• Effect of ErbB4 on Triple Negative Breast Cancer Cell Growth and Migration

      Yousif, Ahmed; The University of Arizona College of Medicine - Phoenix; Salhia, Bodour (The University of Arizona., 2014-04)
      Members of the ErbB subfamily of receptor tyrosine kinases are critical regulators of normal mammary gland development, and alterations in their signaling have been associated with breast tumorigenesis. ErbB4 expression in breast carcinomas predicts improved patient survival and inversely correlates with tumor grade, metastasis and disease recurrence. When examined in the context of the breast cancer molecular subtypes, ErbB4 expression is rarely expressed in the triple-negative tumor subtype, which is associated with poor prognosis. Recently, our lab discovered a genomic context for the loss of ErbB4 expression in metastatic, refractory triple-negative breast cancer (TNBC) samples by next generation sequencing technology. The goal of this study was to examine the effects of ErbB4 overexpression on the growth and migration of TNBC cell lines. A GFP-containing construct was used to overexpress ErbB4 in the ErbB4-negative TNBC cell lines BT-20, BT-549 and MDA-MB-468. An empty vector construct was used as the control. Expression was confirmed by western blot and fluorescence microscopy to detect expression of ErbB4 or GFP respectively. Cell motility and growth was assessed with a transwell migration assay and a sulforhodamine B assay to measure cell density, respectively. Our data indicates that overexpression of ErbB4 resulted in no significant difference in the migration of BT-549 or MDA-MB-468 cells but resulted in a slight increase in the migration of BT-20 cells. ErbB4 had a growth inhibitory effect on BT-549 and BT-20 cells but showed no difference in the growth of MDA-MB-468 cells. This data suggests that multiple ErbB4-mediated mechanisms occur to alter the growth of TNBC cells. Although the translational significance of ErbB4 loss may be in its ability to predict outcome in patients with TNBC, more work is needed to elucidate the molecular mechanisms mediating its function.
    • Correlating IVC Measurements with Intravascular Volume Changes at Three Distinct Measurement Sites

      Yang, Kimberly; The University of Arizona College of Medicine - Phoenix; Wu, Teresa (The University of Arizona., 2014-04)
      Bedside ultrasound of the inferior vena cava (IVC) has grown to be an important tool in the assessment and management of critically ill patients. This study endeavors to examine which location along the IVC is most highly correlated with changes in intravascular volume status: (1) the diaphragmatic juncture (DJ) (2) two centimeters caudal to the hepatic vein juncture (2HVJ) or (3) left renal vein juncture (LRVJ). Data was collected in this prospective observational study on patients in the emergency department who were at least 16 years of age, being treated with intravenous fluids (IVF). Measurements of the IVC were recorded at each site during standard inspiratory and expiratory cycles, and again with the patient actively sniffing to decrease intrapleural pressures. IVF was then administered per the patient’s predetermined treatment, and the same six measurements were repeated after completion of fluid bolus. The difference in caval index (dCI) was calculated for all six data sets and correlated with the mL/kg of IVF administered. There was a statistically significant correlation between mL/kg of IVFs administered and dCI at all three sites (DJ: r = 0.354, p value = 0.0002; 2HVJ: r = 0.334, p value = 0.0003; LRVJ: r = 0.192, p value = 0.03). The greatest correlation between amount of fluids administered and dCI was observed along the IVC at the site 2 cm caudal to the juncture of the hepatic veins (2HVJ). This site is also where the largest change in diameter can be appreciated on ultrasound during intravascular volume resuscitation. Our data also suggests that every mL/kg of IVFs administered should change the dCI by 0.86-1.00%. This anticipated change in IVC diameter can be used to gauge a patient’s response to intravascular volume repletion.
    • Pediatric Out‐of‐Hospital Cardiac Arrest in the State of Arizona

