, increase the visibility of work done by an investigator and his or her institution. The present study, which underwent an analysis of the copyright policies of INESC TEC most relevant scientific publications, allowed not only to realize that publishers are increasingly adopting policies that make it possible to self-archive publications in institutional repositories, all the work of raising awareness, not only for researchers but also for the institution and the whole society. The production of a set of recommendations, which go through the implementation of an institutional policy that encourages the self-archiving of the publications developed in the institutional scope in the repository, serves as a motto for a greater appreciation of the scientific production of INESC TEC

Kidney exchange simulation and optimization

One of the challenges in a kidney exchange program (KEP) is to choose policies that ensure an effective and fair management of all participating patients. In order to understand the implications of different policies of patient allocation and pool management, decision makers should be supported by a simulation tool capable of tackling realistic exchange pools and modeling their dynamic behavior. In this paper, we propose a KEP simulator that takes into consideration the wide typology of actors found in practice (incompatible pairs, altruistic donors, and compatible pairs) and handles different matching policies. Additionally, it includes the possibility of evaluating the impact of positive crossmatch of a selected transplant, and of dropouts, in a dynamic environment. Results are compared to those obtained with a complete information model, with knowledge of future events, which provides an upper bound to the objective values. Final results show that shorter time intervals between matches lead to higher number of effective transplants and to shorter waiting times for patients. Furthermore, the inclusion of compatible pairs is essential to match pairs of specific patient\u2013donor blood type. In particular, O-blood type patients benefit greatly from this inclusion