PubMed | Sonoran Biosciences, Inc., Arizona State University and Banner University Medical Center Phoenix
Type: Journal Article | Journal: Clinical orthopaedics and related research | Year: 2016
The antimicrobial concentration required to kill all the bacteria in a biofilm, known as the minimum biofilm eradication concentration (MBEC), is typically determined in vitro by exposing the biofilm to serial concentrations of antimicrobials for 24 hours or less. Local delivery is expected to cause high local levels for longer than 24 hours. It is unknown if longer antimicrobial exposures require the same concentration to eradicate bacteria in biofilm. Questions/purposes Does MBEC change with increased antimicrobial exposure time?Biofilms were grown for 24 hours using five pathogens (methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa) and then exposed to four antimicrobials regimens: tobramycin, vancomycin, and tobramycin combined with vancomycin in 3:1 and 1:1 ratios by weight in concentrations of 62.5, 125, 250, 500, 1000, 2000, 4000, and 8000 g/mL for three durations, 1, 3, and 5 days, in triplicate. MBEC was measured as the lowest concentration that killed all bacteria in the biofilm determined by 21-day subculture.MBEC was lower when antimicrobial exposure time was longer. For the staphylococcus species, the MBEC was lower when exposure time was 5 days than 1 day in 11 of 12 antimicrobial/microorganism pairs. The MBEC range for these 11 pairs on Day 1 was 4000 to > 8000 g/mL and on Day 5 was < 250 to 8000 g/mL. MBEC for tobramycin/P. aeruginosa was 2000 g/mL on Day 1 and 250 g/mL on Day 5, and for E. coli, 125 g/mL on Day 1 and 62.5 on Day 5.Although antimicrobial susceptibility was lower for longer exposure times in the microorganisms we studied, confirmation is required for other pathogens. Clinical Relevance One-day MBEC assays may overestimate the local antimicrobial levels needed to kill organisms in biofilm if local levels are sustained at MBEC or above for longer than 24 hours. Future studies are needed to confirm that antimicrobial levels achieved clinically from local delivery are above the MBEC at relevant time points and to confirm that MBEC for in vitro microorganisms accurately represents MBEC of in vivo organisms in an clinical infection.
PubMed | Sun Yat Sen University and Banner University Medical Center Phoenix
Type: Journal Article | Journal: Medical physics | Year: 2017
To investigate dosimetric parameters correlated with acute hematologic toxicity (HT) in patients with rectal cancer treated with IMRT and concurrent chemotherapy.We analyzed 127 rectal cancer patients receiving IMRT and concurrent chemotherapy. Whole pelvic bone marrow (PBM) was contoured for each patient including lumbosacral spine (LSSP), ilium and lower pelvic (LP). The equivalent uniform dose (EUD) of each region and the PBM were calculated. Endpoints for HT is grade 3 (HT3+) leukopenia, neutropenia or thrombocytopenia. Normal tissue complication probability (NTCP) was evaluated with the Lyman-Kutcher-Burman (LKB) model. On the basis of our NTCP modeling, we get the value of TDTwenty six patients experienced HT3+. Constrained optimization of the LKB model for HT3+ yielded the parameters m=0.583, n=1, and TDLKB modeling indicates that PBM acts like a parallel organ, implying that the mean dose to the organ is a useful predictor for toxicity. Compared with a Stanford study about anal cancer patients, the patients of anal cancer received chemotherapy with MMC and 5-FU which can cause much more severe HT than 5-FU or FOLFOX in our rectal cancer study. Therefore, the incidence of HT3+ is much higher in anal cancer and resulted in a much lower TD
Barletta J.F.,Midwestern University |
Bruno J.J.,University of Houston |
Buckley M.S.,Banner University Medical Center Phoenix |
Cook D.J.,McMaster University
Critical Care Medicine | Year: 2016
Objectives: Stress ulcer prophylaxis is commonly administered to critically ill patients for the prevention of clinically important stress-related mucosal bleeding from the upper gastrointestinal tract. Despite widespread incorporation of stress ulcer prophylaxis into practice around the world, questions are emerging about its indications and impact. This clinically focused article will review current controversies related to stress ulcer prophylaxis for critically ill adult patients, including bleeding frequency, risk factors, comparative efficacy, adverse effect profile, and overall cost-effectiveness of the available stress ulcer prophylaxis regimens. Data Sources: A MEDLINE search was conducted from inception through August 2015. Study Selection: Selected publications describing stress ulcer prophylaxis in adult patients were retrieved (original research, systematic reviews, and practice guidelines); their bibliographies were also reviewed to identify additional pertinent publications. Data Extraction: Data from relevant publications were abstracted and summarized. Data Synthesis: The existing evidence is organized to describe the patients most likely to benefit from stress ulcer prophylaxis, review the comparative efficacy of proton pump inhibitors and histamine 2 receptor antagonists, the adverse effects of stress ulcer prophylaxis, and overall cost-effectiveness. Conclusions: Many stress ulcer prophylaxis recommendations are based on older studies at risk of bias, which may not be applicable to modern practice. Stress ulcer prophylaxis should be limited to patients considered to be at high risk for clinically important bleeding. When evaluating only the trials at low risk for bias, the evidence does not clearly support lower bleeding rates with proton pump inhibitors over histamine 2 receptor antagonists; however, proton pump inhibitors appear to be the dominant drug class used worldwide today. The current rate of upper gastrointestinal bleeding and the relative adverse effects of acid suppression on infectious risk may drive not only the effectiveness, but also the cost-effectiveness of stress ulcer prophylaxis today. Research is currently underway to better address these issues. © 2016 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.
