• Biological evaluation of potential retinoid X receptor-selective agonists: the search for a more effective treatment for Alzheimer’s disease

      Khan, Zainab; The University of Arizona College of Medicine - Phoenix; Jurutka, Peter (The University of Arizona., 2021)
      Alzheimer’s disease (AD) is the most common form of dementia affecting millions of people; however, treatment options are currently limited. Previous studies have shown potential to slow the progression of AD by 4-[1-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)- ethenyl]benzoic acid (bexarotene), an antineoplastic agent modeled after a vitamin A derivative, in animal models. Bexarotene binds to the retinoid X receptors (RXRs) and stimulates RXR homodimerization and activation of RXR target genes. It also impacts RXR heterodimerization with other nuclear receptors, including the liver-X-receptor (LXR) and retinoic acid receptor (RAR). Bexarotene’s reversal of beta amyloid (Aβ) plaques in mouse models likely occurs via RXR-LXR activation and induction of apolipoprotein E (ApoE) expression. However, bexarotene has many adverse effects, including hyperlipidemia, skin toxicity, hypothyroidism, etc. The current study developed and tested novel bexarotene analogues for their ability to upregulate ApoE expression, crucial in AD neuroprotection, without producing the significant adverse effects of hyperlipidemia and skin toxicity through upregulation of sterol regulatory element-binding protein (SREBP) and activation of RAR, respectively. In order to test bexarotene analogues, luciferase assays were performed in both human colon cancer and human embryonic kidney cell lines. Two screening assays were completed to assess their ability (1) to induce RXR homodimerization through mammalian two-hybrid assays (M2H) and (2) to induce RXR responsive element DNA sequence (RXRE) based transcription. We then assessed the ability of the analogues (1) to induce ApoE expression through LXRE-based luciferase assays, while evaluating their potential for adverse effects through (2) SREBP- and (3) RARE-based reporter systems. Results from the M2H and RXRE assays revealed that our novel analogues produce a wide range of transcriptional activity. LXRE, SREBP, and RARE assays revealed similar results. Specifically, analogue A44 had significantly higher activity with LXRE (p < 0.05) and significantly lower activation via SREBP (p < 0.05) and RARE (p < 0.05) as compared to bexarotene. These assays revealed that our novel bexarotene analogues can potentially be more effective and potent RXR ligands than bexarotene with the capability to circumvent RAR cross-over and elevated SREBP expression, and thus the adverse effects of bexarotene. These analogues may have the potential to slow the progression of AD through increased ApoE expression without the current limitations associated with bexarotene use.
    • The End-to-Side Anastomosis: A Comparative Analysis of Arterial Models in the Rat

      Kaur, Pareena; The University of Arizona College of Medicine - Phoenix; Preul, Mark (The University of Arizona., 2021)
      Background: The end-to-side anastomosis is one of the most common anastomosis configurations used in cerebrovascular surgery. Whereas several living practice models have been proposed for this technique, few involve purely arterial vessels. Objective: The purpose of this study is to compare two arterial models using common carotid (CCA) and common iliac arteries (CIA) in rats. Methods: CIAs and CCAs were exposed in 10 anesthetized rats with their lengths and diameters measured. Also, the mobilization extent of each vessel along its contralateral counterpart was measured after each artery was transected at its proximal exposure point. We also studied the technical advantages and disadvantages of each model for practicing end-to-side anastomosis. Results: The average diameters of the CCA and CIA were 1.1mm and 1.3mm, respectively. The average extents of mobilization along the contralateral vessel were 13.9mm and 10.3mm for CCA and CIA, respectively. The CCA model had the advantages of more arterial redundancy (allowing completing both suture lines extraluminally) and minimal risk of venous injury. The main disadvantage of the CCA model was risk of cerebral ischemia. The CIA model was not limited by ischemia time and provided the technical challenge of microsurgical dissection of the common iliac vein from the CIA, while suffering from limited CIA redundancy. Conclusion: Both CCA and CIA models could be efficiency used for practicing the end-to-side anastomosis technique. Each provides the trainee with a specific set of advantages and disadvantages that could help with optimal selection of the practice model based on trainee’s skill level.
    • Anaplastic Thyroid Cancer: The Trajectory of Prolonged Diagnosis and Short Survival

