Big Data - Epidemiology of Critical Illness and Sepsis

大数据——危重疾病和败血症的流行病学

• 批准号: 10250941
• 负责人: Sameer Kadri
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10250941
• 关键词: Academic Medical Centers; Admission activity; Antibiotics; Antimicrobial Resistance; Bacterial Infections; Big Data; Biological Markers; Blood; Body mass index; Characteristics; Clindamycin; Clinical; Clinical Data; Collaborations; Communities; Complication; Critical Care; Critical Illness; Data; Data Set; Development; Diagnosis; Electronic Health Record; Epidemiology; Exotoxins; Functional disorder; Healthcare; Hematologic Neoplasms; Hospital Mortality; Hospitals; Incidence; Infection; Inflammation; Institutes; Interruption; Intravenous Immunoglobulins; Literature; Measures; Mediating; Medicare/Medicaid; Medicine; Meta-Analysis; Methods; Modeling; Morbidity - disease rate; Mortality Decline; Necrotizing fasciitis; Obesity; Oncology; Organ; Outcome; Patient Care; Patients; Pattern; Performance; Policies; Population; Prevalence; Process; Provider; Publishing; Quality of Care; Randomized Controlled Trials; Reporting; Research; Research Personnel; Risk Adjustment; Risk Factors; Sampling; Sepsis; Septic Shock; Shock; Streptococcal Infections; Streptococcus Group B; Streptococcus pyogenes; Surveys; Syndrome; T-Lymphocyte; Therapeutic; Time; Time Series Analysis; Toxic effect; Undifferentiated; United States; Validation; Variant; Vasoconstrictor Agents; base; beta-Lactams; burden of illness; clinical epidemiology; cohort; cost; cytokine; cytokine release syndrome; epidemiologic data; improved; lung injury; medical schools; mortality; prevent; procalcitonin; randomized trial; repository; smoke inhalation; systematic review; trend

Critical illness and sepsis are associated with significant morbidity and mortality, especially in conditions where existing therapeutic strategies remain suboptimal. Our primary aim is to leverage large repositories of granular clinical data to better understand the clinical epidemiology of critical illness, sepsis and serious infections, including defining illness burden, risk factors and clinical impact. The pathophysiology of organ dysfunction in streptococcal infection is attributed to inflammation mediated by exotoxin-mediated cytokine cascade. Clindamycin neutralizes exotoxin released by Group A Streptococcus. In a large propensity-matched cohort of patients we found that clindamycin added as an adjunct to beta lactam therapy was associated with improved survival in Group A streptococcal infection but also identified a trend toward harm when used in non-Group A, Group B streptococcal infections. These findings warrant confirmation in randomized trials.. Antibiotic overuse remains a significant problem in the critically ill and is associated with toxicity and development of antimicrobial resistance. Among critically ill patients with suspected or confirmed sepsis in a larger cohort of US hospitals, we found that use of procalcitonin significantly reduced duration of antibiotic use without worsening outcomes. We confirmed these findings in a meta-analysis of randomized controlled trials. We also describe real world use patterns of this biomarker using large an enhanced administrative dataset and are in the process of studying its performance characteristics and how providers react to procalcitonin results in patients admitted with clinical indicators of sepsis. Most estimates of sepsis incidence and mortality in existing literature are estimated using claims data. Unfortunately claims based data are subject to a variety of biases. We estimate 10-year trends in the incidence and outcome of septic shock using clinical indicators in a cohort of academic medical centers in the United States and compared it to estimates obtained using claims based data. We found that the prevalence of septic shock was rising and mortality declining over time, albeit, both less vigorously than suggested by claims based methods. In addition, we identified obesity as being associated with better outcomes in more than 50,000 patients with clinical indicators of sepsis at US hospitals. In collaboration with investigators at Harvard Medical School, we were able to study the differences in characteristics and outcomes of sepsis that originates in the community versus the hospital as well as studied variation in identifying sepsis and organ dysfunction using claims versus electronic health records. Along with the same group, we were able to assess how q-SOFA performs to identify patients with undifferentiated sepsis as well as demonstrate a simpler means of measuring organ dysfunction using electronic health records (called the e-SOFA score) that demonstrated equivalent performance characteristics than the more traditional but detailed SOFA score. Bloodstream infection is common cause of critical illness and is often a secondary complication of critical illness and its management. We determined the prevalence of ICU-related bloodstream infection in a large electronic health records-based repository and identify predictors of the same which could inform empiric antibiotic practices. Furthermore, central line-associated bloodstream infections (CLABSI) are associated with reimbursement penalties that were instituted by the Centers for Medicare and Medicaid in 2008, which, we hypothesize, has led to underreporting of CLABSI. We performed an interrupted time series analysis to study the impact of the policy on blood culture sampling, which is essential to the diagnosis of CLABSI. We are currently comparing rates of CLABSI with all cause ICU-related bloodstream infection to understand if reported declines in CLABSI are also seen in other forms of ICU-related bloodstream infection, to gauge the impact of measures to prevent CLABSI which have been intensified nationwide over the last decade. In collaboration with investigators at Harvard Department of Population Medicine, we found that models incorporating electronic health record data accurately predict hospital mortality for patients who meet an operational definition of sepsis based on clinical indicators and outperforms models using administrative data alone. This operational definition may enable more meaningful comparisons of hospital sepsis outcomes and provide an important window into quality of care. We also found that incorporating clinical data into risk adjustment substantially changes rankings of hospitals' sepsis mortality rates compared with using administrative data alone. Comprehensive risk adjustment using both administrative and clinical data is necessary before comparing hospitals by sepsis mortality rates. As part of the ICU-CAR initiative, a research group of critical care and oncology providers, we participated in a study that surveyed clinicians from multiple ICUs in the US caring for patients with hematologic malignancies receiving T-cell directed therapy to understand prevailing practices around the management of cytolike release syndrome T Cell toxicities.

