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Etiologies, Sequelae and ManagementManagement ofof DRYDRY MOUTHMOUTH By Fiona M. Collins, BDS, MBA, MA

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Written for dentists, hygienists and assistants DENTAL LEARNING

Etiologies, Sequelae and Management of Dry Mouth

ABSTRACT EDUCATIONAL OBJECTIVES Dry mouth affects a significant proportion of the population, with The overall goal of this article is to provide the reader with an increased prevalence with age. Etiologies include medication information on the causes and management of the oral use, autoimmune diseases, head and neck radiation, chemotherapy, complications of dry mouth. After competing this article, the reader certain viral infections and a number of other causes. In addition, will be able to: etiologies of transient dry mouth include dehydration, mouth • Review production and the functions of saliva; breathing, snoring, tobacco and alcohol. Given the functions • List and describe etiologies for dry mouth; of saliva, the oral complications of dry mouth are significant, • Describe common oral complications, signs and symptoms including an increased risk of dental caries, dental erosion, oral associated with dry mouth; and, infections and irritations. Patients also experience difficulties eating, • Review options for the prevention, management and treatment drinking, swallowing and talking. The management and treatment of oral complications. of the oral complications of dry mouth is essential to help restore and maintain oral health and quality of life.

ABOUT THE AUTHOR Fiona M. Collins, BDS, MBA, MA INTRODUCTION Dr. Fiona M. Collins has authored and erostomia, dry mouth and hyposalivation are presented CE courses to dental professionals often used interchangeably. However, and students in the United States and inter- is the subjective assessment of dry nationally, and has been an active author, X mouth by the sufferer while hyposalivation is the editor, writer, speaker and trainer for several years. Fiona is a member of the American objective assessment of dry mouth. The overall Dental Association, the ADA Standards prevalence of dry mouth ranges from 10% to 46%, Committee working groups, Chicago Dental Society, and the depending on the study and age group.1 A prevalence of Organization for Safety, Asepsis and Prevention (OSAP). She is the up to 42% has been found for xerostomia and up to ADA representative to AAMI and a Fellow of the Pierre Fauchard 47% for hyposalivation, in both cases with a higher Academy. Dr. Collins earned her dental degree from Glasgow prevalence in women than men.1 Dry mouth also University and holds an MBA and MA from Boston University. AUTHOR DISCLOSURE: Dr. Collins has no financial relation- disproportionately affects the elderly, particularly those ship or interest with the commercial supporter of this course. She living in healthcare or nursing facilities. is the CE Editor for Dental Learning. Dr. Collins can be reached at [email protected].

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Salivary Flow and Production and, 2) Secretion of proteins and peptides by vesicles in the Total salivary production is typically 0.5-1 liter/day in the acinar cells.5 The major neurotransmitters are noradrenaline absence of dry mouth, and up to 1.5 liters/day.2 Stimulated and acetylcholine.6 Mucins are released from the mucous salivary flow is estimated to account for 80% to 90% of acinar cells, primarily following parasympathetic stimula- total saliva produced in a 24-hour period,2 with significantly tion.5,6 The release of amylase from the serous acinar cells is decreased production of saliva at night (~0.1 ml/minute in mediated mainly through noradrenaline release (sympathetic a patient with normal salivary flow).2 The parotid gland stimulation).5 However, amylase is also released as a result of supplies >50% of stimulated salivary flow. Twenty percent parasympathetic stimulation.5,6 Greater fluid flow through the of unstimulated salivary flow is supplied by the parotid, cells is encouraged by acetylcholine, and the rates of secretion 65% by the submandibular gland, and the remainder is and ion concentration are influenced by acetylcholine and from the sublingual and minor salivary glands. (Figure 1) adrenergic activity.6 Unstimulated and stimulated salivary flow of <0.1 ml/minute and <0.7 ml/minute, respectively, are the accepted thresholds Functions of Saliva and Salivary Content for hyposalivation.3,4 Serous saliva is produced mainly by Saliva in health contains ~99% water, plus proteins, pep- the parotid glands, and mucous (thicker) saliva by the minor tides, lipids, electrolytes, enzymes and antimicrobial agents; salivary glands found throughout the oral cavity. Saliva it has a pH of between 6 and 7.2 After exiting the salivary produced by the submandibular and sublingual glands is ducts, saliva becomes ‘whole saliva’ after mixing with gingi- mixed, with serous and mucous components. val crevicular fluid, mucous from the nasopharynx, bacteria, sloughed cells, blood cells, food particles and chemicals / toxins present. Saliva performs many functions, including: 1) aiding digestion through lubrication for solubilizing, chewing and swallowing food; and by enzymes that start digestion such as, amylase, protease and lipase that, respec- tively, break down starches, proteins and lipids; 2) protect- ing and dental hard tissues; 3) aiding speaking and smiling (social interactions) through lubrication; and, 4) influencing taste perceptions.2,7,8 Saliva exerts an antimicrobial effect, helping to maintain and protect dental hard and soft tissues, and protects oral tissues against plaque enzymes, potential toxins and chemi- 2 Figure 1. Unstimulated salivary flow cals, and dehydration. Salivary clearance removes bacteria, fermentable carbohydrates, acids and debris.2,7,8 In addition, saliva contains an extensive array of antibacterial, antiviral The secretion of saliva is primarily controlled by the auto- and anti-fungal agents that help to maintain oral health.9 nomic nervous system, with salivary production stimulated by (Table 1) Interestingly, salivary histatins may play a role in parasympathetic and sympathetic nerve stimulation.2,5,6 This wound healing.10 involves: 1) Secretion of an isotonic primary fluid containing Lubrication is provided by highly viscous, elastic mu- water and ions, mostly due to parasympathetic stimulation; cins that adhere well to oral tissues and offer low solubility,

Copyright 2016 by Dental Learning, LLC. No part of this publication may be reproduced or transmitted in any form without prewritten Managing Editor Creative Director permission from the publisher. BRIAN DONAHUE MICHAEL HUBERT Art Director JOSEPH CAPUTO October 2016 DENTAL LEARNING 3 500 Craig Road, Floor One, Manalapan, NJ 07726 DENTAL LEARNING