      Tully, Jeffrey; The University of Arizona College of Medicine - Phoenix; Buttram, Sandra (The University of Arizona., 2014-04)
      Comprehensive databases which collect data on out of hospital cardiac arrests have been useful in identifying markers of outcome in adults, but this data is limited in children. The Arizona Department of Health Services’ Save Hearts in Arizona Registry and Education (SHARE) database contains data on pediatric cardiac arrests in the field and offers a unique opportunity to examine outcome measures and pre-hospital care. We retrospectively analyzed 312 children (1-215 months) from the SHARE database between 2004-2010. Variables assessed included: bystander cardiopulmonary resuscitation (CPR) administration, transport times and impact of Pediatric Intensive Care Unit (PICU) availability on outcome to hospital discharge. Data were analyzed by t-test and Fisher’s exact test. Of 312 children with out of hospital cardiac arrest, 11 (3.6%) survived to hospital discharge. The low survival rates in this review make statistical comparisons difficult, though potential trends were noted that, with additional numbers to increase power, may provide insight into factors affecting survival from pediatric OHCA that have not been assessed on a wide scale in this vulnerable population.
    • First Kidney Allograft Mismatch and Survival in American Indians

      Thomsen, Chelsea; The University of Arizona College of Medicine - Phoenix; Chakkera, Harini; Williams, Robert (The University of Arizona., 2014-04)
      Over 121,000 individuals are awaiting renal allograft in the United States.1 This ongoing imbalance of supply and demand has made research aiming to improve renal allograft survival a necessity. Details of the collection, distribution, and outcomes of renal allografts found in the United Network for Organ Sharing (UNOS) database were used in a retrospective study to identify and evaluate differences in allograft survival between American Indians and other heritage groups. In particular, the study aimed to identify whether American Indians have a similar distribution of HLA mismatches between recipient and donor when compared to other populations; and whether this impacts overall kidney allograft survival. Contingency table and Cox Regression analyses were applied and found that the Hazard Ratio was greater than 1 for all mismatches; and furthermore, an increase in mismatches was proportional to an increase in hazard ratio that was statistically significant. Recipients with 4, 5, or 6 mismatches showed a hazard ratio of 1.466 (p<0.0564). The HLA-DR allele has been known historically as the most important locus for transplants.2 Better matching, particularly at the DR locus, results in improved kidney survival time. Additionally, age, gender, and transplant era were used as major covariates in allograft survival using a proportional hazards model. Increasing age of recipient is associated with increased kidney survival time, and female gender is associated with decreased kidney survival time. Transplant era had a very high Chi-Square of 40.22 and an overall 5% increased survival with most recent transplants living longer than older era transplants. These results have implications for potential policy changes regarding organ allocation in addition to identifying an increased need in organ donation within specific heritage groups.
    • Standardizing Radiological Findings for Non‐Accidental Trauma in the Pediatric Population

      Sultani, Masoud; The University of Arizona College of Medicine - Phoenix; Richardson, Randy; Valencia, Elizabeth (The University of Arizona., 2014-04-17)
      The objective of this project was to review skeletal survey reports and examine the differences in reporting of non-accidental trauma in patients with similar radiological findings. The overall purpose of this project is to develop a standardized reporting system for radiological findings suspicious for non-accidental trauma. Ten years’ worth of skeletal survey reports were obtained on over 1,500 pediatric patients. These reports were individually reviewed and their findings were categorized in a table separating findings suspicious for non-accidental trauma. After data collection, analysis was completed to inspect the consistency of reports amongst studies with similar fractures specifying non-accidental trauma. The comparison was made between reports containing long bone fractures, metaphyseal corner fractures, rib fractures, or any combination of these. It was concluded that there are inconsistencies in reporting of non-accidental trauma in reports with similar patterns of these fractures. We propose a Skeletal Survey – Reporting and Data System (SS-RADS) score which will help radiologist standardize their reporting methods for more consistent interpretations and clinical outcomes.
    • The Effects of Parent Training in Pivotal Response Treatment (PRT) and Continued Support through Telemedicine on Gains in Communication in Children with Autism Spectrum Disorder

