Intrinsic endothelial hyperresponsiveness to inflammatory mediators drives acute episodes in models of Clarkson disease.

Clarkson disease, or monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome (ISCLS), is a rare, relapsing-remitting disorder featuring the abrupt extravasation of fluids and proteins into peripheral tissues, which in turn leads to hypotensive shock, severe hemoconcentration, and hypoalbuminemia. The specific leakage factor(s) and pathways in ISCLS are unknown, and there is no effective treatment for acute flares. Here, we characterize an autonomous vascular endothelial defect in ISCLS that was recapitulated in patient-derived endothelial cells (ECs) in culture and in a mouse model of disease. ISCLS-derived ECs were functionally hyperresponsive to permeability-inducing factors like VEGF and histamine, in part due to increased endothelial nitric oxide synthase (eNOS) activity. eNOS blockade by administration of N(γ)-nitro-l-arginine methyl ester (l-NAME) ameliorated vascular leakage in an SJL/J mouse model of ISCLS induced by histamine or VEGF challenge. eNOS mislocalization and decreased protein phosphatase 2A (PP2A) expression may contribute to eNOS hyperactivation in ISCLS-derived ECs. Our findings provide mechanistic insights into microvascular barrier dysfunction in ISCLS and highlight a potential therapeutic approach.

Support for Doctoral Nursing Students in PhD Programs in the United States.

BACKGROUND: The number of PhD nursing programs in the U.S. has increased, but the number of nursing students entering and completing these programs remains stagnant. It is crucial to consider innovative approaches to recruit, nurture, and graduate more diverse nursing students. PURPOSE: This article presents the perceptions of PhD nursing students regarding their programs, experiences, and strategies to support their academic success. METHODS: This study used a cross-sectional, descriptive design. Data were obtained from an online 65-question student survey completed between December 2020 and April 2021. RESULTS: A total of 568 students from 53 nursing schools completed the survey. Five themes emerged regarding the barriers students experienced during their programs: Faculty issues, time management and balance, insufficient preparation for dissertation research, financial barriers, and COVID-19 impact. Student recommendations for improving PhD nursing programs were also captured in five themes: Program improvement, coursework improvement, research opportunities, faculty, and dissertation. The low numbers of male, non-binary, Hispanic/Latino, minority, and international survey respondents indicate a need for innovative recruitment and retention strategies to increase diversity of PhD students. CONCLUSION: PhD program leaders should complete a gap analysis based on the recommendations in the new AACN position statement and perceptions of PhD students reported from this survey. By doing so, PhD programs will be better positioned to implement a roadmap for improvement to better prepare the next generation of nurse scientists, leaders, and scholars.

sCD14 and Intestinal Fatty Acid Binding Protein Are Elevated in the Serum of Patients With Idiopathic Anaphylaxis.

BACKGROUND: Intestinal epithelial integrity compromise has been identified in gastrointestinal (GI), atopic, and autoimmune diseases. OBJECTIVE: Episodes of idiopathic anaphylaxis (IA) are often accompanied by GI manifestations. We, therefore, sought to determine whether surrogate markers of GI permeability were aberrant in this patient population. METHODS: Serum concentrations of zonulin, intestinal fatty acid binding protein (I-FABP), and soluble CD14 (sCD14) measured in 54 patients with IA were compared with concentrations in healthy controls (HCs); and correlated with clinical and laboratory parameters. RESULTS: The I-FABP was elevated in sera of patients with IA compared with HCs (median 1,378.0 pg/mL vs 479.0 pg/mL, respectively; P < .001). The sCD14 was also elevated compared with HCs (median 2,017.0 ng/mL and 1,189.0 ng/mL, respectively; P < .001), whereas zonulin was comparable between patients with IA and HCs (median 49.6 ng/mL vs 52.4 ng/mL, respectively; P = .40). The I-FABP was elevated in patients with IA who experienced vomiting and/or diarrhea compared with patients with IA who did not (P = .0091). CONCLUSIONS: The I-FABP and sCD14 are elevated in the serum of patients with IA. Elevations in these biomarkers of IA provides evidence that increased GI permeability, as is observed in other allergic conditions such as food allergy, is a common finding in those with IA and offers possible insight into the pathogenesis of this disease.

Humanities-Based Educational Preparation and Empathy in Novice Nurses: Critical Thinking and Analytic Practice.

