• Modern Techniques of Adjunctive Pain Control Lower Opioid Use, Pain Scores, and Length-of-Stay in Patients Undergoing Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis

      Nabar, Sean J.; The University of Arizona College of Medicine - Phoenix; Shrader, M. Wade (The University of Arizona., 2013-04-17)
      Study Design. Retrospective analysis. Objective. To determine if the use of adjunctive pain medications (subcutaneous bupivacaine, dexmedetomidine infusion, and intravenous ketorolac) will reduce the need for opioids, reduce postoperative pain, and shorten length of hospital stay in patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion. Methods. Retrospective review of children 10 to 18 years with adolescent idiopathic scoliosis receiving posterior spinal fusion surgery over the past 10 years at Phoenix Children’s Hospital. Physicians managed the patients’ pain postoperatively with adjunctive medications in addition to intravenous and oral opioids. Variables of interest were local anesthetic bupivacaine delivered subcutaneously via elastomeric pain pump, sedative/analgesic dexmedetomidine infused for up to 24 hours postoperatively, and the NSAID ketorolac delivered intravenously. These three medications were used either alone or in some combination determined by the physician’s clinical judgment. Primary outcomes analyzed were normalized opioid requirement after surgery, VAS pain scores, and length of stay in the hospital. Results. One hundred and ninety-six children were analyzed with no significant differences in demographics. Univariate analysis showed that all three adjunct medications improved outcomes. A multivariate regression model of the outcomes with respect to the three medication variables of interest was developed to analyze the effects of the three medications simultaneously. The regression analysis showed that subcutaneous bupivacaine significantly reduced normalized opioid requirement by 0.98 mg/kg (P = 0.001) and reduced VAS pain scores by 0.67 points (P = 0.004). Dexmedetomidine significantly reduced the average VAS pain scores in the first 24 hours by 0.62 points (P = 0.005). Ketorolac had no effect in the multiple regression analysis. Conclusion. The use of subcutaneous bupivacaine provides good analgesia with low pain scores. A reduction in opioid requirement is beneficial and may be directly related to presence of the bupivacaine pump, although this may be limited by potential treatment bias. The three adjunct medications improve our outcomes favorably and should be studied prospectively.
    • Monoacylglycerol lipase exerts dual control over endocannabinoid and fatty acid pathways to support prostate cancer

      Ward, Anna; The University of Arizona College of Medicine - Phoenix; Nomura, Daniel (The University of Arizona., 2013-03)
      Cancer cells couple heightened lipogenesis with lipolysis to produce fatty acid networks that support malignancy. Monoacylglycerol lipase (MAGL) plays a principal role in this process by converting monoglycerides, including the endocannabinoid 2-arachidonoylglycerol (2-AG), to free fatty acids. Here, we show that MAGL is elevated in androgen-independent versus androgen-dependent human prostate cancer cell lines, and that pharmacological or RNA-interference disruption of this enzyme impairs prostate cancer aggressiveness. These effects were partially reversed by treatment with fatty acids or a cannabinoid receptor-1 (CB1) antagonist, and fully reversed by co-treatment with both agents. We further show that MAGL is part of a gene signature correlated with epithelial-to-mesenchymal transition and the stem-like properties of cancer cells, supporting a role for this enzyme in pro-tumorigenic metabolism that, for prostate cancer, involves the dual control of endocannabinoid and fatty acid pathways.
    • Myocardial Protection Strategy Utilizing Retrograde Cardioplegia

      Karbasi, Michael; The University of Arizona College of Medicine - Phoenix; Willis, Brigham (The University of Arizona., 2013-03)
      Introduction: Myocardial protection strategies are a central component of neonatal arterial switch operations. Traditionally antegrade cardioplegia through the aortic root has been the method of delivery, but use of retrograde cardioplegia via the coronary sinus has become the standard of practice by many in the field. Methods: After obtaining IRB approval and informed consent, a retrospective chart review was done to assess outcomes between 48 patients receiving antegrade (n= 5) and retrograde (n= 43) cardioplegia during neonatal switch operations. Preoperative demographics and postoperative outcomes were compared between the two groups. Results: Patients from the retrograde cardioplegia group demonstrated a trend towards shorter postoperative ventilation days (6.67 +/- 8.57 vs. 10.2 +/- 10.1) and hospital length of stay (18.3 +/- 15.3 vs. 24.8 +/- 11.8) which were not statistically significant. Patients receiving retrograde cardioplegia demonstrated a trend towards an increased incidence of postoperative arrhythmias which was not statistically significant. The retrograde group also demonstrated an increased cardiopulmonary bypass (CPB) time (95.6 +/- 36.59 vs. 146.74 +/- 44.26) and a trend towards an increased aortic cross clamp (ACC) time (74.4 +/- 24.42 vs. 101.30 +/- 29.56) which was not statistically significant. All patients survived to discharge in both groups. With results trending towards shorter hospital length of stays, postoperative ventilation days and zero mortality in patients receiving retrograde cardioplegia, it can be utilized as a safe and efficacious strategy for myocardial protection during neonatal switch operations.
    • Naloxone Utilization in a Tertiary Care Medical Center

