Longitudinal Learning Plan for Developing Moral Courage

Nursing curriculums strive to prepare students for their role as a professional nurse. Nursing ethics should continue to play a vital role in educating future nurses. Moral courage is one of many important virtues nurse educators should impart on students prior to entering the profession. By using theoretical frameworks and innovative strategies involving moral dilemmas, nurse educators may be better able to foster this complex characteristic in nursing students.     

Outcomes of Patients With Syncope and Suspected Dementia

Objectives

Syncope and near‐syncope are common in patients with dementia and a leading cause of emergency department (ED) evaluation and subsequent hospitalization. The objective of this study was to describe the clinical trajectory and short‐term outcomes of patients who presented to the ED with syncope or near‐syncope and were assessed by their ED provider to have dementia.

Methods

This multisite prospective cohort study included patients 60 years of age or older who presented to the ED with syncope or near‐syncope between 2013 and 2016. We analyzed a subcohort of 279 patients who were identified by the treating ED provider to have baseline dementia. We collected comprehensive patient‐level, utilization, and outcomes data through interviews, provider surveys, and chart abstraction. Outcome measures included serious conditions related to syncope and death.

Results

Overall, 221 patients (79%) were hospitalized with a median length of stay of 2.1 days. A total of 46 patients (16%) were diagnosed with a serious condition in the ED. Of the 179 hospitalized patients who did not have a serious condition identified in the ED, 14 (7.8%) were subsequently diagnosed with a serious condition during the hospitalization, and an additional 12 patients (6.7%) were diagnosed postdischarge within 30 days of the index ED visit. There were seven deaths (2.5%) overall, none of which were cardiac‐related. No patients who were discharged from the ED died or had a serious condition in the subsequent 30 days.

Conclusions

Patients with perceived dementia who presented to the ED with syncope or near‐syncope were frequently hospitalized. The diagnosis of a serious condition was uncommon if not identified during the initial ED assessment. Given the known iatrogenic risks of hospitalization for patients with dementia, future investigation of the impact of goals of care discussions on reducing potentially preventable, futile, or unwanted hospitalizations while improving goal‐concordant care is warranted.

     

Diagnostic and prognostic value of ambulatory ECG (Holter) monitoring in patients with coronary heart disease: a review

Silent ischemia, the most common expression of atherosclerotic heart disease, affects approximately 30–50% of patients during their activities of daily living. The present review provides a comprehensive and practical summary of current knowledge on perioperative myocardial ischemia through MEDLINE searches up to June 2005, using keywords including “silent ischemia,” “transient ischemia,” and “Holter monitoring.” Holter monitoring (i.e., continuous ambulatory ST-segment monitoring) is an effective tool for assessing the frequency and duration of silent transient myocardial ischemia, particularly in patients who are post-acute myocardial infarction (MI), those with acute coronary syndromes (ACS), and in patients in the acute post-operative period. Holter monitoring allows for further risk stratification of patients who have a positive exercise ECG by collecting long-term ECG data on ischemic and arrhythmic events while patients perform routine activities. Both the presence and increased duration of transient ischemia as detected by continuous ST-segment Holter monitoring are associated with increased rates of coronary events and mortality. Holter monitoring may aid in the identification of patients and subgroups of patients with ACS who may derive the greatest benefit from antiplatelet and antithrombotic therapy. Indeed, many ongoing and upcoming trials of pharmacotherapy include ischemia on Holter monitoring as an endpoint.     

Synergistic relationship between hyperglycaemia and inflammation with respect to clinical outcomes in non-ST-elevation acute coronary syndromes: analyses from OPUS-TIMI 16 and TACTICS-TIMI 18.