      Singh, Namrata; The University of Arizona College of Medicine - Phoenix; Melmed, Raun (The University of Arizona., 2014-04)
      Introduction: With the increase in children diagnosed with autism spectrum disorders (ASD) each year comes the need for individualized interventions necessary for children with autism. Many of the treatments currently available are time consuming, costly, and rely heavily on behavioral interventionists despite the lack of qualified interventionists to provide these services. Therefore, there is a growing recognition of the need for efficient, cost-effective treatment models that involves families in the intervention. This study examined the effects of continuous parent training and feedback for 3 months in Pivotal Response Treatment (PRT) through telemedicine on responsivity to language opportunities in children with ASD versus a control group of parents receiving one week of PRT training alone. We hypothesized that with telemedicine support, the child’s verbal communication would increase. Methods: 30 child-parent dyads from Tucson, AZ were enrolled in this randomized control trial. Subjects were 24-60 months of age and met DSM-IV criteria for autism at the time of enrollment. All subjects received one week of intensive parent training at the Southwest Autism Research and Resource Center (SARRC) in PRT. The support group received telemedicine feedback three times weekly for three months. Data was analyzed using two sample t-tests and Wilcoxon rank sum tests. Results: The control group had a mean responsivity in function verbal utterances of 64.3% and the telemedicine group had a 62.7% verbal responsivity rate prior to initiation of telemedicine support. At three month follow-up, the control group had a mean responsivity rate of 58.6% and the telemedicine group had a mean responsivity of 64.3%. A two sample t-test showed a no significant difference between the two groups with a p-value of 0.51. Conclusions: This study did not find any significant difference between the telemedicine and control groups. However, there is a trend towards increased verbal communication in the telemedicine group. We therefore recommend further studies to determine the utility of telemedicine and parent training in PRT in the treatment of children with ASD.
    • Arizona Alzheimer’s Registry: Strategy and Outcomes

      Saunders, Kelley; The University of Arizona College of Medicine - Phoenix; Tariot, Pierre (The University of Arizona., 2014-04)
      Background: The Arizona Alzheimer’s Consortium (AAC) is a statewide Alzheimer’s disease (AD) research consortium. In 2006 the AAC created the Arizona Alzheimer’s Registry (Registry), a screening and referral process for people interested in participating in AD-related research. The Registry goals were to increase awareness of AD research and accelerate enrollment into AAC studies. Registrants were matched to AAC studies according to interest, location, and eligibility. Methods: Anyone age 18 and older was eligible. Registrants were recruited by community outreach, mass mailings, earned and paid media, and the Internet. Those interested received a welcome packet, consent, and questionnaire, which were reviewed by staff via telephone prior to brief cognitive screening. Evaluation of medical history, cognitive status, and interests resulted in a referral to existing AAC studies or being held for future referral. Results: 2263 people contacted the Registry. 1257 consented and 1182 underwent an initial cognitive screening. Earned media was the most effective recruitment strategy. Registrants had a mean age of 68.1 (SD 10.6), 97% were Caucasian, had 15.2 (SD 2.7) mean years of education, and 60% were female. 30% reported a family history of dementia, 20% reported a diagnosis of cognitive impairment or dementia, and 70% subjectively reported normal cognition. Initial telephone assessments revealed 681 with no impairment, 269 with possible cognitive impairment, and 234 with possible dementia. 301 were referred to AAC sites for potential enrollment into a study. Conclusion: The Registry created an infrastructure and process to screen and refer a high volume of eager Registrants. These methods were found to be effective at prescreening individuals for studies, which facilitated AAC research recruitment. The established infrastructure and experiences gained from the Registry have served as the prototype for the web-based Alzheimer’s Prevention Registry, a national registry focusing on AD prevention research.
    • A RCT: Is intraoperative acupuncture at acupuncture‐point P6 plus antiemetics more effective than antiemetic therapy alone in preventing postoperative nausea and vomiting in pediatric patients following tonsillectomy with or without adenoidectomy?

      Pierson, Kasey; The University of Arizona College of Medicine - Phoenix; Kendrick, Angela (The University of Arizona., 2014-04)
      Purpose: Acupuncture at point P6 has proven efficacious in alleviating postoperative nausea and vomiting (PONV). Evidence supporting its use in pediatric patients is not nearly as conclusive. Furthermore, acupuncture’s effects when combined with antiemetics needs to be further elucidated. We conducted a double-blinded, randomized controlled trial to investigate the effects of P6 acupuncture combined with antiemetics on pediatric patients undergoing tonsillectomy. Methods: A total of 109 patients between the ages of 3 – 9 years old were randomly assigned to one of two treatment groups prior to surgery. Each group received standard antiemetic medications while only one group received acupuncture intraoperatively. PONV was assessed via usual protocol while the patients remained at the post-anesthesia care unit (PACU) and Day Stay Unit. A follow-up phone call 24 hours following surgery was conducted to assess for overnight symptoms. Results: 106 patients completed the study with 58 randomly assigned to the Treatment Group, whom receive acupuncture and antiemetic therapy, and 48 to the Control Group, receiving only antiemetic therapy. When comparing baseline characteristics and possible confounding factors for each group, no statistical differences between the groups could be found. For primary outcomes, the only significant difference between the two groups occurred with the incidence of nausea in the PACU following the surgery (P = 0.02), but nausea in the Day Stay Unit trended toward significance (P = 0.06). Retching and vomiting incidence did not occur frequently enough in the hospital to be analyzed. No differences between the Treatment Group and Control group were seen in the 24 hours after the patients were discharged from the hospital. Discussion: With no adverse events from its use and with statistically significant efficacy, P6 acupuncture embodies a useful prophylactic treatment for postoperative nausea in children.
    • Non‐invasive testing to determine cardiac or non‐cardiac etiology of dyspnea in the ED