      Shah, Ruby; The University of Arizona College of Medicine - Phoenix; Rosenfeld, David (The University of Arizona., 2013-03)
      The purpose of this research project was to review the use of naloxone for oversedation events from 2008-2011 at the Mayo Clinic Hospital in Phoenix, Arizona. Opiates are generally an accepted form of acute and chronic pain management. Opiate analgesic use has increased in past decades due to several factors including cultural and healthcare ideas on the importance of pain management, as well as the availability, cost, and marketing of the drugs. Concomitant with the increased use of opiates has been a rise in addiction, diversion, and abuse. In addition, opiate overdose is a potentially lethal consequence. Balancing the use of opiates for effective pain control and the possible risks of opiates is a constant effort for healthcare professionals. Monitoring the use of naloxone has arisen as an effective metric to examine the safety and outcomes of opiate utilization in a hospital setting. Reviewing every dose of naloxone delivered over the years 2008-2011 has allowed us to recognize trends that have led to improvements in patient safety. 154 cases of naloxone use for sedation events were reviewed in a retrospective case controlled unmatched chart review. We were able to determine that patient risk for oversedation is greatest within our surgical practices, especially general and orthopedic, and that the overall risk is greatest within the first 24 hours in all surgical patients. In addition, we were able to determine statistically significant increase in risk with elevated creatinine level, American Society of Anesthesiology (ASA) Class, and patient controlled analgesia (PCA) use compared to our unmatched control group. The significance of these findings is that it identifies certain risk groups and factors that carry increased risk for sedation events, and therefore can lead to improvements in quality and education across the institution.
    • Neurodevelopmental effects of synthetic glucocorticoid at different time point on stress and metabolism gene expression in the developing hypothalamus

      Chong, David; The University of Arizona College of Medicine - Phoenix; Handa, Robert (The University of Arizona., 2013-03)
      The clinical use of synthetic glucocorticoids (sGC) to improve acute respiratory status in newborns with bronchopulmonary dysplasia, have been shown to have the undesired effects of increasing the risk of developing metabolic and neuropsychiatric disease in adulthood. Current data indicate that critical periods of sensitivity exist in fetal development during which exposures, such as sGC use, are more likely to result in long-term disease. In this study, we hypothesize that exposure to the sGC dexamethasone (DEX) at different time points during early development will result in unique expression profiles of hypothalamic genes in the adult rats. Sprague Dawley rat pups were treated with 0.2 mg/kg DEX beginning on postnatal day (PND) 4-6. Brain tissue from offspring was harvested at PND 7, 21, 90 and quantitative real-time PCR (RT-qPCR) was performed to measure the mRNA level of hypothalamic genes involved in metabolic and behavioral regulation. Results were also compared to a previous study in which pregnant Sprague Dawley dams were treated prenatally with DEX (gestational day 18-21). Of the genes we measured, thyrotropin releasing hormone (Trh) expression was decreased in the adult animals when DEX was administered either prenatally or postnatally. Subsequent examination of brain sections by immunohistochemistry (IHC) showed decreases in fiber and neuron counts that were only seen in the offspring treated with DEX prenatally. Further evidence suggesting a critical window of exposure include observations that mRNA coding for somatostatin and oxytocin, and plasma levels of the protein IGF-1 decreased only in the animals treated with DEX postnatally. Collectively, these data demonstrate that permanent effects of sGCs on hypothalamic gene expression are dependent upon the timing of the exposure
    • Organization and role of international collaboration in research production