Figure 2. Functions of saliva

Dental Hard Tissue Protection Oral Mucosa Protection Salivary clearance and dilution Lubcrication: Mucins, PRG Buffering: Bicarbonate, phosphate, sialin, urea Salivary clearance and dilution Supplies: Calcium, phosphate, mucins, proteins, and fluoride (if ingested) Antimicrobial agents: Antibacterial, anti-fungal and anti-viral Antimicrobial agents: Antibacterial Prevents adhesion of microroganisms: Mucins Pellicle formation: Salivary proteins Functions of Saliva Social Activities Nutrition Lubrication: Eating, speaking Bolus Formation: Salivary mucins and smiling Digestion: Salivary enzymes Taste: Zinc, gustin and by protein-rich glycoproteins (PRG).2 In addition, mucins phosphate salts, and are important for the development of the inhibit bacterial and fungal adhesion to, and colonization of, acquired pellicle.8 (Figure 2) oral tissues. Dental hard tissues are protected through lubrica- tion, salivary dilution and by clearance of acids, and salivary Etiologies of Dry Mouth buffering agents that protect against lowering of the pH to Medication use, autoimmune diseases, hormonal the level required for demineralization, and help elevate the changes, head and neck radiation, HIV disease, hepatitis C, pH after acid attacks. Buffering agents include bicarbonate, Parkinson’s disease, neoplasms, nerve damage, and a num- phosphate, sialin and urea. Importantly, saliva is a carrier for ber of other diseases and conditions are etiologic factors for calcium, phosphate and fluorides which help prevent demin- dry mouth. (Table 2) Transient dry mouth can result from eralization and promote remineralization. Salivary proteins dehydration, alcohol use, mouth breathing, stress and other (statherins and proline-rich proteins) help to maintain salivary emotional disturbances. Less frequent causes of dry mouth supersaturation with calcium and phosphate relative to hy- include thyroiditis, cystic fibrosis and primary biliary cir- droxyapatite, inhibiting spontaneous precipitation of calcium rhosis. Chemotherapy can reduce salivary flow and causes

Table 1. Antimicrobial agents in saliva 2,7 Table 2. Factors associated with dry mouth

Antibacterial Etiology of Dry Mouth Mucins Histamine Medication use Auto-immune diseases Lysozyme Immunoglobulins Hormonal changes HIV disease Head and neck radiation Hepatitis C Lactoferrin Defensins Tumors Parkinson’s disease Lactoperoxidase Agglutinin Nerve damage Drug use (street drugs) VEGh Cystatins Lymphoma Sarcoidosis and amyloidosis Antifungal Antiviral Transient dry mouth Mucins Mucins Dehydration Mouth breathing, snoring Histatins Histatins Alcohol use, drug abuse Smoking Immunoglobulins Immunoglobulins Eating disorders Stress, other emotional disturbances

4 Etiologies, Sequelae and Management of Dry Mouth

changes in the consistency of saliva, making it feel thicker. The main mechanisms of action for medication-induced dry While a frequent complaint, this effect is typically tempo- mouth are through an anti-cholinergic or sympathomimetic rary.3,5 Cannabis is anticholinergic and its use causes dry effect, while a number of drugs have a cytotoxic effect mouth,11 and drug abuse with results in or cause reductions in hydration. Anticholinergic drugs severe dry mouth, classic ‘meth mouth,’ rampant caries and interfere with acetylcholine-related salivary production and excessive .12 sympathomimetic drugs interfere with noradrenaline-related salivary production.5,14,21 (Table 3) Medication Use In excess of 500 drugs are associated with dry mouth.13,14 Head and Neck Radiation These include tricyclic antidepressants, psychotropics, anti- Dry mouth occurs in 93% of patients during head and histamines, antihypertensives, anti-emetics, anti-diarrheals, neck radiation therapy, and an estimated 74% to 85% cardiovascular drugs, proton pump inhibitors used for gas- of these patients experience long-term severe dry mouth.3 tric reflux, protease inhibitors, and steroids.5,15,16 The elderly (Figure 4) Decreased salivary function occurs within 1 week are particularly vulnerable to dry mouth, in large part due of the start of therapy, with a dose-response relationship. A to their pattern of medication use,17 as well as the effects of total dose of ≤26 Gy is required to preserve gland function diseases and conditions, rather than aging itself.18 (Figure 3) and for improvement post-therapy. Radiation therapy also The Centers for Disease Control and Prevention estimates results in thicker saliva and other salivary changes within that the elderly in long-term care facilities take on average 2 months – including a decrease in salivary pH and in the 8 drugs daily.19 One study found a correlation between the levels of nitrate and thiocyanate, and an increase in lactate, levels of stimulated and unstimulated salivary flow and formate, sulphate and chloride.23 Radiation-induced damage the number of medications being used, with a significantly is decreased by using intensity-modulated radiation therapy, greater impact on stimulated salivary flow.20 whereby multiple beams are used and arranged to reduce the impact on the parotid gland. This may not protect the Figure 3. Percentage of individuals reporting dry mouth. submandibular glands, still leading to reduced unstimulated salivary flow and nocturnal dry mouth in particular.24,25 Other medications being used to protect against radiation damage include amifostine and botulinum toxin (the same toxin used in ‘Botox treatment’).25,26

Table 3. Common anticholinergic and sympathomimetic drugs

Anticholinergic drugs Sympathomimetic drugs Tricyclic antidepressants Appetite suppressants Atropine Decongestants Antihistamines Bronchodilators Antiemetics Antipsychotics Anti-hypertensives

Adapted from Nederfors et al. Community Dent Oral Epidemiol Serotonin reuptake inhibitors ß-blockers 1997;25:211–216.

October 2016 5 DENTAL LEARNING

Autoimmune Diseases Sjögren syndrome (SS) is a chronic inflammatory Figure 4. Parched oral mucosa in patient with hyposalivation following therapy autoimmune disease affecting the salivary, lacrimal and other exocrine glands.27 Approximately 4 million people in the US alone suffer from this disease, mainly women.28 SS is the autoimmune disease most frequently associated with dry mouth;29 others include diabetes mellitus, rheumatoid arthritis and systemic lupus erythematosis. SS is further addressed in a separate article.