      Xiong, Maggie; The University of Arizona College of Medicine - Phoenix; Milas, Mira (The University of Arizona., 2021)
      Purpose: Anaplastic thyroid cancer (ATC) is almost uniformly lethal in its progression, but due to its rarity and complexity, its presentation is difficult to recognize and manage by physicians and patients alike. Delayed diagnosis is common and makes ATC virtually untreatable. We aim to examine the number of appointments with healthcare providers, imaging studies performed, and admission days as metrics of delayed diagnosis in order to identify opportunities to expedite care of ATC patients in the future. Methods: A retrospective electronic medical record review was conducted to include 8 patients from January 2016 to December 2018. Both pre- and post-diagnosis variables were examined and include: number of unique encounters, type/number of imaging studies, demographics (sex, ethnicity, residence, employment, religion, language, marital status), days admitted inpatient, time to diagnosis, and specific medical specialties utilized. Pre- and post-diagnosis imaging studies included computer tomography (CT), magnetic resonance imaging (MRI), ultrasound (US), radiographs (X-ray), and positron emission tomography (PET). IRB approval was obtained through the UA BEACON© registry. Results: We analyzed 4 women and 4 men with ATC whose mean time to diagnosis (TTD) from initial chief complaint was 53 days. In that time, 12 clinicians per patient (median) provided care. Men had a far longer mean TTD compared to women (75 vs 31 days), as well as longer mean inpatient admission for evaluation (19 vs 11 days). After ATC diagnosis, the median number of encounters per patient rose to 24.5, reflecting multispecialty care required for treatment. Here also, men had more median post-diagnosis specialist encounters than women (41.5 vs 11). Female patients had a median number of 4 imaging studies pre-diagnosis and 2 imaging studies post-diagnosis while male patients had a median number of 6 imaging studies pre-diagnosis and 12.5 imaging studies post-diagnosis. Discussion: This study suggests that male patients with ATC have a more difficult trajectory both pre- and post-diagnosis compared to female patients. They require longer time and more imaging studies before physicians arrive at the ATC diagnosis. Subsequently, men stay longer in the hospital, still with significantly higher numbers of studies and physician encounters. The root causes of this gender discrepancy are unclear and likely multifactorial, but could represent greater ATC disease severity and gender-specific barriers to care. This study highlights the need to recognize early signs of ATC and consider this diagnosis sooner.
    • Chief Complaints: Can They Predict COVID-19 Positive Patients?

      White, Krichelle; The University of Arizona College of Medicine - Phoenix; Heise, William (The University of Arizona., 2021)
      Background: The COVID-19 pandemic has overwhelmed emergent and nonemergent medical facilities with patients often presenting with a vast array of clinical symptoms. We aim to evaluate the chief complaints of patients presenting to Urgent Care and Emergency facilities to better understand which chief complaints are more likely to be associated with these patients being confirmed COVID-19 positive. It is hypothesized that patients who have more commonly associated COVID-19 presenting symptoms will have a greater likelihood of positive test results. Methods: The study was a retrospective computational analysis that investigated the chief complaints of all confirmed and suspected COVID-19 cases presenting to Banner Health facilities within the state of Arizona from March through October 2020. The chief complaint and demographic data were extracted from Cerner’s underlying database. For each of these visits, the full list of chief complaints and patient demographics were extracted from the electronic health record. To more meaningfully characterize the chief complaint list, semantically and clinically similar chief complaints were aggregated. An example of aggregated complaints includes “SOB” and “Dyspnea”. Results: During the study period there were 70,884 unique encounters of COVID-19 suspected patients with 59,225 unique patients identified and 17,408 (29%) being confirmed COVID-19 positive. The twenty unique chief complaints were then correlated by patient encounter. Among the entire study population, “fever” was the most common chief complaint followed by “cough”. “Cough” (48%) and “fever” (41%) were the most common chief complaint for COVID-19 positive patients. Patients who presented with “loss of taste” or “loss of smell” were most likely to test positive with an OR of 5.53, 95% CI 5.12-5.97 and 7.64, 95% CI 6.96-8.39 respectively. Conclusion: Our research highlights an important aspect of the initial evaluation of COVID-19 patients within the clinical setting. Our study identified chief complaints that commonly are associated with the diagnosis of COVID-19 along with those that are less likely to be associated. This effort provides healthcare providers with data to that can better predict and identify patients that have an increased likelihood of being infected with COVID-19 based on their initial chief complaint.
    • Effectiveness of Oral Xa Inhibitors vs. Warfarin in the Prevention of Recurrent Deep Vein Thrombosis, Pulmonary Embolism, and Incidence of Post-Thrombotic Syndrome Following Intervention for First-Time Proximal AcuteIliofemoral, Femoropopliteal, or Popliteal Thrombosis: A Retrospective Chart Review

      Miro, Paulo; The University of Arizona College of Medicine - Phoenix; Thorpe, Patricia (The University of Arizona., 2021)
      BACKGROUND: Anticoagulation is the treatment of deep vein thrombosis (DVT) and prevents thrombus extension and recurrence of DVT. There is limited data on the effectiveness of Oral Xa inhibitors versus Warfarin in the prevention of recurrent DVT, pulmonary embolism (PE), and post-thrombotic syndrome (PTS), specifically in patients who receive intervention for a first-time acute proximal DVT. OBJECTIVES: Add to the literature regarding the effectiveness of Xa inhibitors and Warfarin in the prevention of recurrent DVT, PE, and PTS following a first-time proximal DVT. PATIENTS/METHODS: Retrospective chart review of 35 patients following a first time proximal acute thrombosis and begun on Xa inhibitor or Warfarin as anti-coagulation therapy. Data from 2010 through 2019, with an age range of 18-95, including all genders and ethnicities. Any patients with symptomatic peripheral arterial disease, chronic inflammatory disease, active cancer, history of DVT, inferior vena cava involvement, or with active pregnancy were excluded from the study. A Wilcoxon Rank sum was used to compare continuous variables, and a Chi Squared/Fischer’s Exact method was used to compare categorical variables. RESULTS AND CONCLUSIONS: 18.7% of patients undergoing Warfarin treatment suffered a DVT recurrence by 12 months, while 84.2% of patients undergoing Oral Xa treatment suffered a DVT recurrence by 12 months, a significant difference (p < 0.001). No other outcomes showed a significant difference. This study is limited by a small number of subjects, and lack of standardization across several of the outcome variables. Further research needs to be conducted to clarify the objective of this study.
    • Evaluation of New Targeted Therapies in 3D Culture Models for Pancreatic Cancer