Buckley M.S.,Banner University Medical Center Phoenix |
Reeves B.A.,Banner University Medical Center Phoenix |
Barletta J.F.,Midwestern University |
Bikin D.S.,Banner University Medical Center Phoenix
Annals of Pharmacotherapy | Year: 2016
Background: Phenytoin is a common medication for seizure treatment and prophylaxis in the intensive care unit (ICU). The clinical utility of the Sheiner-Tozer equation for adjusting total phenytoin levels for hypoalbuminemia remains controversial. Objective: The purpose of this study was to evaluate the correlation of this formula in predicting phenytoin serum concentrations. Methods: A retrospective cohort study was conducted in the adult ICU between January 1, 2010, and June 21, 2013. Patients meeting the following study criteria were included: age ≥18 years, admission to the ICU, simultaneously drawn total and free serum phenytoin concentrations with albumin ≤48 hours of phenytoin draws. Study end points were the correlation as well as the level of agreement in the interpretation of the free and adjusted phenytoin concentrations using the Sheiner-Tozer formula in critically ill patients with hypoalbuminemia. Results: A total of 238 patients were analyzed. Mean adjusted total phenytoin and free levels were 16.1 ± 8.1 and 1.5 ± 0.8 µg/mL, respectively (r = 0.817; P < 0.001). Absolute agreement with level interpretation between adjusted total phenytoin and free levels was 77% (κ = 0.633; P < 0.001). Adjusted phenytoin serum concentrations more frequently overestimated the free level. Conclusions: There is a significant correlation between free and adjusted total phenytoin levels using the Sheiner-Tozer equation in critically ill patients. However, disagreement was noted with interpretation, primarily because of the adjusted concentration overestimating the free level. This imprecision may lead to inaccurate decision making regarding the management of phenytoin in this patient population. Thus, free phenytoin levels should be utilized. © The Author(s) 2016.
Muhleisen A.L.,Banner University Medical Center Phoenix |
Muhleisen A.L.,University of Arizona |
Herbst-Kralovetz M.M.,University of Arizona
Maturitas | Year: 2016
For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis. © 2016 Elsevier Ireland Ltd. All rights reserved.
Hsiehchen D.,University of Texas Southwestern Medical Center |
Espinoza M.,Banner University Medical Center Phoenix |
Hsieh A.,Northwestern University
Scientometrics | Year: 2016
Despite the importance and magnitude of biomedical research, little is known about its development and responsiveness to current health needs. Herein, we characterized the evolution of disease specific biomedical research and assess the alignment of research and translational efforts with disease burden. Publication patterns for approximately 2700 diseases indicated a fluid landscape of modern biomedical interests. In studying a subset of diseases with available data, overall measures of disease burden explained a large fraction of publication variance but only a small portion of NIH funding variance. In addition, discrete measures of mortality and morbidity differentially impacted NIH funding levels, research efforts, and the number of clinical trials in the US. Our findings not only scrutinize the relevance of our current biomedical enterprise, but may also serve as a resource for fostering strategies that adequately prepare the scientific community to address future health needs and promote accountability in the allocation of resources. © 2016 Akadémiai Kiadó, Budapest, Hungary
Anand K.,Banner University Medical Center Phoenix |
Sabbagh M.,Santa Fe Institute
Expert Opinion on Investigational Drugs | Year: 2015
Introduction: Alzheimers disease (AD) is a progressive neurodegenerative disorder that is a significant burden to society. With continual expansion of our understanding of the disease, novel therapies are emerging as potential therapeutics to either halt or reverse progression of the disease.Areas covered: This paper aims to provide an overview of current drug therapies aimed at targeting the tau protein. With this protein known to be a noted pathologic finding of the disease, trials of therapeutics aimed at this protein have been under investigation. This article is based on data obtained from PubMed searches, TauRx, ALZFORUM, and Clinicaltrials.gov with search terms including: anti-tau, tau therapeutic agents in AD, Phase 0, I, II, III trials in AD, monoclonal antibodies and vaccines.Expert opinion: Broad-based treatments that target tau, including microtubule stabilization and tau aggregation inhibitors, appear to be of greatest promise. Immunotherapy appears to be relatively safe and efficacious but narrow whereas protein kinase inhibition has not demonstrated clinical benefit to date. © 2015 © Informa UK, Ltd.