AIMS: To investigate the relationship between diabetes and inflammation and the potentially synergistic relationship between hyperglycaemia and inflammation on clinical outcomes in non ST-elevation ACS. METHODS AND RESULTS: The principal analysis was conducted in 2200 patients in OPUS-TIMI 16 with C-reactive protein data available and then validated in the invasive arm of TACTICS-TIMI 18 (n = 929). In addition, two further inflammatory markers [monocyte chemoattractant protein-1 (MCP-1) and von Willebrand factor (vWF)] were assessed in OPUS-TIMI 16. Diabetic patients had higher C-reactive protein and MCP-1 levels vs. non-diabetic patients in OPUS-TIMI 16 (9 vs. 7.8 mg/L, P = 0.002, and 190.6 vs. 170.8 pg/mL, P = 0.04, respectively), higher C-reactive protein levels in TACTICS-TIMI 18 (6.6 vs. 5.2 mg/L, P = 0.0005), and as expected higher glucose levels in both trials. Stratifying by the median C-reactive protein and diabetes in OPUS-TIMI 16, diabetic patients with C-reactive protein greater than or equal to the median were the highest risk group vs. non-diabetic patients with C-reactive protein less than the median (adjusted HR 1.63, 95% CI 1.20-2.23, P = 0.002). Directionally, similar findings were observed for MCP-1 and vWF in OPUS-TIMI 16 and for C-reactive protein in TACTICS-TIMI 18. After adjustment for diabetes, the risk associated with a 1 mmol/L increase in glucose was greater among those with a C-reactive protein greater than or equal to the median (HR 1.07, 95% CI 1.03-1.11) vs. those with a C-reactive protein less than the median (HR 1.02, 95% CI 0.97-1.06). After multivariable adjustment, the synergistic relationship between glucose and C-reactive protein and clinical outcomes remained statistically significant (P = 0.01). A similar pattern was observed in TACTICS-TIMI 18. CONCLUSION: Among ACS patients, diabetes was associated with both greater inflammation and higher glucose levels and patients with both hyperglycaemia and inflammation had worse outcomes. Better control of both inflammation and hyperglycaemia should be assessed in future ACS trials as a means to reduce the cardiovascular risk among diabetics.     

Significance of papillary muscle abnormalities identified by cardiovascular magnetic resonance in hypertrophic cardiomyopathy

Increased thickness of the left ventricular (LV) wall is the predominant feature of the hypertrophic cardiomyopathy (HC) phenotype. The structural characteristics of the LV papillary muscles (PMs) have received little attention. In this study, cardiovascular magnetic resonance (CMR) was used to characterize PM morphology in a large HC population. Cine and delayed enhancement (DE) CMR images were obtained in 201 patients with HC and 43 control subjects. PM number and mass index were greater in patients with HC compared with controls (2.5 vs 2.1, p <0.001, and 6 +/- 2 vs 3 +/- 2 g/m(2), p <0.001, respectively), including 109 (54%) with PM mass > or =7 g/m(2) (> or =2 SDs above the mean for controls). Greater LV wall mass index was associated with more substantial PM mass (r = 0.09, p <0.001). Furthermore, 12 patients with HC (19%) had normal LV mass with localized wall thickness but increased PM mass. In patients with HC with LV outflow obstruction at rest, PMs were positioned closer to the ventricular septum (displaced anteriorly: 58% vs 42% for subjects without obstruction, p = 0.02), with more marked hypertrophy (9 +/- 5 vs 6 +/- 4 g/m(2), p <0.001). Preoperative CMR identified 3 patients with accessory, anteriorly displaced PMs judged to contribute to outflow obstruction, which were resected during septal myectomy. DE of the PMs was identified in 13 patients with HC (6%), including 3 with DE confined to PMs. In conclusion, CMR demonstrates LV PMs to be part of the cardiomyopathic process in HC, with increases in number and mass, and not uncommonly associated with remodeling with DE. The identification of accessory PMs may be useful in planning preoperative strategy.     

The mitochondria‐targeted anti‐oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients

