Elizabeth Crago - Academia.edu (original) (raw)

Papers by Elizabeth Crago

Critical care medicine, 2015

Critical Care Medicine

Introduction: Recent pre-clinical studies provide evidence that epoxyeicosatrienoic acids (EETs) ... more Introduction: Recent pre-clinical studies provide evidence that epoxyeicosatrienoic acids (EETs) are potent regulators of cerebrovascular tone that attenuate cerebral ischemic injury. In humans, EETs are formed from the metabolism of arachidonic acid by CYP2C8/9 and CYP2J2 enzymes and eliminated by soluble epoxide hydrolase (SEH) to form less active dihydroxyeicosatetraenoic acids (DiHETEs). Other studies identified multiple single nucleotide polymorphisms (SNPs) that reduce enzyme activity of CYP2C8/9 and CYP2J2 in-vitro. Methods: This study included 304 Caucasian patients with aSAH. Patients were genotyped for six loss-of-function SNPs in CYP2C8/9 and CYP2J2 using MassARRAY (iPLEX) methods. UPLC-MS/MS methods were used to measure EET and DiHETE levels in CSF twice daily over 14 days. DCI was determined by the concomitant presence of cerebral vasospasm and clinical neurological deterioration. The presence of DCI was compared in the genotype groups using chi-square test and logistic...

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, Jan 29, 2015

Emerging evidence has suggested that patients experiencing aneurysmal subarachnoid hemorrhage (aS... more Emerging evidence has suggested that patients experiencing aneurysmal subarachnoid hemorrhage (aSAH) develop vascular dysregulation as a potential contributor to poor outcomes. Preclinical studies have implicated the novel microvascular constrictor, 20-hydroxyeicosatetraenoic acid (20-HETE) in aSAH pathogenesis, yet the translational relevance of 20-HETE in patients with aSAH is largely unknown. The goal of this research was to determine the relationship between 20-HETE cerebrospinal fluid (CSF) levels, gene variants in 20-HETE synthesis, and acute/long-term aSAH outcomes. In all, 363 adult patients (age 18 to 75) with aSAH were prospectively recruited from the University of Pittsburgh Medical Center neurovascular Intensive Care Unit. Patients were genotyped for polymorphic variants and cytochrome P450 (CYP)-eicosanoid CSF levels were measured over 14 days. Outcomes included delayed cerebral ischemia (DCI), clinical neurologic deterioration (CND), and modified Rankin Scores (MRS) at...

Biological research for nursing, Jan 29, 2014

Biochemical mediators alter cerebral perfusion and have been implicated in delayed cerebral ische... more Biochemical mediators alter cerebral perfusion and have been implicated in delayed cerebral ischemia (DCI) and poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Estrogens (estrone [E1] and estradiol [E2]) are mediators with neuroprotective properties that could play a role in DCI. This study explored associations between plasma estrogen levels and outcomes following aSAH. Plasma samples from 1-4, 4-6, and 7-10 days after hemorrhage from 99 adult aSAH patients were analyzed for estrogen levels using liquid chromatography tandem mass spectrometry. DCI was operationalized as radiographic/ultrasonic evidence of impaired cerebral blood flow accompanied by neurological deterioration. Outcomes were assessed using the Modified Rankin Scale at 3 and 12 months after hemorrhage. Statistical analysis included correlation, regression, and group-based trajectory. Higher E1 and E2 levels were associated with higher Hunt and Hess grade (E1, p = .01; E2, p = .03), the presence of DCI (E...

Biological research for nursing, 2015

Aneurysmal subarachnoid hemorrhage is a type of stroke with high morbidity and mortality. Increas... more Aneurysmal subarachnoid hemorrhage is a type of stroke with high morbidity and mortality. Increased endothelin-1 (ET-1) levels have been associated with increased risk of cerebral vasospasm, which is associated with increased morbidity. The purpose of this study was to investigate the relationships between ET-1 genotypes and ET-1 protein levels in cerebrospinal fluid (CSF) measured 72 hr before angiographic vasospasm measurement in subjects at high risk of cerebral vasospasm. Specifically, this study evaluated the differences between variant positive and variant negative groups of nine different ET-1 single-nucleotide polymorphisms (SNPs) in relationship with the ET-1 protein exposure rate. The CSF ET-1 protein levels were quantified using enzyme-linked immunosorbent assay. One functional SNP and eight ET-1 tagging SNPs were selected because they represent genetic variability in the entire ET-1 gene. The variant negative group of SNP rs2070699 was associated with a significantly hig...

