• Long-Term Ranibizumab Treatment in Neovascular Age-Related Macular Degeneration: A Belgian Subanalysis from the Global Real-World LUMINOUS (TM) Study

      Leys, Anita M; Ramboer, Eva; Favreau, Mérédis; Denhaerynck, Kris; MacDonald, Karen; Abraham, Ivo; Brié, Heidi; Univ Arizona, Ctr Hlth Outcomes & Pharmacoecon Res; Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci; Univ Arizona, Dept Family & Community Med, Coll Med Tucson (DOVE MEDICAL PRESS LTD, 2020-06-02)
      Purpose: To evaluate long-term, real-world treatment patterns and outcomes of ranibizumab 0.5 mg for neovascular age-related macular degeneration (nAMD) in a Belgian cohort. Patients and Methods: This Belgian (BE) cohort of the 5-year global observational LUMINOUS study included 229 patients with nAMD. Outcomes included visual acuity (VA), central retinal thickness (CRT) and safety. Results: The mean age was 79.5 +/- 7.7 years. The majority of patients (67.7%) were female and all patients were Caucasian. Most patients previously received ranibizumab with only 17.5% of patients being treatment-naive. The injection frequency declined over time irrespective of prior treatment status (p<0.0001), with treatment-naive eyes receiving a mean of 4.2 +/- 2.9 yearly injections and prior-ranibizumab eyes 3.6 +/- 2.7. Regression analysis confirmed first-year VA increases for treatment-naive eyes (p=0.002) followed by a slight decrease of -1.8 letters per year. For prior-ranibizumab eyes, the visual changes over 1 year were statistically non-significant (p=0.90) but declined slightly after year one (p<0.0001). Anatomically, the CRT of treatment-naive eyes decreased over time from baseline (p<0.0001), whereas the CRT of prior-ranibizumab eyes remained stable (p=0.43). No new safety findings were identified. Conclusion: LUMINOUS-BE reconfirms the well-characterized benefit-risk profile of ranibizumab for nAMD treatment. The observed low injection frequency reflects a need for more rigorous treatment in real-world settings.
    • Modeling the pasture-associated severe equine asthma bronchoalveolar lavage fluid proteome identifies molecular events mediating neutrophilic airway inflammation

      Bright, Lauren A; Dittmar, Wellesley; Nanduri, Bindu; McCarthy, Fiona M; Mujahid, Nisma; Costa, Lais Rr; Burgess, Shane C; Swiderski, Cyprianna E; Univ Arizona, Coll Agr & Life Sci, Sch Anim Comparat & Biomed Sci (DOVE MEDICAL PRESS LTD, 2019-05-02)
      Background: Pasture-associated severe equine asthma is a warm season, environmentally-induced respiratory disease characterized by reversible airway obstruction, persistent and non-specific airway hyper-responsiveness, and chronic neutrophilic airway inflammation. During seasonal exacerbation, signs vary from mild to life-threatening episodes of wheezing, coughing, and chronic debilitating labored breathing. Purpose: In human asthma, neutrophilic airway inflammation is associated with more severe and steroid-refractory asthma phenotypes, highlighting a need to decipher the mechanistic basis of this disease characteristic. We hypothesize that the collective biological activities of proteins in bronchoalveolar lavage fluid (BALF) of horses with pasture-associated severe asthma predict changes in neutrophil functions that contribute to airway neutrophilic inflammation. Methods: Using shotgun proteomics, we identified 1,003 unique proteins in cell-free BALF from six horses experiencing asthma exacerbation and six control herdmates. Contributions of each protein to ten neutrophil functions were modeled using manual biocuration to determine each protein's net effect on the respective neutrophil functions. Results: A total of 417 proteins were unique to asthmatic horses, 472 proteins were unique to control horses (p<0.05), and 114 proteins were common in both groups. Proteins whose biological activities are responsible for increasing neutrophil migration, chemotaxis, cell spreading, transmigration, and infiltration, which would collectively bring neutrophils to airways, were over-represented in the BALF of asthmatic relative to control horses. By contrast, proteins whose biological activities support neutrophil activation, adhesion, phagocytosis, respiratory burst, and apoptosis, which would collectively shorten neutrophil lifespan, were under-represented in BALF of asthmatic relative to control horses. Interaction networks generated using Ingenuity® Pathways Analysis further support the results of our biocuration. Conclusion: Congruent with our hypothesis, the collective biological functions represented in differentially expressed proteins of BALF from horses with pasture-associated severe asthma support neutrophilic airway inflammation. This illustrates the utility of systems modeling to organize functional genomics data in a manner that characterizes complex molecular events associated with clinically relevant disease.
    • Modulation of breast cancer cell viability by a cannabinoid receptor 2 agonist, JWH-015, is calcium dependent