危重病和败血症与显著的发病率和死亡率相关，特别是在现有治疗策略仍不理想的情况下。我们的主要目标是利用大量的精细临床数据库，更好地了解危重病、败血症和严重感染的临床流行病学，包括定义疾病负担、风险因素和临床影响。 链球菌感染时器官功能障碍的病理生理机制是由外毒素介导的细胞因子级联反应介导的炎症反应。克林霉素可中和A组链球菌释放的外毒素。在一个大的倾向匹配的患者队列中，我们发现克林霉素作为β-内酰胺治疗的辅助治疗与A组链球菌感染的生存率改善相关，但也发现了非A组、B组链球菌感染使用克林霉素时的危害趋势。这些发现需要在随机试验中得到证实。 抗生素过度使用仍然是危重病患者的一个重要问题，与毒性和抗生素耐药性的发展有关。在一个较大的美国医院队列中，我们发现在疑似或确诊败血症的危重患者中，使用降钙素原可显著缩短抗生素使用时间，而不会使结局恶化。我们在随机对照试验的荟萃分析中证实了这些发现。我们还使用大型增强管理数据集描述了该生物标志物的真实的使用模式，并正在研究其性能特征以及供应商如何对因败血症临床指标入院的患者的降钙素原结果作出反应。 现有文献中大多数脓毒症发病率和死亡率的估计值都是使用索赔数据估计的。不幸的是，基于索赔的数据受到各种偏见的影响。我们使用美国一组学术医疗中心的临床指标估计了脓毒性休克发病率和结局的10年趋势，并将其与使用基于索赔的数据获得的估计值进行了比较。我们发现，感染性休克的患病率随着时间的推移而上升，死亡率下降，尽管两者都不如基于索赔的方法所建议的那么有力。此外，我们在美国医院的50，000多名具有脓毒症临床指标的患者中发现肥胖与更好的结局相关。通过与哈佛医学院的研究人员合作，我们能够研究社区与医院败血症的特征和结局的差异，以及研究使用索赔与电子健康记录识别败血症和器官功能障碍的差异。沿着同一组，我们能够评估q-SOFA如何识别未分化脓毒症患者，并证明使用电子健康记录（称为e-SOFA评分）测量器官功能障碍的更简单方法，其表现出与更传统但更详细的SOFA评分相同的性能特征。 血流感染是危重病的常见原因，通常是危重病及其管理的继发性并发症。我们在一个大型的基于电子健康记录的存储库中确定了ICU相关血流感染的患病率，并确定了可以告知经验性抗生素实践的预测因子。此外，中心静脉导管相关血流感染（CLABSI）与医疗保险和医疗补助中心在2008年制定的报销处罚有关，我们假设，这导致了CLABSI的漏报。我们进行了一个中断的时间序列分析，以研究政策的影响，对血培养采样，这是必不可少的诊断CLABSI。我们目前正在比较CLABSI与所有原因ICU相关血流感染的比率，以了解CLABSI报告的下降是否也出现在其他形式的ICU相关血流感染中，以评估过去十年在全国范围内加强的预防CLABSI措施的影响。 与哈佛人口医学系的研究人员合作，我们发现，结合电子健康记录数据的模型可以准确预测符合基于临床指标的脓毒症操作定义的患者的住院死亡率，并且优于仅使用管理数据的模型。这一操作定义可能使医院脓毒症结局的比较更有意义，并为护理质量提供了一个重要的窗口。我们还发现，与仅使用行政数据相比，将临床数据纳入风险调整大大改变了医院败血症死亡率的排名。在比较医院脓毒症死亡率之前，有必要使用管理和临床数据进行综合风险调整。 作为重症监护和肿瘤学提供者研究小组ICU-CAR倡议的一部分，我们参与了一项研究，该研究调查了来自美国多个ICU的临床医生，这些临床医生负责治疗接受T细胞定向治疗的血液恶性肿瘤患者，以了解围绕细胞样释放综合征T细胞毒性管理的流行实践。