Abstract Objectives This study sought to hypothesize that elevated B-type natriuretic peptide (BNP) could act as an endogenous neprilysin inhibitor. Background A hallmark of acute decompensated heart ...failure (ADHF) is the overproduction of natriuretic peptides (NPs) by stretched cardiomyocytes. Various strategies have been developed to potentiate the beneficial effect of the NPs, including the recent use of neprilysin angiotensin receptor inhibitors. Contrary to rodents, human BNP is poorly sensitive to neprilysin degradation while retaining affinity to neprilysin. Methods We enrolled 638 patients presenting to the emergency department with acute dyspnea of which 468 had ADHF and 169 had dyspnea of noncardiac origin. We also included 46 patients with stable chronic heart failure (HF) and 10 age-matched healthy subjects. Plasma samples were collected within 4 h after emergency department admission. BNP, neprilysin concentration and activity, and the neprilysin substrate substance P concentration were measured. Results We found that when plasma BNP rose above 916 pg/ml, neprilysin activity was markedly reduced (p < 0.0001) and stratified 95% of the population into 2 groups: BNP <916 pg/ml/neprilysin activity ≥ 0.21 nmol/ml/min and BNP ≥916 pg/ml/neprilysin activity <0.21 nmol/ml/min with very different prognoses. In vitro, BNP was responsible for neprilysin inhibition. Neprilysin activity was inversely correlated with the concentration of substance P (ρ = −0.80; p < 0.0001). Conclusions Besides being an effector of the cardiac response to cardiomyocyte stretching in ADHF, elevated plasma BNP is also an endogenous neprilysin inhibitor. A biologically relevant BNP threshold discriminates 2 populations of HF patients with different vasoactive peptide profiles and outcome. If confirmed, this may identify an important threshold for managing HF patients.
Background Previous studies, mostly from Europe, suggest that early-life farming exposures protect against childhood asthma and allergy; few data exist on asthma and allergy in adults. Objective We ...sought to examine associations between early-life farming exposures and current asthma and atopy in an older adult US farming population. Methods We analyzed data from 1746 farmers and 1555 spouses (mean age, 63) from a case-control study nested within the Agricultural Health Study. Current asthma and early-life farming exposures were assessed via questionnaires. We defined atopy based on specific IgE > 0.70 IU/mL to at least 1 of 10 allergens measured in blood. We used logistic regression, adjusted for age, sex, race, state (Iowa or North Carolina), and smoking (pack years), to estimate associations between early-life exposures and asthma (1198 cases and 2031 noncases) or atopy (578 cases and 2526 noncases). Results Exposure to the farming environment in utero and in early childhood had little or no association with asthma but was associated with reduced odds of atopy. The strongest association was seen for having a mother who performed farm activities while pregnant (odds ratio, 0.60; 95% CI, 0.48-0.74) and remained significant in models with correlated early-life exposures including early childhood farm animal contact and raw milk consumption. Conclusions In a large US farming population, early-life farm exposures, particularly maternal farming activities while pregnant, were strongly associated with reduced risk of atopy in adults. These results extend previous work done primarily on childhood outcomes and suggest that protective associations of early-life farming exposures on atopy endure across the life course.
Abstract Bombardier CH, Fann JR, Tate DG, Richards JS, Wilson CS, Warren AM, Temkin NR, Heinemann AW, for the PRISMS Investigators. An exploration of modifiable risk factors for depression after ...spinal cord injury: which factors should we target? Objective To identify modifiable risk factors for depression in people with spinal cord injury (SCI). Design Cross-sectional survey. Setting Outpatient and community settings. Participants Community-residing people with SCI (N=244; 77% men, 61% white; mean age, 43.1y; 43% with tetraplegia) who were at least 1 month postinjury. Interventions Not applicable. Main Outcome Measures Depression severity (Patient Health Questionnaire-9 PHQ-9), physical activity (International Physical Activity Questionnaire IPAQ), pleasant and rewarding activities (Environment Rewards Observation Scale EROS), and self-efficacy to manage the effects of SCI (Modified Lorig Chronic Disease Self-Management Scale). Results Greater depression severity was associated with being 20 to 29 years of age, not completing high school, not working or attending school, and being ≤4 years post-SCI. After controlling for demographic and injury characteristics (adjusted R2 =.13), lower EROS scores (change in adjusted R2 =.34) and lower self-efficacy (change in R2 =.13) were independent predictors of higher PHQ-9 scores. Contrary to predictions, physical activity as measured by the IPAQ did not predict depression severity. Conclusions Our findings suggest that having fewer rewarding activities, and to a lesser extent, having less confidence in one's ability to manage the effects of SCI are independent predictors of greater depression severity after SCI. Interventions such as behavior activation, designed to increase rewarding activities, may represent an especially promising approach to treating depression in this population.