      Morris, Jason; The University of Arizona College of Medicine - Phoenix; Wu, Teresa (The University of Arizona., 2014-04)
      Objectives: There were two main objectives of this study. The first was to determine the diagnostic threshold of hemodynamic values derived from impedance cardiography (ICG) and whether these thresholds are sex specific in determining the etiology of shortness of breath (dyspnea) in patients presenting to the emergency department (ED). The second was to compare ICG hemodynamic values with the results of bedside cardiothoracic ultrasonography and B-type natriuretic peptide (BNP) levels in patients with dyspnea in the ED. Methods: A prospective cohort of 50 adult patients presenting to the Maricopa Medical Center ED with dyspnea were evaluated using ICG, bedside cardiothoracic ultrasound, and BNP to determine the etiology of their complaint. The final etiology was determined through review of the treating practitioner’s final diagnosis and evaluation of the data available from the patient’s ED visit. Cardiac and non-cardiac groups were then compared to determine the accuracy, sensitivity, and specificity of ICG, bedside cardiothoracic ultrasound and BNP in identifying the etiology of their complaint. Results: BNP at a threshold of 164 pg/mL proved to be the most accurate with a sensitivity of 84.21%, a specificity of 79.17% and an area under the curve (AUC) of 0.8684 when plotted on a receiver operating characteristics (ROC) curve. Right ventricle diameter during systole was the most accurate bedside ultrasound parameter; at a threshold of 1.71 cm it showed a sensitivity of 77.78%, a specificity of 60.00% and an AUC of 0.7489. Heather index (HI) was the most accurate ICG parameter; at a threshold of 9.2 Ohm/sec2 it showed a sensitivity of 72.41%, a specificity of 85.00%, and an AUC of 0.8405. Only HI showed a significant difference between male and female patients. HI in females at a threshold of 10.4 Ohm/sec2 was 87.50% sensitive and 87.50% specific with an AUC of 0.9297. In males a HI threshold of 6.9 Ohm/sec2 was 69.23% sensitive and 66.67% specific with an AUC of 0.7564. Conclusion: Bedside cardiac ultrasound was technically challenging and the least accurate modality. ICG demonstrated some sex specific thresholds and while an easy to use modality, it was slightly less accurate than BNP which proved to be a simple and accurate modality for determining a cardiac or non-cardiac etiology of dyspnea.
    • Assessment of the baseline thoroughness of cleaning at one hospital dialysis suite

      Molyneux, Melissa; The University of Arizona College of Medicine - Phoenix; Po, John (The University of Arizona., 2014-04)
      One fifth to one third of hemodialysis patients develop infections from bacterial and viral pathogens over the total course of their treatment, many of which are healthcare acquired, leading to significant morbidity and mortality. Over recent years, significant strides have been made to decrease the rate of healthcare-acquired infections (HAIs) by reducing the risk of transmission of pathogens, including increased compliance to hand-washing of healthcare workers (HCW) and improved quality of environmental cleaning. The goal of the project was to improve the thoroughness of cleaning of a hemodyalysis (HD) suite using objective monitoring and a program of education and feedback. To achieve this goal, the project was broken down into three aims: 1. Determine the baseline thoroughness of cleaning using a novel marker system; 2. Educate and provide feedback to hospital administration and environmental services staff involved in overseeing and in cleaning the HD suite, and; 3. Determine if the program improves the thoroughness of cleaning when compared to baseline. Due to institutional constraints, the third aim of the project was not performed. This investigation demonstrated a baseline thoroughness of cleaning for all high-touch surfaces to be 42% of surfaces cleaned, indicating there are opportunities for improvement in the sanitation practices of the hospital hemodialysis suite. Most individual surface types fell below the internal goal of 90% cleaned. Through presenting the baseline data to hospital administration and environmental services staff, areas of potential improvement in hemodialysis suite sanitation practices were identified, which included the assignment of the cleaning of individual surfaces to specific hospital departments. Though the follow-up testing could not be performed, it is likely that the identification of these areas for process improvement resulted in increased cleaning of overlooked surfaces.
    • Fast and Slow Recovery Following Acute Ischemic Stroke