      Vanderah, Todd; Hanlon, Katherine; Lozano-Ondoua, Alysia; Umaretiya, Puja; Symons-Ligouri, Ashley; Chandramouli, Anupama; Moy, Jamie; Kwass, William; Mantyh, Patrick; Nelson, Mark; et al. (DOVE MEDICAL PRESS LTD, 2016-04)
      Introduction: Cannabinoid compounds, both nonspecific as well as agonists selective for either cannabinoid receptor 1 (CB1) or cannabinoid receptor 2 (CB2), have been shown to modulate the tumor microenvironment by inducing apoptosis in tumor cells in several model systems. The mechanism of this modulation remains only partially delineated, and activity induced via the CB1 and CB2 receptors may be distinct despite significant sequence homology and structural similarity of ligands. Methods: The CB2-selective agonist JWH-015 was used to investigate mechanisms downstream of CB2 activation in mouse and human breast cancer cell lines in vitro and in a murine mammary tumor model. Results: JWH-015 treatment significantly reduced primary tumor burden and metastasis of luciferase-tagged murine mammary carcinoma 4T1 cells in immunocompetent mice in vivo. Furthermore, JWH-015 reduced the viability of murine 4T1 and human MCF7 mammary carcinoma cells in vitro by inducing apoptosis. JWH-015-mediated reduction of breast cancer cell viability was not dependent on G alpha(i) signaling in vitro or modified by classical pharmacological blockade of CB1, GPR55, TRPV1, or TRPA1 receptors. JWH-015 effects were calcium dependent and induced changes in MAPK/ERK signaling. Conclusion: The results of this work characterize the actions of a CB2-selective agonist on breast cancer cells in a syngeneic murine model representing how a clinical presentation of cancer progression and metastasis may be significantly modulated by a G-protein-coupled receptor.
    • Parameters associated with efficacy of epidural steroid injections in the management of postherpetic neuralgia: the Mayo Clinic experience

      Ghanavatian, Shirin; Wie, Christopher S; Low, Rhonda S; Butterfield III, Richard J; Zhang, Nan; Dhaliwal, Gurman Singh; Montoya, Jordan M; Swanson, David L; Univ Arizona, Coll Med Phoenix (DOVE MEDICAL PRESS LTD, 2019-04-23)
      Purpose: Thirty percent of patients with postherpetic neuralgia (PHN) receiving conservative treatment report unsatisfactory pain relief. Epidural steroid injections (ESIs) are commonly used as a therapeutic intervention in these patients. In this study, we aimed to determine if there are variables that predict the efficacy of ESI in patients with PHN. Patients and methods: We retrospectively identified patients seen at Mayo Clinic who had PHN and received ESI. From their medical records, we abstracted the demographic variables, concurrent medication use, anatomic approach and medication for ESI, and degree of pain relief at 2 and 12 weeks' postintervention. Results: None of the studied variables were significantly associated with efficacy of ESI in patients with PHN. PHN that began < 11 months before treatment was predictive of a response to ESI at 12 weeks postintervention (positive predictive value, 55%). Patients who reported poor ESI efficacy 2 weeks after the intervention had a 94% chance of still having pain at 12 weeks. Conclusion: For this cohort of patients with PHN being treated with ESI, no demographic characteristics, concurrently used medications, or type of ESI were associated with ESI treatment efficacy at 2 or 12 weeks after the intervention.
    • Phase I dose-escalation trial of intravaginal curcumin in women for cervical dysplasia

