Winners of the Outstanding Dissertation and DNP Project Awards

Background and Significance: Preterm infants experience chronic stress exposure during their extended hospitalization in the neonatal intensive care unit as a result of the medical procedures and nursing care required for their survival. The Neonatal Stress Embedding (NSE) Model theorizes that chronic stress exposure affects multiple biological systems in preterm infants, including functioning of the immune system, autonomic nervous system, and hypothalamic-pituitary-adrenal axis and causes changes in gene expression that result in abnormal brain development and neurodevelopmental impairments. Specifically, the NSE Model posits that chronic stress exposure causes systemic inflammation that damages the immature brain.

Purpose/Objective(s) and/or Specific Aims: The specific aims were to (1) determine the relationships among stress exposure, inflammation, and neurodevelopment in very preterm infants and determine the mediated effect of inflammation on the relationship between stress exposure and neurodevelopment, (2) describe cytokine trajectories in the weeks following birth and determine the effect of stress exposure on these trajectories, and (3) examine the relationship between chronic stress responses and stress exposure in preterm infants.

Methods: This was a non-experimental, repeated measures study of very preterm infants born between 28-31 weeks post-menstrual age (PMA). Infants were enrolled from four neonatal intensive care units in a large Midwest metropolitan area. The Institutional Review Board approved the study, and mothers of eligible infants provided written informed consent prior to the initiation of any study procedures. Cumulative stress exposure was measured using the Neonatal Infant Stressor Scale (NISS) over the first 14 days of life. The NISS provides a count of acute (e.g. intubation, lab draw) and chronic (e.g. mechanical ventilation, sepsis) stressors that is weighted by stressor intensity. Data to complete the NISS were retroactively extracted from the electronic health record. Blood was collected weekly with a clinically-indicated lab draw until 35 weeks PMA to measure inflammation. Inflammation was operationalized as a panel of cytokines and chemokines, quantified by multiplex assay. Average levels of individual cytokines/chemokines and average composite z-scores that included all detectable cytokines/chemokines were used. Neurodevelopment was assessed at 35 weeks PMA using the cluster scores for motor development and vigor (MDV) and alertness/orientation (AO) from the Neurobehavioral Assessment of the Preterm Infant. Hair for the measurement of hair cortisol concentration was collected by shaving at the nape of the infant’s neck at 35 weeks PMA. Multiple linear regression models, conditional process analysis, and linear mixed models were used to analyze the data. Statistical models included interactions with PMA at birth and infant sex and controlled for overall illness acuity.

Results/Findings: Seventy-three infants were enrolled in the study. We quantified plasma interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-1 receptor antagonist (RA) but were unable to measure IL-1β, IL-4, IL-10, and IL-17 in the majority of plasma samples. Although stress exposure did not significantly predict neurodevelopment, some measures of inflammation predicted MDV and AO. TNF-α and IL-1RA were associated with MDV scores. Composite scores of inflammation (i.e. average composite z-scores) were associated with MDV and AO scores. There were significant interactions with PMA and infant sex. In the mediation models, only IL-1RA mediated the effect of stress exposure on neurodevelopment. Linear mixed models revealed significant trends in postnatal cytokines/chemokines that were not affected by stress exposure. Cumulative NISS scores, a measures of stress exposure, did not correlate with hair cortisol concentrations, a measure of chronic stress responses.

Conclusion: While we could not confirm a relationship between stress exposure and neurodevelopment, inflammation may be an important predictor of short-term neurodevelopment. IL-1RA is an important cytokine for studies of preterm infant neurodevelopment. Moreover, composite z-scores may be a better measure of inflammation than individual cytokines/chemokines. Inflammation can be damaging to the immature brain and is a potential mechanism through which early life stress affects long-term outcomes. Stress does not appear to affect cytokine/chemokine trajectories. Cytokine/chemokine levels, most of which decrease over time, may be developmentally regulated or the result of resolving inflammation following preterm birth.

Background and Problem Statement: The prevalence of both type 1 and type 2 diabetes are increasing in the pediatric population (Alberti et al., 2004). In addition to milestones that accompany normal growth and development, children diagnosed with diabetes incur an additional set of challenges, physiologically as well as psychologically. Among youth with diabetes, death is more likely to occur due to an acute complication, such as DKA or hypoglycemia (Saydah et al., 2012). According to a report generated from Epic, the University of Mississippi Medical Center (UMMC) electronic health record, from November 2014 to November 2015 there were 195 hospital encounters including the ICD-10 code for DKA (this includes ER visits and hospital admissions), 141 of which resulted in hospital admissions. Of these 195 encounters, approximately 40% were repeat admissions (University of Mississippi Medical Center, 2019).

Purpose/Objective: The purpose of this scholarly project was to determine the effect of the telehealth RPM system initiative on HbA1c and diabetes-related ER visits and hospital admissions in the pediatric diabetes population at UMMC. The goal of the RPM program was to reduce HbA1c levels, to prevent unnecessary hospital encounters, and to allow the provider to make insulin adjustments between visits, as the pediatric population requires frequent insulin adjustments during periods of growth.

Procedures: UMMC Center for Telehealth, in collaboration with Children’s of Mississippi, Division of Pediatric Endocrinology, began to enroll pediatric patients with type 1 and type 2 diabetes into an RPM (remote patient monitoring) program in November of 2015. Patients receive a blue-tooth glucose meter and an iPad, and blood glucoses are transmitted via cellular service in real-time to the telehealth center, where nurses are monitoring the patients. The setting for the implementation of RPM was outpatient, UMMC, Division of Pediatric Endocrinology. Participants were patients aged 0-18 years with type 1 or 2 diabetes. Outcome data for participants was collected via retrospective chart review, for the 12 months prior to enrollment, and up to 12 months following enrollment. Outcome data collected included: HbA1c levels and diabetes related ER visits and hospital visits. Using SPSS, version 25, descriptive statistics were calculated and the paired t-test was conducted (using a level of significance of ≤ 0.05) to determine whether there was statistical evidence that the mean difference between standard care versus RPM for the outcomes of HbA1c, ER visits, and hospital admissions was significantly significant.

