Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial

Background Results of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects. Methods FOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762. Findings Between Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months. Interpretation Fluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function. Funding UK Stroke Association and NIHR Health Technology Assessment Programme

The aging heart, myocardial fibrosis, and its relationship to circulating C-type natriuretic Peptide.

Myocardial aging is characterized by LV fibrosis leading to diastolic and systolic dysfunction. Studies have established the potent anti-fibrotic and anti-proliferative properties of C-type natriuretic peptide (CNP), however the relationship between circulating CNP, LV fibrosis and associated changes in LV function with natural aging are undefined. Accordingly, we characterized the relationship of plasma CNP with LV fibrosis and function in 2, 11 and 20 month old male Fischer rats. Further in vitro, we establish the anti-proliferative actions of CNP and the participation of the clearance receptor using adult human cardiac fibroblasts. Here we establish for the first time that a progressive decline in circulating CNP characterizes natural aging and is strongly associated with a reciprocal increase in LV fibrosis which precedes impairment of diastolic and systolic function. Additionally we demonstrate in cultured adult human cardiac fibroblasts that the direct anti-proliferative actions of high dose CNP may involve a non-cGMP pathway via the clearance receptor. Taken together these studies provide new insights into myocardial aging and the relationship to the anti-fibrotic and anti-proliferative peptide CNP

Access to primary care and computed tomography use in the emergency department

Abstract Background The decision to obtain a computed tomography CT scan in the emergency department (ED) is complex, including a consideration of the risk posed by the test itself weighed against the importance of obtaining the result. In patients with limited access to primary care follow up the consequences of not making a diagnosis may be greater than for patients with ready access to primary care, impacting diagnostic reasoning. We set out to determine if there is an association between CT utilization in the ED and patient access to primary care. Methods We performed a cross-sectional study of all ED visits in which a CT scan was obtained between 2003 and 2012 at an academic, tertiary-care center. Data were abstracted from the electronic medical record and administrative databases and included type of CT obtained, demographics, comorbidities, and access to a local primary care provider (PCP). CT utilization rates were determined per 1000 patients. Results A total of 595,895 ED visits, including 98,001 visits in which a CT was obtained (16.4%) were included. Patients with an assigned PCP accounted for 55% of all visits. Overall, CT use per 1000 ED visits increased from 142.0 in 2003 to 169.2 in 2012 (p < 0.001), while the number of annual ED visits remained stable. CT use per 1000 ED visits increased from 169.4 to 205.8 over the 10-year period for patients without a PCP and from 118.9 to 142.0 for patients with a PCP. Patients without a PCP were more likely to have a CT performed compared to those with a PCP (OR 1.57, 95%CI 1.54 to 1.58; p < 0.001). After adjusting for age, gender, year of visit and number of comorbidities, patients without a PCP were more likely to have a CT performed (OR 1.20, 95% CI 1.18 to 1.21, p < 0.001). Conclusions The overall rate of CT utilization in the ED increased over the past 10 years. CT utilization was significantly higher among patients without a PCP. Increased availability of primary care, particularly for follow-up from the ED, could reduce CT utilization and therefore decrease costs, ED lengths of stay, and radiation exposure

Increased Computed Tomography Utilization in the Emergency Department and Its Association with Hospital Admission

Introduction: Our goal was to investigate trends in computed tomography (CT) utilization in emergency departments (EDs) and its association with hospitalization. Methods: We conducted an analysis of an administrative claims database of U.S. privately insured and Medicare Advantage enrollees. We identified ED visits from 2005 through 2013 and assessed for CT use, associated factors, and hospitalization after CT, along with patient demographics. We used both descriptive methods and regression models adjusted for year, age, sex, race, geographic region, and Hwang comorbidity score to explore associations among CT use, year, demographic characteristics, and hospitalization. Results: We identified 33,144,233 ED visits; 5,901,603 (17.8%) involved CT. Over time, CT use during ED visits increased 59.9%. CT use increased in all age groups but decreased in children since 2010. In propensity-matching analysis, odds of hospitalization increased with age, comorbidities, male sex, and CT use (odds ratio, 2.38). Odds of hospitalization over time decreased more quickly for patients with CT. Conclusion: CT utilization in the ED has increased significantly from 2005 through 2013. For children, CT use after 2010 decreased, indicating caution about CT use. Male sex, older age, and higher number of comorbidities were predictors of CT in the ED. Over time, odds of hospitalization decreased more quickly for patients with CT