      Gattoc, Leda; Frew, Paula M; Thomas, Shontell N; Easley, Kirk A; Ward, Laura; Chow, H-H Sherry; Ura, Chiemi A; Flowers, Lisa; Univ Arizona, Dept Med (DOVE MEDICAL PRESS LTD, 2016-12)
      Background: This is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia. Objective: The objective of this study was to assess the safety, tolerability, and pharmacokinetics of intravaginal curcumin in healthy women. Study design: We conducted a 3+3 dose-escalation Phase I trial in a group of women aged 18-45 years. Thirteen subjects were given one of four doses of curcumin powder (500 mg, 1,000 mg, 1,500 mg, and 2,000 mg) packed in gelatin capsules, which was administered intra-vaginally daily for 14 days. The primary end point for this study was safety based on severe adverse events regarding laboratory toxicity, clinical findings, and colposcopic abnormalities. We administered an acceptability questionnaire to assess product experience and attributes. Results: No dose-limiting toxicities (0/13) were experienced (95% confidence interval: 0.0%-22.8%) in this study. The pharmacokinetics data demonstrated that curcumin and curcumin conjugates were not measurable in the serum and negligible in the urine of the study participants. Although 23 adverse events occurred during the course of the trial, all events were grade I based on the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 and were resolved by the end of the study in an average of 9 days. Fifty-six percent of the adverse events were related to the study drug, which included genital pruritus (23% of subjects), vaginal discharge (100%), vaginal dryness (15%), abnormal prothrombin (23%), and hypokalemia (8%). Conclusion: Intravaginal curcumin was well tolerated by all subjects and safe. In this Phase I trial, there were no severe adverse events observed at any of the administered dose levels. All adverse events were grade I and did not result in early termination of the study. There was no evidence of systemic absorption or significant local absorption of intravaginally administered curcumin.
    • Point-of-care echocardiography in simulation-based education and assessment

      Amini, Richard; Stolz, Lori; Javedani, Parisa; Gaskin, Kevin; Baker, Nicola; Ng, Vivienne; Adhikari, Srikar; Univ Arizona, Med Ctr, Dept Emergency Med (DOVE MEDICAL PRESS LTD, 2016-05)
      Background: Emergency medicine milestones released by the Accreditation Council for Graduate Medical Education require residents to demonstrate competency in bedside ultrasound (US). The acquisition of these skills necessitates a combination of exposure to clinical pathology, hands-on US training, and feedback. Objectives: We describe a novel simulation-based educational and assessment tool designed to evaluate emergency medicine residents' competency in point-of-care echocardiography for evaluation of a hypotensive patient with chest pain using bedside US. Methods: This was a cross-sectional study conducted at an academic medical center. A simulation-based module was developed to teach and assess the use of point-of-care echocardiography in the evaluation of the hypotensive patient. The focus of this module was sonographic imaging of cardiac pathology, and this focus was incorporated in all components of the session: asynchronous learning, didactic lecture, case-based learning, and hands-on stations. Results: A total of 52 residents with varying US experience participated in this study. Questions focused on knowledge assessment demonstrated improvement across the postgraduate year (PGY) of training. Objective standardized clinical examination evaluation demonstrated improvement between PGY I and PGY III; however, it was noted that there was a small dip in hands-on scanning skills during the PGY II. Clinical diagnosis and management skills also demonstrated incremental improvement across the PGY of training. Conclusion: The 1-day, simulation-based US workshop was an effective educational and assessment tool at our institution.
    • Pulmonary hypertension occurring with diazoxide use in a preterm infant with hypoglycemia

      Kylat, Ranjit I; Univ Arizona, Coll Med, Dept Pediat, Div Neonatal Perinatal Med & Dev Biol (DOVE MEDICAL PRESS LTD, 2019-01-01)
      Pharmacologic modulation to open the KATP channels with diazoxide is useful in treating hyperinsulinemia. Diazoxide is being used more often in neonates with hyperinsulinemic hypoglycemia. This report highlights a case of severe pulmonary hypertension (PH) with re-opening of ductus arteriosus in an extremely premature infant after the use of diazoxide. The rapid onset of PH with respiratory failure was completely reversible. This case emphasizes the need for extreme caution with use of diazoxide in the premature infant population, especially those with chronic lung disease of prematurity. In addition, the use of diazoxide should be limited to the persistent form of congenital hyperinsulinism, after adequate work up has been completed to evaluate for other causes of hypoglycemia. It is postulated that development of PH could be related to KATP agonsim.
    • Relationships between expression of BCS1L, mitochondrial bioenergetics, and fatigue among patients with prostate cancer

