Copyright © 2017, Elsevier Inc. All rights reserved.

Diseases of the Lower Respiratory Tract
Chronic obstructive pulmonary disease (COPD) Asthma (persistent and present most of the time despite treatment) Emphysema Chronic bronchitis Copyright © 2017, Elsevier Inc. All rights reserved.

Bronchial Asthma Recurrent and reversible shortness of breath Occurs when the airways of the lungs become narrow as a result of: Bronchospasms Inflammation of the bronchial mucosa Edema of the bronchial mucosa Production of viscous mucus Copyright © 2017, Elsevier Inc. All rights reserved.

Bronchial Asthma (Cont.)
The alveolar ducts and alveoli remain open, but airflow to them is obstructed. Symptoms Wheezing Difficulty breathing Copyright © 2017, Elsevier Inc. All rights reserved.

Asthma Four categories Intrinsic (occurring in patients with no history of allergies) Extrinsic (occurring in patients exposed to a known allergen) Exercise induced Drug induced Copyright © 2017, Elsevier Inc. All rights reserved.

Asthma (Cont.) Status asthmaticus Prolonged asthma attack that does not respond to typical drug therapy May last several minutes to hours Medical emergency Copyright © 2017, Elsevier Inc. All rights reserved.

Chronic Bronchitis Continuous inflammation and low-grade infection of the bronchi Excessive secretion of mucus and certain pathologic changes in the bronchial structure Often occurs as a result of prolonged exposure to bronchial irritants Copyright © 2017, Elsevier Inc. All rights reserved.

Emphysema Air spaces enlarge as a result of the destruction of alveolar walls. Caused by the effect of proteolytic enzymes released from leukocytes in response to alveolar inflammation The surface area where gas exchange takes place is reduced. Effective respiration is impaired. Copyright © 2017, Elsevier Inc. All rights reserved.

Pharmacologic Overview
Bronchodilators These drugs relax bronchial smooth muscle, which causes dilation of the bronchi and bronchioles that are narrowed as a result of the disease process. Three classes: beta-adrenergic agonists, anticholinergics, and xanthine derivatives Copyright © 2017, Elsevier Inc. All rights reserved.

Bronchodilators: Beta-Adrenergic Agonists
Short-acting beta agonist (SABA) inhalers albuterol (Ventolin) levalbuterol (Xopenex) pirbuterol (Maxair) terbutaline (Brethine) metaproterenol (Alupent) Long-acting beta agonist (LABA) inhalers arformoterol (Brovana) formoterol (Foradil, Perforomist) salmeterol (Serevent) Copyright © 2017, Elsevier Inc. All rights reserved.

Bronchodilators: Beta-Adrenergic Agonists: Newest LABA
LABA inhalers (Cont.) indacterol (Arcapta Neohaler) vilanterol in conjunction with fluticasone (Breo Ellipta) vilanterol in conjunction with the anticholinergic, umeclidinium (Anoro Ellipta) The term Ellipta refers to a new delivery system. Copyright © 2017, Elsevier Inc. All rights reserved.

Bronchodilators: Beta-Adrenergic Agonists (Cont.)
Used during acute phase of asthmatic attacks Quickly reduce airway constriction and restore normal airflow Agonists, or stimulators, of the adrenergic receptors in the sympathetic nervous system Sympathomimetics Copyright © 2017, Elsevier Inc. All rights reserved.