Viral Diseases – HIV and Hepatitis C disease affects ~8% of people in the US liv- ing with HIV infection.30 This results in salivary gland enlarge- ment and dry mouth, as do some of drugs used to manage HIV disease.31 (Figure 5) People infected with Hepatitis C also Figure 5. Dry mouth in patient with HIV experience dry mouth.32

Sequelae, Signs and Symptoms of Dry Mouth Given the functions of saliva, the potential consequences of dry mouth are considerable. Patient complaints include a sticky and/or dry feeling in the mouth, a painful/burning mouth, alterations in taste, stringy or ropey saliva, difficulty speaking, chewing and swallowing food, nocturnal discomfort and dif- ficulty wearing dentures. Patients who have received head and neck radiation therapy experience oral complications as affect- ing every aspect of their lives; they may suffer from depression as a result and may question their will to live.33 Hyposalivation results in dry or parched-looking oral Figure 6. Angular in patient with dry mouth mucosa, dry or cracked , , a parched or globular appearance to the tongue and oral irritations. (Figure 6) A dental mirror sticking to the cheek during an examination is indicative of dry mouth, as is a digit adhering to oral mucosa during palpation.34 Patients with hyposalivation are at increased risk for dental caries and dental erosion due to reduced clearance of bacteria (caries), fermentable carbohydrates (caries), ex- trinsic and intrinsic acids (erosion); reduced/lack of salivary protective factors including antibacterial agents (caries), cal- cium and phosphate; and, reduced buffering capacity with a prolonged dip in pH following acid attacks (caries and

6 Etiologies, Sequelae and Management of Dry Mouth

Screening, Assessing and Diagnosing Dry Mouth Figure 7. Dry mouth patient Dental patients should be screened for dry mouth, start- ing with the medical history form that asks about diseases, conditions, habits and medication use. Since dry mouth may be subjective or objective, the patient’s perception of dry mouth and its level of inconvenience/impact on quality of life should be assessed, as well as salivation. Including ques- tions on dry mouth, dry lips, difficulty speaking, or eating and swallowing without sipping water, helps to discover patient concerns.34,39,40 Other questions to ask include changes in taste, ocular/throat dryness and whether there is a sensation of ‘burning mouth.’ A visual analog scale may also be used to have patients indicate their perceived level of erosion). (Figure 7) As a component of erosive tooth wear, dry mouth/discomfort. patients are also at greater risk for and . With loss of enamel and subsequent exposure, den- Salivary Testing tinal hypersensitivity associated with exposed open dentinal Stimulated and unstimulated salivary flow are measured tubules may be present. Increased levels of dental plaque, separately by having the patient salivate and expectorate food retention, , halitosis, candidal and into a cup for five minutes for each test. For stimulated sa- other oral infections also occur in patients with hyposaliva- liva collection, the patient should first chew gum or paraffin tion. Oral mucositis affects almost all head and neck radia- wax. For unstimulated saliva collection, the patient should tion patients, and up to 40% of high-dose chemotherapy refrain from eating, drinking (except water), smoking, patients.37,38 (Table 4) chewing gum, and consuming caffeine for one hour prior to the test, and sit still while saliva is collected.41 Easy-to-use Table 4. Oral complications of dry mouth chairside tests are also available that measure stimulated Complications and unstimulated salivary flow, unstimulated and stimulated Dry or sticky feeling in mouth Intraoral discomfort salivary pH, buffering capacity and salivary consistency. Laboratory testing may also be indicated, such as minor Burning mouth or tongue Stringy/ropey saliva salivary gland biopsy or identification of autoantibodies Difficulty chewing or swallowing Difficulty eating for Sjögren syndrome; imaging to identify tumors, salivary Difficulty speaking Taste alterations stones and other abnormalities; scans; and, radiopaque Difficulty wearing dentures Nocturnal discomfort fluid-assisted radiography.5 Angular cheilitis Dry or cracked lips Depression Poor quality of life Preventing and Managing the Sequelae of Risk factor for Dry Mouth Management and prevention include thorough oral hy- Dental caries Dental erosion and tooth wear giene, stimulation of saliva (where possible), palliative care Dentinal hypersensitivity Candidal infections and/or treatment to relieve dry mouth and its associated and periodontal disease Oral mucositis symptoms, and treatment to prevent and manage the other Other oral infections Oral irritations potential complications of dry mouth.

October 2016 7 DENTAL LEARNING

Managing and Relieving Dry Mouth Other options Sipping water frequently, and sucking small amounts of ice Dry mouth chewable moisturizing lozenges are available or sugar-free lozenges/candies, may help to relieve discomfort. that contain bicarbonate as a buffering agent, calcium, and ar- Patients should be advised to avoid acidic/sour candies, which ginine (BasicBites, Ortek Therapeutics, Inc). Lozenges are also are highly erosive.42 Chewing sugar-free gum ad libitum can be available that are nonchewable and moisturize as they slowly recommended43,44 – this stimulates saliva (when salivary gland dissolve. A time-release mucoadhesive disc containing xylitol function is present) and helps to remove plaque. Since many is available that helps to moisturize and lubricate the oral patients already enjoy chewing gum, this is not onerous. Xy- cavity (Xylimelts, OraCoat), as well as a muco-adhesive patch litol chewing gum may help as part of a preventive program, (OraMoist, DenTek). Applying vitamin E oil (or from a capsule and chewing gum with casein phosphopeptide-amorphous with a hole in it) directly to the mucosa is also recommended calcium phosphate supplies calcium and phosphate.45 for relief, used 2 or 3 times daily. 54

