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Background There has been significant controversy regarding the effects of pre-hospitalization use of renin-angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID-19 patients. Methods and Results We retrospectively assessed 2,297 hospitalized COVID-19 patients at Tongji Hospital in Wuhan, China, from January 10 to March 30, 2020; and identified 1,182 patients with known hypertension on pre-hospitalization therapy. We compared the baseline characteristics and in-hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non-RAS inhibitors (N=827). Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs. 95/827 (11.5%) patients in the non-RAS inhibitors group (p<0.0001). Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15-0.52, p<0.0001) at 45 days in the RAS inhibitors group compared with non-RAS inhibitors group. Similar findings were observed when patients taking angiotensin receptor blockers (N=289) or angiotensin converting enzyme inhibitors (N=66) were separately compared with non-RAS inhibitors group. The RAS inhibitors group compared with non-RAS inhibitors group had lower levels of C-reactive protein (median 13.5 vs. 24.4 pg/mL; p=0.007) and interleukin-6 (median 6.0 vs. 8.5 pg/mL; p=0.026) on admission. The protective effect of RAS inhibitors on mortality was confirmed in a meta-analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29-0.65, p<0.0001). Conclusions In a large single center retrospective analysis we observed a protective effect of pre-hospitalization use of RAS inhibitors on mortality in hypertensive COVID-19 patients; which might be associated with reduced inflammatory response.
Importance - Whether low levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of sepsis and poorer outcomes is unknown.
Objective - To examine the association between LDL-C levels and risk of sepsis among patients admitted to the hospital with infection.
Design, Setting, and Participants - Cohort study in which deidentified electronic health records were used to define a cohort of patients admitted to Vanderbilt University Medical Center, Nashville, Tennessee, with infection. Patients were white adults, had a code indicating infection from the International Classification of Diseases, Ninth Revision, Clinical Modification, and received an antibiotic within 1 day of hospital admission (N = 61 502). Data were collected from January 1, 1993, through December 31, 2017, and analyzed from January 24 through October 31, 2018.
Interventions - Clinically measured LDL-C levels (excluding measurements <1 year before hospital admission and those associated with acute illness) and a genetic risk score (GRS).
Main Outcomes and Measures - The primary outcome was sepsis; secondary outcomes included admission to an intensive care unit (ICU) and in-hospital death.
Results - Among the 3961 patients with clinically measured LDL-C levels (57.8% women; mean [SD] age, 64.1 [15.9] years) and the 7804 with a GRS for LDL-C (54.0% men; mean [SD] age, 59.8 [15.2] years), lower measured LDL-C levels were significantly associated with increased risk of sepsis (odds ratio [OR], 0.86; 95% CI, 0.79-0.94; P = .001) and ICU admission (OR, 0.85; 95% CI, 0.76-0.96; P = .008), but not in-hospital mortality (OR, 0.80; 95% CI, 0.63-1.00; P = .06); however, none of these associations were statistically significant after adjustment for age, sex, and comorbidity variables (OR for risk of sepsis, 0.96 [95% CI, 0.88-1.06]; OR for ICU admission, 0.94 [95% CI, 0.83-1.06]; OR for in-hospital death, 0.97 [95% CI, 0.76-1.22]; P > .05 for all). The LDL-C GRS correlated with measured LDL-C levels (r = 0.24; P < 2.2 × 10-16) but was not significantly associated with any of the outcomes.
Conclusions and Relevance - Results of this study suggest that lower measured LDL-C levels were significantly associated with increased risk of sepsis and admission to ICU in patients admitted to the hospital with infection; however, this association was due to comorbidities because both clinical models adjusted for confounders, and the genetic model showed no increased risk. Levels of LDL-C do not appear to directly alter the risk of sepsis or poor outcomes in patients hospitalized with infection.
BACKGROUND - Adults hospitalized with community-acquired pneumonia (CAP) are at high risk for short-term mortality. However, it is unclear whether improvements in in-hospital pneumonia care could substantially lower this risk. We extensively reviewed all in-hospital deaths in a large prospective CAP study to assess the cause of each death and assess the extent of potentially preventable mortality.
METHODS - We enrolled adults hospitalized with CAP at five tertiary-care hospitals in the United States. Five physician investigators reviewed the medical record and study database for each patient who died to identify the cause of death, the contribution of CAP to death, and any preventable factors potentially contributing to death.