Three types Nonselective adrenergics Stimulate alpha, beta1 (cardiac), and beta2 (respiratory) receptors Example: epinephrine (EpiPen) Nonselective beta-adrenergics Stimulate both beta1 and beta2 receptors Example: metaproterenol Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Mechanism of Action
Begins at the specific receptor stimulated Ends with dilation of the airways Activation of beta2 receptors activates cyclic adenosine monophosphate (cAMP), which relaxes smooth muscle in the airway and results in bronchial dilation and increased airflow. Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Indications
Relief of bronchospasm related to asthma, bronchitis, and other pulmonary diseases Used in treatment and prevention of acute attacks Used in hypotension and shock Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Contraindications
Known drug allergy Uncontrolled hypertension Cardiac dysrhythmias High risk of stroke (because of the vasoconstrictive drug action) Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Adverse Effects
Alpha and beta (epinephrine) Insomnia Restlessness Anorexia Vascular headache Hyperglycemia Tremor Cardiac stimulation Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Adverse Effects (Cont.)
Beta1 and beta2 (metaproterenol) Cardiac stimulation Tremor Anginal pain Vascular headache Hypotension Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Adverse Effects (Cont.)
Beta2 (albuterol) Hypotension or hypertension Vascular headache Tremor Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Interactions
Diminished bronchodilation when nonselective beta blockers are used with the beta agonist bronchodilators Monoamine oxidase inhibitors Sympathomimetics Monitor patients with diabetes; an increase in blood glucose levels can occur. Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Albuterol (Proventil)
Short-acting beta2-specific bronchodilating beta agonist Most commonly used drug in this class Must not be used too frequently Oral and inhalational use Inhalational dosage forms include metered-dose inhalers (MDIs) as well as solutions for inhalation. Copyright © 2017, Elsevier Inc. All rights reserved.

Beta-Adrenergic Agonists: Salmeterol (Serevent)
Long-acting beta2 agonist bronchodilator Never to be used for acute treatment Used for the maintenance treatment of asthma and COPD and is used in conjunction with an inhaled corticosteroid Salmeterol should never be given more than twice daily nor should the maximum daily dose (one puff twice daily) be exceeded. Copyright © 2017, Elsevier Inc. All rights reserved.

Anticholinergics: Mechanism of Action
Acetylcholine (ACh) causes bronchial constriction and narrowing of the airways. Anticholinergics bind to the ACh receptors, preventing ACh from binding. Result: bronchoconstriction is prevented, airways dilate Copyright © 2017, Elsevier Inc. All rights reserved.

Anticholinergics (Cont.)
Ipratropium (Atrovent), tiotropium (Spiriva), and aclidinium (Tudorza) Indirectly cause airway relaxation and dilation Help reduce secretions in COPD patients Indications: prevention of the bronchospasm associated with chronic bronchitis or emphysema; not for the management of acute symptoms Copyright © 2017, Elsevier Inc. All rights reserved.

Anticholinergics: Adverse Effects
Dry mouth or throat Nasal congestion Heart palpitations Gastrointestinal (GI) distress Headache Coughing Anxiety Copyright © 2017, Elsevier Inc. All rights reserved.

Anticholinergics: Ipratropium (Atrovent)
Oldest and most commonly used anticholinergic bronchodilator Available both as a liquid aerosol for inhalation and as a multidose inhaler Usually dosed twice daily Copyright © 2017, Elsevier Inc. All rights reserved.

Xanthine Derivatives Plant alkaloids: caffeine, theobromine, and theophylline Only theophylline is used as a bronchodilator Synthetic xanthines: aminophylline and dyphilline Copyright © 2017, Elsevier Inc. All rights reserved.

Xanthine Derivatives: Mechanism of Action
Increase levels of energy-producing cAMP This is done by competitively inhibiting phosphodiesterase, the enzyme that breaks down cAMP. Result: decreased cAMP levels, smooth muscle relaxation, bronchodilation, and increased airflow Copyright © 2017, Elsevier Inc. All rights reserved.

Xanthine Derivatives: Drug Effects
Cause bronchodilation by relaxing smooth muscle in the airways Result: relief of bronchospasm and greater airflow into and out of the lungs Also cause central nervous system (CNS) stimulation Copyright © 2017, Elsevier Inc. All rights reserved.

Xanthine Derivatives: Drug Effects (Cont.)
Also cause cardiovascular stimulation: increased force of contraction and increased heart rate, resulting in increased cardiac output and increased blood flow to the kidneys (diuretic effect) Copyright © 2017, Elsevier Inc. All rights reserved.