Journal of Cerebral Blood Flow & Metabolism, 2014

Preclinical studies show that epoxyeicosatrienoic acids (EETs) regulate cerebrovascular tone and ... more Preclinical studies show that epoxyeicosatrienoic acids (EETs) regulate cerebrovascular tone and protect against cerebral ischemia. We investigated the relationship between polymorphic genes involved in EET biosynthesis/metabolism, cytochrome P450 (CYP) eicosanoid levels, and outcomes in 363 patients with aneurysmal subarachnoid hemorrhage (aSAH). Epoxyeicosatrienoic acids and dihydroxyeicosatetraenoic acid (DHET) cerebrospinal fluid (CSF) levels, as well as acute outcomes defined by delayed cerebral ischemia (DCI) or clinical neurologic deterioration (CND), were assessed over 14 days. Long-term outcomes were defined by Modified Rankin Scale (MRS) at 3 and 12 months. CYP2C8*4 allele carriers had 44% and 36% lower mean EET and DHET CSF levels (P=0.003 and P=0.007) and were 2.2- and 2.5-fold more likely to develop DCI and CND (P=0.039 and P=0.041), respectively. EPHX2 55Arg, CYP2J2*7, CYP2C8*1B, and CYP2C8 g.36785A allele carriers had lower EET and DHET CSF levels. CYP2C8 g.25369T and CYP2C8 g.36755A allele carriers had higher EET levels. Patients with CYP2C8*2C and EPHX2 404del variants had worse long-term outcomes while those with EPHX2 287Gln, CYP2J2*7, and CYP2C9 g.816G variants had favorable outcomes. Epoxyeicosatrienoic acid levels were associated with Fisher grade and unfavorable 3-month outcomes. Dihydroxyeicosatetraenoic acids were not associated with outcomes. No associations passed Bonferroni multiple testing correction. These are the first clinical data demonstrating the association between the EET biosynthesis/metabolic pathway and the pathophysiology of aSAH.

Intensive and Critical Care Nursing, 2014

To examine the relationship between regional cerebral oxygen saturation (rSO2), delayed cerebral ... more To examine the relationship between regional cerebral oxygen saturation (rSO2), delayed cerebral ischaemia (DCI), and outcomes after aneurysmal subarachnoid haemorrhage (aSAH). Subjects (n = 163) with aSAH, age 21-75 years, and Fisher grade &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 were included in the study. Continuous rSO2 monitoring was performed for 5-10 days after injury using near-infrared spectroscopy with sensors over the frontal/temporal cortex. rSO2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50 indicated desaturation. DCI was defined as neurological deterioration due to impaired cerebral blood flow. Three- and 12-month functional outcomes were assessed by the modified Rankin scale (MRS) as good (0-3) and poor (4-6). DCI occurred in 57% of patients; of these 66% had rSO2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50. Overall, 56% had rSO2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50 on either side, 21% and 16% had poor MRS at 3 and 12 months. Subjects with rSO2 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50 were 3.25 times more likely to have DCI compared to those with rSO2 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50 (OR 3.25, 95%CI 1.58-6.69), positive predictive value (PPV) = 70%. Subjects with rSO2 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50 were 2.7 times more likely to have poor 3-month MRS compared to those with rSO2 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;50 (OR 2.7, 95%CI 1.1-7.2), PPV = 70%. These results suggest that NIRS has the potential for detecting DCI after aSAH. This potential needs to be further explored in a larger prospective study.

Neurosurgery Quarterly, 2008

... Barr, Taura L. RN, BSN* ; Alexander, Sheila A. RN, PhD; Kerr, Mary E. RN, PhD*; Crago,Eliza... more ... Barr, Taura L. RN, BSN* ; Alexander, Sheila A. RN, PhD; Kerr, Mary E. RN, PhD*; Crago,Elizabeth RN, MSN; Horowitz, Michael MD; Yonas, Howard MD§. Article Outline. Collapse Box Author Information. * National Institute of Nursing Research, Bethesda, MD. ...

Neurocritical Care, 2011

Background-Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathogenesis of vaso... more Background-Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathogenesis of vasospasm and delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients. The aim of this study was to investigate the relationship between cerebrospinal fluid (CSF) ET-1 levels and angiographic vasospasm and DCI.

