Medicine and Health Sciences Commons^™

Measuring The Effects Of Thc On Human Sperm Parameters Using Biomonitoring Analysis, Roxana Amaya-Fuentes, Heather Young, Courtney Irwin, Jonathan Crites, David Moody, Melissa Perry

GW Research Days 2016 - 2020

Marijuana is one of the most common substances used in the United States with more men utilizing marijuana compared to women. The effects of marijuana on the brain are well known, however, there is limited research on its effects on human sperm parameters. We examined the association between THC and human sperm parameters in participants in the Washington D.C. area. Our preliminary results suggested that THC was associated with low sperm morphology.

Background: Marijuana has a long history of human usage for medicinal, ceremonial, and religious purposes. As of January 2018, nine states including Washington D.C. have legalized it for …

Pupillometric Assessment Of Small Doses Of Opioid In A Pediatric Population, David Strum, Elizabeth Malphrus, Kevin Jackson, Julia Finkel

GW Research Days 2016 - 2020

According to the CDC, opioid prescriptions in the United States have more than tripled from 1999-2014, which has correlated with the staggering increase in opioid-involved drug overdose deaths. This pattern of prescription is thought to be a major contributory factor to the increase in drug overdose in America, as four out of five new heroin users started by misusing prescription painkillers. Providers need the means to objectively monitor analgesic efficacy of treatment in patients with pain to mitigate unnecessary analgesic prescribing.

It is well established that mu opioid agonists like morphine cause miosis, an effect to which tolerance does not …

Acute Hepatic Failure And Oral Amiodarone, Hani Alhamoud, Sivateja Mandava, Talal Alzahrani

GW Research Days 2016 - 2020

Introduction:

Amiodarone is associated with serious complications such as lung toxicity, thyroid dysfunction, and QT-prolongation. Further, hepatic failure from the intravenous (IV) formulation of amiodarone is described in numerous case reports and case series. Although there are reports of elevated liver enzymes from the oral formulation of amiodarone, to our knowledge, none have definitively identified a case of acute hepatic failure from the oral formulation alone. In this case, we report an instance of acute hepatic failure after increasing the oral amiodarone dosage as well as rapid recovery following cessation of the medication.

Case report:

A 61-year-old male with a …

Onyx Use In Extracranial Pathologies - A Retrospective Case Review, Faezeh Razjouyan, Rishi Sood, Alex Cho, Anthony Venbrux, Shawn Sarin

GW Research Days 2016 - 2020

Purpose:

Onyx is an embolic agent currently FDA approved for neurointerventional procedures such as in the treatment of aneurysms and arteriovenous malformations. Despite its limited indications, the agent's off-label use in the treatment of extracranial pathologies continues to increase. To date, there has not been a single-center study demonstrating a large number of cases demonstrating safe and effective peripheral embolization with Onyx.

Materials:

We performed a retrospective review of all cases that used Onyx between October 2010 and July 2016 at a single tertiary care academic university urban hospital. Institutional review board approval was appropriately obtained. Initial case selection was …

Cost-Effectiveness Of Alternative Anticoagulation Strategies For Postoperative Management Of Total Knee Arthroplasty Patients, Savannah R. Smith, Jeffrey Katz, Elena Losina

GW Research Days 2016 - 2020

Background: Anticoagulation is essential for deep vein thrombosis (DVT) and pulmonary embolism (PE) prevention following total knee arthroplasty (TKA). Some research has suggested that longer duration anticoagulation can substantially reduce the risks of DVT and PE; however, in the absence of definitive recommendations, physicians are left weighing the risks of DVT and PE against those of anticoagulation, including gastrointestinal (GI) and central nervous system (CNS) hemorrhage and increased likelihood of prosthetic joint infection (PJI). We conducted a cost-effectiveness analysis to evaluate the benefits and risks of 14- and 35-day therapy with the most commonly prescribed anticoagulants post-TKA.