Xanthine Derivatives: Indications
Dilation of airways in asthmas, chronic bronchitis, and emphysema Mild to moderate cases of acute asthma NOT for management of acute asthma attack Adjunct drug in the management of COPD Not used as frequently because of potential for drug interactions and variables related to drug levels in the blood Copyright © 2017, Elsevier Inc. All rights reserved.

Xanthine Derivatives: Adverse Effects
Nausea, vomiting, anorexia Gastroesophageal reflux during sleep Sinus tachycardia, extrasystole, palpitations, ventricular dysrhythmias Transient increased urination Hyperglycemia Copyright © 2017, Elsevier Inc. All rights reserved.

Xanthine Derivatives: Caffeine
Used without prescription as a CNS stimulant or analeptic to promote alertness (e.g., for long-duration driving or studying) Cardiac stimulant in infants with bradycardia Enhancement of respiratory drive in infants Copyright © 2017, Elsevier Inc. All rights reserved.

Xanthine Derivatives: Theophylline
Most commonly used xanthine derivative Oral, rectal, injectable (as aminophylline), and topical dosage forms Aminophylline: intravenous (IV) treatment of patients with status asthmaticus who have not responded to fast-acting beta agonists such as epinephrine Therapeutic range for theophylline blood level is 10 to 20 mcg/mL Most clinicians now advise levels between 5 and 15 mcg/mL. Copyright © 2017, Elsevier Inc. All rights reserved.

Nonbronchodilating Respiratory Drugs
Leukotriene receptor antagonists (montelukast, zafirlukast, and zileuton) Corticosteroids (beclomethasone, budesonide, dexamethasone, flunisolide, fluticasone, ciclesonide, and triamcinolone) Mast cell stabilizers: rarely used cromolyn and nedocromil, which are sometimes used for exercise-induced asthma Copyright © 2017, Elsevier Inc. All rights reserved.

Leukotriene Receptor Antagonists (LTRAs)
Nonbronchodilating Newer class of asthma medications Currently available drugs montelukast (Singulair) zafirlukast (Accolate) zileuton (Zyflo) Copyright © 2017, Elsevier Inc. All rights reserved.

LTRAs: Mechanism of Action
Leukotrienes are substances released when a trigger, such as cat hair or dust, starts a series of chemical reactions in the body. Leukotrienes cause inflammation, bronchoconstriction, and mucus production. Result: coughing, wheezing, shortness of breath Copyright © 2017, Elsevier Inc. All rights reserved.

LTRAs: Mechanism of Action (Cont.)
LTRAs prevent leukotrienes from attaching to receptors on cells in the lungs and in circulation. Inflammation in the lungs is blocked, and asthma symptoms are relieved. Copyright © 2017, Elsevier Inc. All rights reserved.

LTRAs: Drug Effects By blocking leukotrienes: Prevent smooth muscle contraction of the bronchial airways Decrease mucus secretion Prevent vascular permeability Decrease neutrophil and leukocyte infiltration to the lungs, preventing inflammation Copyright © 2017, Elsevier Inc. All rights reserved.

LTRAs: Indications Prophylaxis and long-term treatment and prevention of asthma in adults and children 12 years of age and older NOT meant for management of acute asthmatic attacks Montelukast is also approved for treatment of allergic rhinitis Improvement with their use is typically seen in about 1 week Copyright © 2017, Elsevier Inc. All rights reserved.

LTRAs: Contraindications
Known drug allergy Previous adverse drug reaction Allergy to povidone, lactose, titanium dioxide, or cellulose derivatives is also important to note because these are inactive ingredients in these drugs Copyright © 2017, Elsevier Inc. All rights reserved.

LTRAs: Adverse Effects
zileuton Headache, nausea, dizziness, insomnia zafirlukast and montelukast Headache, nausea, diarrhea Copyright © 2017, Elsevier Inc. All rights reserved.