      Minzer, Brandon; The University of Arizona College of Medicine - Phoenix; Marshall, Randolph (The University of Arizona., 2014-04)
      OBJECTIVE: To investigate the variability in early recovery after hemiparetic stroke. BACKGROUND: Prior work suggests that most hemiparetic patients recover approximately 70% of their initial impairment by 3-months, but the speed of the recovery is unknown. METHODS: We assessed 30 patients with first-ever hemiparetic stroke using the Fugl-Meyer upper extremity score (max score=66) at 24-72 hours (FMInit), 1-week (FM1wk), and 3-months (FM3mo). Patients who did not demonstrate proportional recovery (0.70 x initial impairment) were excluded from analysis. The distribution of recovery at 7-days among the proportional recoverers was characterized and contrasted with recovery at 90-days using the Shapiro-Wilk test for normality and Sarle’s binomial coefficient. Cluster analysis was then used to assess the distribution of recovery rates at 7-days. Tests of differences and association were performed to assess if the early recovery-rate groups differed significantly in clinical and demographic characteristics. RESULTS: Twenty-six of the 30 initial patients were identified as proportional recovers, the other 4 were non-recoverers at 90-days. Among the proportional recoverers, there was a bimodal distribution of recovery at 7-days. Cluster analysis identified patients who achieved virtually all of their total recovery at 7-days (n=13, percent recovery=0.89±0.19; 95%CI:0.79-1.00) and patients who achieved virtually none their total recovery at 7-days (n=13, percent recovery=-0.23±0.77, 95%CI:-0.65-0.19), but went on to achieve the expected recovery at 90 days. Initial stroke severity was the only characteristic that showed a statistically significant correlation with early recovery group membership. SIGNIFICANCE: Patients who demonstrate proportional recovery over the first 3-months fall into 2 distinct early recovery groups, either achieving approximately 90% of their total recovery by 1-week or making little or no recovery early, and only later achieving their total expected recovery. Implications for treatment planning are profound.
    • Control of Late Cornified Envelope Genes Relevant to Psoriasis Risk: Upregulation by 1,25‐Dihydroxyvitamin D3 and Plant‐derived Delphinidin

      Hoss, Elika; The University of Arizona College of Medicine - Phoenix; Whitfield, G. Kerr (The University of Arizona., 2014-04)
      Psoriasis is a chronic inflammatory skin disease featuring abnormal keratinocyte proliferation and differentiation. A genetic risk factor for psoriasis (PSORS4) is a deletion of LCE3B and LCE3C genes encoding structural proteins in differentiated keratinocytes. Because analogs of 1,25-dihydroxyvitamin D3 (1,25D) are used in psoriasis treatment, we hypothesized that 1,25D and other VDR ligands act via the vitamin D receptor (VDR) to upregulate expression of LCE 3A/3D/3E genes, potentially mitigating the absence of LCE3B/LCE3C gene products. This hypothesis was pursued using cultured keratinocytes, quantitative real time PCR (qPCR) to assess LCE gene expression, competition binding assays to assess direct ligand binding to VDR, and reporter gene assays to assess the ability of VDR ligands to activate transcription in a VDR- and VDR response element-dependent fashion. qPCR results in a human keratinocyte line, HaCaT, suggested that 1,25D and selected alternate or candidate VDR ligands might upregulate LCE transcripts. Further experiments in primary human keratinocytes confirmed that 1,25D and 10 µM delphinidin do indeed upregulate all five LCE3 genes (LCE3A–E), especially in calcium-differentiated cultures. Further, competition binding assays revealed that delphinidin does in fact bind VDR, but only weakly (IC50 approximately 1 mM). Finally, 20 µM delphinidin was shown to be capable of upregulating a luciferase reporter gene linked to a vitamin D responsive element found near the LCE3 gene cluster. Taken together, these results are consistent with delphinidin (or a metabolite) stimulating LCE3 transcription in a VDR/VDRE-dependent manner. We propose that upregulation of LCE genes may be part of the therapeutic effect of 1,25D to ameliorate psoriasis by providing sufficient LCE proteins, especially in individuals missing the LCE3B and 3C genes. Results with delphinidin further suggest that this compound or its metabolite(s) might offer an alternative to 1,25D in psoriasis therapy.
    • Interpregnancy Interval and Neonatal Outcomes