Oral Lubricants and Saliva Substitutes Prescription Products Saliva substitutes are viscous and ‘moisturize’ the oral Supersaturated calcium phosphate rinses are also avail- mucosa; they contain xanthan gum, carboxymethylcellulose, able. Originally, this type of rinse came as two vials containing polyacrylic acid or mucin as the thickening agent. Xanthan solutions mixed immediately before use. An effervescent tablet gum and mucin may provide better wetting and flow than version has now been developed (Caphasol, EUSA Pharma), and carboxymethylcellulose, and may be preferred for head and powder sachets that are mixed with water immediately before neck irradiated patients and those with Sjögren syndrome.26,46,47 use are available (NeutraSal, Orapharma; SalivaMAX, Forward Over-the-counter spray saliva substitutes are easy-to-use and Science) Recent studies, and one review, reported improvements portable.26,48 Examples of sprays include Allday Dry Mouth in patients’ perceptions of xerostomia and taste, oral lubrication, Spray (Elevate Oral Care), Biotène Moisturizing Mouth Spray and ease of eating, drinking, swallowing, and talking with use of (GSK), Entertainer’s Secret (KLI Corp.), Moi-Stir (Kingswood supersaturated calcium phosphate rinses.55-58 In one recent study, Laboratories, Inc.), MouthKote (Parnell Pharmaceuticals, Inc.) using a visual analog scale, patients reported an average rating of and Salivart (Gebauer Company). 9 (1 being ‘dry as a desert’ and 10 being normal), compared with Dry mouth moisturizing gels and rinses typically contain an average score of 2 at baseline 28 days earlier prior to using hydroxyethylcellulose, carboxymethylcellulose, or glycerin as supersaturated a calcium phosphate rinse.55 the moisturizing and lubricating agent; buffers to reduce acidity (calcium bicarbonate); antibacterial agents; or, combinations Sialogogues of these. Dry mouth rinses containing fluoride help provide hydrochloride (Salagen; MGI Pharma) and cev- protection against dental caries. Natural-based mouthwashes imeline hydrochloride (Evoxac; Daiichi-Sankyo) are cholinergic containing plant extracts are also available. A recent systematic agents that stimulate salivary gland function. They are indi- review of 36 randomized controlled trials found insufficient cated for severe hyposalivation associated with head and neck evidence to make recommendations on saliva substitutes for radiation or Sjögren syndrome. Pilocarpine is prescribed at a palliative relief of dry mouth.49 However, individual studies dose of 5 mg, three or four times daily for at least 12 weeks to have demonstrated significant benefits – in some cases pro- provide clinical benefit and use must be ongoing. Cevimeline is viding relief without increasing salivation,50 and benefitting prescribed at a dose of 30 mg, 3 times daily.5 Both pilocarpine patients including those with severe hyposalivaton.51-53 Gels are and cevimeline are clinically effective, and pilocarpine has been recommended for night-time use as they are thick and adhere found to be effective during head and neck radiation thera- for long periods of time to the mucosa. py. 59-63 Sialogogues have potentially serious side effects such as

8 Etiologies, Sequelae and Management of Dry Mouth

dizziness, alterations in vision and stomach upset and, rapid or supersaturated calcium and phosphate rinse reduced dental slowed heart rate.64 caries in patients with severe dry mouth. Statistically significant reductions in coronal and root caries, and remineralization of and Prevention existing caries lesions, were observed (p<0.0001).58 Thorough brushing and interdental cleaning are essential. Patients should be advised to brush twice-daily using a soft- Sealants bristled powered toothbrush,45 and fluoride or dry Pit and fissure sealant placement on molar and bicuspid mouth toothpaste containing fluoride. For some patients, using surfaces may also be indicated for at-risk children and adults.72 toothpaste with a low level of SLS, or a dry mouth toothpaste with no SLS, may reduce the risk of aphthous ulcers and irrita- Additional Advice and Recommendations for Patients tions; patients can also experience irritation with strong/minty Patients should be advised to sip water frequently to flavors, therefore a mild-flavored toothpaste is preferable.45 improve oral hydration and comfort, and to sip water during Antibacterial help to control plaque and gingivitis, meals to aid chewing and swallowing. In addition, eating softer and may also reduce halitosis. Selection of oral care products foods can help; foods with sweeteners or flavorings (not sugars should be based on clinical efficacy, safety, and the needs and or spices), and that are favorites, can help increase salivary preferences of the individual patient. flow. A low-sugar diet reduces the risk of caries. Patients should avoid acidic chewing gum, and acidic foods, vegetables and Fluoride, Calcium and Phosphate drinks (including carbonated drinks), as these increase the risk Recommended preventive care includes frequent professional of dental erosion, and should also avoid spicy foods, alcohol, application of 5% sodium fluoride varnish, at least every 3 or 6 street drugs, alcohol-containing rinses, caffeine and smoking as months, as patients with hyposalivation are at high risk for car- these irritate the oral mucosa and increase dryness.48 (Table 5) ies.65 Silver diamine fluoride is now also available in the US, and Using a humidifier at home (and not a dehumidifier) may help, has been shown to be effective in arresting and preventing dental especially at night when salivary flow is lowest. Denture use at caries.66 These are off-label uses. Prescription-level fluoride paste night should be discouraged and dentures must fit well. Den- once or twice daily provides added benefit, increasing protection ture hygiene using a brush and denture cleansers will remove against dental caries and is recommended for at-risk patients.67 debris and microorganisms. Rinsing with baking soda (water Fluorides also help strengthen enamel against erosive acid chal- with 1 teaspoon of baking soda) helps to counteract bacterial lenges.68-70 Rinsing with an alcohol-free fluoride mouthrinse and erosive acids, and to prevent demineralization, by acting as is of benefit, and recommended when the mouth feels dry or a buffer and increasing the intraoral pH. (Table 5) after eating/drinking.67 It is also available as a dry mouth rinse containing aloe vera. Calcium and phosphate products may also Table 5. Additional patient recommendations be recommended. In head and neck radiation patients in one study, caries reductions were observed in patients using a sodium DO AVOID fluoride toothpaste containing amorphous calcium phosphate Sip water frequently and during meals Eating foods with sugars/spices compared to those using a regular fluoride toothpaste.71 Casein Eat softer foods, preferred flavorings Acidic foods and drinks, caffeine Suck sugar-free candies or small pieces phosphopeptide-amorphous calcium phosphate paste with Acidic chewing gum or candies of ice fluoride can be applied at night, and left on the teeth, providing Chew sugar-free gum Acidic/sour/sugar-containing candies a source of calcium, phosphate and fluoride.45 In addition, in one study (n=134) when used up to three to four times daily, to- Use a humidifier, especially at night Alcohol, street drugs, smoking gether with daily use of a prescription-level fluoride toothpaste, Rinse with baking soda Alcohol-containing rinses