      Avedikian, Saro; The University of Arizona College of Medicine - Phoenix; Han, Haiyong (The University of Arizona., 2021)
      Pancreatic Ductal Adenocarcinoma (PDAC) is a deadly cancer that displays a highly heterogeneous and complex tumor microenvironment. Novel therapeutic agents that target DNA regulatory networks known as super-enhancers (SEs) have recently gained attention in the potential treatment of PDAC. In order to accurately study the effects of super-enhancer inhibitors, cell culture models that accurately mimic the tumor microenvironment are necessary. In this experiment, two PDAC cell lines (B011 and B028) are grown under both 3D and 2D culture conditions and the growth inhibitory effects of three super-enhancer inhibitors (triptolide, THZ1, and THZ2) are determined. The 3D PDAC cell cultures of the B011 cell line demonstrate greater resistance to all three drugs tested from the class of super-enhancer inhibitors. Based on these findings, 3D PDAC culture models may provide more accurate means to study novel chemotherapy agents than traditional 2D culture methods. The implications of this are significant as it may pave the way for quick and affordable precision medicine modalities in the future for the treatment of PDAC.
    • Referral Patterns to Pediatric Pulmonology for Asthma-like Symptoms

      Prynn, Tory; The University of Arizona College of Medicine - Phoenix; Drewek, Rupali (The University of Arizona., 2021)
      Objective: This study aimed to characterize referrals for asthma-like symptoms to a pediatric pulmonology clinic, evaluate consult interventions, and identify opportunities for improving access. Methods: A retrospective chart review examined patients ages 5-18 years, referred to the pulmonology clinic at Phoenix Children’s Hospital between July 2016 and July 2019. Descriptive statistics summarized demographics, prior asthma diagnosis, ICS use and compliance, reason for referral and intervention during consult. An appropriate referral was defined as prior asthma and ICS Step 3. Results: The total 171 study subjects had mean (standard deviation) age of 9.4 (3.8) years, with 100 (58%) males, and prior asthma diagnosis in 105 (61%). The most common reason for pulmonology referral was asthma in 90 (53%) patients, of which 70 (78% of 90) had prior asthma. Among 105 patients with asthma, 79 (76%) had a history of ICS, with 33 (42% of 79) patients reporting spacer compliance issues. The rate of appropriate referrals was 0.11 (95% confidence interval: 0.06-0.16). During the pulmonology consult, nearly half 10 (53%) of 19 patients appropriately referred received an ICS step up. Among 151 inappropriate referrals, ICS was initiated for 91 (60%) and increased for 45 (30%). Education was provided to all patients during pulmonology consult. Conclusions: Mild-to-moderate asthma can be effectively treated by primary care providers (PCPs) with implementation of ICS, thus prioritizing healthcare resource utilization by enabling the pulmonologist to see higher acuity patients sooner. Further study is warranted to identify strategies and tools for PCPs to optimize asthma management.
    • REVAMP: A prospective study on the impact of virtual medicine on CPAP compliance and satisfaction of care

      Lee, David; The University of Arizona College of Medicine - Phoenix; Pineda, Lilibeth (The University of Arizona., 2021)
      Although continuous positive airway pressure (CPAP) is the gold standard treatment for the chronic sleep disorder, obstructive sleep apnea (OSA), compliance with the CPAP machine among patients continues to be a challenge. REVAMP (Remote Veterans Apnea Management Platform) is a personalized, interactive web platform and mobile app that enables veterans to be evaluated for their OSA and better optimize their management of OSA. REVAMP aims to improve transparency and access to healthcare, reduce patient burdens of traveling and wait times, and establishes better communication with patients and their healthcare team. The purpose of this project was to assess whether the utilization of REVAMP improves the compliance of CPAP for rural Arizona veterans diagnosed with OSA compared to veterans who do not use any additional aide or intervention for their CPAP machine. From 2016 to 2020 for patients from the Phoenix VA Health Care System, 50 patients were randomly selected for a control population and 51 patients were randomly selected from the population enrolled in REVAMP with CPAP compliance as the primary outcome measured. CPAP compliance is defined as 30 nights of CPAP usage for >=4 hours per night at least 70% of nights used. CPAP compliance data came from each patient’s CPAP machine that has its data collected via a wireless modem and stored onto the REVAMP or Resmed Airview platforms that are accessed by a secure VA account. The REVAMP population presented an overall 60.8% compliance rate compared to the 24.0% overall CPAP compliance rate for the control population. The REVAMP mean CPAP usage (%) was found to be 75.2 +/- 33.0 compared to the control population with mean CPAP usage (%) 45.1 +/- 40.4 (p < 0.0001) and a mean CPAP usage >=4 hours per night (%) as 62.5 +/- 37.1 compared to the control population of mean CPAP usage >=4 hours per night (%) as 32.6 +/- 37.4 (p < 0.0001). Based on these findings, there is strong evidence to suggest that interventions like REVAMP that increase education, transparency, and communication with a patient’s healthcare team increase compliance rates for treatments like CPAP. It is also possible that patients who enroll in REVAMP are a self-selecting population who are more motivated to seek out interventions to improve their condition, and further studies should investigate such manners.
    • Impact of Prenatal Visit Utilization on Pregnancy Outcomes within Differing Risk Populations