Outcomes: Hemoglobin A1c levels decreased from baseline for patients enrolled for up to 3 months (p=0.146), 9 months (p=0.142), and 12 months (p=0.007), and increased for those enrolled for up to 6 months (p=0.743). Emergency room visits decreased for those enrolled for up to 3 months (p=0.037), 6 months (p=0.388), and 9 months (0.054); however an increase was noted for patients enrolled for up to 12 months (p=0.822). Finally, for hospital admissions, a decrease was found in those enrolled for up to 3 months (p=0.138), 6 months (p=0.005), 9 months (p=0.021), and 12 months (p=0.819).

Conclusion: Consistent with the findings of other meta-analyses focusing on the use of outpatient telehealth, this study’s intervention also resulted in a more substantial decrease in HbA1c than with standard care alone. This may be due to the fact that there was increased contact with the telehealth RPM staff. Additionally, patients in this study received goal-specific education modules via the iPad, which may have also attributed to an overall increase in compliance with diabetes self-management. The ability of the healthcare provider to make insulin adjustments as necessary between visits likely contributed to a decrease in HbA1c levels as well.

 

Background and Significance: While researchers are modeling the social contexts in which people are living in studying health and disease, these social determinants of health (SDH) are often conceptualized and measured very differently. Both of these applications of SDH require reliable and valid measures. The construct of Social Stability (SS) developed by German and colleagues (2009) had several advantages: 1) more than one SS domain is necessary to create stability; 2) the inter-connectedness of domains; and 3) the importance of using a defined period of time in measurement. The six domains include: housing, residential/moving, income, employment, legal, and relationship stability over 12 months.

Purpose/Objective(s) and/or Specific Aims: The overall aim of this dissertation was to develop evidence for the use of SS in research and clinical practice. To examine reliability and validity, German’s SS measure was examined in a new population. In addition to overall stability, the prevalence and covariates of individual indicators were explored. Lastly, the relationship of SS to syndemic (co-occurring, interacting) risk behaviors (sexual, substance use, violence) was examined.

Methods: A cross-sectional analysis was conducted from a population (n=503) of heterosexuals at high-risk for HIV infection from the 2013 Baltimore site of National HIV Behavioral Surveillance Study. Data collection occurred via respondent driven sampling (RDS) where study seeds give coupons to potentially eligible participants and refer recruits to study site. This “weighted snowball” approach facilitates recruitment of often hidden populations. The final sample was predominantly African American, half male, with a median age of 37. The SS measure is a self-reported assessment of the six domains over the past year. Outcome variables include sexual risk, violence exposure, and alcohol and drug use variables. Sexual risk indicators include sexually transmitted infection (STI) or HIV diagnosis, multiple partners (2 or more sexual partners in the past year), concurrent partners (having sex with 2 or more partners during same time period), and exchange sex (receiving or giving drugs, money other goods for sex). Violence variables include experiencing threat by weapon, being in physical fight, experiencing physical violence from a partner, or forced sexual encounters. Both SS domain indicators and outcomes were analyzed for individual prevalence and in combination. A syndemic outcome was the co-occurrence of 2 or more of the risk indicators. Descriptive and latent class analyses (LCA) were used to characterize the prevalence and patterns of SS and risk behaviors and to identify SS subgroups. Logistic and latent class regression was applied to model the relationships of SS to risk behaviors and demographic covariates.

Results/Findings: Co-occurrence of SS indicators was common, with an average of 3.4 (SD=1.2) out of 6 indicators of stability. LCA showed evidence for 3 sub-classes: Class 1: overall high stability; Class 2: residential instability (moved in past year); and Class 3: low stability (income, employment instability). Perception or history of stability did not contribute to any improvement in identifying latent classes. Education was an influential covariate in LCA. Those with high school education/GED were nine times more likely to be in “high” vs. “low” SS class (OR=9.37; 95%CI: 2.75-31.82). The most common syndemic risk behaviors were sex-violence-drug, occurring in 18% of the sample. Ordinal and latent measurements of SS reliably predicted individual and combinations of sexual-substance use and violence risks. The latent approach showed higher odds of co-occurring risk for low vs. high SS class (OR= 6.25; 95%CI=2.46, 15.96) compared to using categories for low vs. high SS (OR=2.69; 95%CI=1.29, 5.59).

Conclusion: German’s measure of social stability captures inter-related social conditions across populations and identifies distinct subgroups of in/stability. Each domain of SS should be included and examined, with specific consideration for moving residence which was found to be important in the population studied. Further, ordinal and latent measurements of SS were reliably associated with risk in this population, demonstrating that as SS accumulates, co-occurring (or syndemic) risk diminishes. Furthermore, latent class analysis, which develops classes based on patterns of answers to a set of categorical variables, is a good approach to examine co-occurring predictors.

Background and Problem Statement: Sleep and epilepsy have a complex reciprocal relationship. Sleep-related breathing disorders that can occur in epilepsy are well recognized and a potentially dangerous risk factor for cardiovascular diseases, perioperative morbidities, increase in body mass index, cognitive impairment, unintentional injuries, changes in neuroendocrine, immune and inflammatory systems, depression, sudden unexpected death in epilepsy, increased frequency of seizures, and overall decreased quality of life (Faraut et al, 2012; Panossian et al., 2013). Undiagnosed and untreated obstructive sleep apnea (OSA) is also a potential dangerous risk factor for increased seizure frequency, particularly nocturnally, for adult patients with epilepsy. The American Academy of Neurology (AAN) in their clinical quality measures, indicate a need for provider’s to address safety issues and to intervene to reduce seizure frequency to zero. Patients can easily be screened for OSA with established markers that are strategically placed in the electronic health record (EHR) platform as a reminder to complete.