ABSTRACT: Empathy has been associated with improved patient outcomes in practicing nurses, but empathy levels have been shown to decline in nursing students with increased clinical exposure. Integrating content from the humanities in the nursing classroom, not common in nursing education, supports professional empathy development and maintenance. Whether competencies gained from humanities-based liberal education courses support empathy in nursing students as they emerge into practice is not known. The purpose of this quantitative, nonexperimental, descriptive, pilot research was to explore the relationship between humanities-based liberal education and empathy in recently graduated, baccalaureate-prepared practicing nurses ( n = 40).

Overtime and alertness of rotating-shift nurses: An observational study using ecological momentary assessment.

AIMS AND OBJECTIVES: This study aimed to determine the effect of overtime on alertness at work among rotating-shift nurses in South Korea and to investigate whether these effects of overtime vary across the different types of shifts. BACKGROUND: Nurse overtime is prevalent in healthcare settings to manage nursing shortages and staffing needs; however, it negatively affects patient and nurse outcomes. Furthermore, little attention has been paid to the effects of previous overtime shifts and overtime for consecutive shifts on alertness during work. DESIGN: A prospective observational study was employed. The study followed STROBE checklist for observational studies. METHODS: Data were collected between June 2019 and February 2020 from 82 nurses who worked in acute care hospitals. An ecological momentary assessment was used to capture real-time data of overtime and alertness. Alertness scores were estimated using the sleep/wake data measured by an actigraph. Mixed-effect models were employed to investigate the association between overtime and alertness. RESULTS: A majority of the shift nurses worked overtime. Episodes of a decline in alertness scores to the level of increased accident or serious error risk (alertness score ≤80) were most frequently seen during night shifts (98.9%), followed by day (59.8%) and evening shifts (10.1%). Previous-day overtime hours and consecutive overtime days were associated with decreased alertness scores during work. A significantly positive correlation was observed between alertness scores ≤80 and previous-day overtime hours and consecutive overtime days in all shifts. CONCLUSIONS: The study findings indicate that a majority of nurses who work overtime experience decreased alertness while on duty. RELEVANCE TO CLINICAL PRACTICE: Policy development at the government, organisational and unit level is needed to guarantee adequate rest for shift nurses by adjusting work schedules and assignments and limiting overtime.

Primary care nurses' perception of leadership and the influence of individual and work setting characteristics: A descriptive study.

AIMS: The aim of this study is to describe primary care nurses' perceptions of their formal leaders' leadership behaviours and outcomes and explore differences based upon nurses' individual and work setting characteristics. BACKGROUND: Formal nursing leadership is positively associated with patient, nurse workforce and organizational outcomes, yet no studies have examined primary care nurses' perception of formal leadership behaviours and outcomes in the United States. METHODS: Cross-sectional survey data from 335 primary care nurses were analysed to assess perceived leadership behaviours associated with transformational, transactional and passive-avoidant leadership styles, perceived leadership outcomes and individual and work setting characteristics. RESULTS: Positive leadership behaviours (transformational) were lower than those reported for other settings. There were significant differences in nurses' perceptions of their leaders' leadership behaviours and outcomes based upon individual and work setting characteristics. CONCLUSION: This study confirmed differences in perception of leadership and that individual and work setting characteristics influence nurses' perception of their leaders in primary care. IMPLICATIONS FOR NURSING MANAGEMENT: Leaders must be versatile and consider the unique needs of each staff member and the influence of clinic characteristics.

Occupational fatigue, workload and nursing teamwork in hospital nurses.

AIMS: To evaluate the relationships between workload, nursing teamwork and nurse fatigue and the moderating effect of nursing teamwork on the relationship between workload and fatigue. DESIGN: This cross-sectional online survey study used data from 810 United States hospital nurses collected between March and April 2021. METHODS: Workload, nursing teamwork and fatigue were measured using the Quantitative Workload Inventory, the Nursing Teamwork Survey, and the Occupational Fatigue Exhaustion Recovery scale. Hierarchical multiple linear regression models were used. RESULTS: All the nursing teamwork subscales (i.e. trust, team orientation, backup, shared mental model, team leadership) were significantly negatively related to acute and chronic fatigue. Nursing teamwork components of team orientation, shared mental model and team leadership moderated the relationship between workload and chronic fatigue. The relationships between workload and chronic fatigue were stronger when these components of nursing teamwork were high. No moderating effects were found with acute fatigue. CONCLUSION: Efforts to increase nursing teamwork may be a promising strategy in managing nurse fatigue. It is equally important to monitor and modify high workload to protect nurses from elevated fatigue. IMPACT: WHAT PROBLEM DID THE STUDY ADDRESS?: Fatigue is negatively associated with the health and safety of hospital nurses and patients. Nursing teamwork has been shown to improve the nursing care of hospitalized patients; yet, it is rarely explored in relation to nurse fatigue. WHAT WERE THE MAIN FINDINGS?: Greater nursing teamwork is significantly associated with lower acute and chronic fatigue. The relationships between workload and chronic fatigue were stronger when nursing teamwork (i.e. team orientation, shared mental model and team leadership) was high than when nursing teamwork was low. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: Improving nursing teamwork, in addition to monitoring and modifying workloads, can be a promising approach for managing fatigue in healthcare organizations.