      Young, Rebecca; The University of Arizona College of Medicine - Phoenix; Erickson, Laurie (The University of Arizona., 2021)
      Objectives: To investigate the association between number and timing of prenatal visits (PNV) and pregnancy outcomes within differing maternal risk populations [non-high-risk (“non-HR”) and high-risk (“HR”)]. Methods: Retrospective study of mothers who delivered at Banner University Medical Center Phoenix during the 2017 calendar year. Inclusion criteria included maternal documentation at time of delivery of either: complete absence of PNV or complete PNV records. Maternal groups were either classified as “non-HR” or “HR” if received any of the following diagnoses: advanced maternal age (AMA), obesity, diabetic (DM) disorders, hypertensive (HTN) disorders, or asthma. Data collection included total PNV quantity per pregnancy and trimester. Pregnancy outcomes included labor interventions, labor complications, delivery complications, and adverse neonatal outcomes. Result: Of 503 mothers in the cohort, 324 met inclusion criteria and were evenly split between non-HR (159, 49.07%) and HR mothers (165, 50.93%). Pregnancy outcomes were then compared within same risk group depending on total pregnancy PNV utilization category [low (≤8 PNV), mid (9-11 PNV), and (≥12 PNV] and frequency of PNV per trimester (“T1,” “T2,” or “T3”). Non-HR mothers with a higher total PNV category were more likely to have labor interventions (odds ratio [OR] 4.02; 95% confidence interval [CI] 1.26-12.9, p = 0.019). Non-HR mothers with higher quantities of PNV in T3 were less likely to have labor interventions (OR 0.69; 95% CI 0.48-0.98, p = 0.039). HR mothers with higher PNV quantities in T1 and T2 were less likely to have labor interventions (T1: OR 0.34; 95% CI 0.13-0.91, p = 0.032) (T2: OR 0.42; 95% CI 0.21- 0.84, p = 0.015). HR mothers with higher quantities of PNV in T2 were less likely to have labor complications (OR 0.70; 95% CI 0.51-0.98, p = 0.043). Conclusions for Practice: Labor interventions were less likely found by non-HR mothers with higher quantities of PNV in T3 and by HR mothers with higher quantities of PNV in T1 and T2. Labor interventions were more likely found by non-HR mothers with a higher total PNV category. Labor complications were less likely found by HR mothers with higher quantities of PNV in T2. Limitations include small sample size and study would therefore benefit from further investigation. Anticipated clinical benefits could include contributing to the development of tailored PNV recommendations dependent on maternal health history ultimately resulting in increased cost savings, decreased unnecessary interventions, and decreased poor outcomes.
    • A Case Study: The Effect of Hormone Therapy on Vascular Function in a Male-to-Female Transgender Endurance Athlete

      Statham, Sally; The University of Arizona College of Medicine - Phoenix; Angadi, Siddhartha (The University of Arizona., 2021)
      The aim of this case study was to assess vascular function in a 27-year-old male-to-female transgender endurance athlete before hormone therapy and during treatment with gender affirming hormone therapy (GAHT) in an effort to better understand the effects of estrogen therapy and testosterone blockade on male vascular physiology. Testing occurred at 4-8 week intervals for 19 months. At each visit, testing included measurement of blood hormone levels including free testosterone, total testosterone and estradiol, resting heart rate and blood pressure, non-invasive central blood pressure measurements, pulse wave velocity (PWV), ultrasound quantified arterial flow mediated dilation (FMD), and dual-energy x-ray absorptiometry (DEXA) scans. These data were analyzed over time to observe gross trends and then analyzed for correlation. Visceral body fat measured remained unchanged from baseline after 15 months gender affirming hormone therapy. Systolic and diastolic blood pressures increased throughout treatment and systolic pressures were positively correlated with time. PWV showed signs of decreasing arterial stiffness after initiation of GAHT, but returned to baseline by the end of the study. FMD trended downwards initially with GAHT, indicating reduced vascular reactivity, but returned towards baseline following sustained treatment with GAHT. More research is needed to examine the long-term effects of gender affirming hormone therapy on vascular function, blood pressure, and vascular stiffness.
    • “Hey Doc, I think I have a Problem.” A Survey Investigating Self-Reported Physician Preparedness and Comfort Levels with Management and Counseling of Patients with a Substance Use Disorder

