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Publication The irritability of the vagus nerves of dogs, as shown by the rheobase and chronaxie, in some types of tetany; and their relief by calcium salts(University of Kansas, 1931-05-31) Woodbury, Robert A.Publication Pharmacodynamic reactions of respiratory depressants and analeptics after their injection into the great cistern of the dog(University of Kansas, 1934-05-31) Rice, James CarlPublication An experimental analysis of the motor cell columns in the cervical enlargement of the spinal cord in the albino rat(University of Kansas, 1927-05-31) Goering, Joseph H.Publication Reflective Practice as a Tool to Overcome the Barriers to Adverse Childhood Experiences Screening in Adults(University of Kansas, 2019-12-31) Shaw, Erika DrewProblem: There is a significant dose-dependent relationship between traumatic experiences faced in childhood and poor adult health outcomes including substance abuse, chronic psychological and physical disease, and early mortality. Childhood trauma alters the chemistry of the developing brain and body, negatively influencing long-term health. The Adverse Childhood Experiences (ACE) screening tool is a binary response questionnaire consisting of ten questions that assess for history of childhood trauma. Despite mounting evidence to support the use of this tool and the great potential to enhance preventive, trauma-informed care, screening of adults for Adverse Childhood Experiences in primary care is not common practice. Perceived barriers to implementation cited by providers include time constraints, lack of training and confidence in screening and management of patients with a history of childhood trauma. Duchesne Clinic began the process of screening for ACEs by admission staff during the qualifying process. However, providers required support and guidance as they began to discuss the screening results with their patients and integrate ACE screening scores into plans of care. Project Aim: The aim of this project was to implement a guided reflective practice intervention with Duchesne Clinic providers to facilitate management of patients with high ACE scores. Project Method: This was a quality improvement (QI) DNP project at a safety net clinic in Kansas City, KS. Pre and post-intervention survey data was analyzed to assess changes in providers’ confidence and perceived barriers to management of patients with high ACE scores after four weeks of guided reflective practice intervention. Additionally, thematic analysis was performed to identify themes expressed by the providers in their reflection of their encounters with patients and their perceptions regarding management of patients with high ACE scores. Findings: Each of the seven questions on the ACE Provider Questionnaire yielded mean gains ranging between 0.25 to 1.2. A thematic analysis of the notes taken during all the interviews over the four-week guided reflective practice intervention produced the following themes: time as a barrier; feeling unprepared and unable to help patients with trauma history; re-traumatization; and strategies and tools for caring for patients with a history of trauma. Conclusions: Guided reflective practice was a successful tool to assist the providers at Duchesne Clinic to gain confidence and reduce the barriers to caring for patients with high ACE scores. Additionally, the sessions facilitated rich, honest and productive conversations between the Project Director, the Medical Director of Duchesne and each of the five providers and yielded a set of best practices for ACE screening and management at Duchesne Clinic.Publication Evaluating the Initial Management and Referral Process for Patients with Diabetic Foot Ulcers(University of Kansas, 2019-12-31) Westfall, Aren EmmalineApproximately 10% of the U.S. population is living with diabetes. Diabetic foot ulcers (DFU) are one of the most prevalent and debilitating complications. One in four people with diabetes will develop a DFU at some point in their lifetime. The consequences of non-healing DFUs include risk of amputation, further disease complications, increased risk of mortality, and more frequent and extended hospital stays. Adhering to evidence-based guidelines, which include recommendations for DFU prevention, assessment, and management, is crucial for achieving complete healing and reducing risks for poor outcomes. However, research has consistently shown a significant gap in the use of these guidelines in primary care, where DFU prevention should occur and DFU assessment and management most often begins. Objective: The purpose of this quality improvement project was to evaluate the initial management and current referral process for DFU patients and make recommendations for improvements based on current evidence-based practice guidelines for DFU management. Methods: A retrospective chart review was performed at the University of Kansas Hospital’s Outpatient Burn and Wound Care Center to evaluate for adherence to evidence-based practice guidelines for initial management and referral for DFU care by referring providers. Factors associated with lack of adherence to guidelines were identified via the collection of variables from 70 randomly selected patient charts, including specific data points related to DFU prevention, assessment, and management. Descriptive statistics were utilized to analyze the data collected using means for continuous variables and frequencies and percentages for categorical variables. Results: Retrospective data indicates that evidence-based guidelines were poorly implemented for DFU assessment and management in the