October 2016 9 DENTAL LEARNING

Managing Oral Mucositis oral suspension, nystatin pastilles and amphotericin loz- General guidelines include use of a soft-bristled toothbrush, enges.77 In severe cases, systemic ketoconazole or flucon- replaced on a regular basis,73 regular oral hygiene, and regular azole may be required. If a denture wearer is experiencing professional and preventive care. Specifically for patients who candidiasis, an antifungal ointment should also be used have received high-dose chemotherapy and total body irradia- under the denture when wearing it. The wearer should also tion, keratinocyte growth factor-1 (palmiferin) is recommended be advised to clean the denture by soaking it overnight in and FDA-approved for the prevention of mucositis.38 Based chlorhexidine gluconate rinse. on a recent systematic review, there is currently insufficient evidence to make an evidence-based recommendation on the Emerging and Potential Treatments for Hyposalivation use of supersaturated calcium phosphate rinses.73 However, Hyposalivation treatments being investigated and/or individual studies have reported on the efficacy of supersatu- already in use on a small scale include acupuncture, electrical rated calcium phosphate rinses and success in managing oral nerve stimulation (including via an osseointegrated dental im- mucositis, and in reducing its occurrence and severity, and the plant) and extra- and intra-oral reservoir hydration devices.25,78 associated pain.56,74,75 This rinse can be used at least 4 and up Replacement full dentures with reservoirs containing saliva to 10 times daily to treat oral mucositis and relieve symptoms, substitute may also provide relief.79Acupuncture has been and patients should avoid eating or drinking for at least 15 shown to help for head and neck radiation patients, with the minutes after use. Another option for the management of benefit maintained for 6 months and lasting up to 3 years if ad- oral mucositis is a prescription rinse containing glycerin and ditional acupuncture therapy is provided.80,81 Overall, however, carbomers (MuGard, AMAGPharma), using up to 10 ml four there is currently insufficient evidence on the efficacy of electro- to six times daily. stimulation devices in relieving the discomfort associated with dry mouth, and low evidence on the effects of acupuncture.82 Relieving Pain from Oral Irritations and Oral Mucositis More promising potential therapies for the future treatment of Pain relief from mucositis may involve local application of dry mouth include the use of growth factors, stem cell therapy analgesic agents and rinses, and for relief from severe and the development of artificial salivary glands.25 pain. Palliative care of localized oral irritations can be achieved using topical analgesic pastes containing 20% benzocaine or Summary 2% lidocaine. For extensive areas, a barrier cream or rinse is Dry mouth is a debilitating condition that significantly recommended. Mucoadhesive rinses are available that provide affects oral health and quality of life. The prevention, manage- a coating and protective barrier (Rincinol, Sunstar Americas; ment and treatment of the oral complications of dry mouth Gelclair, OSI Pharamaceuticals). ‘Magic mouthwash’ contains must be tailored to the needs of individual patients. Manage- viscous lidocaine, Maalox, and Benadryl and can be used to ment and treatment protocols are aimed at relieving dry mouth manage extensive oral irritations/ulcerations and oral mucosi- and the associated discomfort, reducing the risk of disease and tis.73 If severe pain is present, a 2% morphine mouthwash may conditions associated with xerostomia and managing these be indicated and may be prescribed in specialist settings.73 should they occur, and improving quality of life. Future thera- pies are promising, including biologic and tissue regenerative Candidal Infections interventions that would restore salivary function. can be treated with topical nys tatin or clotrimazaole, often applied as a cream or ointment.76 Acknowledgement Topical nystatin is applied as a thin layer 4 times per day. Figures 4 and 6 courtesy of Sandra Boody, RDH; Figure 5 courtesy of Dr. David Reznik and HIVdent; and, Figure 7 courtesy of Dr. John Comisi. Other antifungal options include miconazole gel, nystatin