      Khan, Mohammad; The University of Arizona College of Medicine - Phoenix; Heise, Will (The University of Arizona., 2021)
      Objectives: Given that substance use disorders are an increasing problem in the state of Arizona, physician preparedness to have these difficult conversations regarding substance use disorder disclosure is important. We investigated physician attitudes regarding preparedness to understand how physicians in the Greater Phoenix Area feel regarding this difficult conversation. Methods: We used Qualtrics software to design a survey that was administered to physicians via the local hospital listserve. This survey used a series of questions investigating physician preparedness on a scale of 1-10, with 10 being the most prepared. We also used a paper version of the survey at the 2018 Arizona Association of Family Practitioners winter conference to collect data. Our total response rate 135 surveys, with 112 online and 23 on paper. Of these, 103 were complete and analyzed. Results: Physician preparedness scores from 1-10 were averaged and compared. The overall preparedness score reported by physicians with the standard deviation for alcohol use disorder was 7.21 (1.98), for opioid use disorder was 6.75 (2.13), and for methamphetamine use disorder, the value was 5.47 (2.82). Buprenorphine prescribing privileges were associated with statistically significant increased scores in physician preparedness in all three cases (p-values of 0.01 or less). Physician ability to impact long term outcomes for a patient with drug use disorder was closely associated with how well-equipped the physician’s practice was with a correlation of 0.7 and a p value of <0.0001. Conclusions: Physicians self-reported the most preparedness to address alcohol use disorder, followed by opioid use disorder, and then methamphetamine use disorder. The buprenorphine prescribing privileges are very well associated with increased physician ability to interact with and improve patient outcomes.
    • How does HIV knowledge, attitudes and behaviors of young adults in Arizona compare to those of China and Taiwan?

      Cox, Analissa; The University of Arizona College of Medicine - Phoenix; Cevallos, Manuel (The University of Arizona., 2021)
      INTRODUCTION: The Centers for Disease Control (CDC) 2018 HIV Surveillance Report indicates that 13.6 per 100,000 people were diagnosed with HIV in the United States2. In Arizona specifically, this value was 12.7 per 100,000 in 20182. According to the Arizona Department of Health, groups most susceptible to contracting HIV in Arizona are African Americans, men, men having sex with men (MSM), and those ages 20-293. These data can be compared to countries, like China and Taiwan, that studied their college students using the International AIDS Questionnaire – English (IAQ-E). METHODS: The IAQ-E is a knowledge, attitudes, and behaviors (KAB) assessment that tells us the respondents’ level of understanding given different facts, myths, risks, and attitudes. We sought to assess the KAB of young Arizonans by presenting them with the IAQ-E and assessing respondents’ level of agreement using a Likert scale (strongly disagree =1 to strongly agree = 5). HYPOTHESIS: Based on Arizona’s sexual education curriculum and overall cultural stigma, we hypothesized that the results would show relatively moderate knowledge and negative attitudes and understanding of behaviors related to HIV/AIDS. RESULTS: The IAQ-E and demographic survey was distributed to college students in Arizona using Qualtrics, totaling 591 participants. The average age range was between 21-22, 77.2% biologically female, 19.9% biologically male and almost 3% non-binary/other or transgender, 2.2 % African American, and 22.84% identified with the LGBTQ community. Overall, students in Arizona have higher knowledge of HIV/AIDS compared to both China and Taiwan, and their attitudes were more positive than China, yet more negative than Taiwan. The behaviors showed positive understanding in all three groups, despite culture differences. Arizona participants exhibited increasing levels of understanding with increasing age (p <0.0001), increasing GPA (p <0.0001), and being married (p 0.002). CONCLUSION: The purpose of this project was to better understand the general knowledge, attitudes and behaviors regarding HIV/AIDS in young Arizonans and compare that to other countries. Understanding these differences can help design targeted public health interventions to decrease future transmission within the state and beyond.
    • Assessing Middle Cerebral Artery Blood Flow Velocities and Outcomes in Pediatric Severe Traumatic Brain Injury using Transcranial Doppler Ultrasound

      Maykowski, Philip; The University of Arizona College of Medicine - Phoenix; Adelson, P. David (The University of Arizona., 2021)
      Objective: To assess the impact cerebrovascular flow velocities of pediatric traumatic brain injury (TBI) patients using transcranial doppler (TCD) and to assess for acute and long-term clinical correlations. Methods: This is a retrospective study of pediatric patients who suffered a severe TBI defined as Glasgow Coma Scale < 8. A total of 47 patients were treated between January 2014 and August 2018 and all patients received TCD assessments for cerebral blood flow velocity for a total of 210 measurements. The primary outcome measure was the correlation between middle cerebral artery (MCA) mean flow velocities (MFVs) and clinical characteristics. MCA velocities were identified as high flow or low flow states using age-adjusted standardized velocities. Persistent low flow states were defined as >50% of TCD recordings per patient displaying the specified flow state without resolution to a flow state within 2 standard deviations of age-sex defined normal. Secondary outcomes included mortality and the global function using Pediatric Glasgow Outcome Scale-Extended (GOS-E Peds) at 3, 6 and 12 month and the association of the TCD findings to other physiologic variables at the time of scanning. Results: Of the 47 patients, the mean age was 8.24 years (+ 5.82) and there were 33 (70%) males and 24 (51%) Hispanic. At least 1 low flow velocity (>2 SDs below agenormalized mean) was identified in 20 (43%) patients and at least one high flow (>2 SDs above age-normalized mean) in 10 (21%) patients. There were no associations between demographics and single episodes of low or high flow velocity, however, patients aged >5 and <10 and non-Hispanic patients were more likely to have persistent low flow states. Persistent low flow states were significantly associated with mortality (p=0.014). Conclusions: TCD can be used to assess cerebrovascular function following pediatric TBI and may be used to for earlier identification of abnormal flow velocities.
    • Did the Millennium Development Goal Target 7c (to halve between 1990 and 2015 the proportion of the global population without sustainable access to safe drinking water) Reduce the Prevalence of Diarrheal Illness in the Dominican Republic

