Impact of Gender on Infected Hospitalized Patients

尽管有效的抗生素和支持的可用性，传染病继续导致老年人，危重病患者和住院患者中不可接受的高发病率和死亡率。 最近的动物和人类研究表明，在实验和临床环境中，性别对感染的易感性和死亡率都有重大影响。 然而，这方面的所有临床研究要么规模较小，要么基于前瞻性收集数据的回顾性分析。 动物研究支持的这些可能的结果差异的一种解释是，雌二醇循环水平升高（见于绝经前成年女性，特别是在排卵期）和全身睾酮水平降低具有免疫“保护”作用，由细胞因子反应的变化介导。 然而，另一种可能性与作为患者死亡决定因素的社会/家庭价值观差异有关，包括死亡模式（撤回支持vs.不可逆的生理崩溃）和关于长期高生活质量生存可能性的假设。 在本研究中要检验的假设是，在控制混杂变量后，高全身雌激素和低全身睾酮水平（主要在绝经前女性）与医院感染发生率降低相关，但女性（特别是老年女性）每次感染的死亡率较高，并取决于激素和社会变量。目标1.在控制多个预定义的混杂变量（包括性别）后，前瞻性地确定危重人群中医院感染的发生率和相关死亡率。目标二。确定性激素状态、全身细胞因子水平与医院感染的发生率和结局之间的关系，以及感染和生命终结决定对研究中死亡患者结局的相对贡献。希望从拟议的研究中获得的数据可以用于设计利用激素操纵的干预性研究，以改善其他致命传染病的结果。

Despite the availability of effective antibiotics and support, infectious diseases continue to cause an unacceptably high morbidity and mortality among elderly, critically ill, and hospitalized patients. Recent animal and human studies imply a significant gender-related influence on both susceptibility to and mortality from infection in both experimental and clinical settings. All clinical studies in this regard, however, have been either small or based on retrospective analysis of prospectively collected data. One explanation for these possible differences in outcome that is supported by animal studies is that elevated circulating levels of estradiol (seen in pre-menopausal adult females, particularly in the peri- ovulatory period) and low systemic testosterone levels are immunologically "protective," mediated by changes in cytokine response. An alternative possibility, however, is related to differences in social/family values that are determinants of patient death, including mode of death (withdrawal of support vs. irreversible physiologic collapse) and assumptions regarding the likelihood of long- term, high quality of life survival. The hypothesis to be tested in this study is that after controlling for confounding variables, high systemic estrogen and low systemic testosterone levels (largely in pre-menopausal women) are associated with a decreased incidence of nosocomial infection, yet the mortality per infection is higher for women (particularly older women) and is dependent on both hormonal and social variables. Aim 1. To prospectively determine the incidence of and associated mortality from nosocomial infections in a critically ill population after controlling for multiple pre-defined confounding variables, including gender. Aim 2. To determine the relationship between sex hormonal status, systemic cytokine levels, and the incidence of and outcome from nosocomial infections, as well as the relative contribution of infection and end of life decisions to outcome in patients dying under study. It is hoped that data obtained from the proposed research can be used to design interventional studies utilizing hormonal manipulation to improve outcomes from otherwise lethal infectious diseases.