Purpose/Objective: The DNP student developed, implemented, and evaluated the effectiveness of adding an EHR alert with Assessment of Obstructive Sleep Apnea (AOSA) for assessment of patients with epilepsy by determining the percentage of patients referred for polysomnography (PSG). A 3-month retrospective chart review of adults with epilepsy was conducted to determine the percentage of patients screened for OSA and referred for PSG. The AOSA was added to the EHR to cue neurology providers to screen for OSA for 3 months. Percentages of referrals of patients with epilepsy for PSG before and after adding the AOSA EHR alert were compared.

Procedures: An urban university hospital was the setting for this study. Adult patients 18 years of age and older with epilepsy from the hospital’s seizure and neurology clinics were included. Children were excluded due to their sleep/wake cycle continuing to mature, changing body mass index (BMI), genetics, mandible, airway, tonsils and adenoid growth, and the behavioral factor of sleep-onset association disorder. After approval by the institutional review board, a review of the literature was conducted and an assessment tool was developed with 12 primary and 9 secondary risk factors with subsequent ordering of a PSG if >2 risk factors were present. The board-certified sleep medicine physician provided content validity. The AOSA tool was embedded in the EHR after approval by the institution’s EPIC steering committee. A 3-month retrospective chart review was conducted with the collection of sex, age, and data from OSA screening performed and referral for PSG. A second set of 3-month data were collected after inclusion and implementation of the AOSA in the EHR. The percentage of adult patients screened and referred for a PSG before and after integration of the AOSA in the EHR was determined. Pearson’s Chi Squared test (x2) was used for data analysis. The GraphPad Prism 7 program was used to calculate the Chi-Squared test for the quantitative data to determine if an increased proportion of patients were screened as positive for OSA with an EHR alert and referred for a PSG.

Outcomes: The three-month retrospective chart review indicated that no patients were formally screened for OSA prior to introduction of the EHR alert, yet 25 (7.2%) of the 346 subjects were sent for a PSG, presumably based on patient report, history and exam findings. Following the addition of a simple AOSA tool in the neurology section of the EHR, 405/414 patients (97.8%) of patients were screened for OSA and 134/405 (33.1%) were referred for a PSG. There was a significantly increased number of patients identified with OSA after the implementation of the AOSA (x2 value = 74.7, df = 1, p<0.001).

Conclusion: The results of this quality improvement project supported the assessment of adult patients with epilepsy for OSA with a prompt in the EHR. The added prompt increased the percentage of patients receiving a referral for a PSG to objectively determine OSA. In view of the clinical and public health implications of untreated OSA, screening in high-risk populations, such as patients with epilepsy, warrants implementation. Adoption of screening tools into the EHR may help to facilitate practice transformation and identify OSA as a potential risk factor for the proliferation of seizures in patients with epilepsy.

Irritable bowel syndrome (IBS) is a common disorder of the gastrointestinal tract, associated with high psychological comorbidity, diminished quality of life, and lacks efficacious clinical interventions. Stress has been depicted as a relevant factor in the development and maintenance of IBS symptoms, with patients displaying alterations in the "brain-gut axis" or BGA. The purpose of this dissertation study was to explore physiological and psychological indicators of stress in patients with IBS in comparison to healthy controls (HC), evaluated within the contextual framework of the BGA. Specific aims were to: 1) Investigate physiological correlates of perceived stress 2) Examine the association between perceived stress and quality of life 3) Explore patterns of stress-related neuroendocrine genes 4) Identify circulating proteins that differentiate IBS patients from HC.

This three-part investigation analyzed participant data from a parent investigation at the National Institutes of Health. Participants included males and females who identified either as HC or patients with IBS. The first investigation (N=101) revealed differential findings in psychological stress markers by IBS diagnosis, as well as sex, race and subtype differences in the stress response of IBS participants. These findings were used to optimize the second investigation, which analyzed expression levels of genes that may affect psychological and gastrointestinal processes, through the creation of a custom PCR array. IBS participants were found to differ from HC (N=48) in expression levels of six genes associated with immune activation, stress, psychological and antimicrobial processes. Additional analyses within female IBS participants, revealed a significant difference between subtypes in gene expression levels related to pain sensation. The third dissertation study harnessed the power of shotgun proteomic analysis, to identify circulating serum proteins that differentiate a homogenous set of IBS participants from well-matched HC (N=6). Analysis of 1,317 proteins revealed a significant difference in 12 proteins between IBS and HC participants, with biological associations including platelet activation/degranulation, platelet alpha granule lumen, secretion by cell and extracellular region.

This dissertation investigation revealed preliminary though promising findings of psychological, physiological, genomic and proteomic differences between IBS participants and HC, and within IBS participants. By exploring downstream effects of noted sex and subtype differences, this study may foster insight on physiological underpinnings of IBS and promote understanding of BGA dysregulation. By illustrating the heterogeneity of the IBS patient population, this study highlights the importance of an individualized approach to patient care, thus working to improve clinical outcomes of patients living with the disorder.

Honorable Mention went to:

Latefa Dardas, PhD, RN, CDE; Duke University
A Nationally Representative Survey of Depression Symptoms among Jordanian Adolescents: Associations with Depression Stigma, Depression Etiological Beliefs, and Likelihood to Seek Help for Depression.

Purposes/Aims: This project was designed to identify and evaluate key challenges a rural hospital has in providing a reliable best practice response for an Emergency Cesarean Section (ECS). Decision to Incision times (DIT) when confronted with an ECS along with newborn outcomes were studied. The study also conducted and analyzed staff questionnaires to evaluate staff attitudes, perceptions, role clarifications, driving and restraining forces in an ECS.