      Frazier, Weston; The University of Arizona College of Medicine - Phoenix; Beyda, David (The University of Arizona., 2021)
      Background: Waterborne diseases are caused by a variety of microorganisms, biotoxins, and toxic contaminants, which lead to devastating illnesses. According to the World Health Organization, diarrheal illnesses are the ninth leading cause of death worldwide. Developing countries are at especially high risk due to the lack of quality infrastructure and the Dominican Republic is no exception. Access to a quality public water supply has been shown to significantly reduce the incidence of diarrheal illnesses worldwide and in 2012, the Dominican government celebrated as achieved the completion of the Millennium Development Goal Target 7c (to halve between 1990 and 2015 the proportion of the global population without sustainable access to safe drinking water). Our aim was to determine whether the initiative was successful at reducing the prevalence of diarrheal illnesses across the country. Methods: This is a cross-sectional study that obtained data using the Demographic and Health Surveys Database. Census data from the Dominican Republic was obtained from 2002, 2007 and 2013 Since the Millennium Development Goal Target 7c was celebrated as complete in 2012, data from 2002 and 2007 censuses were used to compare the change in prevalence of diarrheal illness in the 2013 census data. Odds ratio values and 95% confidence intervals were then calculated to evaluate various demographics and outcomes. Findings: Census data from the Dominican Republic including the years 2002, 2007, and 2013 actually revealed a steadily increasing prevalence when participants were asked if they had, “Diarrhea within the last 2 weeks (2002: 15.6%, 2007: 16.5%, and 2013: 17.7%; p=0.03).” This increase was observed throughout the course of the Millennium Development Goal Target 7c, which began in 1990 and was celebrated as accomplished in 2012. Before 2012, a total of 16.1% of participants reported that they had, “Diarrhea within the last 2 weeks”, while after 2012, 17.7% of participants reported that they had (p=<0.0001). This resulted in an odds ratio of 1.23 (p=<0.0001) with the current water supply. Other data that supports the poor state of the current water supply is the increased odds of having diarrhea when water is piped into the dwelling or brought in by a tanker, with odds ratios of 1.24 (p=<0.0001) and 1.11 (p= 0.043) when compared to a bottled water source respectively. Higher education decreased the odds of contracting diarrheal illness with an odds ratio of 0.77 (p=0.003). Secondary and higher education also decreased the risk of blood in the stool with odds ratios of 0.44 (p=0.01) and 0.45 (p=0.03) respectively. Interpretation: It appears the Millennium Development Goal Target 7c (to halve between 1990 and 2015 the proportion of the global population without sustainable access to safe drinking water), was ineffective at reducing the prevalence of diarrhea in the Dominican Republic. In fact, the prevalence has increased throughout the course of the initiative. The increase was especially notable in populations that used water piped into dwellings and tanker truck water sources. This is precisely the water supply that the initiative set out to improve. Using diarrhea as a single factor to determine the water quality in the Dominican Republic, it appears that the state of the country’s water is significantly worse than before.
    • Validation of PI-RADS v2 Scores at Various Non-University Radiology Practices

      Austin, Evan; The University of Arizona College of Medicine - Phoenix; Chang, John (The University of Arizona., 2021)
      Purpose: Validate the second version of the Prostate Imaging Reporting and Data System (PIRADSv2) scores in predicting positive in-bore MRI guided targeted prostate biopsy results across different non-university related institutions. Materials and Methods: This was a retrospective review of 147 patients who underwent multiparametric magnetic resonance imaging followed by in-bore MRI guided targeted prostate biopsy from 2014-2018. Lesions were rated according to PI-RADS v2 criteria. Scores were compared to MR-guided biopsy results and pre-biopsy PSA values. Results: Prostate Cancer (PCa) was detected in 54% (80/147) of patients, with more prostate cancer being detected with each increase in PI-RADS scores. Biopsy results with PI-RADS 3, 4, and 5 lesions resulted in PCa in 25.6% (10/39), 58.1% (33/55), and 86.0% (37/43) respectively. Clinically significant PCa (Gleason score ≥7) was detected in 17.9% (7/39), 52.7% (29/55), and 72% (31/43) of cases for PI-RADS 3, 4, and 5 lesions respectively. When PI-RADS scoring/biopsy results were compared across different institutions, there was no difference in the PI-RADS scoring or in positive biopsy rates.. The sensitivity, specificity, PPV, and NPV for PIRADS 3-4 were not statistically different across the institutions for detecting Gleason 7 or greater lesions. Conclusion: Our results agree with prior studies that higher PI-RADS scores are associated with clinically significant PCa and suggest lesions with PI-RADS 3-5 have sufficient evidence to warrant biopsy. Comparison of PI-RADS across different types of non-university practices revealed no difference in scoring/biopsy outcome, suggesting that PI-RADS v2 can be easily applied outside of the university medical center setting.
    • Shift in electrocorticography electrode locations after surgical implantation in children