Occupational fatigue, individualized nursing care, and quality of nursing care among hospital nurses.

PURPOSE: This study aimed to evaluate the relationships among nurse fatigue, individualized nursing care, and nurse-reported quality of care. DESIGN: The study used a cross-sectional design. Data from 858 registered nurses providing bedside care in hospitals were collected between March and April 2021 in the United States. METHODS: Participants completed a self-administered online survey, including the Occupational Fatigue Exhaustion Recovery scale, the Individualized Care Scale-Nurse version, and a single item assessing nursing care quality. Relationships among the study variables were examined using multiple linear and logistic regression models. FINDINGS: Nurses' higher levels of acute fatigue were significantly associated with decreased perceptions of individualized nursing activities provided to patients on their last shifts, specifically related to personal life condition and decision-making control. Nurses' higher levels of chronic fatigue were significantly associated with decreased perception of individualized nursing activities provided to patients on their last shifts related to clinical condition, personal life condition, and decision-making control. Nurses with higher levels of acute or chronic fatigue, and who perceived their nursing care activities as less individualized were less likely to assess their quality of care as excellent. CONCLUSION: These findings suggest that addressing hospital nurses' acute and chronic fatigue may contribute to promoting the delivery of individualized nursing care and in improving patients' quality of care. CLINICAL RELEVANCE: Healthcare institutions are encouraged to regularly monitor and manage nurse fatigue to improve the delivery of individualized and quality nursing care to their patients.

The state of mental health and healthy lifestyle behaviors in nursing, medicine and health sciences faculty and students at Big 10 Universities with implications for action.

BACKGROUND: High rates of mental health conditions and poor healthy lifestyle behaviors are reported in nurses, other clinicians, and health science students but have not been compared across different professions. PURPOSE: The purpose of this study was threefold: (1) describe rates of mental health problems and healthy lifestyle behaviors across the Big 10 health professional faculty and students, (2) compare the health and healthy lifestyle behaviors of the Big 10 health sciences faculty and students across health sciences' professions, and (3) identify factors predictive of depression, stress, and anxiety. METHODS: Faculty and students from eight health science colleges at the Big 10 Universities responded to the study survey, which included: demographics, healthy lifestyle behavior questions, and three valid/reliable mental health scales. Descriptive statistics described the findings and multiple linear regression identified factors associated with mental health conditions. RESULTS: Eight-hundred and sixty-nine faculty and 1087 students responded. Approximately 50% of faculty and students reported 7 h of sleep/night, a third achieved 150 min of physical activity/week; 5.5%-9.9% screened positive for depression; and 11.5%-25.5% had anxiety. Age, sleep, and physical activity were associated with lower depression and anxiety. CONCLUSIONS: University leadership must build wellness cultures that make healthy lifestyle behaviors easy to engage in and enhance mental well-being.

CE: Nurses Are More Exhausted Than Ever: What Should We Do About It?

ABSTRACT: For nurses, the challenges posed by demanding work environments and schedules often lead to fatigue, and this can be exacerbated during crises like the COVID-19 pandemic. In this article, the authors discuss causes and challenges of nurse fatigue and consider several evidence-based strategies and solutions for individual nurses and organizations. Barriers to implementation, including a negative workplace culture and inadequate staffing, are also described, and several resources are presented.

Assessment of Osteoporosis and Fracture Risk in Mastocytosis within a North American Cohort.