      Hefley, Erin; The University of Arizona College of Medicine - Phoenix; Coonrod, Dean (The University of Arizona., 2014-04)
      Objectives: Interpregnancy interval (IPI), the time period between the end of one pregnancy and the conception of the next, can have a significant impact on maternal and infant outcomes. This study examines the relationship between interpregnancy interval and neonatal outcomes of low birth weight, preterm birth, and specific neonatal morbidities. Study Design: Retrospective cohort study comparing neonatal outcomes across 6 categories of IPI using data on 202,600 cases identified from Arizona birth certificates and the Newborn Intensive Care Program data. Comparisons between groups were made using odds ratios and 95% confidence intervals, and multivariable logisitic regression analysis. Results: Interpregnancy intervals of < 12 months and ≥ 60 months were associated with low birth weight, preterm birth, and small for gestational age births. The shortest and longest IPI categories were also associated with specific neonatal morbidities, including periventricular leukomalacia, bronchopulmonary dysplasia, intraventricular hemorrhage, apnea bradycardia, respiratory distress syndrome, transient tachypnea of the newborn, and suspected sepsis. Relationships between interpregnancy interval and specific neonatal morbidities did not remain significant when adjusted for birth weight and gestational age. Conclusions: Significant differences in neonatal outcomes (preterm birth, low birth weight, and small for gestational age) were observed between IPI categories. Consistent with previous research, interpregnancy intervals < 12 months and ≥ 60 months appear to be associated with increased risk of poor neonatal outcomes. Any difference in specific neonatal morbidities between IPI groups appears to be mediated through increased risk of low birth weight and preterm birth by IPI.
    • Disclosure and Assent in Pediatric HIV

      Greene, Morgan; The University of Arizona College of Medicine - Phoenix; Piatt, Janice (The University of Arizona., 2014-04)
      The purpose of this study was to examine health care providers’ experiences regarding the processes of disclosure and assent in pediatric HIV/AIDS patients. The study population included providers who were involved with the care of pediatric HIV/AIDS. A survey was distributed through email and asked questions to explore provider demographics, the average age of assent to treatment and research, the average age of disclosure of HIV, what factors determine the age of disclosure, barriers to disclosure, provider opinions, and provider perceptions of conflict within the disclosure process. While results showed that there are wide variations among individual patients and providers, most providers agree that disclosure should occur in older school age children (between ages 6-10 years), which is also the time that they typically are able to assent to treatment and clinical trials. Providers often agreed that there is a conflict between the ages of disclosure and assent. Parental concerns (fear of stigma, inappropriate disclosure, and personal guilt) were most often the reason for delays in the disclosure process. The disclosure process was felt to be most effective when done in a step-wise manner that includes multiple practitioners and counseling with families.
    • Abnormal Face‐hand Testing is Associated with Anosognosia in Patients with Neuropathologically‐confirmed Alzheimer’s Disease

      Derksen, Brenna; The University of Arizona College of Medicine - Phoenix; Jacobson, Sandra (The University of Arizona., 2014-04)
      Objective To investigate whether specific elements of the neurological and neuropsychological evaluation are associated with anosognosia for memory impairment in subjects with neuropathologically-confirmed Alzheimer’s disease. Methods Included were subjects from the Arizona Study of Aging and Neurodegenerative Disease with clinically documented dementia and neuropathological confirmation of AD for whom anosognosia could be confirmed based on antemortem data. Anosognosia was defined by a discrepancy between 1) the patient’s self-report and results of testing, and/or 2) the patient’s self-report and the caregiver’s report regarding memory impairment. The anosognosic and non-anosognosic groups were compared on targeted clinical, cognitive, and neuropathological findings. Results Of 61 subjects included, 34 were diagnosed as anosognosic, and 27 non-anosognosic. The anosognosic group performed worse on two tests of frontal systems function - letter fluency (COWAT) (p=0.010) and a score derived from the Trailmaking test (Trailmaking B time – Trailmaking A time) (p=0.015). In addition, significantly more anosognosic subjects (92%) had abnormal results on face-hand testing (double simultaneous stimulation) compared to non-anosognosic subjects (62% abnormal; p=0.018). Significance In this study of patients with moderate Alzheimer’s disease (mean CDR=2), the anosognosic group showed significantly greater impairment on tests of frontal/executive function. In addition, this group had a significantly higher rate of abnormal face-hand testing, consistent with right parietal pathology. The FHT, which takes about 30 seconds to administer, may prove useful as a marker for anosognosia risk in AD.
    • A Standardized Template for Measuring and Reporting Telephone Cardiopulmonary Resuscitation