Rationale/Background: American Congress of Obstetrics and Gynecology (ACOG) recommend that obstetrical services be able to reliably perform an ECS DIT in 30 minutes or less. Seventy percent of neonatal brain injury may occur in the intrapartum period (AWHONN, 2015). Rural hospitals often perform all cesarean sections in the operating room domain with experienced operating room staff rather than obstetrical nurses trained in circulation and scrub. Rural hospitals are fraught with challenges around 24/7- hour/day availability of skilled anesthesia and surgical staff needed for an ECS. The Institute of Medicine, (2005) remarked that rural hospitals do not regularly have the census to finance operating rooms and anesthesia to be in house always. Rural multidisciplinary staff often feel unsupported and feel incompetent with oversaturated responsibilities. Night shifts (PM) and weekends are left vulnerable to prolonged DIT’s for an ECS.

Methods: Five years of Emergency Cesarean Section outcomes were analyzed (records review) to evaluate a rural hospital system in providing a reliable “best practice” response as recommended by ACOG. Outcomes (DIT’s and newborn) evaluated, included pre-intervention and post-intervention quality improvement(QI) project initiated by this author. Statistical tests include: t-Test for independent groups and mean scores, 5-minute Apgar mean scores, with nominal data for infant respiratory distress and hospital transfer. Staff questionnaires included a Likert scale that involved questions about staff encounters when an ECS was performed. The questionnaire also employed a ranking section about the staff’s personal perceptions about restraining and driving forces as described by the Kurt Lewin theory.

Outcomes achieved: Decision to Incision t-Test for independent groups analyzed, not statistically significant, (n=19, t=.88, alpha .05, two tailed, critical value,211, df17). Clinical significant ascertained that mean DIT scores were improved post-intervention by 7 minutes. Pre-intervention=DIT @ 37.2 minutes and Post-intervention=DIT @ 30.2 minutes. Evening shift (PM) and weekend, overall scores, demonstrated prolonged DIT mean scores, AM (n=8) =26 minute, PM/weekend (n=11) =42.3 minutes. Pre-implementation DIT AM=37.2-minute, Post implementation=25.6 minutes. Pre-implementation DIT PM/Weekend=41.2 minutes, Post=41.8 minutes. Staff questionnaires revealed that the staff believes that “best practices” are attainable for an ECS in this facility. The staff questionnaires also ranked that there was a lack of training surrounding an ECS, rural skill oversaturation requirements, and unity resistance between the Operating Room staff and Labor and Delivery staff when an ECS was called. The staff ranked the chief driving force as the importance of good newborn outcomes.

Conclusions: Recommendations include; (1) Improving this rural hospital’s health policies towards reducing PM/Weekend DIT times, thus reflecting “Best Practice”. (2) To continue the QI project, taking into consideration staffs’ desire to initiate and continually improve a rapid response plan when encountered with an ECS.

The dramatic increase in the consumption of controlled substances in North Carolina and across the nation has created a public health crisis with epidemic levels of medication diversion, misuse, abuse, unintentional overdose and death. Primary care providers are the principal prescribers of controlled substances and therefore at greatest risk of encountering patients that abuse medications. Guidelines recommend patient agreements with specific monitoring requirements when prescribing Schedule II medications (opioids and stimulants). Studies have focused solely on opioids and excluded stimulants and adherence to all recommended monitoring requirements has not been fully evaluated in the literature. Patient agreements were not previously used in the project practice site.

Implement a Schedule II controlled substance patient agreement and measure fidelity to components of the agreement.

A quality improvement framework using Plan-Do-Check-Act was used to design and implement the project. An opioid and stimulant prescribing policy and patient agreement was developed from sample agreements and based upon existing evidence with input from the practice partners. The policy applied to all patients aged 19 and over prescribed a long-term Schedule II medication for the chronic conditions of pain and/or attention deficit hyperactivity disorder. Examples of Schedule II narcotics include: hydrocodone, hydromorphone, oxycodone, fentanyl and methadone. Stimulants include: amphetamine, methamphetamine, and methylphenidate. All providers in the clinic received education about the policy. Adherence to the following outcome measures (elements of the protocol) were evaluated monthly: patient signed Schedule II agreement on file, prescription monitoring program (pmp) checked prior to writing a Schedule II prescription, urine toxicology screens, and prescriptions written without a mandatory visit. Monthly feedback was given to the providers over the course of the project. Modifications to improve adherence were made as needed. Outcomes were compared seven months pre- to seven months post-implementation of the patient agreement. Wilcoxon signed rank test and McNemar test were used to analyze differences in adherence between the pre and post implementation time period.

Fifty patients met study criteria and were included in the analysis. The mean (SD) age was 50.7 (16.3). The majority of patients were white (96.0%) and female (62.0%). An almost equal proportion of patients received medication for chronic pain (50%) and attention deficit hyperactivity disorder (46%). Four percent of participants received medication for both diagnoses. The percent of guideline adherence to each outcome improved from pre to post implementation: Signed agreement in chart (0%, 94%); urine screen guideline (5.3%, 71.1%); pmp checks (11.3%, 99.0%); prescriptions written without a visit guideline deviation, (20.6%, 0). All changes were significant (p < .001).

Implementation of a Schedule II controlled substance patient agreement and prescribing policy in a small primary care practice was feasible and adherence to the policy was excellent over a 7-month period.

Dissemination: The manuscript is under review for publication in the Journal of Family Medicine and Primary Care. The journal audience is family practice providers who frequently struggle with the complexity of prescribing chronic opioids. The project results will be shared at an evidence-based research conference scheduled for September 2016 at UCLA.

Continued implementation: All providers in the practice continue to follow the policy and are initiating patient agreements for new patients as well as following all aspects of the protocol. Monitoring for adherence is ongoing.

Sustainability and cost: The cost of implementation was not measured directly, but has proven to be minimal. In North Carolina, the prescription-monitoring program is state funded with free access to registered users. All project-associated tasks such as presentation and explanation of the patient agreement and urine collection were completed within the normal workday and did not require additional man-hours. In March 2016, the Centers for Disease Control and Prevention (CDC) issued the Guideline for Prescribing Opioids, http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm.