Corticosteroids (Glucocorticoids)
Antiinflammatory properties Used for chronic asthma Do not relieve symptoms of acute asthma attacks May be administered IV Oral or inhaled forms Inhaled forms reduce systemic effects May take several weeks before full effects are seen Copyright © 2017, Elsevier Inc. All rights reserved.

Corticosteroids: Mechanism of Action
Stabilize membranes of cells that release harmful bronchoconstricting substances These cells are called leukocytes, or white blood cells. Increase responsiveness of bronchial smooth muscle to beta-adrenergic stimulation Dual effect of both reducing inflammation and enhancing the activity of beta agonists Copyright © 2017, Elsevier Inc. All rights reserved.

Corticosteroids: Mechanism of Action (Cont.)
Corticosteroids have also been shown to restore or increase the responsiveness of bronchial smooth muscle to beta-adrenergic receptor stimulation, which results in more pronounced stimulation of the beta2 receptors by beta agonist drugs such as albuterol. Copyright © 2017, Elsevier Inc. All rights reserved.

Inhaled Corticosteroids
beclomethasone dipropionate (Beclovent) budesonide (Pulmicort Turbuhaler) dexamethasone sodium phosphate (Decadron Phosphate Respihaler) flunisolide (AeroBid) fluticasone (Flovent) triamcinolone acetonide (Azmacort) ciclesonide (Omnaris) Copyright © 2017, Elsevier Inc. All rights reserved.

Inhaled Corticosteroids: Indications
Primary treatment of bronchospastic disorders to control the inflammatory responses that are believed to be the cause of these disorders Persistent asthma Often used concurrently with the beta-adrenergic agonists Systemic corticosteroids are generally used only to treat acute exacerbations, or severe asthma IV corticosteroids: acute exacerbation of asthma or other COPD Copyright © 2017, Elsevier Inc. All rights reserved.

Inhaled Corticosteroids: Contraindications
Drug allergy Not intended as sole therapy for acute asthma attacks Hypersensitivity to glucocorticoids Patients whose sputum tests positive for Candida organisms Patients with systemic fungal infection Copyright © 2017, Elsevier Inc. All rights reserved.

Inhaled Corticosteroids: Adverse Effects
Pharyngeal irritation Coughing Dry mouth Oral fungal infections Systemic effects are rare because low doses are used for inhalation therapy. Copyright © 2017, Elsevier Inc. All rights reserved.

Inhaled Corticosteroids: Drug Interactions
Drug interactions are more likely to occur with systemic (versus inhaled) corticosteroids. May increase serum glucose levels, possibly requiring adjustments in dosages of antidiabetic drugs Cyclosporine and tacrolimus Itraconazole Phenytoin, phenobarbital, and rifampin Copyright © 2017, Elsevier Inc. All rights reserved.

Phosphodiesterase-4 Inhibitor
roflumilast (Daliresp) Indicated to prevent coughing and excess mucus from worsening and to decrease the frequency of life-threatening COPD exacerbations Adverse effects include nausea, diarrhea, headache, insomnia, dizziness, weight loss, and psychiatric symptoms. Copyright © 2017, Elsevier Inc. All rights reserved.

Monoclonal Antibody Antiasthmatic
omalizumab (Xolair) Selectively binds to the immunoglobulin E, which in turn limits the release of mediators of the allergic response Omalizumab is given by injection Potential for producing anaphylaxis Monitor closely for hypersensitivity reactions. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications Encourage patients to take measures that promote a generally good state of health so as to prevent, relieve, or decrease symptoms of COPD. Avoid exposure to conditions that precipitate bronchospasm (allergens, smoking, stress, air pollutants). Adequate fluid intake Compliance with medical treatment Avoid excessive fatigue, heat, extremes in temperature, and caffeine. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications (Cont.)
Encourage patients to get prompt treatment for flu or other illnesses and to get vaccinated against pneumonia or flu. Encourage patients to always check with their physicians before taking any other medication, including over-the-counter (OTC) medications. Copyright © 2017, Elsevier Inc. All rights reserved.