Kang A.M.,Banner University Medical Center Phoenix |
Kang A.M.,University of Arizona |
Brooks D.E.,Banner University Medical Center Phoenix |
Brooks D.E.,University of Arizona
Pediatrics | Year: 2016
BACKGROUND: Anticipatory guidance and prevention efforts to decrease poisonings in young children have historically focused on restricting access to minimize exploratory ingestions. Because infants through 6 months of age have limited mobility, such exposures are expected to be less frequent and therapeutic (or dosing) errors should be more frequent. Although recent prevention efforts target some types of therapeutic errors, the epidemiology of these exposures is not well characterized in this age group. This could have important implications for the effectiveness of current prevention efforts. METHODS: A 10-year (2004-2013) retrospective review of exposure calls for infants through 6 months of age was conducted on National Poison Data System files. RESULTS: A total of 271 513 exposures were reported, of which 96.7% were unintentional. Of these, the most common reasons were general unintentional (50.7%), which includes exploratory exposures, and therapeutic error (36.7%). Among the latter, 47.0% involved quantitative dosing errors (a different amount than intended) and 42.8% involved nonquantitative dosing errors (a medication given twice or too soon, the wrong medication, or wrong route). Most exposures (97.5%)occurred in the home but only 85.2% of calls came from the home;80.4% ofself-referrals to a healthcare facility were not admitted. CONCLUSIONS: General unintentional (including exploratory) exposures and therapeutic errors both comprise a large proportion of calls in this age group. Among therapeutic errors, quantitative and nonquantitative dosing errors are equally concerning. There areappreciablenumbers of patients presenting to healthcare prior topoison centerconsultation. These data can help target future anticipatory guidance and prevention measures. Copyright © 2016 by the American Academy of Pediatrics.
Kelly L.,Arizona State University |
Runge J.,HonorHealth Scottsdale Shea Medical Center |
Spencer C.,Banner University Medical Center Phoenix
Journal of Nursing Scholarship | Year: 2015
Purpose: To examine compassion fatigue and compassion satisfaction in acute care nurses across multiple specialties in a hospital-based setting. Design: A cross-sectional electronic survey design was used to collect data from direct care nurses in a 700-bed, quaternary care, teaching facility in the southwestern United States. Methods: A total of 491 direct care registered nurses completed a survey measuring their professional quality of life (burnout, secondary traumatic stress, and compassion satisfaction). Analysis was conducted to assess for differences between demographics, specialties, job satisfaction, and intent to leave their current position. Findings: Significant predictors of burnout included lack of meaningful recognition, nurses with more years of experience, and nurses in the "Millennial" generation (ages 21-33 years). Receiving meaningful recognition, higher job satisfaction, nurses in the "Baby Boomer" generation (ages 50-65 years), and nurses with fewer years of experience significantly predicted compassion satisfaction. No significant differences were noted across nurse specialties, units, or departments. Conclusions: This study adds to the literature the impact meaningful recognition may have on compassion satisfaction and fatigue. Our findings provide a potential explanation for the lack of retention of nurses in the millennial generation who leave their positions with limited years of experience. Based on our research, meaningful recognition may increase compassion satisfaction, positively impact retention, and elevate job satisfaction. Clinical Relevance: Compassion fatigue in nurses has clear implications for nursing retention and the quality of care. Organizations willing to invest in reducing compassion fatigue have the potential to improve financial savings by reducing turnover and adverse events associated with burnout. © 2015 Sigma Theta Tau International.
PubMed | Clinical Translational Science Institute, University of Kansas Medical Center and Banner University Medical Center Phoenix
Type: | Journal: Liver international : official journal of the International Association for the Study of the Liver | Year: 2016
Hypoxic hepatitis is a clinical condition precipitated by prolonged periods of oxygen deprivation to the liver. It can have several underlying causes. Despite its prevalence in critically ill patients, which can reach upwards of 10%, very little is known about the mechanisms of injury. Thus, we set out to measure previously identified circulating biomarkers in an attempt to describe mechanisms of injury following hypoxic hepatitis.Plasma from patients diagnosed with hypoxic hepatitis was collected for this study. Biomarkers of hepatocellular injury, mitochondrial damage and cell death were measured. These results were compared against results obtained from well-characterized acetaminophen overdose patients.At peak injury, ALT measured 4082606U/L and gradually decreased over 5days, corresponding to the clinically observed pattern of hypoxic hepatitis. Levels of GDH showed a similar pattern, but neither ALT nor GDH were significantly higher in these patients than in acetaminophen patients. Plasma levels of DNA fragments mimicked hepatocellular injury as measured by ALT and miRNA-122. Interestingly, we found a significant increase in caspase-cleaved cytokeratin-18; however, the full-length form greatly exceeded the cleaved form at the time of maximum injury (4583712085 vs 25281074U/L). We also found an increase in acHMGB1 at later time points indicating a possible role of inflammation, but cytokine levels at these times were actually decreased relative to early time points.The mechanism of injury following hypoxic hepatitis involves mitochondrial damage and DNA fragmentation. Importantly, necrosis, rather than apoptosis, is the main mode of cell death.