The protocol we implemented included almost all aspects of the guideline, which should increase the probability of associated costs being covered by insurance. All of these factors enhance the project’s sustainability.

People with type 1 diabetes mellitus (T1DM) experience high glucose variability and frequent hyperglycemia. Poor glucose control is known to contribute to accelerated cardiovascular disease (CVD), a leading cause of death in people with T1DM; however poor glucose control does not completely explain the increased risk. Good sleep also has been shown to play an important role in maintaining cardiovascular and metabolic health. Sleep quality is reduced in people with T1DM, but the reasons for poor sleep quality are not known. There has been minimal research into the relationship between glucose variability and sleep disruption in young adults with T1DM.

Hypotheses and Specific Aims: To test the hypotheses that glucose variations are causally related to sleep disruption and that sleep disruption mediates inflammation and CVD risk in individuals with T1DM, two aims were proposed: 1) to quantify sleep disturbances and to determine their relationship to glucose variability and 2) to define the relationship between sleep disruption and markers of CVD risk in young adults with T1DM.

A prospective, cross-sectional design was used. Young adults, age 18-30, who had diabetes for at least 5 years, wore an insulin pump and had a normal sleep schedule were enrolled. Subjects wore a continuous glucose monitor (CGM) and a sleep/activity monitor in home for three days and two nights and underwent a formal sleep study, polysomnography (PSG), while wearing the CGM in the laboratory at the University of Illinois at Chicago on the third night. The CGM is a validated tool that provides an updated glucose value every five minutes. Total time in bed was between 7-8 hours; blood was drawn just before lights out (pre-sleep); at lights on (awakening) and one hour after lights on(1-hr post awakening) to measure amounts of CVD risk markers, inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). The amount of power in five electroencephalogram (EEG) Bands – Delta and Theta (characteristic of sleep); Alpha, Beta and Gamma (characteristic of wakefulness) – was tracked throughout the PSG study night. Wavelet coherence analysis was applied to determine time varying and frequency specific relationship between glucose levels and the five EEG bands. Granger causality analysis along with vector coefficient analysis was applied to the glucose and five EEG bands to determine if potential causal interactions between glucose and EEG during sleep. Levels of IL-6 and TNF-α were determined using Enzyme linked immunosorbent assays (ELISA) and one-way ANOVA (Scheffe’s test for multiple comparisons) was applied to compare between the pre-sleep, awakening and 1-hour post awakening time points.

27 subjects (11 males, average age 23.9±4.1 years) were included in the analysis. Wavelet Coherence Analysis revealed a strong time-varying and frequency specific coupling between glucose and EEG, rapid fluctuations were more strongly coupled and exhibited more instances of strong coupling through the night (p<0.0001). 96.2% of subjects exhibited at least one instance of significant Granger causality between Glucose and EEG bands. Increasing glucose was causally related to increasing Alpha and decreasing Theta and Delta power, changes in the EEG signal which are consistent with an arousal or sleep disturbance (p=0.01). Increases in Delta (increases during deep sleep) consistently caused increasing glucose levels while increasing Theta (increases during rapid eye movement sleep) caused decreasing glucose. TNF-α was higher on awakening (1.44±0.66 pg/ml [SD]) and 1-hour post awakening (1.6±0.62 pg/ml) compared to pre-sleep (0.96±0.48pg/ml) (p<0.0001 for each). Subjects with good glycemic control exhibited a normal pattern of decreased IL-6 upon awakening.

Findings from the present study support a potential bi-directional causal relationship between glucose and brain activity during sleep. Increasing glucose led to changes associated with a sleep disturbance (increasing arousals and awakenings). Further, normal changes in the sleep process, were causally related to changes in glucose. The current findings also support that the sleep period may play an important role in increasing inflammation, a key mechanism in development of cardiovascular disease in people with T1DM. Collectively, findings from this study highlight the importance of the sleep period for glycemic control and inflammation in people with T1DM.

Sleep is a potentially modifiable behavior is increasingly recognized as playing an important role in maintenance of health. The findings from this study highlight that glucose variability during sleep may play an important role in disturbance of sleep, but also that sleep may influence glycemic control. This foundational evidence provide motivation for future interventional studies aimed to determine the mechanisms underlying the relationship between glucose variability and sleep disruption as well as the role of this relationship in development of CVD. Understanding how glucose variability and sleep disruption accelerates CVD may allow for improved diabetes nursing management strategies. Nursing interventions aimed at improving glycemic variability or minimizing sleep disturbances may help to improve glycemic control, decrease CVD development and ultimately improve quality of life in people with T1DM.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a protein that selectively induces apoptotic cell death via TRAIL receptor (TRAIL-R) activation in cancer cells. TRAIL-R agonists have been well-tolerated but demonstrated very little activity in patients. Interestingly, triple negative breast cancer (TNBC) cells were found to be sensitive to TRAIL-induced apoptosis while breast cancer cells representative of the other subtypes (estrogen/progesterone receptor positive or HER2 amplified) were comparatively resistant in vitro. Characterizing regulators and predictive biomarkers of TRAIL-R agonist sensitivity may help identify TRAIL-R sensitizing combinatorial therapies and TNBC-affected patients who might benefit the most from a TRAIL-R agonist therapy.