      Hsieh, David; The University of Arizona College of Medicine - Phoenix; Whitfield, G. Kerr (The University of Arizona., 2013-03)
      The prevalence of multi-national and cross-disciplinary collaborative in the production of knowledge defines modern science as a social enterprise that extends beyond political, social, and geographic boundaries. The purpose of this study was to assess global trends in the composition and impact of multinational research teams. By examining the bibliometric data of 3.7 million primary research articles published from 1975 to 2005, it was ascertained that the frequency and scale of international collaborations has increased globally. Of note, the publications of many countries associated with lower research output were more often consistently affiliated with other nations across the time frame studied. By analyzing the number of times a publication is cited, it was discovered that multinational research studies have a greater research impact than research without an international presence, although the number of affiliated nations does not strictly correlate with citations. Taken together, this study provides insight into the dynamics of research teams which may better inform us how scientific partnerships between countries may be fostered and which collaborations may be advantageous.
    • Pain Scales in the ED: Can They Predict Admission for Abdominal Pain?

      Johnson, Annelyssa; The University of Arizona College of Medicine - Phoenix; Sarko, John; Smith, Ed (The University of Arizona., 2013-03)
      OBJECTIVES and HYPOTHESIS: The purpose of this project was to assess whether pain scales have an association with the disposition of adult emergency department patients with abdominal pain. It is hypothesized that higher pain scores are associated with a greater likelihood of admission. METHODS: One hundred forty-nine patients (63 admitted and 86 discharged) 18 years and older who were evaluated for abdominal pain in the emergency department (ED) at Maricopa Medical Center were identified retrospectively through a case-control chart review. Demographic variables were compared to assess pain in different groups. Receiver operating characteristics curves (ROC) were created for initial, final, and change in pain scores. Logistic regression was performed to assess the interaction of the prespecified variables initial pain, presence of comorbidities, duration of pain, patient temperature, white blood cell count, and age. RESULTS: In an unadjusted analysis, patients with a higher initial pain score were admitted more often. There was no difference in final or change in pain score and disposition. Men had higher initial pain scores but women were more often admitted. No difference was found between races in pain scores. Patients with surgical diagnoses were admitted more often, and those with nonspecific or OB/GYN-related diagnoses were more often discharged. Patients were less likely to be admitted if imaging was not done. In an adjusted analysis, age was the only variable associated with an increased chance of admission, with an odds ratio of 1.048 (95% confidence interval 1.016-1.082) for each one-year increase. The initial pain score was not associated with admission in the adjusted analysis (odds ratio 1.095 (95% confidence interval 0.943-1.272)).
    • Patient Attitudes Regarding Medical Student Involvement in a Primary Care Setting

      Kaser, Scott; The University of Arizona College of Medicine - Phoenix; Carroll, Andrew (The University of Arizona., 2013-03)
      Previous studies on patient comfort with medical student involvement have consistently reported positive or neutral results within multiple specialties. The objective of this study was to examine patient attitudes toward medical students in a private family practice setting. This study also looked to examine whether recent medical student interaction alters patient attitude and if patient attitude can be improved with the prospect of providing feedback. It was hypothesized that there would be a positive pre-to-post test change in patient attitudes and that patients would respond positively to the prospect of providing feedback. Ninety-nine consecutive consenting adult patients completed a self-administered questionnaire before and after their office visit, which included a medical student interaction. Patient demographics (age, gender, race, prior student exposure, # years with doctor) as well as their attitudes toward the involvement of medical students were recorded. Data were collected for 10 months at Renaissance Medical Group, a private family practice with one physician provider. Data were compiled in Excel and analyzed with STATA12. Paired two-tailed T-tests and ANOVA were used to determine statistical significance. The results demonstrated that, prior to medical student interaction on 8 of 9 measures, patients have positive attitudes toward medical students. After medical student interaction, on 7 of 9 measures, respondents changed their response to a more positive position (P<=0.05). In addition, patients demonstrated a willingness to provide feedback to the medical student, but providing this feedback would not significantly alter their patient care experience. There were also statistically significant demographic differences on specific measures. This study provides evidence that patients respond positively to medical student interaction in the private Family Medicine setting. This study also demonstrates areas in which the patient care experience can be improved and provides the basis for further study on the patient - medical student interaction.
    • Postpartum Depression Tool in Burmese Women