BACKGROUND: Systemic mastocytosis (SM), a clonal expansion of mast cells affecting multiple organs including the skeletal system, puts patients at risk for osteoporosis and fractures. Various aspects of skeletal disease in SM have been reported among European cohorts. OBJECTIVE: To determine fracture prevalence and risk predictors in SM in a North American (NA) cohort and compare findings with studies of other populations. METHODS: Fifty patients, aged 25-74 years, were grouped based on fracture type and history. Data collected included laboratory findings and radiographic markers such as serum tryptase, bone turnover markers, dual-energy x-ray absorptiometry images, and trabecular bone scores. We performed univariate and multivariate analyses of these findings. RESULTS: Fracture history was found in 74% of patients. Significantly different median age, body mass index, dual-energy x-ray absorptiometry scores, and alkaline phosphatase levels were observed between fracture groups, consistent with French and Dutch studies. Significant findings included the difference in trabecular bone scores among fracture groups, the association between alkaline phosphatase and fracture type and occurrence, and the model for predicting fracture risk based on DXA spine T-scores, alkaline phosphatase, and age (81.3% accuracy and 77.1% sensitivity). CONCLUSIONS: Our findings in an NA cohort are in overall agreement with those reported in European studies of skeletal disease and fracture risk for individuals with SM. We include an interactive calculator designed from a predictive model based on the NA cohort, which may be used for improved screening for fracture risk.

Effects of Work Environments and Occupational Fatigue on Care Left Undone in Rotating Shift Nurses.

PURPOSE: This study aimed to examine the effects of work environments and occupational fatigue on care left undone in rotating shift nurses, and to identify the indirect (mediation) effect of work environments on care left undone through nurses' occupational fatigue in South Korean acute care hospitals. DESIGN: This study employed a cross-sectional design using an online survey to collect data from 488 rotating shift nurses of acute care hospitals in Korea between November and December 2018. METHODS: A mobile schedule management application for shift nurses was used to advertise the study and to send a link to the online survey. The survey included questions on the nurses' work environment characteristics, care left undone activities, and the Korean version of the Occupational Fatigue Exhaustion/Recovery scale. Poisson regression was used to explore the relationships among work environments, occupational fatigue, and care left undone. Hayes' Model 4 and a bootstrapping analysis were used to identify the mediating effect of occupational fatigue on the relationship between work environments and care left undone. FINDINGS: The average number of tasks left undone was 3.45 (SD = 2.19). The higher the acute and chronic fatigue levels noted among nurses, the higher were the occurrences of care left undone. Conversely, the higher the intershift recovery level, the lower were the occurrences of care left undone. The results showed a positive relationship between care left undone and overtime hours and the number of patients per nurse. Moreover, nurses' occupational fatigue mediated the relationship between work environments and care left undone. Night shifts per month and the number of consecutive days off had an indirect effect on care left undone through occupational fatigue. CONCLUSIONS: High levels of occupational fatigue and poor intershift recovery among nurses can lead to care left undone. Nurses' occupational fatigue mediates the effect of work environment on care left undone. CLINICAL RELEVANCE: It is crucial for healthcare administrators and leaders to develop policies and mandatory regulations to facilitate better working conditions for nurses, consequently reducing their occupational fatigue and decreasing the occurrence of care left undone in acute care hospitals.

A randomized double-blind, placebo-controlled study of omalizumab for idiopathic anaphylaxis.

BACKGROUND: Idiopathic anaphylaxis (IA) is a diagnosis of exclusion, thus taking away the option of therapeutic management focused on eliminating the inciting agent. Epinephrine and antihistamines followed by systemic corticosteroids are the mainstays of therapy for acute events. There is no prophylactic therapy that reliably prevents anaphylaxis. OBJECTIVE: We sought to determine the efficacy of omalizumab in the management of patients with frequent episodes of IA in a double-blind, placebo-controlled trial. METHODS: We prospectively enrolled 19 patients with frequent IA (≥6 episodes/y) who then underwent a medical evaluation that included a serum tryptase determination, mutational analysis for KIT D816V, and bone marrow evaluation to rule out a clonal mast cell disorder. Computer-generated random numbers were provided by the study pharmacist. The primary end point was anaphylactic events in the 6 months after baseline. Sixteen patients completed the primary trial. RESULTS: No statistically significant difference was demonstrated between the placebo and treated groups. There was a trend for efficacy in the treatment group, particularly after 60 days. Overall, the safety profile was favorable without long-term side effects. CONCLUSIONS: Omalizumab was safely administered to a difficult-to-treat patient population with IA. The efficacy results trended modestly in favor of the treatment group, but no statistically significant differences were detected.

Erratum: Author Correction: A natural mouse model reveals genetic determinants of systemic capillary leak syndrome (Clarkson disease).

[This corrects the article DOI: 10.1038/s42003-019-0647-4.].