The first objective was to characterize the protein, gp78, as a negative regulator of TRAIL-induced apoptosis in breast cancer cells. The second objective was to evaluate the sensitivity of different subtypes of breast cancer cells in vitro to drozitumab, a TRAIL-R agonist that was well-tolerated in patients. The third objective was to identify potentially predictive biomarkers of TRAIL-R agonist sensitivity. The fourth objective was to evaluate expression of the potentially predictive biomarkers in patient samples. To address the first objective in evaluating the negative regulatory effects of gp78 on TRAIL pathway sensitivity, gp78 function was transiently inhibited using 10 gp78-targeting siRNAs in the TNBC cell lines MB231. gp78 function was also chronically inhibited by generating MB231 cells with stable gp78 knockdown. Cells with and without gp78 knockdown were then treated with and without TRAIL, and loss in cell viability and caspases-3/7 activity, which is a direct measure of TRAIL pathway activation, were assessed. To address the second objective, a panel of breast cancer cell lines representative of the different subtypes of disease (estrogen/progesterone receptor positive, HER2 amplified, and TNBC) were treated with and without drozitumab and evaluated for loss in viability. To address the third objective, immunoblot analyses were used to assess for potentially predictive protein markers of drozitumab sensitivity in the cell lines used in the second objective. Finally, to address the fourth objective, 177 TNBC tumor samples from a publically available cDNA microarray dataset were evaluated for the differential transcriptional regulation of genes whose protein products were identified as potentially predictive biomarkers of drozitumab sensitivity in the third objective. Additionally, 53 TNBC tumor samples were evaluated using immunohistochemistry to assess the protein expression of the identified potentially predictive biomarkers using a clinically relevant assay system.

The results from the first objective indicated that gp78 inhibited TRAIL-induced apoptosis in breast cancer cells in a mechanism that was dependent on the cell death-mediating proteins, caspases. The findings from the second objective demonstrated that TNBC cells, but not breast cancer cells representative of the other subtypes of breast cancer, were sensitive to drozitumab-induced cell death. In the third objective, the proteins Axl and vimentin were expressed only in the breast cancer cells that were sensitive to drozitumab-induced cell death. Axl and vimentin were thus selected as candidate predictive biomarkers of TRAIL-R sensitivity. Finally, in the fourth objective, Axl and imentin were found to be highly transcriptionally co-expressed (p<0.0001) in the cDNA microarray datasets of 177 TNBC tumors and were also highly co-expressed in the top quartile of Axl and vimentin-expressing tumor samples in the 53 TNBC tumor samples characterized by immunohistochemistry.

The findings from this study demonstrate that gp78 negatively regulates TRAIL-induced apoptosis in a caspase-dependent manner. TNBC cells were also determined to be sensitive to drozitumab, a TRAIL-R agonist, and those cells also expressed the proteins Axl and vimentin. Axl and vimentin were identified as candidate predictive biomarkers of drozitumab sensitivity and were determined to be expressed in human TNBC tumors at the transcriptional and protein levels. Therefore, Axl and vimentin expression in tumors may be utilized to aid in the selection of TNBC-affected patients who might benefit from a TRAIL-R agonist therapy.)

The findings from this study characterize the protein gp78 as a novel negative regulator of TRAIL-induced apoptosis. Little is known about the regulatory mechanisms that govern TRAIL sensitivity in cancer cells. Therefore, these findings contribute significantly to an area of TRAIL-related research that has been poorly described. The gp78 protein may also provide information about targetable pathways in cancer cells that could be inhibited or enhanced pharmacologically to promote TRAIL-R agonist activity in patients. The identification of the potentially predictive biomarkers of TRAIL-R agonist sensitivity, Axl and vimentin, may also aid in promoting TRAIL-R agonist activity in patients by helping identify those individuals whose TNBC tumors would most likely respond to a TRAIL-R agonist. In light of the limited success of TRAIL-R agonist strategies tested in clinical trials to date, using predictive biomarkers is a novel but potentially highly useful system for selecting patients for TRAIL-R agonist treatment. Collectively, these findings reflect elements from across the translational spectrum with respect to describing the fundamental regulatory processes of a biological system to the application of clinically relevant strategies for improving therapeutic effectiveness in patients.

Honorable Mention went to:

Veronica Brady, PhD, RN, FNP-BC, BC-ADM, CDE; University of Texas Health Science Center at Houston
Prevalence of Steroid Induced Hyperglycemia in Patients with Mantle Cell Carcinoma Receiving High Dose Steroid

Ariana Chao, PhD, FNP; Yale University
Obesity-Related Eating Phenotypes and the Relationships with Food Cravings, Stress, and Metabolic Abnormalities

Cesarean delivery is the most common major surgical procedure in the United States, representing 38.2% of live births in 2012 (Boyle et al., 2013). Infants delivered by cesarean section may face a more difficult transition to extrauterine life due to retained fluid within the alveoli (Blake & Murray, 2006). Skin-to-skin contact (SSC) and breastfeeding have been shown to help these newborns. However, one large urban medical center in the Southwest US did not have a policy to support immediate SSC and breastfeeding after cesarean delivery. This was a barrier to obtaining “Baby-Friendly Hospital” status (Baby-Friendly USA, Inc., 2012), despite being a Magnet hospital credited by the American Nurses Credentialing Center for excellence in patient care – with a level III perinatal and neonatal unit. The medical center is a busy urban academic hospital with 5,847 infant deliveries in 2013.

An evidence-based pilot protocol for SSC in the operating room (OR) immediately following a cesarean delivery was implemented in order to provide clinical impact data. Immediate SSC in the OR helps newborns adapt to extrauterine life and assists with infant-parent bonding and breastfeeding success. SSC can decrease the amount of time the infant spends in the Neonatal Intensive Care Unit (NICU), resulting in fewer nursing hours and overall cost savings for both hospital and patients.

The EBP project was conducted with approval from the Institutional Review Board at Arizona State University with reciprocal hospital agreement. The 7-step Iowa Model of Evidence-Based Practice (EBP) guided the EBP project. Step 1: topic selection (discussed above). Step 2: EBP team was formed and met biweekly, with members including project lead (L&D nurse and DNP student), L&D nurse manager, surgical scrub technician, obstetrician, nursing representative from the nursery team, and anesthesiologist. Step 3: systematic evidence retrieval to support the “triggering" question. Step 4: EBP team critically appraised the evidence to build obstetric section stakeholder buy-in. Step 5: development of standards for the pilot SSC protocol. Step 6: 3-month implementation of the pilot SSC protocol for all mother-infant dyads admitted for scheduled or repeat cesarean delivery with a live, singleton fetus greater than 37 weeks gestation, with no pre-existing medical complications or fetal anomaly (n=193). Nursery staff tracked neonatal outcomes including temperature, respirations, glucose, and disposition during the two-hour transition after birth. These data were compared to historical data for mother-infant dyads meeting protocol inclusion criteria in the 3 months prior to protocol implementation (n=302). A double-entry process was used to verify the data. Data were analyzed using chi-square test to compare rates of SSC application and infant disposition, and paired t-test to compare pre- and post-protocol neonatal outcomes including temperature, heart rate, respiratory rate, and blood glucose. Step 7: evaluation of the overall SSC procedure, including process review, outcomes data, and staff feedback for protocol evaluation and modification.