10 Etiologies, Sequelae and Management of Dry Mouth

References and neck radiation therapy. Oral Surg Oral Med Oral Pathol Oral Radiol. 2013;116(1):e37–e51. 1. Hopcraft MS, Tan C. Xerostomia: an update for clinicians. Aust Dent J. 2010;55(3):238-44. 26. Vissink A, Panders AK, Gravenmade EJ, Vermey A. Treatment of oral symp- toms in Sjögren’s syndrome. Scand J Rheumatol Suppl. 1986;61:270-3. 2. Humphrey SP, Williamson RT. A review of saliva: normal composition, flow, and function. J Prosthet Dent. 2001;85:162-9. 27. Sullivan DA, Bélanger A, Cermak JM, et al. Are Women With Sjogren’s Syndrome Androgen-deficient? J Rheumatol. 2003;30:2413-9. 3. Jensen S, Pedersen A, Vissink A, et al. A systematic review of salivary gland hypofunction and xerostomia induced by cancer therapies: prevalence, severity 28. Sjogrens Syndrome Foundation. About Sjogrens. Available at: http://www. and impact on quality of life. Support Care Cancer. 2010;18:1039-60. sjogrens.org/home/about-sjogrens. 4. Navazesh M, Christensen CM, Brightman VJ. Clinical criteria for the diagnosis 29. Jensen SB, Vissink A. Salivary gland dysfunction and xerostomia in Sjögren's of salivary gland hypofunction. J Dent Res. 1992;71:1363-9. syndrome. Oral Maxillofac Surg Clin North Am. 2014;26(1):35-53. 5. Porter SR, Scully C, Hegarty AM. An update of the etiology and management 30. Williams FM, Cohen P, Jumshyd J, Reveille JD. Prevalence of diffuse lym- of xerostomia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;97:28-46. phocytosis syndrome among human immunodeficiency virus type 1-positive outpatients. Arthritis Rheum. 1998;41:863-8. 6. Proctor GB, Carpenter GH. Regulation of salivary gland function by auto- nomic nerves. Auton Neurosci. 2007;133(1):3-18. 31. Mbopi-Kéou FX, Bélec L, Teo CG, et al. Synergism between HIV and other viruses in the Mouth. Lancet Infectious Dis. 2002;2:416-24. 7. van Nieuw Amerongen AV, Veerman EC. Saliva – the defender of the oral cav- ity. Oral Dis. 2002;8(1):12-22. 32. Porter SR. Plenary abstract: Xerostomia: prevalence, assessment, differential diagnosis and implications for quality of life. Oral Dis. 2010;16(6):501-2. 8. Pedersen AM, Bardow A, Jensen SB, Nauntofte B. Saliva and gastrointestinal functions of taste, mastication, swallowing and digestion. Oral Dis. 2002;8:117-29. 33. Dirix P, Nuyts S, Vander Poorten V, et al. The influence of xerostomia after radiotherapy on quality of life. Support Care Cancer. 2007;16:171-9. 9. van Nieuw Amerongen A, Bolscher JGM, Veerman EC. Salivary Proteins: Protective and Diagnostic Value in Cariology? Caries Res. 2004;38:247-53. 34. Guggenheimer J, Moore P A. Xerostomia: etiology, recognition and treat- ment. J Am Dent Assoc. 2003;143:61-9. 10. Oudhoff MO, Bolscher JGM, Nazmi K, et al. Histatins are the major wound- closure stimulating factors in human saliva as identified in a cell culture assay. 35. Bartlett DW. The role of erosion in tooth wear: aetiology prevention and FASEB J. 2008;22:3805-12. management. Int Dent J. 2005;55(S4): 277-284. 11. Veitz-Keenan A, Spivakovsky S. Cannabis use and oral diseases. Evid Based 36. Redding SW, Zellars RC, Kirkpatrick WR, et al. Epidemiology of oropharyn- Dent. 2011;12(2):38. geal Candida colonization and infection in patients receiving radiation for head and neck cancer. J Clin Microbiol. 1999;37(12):3896-3900. 12. Hamamoto DT, Rhodus NL. abuse and dentistry. Oral Dis. 2009;15(1):27-37. 37. Vera-Llonch M, Oster G, Hagiwara M, Sonis S. Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma. Cancer. 13. Fox PC. Acquired salivary dysfunction. Drugs and radiation. Ann NY Acad 2006;106:329-36. Sci. 1998;15:132-7. 38. Lalla RV, Bowen J, Barasch A, et al. MASCC=ISOO Clinical Practice Guide- 14. Scully C. Drug effects on salivary glands: dry mouth. Oral Dis. 2003; 9(4):165-76. lines for the Management of Mucositis Secondary to Cancer Therapy. Cancer. 15. Nederfors T, Isaksson R, Mörnstad H, Dahlöf C. Prevalence of perceived 2014;1453-61. symptoms of dry mouth in an adult Swedish population-relation to age, sex and 39. Fox PC, Busch KA, Baum BJ. Subjective reports of xerostomia and objective pharmacotherapy. Community Dent Oral Epidemiol. 1997;25:211-6. measures of salivary gland performance. J Am Dent Assoc. 1987;115:581-4. 16. Scully C, Felix DH. Oral medicine — update for the dental practitioner: dry 40. Navazesh M. Identifying those at risk. Dimensions of Dental Hygiene. mouth and disorders of salivation. Br Dent J. 2005;199(7):423-7. 2004;2:24,26–27. 17. Liu B, Dion MR, Jurasic MM, et al. Xerostomia and salivary hypofunction in 41. Navazesh M, Kumar SK. Measuring salivary flow: challenges and opportuni- vulnerable elders: prevalence and etiology. Oral Surg Oral Med Oral Pathol Oral ties. J Am Dent Assoc. 2008;139 Suppl:35S-40S. Radiol. 2012;114(1):52-60. 42. Jensdottir T, Nauntofte B, Buchwald C, et al. Effects of sucking acidic candies 18. Atkinson JC, Grisius M, Massey W. Salivary hypofunction and xerostomia: on saliva in unilaterally irradiated pharyngeal cancer patients. Oral Oncol. diagnosis and treatment. Dent Clin N Am. 2005;49:309-26. 2006;42(3):317-22. 19. Centers for Disease Control and Prevention. Oral Health for Older Ameri- 43. Itthagarun A, Wei SH. Chewing gum and saliva in oral health. J Clin Dent. cans. Available at: http://www.cdc.gov/oralhealth/publications/factsheets/ 1997;8(6):159-62. adult_oral_health/adult_older.htm. 44. Bots CP, Brand HS, Veerman EC, et al. Chewing gum and a saliva substitute 20. Närhi TO, Meurman JH, Ainamo A. Xerostomia and hyposalivation: causes, alleviate thirst and xerostomia in patients on haemodialysis. Nephrol Dial Trans- consequences and treatment in the elderly. Drugs Aging. 1999;15(2):103-16. plant. 2005;20(3):578-84. 21. Felix DH, Luker J, Scully C. Oral Medicine: 4. Dry Mouth and Disorders of 45. John Hopkins Jerome L. Greene Sjögren’s Syndrome Center, Baer A, Papas Salivation. Dental Update; December 2012:738-43. A, Singh M, Sciubba J. Preventing Dental Decay: A Guide for Salivary Hypofunc- 22. Eisbruch A, Ten Haken RK, Kim HM, et al. Dose, volume, and function tion Patients. Available at: http://www.hopkinssjogrens.org/disease-information/ relationships in parotid salivary glands following conformal and intensity-modulated treatment/preventing-dental-decay/. irradiation of head and neck cancer. Int J Radiat Oncol Biol Phys. 1999;45(3):577-87. 46. Van der Reijden WA, Van der Kwaak H, Vissink A, et al. Treatment of xerosto- 23. Pow EHN, Chen Z, Kwong DLW, Lam OLT. Salivary Anionic Changes after mia with polymer-based saliva substitutes in patients with Sjögren’s syndrome. Radiotherapy for Nasopharyngeal Carcinoma: A 1-Year Prospective Study. PLoS Arthritis Rheum. 1996;39:57-69. ONE. 2016;11(3):e0152817. 47. Vissink A, ‘s-Gravenmade EJ, Panders AK, et al. A clinical comparison be- 24. Scrimger R. Salivary gland sparing in the treatment of head and neck cancer. tween commercially available mucin- and CMC-containing saliva substitutes. Int Expert Rev Anticancer Ther. 2011;11:1437-48. J Oral Surg. 1983;12:232-8. 25. Sasportas LS, Hosford AT, Sodini MA, et al. Cost-effectiveness landscape 48. Silvestre FJ, Minguez MP, Suñe-Negre JM. Clinical evaluation of a new analysis of treatments addressing xerostomia in patients receiving head