      Dameff, Christian; The University of Arizona College of Medicine - Phoenix; Bobrow, Bentley (The University of Arizona., 2014-04)
      Abstract Background: Bystander cardiopulmonary resuscitation (CPR) improves out-of-hospital cardiac arrest (OHCA) survival. Telephone CPR (TCPR) comprises CPR instruction given by emergency dispatchers to bystanders responding to OHCA and the CPR performed as a result. TCPR instructions improve bystander CPR rates, but the quality of the instructions varies widely. No standardized system exists to critically evaluate the TCPR intervention. Methods: Investigators developed a novel, standardized system to analyze audio recordings of suspected OHCA calls from a large regional 9-1-1 dispatch center. As the initial step of a TCPR quality improvement initiative, baseline data were obtained from October 2010 to November 2011. Dispatcher recognition of CPR need, delivery of TCPR instructions, and bystander CPR performance were documented. Results: A total of 590 calls were analyzed. CPR was indicated in 317 calls and already in progress in 94. Dispatchers recognized the need for TCPR in 176 of the 223 (79%) remaining calls. CPR instructions were started in 65/223 (29%) and bystander CPR resulting from TCPR instructions was started in 31/223 (14%). Median time intervals were: recognition of CPR need [69s (IQR: 44, 104.5)], initiation of CPR instructions [175s (IQR: 139, 207)], and first chest compression [251s (IQR: 189, 306)]. Conclusion: It is feasible to employ a simple data collection and reporting system for critical evaluation of the TCPR intervention. A standardized methodology for measuring TCPR is necessary to perform on-going quality improvement, to establish performance standards, and for future research on how to optimize bystander CPR rates and OHCA survival.
    • Key Attributes in Obtaining Better Outcomes and Reduced Costs in the Healthcare System

      Cowdell, Colt; The University of Arizona College of Medicine - Phoenix; Cortese, Denis (The University of Arizona., 2014-04)
      Objective/Hypothesis: The United States does not universally produce optimal levels of healthcare delivery, however, there are pockets throughout the country where organizations have utilized innovative strategies to produce high-value healthcare (better outcomes at lower costs). Our project aimed to identify factors that result in, or impede, the delivery of high-value healthcare. We hypothesized that there are common factors assisting or inhibiting organizations from producing high-value healthcare. Methods: We performed an analysis of innovative delivery models utilized at 10 different healthcare organizations throughout the country. The analysis included a literature search pertinent to each innovation we selected, a telephone interview with executives at the organization, integration of information we obtained into a pre-established template, a follow-up questionnaire, and finally an integration of new data from the questionnaire. Results: 10 different enablers were found to be common among the organizations. These included: shared vision, provider leadership, front-line empowerment, defined population, patient centeredness, co-creation with customer, information technology, culture of learning, presence of a willing payer, and a clear business case. The organizations ranked provider leadership and shared vision to be the two most important enablers. Three common barriers to success were found among the organizations and included government regulations, provider culture, and reimbursement. Provider culture was assessed as the most important barrier to overcome in the follow up questionnaire. Significance: The United States spends more overall and more per capita than any other country on healthcare, yet we are ranked 37th in the world for healthcare performance on average.1 Moreover, there is significant variability in mortality rates, access, safety, and patient satisfaction throughout the country.2 The information from this study provides a better understanding of how effective organizations are producing higher value healthcare and may act as a roadmap for organizations actively looking to produce better outcomes while lowering their costs.
    • Intravenous Immunoglobulin Use in the Treatment of Toxic Epidermal Necrolysis and Stevens-Johnson Syndrome: A 10-year Retrospective Analysis of Patients of a Single Burn Center