Background: Anticoagulation is …

Sptransformer Proteins From The Purple Sea Urchin Opsonize Bacteria, Augment Phagocytosis, And Retard Bacterial Growth, H. Y. Chou, C. Lun, L. C. Smith

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The purple sea urchin, Strongylocentrotus purpuratus, has a complex and robust immune system that is mediated by a number of multi-gene families including the SpTransformer (SpTrf) gene family (formerly Sp185/333). In response to immune challenge from bacteria and various pathogen-associated molecular patterns, the SpTrf genes are up-regulated in sea urchin phagocytes and express a diverse array of SpTrf proteins. We show here that SpTrf proteins from coelomocytes and isolated by nickel affinity (cNi-SpTrf) bind to Gram-positive and Gram-negative bacteria and to Baker’s yeast, Saccharomyces cerevisiae, with saturable kinetics and specificity. cNi-SpTrf opsonization of the marine bacteria, Vibrio diazotrophicus, augments phagocytosis, …

Effects Of Clinical Pathway Implementation On Antibiotic Prescriptions For Pediatric Community-Acquired Pneumonia., Daniele Donà, Silvia Zingarella, Andrea Gastaldi, Rebecca Lundin, Giorgio Perilongo, Anna Chiara Frigo, Rana F Hamdy, Theoklis Zaoutis, Liviana Da Dalt, Carlo Giaquinto

Pediatrics Faculty Publications

BACKGROUND: Italian pediatric antimicrobial prescription rates are among the highest in Europe. As a first step in an Antimicrobial Stewardship Program, we implemented a Clinical Pathway (CP) for Community Acquired Pneumonia with the aim of decreasing overall prescription of antibiotics, especially broad-spectrum.

MATERIALS AND METHODS: The CP was implemented on 10/01/2015. We collected antibiotic prescribing and outcomes data from children aged 3 months-15 years diagnosed with CAP from 10/15/2014 to 04/15/2015 (pre-intervention period) and from 10/15/2015 to 04/15/2016 (post-intervention period). We assessed antibiotic prescription differences pre- and post-CP, including rates, breadth of spectrum, and duration of therapy. We also compared …

Internal Medicine Resident Perspectives Regarding Broad-Spectrum Antibiotic Usage., Ann M Laake, Gayle Bernabe, James Peterson, Angelike P Liappis

Medicine Faculty Publications

Focus groups held with internal medicine residents discussed their perspectives regarding broad-spectrum antibiotic (BSA) usage. Residents knew of BSA-associated adverse events, but they did not associate such events with increased patient morbidity and mortality, and they were more likely to use BSA in situations with diagnostic uncertainty and sick patients.

Effect Of Immediate Initiation Of Antiretroviral Therapy On Risk Of Severe Bacterial Infections In Hiv-Positive People With Cd4 Cell Counts Of More Than 500 Cells Per Μl: Secondary Outcome Results From A Randomised Controlled Trial., Jemma O'Connor, Michael J Vjecha, Andrew N Phillips, Brian Angus, David Cooper, Fred Gordin, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.

METHODS: The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells …

Mitochondria Mediate Cell Membrane Repair And Contribute To Duchenne Muscular Dystrophy., Maria C Vila, Sree Rayavarapu, Marshall W Hogarth, Jack H Van Der Meulen, Adam Horn, Aurelia Defour, Shin'ichi Takeda, Kristy J. Brown, Yetrib Hathout, Kanneboyina Nagaraju, Jyoti K. Jaiswal

Genomics and Precision Medicine Faculty Publications

Dystrophin deficiency is the genetic basis for Duchenne muscular dystrophy (DMD), but the cellular basis of progressive myofiber death in DMD is not fully understood. Using two dystrophin-deficient mdx mouse models, we find that the mitochondrial dysfunction is among the earliest cellular deficits of mdx muscles. Mitochondria in dystrophic myofibers also respond poorly to sarcolemmal injury. These mitochondrial deficits reduce the ability of dystrophic muscle cell membranes to repair and are associated with a compensatory increase in dysferlin-mediated membrane repair proteins. Dysferlin deficit in mdx mice further compromises myofiber cell membrane repair and enhances the muscle pathology at an asymptomatic …

Unmasking Of Myoclonus By Lacosamide In Generalized Epilepsy, Daniel Birnbaum, Mohamad Z. Koubeissi

Neurology Faculty Publications

Lacosamide is a new-generation antiseizure medication that is approved for use as an adjunctive treatment and monotherapy in focal epilepsy. Its use in generalized epilepsy, however, has not been adequately evaluated in controlled trials. We report a 67-year-old woman who experienced new-onset myoclonic seizures after initiation of lacosamide. We presume that she had an undiagnosed generalized epilepsy syndrome, likely juvenile myoclonic epilepsy. Myoclonic seizures were not reported before introducing lacosamide and completely resolved after lacosamide was discontinued. This suggests that lacosamide may have the potential to worsen myoclonus, similar to what has been reported with another sodium channel agent, lamotrigine, …

Using Diagnostic Tests To Inform Better Care, Save Lives And Fight Antibiotic Resistance: A Factsheet For Healthcare Professionals, Antibiotic Resistance Action Center (Arac)

Antibiotic Resistance Action Center (ARAC)

No abstract provided.

