Impact of immunosuppression variability on outcomes after liver transplantation

免疫抑制变异对肝移植术后结局的影响

基本信息

  • 批准号:
    10457000
  • 负责人:
  • 金额:
    $ 16.92万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-01 至 2024-03-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Over 95% of liver transplant (LT) recipients have only one opportunity to receive a new liver during their lifetimes and long-term patient survival depends upon prolonged graft functioning. As a result of advances in immunosuppression (IS), over 70% of recipients survive more than 5 years after LT, yet wide variability exists in clinical outcomes at the center-level. Most late post-LT deaths are not directly due to liver failure, but reflect the adverse consequences of prolonged IS therapy. Due to the lack of national recommendations to guide IS after LT, its management differs across centers. Moreover, comparative efficacy and safety data for IS regimens are only available from small trials and meta-analyses. Their interpretation and generalizability are limited due to the following factors: 1) care is often provided in settings that do not reflect “real world” clinical practice; 2) few IS regimens are compared, often at a single time point; 3) late or rare outcomes are missed, and 4) publication bias is evident. Population-level research is therefore needed to evaluate comprehensively the comparative effectiveness and safety of IS regimens for LT. Understanding center differences in IS management will also identify suboptimal practices, and further encourage the development of standardized guidelines. Since fewer than 10% of the observed variability in post-transplant outcomes can be explained by pre-LT factors, we hypothesize that targeting differences in post-LT management, such as IS regimen selection, has the potential to change practice and improve outcomes on a wider scale. Using a novel linkage of transplant data from the United Network for Organ Sharing and Medicare claims, the primary aims of the proposed research are the following: Aim 1 – to describe center variability in IS management in the US; Aim 2 – to evaluate the association between IS regimen and the risks of graft failure and mortality; and Aim 3 – to determine the association between IS regimen and the risks of acute rejection, severe infection and de novo cancer as potential mechanisms for the relationships identified in Aim 2. This proposal will also foster Dr. Bittermann's career development into a fully independent NIH-funded clinical investigator with a scientific focus in LT pharmacoepidemiology and practice variability, facilitated through a comprehensive mentorship plan. This will be accomplished by: 1) additional coursework on advanced methodologies through the Center for Clinical Epidemiology and Biostatistics (CCEB) at the University of Pennsylvania, 2) direct implementation of these acquired techniques under the close supervision of a carefully selected team of faculty with extensive expertise in pharmacoepidemiology, transplant hepatology, and outcomes research, as well as longstanding experience with successfully mentoring prior grant recipients, 3) involvement in the Center for Pharmacoepidemiology Research and Training in the CCEB, and 4) development and submission of future grants during the latter part of the award period to further IS and related post-transplant management issues in LT recipients.
项目总结 超过95%的肝移植(LT)接受者在接受肝移植期间只有一次接受新肝脏的机会 寿命和患者的长期存活取决于移植物功能的延长。由于在以下方面的进步 免疫抑制(IS),超过70%的受者在移植后存活超过5年,但存在很大的差异 在中心层面的临床结果方面。大多数肝移植术后晚期死亡不是直接由肝功能衰竭引起的,而是反映了 长期的不良后果是治疗。由于缺乏指导IS的国家建议 在LT之后,它的管理在不同的中心有所不同。此外,IS的有效性和安全性的比较数据 只有通过小规模试验和荟萃分析才能获得治疗方案。它们的解释和泛化是 由于以下因素而受到限制:1)提供护理的环境通常不能反映“真实世界”的临床 实践;2)比较很少的IS方案,通常在单个时间点;3)错过较晚或罕见的结果, (4)发表偏见明显。因此,需要进行人口层面的研究,以全面评估 比较不同IS方案治疗LT的有效性和安全性。了解IS中的中心差异 管理层还将确定不太理想的做法,并进一步鼓励标准化的发展 指导方针。由于移植后结果中观察到的变异性不到10%,可以用以下方式解释 在肝移植前的因素中,我们假设肝移植后管理中的靶向性差异,如IS方案 这种选择,有可能在更大范围内改变做法和改善结果。使用一种新的连杆机构 来自器官共享和医疗保险索赔联合网络的移植数据, 建议的研究如下:目标1-描述美国信息系统管理中的中心变异性;目标2 -评估IS方案与移植失败和死亡风险之间的联系;和目标3-至 确定IS方案与急性排斥、严重感染和新生风险之间的关系 癌症是目标2中确定的关系的潜在机制。 Bittermann的职业发展成为一名完全独立的、专注于科学的NIH资助的临床研究员 在LT药物流行病学和实践变异性方面,通过一个全面的指导计划加以促进。 这将通过以下方式实现:1)通过中心提供关于高级方法的额外课程 宾夕法尼亚大学临床流行病学和生物统计学(CCEB),2)直接实施 这些技术是在精心挑选的教员团队的密切监督下获得的,这些教员具有广泛的 在药物流行病学、移植肝病学和结果研究方面的专业知识,以及长期的 成功指导以前的赠款获得者的经验,3)参与中心 CCEB药物流行病学研究和培训,以及4)未来的发展和提交 在获奖期的后半部分提供赠款,以进一步解决信息系统和相关的移植后管理问题 它的接受者。

项目成果

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Therese Bittermann其他文献

Therese Bittermann的其他文献

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{{ truncateString('Therese Bittermann', 18)}}的其他基金

Impact of mammalian target of rapamycin inhibitor therapy on aging-related outcomes
雷帕霉素抑制剂治疗哺乳动物靶标对衰老相关结果的影响
  • 批准号:
    10564036
  • 财政年份:
    2023
  • 资助金额:
    $ 16.92万
  • 项目类别:
2/4-American Consortium of Early Liver Transplantation-Prospective Alcohol-associated liver disease Cohort Evaluation (ACCELERATE-PACE)
2/4-美国早期肝移植联盟-前瞻性酒精相关性肝病队列评估(ACCELERATE-PACE)
  • 批准号:
    10711336
  • 财政年份:
    2023
  • 资助金额:
    $ 16.92万
  • 项目类别:
Impact of immunosuppression variability on outcomes after liver transplantation
免疫抑制变异对肝移植术后结局的影响
  • 批准号:
    10215492
  • 财政年份:
    2018
  • 资助金额:
    $ 16.92万
  • 项目类别:
Impact of immunosuppression variability on outcomes after liver transplantation
免疫抑制变异性对肝移植术后结局的影响
  • 批准号:
    10671218
  • 财政年份:
    2018
  • 资助金额:
    $ 16.92万
  • 项目类别:

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