      Belmonte, Chari; The University of Arizona College of Medicine - Phoenix; Veres, Sharry (The University of Arizona., 2013-04-12)
      Background: In the United States, the prevalence of postpartum depression is 10-15%. There is limited study on the appropriate postpartum screening tool for Burmese refugees in the United States. Hypothesis: The Burmese and Karenni versions of Edinburgh Postnatal Depression Scale (EPDS) are appropriate to use as a tool for screening postpartum depression in Burmese refugees. Aims: This study examines the views of Burmese refugees on the questions of Edinburgh Postnatal Depression Scale as a routine screening for postnatal depression and their opinion and experiences on postpartum depression. Methods: A qualitative approach was chosen to complete this study. A medical student and a Burmese interpreter participated in a one-on-one interview with 30 Burmese women sharing their views and opinions on translated EPDS and postpartum depression. Results: Thirty Burmese women were interviewed in the Phoenix area. The qualitative analysis indicate that the EPDS screening turned out to be a useful and culturally appropriate tool for the Burmese refugees to screen postpartum depression in this specific population. Conclusions: Without consistent and culturally appropriate screening for Burmese women, it would be hard to treat Burmese women for postpartum depression. Our study shows that acceptability for routine screening with a translated EPDS amongst health visitors is possible to achieve. Using the Edinburgh Postnatal Depression Scale in Burmese and Karenni language should be considered when seeing Burmese refugees in the clinic.
    • Prevalence of Imploding, Exploding and Ocular Headache Types in a Women’s Health Outpatient Practice

      Patel, Salma; The University of Arizona College of Medicine - Phoenix; Files, Julia (The University of Arizona., 2013-03)
      Objectives: (i) Determine the prevalence of imploding, exploding and/or ocular headaches in women with migraine in a primary care practice of women (ii) Investigate the concordance of physician diagnosis with patient self-diagnosis of pain directionality (iii) Assess correlation between the type of headache and severity of migraines, reproductive stage, and response to acute and prophylactic treatments Background: botulinum toxin A is a drug made from the toxin produced by Clostridium botulinum that works by weakening or paralyzing certain muscles or by blocking certain nerves.17 Recent migraine trials evaluating the efficacy of botulinum toxin A therapy noted differences in the efficacy of botulinum toxin A therapy based on directionality of pain ((imploding exploding and ocular). 5,6,7 However, the prevalence of these migraine types and their responses to conventional migraine prevention therapies has not yet been assessed. Methods: 201 patients participated in structured clinician-administered interviews and completed written questionnaires. Directionality of migraines were determined by both patients and physicians. Descriptive statistics, kappa coefficients and Kruskal-Wallis tests were used to assess migraine prevalence, physician-patient diagnosis concordance and association of migraine to severity, treatment and reproductive stage respectively. Results: 201 patients were enrolled with average age of 46. All patients reported directionality of their migraine and prevalence varied depending upon the method used to assign directionality and were: 33%-42% imploding headaches with or without ocular pain, 18%-44% exploding headaches with or without ocular pain, 7%-39% had ocular pain only, and 8%-13% had imploding and exploding headaches with or without ocular pain. The concordance between physician diagnosis of headache directionality with patient written response, between physician diagnosis and patient diagnosis via selection of representative picture, and between patient diagnosis via written question and via selection of representative pictures were week to moderate using Kappa coefficient. No correlation between the type of headache and severity of migraines, reproductive stage, and response to acute and prophylactic treatments was found (p>0.05). Conclusion: Improved methods of determining pain directionality and target therapy are needed.
    • Randomized comparison of the portable laparoscopic trainer to a standardized trainer