primary care setting. In a sample of 70 patients, neuropathy assessments were done 21.4% of the time, ischemia assessments 45.7%, and infection assessments 87.1% in the primary care setting. In contrast, all three of these assessments were performed 100% of the time at the specialty wound clinic. Making a referral was the most common management strategy utilized by primary care providers for treating a DFU and was applied 75.7% of the time, although only 23% of these referrals were made to a wound care clinic. Debridement and offloading were infrequently seen in primary care with the former being utilized in 10% of cases and the latter 18.6%. Most often, referrals to wound care were made by a specialist, which was the case 49% of the time. Sixty-one percent of patients required more than one referral before being evaluated by a wound care specialist. Average total duration of a DFU from onset to resolution was 104 days (range 13-248). Conclusion: The results of this study indicate that the initial management and referral process of DFU’s is currently inadequate and not in line with current evidence-based practice guidelines for DFU management. Further research is needed to explore the reasons for provider noncompliance in order to determine appropriate interventions to facilitate improvements in adherence to guidelines.Publication Proactive Advance Care Planning in Rural Primary Care(University of Kansas, 2019-12-31) Trimble, ChelseaRelying on a family member to make medical decisions on behalf of a person who is unable to speak for themselves can cause unnecessary stress, cost, and dissatisfaction for both patients and their family. Making decisions without knowing a person’s preference for care often leads to a poorer quality of life and discordant care. Without an advance directive to guide care, family members are left to assume the patient’s wishes which can cause them to second guess a decision. Lack of knowledge and understanding are among the top reasons for not completing advance directives. As part of routine check-ups or well visits, primary care providers have the responsibility to introduce advance care planning to patients while patients are of sound mind and continue this discussion to include caregivers and/or family members. This quality improvement project helped facilitate a new process for beginning the advance care planning conversation in one rural Midwest primary care clinic. Current practices were identified to develop methods for change followed by an eight- week period where educational materials were offered to patients being seen for wellness visits which allowed the provider an opportunity to introduce advance care planning. Ancillary staff helped identify patients meeting inclusion criteria and facilitate a post-educational handout regarding patient satisfaction that was used to measure outcomes of implementing a standardized process. Keywords: advance care planning, rural communities, primary carePublication Determining Best Practice for Colonoscopy Preparation for Persons with Constipation(University of Kansas, 2019-12-31) Smith, Michele DianeAbstract According to the American Cancer Society, colorectal cancer is estimated to affect 145,000 people and is expected to cause over 51,000 deaths in the year 2019. The way to prevent colorectal cancer is by early detection through colonoscopy starting at age 50 or, age 40 if there is a strong family history. To cleanse the bowel for this procedure, patients drink a preparation (prep) fluid that induces bowel evacuation. If the preparation is poor, polyps, abnormal tissue, or masses can be missed warranting a repeat procedure. The purpose of this project was focused on determining the best practice for bowel prep for patients with a history of constipation. The project utilized retrospective chart review and assessed the frequency of poor prep diagnoses in persons with a history of constipation and association with the type of prep prescribed for colonoscopy at two Gastrointestinal (GI) clinic locations associated with a Midwest medical center. The overall rate of poor bowel prep was 34% but there was no statistical difference between each clinic’s bowel prep practice in the rates of poor prep among this population. This project also determined that the current rate of repeat colonoscopy completion due to poor bowel prep was 62.5%, 25% of patients at Clinic 1 and 37.5% of patients at Clinic 2. Clinician-perceived barriers to bowel prep standardization included barriers such as: cost to the patient, poor understanding of instructions, and fluid restrictions for comorbidities. The findings from this project determined that there is no need for bowel prep standardization across clinic sites based on prep, as best practice was not determined based on this project, however, prep should be based on patient preference, cost, price, and ability to understand instructions. Keywords: colonoscopy prep, poor colonoscopy prep, constipation and colonoscopy prepPublication Evaluation of a Chronic Care Management Program in a Rural Primary Care Clinic(University of Kansas, 2019-12-31) Pimple, CathyEvidence supports that Chronic Care Management (CCM) is a critical component of primary care that contributes to better outcomes and higher satisfaction for patients and providers. Unfortunately, the spread of CCM services for Medicare beneficiaries to improve outcomes, lower costs, and compensate providers for care coordination has been found to be low among primary care practices. The purpose of this project was to evaluate the implementation and outcome of a chronic care management program in a rural primary care