RESULTS - Among 2,320 enrolled patients, 52 (2.2%) died during initial hospitalization. Among these 52 patients, 33 (63.4%) were ≥ 65 years old, and 32 (61.5%) had ≥ two chronic comorbidities. CAP was judged to be the direct cause of death in 27 patients (51.9%). Ten patients (19.2%) had do-not-resuscitate orders prior to admission. Four patients were identified in whom a lapse in quality of care potentially contributed to death; preexisting end-of-life limitations were present in two of these patients. Two patients seeking full medical care experienced a lapse in in-hospital quality of pneumonia care that potentially contributed to death.
CONCLUSIONS - In this study of adults with CAP at tertiary-care hospitals with a low mortality rate, most in-hospital deaths did not appear to be preventable with improvements in in-hospital pneumonia care. Preexisting end-of-life limitations in care, advanced age, and high comorbidity burden were common among those who died.
Copyright © 2018 American College of Chest Physicians. All rights reserved.
BACKGROUND - Critically ill patients with acute kidney injury (AKI) can be divided into two subphenotypes, resolving or nonresolving, on the basis of the trajectory of serum creatinine. It is unknown if the biology underlying these two AKI recovery patterns is different.
METHODS - We measured eight circulating biomarkers in plasma obtained from a cohort of patients admitted to an intensive care unit (ICU) (n = 1241) with systemic inflammatory response syndrome. The biomarkers were representative of several biologic processes: apoptosis (soluble Fas), inflammation (soluble tumor necrosis factor receptor 1, interleukin 6, interleukin 8) and endothelial dysfunction, (angiopoietin 1, angiopoietin 2, and soluble vascular cell adhesion molecule 1). We tested for associations between biomarker levels and AKI subphenotypes using relative risk regression accounting for multiple hypotheses with the Bonferroni correction.
RESULTS - During the first 3 days of ICU admission, 868 (70%) subjects developed AKI; 502 (40%) had a resolving subphenotype, and 366 (29%) had a nonresolving subphenotype. Hospital mortality was 12% in the resolving subphenotype and 21% in the nonresolving subphenotype. Soluble Fas was the only biomarker associated with a nonresolving subphenotype after adjustment for age, body mass index, diabetes, and Acute Physiology and Chronic Health Evaluation III score (p = 0.005).
CONCLUSIONS - Identifying modifiable targets in the Fas-mediated pathway may lead to strategies for prevention and treatment of a clinically important form of AKI.
BACKGROUND - The clinical significance of pneumonia visualized on CT scan in the setting of a normal chest radiograph is uncertain.
METHODS - In a multicenter prospective surveillance study of adults hospitalized with community-acquired pneumonia (CAP), we compared the presenting clinical features, pathogens present, and outcomes of patients with pneumonia visualized on a CT scan but not on a concurrent chest radiograph (CT-only pneumonia) and those with pneumonia visualized on a chest radiograph. All patients underwent chest radiography; the decision to obtain CT imaging was determined by the treating clinicians. Chest radiographs and CT images were interpreted by study-dedicated thoracic radiologists blinded to the clinical data.
RESULTS - The study population included 2,251 adults with CAP; 2,185 patients (97%) had pneumonia visualized on chest radiography, whereas 66 patients (3%) had pneumonia visualized on CT scan but not on concurrent chest radiography. Overall, these patients with CT-only pneumonia had a clinical profile similar to those with pneumonia visualized on chest radiography, including comorbidities, vital signs, hospital length of stay, prevalence of viral (30% vs 26%) and bacterial (12% vs 14%) pathogens, ICU admission (23% vs 21%), use of mechanical ventilation (6% vs 5%), septic shock (5% vs 4%), and inhospital mortality (0 vs 2%).
CONCLUSIONS - Adults hospitalized with CAP who had radiological evidence of pneumonia on CT scan but not on concurrent chest radiograph had pathogens, disease severity, and outcomes similar to patients who had signs of pneumonia on chest radiography. These findings support using the same management principles for patients with CT-only pneumonia and those with pneumonia seen on chest radiography.
Copyright © 2017 American College of Chest Physicians. All rights reserved.
BACKGROUND - Extracorporeal membrane oxygenation is a resource-intensive mode of life-support potentially applicable when conventional therapies fail. Given the initial success of extracorporeal membrane oxygenation to support neonates and infants in the 1980s, indications have expanded to include adolescents, adults, and selected moribund patients during cardiopulmonary resuscitation. This single-institution analysis was conducted to evaluate programmatic growth, outcomes, and risk for death despite extracorporeal membrane oxygenation across all ages and diseases.
