A targeted analytical framework to optimize posthospitalization delirium pharmacotherapy in patients with Alzheimers disease and related dementias

精神错乱(精神状态的急性障碍)发生在46-56%的痴呆症患者(PLWD)中 在住院期间。阿尔茨海默病和相关痴呆症(ADRD)是最危险的因素之一 在住院期间出现精神错乱。虽然非标签使用，抗精神病药物(APM)是 最常用的药物疗法是处理精神障碍的心理症状。因为PLWD 通常因急性疾病而从精神错乱中恢复的时间较长，约30%的新患者 住院期间启动APM的患者已出院，60%的APM患者已出院 持续&gt；6周。由于非处方药可能会引起许多危及生命的不良反应，因此 在住院后及时停止使用。然而，几个关键的知识差距限制了 产生必要的证据来指导这样的去处方过程：1)目前没有直接的数据来自 停用APM治疗神志不清的随机对照试验(RCT) 当患者处于急性精神错乱状态时，招募并同意PLWD或他们的医疗代理人 参与随机对照试验，任何干预性研究都将严重低估常规可见的脆弱的PLWD 关心。2)在非随机化设置中，当比较不同的 用于治疗急性精神错乱的药物的停药策略以及所需的详细临床信息 这种分析在常规护理数据中通常是不可用的。我们的目标是建立一个分析性的 支持比较持续和多次停药的有效因果效果估计的框架 帕金森病后精神障碍患者的APM治疗策略(例如，突然停止与逐渐减少剂量相比) 住院治疗。我们将集成电子健康记录(EHR)、国家索赔数据和多个临床 评估数据，涵盖2013年至2026年的502,000个可编程逻辑器件，并使用高维机- 学习辅助混合调整和表型算法。我们的具体目标包括1)整合 包含联邦医疗保险索赔数据、最小数据集(MDS)、结果和评估信息集的电子病历 (OASIS)和住院康复机构患者评估工具(IRF-PAI)，并开发新的 确定关键临床表型的算法；2)评估APM的使用/停用模式和风险 PLWD患者住院后长期使用APM治疗精神分裂症的影响因素；3)评估APM对健康的影响 不同的APM停用策略(考虑剂量减少量和减药率)与继续使用 PLWDS患者入院后精神障碍的APMS分析主要临床表型的亚群效应，典型与非典型。 非典型急性呼吸综合征，以及入院类型也将确定。这项提议将产生证据，反映 提供常规护理，以告知患有精神错乱的PLWD患者出院后APM管理。它还将建立一个 评估非处方药物疗法对健康影响的通用分析框架 精准医学需要详细的治疗效果异质性评价。

Delirium (acute disturbance in mental status) occurs in 46-56% of persons living with dementia (PLWDs) during hospitalization. Alzheimer’s disease and related dementias (ADRD) are among the strongest risk factors for developing delirium during hospitalization. Although an off-label use, antipsychotic medications (APMs) are the most commonly used pharmacotherapy to manage psychological symptoms of delirium. Because PLWDs often have a prolonged recovery course from delirium due to acute illness, ~30% of the patients who newly initiate an APM during hospitalization are discharged with them, and >60% of those discharged with an APM persist for >6 weeks. Since APMs may cause numerous life-threatening adverse reactions, it is critical to discontinue them after hospitalization in a timely fashion. However, several critical knowledge gaps limit the necessary evidence generation to guide such a deprescribing process: 1) There is currently no direct data from randomized control trials (RCT) on discontinuation of APMs used for delirium because it is extremely difficult to recruit and consent PLWDs or their healthcare proxies when the patient is in an acute delirious state to participate in an RCT, and any interventional study would severely underrepresent frail PLWDs seen in routine care. 2) In the non-randomized settings, adjusting for confounding is challenging when comparing different deprescribing strategies of a medication used for acute delirium, and the detailed clinical information required for such analyses is not typically available in routine care data. Our objective is to establish an analytical framework that enables valid causal effect estimation comparing continuation and multiple deprescribing strategies (e.g., abrupt discontinuation vs. gradual dose reduction) of APMs in PLWDs with delirium after hospitalization. We will integrate electronic health records (EHR), national claims data, and multiple clinical assessment data, covering >502,000 PLWDs from 2013 to 2026, and employ high-dimensional machine- learning aided confounding adjustment and phenotyping algorithms. Our specific aims include 1) To integrate EHR with Medicare claims data, Minimum Data Set (MDS), Outcomes and Assessment Information Set (OASIS), and Inpatient Rehabilitation Facility Patient Assessment Instrument (IRF-PAI) and to develop novel algorithms to determine key clinical phenotypes; 2) To assess APM utilization/discontinuation patterns and risk factors of prolonged use of APMs for delirium in PLWDs after hospitalization; 3) To assess the health impact of different discontinuation strategies (considering the amount and rate of dose reduction) of APMs vs. continuing APMs in PLWDs with delirium after hospitalization. The subgroup effects by key clinical phenotypes, typical vs. atypical APMs, and type of admission will also be determined. This proposal will generate evidence reflecting routine care delivery to inform post-discharge APM management in PLWDs with delirium. It will also establish a generalizable analytical framework assessing the health effects of deprescribing pharmacotherapies for delirium with detailed treatment effect heterogeneity evaluation necessary for precision medicine.