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artificial saliva in spray form for patients with dry mouth.Med Oral Patol Oral Cir J Dent. 2009;37(8):591-5. Bucal. 2009;14(1):E8-E11. 71. Papas A, Russell D, Singh M, et al. Caries clinical trial of a remineralising 49. Furness S, Worthington HV, Bryan G, et al. Interventions for the management toothpaste in radiation patients. Gerodontol. 2008;25(2):76-88. of dry mouth: topical therapies. Cochrane Database of Systematic Reviews. 72. Plemons JM, Al-Hashimi I, MarekCL, American Dental Association Council 2011;12:CD008924. on Scientific Affairs. Managing xerostomia and salivary gland hypofunction. Feb- 50. Ramos-Casals M, Brito-Zerón P, Sisó-Almirall A, Bosch X, Tzioufas AG. Topi- ruary 2015. Available at: http://www.ada.org/~/media/ADA/Science%20and%20 cal and systemic medications for the treatment of primary Sjögren’s syndrome. Research/Files/CSA_Managing_Xerostomia.pdf?la=en. Nat Rev Rheumatol. 2012;8:399-411. 73. Healthways, Inc., Science and Medical Integrity, SD/AP. 2010 Oral Mucositis, 51. Shahdad SA, Taylor C, Barclay SC, et al. A double-blind, crossover study of Care Guide. Available at: https://www.express-scripts.com/art/corporate/pdf/ Biotène Oralbalance and BioXtra systems as salivary substitutes in patients with Oral_Mucositis_Care_Guide.pdf. post-radiotherapy xerostomia. Eur J Cancer Care (Engl). 2005;14(4):319-26. 74. Quinn B. Efficacy of a supersaturated calcium phosphate oral rinse for the 52. Sugiura Y, Soga Y, Tanimoto I, et al. Antimicrobial effects of the saliva substi- prevention and treatment of oral mucositis in patients receiving high-dose can- tute, Oralbalance, against microorganisms from oral mucosa in the hematopoi- cer therapy: a review of current data. Eur J Cancer Care (Engl). 2013;22(5):564-79. etic cell transplantation period. Support Care Cancer. 2008;16(4):421-4. 75. Dass K, Armstrong J, Goodwin J, et al. Efficacy of NeutraSal (Supersaturated 53. Epstein JB, Emerton S, Le ND, Stevenson-Moore P. A double-blind crossover Calcium Phosphate Rinse) in the Prevention and Treatment of Chemotherapy- trial of Oral Balance gel and Biotene toothpaste versus placebo in patients with induced or Radiotherapy-induced Oral Mucositis. ASTRO 2012 Study Registry xerostomia following radiation therapy. Oral Oncol.1999;35(2):132-7. Abstract; presented May 2012. 54. Sjögren’s Syndrome Foundation. Simple Solutions for Treating Dry Mouth. 76. Worthington HV, Clarkson JE, Khalid T, et al. Interventions for treating oral Available at: www.sjogrens.org. candidiasis for patients with cancer receiving treatment. Cochrane Database 55. Fritz JA. The efficacy of NeutraSal in patients with medication-induced xero- Syst Rev. 2010;(7):CD001972. stomia. 2011. Available at: www.neutrasal.com. 77. Pappas PG, Kauffman CA, Andes D, et al; Infectious Diseases Society 56. Levin EZ. Management of xerostomia and microflora with supersaturated of America. Clinical practice guidelines for the management of candidiasis: calcium phosphate rinse. 2013. Available at: www.neutrasal.com. 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 57. Papas AS, Clark RE, Martuscelli G, et al. A prospective, randomized trial for 2009;48(5):503-535.70. the prevention of mucositis in patients undergoing hematopoietic stem cell 78. Yamamoto K, Nagashima H, Yamachika S, et al. The application of a night transplantation. Bone Marrow Transplant. 2003;8:705-12. guard for sleep-related xerostomia. Oral Surg Oral Med Oral Pathol Oral Radiol 58. Singh ML, Papas AS. Long-term clinical observation of dental caries in sali- Endod. 2008;106(3):e11-4. vary hypofunction patients using a supersaturated calcium-phosphate remineral- 79. Hirvikangas M, Posti J, Mäkilä E. Treatment of xerostomia through use izing rinse. J Clin Dent. 2009;20(3):87-92. of dentures containing reservoirs of saliva substitute. Proc Finn Dent Soc. 59. Gupta A, Epstein JB, Sroussi H. Hyposalivation in Elderly Patients. J Can 1989;85(1):47-50. Dent Assoc. 2006;72(9):841–6. 80. Blom M, Lundeberg T. Long-term follow-up of patients treated with acu- 60. Wu CH, Hsieh SC, Lee KL, et al. Pilocarpine hydrochloride for the treatment puncture for xerostomia and the influence of additional treatment. Oral Dis. of xerostomia in patients with Sjögren’s syndrome in Taiwan—a double-blind, 2000;6:15-24. placebo-controlled trial. J Formos Med Assoc. 2006;105(10):796–803. 81. Johnstone PA, Peng YP, May BC, et al. Acupuncture for pilocarpine-resistant 61. Petrone D, Condemi JJ, Fife R, et al. A double-blind, randomized, placebo- xerostomia following radiotherapy for head and neck malignancies. Int J Radiat controlled study of cevimeline in Sjögren's syndrome patients with xerostomia Oncol Biol Phys. 2001;50:353-7. and keratoconjunctivitis sicca. Arthr Rheumatism. 2002;46:748-54. 82. Furness S, Bryan G, McMillan R, et al. Interventions for the management of 62. Nusair S, Rubinow A. The use of oral pilocarpine in xerostomia and Sjögren’s dry mouth: non-pharmacological interventions. Cochrane Database Syst Rev. syndrome. Semin Arthritis Rheum. 1999;28:360-7. 2013;9:CD009603. 63. Haddad P, Karimi M. A randomized, double-blind, placebo-controlled trial of concomitant pilocarpine with head and neck irradiation for prevention of radiation-induced xerostomia. Radiother Oncol. 2002;64(1):29-32. Webliography 64. MedicineNet. Pilocarpine, Salagen. Available at: http://www.medicinenet. Centers for Disease Control and Prevention. Oral Health for Older Americans. com/pilocarpine-oral/article.htm. Available at: http://www.cdc.gov/oralhealth/publications/factsheets/adult_oral_ 65. Weyant RJ, Tracy SL, Anselmo T et al. Topical fluoride for caries prevention. health/adult_older.htm. Executive summary of the updated clinical recommendations and supporting systematic review. J Am Dent Assoc. 2013;144(11):1279-91. Healthways, Inc., Science and Medical Integrity, SD/AP. 2010 Oral Mucositis, 66. Rosenblatt A, Stamford TC, Niederman R. Silver diamine fluoride: a caries Care Guide. Available at: https://www.express-scripts.com/art/corporate/pdf/ "silver-fluoride bullet".J Dent Res. 2009;88(2):116-25. Oral_Mucositis_Care_Guide.pdf. 67. Jenson L, Budenz AW, Featherstone JDB, et al. Clinical protocols for caries John Hopkins Jerome L. Greene Sjögren’s Syndrome Center, Baer A, Papas A, management by risk assessment. J Calif Dent Assoc. 2007;35(1):714-23. Singh M, Sciubba J. Preventing Dental Decay: A Guide for Salivary Hypofunc- 68. Ren Y-F, Liu X, Fadel N, et al. Preventive effects of dentifrice containing 5000 tion Patients. Available at: http://www.hopkinssjogrens.org/disease-information/ ppm fluoride against dental erosion in situ.J Dent. 2011;39(10):672-8. treatment/preventing-dental-decay/. 69. Carvalho TS, Colon P, Ganss C, et al. Consensus report of the European Fed- Sjogrens Syndrome Foundation. About Sjogrens. Available at: http://www. eration of Conservative Dentistry: erosive tooth wear—diagnosis and manage- sjogrens.org/home/about-sjogrens. ment. Clin Oral Invest. 2015;19:1557–61. 70. Wiegand A, Bichsel D, Magalhães AC, et al. Effect of sodium, amine and stannous fluoride at the same concentration and different pH on in vitro erosion.