      Munter, Bryce; The University of Arizona College of Medicine - Phoenix; Foldes, Stephen (The University of Arizona., 2021)
      Interpreting electrocorticography (ECoG) in the context of neuroimaging requires that multimodal information be integrated accurately. However, the implantation of ECoG electrodes can shift the brain impacting the spatial interpretation of electrode locations in the context of pre-implant imaging. We characterized the amount of shift in ECoG electrode locations immediately after implant in a pediatric population. Electrode-shift was quantified as the difference in the electrode locations immediately after surgery (via post-operation CT) compared to the brain surface before the operation (preimplant T1 MRI). A total of 1140 ECoG contracts were assessed across 18 patients ranging from 3 to 19 (12.1 ± 4.8) years of age who underwent intracranial monitoring in preparation for epilepsy resection surgery. Patients had an average of 63 channels assessed with an average of 5.64 ± 3.27 mm shift from the pre-implant brain surface within 24 h of implant. This shift significantly increased with estimated intracranial volume, but not age. Shift also varied significantly depending of the lobe the contact was over; where contacts on the temporal and frontal lobe had less shift than the parietal. Furthermore, contacts on strips had significantly less shift than those on grids. The shift in the brain surface due to ECoG implantation could lead to a misinterpretation of contact location particularly in patients with larger intracranial volume and for grid contacts over the parietal lobes.
    • Current Trends of Clostridioides difficile infections (CDI) in the United States: Results from the National Inpatient Sample Database

      Zamarripa, Alec; The University of Arizona College of Medicine - Phoenix; Kannadath, Bijun (The University of Arizona., 2021)
      Background Clostridioides difficile infection (CDI) is a cause of significant hospital morbidity and mortality in the United States. Objective Our aim was to analyze the current trends of CDI burden using the National Inpatient Sample (NIS) database, which tracks all hospital discharges in the United States. Methods Using the NIS, all adult discharges (age ≥ 18 years) between 2012 and 2017 were evaluated. Discharges with CDI were identified based on the appropriate ICD9 (00845) and ICD10 (A047, A0471, A0472) codes. All data was analyzed after applying recommended weights using Stata Statistical Software: Release 16. (College Station, TX) and pandas statistical package in Python. Main Measures The overall CDI trends, including incidence, mortality, age, and length of stay were analyzed. The incidence and mortality rates were also analyzed with respect to race, sex, comorbidity (diabetes, hypertension, hyperlipidemia), and hospital location, size, and ownership. Key Results Records representing 181,132,460 adult discharges in the United States over 6 years (2012 – 2017) were included in the analysis; of these, 2,088,825 (1.15%) discharges had CDI. Overall incidence increased until peaking in 2015 at 1.21%, before declining to 1.06% in 2017. Despite the fluctuation in incidence rate, the mortality rate exhibited a steady decrease from 7.32% in 2012 to 6.25% in 2017. Also, the average length of stay decreased from 10.6 days to 9.9 days, along with average age of CDI patients dropping from 67.9 years to 66.2 years. Incidence and mortality rates were consistently higher in males compared to females. Incidence was typically higher in White Americans; however, Asians/Pacific Islanders regularly demonstrated the highest mortality rates during the study period. Finally, incidence and mortality rates were highest in large-bedded, urban teaching hospitals. Conclusion Improvement in overall mortality rate (Δ -1.07%) outpaced improvement in the incidence rate (Δ -0.09%), which may be indicative of improved diagnosis and management of CDI. Specifically, the adoption of oral vancomycin and fidaxomicin as standard treatments may be a key reason for our findings. However, primary prevention efforts are still struggling to effectively control the spread of CDI, especially in large-bedded, urban teaching hospitals – this may be due in part to a higher acuity patient population. Despite limitations, these findings suggest a lessening of overall burden of CDI in the United States.
    • Increased Risk of Depression in Patients with Crohn’s Disease