      Fox, Joe; The University of Arizona College of Medicine - Phoenix; Castle, Erik (The University of Arizona., 2013-04-12)
      PURPOSE: To evaluate the effectiveness of the portable laparoscopic trainer in improving skills in novice subjects. MATERIALS AND METHODS: Twenty-nine medical students with no prior surgical experience were recruited and given a pretest of three tasks on a standardized laparoscopic trainer. Subjects were evaluated objectively and subjectively. Fifteen subjects were randomized to receive a portable laparoscopic trainer and 14 subjects were assigned to the standardized laparoscopic trainers at our facility. The portable trainer group was advised but not required to complete at least 3 hours of training. The group at the facility had a proctored 1-hour session each week for 3 weeks. Each subject was then retested and evaluated with the same pretest tasks. Objective and subjective improvements between the groups were compared. HYPOTHESIS: Both the portable and standardized trainer groups were expected to improve comparably based on objective and subjective measures. The portable group had a theoretical objective advantage due to unlimited practice time and the standardized group had the advantage of proctored training sessions, thought to increase subjective performance. RESULTS: Baseline demographics and pretest scores were similar between both groups. All students in the facility group completed the three 1-hour proctored sessions. The portable trainer group reported an average 204 minutes of practice. Objectively, the facility group did better on the post-test in overall time, and in two exercises. Subjectively, the facility group had a significant improvement compared with the portable trainer group (4.6 versus 2.4 point average increase, P=0.03). CONCLUSIONS: Both groups showed objective and subjective improvement after a 3-week period of training. The portable trainer group did report longer average practice time, but this made no significant difference in subjective or objective improvement. The portable laparoscopic trainer is an effective method for improvement of basic inferior compared to proctored sessions on a standard trainer.
    • Safety and efficacy of lung recruitment maneuvers in post-­‐operative pediatric cardiac surgical patients

      Morandi, Tiffany; The University of Arizona College of Medicine - Phoenix; Willis, Brigham C. (The University of Arizona., 2013-03)
      OBJECTIVE: To demonstrate the safety of lung recruitment maneuvers in post-operative pediatric cardiac surgical patients. To assess the ability of lung recruitment maneuvers to improve lung function. HYPOTHESIS: We hypothesize that ventilator recruitment strategies be well-­tolerated in cardiac patients, and that they may benefit such patients by improving physiologic variables such as lung function and oxygenation. METHODS: Sixty‐two pediatric post-operative cardiac surgical patients were randomly selected to include in this retrospective chart review. Study subjects were selected from all patients who met inclusion criteria in the year immediately following implementation of a lung recruitment protocol in a local free‐standing pediatric hospital. Physiologic variables before, during, and after lung recruitment were recorded as well as patient demographics, diagnoses, morbidities and mortality. RESULTS: A statistically significant increase in dynamic compliance of the lungs and renal non-invasive regional oximetry was noted immediately after each recruitment maneuver. There was no statistically significant change in blood pressure, heart rate or oxygen saturation during the maneuvers. There was a transient increase in central venous pressure during the maneuvers (average increase < 1 mmHg). Of the 62 patients, there were 7 cases of pneumonia and 5 cases of small pneumothorax, often resolving without intervention. Significance: Demonstrating recruitment maneuvers are safe in pediatric patients with cardiac disease will allow practitioners to confidently utilize them when caring for ventilated patients. Such patients may benefit from potential improvements in lung function and decreased ventilator-associated morbidities.
    • Serum Uric Acid and Type 2 Diabetes

      Dille, Renee; The University of Arizona College of Medicine - Phoenix; Weil, E. Jennifer (The University of Arizona., 2013-03)
      Objectives: In recent years, serum uric acid has emerged as a possible risk factor for type 2 diabetes mellitus (T2DM). It remains unclear if this is independent of other well-known risk factors related to the metabolic syndrome. This retrospective epidemiologic study attempts to clarify the relationship between uric acid and T2DM, as well as to assess uric acid as a predictor for future diabetes development. Methods: Data was collected by the NIDDK biennial study from Pima Indians in Arizona over several decades. A cross sectional analysis using multivariate logistic regression and a survival analysis using a Cox proportional hazards model were created. Sex and body mass index (BMI) were hypothesized to create significant interactions with other variables. Interactions were confirmed by log likelihood tests, so the data was analyzed stratifying by sex. An interaction term between body mass index and uric acid was also included in analyses performed in women, as it was found to be significant in women only. Results: The cross sectional analysis showed that men with diabetes are significantly more likely to be older (OR=1.033, p<0.0001), have a higher BMI (OR=1.117, p<0.0001), mean arterial pressure (MAP) (OR=1.020, p=0.0024), cholesterol (OR=1.003, p=0.003), and lower uric acid (OR=0.625, p<0.0001) than men without diabetes. Uric acid levels did not correlate with diabetes status in women, but an interaction between uric acid and BMI was significant (p=0.0094). A goodness of fit test of the models comparing predicted to observed outcomes were significant with an R-squared value of almost 0.90 in both sexes. The survival analysis in women demonstrated that BMI (p=<0.0002) and uric acid (p=0.0209) both confer risk for diabetes development, and a significant interaction between BMI and uric acid exists with a negative parameter estimate. A nested analysis of the effect of uric acid assessed in BMI quartiles demonstrated an increased risk in normal to moderately overweight individuals, and a hazard ratio under 1 in more obese individuals. Results in men demonstrated no significance of uric acid (p=0.6571). Conclusion: The relationship between serum uric acid and diabetes varies significantly by sex, and BMI appears to have a confounding relationship with uric acid, especially in women. Uric acid is lower in men with current diabetes, confirming previous studies, which may be due to renal hyperfiltration or induction of uric acid as an antioxidant response to diabetes. In women, elevated uric acid confers higher risk of future development of T2DM. Why this was not shown in men is unclear. Utilizing uric acid in clinical practice as a screening tool is limited by interactions between uric acid and other metabolic risk factors, specifically BMI, as well as variations influenced by diet and renal function.
    • Success Rates for Reduction of Pediatric Distal Radius and Ulna Fractures by ED Physicians