clinic for sustainability and effectiveness. The project consisted of three aims: (1) evaluate the structure and process of a CCM program in a rural primary care clinic for patients with chronic conditions; (2) evaluate the CCM program sustainability; and (3) evaluate the program effectiveness through quality patient outcomes, resource utilization, and patient and provider satisfaction. The project design was a program evaluation using a single group interrupted time series that provided a process of collecting, analyzing and using data to measure both formative and summative outcomes of a CCM program. The key findings included program sustainability and positive benefits towards patient outcomes and both patient and provider satisfaction. Rural primary care practice settings benefit from the implementation of a CCM program through improved health outcomes and satisfaction. Strategic operational design influences the ease of implementation and sustainability of the program.Publication Improving Diagnosis and Treatment of Hypertension in a Family Practice Clinic Following the Implementation of an Educational Intervention(University of Kansas, 2019-12-31) Owen, JulianneProblem: Hypertension (HTN) affects over a third of all American adults, 20% of which are undiagnosed and untreated. HTN leads to greater morbidity and mortality, placing a person at a significantly greater risk for cardiovascular events and chronic kidney disease. The majority of those 13 million people with undiagnosed HTN visit their healthcare provider two or more times a year. Many patients presenting with elevated blood pressure (BP) measurements in primary care clinics in Kansas City often remain undiagnosed for HTN, which is likely to lead to poorer health outcomes. No facility-specific protocols exist to encourage follow-up in patients at high risk for HTN to address this problem. Project Aim: The aim for this quality improvement (QI) project was to determine the effectiveness of an educational intervention on the rates of diagnosis and treatment of HTN in a primary care clinic in Kansas City. Project Method: This QI project used the plan-do-study-act (PDSA) model to determine if diagnosis of HTN increased after eight weeks of the implementation of an instrument that encouraged follow-up in patients found with a BP of 130/80 or greater. The handout to patients with high BP consisted of four components: (1) brief education related to HTN, (2) lifestyle changes to decrease BP, (3) instructions for obtaining self-measured BPs, and (4) instructions to make a follow-up clinic appointment if their BP remains elevated. Data were gathered to evaluate if there was a reduction in the amount of undiagnosed HTN and in the average BPs of those seen in the clinic after the intervention. The patients included in this project were required to be English-speaking, between the ages 18 and 65, and had to have visited a specific primary care clinic in Olathe, Kansas, between May 20 and August 9, 2019. Findings: A total of 635 patient records were reviewed during the pre- and post-intervention phases. The number of undiagnosed HTN patients before the intervention was 91 of 301 participants, for a total of 30.2%. The number of undiagnosed hypertensive patients after the intervention was 120 of 334 participants, for a total of 35.9%. An estimated 424 patients had undiagnosed HTN during the eight-week intervention period, but only 233 educational handouts were provided. The fact that only 55% of eligible patients received the intervention can be explained by patient refusal and lack of staff consistently offering the handout to eligible patients. There was no improvement in the pre-intervention means of systolic and diastolic BPs to the post-intervention BPs (121.1 mm Hg, 122.3 mm Hg) and (76.3 mm Hg, 78.6 mm Hg) respectively. Conclusion: Primary care providers will frequently observe undiagnosed HTN. Thus, more structured protocols need to be developed to provide more consistent diagnosis and treatment for HTN in order to prevent the long-term consequence of HTN. This DNP project did not demonstrate a statistically significant improvement in BP measurements or the rate of undiagnosed HTN. However, the data indicated a significant proportion of patients seen during the project timeline had undiagnosed HTN, suggesting this is a practice problem at this clinic and future education and assessment of HTN needs to be implemented.Publication Improving Skin Protection Practices in Rural Kansas 6th Graders(University of Kansas, 2019-12-31) Miller, Jeanette KProblem: Skin cancer is a common cancer in the United States and often preventable with the use of sun modification behaviors (sunscreen, long sleeves, hats and sunglasses) (Centers for Disease Control [CDC], 2018). Prevention is a key to decreasing skin cancer incidence, its associated morbidity and healthcare costs. A low rate of skin protection education can be a contributing factor of sun damage especially in rural areas where there is greater exposure to the sun with farming, outdoor activities and low resources for educational interventions (Chun, Ohanehi, & Redican, 2015). Children and adolescents generally experience more cellular skin damage from ultraviolet (UV) radiation due to a thinner stratum corneum (Kunene et al., 2017). The majority of sun damage occurs prior to 18 years of age, a time when most school age children are involved in outdoor activities with misconceptions that skin protection is not important (Butera, Clark, Georges, & Bush, 2015). Project Aims: The overall aim of this DNP project is to improve skin protection practices in 6th graders in