Journal of Neurosurgery, 2014

Haptoglobin allele heterogeneity has been implicated in differential reactive oxidant inhibition ... more Haptoglobin allele heterogeneity has been implicated in differential reactive oxidant inhibition and inflammation. Haptoglobin α2-α2 has a lower affinity for binding hemoglobin, and when bound to hemoglobin, is cleared less easily by the body. The authors hypothesized that haptoglobin α2-α2 genotype should be less protective for downstream injury after aneurysmal subarachnoid hemorrhage (aSAH) and should portend a worse outcome. Patients with Fisher Grade 2 or higher aSAH were enrolled in the study. Genotyping for haptoglobin genotype was performed from blood and/or CSF. Demographic information, medical condition variables, and hospital course were abstracted from the medical record upon enrollment into the study. Outcome data (modified Rankin Scale score, Glasgow Outcome Scale score, and mortality) were collected at 3 months posthemorrhage. The authors enrolled 193 patients who ranged in age from 18 to 75 years. Only Caucasians were used in this analysis to minimize bias from variable haptoglobin allele frequencies in populations of different ancestral backgrounds. The sample had more women than men (overall mean age 54.45 years). Haptoglobin α2 homozygotes were older than the other individuals in the study sample (57.27 vs 53.2 years, respectively; p = 0.02) and were more likely to have Fisher Grade 3 SAH (p = 0.02). Haptoglobin α2-α2 genotype, along with Fisher grade and Hunt and Hess grade, was associated with a worse 3-month outcome compared to those with the haptoglobin α1-α1 genotype according to modified Rankin Scale score after controlling for covariates (OR 4.138, p = 0.0463). Patients with aSAH who carry the haptoglobin α2-α2 genotype had a worse outcome. Interestingly, the presence of a single α-2 allele was associated with worse outcome, suggesting that the haptoglobin α-2 protein may play a role in the pathology of brain injury following aSAH, although the mechanism for this finding requires further research. The haptoglobin genotype may provide additional information on individual risk of secondary injury and recovery to guide care focused on improving outcomes.

Journal of Neuroscience Nursing, 2003

Patients experiencing subarachnoid hemorrhage (SAH) symptoms may delay seeking medical attention,... more Patients experiencing subarachnoid hemorrhage (SAH) symptoms may delay seeking medical attention, not realizing the severity of these symptoms. The purposes of this study were to determine (a) the length of time between the development of SAH symptoms in patients and when treatment was initially sought and (b) whether the delay in hospital admission had an effect on patient outcomes. Inclusion criteria were age (18-75 years) and diagnosis of severe SAH. Consent was obtained on 90 eligible patients admitted to the neurovascular intensive care unit. Outcomes were assessed at 3 months using the Glasgow Outcome Scale (GOS) and Modified Rankin Scale (MRS). Initial time delay, calculated by subtracting the time of initial symptom development from the time of admission to the emergency department (ED), ranged from 0.08 to 103 hours. There was no relationship between the initial time delay and GOS or MRS scores. There was a significant difference between the time to initial ED admission to a trauma ED and to a community ED; patients were admitted within 2.7 hours to a trauma ED admission, compared to 7 hours for a community ED admission. There was a significant relationship between the Hunt and Hess Scale and GOS and between the Hunt and Hess and MRS. There was a significant relationship between the Fisher Grade and GOS and between the Fisher Grade and MRS. This study shows that patients may delay treatment for nearly 7 hours after initial symptoms develop. This suggests that laypersons are not aware of SAH symptoms, thereby delaying ED admission and care. The study also suggests that more severe symptoms upon admission to the ED were related to poorer outcomes. Initial clinical presentation is a useful predictor for SAH outcomes. This study supports the idea that the general public needs to be educated on the symptoms of SAH.

Journal of Neuroscience Nursing, 2009

Stroke is one of the leading causes of death and disability annually, and one of the larger popul... more Stroke is one of the leading causes of death and disability annually, and one of the larger populations for which neuroscience nurses care. Differences in gender have been identified as a risk factor for stroke repeatedly throughout the literature. The purpose of this evidence-based literature review is to provide information to healthcare professionals regarding stroke and its relationship with estrogen, the major female sex hormone. Background information on the three types of stroke is outlined, and information on estrogen compounds and hormone replacement therapy is detailed. A review of articles relating estrogen and/or hormone replacement therapy with stroke was performed. Fifty-seven articles met the criteria for inclusion in the review, 19 articles support the use of estrogen and/or an estrogen-related compound in the prevention or treatment of stroke, 6 articles claim estrogen and/or estrogen-related compounds are risk factors for stroke, and 11 articles remain inconclusive with regard to an estrogen and stroke relationship.