      Kaye, Bryan; The University of Arizona College of Medicine - Phoenix; Bulloch, Blake (The University of Arizona., 2013-03)
      Objective: To determine the success rates for reduction of pediatric distal radius and/or ulna fractures by emergency department (ED) physicians. Methods: We conducted a retrospective study of children <18 years of age who presented to a large, urban free standing children’s hospital between January 1, 2009 and December 31, 2010 with a fracture of the radius and/or ulna. Patients were excluded if they had an open fracture, were taken directly to the operating room without attempted ED manipulation, or had additional fractures besides isolated radius/ulna fractures. The primary endpoint was the proportion of successful reductions of closed forearm fractures in the ED, as defined by first orthopedic follow up visit. Results: All reductions were performed by Board certified/eligible Pediatric Emergency Medicine (PEM) physician or PEM fellow. There were a total of 15 different PEM faculty and 10 PEM fellows that were involved in the fracture reductions during the study period. There were 295 forearm fractures reduced in the ED during the study period. The mean age was 8.27 years (median 8 years; range 1 to 16) and males comprised 69.2% (n=204) of the study group. A total of 225 (76.3%) fractures were of the distal forearm and 70 involved the midshaft (23.7%). All but 67 (22.7%) patients returned for their orthopedic follow up exam. A total of 33 (14.5%) of all patients required re-manipulation at follow up; 24 in the distal forearm fracture group (22 were closed reductions and 2 open reduction with internal fixation [ORIF]), versus 9 in the midshaft group (7 closed reductions and 2 ORIF). Conclusion: The literature reveals that between 7% and 39% of children who have fracture reductions in the ED by orthopedics will require re-manipulation. Our rate of 14.5% is consistent within that range. With training, pediatric ED physicians have similar success rates as orthopedists in the reduction of forearm fractures.
    • Survey of Primary Care Offices: Triage of Poisoning Calls

      Austin, Travis; The University of Arizona College of Medicine - Phoenix; Brooks, Daniel (The University of Arizona., 2013-03)
      Poison control centers hold great potential for saving health care resources particularly by preventing unnecessary medical utilization. We developed a four-question survey with three poisoning-related scenarios, based on common calls to our poison center, and one question regarding after-hours calls. We identified primary care provider offices in our poison center's region from an internet search. We contacted these offices via telephone and asked to speak to an office manager or someone responsible for triaging patient phone queries. Using a scripted form, trained investigators questioned 100 consecutive primary care provider offices on how they would handle these poisoning-related calls if there was no poison center available for patient referral. It was hypothesized that a substantial proportion of these poisoning-related calls would be triaged to 911 or an emergency department. Results of our survey suggest that 82.5% of poisoning-related calls to primary care offices would be referred to 911 or an emergency department if there was no poison center. These results further support the role that poison centers play in patient care and health care utilization.
    • Systematic Review on the Relationship Between Marijuana Use