There were no baseline demographic differences between pre- and post-intervention groups. Neonatal outcomes were significantly different for infant temperature (SSC = lower), heart rate (SSC = lower), respiratory rate (SSC = lower), and blood glucose (SSC = higher) between pre- and post-intervention groups. Notably, SSC resulted in statistically and clinically significant reduction in hypoglycemia (p = .002). Additional outcomes included an increase in exclusive breastfeeding by 38.3% (p=0.000) in the intervention group, and an 84% decrease in NICU admissions (p=0.000) in the intervention group. SSC in the OR is a valuable and feasible intervention following a cesarean delivery, with no additional expense to the facility, and potential for significant cost savings due to deceased NICU admissions. This EBP outcome supports the American Academy of Pediatrics’ (AAP) recommendation for SSC in the first hour after birth (AAP, 2005) and promotes exclusive breastfeeding, one of the Joint Commission’s mandated initiatives (United States Breastfeeding Committee [USBC], 2010) and Healthy People 2020 goal ((Office of Disease Prevention and Health Promotion, 2015). The average cost of NICU admission for a normal term infant for hypoglycemia and hypothermia is $76,164 (March of Dimes Perinatal Data Center, 2011). This EBP SSC intervention reduced NICU admissions by 84% for normal term cesarean section births, representing $2 million cost savings to the hospital over 3 months.

The results of this EBP study led to the medical center including the SSC intervention in all new hire training and required annual skills competency training for seasoned employees. This training addition required minimal resources and additional costs or staffing.

The SSC intervention is included in the existing charting system. This EBP project has been disseminated at the following events:

• Arizona Nurses Association Conference, October 2014 – poster
• Highlighted in the Chief Nursing Officer’s Weekly Journal - October 2014
• Medical Center’s Poster Walk Showcase, November 2014
• Voted as the “Best Practice” Innovation for the medical center
• Systemwide Shared Governance Conference April 2015 - podium
• Advance Practice Neonatal Forum in Washington, D.C., May 2015 – podium and poster
• Highlighted as part of the medical center’s Magnet Documentation and presented to Magnet recertification evaluators, July 2015
• Invited podium presentation at the National Phoenix Perinatal Associate Challenges in Obstetric Care Conference, April 2016

Honorable Mention went to:

Susan Klein, DNP, FNP-C, OCN; University of San Diego
Transition After Breast Cancer Treatment: Implementing Survivorship Care Plans

Background and Significance:  Retinopathy of prematurity (ROP) is a potentially blinding disorder estimated to affect 14,000 to 16,000 infants with 500-700 becoming legally blind annually. It is known to be associated with preterm birth, low birth weight, and the use of oxygen. An optimal oxygen saturation range of 85-93% is often targeted to minimize the risk of either hypoxia or hyperoxia. Maintaining premature infants within the targeted range can be difficult with many infants spending significant amounts of time both above 93% and below 85%.

Purpose/Objective(s) and/or Specific Aims: The purpose of this research was to evaluate whether the development of ROP can be explained by the average percentage of time in a 24-hour period that the infant spends out of the targeted oxygen saturation range in the weeks prior to the development of ROP or retinal maturity. Additionally, the effect of higher oxygen saturation targets while an infant is receiving 21% oxygen was evaluated to determine whether this increases the risk of developing ROP.  Finally, the study addressed whether death before discharge can be explained using the average percentage of time during 24-hours that the infant spends out of the targeted oxygen saturation range.

Methodology/Procedures: The study used an observational, retrospective, and longitudinal design, tracking standard practice in a level IV referral center NICU. Weekly 24-hour histogram reports, generated from the Phillips IntelliVue™ Monitor detailing individual patient oxygen saturation levels, were collected and evaluated for the percentage of time the infant spent above and/or below a targeted saturation of 85% and 93%. Multinomial logistic regression was used to evaluate nested patient data of at-risk infants cared for at Primary Children’s Hospital, a free-standing children’s hospital, over a 3-year period. Data were entered longitudinally until retinal maturity/ROP occurred (N=241ROP study) or until death/discharge (N=250 survival study). Infants were excluded from both studies if ROP was present prior to admission, or death/discharge occurred without an eye exam or data collection.  Survival analysis using a discrete-time hazard model was used to explain the risk of developing ROP (stage 1 or ≥ stage 2) or death, associated with the time above and below the targeted range, controlling for the effects of gestational age and birth weight using logistic regression. The ROP model included a cubic time trend to reflect the average change in probability of developing ROP, and the survival model used a quadratic time trend for the risk of death.

Results/Findings: The total time the infant was out of targeted saturation range had no effect on the development of ROP. However, for every 2.7% of the time the infant spent ≤ 85%, the risk for ROP increased by 48% (p<0.038), and the risk of death increased by 11% (p<.001). The percentage of time an infant spent >93% decreased their risk of ROP and death. For every 10% of time spend >93%, the risk of ROP decreased 21%, and the risk of death decreased 11%. The time breathing 21% oxygen was added into the regression equation at all levels, it was not found to be significant for the prediction of ROP.