Critical Care Medicine, 2006

Biological Research For Nursing, 2013

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease that affects approximately 30,... more Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease that affects approximately 30,000 people a year in the United States. Delayed cerebral ischemia (DCI) and cerebral vasospasm (CV) are common complications after aSAH. In addition, aSAH patients have a high risk of poor long-term outcomes. Endothelin-1 (ET-1), a potent vasoconstrictor, or its two types of receptors, ET receptor A (ETA) and ET receptor B (ETB), may play a role in the pathogenesis of DCI and CV. Genetic variations within the ET-1, ETA, or ETB genes may also account for variance observed in the outcomes of aSAH patients. The purpose of this study was to describe the distribution of the Lys198Asn polymorphism, a known functional SNP in the ET-1 gene, and tagging SNPs of the ET-1, ETA, and ETB genes in individuals recovering from aSAH. This study also investigated the relationships among the ET polymorphisms, DCI, and global functional outcomes measured at 3 and 6 months after aSAH. Participants included individuals aged 18-75 years with a diagnosis of aSAH. There was a trend found between the variant allele of an ET-1 SNP (rs6912834) and angiographic vasospasm. There were also associations found between two ETB SNPs (rs9574124 and rs3027111) and poor outcomes as measured by the Glasgow Outcome scale at 3 months. These findings support the role of ET-1 and ETB in recovery following aSAH.

Stroke; a journal of cerebral circulation, 2016

The utility of prophylactic antiepileptic drug (AED) administration after spontaneous subarachnoi... more The utility of prophylactic antiepileptic drug (AED) administration after spontaneous subarachnoid hemorrhage remains controversial. AEDs have not clearly been associated with a reduction in seizure incidence and have been associated with both neurological worsening and delayed functional recovery in this setting. We retrospectively analyzed a prospectively collected database of subarachnoid hemorrhage patients admitted to our institution between 2005 and 2010. Between 2005 and 2007, all patients received prophylactic AEDs upon admission. After 2007, no patients received prophylactic AEDs or had AEDs immediately discontinued if initiated at an outside hospital. A propensity score-matched analysis was then performed to compare the development of clinical and electrographic seizures in these 2 populations. Three hundred and fifty three patients with spontaneous subarachnoid hemorrhage were analyzed, 43% of whom were treated with prophylactic AEDs upon admission. Overall, 10% of patien...

Lewis S Medical Surgical Nursing Assessment and Management of Clinical Problems, 2004

Neurocritical Care, Jan 28, 2009

Introduction Cardiac morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH) are a... more Introduction Cardiac morbidity and mortality after aneurysmal subarachnoid hemorrhage (SAH) are attributable to myocardial injury, decreased ventricular function, and ventricular arrhythmia (VA). Our objective was to test the relationships between QTc prolongation, VA, and survival after SAH. Methods In 200 subjects with acute aneurysmal SAH, electrocardiograms, echocardiograms, and telemetry were evaluated. Serum electrolytes and troponin were also evaluated. Results Initial QTc (mean 460 ± 45 ms) was prolonged (C470 ms) in 38% of subjects and decreased on follow-up (469 ± 49 initial vs. 435 ± 31 ms follow-up; N = 89; P < 0.0001). VA was present in 14% of subjects, 52% of subjects with VA had QTc C 470 ms, and initial QTc trended toward longer duration in subjects with VA (474 ± 61 vs. 457 ± 42 ms; P = 0.084). Multivariate analysis demonstrated significant predictors of VA after SAH were increasing age (OR 1.3/5 years; P = 0.025), increasing stroke severity (OR 1.8; P = 0.009), decreasing heart rate (OR 0.5/10 beats/min; P= 0.006), and the absence of angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist use at SAH onset (OR 0.10; P = 0.027). All-cause mortality was 19% (25/135) at 3 months and subjects with VA had significantly higher mortality than those without VA (37% vs. 16%; P = 0.027).

The Journal of Nursing Administration, Nov 1, 2009

The aim of this study was to explore the experiences of nurses and physicians who use a clinical ... more The aim of this study was to explore the experiences of nurses and physicians who use a clinical decision support system (CDSS) in the critical care area, focusing on clinicians&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; motives and values related to decisions to either use or not use this optional technology. Information technology (IT) has been demonstrated to positively impact quality of patient care. Decision-support technology serves as an adjunct to, not as a replacement for, actual clinical decision making. Nurse administrators play an imperative role in the planning and implementation of IT projects and can benefit from understanding clinicians&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; affective considerations and approaches to the technology. This qualitative study used grounded theory methods. A total of 33 clinicians participated in in-depth structured interviews probing their professional concerns with how the technology is used. Data were analyzed using the constant comparative method. Medical staff were frustrated by perceived lack of planning input before system implementation. Both nurse and physician cohort groups were dissatisfied with preimplementation education. Barriers to system use were identified in significant detail by the participants. Both nurses and physicians should be involved in preimplementation planning and ongoing evaluation of CDSSs. There is a need for a systematic review or Cochrane meta-analysis describing the affective aspects of successful implementations of decisional technology in critical care, specifically from the perspective of nursing administrators.