      Hsiao, Chao-Pin; Chen, Mei-Kuang; Veigl, Martina L; Ellis, Rodney; Cooney, Matthew; Daly, Barbara; Hoppel, Charles; Univ Arizona, Dept Psychol (DOVE MEDICAL PRESS LTD, 2019-07-18)
      Introduction: Cancer-related fatigue (CRF) is the most debilitating symptom with the greatest adverse side effect on quality of life. The etiology of this symptom is still not understood. The purpose of this study was to examine the relationship between mitochondrial gene expression, mitochondrial oxidative phosphorylation, electron transport chain complex activity, and fatigue in prostate cancer patients undergoing radiotherapy (XRT), compared to patients on active surveillance (AS). Methods: The study used a matched case-control and repeated-measures research design. Fatigue was measured using the revised Piper Fatigue Scale from 52 patients with prostate cancer. Mitochondrial oxidative phosphorylation, electron-transport chain enzymatic activity, and BCS1L gene expression were determined using patients' peripheral mononuclear cells. Data were collected at three time points and analyzed using repeated measures ANOVA. Results: The fatigue score was significantly different over time between patients undergoing XRT and AS (P<0.05). Patients undergoing XRT experienced significantly increased fatigue at day 21 and day 42 of XRT (P<0.01). Downregulated mitochondrial gene (BC1, ubiquinol-cytochrome c reductase, synthesis-like, BCS1L, P<0.05) expression, decreased OXPHOS-complex III oxidation (P<0.05), and reduced activity of complex III were observed over time in patients with XRT. Moreover, increased fatigue was significantly associated with downregulated BCS1L and decreased complex III oxidation in patients undergoing XRT. Conclusion: Our results suggest that BCS1L and complex III in mitochondrial mononuclear cells are potential biomarkers and feasible therapeutic targets for acute XRT-induced fatigue in this clinical population.
    • Renal replacement therapy in patients with acute respiratory distress syndrome: a single-center retrospective study

      Dill, Joshua; Bixby, Billie; Ateeli, Huthayfa; Sarsah, Benjamin; Goel, Khushboo; Buckley, Ryan; Finkelshteyn, Ilya; Thajudeen, Bijin; Kadambi, Pradeep V; Bime, Christian; et al. (DOVE MEDICAL PRESS LTD, 2018)
      Patients with acute respiratory distress syndrome (ARDS) who develop acute kidney injury have increased mortality and frequently require renal replacement therapy (RRT). The optimal timing for initiation of RRT after onset o f ARDS to improve survival is not known. Methods: We retrospectively reviewed clinical data on patients admitted to our health system over a 2-year period. Individual charts were carefully reviewed to ascertain that patients met the Berlin criteria for ARDS and to categorize RRT utilization. The Kaplan Meier analysis was conducted to compare early (48 pound hours postintubation) versus late (>48 hours postintubation) initiation of RRT. Associations between RRT initiation and mortality were evaluated using Cox proportional hazards regression. Results: A total of 75 patients were identified with ARDS, 95% of whom received RRT. Mortality of patients who required RRT was 56%. The main indications for RRT initiation were fluid overload (75%), metabolic acidosis (64%), and hyperkalemia (33%). The Kaplan-Meier analysis comparing early initiation of RRT to late initiation of RRT showed no survival benefit. Cox proportional hazard models testing the association between timing of RRT initiation with survival and adjusting for sex, race, ethnicity, and Acute Physiology and Chronic Health Evaluation II score did not reach statistical significance (HR=0.94, 95% CI=0.48-1.86). Conclusion: Timing of RRT initiation was not associated with a survival benefit. Prospective study in the utilization and outcomes of RRT in ARDS could assist in optimizing its usage in this population.
    • A retrospective analysis of intraocular pressure changes after cataract surgery with the use of prednisolone acetate 1% versus difluprednate 0.05%