Antibiotic Resistance And Diagnostic Tests: What You Need To Know, Antibiotic Resistance Action Center (Arac)

Antibiotic Resistance Action Center (ARAC)

No abstract provided.

Unleashing The Power Of Diagnostic Tests In The Fight Against Antibiotic Resistance, Antibiotic Resistance Action Center (Arac)

Antibiotic Resistance Action Center (ARAC)

No abstract provided.

Risk Of Gastrointestinal Bleeding Among Dabigatran Users – A Self Controlled Case Series Analysis, Wenze Tang, Hsien-Yen Chang, Meijia Zhou, Sonal Singh

Epidemiology Faculty Publications

This article aims to evaluate the real world risk of gastrointestinal bleeding among users naïve to dabigatran. We adopted a self-controlled case series design. We sampled 1215 eligible adult participants who were continuous insured users between July 1, 2010 and March 31, 2012 with use of dabigatran and at least one gastrointestinal bleeding episode. We used a conditional Poisson regression to estimate incidence rate ratios. The population consisted of 64.69% of male and 60.25% patients equal to or greater than age 65 at start of observation. After adjustment for time-variant confounders, the incidence rate of gastrointestinal bleeding was similar during …

Combating Antibiotic Resistance: A Policy Roadmap To Reduce Use Of Medically Important Antibiotics In Livestock, Expert Commission On Addressing The Contribution Of Livestock To The Antibiotic Resistance Crisis 2017

Antibiotic Resistance Action Center (ARAC)

No abstract provided.

Use Of A Modified Greenscreen Tool To Conduct A Screening-Level Comparative Hazard Assessment Of Conventional Silver And Two Forms Of Nanosilver., Jennifer Sass, Lauren Heine, Nina Hwang

Environmental and Occupational Health Faculty Publications

BACKGROUND: Increased concern for potential health and environmental impacts of chemicals, including nanomaterials, in consumer products is driving demand for greater transparency regarding potential risks. Chemical hazard assessment is a powerful tool to inform product design, development and procurement and has been integrated into alternative assessment frameworks. The extent to which assessment methods originally designed for conventionally-sized materials can be used for nanomaterials, which have size-dependent physical and chemical properties, have not been well established. We contracted with a certified GreenScreen profiler to conduct three GreenScreen hazard assessments, for conventional silver and two forms of nanosilver. The contractor summarized publicly …

Expanding The Phenotype Associated With Naa10-Related N-Terminal Acetylation Deficiency., Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas Ahmew, +Several Additional Authors

Pediatrics Faculty Publications

N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ …

Beer Potomania: A Challenging Case Of Hyponatremia, Hind Rafei, Raza Yunus, Parvinder S. Khurana

Medicine Faculty Publications

Beer potomania is a syndrome of hyponatremia associated with excessive beer drinking. Little or no salt content of beer results in marked reduction in the solute load to the kidney. This leads to impaired water clearance and dilutional hyponatremia. A 66-year-old man with history of alcoholism and alcoholic cardiomyopathy presented to the emergency room with tremors of his upper and lower extremities. He had a significant history of alcohol consumption, usually drinking 4 - 5 cans of beer per night for the past 34 years. In addition, he had consumed a fifth of a vodka bottle the day before presentation. …

Neonatal Pain Management: Still In Search For The Holy Grail., Karel Allegaert, John N. Van Den Anker

Pediatrics Faculty Publications

Inadequate pain management but also inappropriate use of analgesics in early infancy has negative effects on neurodevelopmental outcome. As a consequence, neonatal pain management is still in search for the Holy Grail. At best, effective pain management is based on prevention, assessment, and treatment followed by a re-assessment of the pain to determine if additional treatment is still necessary. Unfortunately, epidemiological observations suggest that neonates are undergoing painful procedures very frequently, unveiling the need for effective preventive, non-pharmacological strategies. In addition, assessment is still based on validated, multimodal, but subjective pain assessment tools. Finally, in neonatal intensive care units, there …

Fbxo30 Regulates Mammopoiesis By Targeting The Bipolar Mitotic Kinesin Eg5., Yan Liu, Yin Wang, Zhanwen Du, Xiaoli Yan, Pan Zheng, Yang Liu