a rural Kansas town. The Project Director will: (1) assess perceptions regarding skin protection usage, (2) identify the barriers to skin protection in preadolescents, and (3) assess if the preadolescents after a skin cancer and protective sun health educational program intend to change any needed sunscreen practices. Project Method: This quality improvement project will be conducted at a grade school in Onaga Kansas. The sample will be approximately nineteen 6th grade students. Using a self-reported pre-test/post-test design, the Project Director assessed the perceptions, barriers, and the intent to change current skin protection practices of these 6th graders following the SunWise educational sun protective package. This presentation included a 60-minute session consisting of a SunWise PowerPoint presentation and an interactive program utilizing an ultraviolet (UV)/Skin Protection Factor (SPF) Frisbee demonstration. Descriptive statistics in the form of the Fishers exact test was utilized to evaluate the pre-post test scores related to the knowledge, benefits, and intent to change any needed sun practices in this rural Kansas preadolescent sample. Results: Pre- and post SunWise questionnaires were completed by nineteen rural Kansas 6th graders. The Fisher Exact test was used to calculate statistical significance (p=<0.05). There was statistical significance found related to perception: Tans look healthy (p<0.001); Do you like to tan (p=0.021); and Keeping your skin safe (p<0.001). Statistical significance was also found related to improvement in knowledge: What SPF sunscreen will you use (p<0.001); and When you need the most sun protection (p<0.001). There was limited intended behavioral practice change with playing in the shade increasing from 21% to 73% (p=0.002) and intentions to use sunscreen increasing from 42% to 73% (p=0.001). There were no significant findings for increased barrier use: Hats (p=0.723); Long-sleeves (p=0.232); and Sunglasses (p=0.068). Conclusion: The SunWise sun protection educational intervention is an effective model for skin health in the rural adolescent population. Improvement in perception, knowledge with limited improvement in intent to change behavioral practices were found following this DNP project.Publication Assessing Health Literacy Levels of Hispanic Patients with Type 2 Diabetes at a Federally Qualified Health Center in Rural Kansas(University of Kansas, 2019-12-31) Lapointe, KarliProblem: Hispanic adults have been associated with the lowest levels of health literacy (U.S. Department of HHS, 2010). The high prevalence of low health literacy and type 2 diabetes (T2D) among the Hispanic population likely contributes to the disproportionate burden of diabetes-related complications among Hispanic populations (Chukwueke & Cordero-MacIntyre, 2010). Project Aims: The aim of this project was to determine the readability level of current diabetes education materials provided to patients and assess the health literacy level of Hispanic patients with T2D in a health center in rural Kansas. Project Method: The Fry Readability Formula was used to assess the readability level of current diabetes patient education materials (PEMs) in both English and Spanish. The Newest Vital Sign (NVS) screening tool was administered to 25 Hispanic patients with T2D. NVS scores of 0 to 3 were indicated at risk for limited health literacy; while, those scored 4 to 6 were considered to have adequate health literacy. Results: The Fry Readability Formula estimated diabetes PEMs were written at an eighth-grade reading level. Out of the 25 patients who participated in the study, 20 (80%) scored at risk for limited health literacy via the NVS assessment. Further analysis found a significant association between health literacy level and gender (p=0.0092) and native language (p=0.041227). Conclusion: Findings from this study revealed an overall gap between the average health literacy level of the study sample and the estimated readability level of current diabetes PEMs. In order to improve the delivery of diabetes self-management education and support (DSME/S) among this population, providers must be aware of patients with limited health literacy and incorporate more effective teaching strategies to ensure an understanding.Publication A Quality Improvement Project Assessing Prevalence of Depression in Orthopedic Spine Patients(University of Kansas, 2019-12-31) Herman, Danielle MarieIndividuals with back pain who have spine conditions or are undergoing spine surgery may have depression that can lead to negative post-surgical outcomes, such as complications and poor quality of life. Currently depression is not assessed as part of the treatment plan or preoperative visit for spine patients at an urban academic medical center. This project determined the prevalence of depression and need for routine depression screening and referral in orthopedic spine patients at an urban academic medical center. Inclusion criteria were: adults ages 21 and up; the ability to speak, read, and write English; and a candidate for spine surgery or other spine treatment. Current clinic practices for depression screening and referral were evaluated. To establish a depression prevalence rate, eligible participants were invited to be screened for depression using the Patient Health Questionnaire (PHQ-9) tool. The average PHQ-9 score was 11, correlating with moderate depression. Participants scoring above 10 reported depression caused by pain and loss of function in daily activities prior to and after spine care treatment. Recognizing depression in spine patients prior to surgery could lead