Summary Background In survivors of Ebola virus disease, clinical sequelae including uveitis, arthralgia, and fatigue are common and necessitate systematic follow-up. However, the infection risk to ...health-care providers is poorly defined. Here we report Ebola virus RT-PCR data for body site and fluid samples from a large cohort of Ebola virus survivors at clinic follow-up. Methods In this cross-sectional cohort study, consecutive survivors of Ebola virus disease attending Kerry Town survivor clinic (Freetown, Sierra Leone), who had been discharged from the Kerry Town Ebola treatment unit, were invited to participate. We collected and tested axillary, blood, conjunctival, forehead, mouth, rectal, semen, urine, and vaginal specimens for presence of Ebola virus using RT-PCR. We regarded samples to be positive for Ebola virus disease if the cycle threshold was 40 or lower. We collected demographic data from survivors of their age, sex, time since discharge from the treatment unit, and length of acute admission in the Ebola treatment unit using anonymised standard forms. Findings Between April 2, and June 16, 2015, of 151 survivors of Ebola virus disease invited to participate, 112 (74%) provided consent. The median age of participants was 21·5 years (IQR 14–31·5) with 34 (30%) participants younger than 16 years. 50 (45%) of 112 participants were male. We tested a total of 555 specimens: 103 from the axilla, 93 from blood, 92 from conjunctiva, 54 from forehead, 105 from mouth, 17 from the rectum, one from semen, 69 from urine, and 21 from the vagina. The median time from Ebola treatment unit discharge to specimen collection was 142 days (IQR 127–159). 15 participants had a total of 74 swabs taken less than 100 days from discharge. The semen sample from one participant tested positive for Ebola virus at 114 days after discharge from the treatment unit; specimens taken from the axilla, blood, conjunctiva, forehead, mouth, rectum, and urine of the same participant tested negative. All specimens from the other 111 participants tested negative. Interpretation Patients recovering from Ebola virus disease who do not meet the case definition for acute disease pose a low infection risk to health-care providers 6 weeks after clearance of viraemia. Personal protective equipment after this time might be limited to standard barrier precautions, unless contact with fluids from sanctuary sites is envisaged. Funding Save the Children International, Public Health England.
IMPORTANCE: Depression is prevalent and associated with negative outcomes in individuals with spinal cord injury (SCI). Antidepressants are used routinely to treat depression, yet no ...placebo-controlled trials have been published in this population to our knowledge. OBJECTIVE: To determine the efficacy and tolerability of venlafaxine hydrochloride extended-release (XR) for major depressive disorder (MDD) or dysthymic disorder in persons with chronic SCI. DESIGN, SETTING, AND PARTICIPANTS: Multisite, randomized (1:1), double-blind, placebo-controlled Project to Improve Symptoms and Mood After SCI (PRISMS) trial. All research staff conducting screening, intervention, and outcome procedures were blinded to randomization status. We screened 2536 patients from outpatient clinics at 6 SCI treatment centers in the United States and randomized 133 participants into the trial. Participants were 18 to 64 years old and at least 1 month after SCI, with MDD or dysthymic disorder. Seventy-four percent of participants were male, and participants were on average 40 years old and 11 years after SCI. Forty-seven percent had cervical injuries, 53.4% had American Spinal Injury Association injury severity A (complete injury) SCI, 24.1% had at least 2 prior MDD episodes, and 99.2% had current MDD. Common comorbidities included chronic pain (93.9%), significant anxiety (57.1%), and history of substance dependence (44.4%). INTERVENTIONS: Twelve-week trial of venlafaxine XR vs placebo using a flexible-dose algorithm. MAIN OUTCOMES AND MEASURES: The Hamilton Depression Rating Scale (HAM-D 17-item version and Maier subscale, which focuses on core depression symptoms and excludes somatic symptoms) over 12 weeks. RESULTS: Mixed-effects models revealed a significant difference between the venlafaxine XR and placebo groups in improvement on the Maier subscale from baseline to 12 weeks (treatment effect, 1.6; 95% CI, 0.3-2.9; P = .02) but not on the HAM-D 17-item version (treatment effect, 1.0; 95% CI, −1.4 to 3.4; P = .42). Participants receiving venlafaxine XR reported significantly less SCI-related disability on the Sheehan Disability Scale at 12 weeks compared with placebo (treatment effect, 4.7; 95% CI, 1.5-7.8; P = .005). Blurred vision was the only significantly more common new or worsening adverse effect in the venlafaxine XR group compared with the placebo group over 12 weeks. CONCLUSIONS AND RELEVANCE: Venlafaxine XR was well tolerated by most patients and an effective antidepressant for decreasing core symptoms of depression and improving SCI-related disability. Further research is needed to determine the optimal treatment and measurement approaches for depression in chronic SCI. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00592384
Growing evidence reveals the importance of improving safety culture in efforts to eliminate health care-associated infections. This multisite, cross-sectional survey examined the association between ...professional role and health care experience on infection prevention safety culture at 5 hospitals. The findings suggest that frontline health care technicians are less directly engaged in improvement efforts and safety education than other staff and that infection prevention safety culture varies more by hospital than by staff position and experience.
Abstract Background Although Emergency physicians frequently intubate patients, management of mechanical ventilation has not been emphasized in emergency medicine (EM) residency curricula. Objectives ...The objective of this study was to quantify EM residents' education, experience, and knowledge regarding mechanical ventilation. Methods We developed a survey of residents' educational experiences with ventilators and an assessment tool with nine clinical questions. Correlation and regression analyses were performed to evaluate the relationship between residents' scores on the assessment instrument and their training, education, and comfort with ventilation. Results Of 312 EM residents, 218 responded (69.9%). The overall correct response rate for the assessment tool was 73.3%, standard deviation (SD) ± 22.3. Seventy-seven percent (n = 167) of respondents reported ≤ 3 h of mechanical ventilation education in their residency curricula over the past year. Residents reported frequently caring for ventilated patients in the ED, as 64% (n = 139) recalled caring for ≥ 4 ventilated patients per month. Fifty-three percent (n = 116) of residents endorsed feeling comfortable caring for mechanically ventilated ED patients. In multiregression analysis, the only significant predictor of total test score was residents' comfort with caring for mechanically ventilated patients (F = 10.963, p = 0.001). Conclusions EM residents report caring for mechanically ventilated patients frequently, but receive little education on mechanical ventilation. Furthermore, as residents' performance on the assessment tool is only correlated with their self-reported comfort with caring for ventilated patients, these results demonstrate an opportunity for increased educational focus on mechanical ventilation management in EM residency training.
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