Perform a thorough assessment before beginning therapy, including: Skin color Baseline vital signs Respirations (should be between 12 and 24 breaths/min) Respiratory assessment, including pulse oximetry Sputum production Allergies History of respiratory problems Other medications Copyright © 2017, Elsevier Inc. All rights reserved.

Teach patients to take bronchodilators exactly as prescribed. Ensure that patients know how to use inhalers and MDIs and have patients demonstrate use of the devices. Monitor for adverse effects. Copyright © 2017, Elsevier Inc. All rights reserved.

Audience Response System Question
Which medication will the nurse teach a patient with asthma to use when experiencing an acute asthma attack? albuterol (Ventolin) salmeterol (Serevent) theophylline (Theo-Dur) montelukast (Singulair) Correct answer: A Rationale: Albuterol (Ventolin) is a SABA. Patients must be taught to use the SABAs as rescue treatment. Salmeterol (Serevent) is a long-acting bronchodilator. Because the LABAs have a longer onset of action, they must never be used for acute treatment . Because of their relatively slow onset of action, xanthines such as theophylline (Theo-Dur) are more often used for the prevention of asthmatic symptoms than for the relief of acute asthma attacks. Montelukast (Singulair) is an LTRA and is used primarily for oral prophylaxis and long-term treatment of asthma. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Monitor for therapeutic effects: Decreased dyspnea Decreased wheezing, restlessness, and anxiety Improved respiratory patterns with return to normal rate and quality Improved activity tolerance Decreased symptoms and increased ease of breathing Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications: Beta-Adrenergic Agonists
Albuterol, if used too frequently, loses its beta2-specific actions at larger doses. As a result, beta1 receptors are stimulated, causing nausea, increased anxiety, palpitations, tremors, and increased heart rate. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications: Beta-Adrenergic Agonists (Cont.)
Ensure that patients take medications exactly as prescribed, with no omissions or double doses. Inform patients to report insomnia, jitteriness, restlessness, palpitations, chest pain, or any change in symptoms. Copyright © 2017, Elsevier Inc. All rights reserved.

A patient with chronic bronchitis calls the office for a refill of his albuterol inhaler. He just had the prescription filled 2 weeks ago, but he says it is empty. When asked, he tells the nurse, “I use it whenever I need it, but now when I use it, I feel so sick. I’ve been needing to use it more often.” What is the most appropriate action by the nurse? The nurse should confirm the pharmacy location for the needed refill. The nurse should ask the patient to come to the office for an evaluation of his respiratory status. The nurse should tell the patient not to use this drug too often. The nurse should consult the prescriber for a different inhaler prescription. Correct answer: B Rationale: Although it is true that the patient should be reminded about the correct use of this inhaler, it is evident that he has used it too often and that his respiratory status should be evaluated to see if an adjustment in the prescription should be made. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Nursing Implications: Xanthine Derivatives
Contraindications: history of PUD or GI disorders Cautious use: cardiac disease Timed-release preparations should not be crushed or chewed (cause gastric irritation). Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications: Xanthine Derivatives (Cont.)
Be aware of drug interactions with cimetidine, oral contraceptives, allopurinol, certain antibiotics, influenza vaccine, and others. Cigarette smoking enhances xanthine metabolism. Interacting foods include charcoal-broiled, high-protein, and low-carbohydrate foods. These foods may reduce serum levels of xanthines through various metabolic mechanisms. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications: LTRAs
Ensure that the drug is being used for chronic management of asthma, not acute asthma. Teach the patient the purpose of the therapy. Improvement should be seen in about 1 week. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications: LTRAs (Cont.)
Advise patients to check with prescriber before taking OTC or prescribed medications to determine drug interactions. Assess liver function before beginning therapy and throughout. Teach patients to take medications every night on a continuous schedule even if symptoms improve. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications: Inhaled Corticosteroids
Teach patients to gargle and rinse the mouth with lukewarm water afterward to prevent the development of oral fungal infections. If a beta-agonist bronchodilator and corticosteroid inhaler are both ordered, the bronchodilator should be used several minutes before the corticosteroid to provide bronchodilation before administration of the corticosteroid. Copyright © 2017, Elsevier Inc. All rights reserved.