to earlier interventions, such as counseling, that could promote positive surgical outcomes including better quality of life, stronger self-efficacy in post-operative recovery, and a decrease in depressive symptoms. Initiating counseling along with conservative management of spine conditions and pain could enhance non-surgical treatment. Keywords: spine surgery, depression, Patient Health Questionnaire, perioperative screening, surgical outcomes.Publication Early Recognition of Sepsis in Outpatient Ambulatory Settings: An Educational Program for Primary Care Providers in Rural, South Central Kansas(University of Kansas, 2019-12-31) Heidner, Regina LAbstract Background and Review of Literature: Sepsis is a life-threatening, dysregulated human response to infection. It claims more lives than breast, lung or prostate cancer. Sepsis affects annually, 1.7 million Americans and 10,000 Kansas. The mortality rate can reach 50-80% if treatment is delayed. Early identification, prevention, and intervention, beginning in the community, before emergency room admission, is necessary. It is important to educate primary care providers and community members on early sepsis prevention, early identification, treatment, and recognition of high-risk groups. Purpose: The purpose of this quality improvement project was to increase knowledge about sepsis among community-based, primary care providers such as nurse practitioners, physician assistants, and physicians in ambulatory settings in rural, South-Central Kansas. Methods: A single group, pretest-posttest approach was used for this quality improvement project. An online educational module on sepsis early identification and treatment, created by TMF Health Quality Institute (2018), was synchronously presented to primary care providers employed in a rural, primary care health organization. Knowledge acquisition was measured using a test provided by TMF(2018). Result: Three providers participated. The overall percent increase in test scores from pretest to posttest was 16.6%. Pretest scores were low ranging from 40% -70%. Posttest scores were 70%. Discussion: Low pretest scores indicated a need for this education. The results showed an average 16.6% increase on test scores. Test score improvement demonstrated knowledge attained from the education provided and that this educational method and material was effective. This or similar projects delivered to primary care providers in an outpatient clinic could be beneficial. Keywords: sepsis, early recognition, ambulatory setting, primary carePublication SCREENING FOR DEPRESSION IN POST-STEM CELL TRANSPLANT PATIENTS USING THE PATIENT HEALTH QUESTIONNAIRE (PHQ)-2 AND PHQ-9(University of Kansas, 2019-12-31) Foss, Margaret AProblem: Clinical depression is a complication of stem cell transplantation. Depression can decrease adherence to treatment, worsen transplant outcomes, and increase mortality. At the University of Kansas Cancer Center (KUCC)’s Blood and Marrow Transplant (BMT) clinic, new patients are screened for depression using the Distress Thermometer during their first visit. This screening practice does not identify depression among patients after transplant. It was therefore important to implement standardized depression screening for post-stem cell transplant patients. Project Aims: The project aims of this quality improvement (QI) were: 1) to implement standardized screening tools (PHQ-2 and PHQ-9) for depression in this high-risk post-transplant patient population over 30 days, 2) to evaluate the effectiveness of PHQ-2 and PHQ-9 in detecting depression in post-transplant patients, and 3) to obtain feedback of the new screening process for depression from the medical assistants. Project Methods: The Plan-Do-Study-Act cycle guided this QI project. All post-stem cell transplant patients were screened for depression using PHQ-2 and if their scores were positive, they were screened with the PHQ-9. Patients screened positive on the PHQ-9 were assessed by their healthcare providers on the same day of their visits. Providers would initiate an antidepressant medication and/or refer the patient to mental health services. The following information was reported for a 30-day implementation period: the number of patients who were screened positive for depression by the PHQ-2 and PHQ-9, the number referrals to mental health services, and the number of antidepressants prescribed. Medical assistant feedback regarding the new screening process for depression were also reported. Findings: During the 30-day screening period, more than 200 post-transplant patients were screened for depression. Chart review were performed on a total of 101 randomly selected patients. Most of these patients (n = 100) were screened for depression using PHQ-2 and PHQ-9. Nine patients had a positive PHQ-2 score (≥ 3) and received additional screening of PHQ-9. Eight patients were screened positive on the PHQ-9 (≥ 5) with four patients being newly diagnosed with depression. These four patients were either referred to mental health service and/or started on antidepressants. Medical assistant (MA) survey results showed that patients were willing to answer PHQ questions to the MA and the screening process took less than 3 minutes to complete. Most MA’s expressed their willingness to continue PHQ screening. Conclusion: The new screening process for depression using PHQ-2 and PHQ-9 was effective to identify patients with depression. It was also useful for healthcare providers to reassess the treatment plans for those with existing diagnosis of depression. It is recommended that the PHQ results should be automatically shown to