METHODS - Beginning in 1989, we registered prospectively all extracorporeal membrane oxygenation patient data with the Extracorporeal Life Support Organization. We queried this registry for our institution-specific data to compare the parameter of "discharge alive" between age groups (neonatal, pediatric, adult), disease groups (respiratory, cardiac, cardiopulmonary resuscitation), and modes of extracorporeal membrane oxygenation (veno-venous; veno-arterial). Extracorporeal membrane oxygenation-specific complications (mechanical, hemorrhagic, neurologic, renal, cardiovascular, pulmonary, infectious, metabolic) were analyzed similarly. Descriptive statistics, Kaplan-Meier, and linear regression analyses were conducted.
RESULTS - After 1,052 extracorporeal membrane oxygenation runs, indications have expanded to include adults, to supplement cardiopulmonary resuscitation, to support hemodialysis in neonates and plasmapheresis in children, and to bridge all age patients to heart and lung transplant. Overall survival to discharge was 52% and was better for respiratory diseases (P < .001). Probability of individual survival decreased to <50% if pre-extracorporeal membrane oxygenation mechanical ventilation exceeded respectively 123 hours for cardiac, 166 hours for cardiopulmonary resuscitation, and 183 hours for respiratory diseases (P = .013). Complications occurred most commonly among cardiac and cardiopulmonary resuscitation runs (P < .001), the veno-arterial mode (P < .001), and in adults (P = .044).
CONCLUSION - Our extracorporeal membrane oxygenation program, an Extracorporeal Life Support Organization-designated Center of Excellence, has experienced substantial growth in volume and indications, including increasing age and disease severity. Considering the entire cohort, pre-extracorporeal membrane oxygenation ventilation exceeding 7 days was associated with an increased probability of death.
Copyright © 2017 Elsevier Inc. All rights reserved.
OBJECTIVE - To determine if beta-(β)-blockers improve outcomes after acute traumatic brain injury (TBI).
BACKGROUND - There have been no new inpatient pharmacologic therapies to improve TBI outcomes in a half-century. Treatment of TBI patients with β-blockers offers a potentially beneficial approach.
METHODS - Using MEDLINE, EMBASE, and CENTRAL databases, eligible articles for our systematic review and meta-analysis (PROSPERO CRD42016048547) included adult (age ≥ 16 years) blunt trauma patients admitted with TBI. The exposure of interest was β-blocker administration initiated during the hospitalization. Outcomes were mortality, functional measures, quality of life, cardiopulmonary morbidity (e.g., hypotension, bradycardia, bronchospasm, and/or congestive heart failure). Data were analyzed using a random-effects model, and represented by pooled odds ratio (OR) with 95% confidence intervals (CI) and statistical heterogeneity (I).
RESULTS - Data were extracted from 9 included studies encompassing 2005 unique TBI patients with β-blocker treatment and 6240 unique controls. Exposure to β-blockers after TBI was associated with a reduction of in-hospital mortality (pooled OR 0.39, 95% CI: 0.27-0.56; I = 65%, P < 0.00001). None of the included studies examined functional outcome or quality of life measures, and cardiopulmonary adverse events were rarely reported. No clear evidence of reporting bias was identified.
CONCLUSIONS - In adults with acute TBI, observational studies reveal a significant mortality advantage with β-blockers; however, quality of evidence is very low. We conditionally recommend the use of in-hospital β-blockers. However, we recommend further high-quality trials to answer questions about the mechanisms of action, effectiveness on subgroups, dose-response, length of therapy, functional outcome, and quality of life after β-blocker use for TBI.
STUDY OBJECTIVE - Induction doses of etomidate during rapid sequence intubation cause transient adrenal dysfunction, but its clinical significance on trauma patients is uncertain. Ketamine has emerged as an alternative for rapid sequence intubation induction. Among adult trauma patients intubated in the emergency department, we compare clinical outcomes among those induced with etomidate and ketamine.
METHODS - The study entailed a retrospective evaluation of a 4-year (January 2011 to December 2014) period spanning an institutional protocol switch from etomidate to ketamine as the standard induction agent for adult trauma patients undergoing rapid sequence intubation in the emergency department of an academic Level I trauma center. The primary outcome was hospital mortality evaluated with multivariable logistic regression, adjusted for age, vital signs, and injury severity and mechanism. Secondary outcomes included ICU-free days and ventilator-free days evaluated with multivariable ordered logistic regression using the same covariates.