      Janousek, Alyssa; The University of Arizona College of Medicine - Phoenix; Campos-Outcalt, Douglas (The University of Arizona., 2013-03)
      Objective: To develop a systematic review on the association between marijuana use and cyclic vomiting sydrome for the Arizona Department of Health Services. The review attempted to answer the key question of whether there is an association between marijuana use and cyclic vomiting syndrome and if so, whether marijuana use causes cyclic vomiting syndrome. Methods: The databases MEDLINE (PubMed), The Chocrane Library, CINAHL (EBSCO), psycINFO, Web of Science, and Google Scholar were searched for the topics of marijuana use and cyclic vomiting syndrome multiple times from September 2012 – November 2012. The quality of each pertinent study was assessed by two reviewers. Case-control and cohort studies were assessed using the Newcastle-Ottowa Assessment Scale.45 Case series’ were assessed using the criteria laid out in Guise et al.’s systematic review which was adapted from Deeks et al. and Agency for Healthcare Research and Quality.15,11,1 Literature reviews were assessed using the AMSTAR criteria.35 Overall quality of evidence and causation were determined using the GRADE methodology and the Bradford Hill criteria, respectively.16,18 Results: A total of 95 articles were identified and 37 of these were found to address the key question in some way. The study designs of identified articles were 1 case-control study, 3 cohort studies, 4 case series, 24 case reports, and 5 literature reviews. The majority of reviewed studies report an association between marijuana use and cyclic vomiting syndrome or cannabinoid hyperemesis syndrome with marijuana use preceding the onset of vomiting symptoms. However, the overall body of evidence reviewed is of very low quality and does not meet criteria to demonstrate causation. Significance: The majority of reviewed studies suggest an association between marijuana use and cyclic vomiting syndrome or cannabinoid hyperemesis syndrome though no studies suggested any evidence as to whether marijuana use causes cyclic vomiting syndrome or cannabinoid hyperemesis syndrome. The entire body of evidence reviewed, however, is of very low quality and therefore no definitive conclusions can be drawn from this review about the association between marijuana and cyclic vomiting syndrome or whether marijuana use causes cyclic vomiting syndrome.
    • Targeting Invasive Glioblastoma via the TROY-JAK1 Signaling Pathway

      Kahn, Allon; The University of Arizona College of Medicine - Phoenix; Tran, Nhan (The University of Arizona., 2013-03)
      Objective and Hypothesis: Glioblastoma multiforme, the most common and lethal primary brain neoplasm in adults, has been historically difficult to treat, as its invasion into contiguous brain tissue mitigates the benefit of surgical resection. Furthermore, its unique ability to evade apoptosis and selectively induce proliferation promotes chemotherapeutic resistance and explains the lack of substantial survival improvement despite decades of research. The orphan transmembrane receptor, TROY, has been shown to influence glioma cell migration and survival. While TROY downstream signaling presents a potential therapeutic target, the detailed pathway has yet to be fully elucidated. We identified the non-receptor tyrosine kinase, JAK1,as a candidate binding partner and hypothesized that JAK1 is a downstream mediator of TROY-induced glioma invasion, ultimately seeking to validate the potential therapeutic potential of this interaction. Methods: TROY-JAK1 binding was assessed by co-immunoprecipitation of JAK1 with immunoblotting for TROY. The mechanism of this JAK1-TROY interaction was assessed by western blottingfor phosphorylated JAK1 and STAT3 in wild type vs. TROY-overexpressing glioma cells. Finally, an in-vitro radial migration assay was performed under siRNA depletion of JAK1 to assess functional validation. Results: JAK1 was confirmedas a TROY binding partner by co-immunoprecipitation, with immunoblotting demonstrating that TROY-overexpression induces JAK1 phosphorylation. siRNA-mediated depletion of JAK1 also resulted in decreasedphosphorylated STAT3 level. Finally, a radial migration assay performed on wild-type and TROY-overexpressing T98G cells with and without JAK1 depletion demonstrated statistically significant reductions in migration rate in both JAK1-depleted groups compared to controls. Significance: This study identified and confirmed JAK1 as a downstream mediator of TROY signaling and demonstrated that JAK1 depletion results in mitigation of the pro-migratory effect of TROY overexpression. Thus, JAK1 provides a potential novel therapeutic target for disruption of glioblastoma TROY signaling in vivo andmay contribute to the development of more efficacious chemotherapeutic agents.
    • TDP-43 Deposition in Prospectively Followed, Cognitively Normal Elderly Individuals: A Correlative Study