      Smith, Savion; The University of Arizona College of Medicine - Phoenix; Alishahi, Yasmin (The University of Arizona., 2021)
      Introduction Individuals with IBD have been shown to be at an increased risk of developing depression and anxiety. Previous work has demonstrated patients with UC were more likely to report depressive symptoms preceding their diagnosis of IBD than the general population. Young patients with CD also have a greater risk for developing anxiety disorders. One study demonstrated mental conditions are often diagnosed within one year prior to UC diagnosis. This signifies that psychiatric disorders may either be a consequence of early symptoms of the undiagnosed gastrointestinal condition or may increase an individual’s susceptibility to develop IBD. Psychological disease may amplify symptom severity, particularly abdominal pain perception in adults with IBD. Previous work has demonstrated that psychological state may influence perception of abdominal pain and patients with depression were more likely to take IBD-related disability. Methods This was a retrospective chart review. We used a subset of Veterans charts from the national VA database. Patient charts were divided into two groups: CD with depression and CD without depression (control). From the CD with depression group, all patients with a diagnosis of Crohn’s disease with depression were used, however, patients with a diagnosis of CD who did not receive treatment at the VA were excluded. Patients were considered in remission if their most recent colonoscopy showed no active disease. Patients were considered to have active disease if their most recent colonoscopy demonstrated signs of inflammation. When reported, depression severity was recorded in charts as mild, moderate or severe. From this we created a depression severity score by converting them to numerical values (mild=1, moderate=2, severe=3). Severity score is recorded as an average of these values. Results A total of 159 patient charts were included in this study, 122 from the Depression group and 37 from the no depression group. The odds of active Crohn’s Disease increased with depression (odds ratio [OR], 2.88; 95% confidence interval [CI], 1.21-6.81; p>0.016). The odds of depression also increased with substance abuse (odds ratio [OR], 3.87; 95% confidence interval [CI], 1.28-11.7; p>0.016) and PTSD (odds ratio [OR], 6.39; 95% confidence interval [CI], 1.85-22.0; p>0.003). Mean depression severity score of remission patients was 2.00 and mean depression severity score for active Crohn’s patients was 2.06. Notably, patients the odds of having more severe depression were higher for tobacco users (users: odds ratio [OR], 2.14; mean [SD], 2.14 [0.38]; 95% confidence interval [CI], 0.35-6.14; p>0.59; non-users: mean [SD], 1.96 [0.77]) and patients with substance abuse (users: odds ratio [OR], 2.37; 95% confidence interval [CI], 0.69-8.20; mean [SD], 2.21 [0.58]; p>0.17; non-users: mean [SD], 1.88 [0.77]) . Discussion These findings provide additional evidence that depression is associated with increased Crohn’s disease activity in the Veteran population. Based on this data, one may consider that treating an individual’s depression may reduce the frequency and severity of Crohn’s disease activity. There may be benefits to holistically treating a patient’s IBD through also evaluating and monitoring his or her psychological health. Other studies have demonstrated the likelihood that psychiatric disorders often co-exist with inflammation, infections, and autoimmune diseases. Furthermore, our data demonstrated strong associations found between substance abuse and the likelihood of depression. Interestingly, our results indicated no association for the measured CRP and calprotectin between the Crohn’s Disease with depression and the Crohn’s disease without depression groups.
    • Chest Compression Release Velocity Factors During Out-of-Hospital Cardiac Resuscitation

      Beger, Samuel; The University of Arizona College of Medicine - Phoenix; Bobrow, Bentley (The University of Arizona., 2021)
      Background: Higher chest compression release velocity (CCRV) has been associated with better outcomes after out-of-hospital cardiac arrest (OHCA), and patient factors have been associated with variations in chest wall compliance and compressibility. We evaluated whether patient sex, age, weight, and time in resuscitation were associated with CCRV during pre-hospital resuscitation from OHCA. Methods: Observational study of prospectively collected OHCA quality improvement data in two suburban EMS agencies in Arizona between 10/1/2008 and 12/31/2016. Subject-level mean CCRV during the first 10 minutes of compressions was correlated with categorical variables by the Wilcoxon rank-sum test and with continuous variables by the Spearman’s rank correlation coefficient. Generalized estimating equation and linear mixed-effect models were used to study the trend of CCRV over time. Results: During the study period, 2,535 adult OHCA cases were treated. After exclusion criteria, 1,140 cases remained for analysis. Median duration of recorded compressions was 8.70 minutes during the first 10 minutes of CPR. An overall decline in CCRV was observed even after adjusting for compression depth. The subjectlevel mean CCRV was higher for minutes 0-5 than for minutes 5-10 (mean 347.9 mm/s vs. 339.0 mm/s, 95% CI of the difference -12.4 ~ -5.4, p < 0.0001). Males exhibited a greater mean CCRV compared to females [344.4 mm/s (IQR 307.3-384.6) vs. 331.5 mm/s (IQR 285.3-385.5), p=0.013]. Mean CCRV was negatively correlated with age and positively correlated with patient weight. Conclusion: CCRV declines significantly over the course of resuscitation. Patient characteristics including male sex, younger age, and increased weight were associated with a higher CCRV.
    • Resolution of Diabetes Mellitus with Laparoscopic Sleeve Gastrectomy

      Daas, Eshaan; The University of Arizona College of Medicine - Phoenix; Soto, Flavia (The University of Arizona., 2021)
      Background: Laparoscopic sleeve gastrectomy (LSG) is a proven intervention to induce weight loss. Its applications as a surgical procedure may extend beyond body weight control to the realm of metabolic therapy in chronic conditions such as diabetes mellitus (DM), which results from the dysregulation of blood glucose levels. Objective: The aim of this study is to evaluate the improvement and resolution of diabetes following sleeve gastrectomy at our facilities. Setting: Two affiliated non-profit surgery centers, United States Methods: Eighty-two adult diabetic patients were treated with sleeve gastrectomy. We conducted a single point analysis of our existing longitudinal data for that calendar year through a retrospective chart review. Statistical outcomes were determined for anthropometric data unique to patients with DM including prescribed medications, Hemoglobin A1C, excessive weight loss (EWL), and body mass index (BMI). Results: Time was a significant predictor of diabetic resolution after six months post-op in patients who originally presented with Type 1 DM and change in hemoglobin A1C values held a significant association to improvement of Type 1 diabetes. BMI and EWL displayed a positive correlation to resolution at all time points of interest. Conclusions: There are differences between the post-operative improvements in diabetic status following sleeve gastrectomy depending on the initial diagnosis of insulin-dependent or insulinindependent DM. Pathophysiological mechanism of a patient’s diabetic condition, specifically auto-immune destruction of pancreatic beta cells, may contribute to the variable metabolic response following sleeve gastrectomy.