the healthcare provider in the best practice advisory in assessment and plan. This will help better optimize PHQ use in the BMT clinic.Publication Improving Transitions of Care between a Skilled Nursing Facility and Primary Care Providers(University of Kansas, 2019-12-31) Cvetan, TracyThe number of patients discharged to skilled nursing facilities (SNFs) after hospitalization continues to increase. Current research has focused on how to improve hospital to SNF or community transitions, with very few studies focusing on the transition from the SNF to the community. The purpose of this project was to identify whether the use of a standardized SNF discharge packet would improve the transfer of patient information between SNF and outpatient primary care providers (PCPs). Utilizing the Centers for Medicare & Medicaid Services guidelines, a standardized discharge packet was created for use at a suburban SNF in the Midwest. Participants in this project received rehabilitation services at the SNF and were discharged to the community, independent-living, or an assisted-living community and followed with a PCP at the university health system. The discharge packet was completed 24-48 hours prior to the patient’s discharge and sent to the care transition center within a university health system upon SNF discharge. The care transition center was then responsible for ensuring that a follow-up discharge appointment was made with the primary care provider with 14 days after SNF discharge and that the discharge paperwork was available for the primary care provider to review prior to the patient visit. Of the ten patients included in the QI initiative, sixty percent of patients were seen by their PCP within 14 days after SNF discharge. Only 10% of patients visited the ED or were hospitalized prior to their PCP follow-up. PCP’s contacted via survey agreed that the care transition center helped improve communication between providers, but noted that some pertinent patient information continued to be missing. Further inquiry into the current process of uploading patient information to the electronic health record is needed to ensure that discharge paperwork is present for providers to review prior to the patient follow-up. Keywords: transitions of care, care transitions, skilled nursing facility, and communityPublication Measuring Individual Treatment Benefits Using Longitudinal Outcomes from Clinical Trials or Hospital Data(University of Kansas, 2019-12-31) ZHANG, XUANIt is increasingly recognized that a patient’s response to a medical treatment is a statistically heterogeneous phenomenon. The average treatment effects may not represent a heterogeneous population of patients. The benefits each patient receive from the treatment could differ, requiring measurement of treatment benefits at the patient level. Despite of the development of methods in this field, new methods are needed for predicting individual treatment benefits using longitudinal binary outcomes or hospital data with nonignorable missingness. This dissertation has three main chapters. Chapter 1 introduces a method for predicting individual treatment benefits based on a personalized medicine model that implements random effects logistic regression of binary outcomes that may change over time. The method uses empirical Bayes (EB) estimators based on patients’ characteristics and responses to treatment. The prediction performance is evaluated in simulated new patients using correlations between the predicted and the true benefits as well as relative biases of the predicted benefits versus the true benefits. As an application, the method is used to examine changes in the disorganized dimension of antipsychotic-naïve patients from an antipsychotic randomized clinical trial. Chapter two of the dissertation presents a method for predicting individual treatment benefits with a novel 2-dimensional personalized medicine model that handles non-ignorable missingness due to hospital discharge and evaluate its reliability and accuracy by simulations. The longitudinal outcome of interest is modeled simultaneously with the hospital length of stay through a joint mixed model. The method is illustrated with an application assessing individual pain management benefits post spine fusion surgery. EB-Predicted individual benefits are compared with Monte-Carlo computed benefits. Pearson’s correlations and relative biases are used to assess the prediction accuracy. Finally, Chapter three of the dissertation applies the methodology developed in Chapter two to analyze with more clinical detail the impact of depression and age on individual benefits of postoperative pain management in lumbar spinal fusion patients using Cerner HealthFacts® electronic health records. The developed joint multivariate mixed model of pain scores and length of hospital stay is used to analyze individual benefits. The effects of depression and age on the amount and rate of change of the pain management benefits are evaluated, as well as the association between individual benefits and post-surgical hospital length of stay. We conclude that the utilization of the EB prediction of individual treatment benefits is useful in the analyses of treatment effects using not only clinical trial data but also electronic health records. Predicted individual treatment benefits are accurate when model parameters are reliably estimated.Publication A new role for NKG2D signaling in CD8+ T cells and autoimmune diabetes(University of Kansas, 2019-12-31) Trembath, Andrew PeterThe demands placed on the immune system are immense and highly complex. It must protect the body against untold