      Arnold, Stacy J.; The University of Arizona College of Medicine - Phoenix; Beach, Thomas; Dugger, Brittany (The University of Arizona., 2013-03)
      TAR DNA-binding protein 43 (TDP-43) has been heavily researched in recent years due to its involvement in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Numerous studies have also sought to investigate the frequency of TDP-43 deposition in other neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, with very few studies focusing on the relationship of TDP-43 to pathological and clinical parameters within cognitively normal subjects. We sought to explore the deposition of TDP-43 and its relation to pathological and clinical parameters in a series of prospectively followed, cognitively normal, elderly individuals whom have come to autopsy. We screened thick, coronal sections of mesial temporal lobe; containing hippocampus and/or amygdalar regions from a series of 110 cognitively normal subjects (age range 71-100 years) using immunohistochemical methods for phosphorylated TDP-43. Consistent with previous results, we found a 36.4% incidence of pathologic TDP-43. Deposition was detected in the form of dendritic neurites, intranuclear inclusions, and perikaryal cytoplasmic neuronal inclusions. With respect to other concomitant pathologies commonly found in elderly individuals, cases with TDP-43 had a greater proportion of cases with argyrophilic grains (ARG) (40% vs. 18.6%). There was not greater prevalence or densities of other concomitant pathologies, including cerebral white matter rarefaction, incidental Lewy bodies, neurofibrillary tangles or amyloid plaques in TDP-43 positive cases. These results indicate deposition of TDP-43 occurs in a substantial subset of cognitively normal elderly subjects and is more common in those with argyrophilic grains.
    • Valproic Acid-Induced Gait Disturbance and Cognitive Impairment that was Reversible

      Evans, Matt; The University of Arizona College of Medicine - Phoenix; Yaari, Roy (The University of Arizona., 2013-03)
      Clinicians should be aware that treating patients with Valproic Acid (VPA) can cause cognitive and neurological decline in a small percentage of patients. A 67-year-old female with urinary incontinence, who had taken VPA without major complaints for 15 years to control her seizures, presented with abnormal gait and cognitive impairment that was significantly impacting her day-to-day level of functioning. Initially normal pressure hydrocephalus was suspected, but large volume LP did not show significant improvements in gait or cognition. Discontinuation of VPA reversed her symptoms over the next two months. The hypothesis of this project was that clinical judgment combined with objective criteria could be used to support the argument that this patient’s symptoms were likely an adverse drug reaction to VPA. The Naranjo adverse drug reaction scale was used as an objective measure and indicated that this patient’s likelihood of an adverse drug reaction to VPA was “probable”. Imaging findings consistent with the literature demonstrated reversible cortical pseudoatrophy and enlargement of the lateral ventricles, although changes in ventricular size did not reach statistical significance by two-tailed t-test. This case exemplifies the adverse effects of VPA, which can cause reversible neurological symptoms even in long-term treated patients and can present as parkinsonism or other dementia syndromes such as normal pressure hydrocephalus.
    • What’s in your sample closet? A cross-sectional study to quantify the number of expired samples and to evaluate novelty and usefulness of sample closet medications

      Evans, Kari; The University of Arizona College of Medicine - Phoenix; Brown, Steven (The University of Arizona., 2013-03)
      Background Many physicians dispense drug samples in their offices. In general, evidence suggests that drug samples provide minimal benefit to patients. Objective and Hypothesis To quantify the number of expired sample closet medications and to analyze the medications most commonly found for their novelty and usefulness. We hypothesized that the medications found in local sample closets will often be expired and will not be novel or useful. Methods We inventoried ten sample closets in primary care clinics. We quantified the number of expired medications and analyzed the 23 medications found in seven or more closets. To assess novelty, we determined if the sample medication: had a new mechanism of action, had a generic on market with same mechanism of action, and had a generic medication on market for the same indication. To assess usefulness, we determined if the sample medication had improved patient oriented outcomes, safety, and tolerability. We noted the cost of a one-month supply for the typical starting dose of each sample medication. Results Of the 12,581 drug packages and boxes we inventoried, 14% of were expired. Ninety-six percent (n=22) of sample closet medications had a generic medication on the market for the same indication and 74% (n=17) had a generic medication on the market with the same mechanism. Only 3 medications (13%) had evidence of superior patient oriented outcomes when compared to other medications for the same indication. Six medications (26%) demonstrated superior safety and tolerability. Only one medication (4%) was recommended as first line therapy in an evidence-based guideline. The mean cost for a one month supply of a typical starting dose was 178 dollars. Significance and Conclusions. Sample closet medications are often expired, have limited novelty and usefulness, and are expensive. The widespread use of sample medications should be re-examined.