Medication Adherence in Children Who Had a Liver Transplant (MALT)

描述(由申请人提供)：这项修订后的多中心建议利用现有的儿科肝脏移植研究(SPLIT)登记，并增加了其他预期获得的数据，以测试接受肝移植的儿童对免疫抑制药物依从性的客观衡量。不粘连是儿科肝移植长期存活者发生器官排斥反应的最重要原因。为了有效地解决这一重要的风险因素，第一步是评估一种方法，可以识别这些儿童中的不依从性。作为移植中心临床实践的一部分，药物血液水平可以用来确定患者是否依附。计算每个患者的药物血药浓度随时间的波动程度将识别出不依从性(更大的波动=更少的服药一致性=更少的依从性)。药物血药浓度的波动程度与排斥反应有关。这笔赠款评估了这种方法的使用(计算药物血液水平的变异性)以及在一大群移植患者中遵守的其他辅助措施。它决定了依从性的“门槛”(不依从性何时开始与器官排斥有关)。这项建议还利用前瞻性跟踪的队列来评估不遵守的心理社会预测因素。这些预测因素可以用来为干预努力提供信息，以提高遵从性。由于这项建议将验证一种临床上有用的评估依从性的方法，结果有望提高儿童移植受者的存活率并减少排斥反应。这些结果也有望为其他领域的依从性研究提供参考：这种新颖、客观的不依从性生物标记可以在其他人群中使用。此外，该检测方法将为支持移植环境中的依从性研究(如治疗策略)提供必要的基础，其结果可推广到其他环境。公共卫生相关性：接受器官移植的儿童的生存依赖于免疫抑制药物，但许多人停止服用。这项提案将验证一种识别因不服药而面临风险的儿童的方法。这一结果将有助于移植中心识别这些儿童，并提高移植后的总体存活率，还将为儿童可能不按处方服用药物的其他医学领域提供信息。

DESCRIPTION (provided by applicant): This revised multi-center proposal takes advantage of the existing Studies in Pediatric Liver Transplant (SPLIT) registry augmented by additional prospectively-obtained data to test an objective measure of adherence to immunosuppressant medications in children who had a liver transplant. Nonadherence is the most important reason for organ rejection in long term survivors of pediatric liver transplantation. In order to address this important risk-factor effectively, the first step is to evaluate a method that would identify nonadherence in these children. Medication blood levels that are obtained as a part of clinical practice in transplant centers can be used to determine whether the patient is adherent or not. Calculating the degree of fluctuation of medication blood levels over time for each patient would identify nonadherence (more fluctuation = less consistent medication-taking = less adherence). The degree of fluctuation in medication blood levels is correlated with rejection episodes. This grant evaluates the use of this method (calculating the variability in medication blood levels) along with other ancillary measures of adherence in a large group of transplant patients. It determines a "threshold" of adherence (when does nonadherence begin to be associated with organ rejection). This proposal also takes advantage of the prospectively-followed cohort to evaluate psychosocial predictors for nonadherence. Those predictors can be used to inform intervention efforts to improve adherence. Since this proposal will validate a clinically- useful method to assess adherence, the results are expected to enhance survival and reduce rejections in pediatric transplant recipients. Results are also expected to inform adherence research in other fields: the novel, objective, biological marker for nonadherence can be used in other populations. Furthermore, the detection method will provide the essential basis to support adherence research in the transplant setting (such as treatment strategies), results from which can be generalized to other settings. PUBLIC HEALTH RELEVANCE: The survival of children who have received an organ transplant is dependent on immunosuppressant medications, but many stop taking them. This proposal will validate a method to identify children who are at risk because of not taking their medications. The results will help transplant centers identify these children and improve overall post transplant survival, and will also inform other areas of medicine in which children may not take their medications as prescribed.