threats while maintaining a balance between immune defense and autoimmune damage. One major player in immune recognition is the receptor Natural-Killer-Group-2-Member-D (NKG2D), best known for its expression on natural killer (NK) cells and CD8+ T cells, where it recognizes NKG2D ligands expressed by stressed cells following viral infection or cancerous transformation. NKG2D is most well studied for its role in tumor immunity, for which NKG2D based therapies are currently being developed clinically. Despite this, it is apparent that NKG2D has other poorly understood immune regulating functions, such as its implicated involvement in type 1diabetes and other autoimmune disorders. However, the mechanism by which NKG2D signaling affects diabetes has been unclear. We therefore sought to further clarify the role NKG2D plays in autoimmune diabetes development. Canonically, NKG2D engaging NKG2D ligand results in immune killing of the infected or damaged ligand-bearing cell by NK cells, and costimulation of CD8+ cytotoxic lymphocytes (CTL) augmenting CTL responses and target cell killing. However, we and others have observed robust expression of NKG2D ligands by seemingly healthy immune cells. In the work presented in this dissertation, I show the work I performed to investigate how this expression by seemingly healthy cells affects the immune response. In particular I focused on CD8+ T cells, which express both NKG2D and NKG2D ligands after activation, and play a key role in the development of autoimmune diabetes. Using the non-obese diabetic (NOD) mouse model of autoimmune diabetes, I found that engagement of the NKG2D ligand H60a, expressed by NOD T cells, during CD8+ T cell differentiation resulted in decreased cytokine production upon later antigen stimulation. This correlated with other findings from our lab showing decreased incidence of autoimmune diabetes in microbiota-depleted NKG2D sufficient versus NKG2D deficient NOD mice. Further, I showed that this correlated with NKG2D signaling driving an increase in CD8+ T cells with a central memory phenotype in both mouse and human cells. I then found significantly reduced transfer of NOD diabetes by these central memory phenotype CD8+ T cells compared to effector/effector memory CD8+ T cells. NKG2D on human CD8+ T cells increases generation of a subset of CD8+ central memory phenotype T cells that match the surface phenotype of a described regulatory CD8+ T cell population. Finally, I found that NKG2D stimulation increased expression of the inhibitory receptor PD-1 by NOD CD8+ T cells. I therefore suggest a previously undescribed role for NKG2D signaling between healthy cells in immunity and immune regulation, and take steps towards answering critical questions to determine whether modulation of NKG2D signaling could be used in intervention strategies in type 1 diabetes.Publication Guided Reflective Writing and Student Clinical Judgment Development: A Descriptive Study of Nursing Student and Faculty Perspectives(University of Kansas, 2019-12-31) Smith, Tanya LynnetteLiterature supports guided reflection and clinical judgment development as key components to enhancing students’ knowledge and preparation for complex nursing care. Faculty are challenged to prepare new nurses to enter the complex health care arena and often note problems in helping students transition classroom learning to clinical application. The National Council of State Boards of Nursing (NCSBN) recognizes and supports teaching clinical judgment in nursing curricula to better prepare nursing students for professional practice (2018). Guided reflective writing provides opportunities for nursing students to synthesize and evaluate evidence related to clinical experiences and may support clinical judgment development. The purpose of this qualitative descriptive study was to examine student and faculty perspectives of the benefits and challenges of guided reflective writing for clinical judgment development following clinical experiences. A convenience sample of Junior (n=28) and Senior (n=19) nursing students and faculty (n=4) were recruited from a baccalaureate degree nursing program at a small Midwestern university. These students used the Guided Reflective Writing Assignment organized by Tanner’s Clinical Judgment Model (2006). Student participants were asked to participate in an open-ended survey regarding their experience of the Guided Reflective Writing Assignment post-clinical. A focus group gained faculty perspectives of the assignment. Methods to assure trustworthiness included follow-up participant interviews and artifact analysis. Qualitative data was analyzed using content analysis to identify themes from the responses. An organizing frame relevant to reflective writing and clinical judgment for patient care emerged from the group descriptors. Since different student levels provided different perspectives of the assignment, a final theme for each student group was developed: 1) Organizes basic nursing care (Junior One students) and 2) Sense of wholeness (Senior Two students). Progression in clinical judgment from Junior One to Senior Two students was supported with participant comments. Faculty concurred with students’ perspectives with their final theme, Encourages deep thinking. Study findings reflect support and value of the Guided Reflective Writing Assignment for assisting students gain clinical judgment skills. The study helps advance the science of learning and leads to further research opportunities and implications for nursing students, faculty, graduates, and patient care.Publication Novel Statistical Methods for Missing Data and