Conclusion(s): The optimal saturation range for infants at risk for ROP is not known. These data raise concerns about the appropriateness of the current saturation targets of 85%-93%. This supports the current recommendation of many that the targeted saturation range for this population should be higher. A low saturation level of 85% cannot be recommended as safe given the results of this study.  The upper limit of time for saturations >93% to be beneficial remains unknown and needs further research.

Implications/Recommendations for the Profession and/or Science: This is the first study to report the impact of the time a premature infant spends out of the targeted saturation range of 85-93%. It is also the first study to report the effects of high saturations while the infant is breathing 21% oxygen on the development of ROP.  The current research study provides important information on the effects of time spent with both low and high oxygen saturations on the development of ROP and death.  Infants in this study population largely represent infants in phase 2 ROP (31-44 weeks). It has shown that low saturations (≤ 85%) are detrimental, with increased risk for the outcomes of both ROP and/or death, while  high saturations (> 93%) improves the risk of both of these outcomes. This study also supports the use of oxygen saturation histogram data in clinical practice to evaluate an infant’s ability to maintain a given saturation target to help guide respiratory management decision-making within this high risk population. These monitoring tools can help answer important clinical questions about the impact and management of low and/or high saturations.

Honorable mention went to:

Qiaohong Guo, PhD, RN, University of Massachusetts Amherst School of Nursing
A Preliminary Model of Dignity Management in Hospice

Angela Smith Lillehei, PhD, MPH, RN, University of Minnesota School of Nursing
Effects of Lavender Aromatherapy via Inhalation and Sleep Hygiene on Sleep in College Students with Self-reported Sleep Issues

Background and Problem: Pediatric Nurse Practitioner (PNP) encounter children with concerns for a mental health disorder in their clinical practice, with only 20 percent of these children having any treatment often due to barriers to care such as poor mental health care access, social stigma, or other parental factors.  Anxiety disorders are the most common pediatric mental health disorder an estimated prevalence of 5 to 18 percent.  An estimated $247 billion is spent each year on childhood mental disorders including anxiety with 75 percent of these children presenting to the primary care setting for diagnosis and management. Because of the impact on children, families, and communities, children's mental disorders are an important public health issue in the States.

Purpose/Objective(s): The purpose of this capstone project was to offer evidence-based treatment option for PNP in the primary care setting for children with an anxiety disorder.  The primary care setting in the model of care discussed by the Substance Abuse and Mental health Services Administration (SAMHSA –HRSA Center for Integrated Health Solutions) can be a location for screening (S) and brief intervention (B-I) before referral to subspecialty if needed.  The brief intervention, Creating Opportunities for Personal Empowerment (COPE), is a manualized 7 –session program, that can be delivered by a trained PNP to offer skills similar to Cognitive Behavioral Therapy.  

Procedures: This was a pilot study completed at a Federally Qualified Health Clinic in the rural Northwest area of Florida.  A convenience sample of 14 children ages 8 to 13 years was utilized once they met the criteria of having an anxiety disorder based on DSM 5 criteria.  Exclusion criteria included any mental retardation, psychosis, or current suicidal thoughts.  The intervention, COPE appointments were 30 minutes in length and scheduled at the families preferred time.  The core concept which is a subset of techniques in CBT was presented to the child; then reinforced through games, interactive activities, and finally real life application of these concepts.

Anxiety symptom reduction has been considered the gold standard of improvement after intervention which was measured utilizing the reliable SCARED symptom checklist with a score less than 25 equaling no anxiety symptoms. Level of functioning was assessed using the Clinical Global Impressions Scale.  Children assess their improvement in functioning by answering the question “After the COPE program, how is your home and school life?”  Improvement is seen with a score of 2 or higher (much improved to very much improved) which is consistently used in the literature with pediatric anxiety.  Cognitive - behavioral skills learned through the COPE program were assessed through a 15 question content quiz given before and after all 7 sessions were complete. Finally, program satisfaction was measured through open-ended questions for both the parent and child.

Outcome(s): Children who participated had significant decreases in anxiety symptoms (13.88 points, SD = 17.96, 95% CI -1.13, 28.89) and on post assessment 50 percent of the participants no longer met criteria for an anxiety diagnosis.   They also had increases in knowledge of cognitive – behavioral coping skills (M=11.38, CI 5.99, 8.26, p = 0.00) and 100% showed improved functioning at both school and home on self-evaluation.  Evaluations by parents and children were positive with 100 % of participants and parents preferring delivery of COPE in the primary care setting and recommending the program to another child.

Conclusion(s): COPE visits fit into the fast - paced pediatric practice in 20 - 30 minute sessions.  COPE sessions were billed and all were reimbursed by the insurance providers at the higher CPT code for time of over 50% of the visit in counseling (99214) indicating this is a cost effective intervention in primary care.  Post COPE evaluations indicated improved patient outcomes. There was one child who had a worsening of anxiety score on SCARED after COPE delivery.  This child was dealing with social changes that were identified during individual sessions.  With the S-B-I-R-T treatment model in mind after COPE sessions were completed then the patient was referred to a mental health provider for a longer intervention.

Implications for Practice or System Change(s): With the call to arms across both psychiatric and pediatric organizations to offer effective, evidence-based mental health treatment no matter the treatment location, the PNP is in a unique opportunity to intervene early in the child’s anxiety diagnosis.  With early, effective interventions this anxiety diagnosis will be less likely to follow the child into adulthood.

The Triple Aim of Healthcare views successful interventions that are cost effective, patient centered and improve patient outcomes.  The COPE program meets these three criteria, which was disseminated at the DNP Convention (Fa    ll of 2014).  PNPs continue to practice in the front lines in rural areas, with the largest need for mental health support.  To offer this program to other PNPs this project will be presented at the National Association for Pediatric Nurse Practitioners conference in March.  Journal submission has also been completed for consideration for the Journal of Pediatric Healthcare.  The lead researcher continues to perform COPE in her daily practice, with 10 children completing since the project ended.

Honorable mention went to:

Kathryn Evans Kreider, DNP, FNP-BC, Duke University School of Nursing