Background: Increased oxidative stress and subsequent mitochondrial damage are important pathways for liver damage in chronic hepatitis C virus (HCV) infection; consequently, therapies that decrease mitochondrial oxidative damage may improve outcome. The mitochondria‐targeted anti‐oxidant mitoquinone combines a potent anti‐oxidant with a lipophilic cation that causes it to accumulate several‐hundred fold within mitochondria in vivo. Aims: In this phase II study, we investigated the effect of oral mitoquinone on serum aminotransferases and HCV RNA levels in HCV‐infected patients. Methods: Thirty HCV patients who were either non‐responders or unsuitable candidates for standard‐of‐care (pegylated interferon plus ribavirin) were randomized to receive mitoquinone (40 or 80 mg) or placebo once daily for 28 days, and serum aminotransferases and HCV RNA levels were measured. Results: Both treatment groups showed significant decreases in absolute and percentage changes in serum alanine transaminase (ALT) from baseline to treatment day 28 (P<0.05). There was also a significant difference between incremental area under the curve for ALT between baseline and day 28 for the 40 mg treatment group against placebo (P<0.05). The differences in plasma ALT activity from baseline to day 28 in both mitoquinone groups compared with placebo did not reach significance (P>0.05). There was no change in HCV load on mitoquinone treatment. Conclusions: Administration of the mitochondria‐targeted anti‐oxidant mitoquinone significantly decreased plasma ALT and aspartate aminotransferase in patients with chronic HCV infection, and this suggests that mitoquinone may decrease necroinflammation in the liver in these patients. As mitochondrial oxidative damage contributes to many other chronic liver diseases, such as steatohepatitis, further studies using mitochondria‐targeted anti‐oxidants in HCV and other liver diseases are warranted.     

Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma

RATIONALE: Asthma is characterized by both chronic inflammation and remodeling of the airways. Proteases are important mediators of inflammation, cytokine activation, and tissue remodeling. OBJECTIVES: This study investigated matrix metalloproteinase-9 (MMP-9) and neutrophil elastase (NE) enzyme activity in the sputum of subjects with different inflammatory phenotypes of asthma (eosinophilic, neutrophilic, and paucigranulocytic asthma) and in healthy control subjects. METHODS AND MEASUREMENTS: Nonsmoking adults with asthma and healthy control subjects underwent hypertonic saline challenge and sputum induction. Selected sputum portions were dispersed with dithiothreitol and assayed for MMP-9 and NE enzyme activity. MAIN RESULTS: Subjects with eosinophilic asthma had significantly more active MMP-9 (39 ng/ml) compared with those with neutrophilic asthma (10 ng/ml) and control subjects (2.5 ng/ml, p < 0.01). Although there were high levels of total MMP-9 in neutrophilic asthma (5,273 ng/ml), most (> 99%) was inactivated (and bound to tissue inhibitor of metalloproteinase-1). In neutrophilic asthma, more subjects had NE activity (39%) compared with both healthy control subjects (0%), subjects with eosinophilic asthma (6%), or subjects with paucigranulocytic asthma (0%, p < 0.05). There were strong and consistent positive correlations between interleukin-8, neutrophils, and proteolytic enzymes. MMP-9 was inversely correlated with NE (r = -0.93). CONCLUSIONS: Proteolytic enzyme activity in asthma is dependent on the underlying inflammatory phenotype and is differentially regulated with MMP-9 activity a feature of eosinophilic inflammation, and active NE in neutrophilic inflammation.     

Genetic variation in resistance to repeated infections with Heligmosomoides polygyrus bakeri, in inbred mouse strains selected for the mouse genome project

Since the publication of the mouse genome, attention has focused on the strains that were selected for sequencing. In this paper we report the results of experiments that characterized the response to infection with the murine gastrointestinal nematode Heligmosomoides polygyrus of eight new strains (A/J, C57BL/6, C3H, DBA/2, BALB/c, NIH, SJL and 129/J), in addition to the well-characterized CBA (poor responder) and SWR (strong responder) as our controls. We employed the repeated infection protocol (consisting of 7 superimposed doses of 125L3 each administered at weekly intervals, faecal egg counts in weeks 2, 4 and 6 and assessment of worm burdens in week 6) that was used successfully to identify quantitative trait loci for genes involved in resistance to H. polygyrus. SWR, SJL and NIH mice performed indistinguishably and are confirmed as strong responder strains to H. polygyrus. CBA, C3H and A/J mice all tolerated heavy infections and are assessed as poor responders. In contrast, DBA/2, 129/J and BALB/c mice performed variably between experiments, some tolerating heavy worm burdens comparable to those in poor responders, and some showing evidence of resistance, although only in one experiment with female 129/J females and one with female BALB/c was the pattern and extent of worm loss much like that in SWR mice. Because the genetic relationships between six of the strains exploited in this study are now well-understood, our results should enable analysis through single nucleotide polymorphisms and thereby provide more insight into the role of the genes that control resistance to H. polygyrus.