Pediatrics Faculty Publications

Fbxo30 is an orphan member of the F-box protein family with no known substrate or function. Here we report that, while Fbxo30^−/− mice exhibit normal development, growth, lifespan, and fertility, the females fail to nurture their offspring as a result of defective mammopoiesis. Mass spectrometry analysis of Fbxo30-associated proteins revealed that Fbxo30 specifically interacts with the bipolar spindle kinesin EG5 (encoded byKif11). As a result, Fbxo30 targets Eg5 for ubiquitinylation and controls its oscillation during the cell cycle. Correlated with EG5 dysregulation, Fbxo30^−/− mammary epithelial cells exhibit multiple defects in centrosome homeostasis, mitotic spindle …

Add-On Laba In A Separate Inhaler As Asthma Step-Up Therapy Versus Increased Dose Of Ics Or Ics/Laba Combination Inhaler., David B Price, Gene Colice, Elliot Israel, Nicolas Roche, Dirkje S Postma, Theresa W Guilbert, Willem M C Van Aalderen, Jonathan Grigg, Elizabeth V Hillyer, Victoria Thomas, Richard J Martin

Medicine Faculty Publications

Asthma management guidelines recommend adding a long-acting β2-agonist (LABA) or increasing the dose of inhaled corticosteroid (ICS) as step-up therapy for patients with uncontrolled asthma on ICS monotherapy. However, it is uncertain which option works best, which ICS particle size is most effective, and whether LABA should be administered by separate or combination inhalers. This historical, matched cohort study compared asthma-related outcomes for patients (aged 12-80 years) prescribed step-up therapy as a ≥50% extrafine ICS dose increase or add-on LABA, via either a separate inhaler or a fine-particle ICS/LABA fixed-dose combination (FDC) inhaler. Risk-domain asthma control was the primary end-point …

Is Androgen Excess Masked In Alopecia Areata Patients: A Retrospective Data Analysis Of 1,587 Patients, G. Cheyana Ranasinghe, Melissa Piliang, Wilma Bergfeld

GW Research Days 2016 - 2020

Studies on the pathophysiology and comorbidities associated with alopecia areata (AA) are limited. The purpose of this study was to determine the prevalence of androgen excess in AA and its subtypes, in relation to demographics and comorbidities. Medical records of 1,587 Patchy AA, AT, AU, and ophiasis patients seen in the Department of Dermatology at the Cleveland Clinic Foundation in Ohio between 2005 and 2015 were reviewed. Out of this cohort, 226 patients met the inclusion criteria. There is evidence that patients with AA had significantly greater prevalence of polycystic ovary syndrome (PCOS) than the general population (p<0.001). Androgen excess was identified in 42.5% (n=96) of the 226 patients with AA or any subtype (p<0.001). The androgen excess group was significantly more likely to present with irregular menses, hirsutism, adult acne, PCOS, and/or ovarian cysts (p<0.001). This study was limited by being retrospective. Our study demonstrated that AA is associated with androgen excess.

Perioperative Aspirin Recommendations In Children With Fenestrated Fontan Undergoing Adenotonsillectomy, Mariam Ashraf, Pamela A. Mudd, Jamie Mcelrath Schwartz, Karen Thompson

GW Research Days 2016 - 2020

Objective: Pediatric patients who have undergone the Fontan procedure are often on a long term aspirin regimen which can complicate perioperative management. In high risk procedures such as adenotonsillectomy, hemorrhage can be a significant complication and aspirin use may increase the risk. There is a need for evidence-based protocol on how to manage aspirin intake in the perioperative period for Fontan patients. We report the case of a patient with Fontan palliation who underwent adenotonsillectomy and presented with postoperative hemorrhage.

Methods: PubMed was searched for guidelines, case reports, and reviews on pediatric Fontan patients, adenotonsillectomy, and perioperative aspirin …

Different Vancomycin Immunoassays Contribute To The Variability In Vancomycin Trough Measurements In Neonates, Janko Samardzic, Anne Smits, Isabel Spriet, Ivan Soldatovic, Andrew Atkinson, Milica Bajcetic, John N. Van Den Anker, Karel Allegaert