RESULTS - The analysis included 968 patients, including 526 with etomidate and 442 with ketamine. Hospital mortality was 20.4% among patients induced with ketamine compared with 17.3% among those induced with etomidate (adjusted odds ratio [OR] 1.41; 95% confidence interval [CI] 0.92 to 2.16). Patients induced with ketamine had ICU-free days (adjusted OR 0.80; 95% CI 0.63 to 1.00) and ventilator-free days (adjusted OR 0.96; 95% CI 0.76 to 1.20) similar to those of patients induced with etomidate.
CONCLUSION - In this analysis spanning an institutional protocol switch from etomidate to ketamine as the standard rapid sequence intubation induction agent for adult trauma patients, patient-centered outcomes were similar for patients who received etomidate and ketamine.
Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
BACKGROUND - The incidence of hypertensive emergency in US emergency departments (ED) is not well established.
METHODS AND RESULTS - This study is a descriptive epidemiological analysis of nationally representative ED visit-level data from the Nationwide Emergency Department Sample for 2006-2013. Nationwide Emergency Department Sample is a publicly available database maintained by the Healthcare Cost and Utilization Project. An ED visit was considered to be a hypertensive emergency if it met all the following criteria: diagnosis of acute hypertension, at least 1 diagnosis indicating acute target organ damage, and qualifying disposition (admission to the hospital, death, or transfer to another facility). The incidence of adult ED visits for acute hypertension increased monotonically in the period from 2006 through 2013, from 170 340 (1820 per million adult ED visits overall) to 496 894 (4610 per million). Hypertensive emergency was rare overall, accounting for 63 406 visits (677 per million adult ED visits overall) in 2006 to 176 769 visits (1670 per million) in 2013. Among adult ED visits that had any diagnosis of hypertension, hypertensive emergency accounted for 3309 per million in 2006 and 6178 per million in 2013.
CONCLUSIONS - The estimated number of visits for hypertensive emergency and the rate per million adult ED visits has more than doubled from 2006 to 2013. However, hypertensive emergencies are rare overall, occurring in about 2 in 1000 adult ED visits overall, and 6 in 1000 adult ED visits carrying any diagnosis of hypertension in 2013. This figure is far lower than what has been sometimes cited in previous literature.
© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
BACKGROUND - Acute kidney injury (AKI) is common among intensive care unit (ICU) patients. AKI is highly heterogeneous, with variable links to poor outcomes. Current approaches to classify AKI severity and identify patients at highest risk for poor outcomes focus on the maximum change in serum creatinine (SCr) values. However, these scores are hampered by the need for a reliable baseline SCr value and the absence of a component differentiating transient from persistent rises in SCr. We hypothesized that identification of resolving or nonresolving AKI subphenotypes based on the early trajectory of SCr values in the ICU would better differentiate patients at risk of hospital mortality.
METHODS - We performed a secondary analysis of two prospective studies of ICU patients admitted to a trauma ICU (group 1; n = 1914) or general medical-surgical ICUs (group 2; n = 1867). In group 1, we tested definitions for resolving and nonresolving AKI subphenotypes and selected the definitions resulting in subphenotypes with the greatest separation in risk of death relative to non-AKI controls. We applied this definition to group 2 and tested whether the subphenotypes were independently associated with hospital mortality after adjustment for AKI severity.
RESULTS - AKI occurred in 46% and 69% of patients in groups 1 and 2, respectively. In group 1, a resolving AKI subphenotype (defined as a decrease in SCr of 0.3 mg/dl or 25% from maximum in the first 72 h of study enrollment) was associated with a low risk of death. A nonresolving AKI subphenotype (defined as all AKI cases not meeting the "resolving" definition) was associated with a high risk of death. In group 2, the resolving AKI subphenotype was not associated with increased mortality (relative risk [RR] 0.86, 95% CI 0.63-1.17), whereas the nonresolving AKI subphenotype was associated with higher mortality (RR 1.68, 95% CI 1.15-2.44) even after adjustment for AKI severity stage.
CONCLUSIONS - The trajectory of SCr levels identifies AKI subphenotypes with different risks for death, even among AKI cases of similar severity. These AKI subphenotypes might better define the patients at risk for poor outcomes who might benefit from novel interventions.