Impact of statins and ACE inhibitors on outcomes for pneumonia and sepsis

描述(由申请人提供)：项目摘要：在美国，65岁人群中与传染病相关的住院率和死亡率一直保持稳定或显著上升，其中大多数死亡与社区获得性肺炎(CAP)和败血症有关。细胞因子在细菌感染性疾病患者的宿主防御机制中发挥核心作用，但也可能导致感染性休克或急性呼吸窘迫综合征，几种常见的药物，包括他汀类药物、血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂(ARB)已被证明可以减少由细胞因子引起的全身炎症。几项小型研究表明，因感染疾病住院治疗的他汀类药物或血管紧张素转换酶抑制剂的患者改善了临床结果。然而，需要进一步的研究来澄清这些药物是否对CAP和脓毒症患者的护理有益。这项研究的目的是：1)确定门诊使用感兴趣的药物与临床结果之间的关系，包括败血症和CAP住院患者的30天死亡率、住院时间(LOS)和机械通气率。2)确定CAP和脓毒症患者住院期间持续服用感兴趣药物的特性与临床结果之间的关系。3)研究最常用的ACE抑制剂和他汀类药物的用药剂量对CAP合并脓毒症住院患者30天死亡率的影响。这项拟议的研究是对从几个VA来源收集并合并的数据进行的回溯性队列研究二次数据分析，以检查ACE抑制剂、ARB和他汀类药物对CAP和脓毒症住院患者重要临床结局的影响。该队列将包括2002-2005财政年度在退伍军人事务部(VA)医院住院的所有患有CAP或脓毒症的患者，他们在入院前至少接受了一年的初级护理。使用退伍军人管理局卫生保健系统的临床数据库，获得的数据包括人口统计数据、共病情况、门诊和住院患者使用的药物以及住院患者的实验室数据。将对脓毒症和CAP患者进行单独的分析。主要结果将是30天的死亡率，次要结果将是住院时间和机械通气率。初步分析将使用广义线性混合效应模型检验感兴趣的药物对临床结果的影响。相关性：这项研究的结果将被用来确定a)是否应该进行随机对照试验，测试这些药物对传染病结局的影响，以及b)更好地了解这些药物是否应该常规推荐给肺炎和/或败血症的高危人群。

DESCRIPTION (provided by applicant): Project Summary: In the United States, rates of infectious disease-related hospitalizations and mortality have remained stable or increased significantly for those > 65 years of age, and the majority of these deaths are related to community-acquired pneumonia (CAP) and sepsis. Cytokines play a central role in the host defense mechanisms for patients with bacterial infectious diseases but may lead to septic shock or acute respiratory distress syndrome, and several common medications including statins, ACE inhibitors, and angiotensin receptor blockers (ARBs) have been demonstrated to reduce systemic inflammation due to cytokines. Several small studies have demonstrated that patients on statins or ACE inhibitors hospitalized with infectious disorders have improved clinical outcomes. However, further research is needed to clarify whether these medications may be beneficial in the care of patients with CAP and sepsis. The aims of this study are: 1) Determine the association between the outpatient use of medications of interest and clinical outcomes, including 30-day mortality, length of stay (LOS), and rates of mechanical ventilation for patients hospitalized with sepsis and CAP. 2) Determine the association between the inpatient continuation of medications of interest properties and clinical outcomes for patients hospitalized with CAP and sepsis. 3) To examine the impact of medication dosage of the most commonly used ACE inhibitor and statin upon 30-day mortality for patients hospitalized with CAP and sepsis. The proposed study is a retrospective, cohort study secondary data analysis of data gathered from several VA sources and merged to examine the impact of ACE inhibitors, ARBS, and statins upon important clinical outcomes for patients hospitalized with CAP and sepsis. The cohort will consist of all patients hospitalized in Department of Veterans Affairs (VA) hospitals with either CAP or sepsis in fiscal years 2002-2005 who received at least 1 year of primary care prior to admission. Data to obtained includes demographics, comorbid conditions, medications used as an outpatient and inpatient, and inpatient laboratory data, using the clinical databases of the VA health care system. Separate analyses will be performed for patients with sepsis and CAP. The primary outcome will be 30-day mortality, and secondary outcomes will be length of stay and rates of mechanical ventilation. The primary analyses will examine the impact of the medications of interest upon the clinical outcomes using generalized linear mixed-effect models. Relevance: Findings from this study will be used to determine a) whether randomized controlled trials testing the impact of these drugs on infectious disease outcomes should be conducted, and b) to better understand if these medications should be routinely recommended for populations at high-risk for pneumonia and/or sepsis.