Nursing Implications: Inhaled Corticosteroids (Cont.)
Teach patients to monitor disease with a peak flow meter. Encourage use of a spacer device to ensure successful inhalations. Teach patient how to keep inhalers and nebulizer equipment clean after use. Copyright © 2017, Elsevier Inc. All rights reserved.

Inhalers: Patient Education
For any inhaler prescribed, ensure that the patient is able to self-administer the medication. Provide demonstration and return demonstration. Ensure that the patient knows the correct time intervals for inhalers. Provide a spacer if the patient has difficulty coordinating breathing with inhaler activation. Ensure that the patient knows how to keep track of the number of doses in the inhaler device. Copyright © 2017, Elsevier Inc. All rights reserved.

A patient is prescribed two different types of inhaled medications for treatment of COPD. After administering the first medication, how long should the nurse wait to administer the second medication? 1 minute 5 minutes 10 minutes 15 minutes Correct answer: B Rationale: If a second puff of the same drug is ordered, instruct the patient to wait 1 to 2 minutes between puffs. If a second type of inhaled drug is ordered, instruct the patient wait 2 to 5 minutes between the medications or to take as prescribed. Bronchodilators are usually administered first. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Case Study The nurse is providing teaching to a group of individuals with COPD at a community center. Which statement by one of the attendees indicates that further teaching is needed? “If I develop a puffy face, I will stop taking methylprednisolone (Medrol) immediately.” “I will inform my prescriber of any weight gain of 2 lb or more in 24 hours or 5 lb or more in 1 week.” “I use omalizumab (Xolair) to control my asthma but not for an acute asthma attack.” “When taking theophylline (Theo-Dur), I will advise my prescriber if I experience epigastric pain.” Correct answer: A Rationale: Patients should be taught to not stop systemic corticosteroids abruptly. Patients should be educated about the possibility of Addisonian crisis, which may occur if a systemic corticosteroid is abruptly discontinued. These drugs require weaning before discontinuation of the medication. Patients should monitor their weight daily and report the increase stated. Omalizumab (Xolair) is used for the treatment of moderate to severe asthma and not for aborting acute asthma attacks. Adverse effects of theophylline (Theo-Dur) that should be reported immediately to the prescriber include epigastric pain. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Case Study (Cont.) One of the attendees expresses concern regarding her granddaughter’s asthma. The attendee tells the nurse that she is afraid that she will not know which of her granddaughter's medications to give first in case of an asthma attack. Which medication should the nurse inform the attendee to administer first for an acute asthma attack? ipratropium (Atrovent) albuterol (Proventil) budesonide (Pulmicort Turbuhaler) montelukast (Singulair) Correct answer: B Rationale: Albuterol (Proventil) is a short-acting beta2 agonist indicated for treatment of acute asthma attacks. Ipratropium (Atrovent) is an anticholinergic not indicated for treatment of acute asthma attacks. Budesonide (Pulmicort Turbuhaler) is an inhaled corticosteroid that should not be used in an acute asthma attack. Montelukast (Singulair) is a leukotriene receptor agonist used for long-term management of asthma, not for acute exacerbations. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

Case Study (Cont.) One of the attendees tells the nurse that he has asthma and is being treated with a short-acting inhaled beta2 agonist. The nurse identifies this treatment as which step of the stepwise therapy for the treatment of asthma? Step 1 Step 2 Step 3 Step 4 Correct answer: A Rationale: Step 1 includes use of a short-acting inhaled beta2 agonist as needed. Copyright © 2017, Elsevier Inc. All rights reserved. Elsevier items and derived items © 2009, 2005, 2001 by Saunders, an imprint of Elsevier Inc.

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