      Kusne, Yael; Kang, Paul; Fintelmann, Robert; Univ Arizona, Coll Med (DOVE MEDICAL PRESS LTD, 2016-11)
      Purpose: To compare the effect of topical prednisolone acetate 1% (PA) used after routine cataract surgery to the effect of difluprednate 0.05% (DFBA) used for the same indication on intraocular pressure (IOP). Methods: An electronic query was created to gather information from all cataract surgeries between January 2010 and January 2015 within the electronic health record database at Barnet Dulaney Perkins, a multicenter, multiphysician private practice in Phoenix, Arizona. Information collected included age, sex, diabetes status, glaucoma history, medication regimen (use of PA or DFBA), and IOP before surgery, 5-10 days postoperatively (TP1) and 3-6 weeks postoperatively (TP2). Postoperative IOP measurements were compared to baseline IOP measurement in each patient. Results: Regardless of steroid used, all patients in this study experienced an increase in IOP within TP1 and returned to baseline IOP (+/- 2.0 mmHg) by TP2. Patients who received DFBA showed a statistically significant increase in IOP at TP1 compared to those on PA (P<0.001) with the mean IOP an average 0.60 mmHg higher (95% CI = 0.3, 0.9). The odds ratio of a clinically significantly increased IOP at TP1 (defined as overall IOP >= 21 mmHg and an increase of >= 10 mmHg) in DFBA-treated patients was 1.84 (95% CI = 1.4, 2.6). In patients treated with PA, 3% reached a significantly increased IOP, compared to 4.4% of patients in the DFBA group (P<0.05). Risk factors for increased IOP were identified, and include advanced age (>75) (P<0.005) and a history of glaucoma (P<0.001). Conclusion: In postoperative cataract patients, use of DFBA increased the risk of a clinically significant IOP increase.
    • Shadowing emergency medicine residents by medical education specialists to provide feedback on non-medical knowledge-based ACGME sub-competencies

      Waterbrook, Anna L.; Ellinwood, Karen C. Spear; Pritchard, T. Gail; Bertels, Karen; Johnson, Ariel C.; Min, Alice; Stoneking, Lisa R.; Univ Arizona, Coll Med, Dept Emergency Med; Univ Arizona, Coll Med, Dept Obstet & Gynecol; Univ Arizona, Coll Med, Dept Pediat; et al. (DOVE MEDICAL PRESS LTD, 2018)
      Objective: Non-medical knowledge-based sub-competencies (multitasking, professionalism, accountability, patient-centered communication, and team management) are challenging for a supervising emergency medicine (EM) physician to evaluate in real-time on shift while also managing a busy emergency department (ED). This study examines residents' perceptions of having a medical education specialist shadow and evaluate their nonmedical knowledge skills. Methods: Medical education specialists shadowed postgraduate year 1 and postgraduate year 2 EM residents during an ED shift once per academic year. In an attempt to increase meaningful feedback to the residents, these specialists evaluated resident performance in selected nonmedical knowledge-based Accreditation Council of Graduate Medical Education (ACGME) sub-competencies and provided residents with direct, real-time feedback, followed by a written evaluation sent via email. Evaluations provided specific references to examples of behaviors observed during the shift and connected these back to ACGME competencies and milestones. Results: Twelve residents participated in this shadow experience (six post graduate year 1 and six postgraduate year 2). Two residents emailed the medical education specialists ahead of the scheduled shadow shift requesting specific feedback. When queried, five residents voluntarily requested their feedback to be included in their formal biannual review. Residents received milestone scores and narrative feedback on the non-medical knowledge-based ACGME sub-competencies and indicated the shadow experience and subsequent feedback were valuable. Conclusion: Medical education specialists who observe residents over the course of an entire shift and evaluate non-medical knowledge-based skills are perceived by EM residents to provide meaningful feedback and add valuable information for the biannual review process.
    • A student-implemented elective to improve medical student confidence in providing diabetes self-management support