Pediatrics Faculty Publications

Substantial interassay variability (up to 20%) has been described for vancomycin immunoassays in adults, but the impact of neonatal matrix is difficult to quantify because of blood volume constraints in neonates. However, we provide circumstantial evidence for a similar extent of variability. Using the same vancomycin dosing regimens and confirming similarity in clinical characteristics, vancomycin trough concentrations measured by PETINIA (2011-2012, n = 400) were 20% lower and the mean difference was 1.93 mg/L compared to COBAS (2012–2014, n =352 ) measurements. The impact of vancomycin immunoassays in neonatal matrix was hereby suggested, supporting a switch to more advanced techniques …

Comparison Of Drug Delivery With Autoinjector Versus Manual Prefilled Syringe And Between Three Different Autoinjector Devices Administered In Pig Thigh, Robert Hill, John Wilmot, Beth Belluscio, Kevin Cleary, David Lindisch, Robin Tucker, Emmanuel Wilson, Rajesh Shukla

Radiology Faculty Publications

Parenteral routes of drug administration are often selected to optimize actual dose of drug delivered, assure high bioavailability, bypass first-pass metabolism or harsh gastrointestinal environments, as well as maximize the speed of onset. Intramuscular (IM) delivery can be preferred to intravenous delivery when initiating intravenous access is difficult or impossible. Drugs can be injected intramuscularly using a syringe or an automated delivery device (autoinjector). Investigation into the IM delivery dynamics of these methods may guide further improvements in the performance of injection technologies. Two porcine model studies were conducted to compare differences in dispersion of injectate volume for different methods …

Micrornas Are Involved In The Development Of Morphine-Induced Analgesic Tolerance And Regulate Functionally Relevant Changes In Serpini1., Jenica D. Tapocik, Kristin Ceniccola, Cheryl L. Mayo, Melanie L. Schwandt, Matthew Solomon, Bi-Dar Wang, Truong V. Luu, Jacqueline Olender, Thomas Harrigan, Thomas M. Maynard, Greg I. Elmer, Norman H. Lee

Pharmacology and Physiology Faculty Publications

Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The …

Treatment Of Men For “Low Testosterone”: A Systematic Review, Samantha Huo, Anthony R. Scialli, Sean Mcgarvey, Elizabeth Hill, Buğra Tügertimur, Alycia Hogenmiller, Alessandra I. Hirsch, Adriane Fugh-Berman

Pharmacology and Physiology Faculty Publications

Testosterone products are recommended by some prescribers in response to a diagnosis or presumption of “low testosterone” (low-T) for cardiovascular health, sexual function, muscle weakness or wasting, mood and behavior, and cognition. We performed a systematic review of 156 eligible randomized controlled trials in which testosterone was compared to placebo for one or more of these conditions. We included studies in bibliographic databases between January 1, 1950 and April 9, 2016, and excluded studies involving bodybuilding, contraceptive effectiveness, or treatment of any condition in women or children. Studies with multiple relevant endpoints were included in all relevant tables. Testosterone supplementation …

A Single Center Observational Study On Emergency Department Clinician Non-Adherence To Clinical Practice Guidelines For Treatment Of Uncomplicated Urinary Tract Infections, Catherine Zatorski, Mark Zocchi, Sara Cosgrove, Cynthia Rand, Gillian Brooks, Larissa May

Emergency Medicine Faculty Publications

Background

The Emergency Department (ED) is a frequent site of antibiotic use; poor adherence with evidence-based guidelines and broad-spectrum antibiotic overuse is common. Our objective was to determine rates and predictors of inappropriate antimicrobial use in patients with uncomplicated urinary tract infections (UTI) compared to the 2010 International Clinical Practice Guidelines (ICPG).

Methods

A single center, prospective, observational study of patients with uncomplicated UTI presenting to an urban ED between September 2012 and February 2014 that examined ED physician adherence to ICPG when treating uncomplicated UTIs. Clinician-directed antibiotic treatment was compared to the ICPG using a standardized case definition for …

Biosimilars: Potential Implications For Clinicians, Misty G. Eleryan, Sophia Akhiyat, Monica Rengifo-Pardo, Alison Ehrlich

Dermatology Faculty Publications

With the expiration of patent protection for several biologics looming, the production of highly similar therapeutic agents has begun to emerge on the pharmaceutical market. These alternative drugs are referred to as biosimilars. Many anticipate that the introduction of these agents will result in a reduction in health care costs, which may create a more affordable biopharmaceutical market and also improve patient access. In contrast to generics, which are exact copies of their original products, biosimilars are not identical to their reference products. Due to concern about the safety and efficacy of biosimilars, separate regulatory approval pathways have been developed …