Impact of Gender on Infected Hospitalized Patients

描述(由申请人提供)： 传染病继续在老年、危重病人和住院病人中造成令人无法接受的高发病率和死亡率。动物和人类研究表明，性别对感染的易感性和死亡率都有重大影响。然而，到目前为止，所有的临床研究要么规模较小，要么基于回溯性信息。动物研究支持的这些可能的结局差异的一种解释是，通过细胞因子和生物反应性中介反应的变化，调节循环中的雌二醇和睾酮水平可能具有免疫“保护性”。另一种可能性是，社会/家庭价值观中的性别差异是患者死亡的决定因素，包括死亡模式(停止支持与不可逆转的生理崩溃)和关于长期、高质量生活生存可能性的假设。有待检验的假设(根据初步数据产生)是，尽管在控制了入院诊断和疾病严重程度后，男性和女性的感染发生率相似，但两性的雌二醇水平高与更高的死亡率相关，死亡率也将高度依赖于生命末期的决定和其他社会变量。目的1.在控制了包括性别在内的多个预先定义的混杂变量后，前瞻性地确定危重人群医院感染的发生率和相关死亡率。目的2.确定性激素状况、全身细胞因子水平与医院获得性感染的发生率和转归之间的关系，以及感染和临终决定对死亡患者转归的相对贡献。 从这项研究获得的数据将被用来设计干预研究，利用激素操纵，即替代或阻断，以改善其他致命传染病的结果。

DESCRIPTION (provided by applicant): Infectious diseases continue to cause an unacceptably high morbidity and mortality among elderly, critically ill, and hospitalized patients. Animal and human studies imply a significant gender-related influence on both susceptibility to and mortality from infection. All clinical studies to date, however, have been either small or based on retrospective information. One explanation for these possible differences in outcome supported by animal studies is that modulation of circulating levels of estradiol and testosterone may be immunologically "protective," mediated by changes in cytokine and biologically reactive intermediary response. Another possibility is that gender differences in social/ family values 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 (generated from preliminary data) is that although the incidence of infection is similar for men and women after controlling for admission diagnosis and severity of illness, high estradiol levels in both sexes is associated with higher mortality, and that mortality will also be highly dependent on end of life decisions among other social variables. Aim 1. To prospectively determine the incidence of and associated mortality from hospital-acquired 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 hospital-acquired infections, as well as the relative contribution of infection and end of life decisions to outcome in patients dying under study. Data obtained from this research will be used to design interventional studies utilizing hormonal manipulation, i. e., replacement or blockade, to improve outcomes from otherwise lethal infectious diseases.