Increased Computed Tomography Utilization in the Emergency Department and Its Association with Hospital Admission

Introduction: Our goal was to investigate trends in computed tomography (CT) utilization in emergency departments (EDs) and its association with hospitalization. Methods: We conducted an analysis of an administrative claims database of U.S. privately insured and Medicare Advantage enrollees. We identified ED visits from 2005 through 2013 and assessed for CT use, associated factors, and hospitalization after CT, along with patient demographics. We used both descriptive methods and regression models adjusted for year, age, sex, race, geographic region, and Hwang comorbidity score to explore associations among CT use, year, demographic characteristics, and hospitalization. Results: We identified 33,144,233 ED visits; 5,901,603 (17.8%) involved CT. Over time, CT use during ED visits increased 59.9%. CT use increased in all age groups but decreased in children since 2010. In propensity-matching analysis, odds of hospitalization increased with age, comorbidities, male sex, and CT use (odds ratio, 2.38). Odds of hospitalization over time decreased more quickly for patients with CT. Conclusion: CT utilization in the ED has increased significantly from 2005 through 2013. For children, CT use after 2010 decreased, indicating caution about CT use. Male sex, older age, and higher number of comorbidities were predictors of CT in the ED. Over time, odds of hospitalization decreased more quickly for patients with CT

Circulating aldosterone and natriuretic peptides in the general community: relationship to cardiorenal and metabolic disease

We sought to investigate the role of aldosterone as a mediator of disease and its relationship with the counter-regulatory natriuretic peptide (NP) system. We measured plasma aldosterone (n=1674; aged≥45 years old) in a random sample of the general population from Olmsted County, MN. In a multivariate logistic regression model, aldosterone analyzed as a continuous variable was associated with hypertension (odds ratio [OR]=1.75; 95% confidence interval [CI]=1.57-1.96; P<0.0001), obesity (OR=1.34; 95% CI=1.21-1.48; P<0.0001), chronic kidney disease (OR=1.39; 95% CI=1.22-1.60; P<0.0001), central obesity (OR=1.47; 95% CI=1.32-1.63; P<0.0001), metabolic syndrome (OR=1.41; 95% CI=1.26-1.58; P<0.0001), high triglycerides (OR=1.23; 95% CI=1.11-1.36; P<0.0001), concentric left ventricular hypertrophy (OR=1.22; 95% CI=1.09-1.38; P=0.0007), and atrial fibrillation (OR=1.24; 95% CI=1.01-1.53; P=0.04), after adjusting for age and sex. The associations with hypertension, central obesity, metabolic syndrome, triglycerides, and concentric left ventricular hypertrophy remained significant after further adjustment for body mass index, NPs, and renal function. Furthermore, aldosterone in the highest tertile correlated with lower NP levels and increased mortality. Importantly, most of these associations remained significant even after excluding subjects with aldosterone levels above the normal range. In conclusion, we report that aldosterone is associated with hypertension, chronic kidney disease, obesity, metabolic syndrome, concentric left ventricular hypertrophy, and lower NPs in the general community. Our data suggest that aldosterone, even within the normal range, may be a biomarker of cardiorenal and metabolic disease. Further studies are warranted to evaluate a therapeutic and preventive strategy to delay the onset and progression of disease, using mineralocorticoid antagonists or chronic NP administration in high-risk subjects identified by plasma aldosterone