      Fazel, Maryam; Fazel, Mohammad; Bedrossian, Nora; Picazo, Fernando; Pendergrass, Merri; Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci; Univ Arizona, Coll Med, Dept Med; Univ Arizona, Coll Med; Univ Arizona, Coll Med, Div Endocrinol, Dept Med (DOVE MEDICAL PRESS LTD, 2016-10)
      Background: The purpose of this study was to develop a preclerkship elective and assess its effectiveness in supplementing medical students' education. Methods: A group of medical students under the guidance of two faculty advisors developed an elective consisting of six sessions covering a variety of practical aspects of diabetes care/education taught by an interprofessional team. Following the course completion, a survey was emailed to the enrollees who attended at least one session. The results were analyzed using Wilcoxon signed-rank and descriptive analyses. Results: A total of 14 medical students were enrolled (nine first year and five second year). An average of 4.4 sessions/student was attended. Thirteen students attended at least one session and were surveyed. The survey response rate was similar to 62% (8/13). All eight students indicated that the course was valuable and would recommend it to their colleagues. A Wilcoxon signed-rank test revealed a statistically significant increase in students' confidence in all five areas assessed following participation in the course, P<0.05 with a large effect (r>0.5). Conclusion: This study suggests the feasibility of developing disease state-specific preclerkship elective courses and that such courses can be beneficial in supplementing medical student education with practical knowledge.
    • Tumor suppressor ING4 inhibits estrogen receptor activity in breast cancer cells

      Keenen, Madeline; Kim, Suwon; Univ Arizona, Coll Med, Dept Basic Med Sci (DOVE MEDICAL PRESS LTD, 2016-11)
      Resistance to antiestrogen therapy remains a significant problem in breast cancer. Low expression of inhibitor of growth 4 (ING4) in primary tumors has been correlated with increased rates of recurrence in estrogen receptor-positive (ER+) breast cancer patients, suggesting a role for ING4 in ER signaling. This study provides evidence that ING4 inhibits ER activity. ING4 overexpression increased the sensitivity of T47D and MCF7 ER+ breast cancer cells to hormone deprivation. ING4 attenuated maximal estrogen-dependent cell growth without affecting the dose-response of estrogen. These results indicated that ING4 functions as a noncompetitive inhibitor of estrogen signaling and may inhibit estrogen-independent ER activity. Supportive of this, treatment with fulvestrant but not tamoxifen rendered T47D cells sensitive to hormone deprivation as did ING4 overexpression. ING4 did not affect nuclear ER alpha protein expression, but repressed selective ER-target gene transcription. Taken together, these results demonstrated that ING4 inhibited estrogen-independent ER activity, suggesting that ING4-low breast tumors recur faster due to estrogen-independent ER activity that renders tamoxifen less effective. This study puts forth fulvestrant as a proposed therapy choice for patients with ING4-low ER+ breast tumors.
    • Two-Year Integrated Efficacy And Safety Analysis Of Benralizumab In Severe Asthma

      FitzGerald, J Mark; Bleecker, Eugene R; Bourdin, Arnaud; Busse, William W; Ferguson, Gary T; Brooks, Laura; Barker, Peter; Martin, Ubaldo J; Univ Arizona, Coll Med, Div Pharmacogen; Univ Arizona, Coll Med, Div Genet Genom & Precis Med (DOVE MEDICAL PRESS LTD, 2019-12-09)
      Background: Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody. Treatment with benralizumab significantly reduces exacerbations and improves lung function after 1 year for patients with severe, uncontrolled eosinophilic asthma. Objective: We explored whether benralizumab efficacy was sustained after an additional year of treatment while maintaining an acceptable safety profile. Methods: Data from the pivotal 48-week SIROCCO and 56-week CALIMA studies were integrated with data from the predefined 56-week adult phase of the BORA extension study to provide a 2-year integrated efficacy and safety analysis of benralizumab. BORA enrolled patients who had completed SIROCCO or CALIMA. Patients receiving benralizumab 30 mg subcutaneously, either every 4 weeks (Q4W) or every 8 weeks (Q8W; first three doses Q4W), were assessed. Efficacy was evaluated based on baseline blood eosinophil counts from the pivotal studies (>= 300 and <300 cells/mu L). Results: Mean treatment exposures were 24.3 (Q4W, n=518) and 24.6 (Q8W, n=512) months. Exacerbation frequency reductions observed in SIROCCO/CALIMA were maintained; 50% of the patients had no exacerbations during the 2-year study period (crude exacerbation rate, Q8W: 0.56 exacerbations/year for patients with blood eosinophil counts >= 300 cells/mu L). Lung function improvements with benralizumab were maintained for 2 years, as represented by increases in mean prebronchodilator forced expiratory volume in 1 second from baseline of 0.343 L and 0.364 L with 1 and 2 years of benralizumab Q8W treatment, respectively, for patients with blood eosinophil counts >= 300 cells/mu L. Health-related quality of life improvements with benralizumab observed in the pivotal studies were also sustained. Adverse events and serious adverse event rates were similar between the BORA extension and SIROCCO/CALIMA periods, with no new or unexpected occurrence of adverse events. Conclusion: This benralizumab 2-year integrated analysis further supports long-term use of benralizumab for patients with severe, uncontrolled eosinophilic asthma.
    • Unusual etiology of gastrointestinal symptoms: the case of jojoba butter