Multiplicity in Alzheimer’s Research(University of Kansas, 2019-12-31) Montgomery, RobertThe application of statistical procedures to real data sets seldom proceeds as seamlessly as a textbook problem where all assumptions are verified, and sample sizes are adequate. Common issues include lack of adherence to the statistical analysis plan, missing data and in early stage research, small sample sizes and a large number of variables of interest, i.e. multiplicity considerations. We present novel statistical methodologies that have been developed for use in these adverse scenarios with applications to research into Alzheimer's Disease. Specifically, we have developed an approach for the analysis of paired categorical data when the pairing has been lost, in the context of a study examining the effectiveness of a type of therapy on perceptions of Alzheimer's. We used a weighted bootstrap approach to compare the euclidean distance between the pre and post centers of mass the pre and post therapy groups and despite the loss of the pairing, were able to make conclusions about the research hypothesis. In addition, we developed a new global hypothesis test, the Prediction Test, which is intended for use in early stage research when the sample size is small and the number of endpoints of interest is large. We utilize researcher's predictions about the direction different endpoints will move, e.g. increase/decrease, and weight these predictions based on the sample correlation matrix. Using this test, we are able to come to a go/no-go decision concerning the feasibility of continuing to study the current research hypothesis, a common concern in early and exploratory studies. The prediction test had good power properties even for very small sample sizes and a large number of variables of interest, a situation in which most tests fail, while also controlling the Type I error rate. We demonstrate the methodology with a data set consisting of Arterial Spin Labeling (ASL) measures on older adults before and after a 12-week exercise regimen. The research hypothesis for this study was that the exercise intervention would alter the structural/functional aspects of the brain, specifically that ASL would increase in the different regions of the brain. We then provide extensions to the predictions that can be made in the Prediction Test and compare the method to a Linear Mixed Model and a set of t-test on a data set consisting of Diffusion Tensor Imaging (DTI) measures on pre and post kidney transplant patients. The research hypothesis of this study is that kidney transplantation will lead to a normalization of DTI measures, which are emerging bio markers for cognition and Alzheimer's Disease. We also discuss power calculations and conduct a simulation comparison between a set of t-tests and the prediction test.Publication Trajectories of Glycemic Control with Clinical Pharmacy Specialist Management of Veterans with Type 2 Diabetes(University of Kansas, 2019-12-31) Grabarczyk, TedPurpose: Prior evidence suggests that early, improved control of glycemic control likely lowers the risk of some combination of microvascular and/or macrovascular complications. Furthermore, growing evidence suggests that not only achieving a certain degree of control, but how that control varies also may matter in terms of outcomes. Finally, there is some initial evidence that clinical pharmacy specialist (CPS) services can, on average, lower glycosylated hemoglobin (HbA1c) and improve glycemic control. However, there is insufficient evidence characterizing variation in glycemic control outcomes in patients receiving CPS management of diabetes and factors associated with greater chance of success with that management. Methods: This is an observational, multicenter, retrospective cohort study of Veterans with type-2 diabetes in Veterans Integrated Service Network 15 managed by clinical pharmacy specialists between 7/1/2013 and 7/1/2017 with a baseline HbA1c level ≥ 8%. Glycosylated hemoglobin measurements were collected for two years following the index date and used to group patients into distinct patterns of HbA1c trajectories over time using group-based trajectory modeling and posterior probabilities of group membership. Characteristics associated with successful HbA1c trajectories and association of assigned trajectories with all-cause and diabetes-related hospitalizations were analyzed using logistic regression. Results: A total of 4,119 Veterans were included and successfully divided into six distinct HbA1c trajectory groups: High Gradually Decreasing (n=325, 7.9%), Moderate Early Decline (n=1692, 41.1%), Large Early Decline (n=231, 5.6%), Uncontrolled Stable (n=1468, 35.6%), Early Decline / Subsequent Increase (n=266, 6.5%), and Very Uncontrolled Stable (n=137, 3.3%). The Large Early Decline, Moderate Early Decline, and High gradually decreasing groups were classified as successful. Successful trajectories were more likely to reach a target HbA1c of ≤ 7%, have shorter duration of pharmacist management, greater utilization of nutrition clinic services. The distinguishing factor between successful and less successful trajectories appears to be the progress made within the first six months of pharmacist management. Conclusion: Patients managed for diabetes can be grouped into distinct patterns of change in glycemic control over time. The first six months of the clinical pharmacist/patient relationship may be important in determining a patient’s overall success. Future research is needed to identify pharmacist interventions that increase the likelihood of achieving successful glycemic control trajectory patterns.