      Cooper, Ryan; The University of Arizona College of Medicine - Phoenix; Pressman, Melissa; Foster, Kevin (The University of Arizona., 2014-04)
      Stevens - Johnson syndrome and Toxic Epidermal Necrolysis Syndrome are rare, but serious conditions affecting skin and mucous membranes that are primarily treated with supportive care. Other more specific therapies have limited evidence to support the benefit of their use; one such treatment is intravenous immunoglobulin (IVIG). The use of IVIG in the treatment of these syndromes remain controversial due to mixed results demonstrated in the literature, and at present is not considered a component of the standard of care. This study seeks to provide additional data regarding the efficacy of IVIG treatment on mortality in a small cohort of patients presenting with these syndromes at a regional burn center over a 10-year period; data was retrospectively collected from patient medical records. On analysis of this data, IVIG use showed a potential, but not significant. improvement on mortality in comparison to the non-treatment group. Compared with the non-treatment group, odds ratios for death were 0.81 (95% CI 0.3-2.0) for IVIG. There is ultimately no new evidence that the benefit of IVIG in the treatment of Stevens - Johnson syndrome and Toxic Epidermal Necrolysis Syndrome is anything more than potential. Further investigation should include a rigorous analysis and comparison of different dosing regimens.
    • The Effect of Two Surgeons on Operative Time, Anesthesia Time, and Blood Loss in Pediatric Patients with Neuromuscular Scoliosis Undergoing Posterior Spinal Fusion Surgery

      Cowan, Kirsten; The University of Arizona College of Medicine - Phoenix; Shrader, M. Wade (The University of Arizona., 2014-04)
      Objective The goal of this study was to investigate the effect of using a two attending surgeon approach on operative time, anesthesia time, and estimated blood loss in patients with neuromuscular scoliosis undergoing posterior spinal fusion surgery. Methods This was a retrospective chart review study of patients with neuromuscular scoliosis who underwent posterior spinal fusion surgery at Phoenix Children’s Hospital in 2011 and 2012. Results Results from 70 patients showed a significant reduction in operative and anesthesia times for patients with two attending surgeons as opposed to one. Mean operative time for the two surgeon group was 3 hours 30 minutes (SD = 49 minutes) and was significantly shorter than 4 hours 26 minutes (SD = 1 hour 22 minutes), the mean operative time for the one surgeon group, t (56) =3.44, p = .001. Mean anesthesia time for the two surgeon group was 5 hours 28 minutes (SD = 55 minutes) and was significantly shorter than 6 hours 9 minutes (SD = 1 hour 28 minutes), the mean anesthesia time for the one surgeon group, t (57) = -2.34, p = .023. There was no significant difference in estimated blood loss found between the groups. The mean blood loss for the two surgeon group was 1202.1 ml( SD = 1033.1) versus 1042.1 ml (SD = 959.41) for the one surgeon group, t(68) = .671, p = .50. This pattern of results remained the same in subgroup analysis designed to compare cases with similar severity of presentation. Significance Patients with neuromuscular scoliosis may benefit from a two attending surgeon approach to posterior spinal fusion. More studies are needed to determine modifiable risk factors for excessive blood loss in neuromuscular scoliosis patients as well as to investigate the effect of using a two surgeon approach on specific post-operative complications.
    • SIRT3: Molecular Signaling in Insulin Resistance

      Barber, Collin; The University of Arizona College of Medicine - Phoenix; Mandarino, Lawrence (The University of Arizona., 2014-04)
      Post-translational modification of intracellular proteins through acetylation is recognized as an important regulatory mechanism of cellular energy homeostasis. Specific proteins called sirtuins deacetylate other mitochondrial proteins involved in glucose and lipid metabolism, activating them in metabolic processes. SIRT3 is a sirtuin of particular interest as it is found exclusively in mitochondria and has been shown to affect a variety of cellular metabolic processes. The activity of this enzyme is related to cellular insulin sensitivity. This study attempted to identify the relationship between insulin sensitivity and change in amount of SIRT3 following a bout of exercise in non-diabetic individuals. We find a moderate inverse correlation between insulin sensitivity and increase in SIRT3 abundance following exercise. This suggests that this protein may not be involved directly in cells’ ability to regulate energy homeostasis or that it may act through another mechanism not investigated in this study.