      Minckler, Michael; Fisher, Joseph; Bowers, Rachel; Amini, Richard; Univ Arizona, Dept Emergency Med; Univ Arizona, Coll Med (DOVE MEDICAL PRESS LTD, 2017-02)
      Background: Jojoba butter is cyanogenic and has gained attention among herbal supplement consumers due to claims that it may aid in weight loss. Jojoba butter is extracted from the seeds of jojoba shrubs found in the Sonoran Desert. The seeds have long been recognized as inedible, however clinical symptoms following ingestion are not well documented. Case report: This report describes a patient who developed restlessness and gastrointestinal complaints following ingestion of homemade jojoba seed butter. The patient's presentation following ingestion is discussed, as well as effective workup and treatment. In our case, the patient was monitored and received fluid resuscitation, lorazepam, and diphenhydramine for symptomatic therapy. Conclusion: This case describes the gastrointestinal sequela and effective management following ingestion of jojoba butter.
    • Use of immediate-release opioids as supplemental analgesia during management of moderate-to-severe chronic pain with buprenorphine transdermal system

      Silverman, Sanford; Raffa, Robert B; Cataldo, Marc; Kwarcinski, Monica; Ripa, Steven R.; Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol (DOVE MEDICAL PRESS LTD, 2017-05)
      Background: The buprenorphine transdermal system (BTDS) is approved in the US for the management of chronic pain. Due to its high affinity for mu-opioid receptors with a slow dissociation profile, buprenorphine may potentially displace or prevent the binding of competing mu-opioid-receptor agonists, including immediate-release (IR) opioids, in a dose-dependent manner. Health care professionals may assume that the use of IR opioids for supplemental analgesia during BTDS therapy is not acceptable. Materials and methods: This post hoc analysis evaluated the use of IR opioids as supplemental analgesia during the management of moderate-severe chronic pain with BTDS at 52 US sites (BUP3015S, NCT01125917). Patients were categorized into IR-opioid and no-IR-opioid groups. At each visit of the extension phase, adverse events, concomitant medications, and information from the Brief Pain Inventory (BPI) were recorded. Results: The most common supplemental IR opioids prescribed during BTDS treatment (n=354) were hydrocodone-acetaminophen and oxycodone-acetaminophen. The mean daily dose of IR opioids (morphine equivalents) for supplemental analgesia was 22 mg. At baseline, BPI pain intensity and BPI - interference scores were higher for patients in the IR-opioid group. In both treatment groups, scores improved by week 4, and then were maintained throughout 6 months of the open-label extension trial. The incidence of treatment-emergent adverse events was similar in both groups. Conclusion: Patients who were prescribed IR opioids reported lower scores for BPI pain intensity and pain interference to levels similar to patients receiving BTDS without IR opioids, without increasing the rate or severity of treatment-emergent adverse events. Patients prescribed concomitant use of IR opioids with BTDS had greater treatment persistence. The results of this post hoc analysis provide support for the concomitant use of IR opioids for supplemental analgesia during the management of moderate-severe chronic pain with BTDS.