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: 10473358
• 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/10473358
• 关键词: Academic Medical Centers; Adrenal Cortex Hormones; Antibiotics; Antimicrobial Resistance; Bacterial Infections; Big Data; Biological Markers; Blood; Body mass index; COVID-19; COVID-19 mortality; COVID-19 patient; Centers for Disease Control and Prevention (U.S.); Characteristics; Clindamycin; Clinical; Clinical Data; Clinical Trials; Code; Collaborations; Communities; Complication; Critical Care; Critical Illness; Data; Data Set; Development; Diagnosis; Disease; Electronic Health Record; Epidemiology; Exotoxins; FDA Emergency Use Authorization; Functional disorder; Healthcare; Hematologic Neoplasms; Hospital Mortality; Hospitalization; Hospitals; Hydroxychloroquine; 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; Pharmaceutical Preparations; Policies; Population; Prevalence; Process; Provider; Publishing; Quality of Care; Randomized Controlled Trials; Reporting; Research; Research Personnel; Risk; Risk Adjustment; Risk Factors; Sampling; Sepsis; Septic Shock; Severity of illness; Shock; Streptococcal Infections; Streptococcus Group B; Streptococcus pyogenes; Surveys; 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; drug repurposing; epidemiologic data; improved; indexing; lung injury; medical schools; mortality; opioid use; opioid user; prevent; procalcitonin; randomized trial; repository; smoke inhalation; systematic review; trend; uptake; variants of concern

Critical illness and sepsis (including critical disease from COVID-19) 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. Our study on short stays for sepsis underscore the incomplete uptake of Sepsis-3 definitions, the breadth of illness severities encompassed by both traditional and new sepsis definitions, and the possibility that some patients with sepsis recover very rapidly. Our study on association between opioid use and sepsis highlight the disproportionately high mortality burden associated with younger opioid users developing sepsis. 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 cytokine release syndrome T Cell toxicities. In collaboration with the CDC, we found that hospital surges are detrimental to survival for patients admitted with COVID-19. We also found that the risk of COVID-19 reinfection remained low up to 9 months since index infection but our findings do not include the period where variants of concern were prevalent in the U.S. We found that hydroxychloroquine use fell sharply even before the emergency use authorization for this drug was revoked. We also found that corticosteroids were being used frequently in ventilated COVID-19 patients well before its benefit was publicly known from clinical trials.

危重疾病和败血症（包括COVID-19引起的危重疾病）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临床数据来更好地了解危重疾病、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。