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1. Xerostomia is the ______assessment of dry mouth by the suf- 7. In head and neck radiation patients, reduced salivary function ferer while hyposalivation is the ______assessment of dry mouth. ______. a. subjective; subjective a. occurs within 1 week of therapy starting b. subjective; objective b. is always reversible c. objective; subjective c. results in thinner saliva d. objective; objective d. increases the amount of antimicrobial agents contained in saliva

2. Unstimulated and stimulated salivary flow of ______, especr - 8. Protection against radiation-modulated damage is helped by tively, are the accepted thresholds for hyposalivation. using. a. <0.1 ml/minute and 0.5 ml/minute a. intensity-increased radiation therapy b. <0.1 ml/minute and 0.6 ml/minute b. amifostine c. <0.1 ml/minute and 0.7 ml/minute c. antioxidants d. none of the above d. attenuation

3. Some of the functions of saliva are to ______. 9. A sticky and/or dry feeling in the mouth and alterations in taste, a. protect dental hard tissues and oral mucosa stringy or ropey saliva are ______. b. aid digestion and influence taste perception a. inevitable in patients taking antibiotics c. aid speaking and smiling b. frequent complaints for dry mouth patients d. all of the above c. infrequent complaints for dry mouth patients d. rarely debilitating 4. Saliva contains an extensive array of anti-bacterial, antiviral and anti-fungal agents that help to maintain oral health. 10. ______is not one of the signs of dry mouth. a. True a. parched-looking oral mucosa b. False b. angular cheilitis c. a parched appearance to the tongue 5. Statherins and proline-rich proteins ______. d. allergic mucositis a. help to maintain salivary supersaturation with calcium and phosphate relative to hydroxyapatite 11. Patients with hyposalivation are at increased risk for b. reduce the intraoral pH ______. c. provide intraoral moisture a. dental caries d. aid speaking and eating b. dental erosion c. oral infections and irritations d. all of the above 6. Anticholiner gic drugs interfere with noradrenaline-related salivary production and sympathomimetic drugs interfere with acetylcho- line-related salivary production. a. True b. False

October 2016 13 DENTAL LEARNING

CEQuiz

12. A patient’s perception of dry mouth and its level of inconve- 17. Patients with dry mouth can be advised to ______. nience/impact on quality of life should be assessed, because this a. brush twice-daily using a soft-bristled powered toothbrush will be indicate ______. b. use a dehumidifier a. the level of salivation c. avoid foods containing any preservatives b. how much fluoride is contained in the excreted saliva d. rinse with an alcohol-containing mouthrinse for its antimicrobial c. whether any treatment or prevention is needed activity d. the patient’s subjective assessment of his/her condition

13. Patients with dry mouth can be advised to suck small amounts 18. ______are recommended to help reduce demineralization. of ice or sugar-free lozenges/candies and to avoid acidic/sour a. fluoride varnish applications candies. b. xylitol rinses a. True c. calcium lavages b. False d. titanium oxide pastes

14. Saliva substitutes ______. 19. If a denture wearer is experiencing candidiasis, he/she can be ad- a. are ultra-thick and nourish the oral mucosa vised to clean the denture by soaking it overnight in a ______b. contain a strong flavoring agent rinse. c. provide palliative relief from dry mouth a. chlorhexidine gluconate d. should only be recommended if the patient's dry mouth is severe b. supersaturated calcium phosphate rinse c. 0.05% or 0.2% fluoride rinse 15. Supersaturated calcium phosphate rinses have been reported by d. baking powder patients or clinicians to ______. a. improve their ability to eat and drink 20. Management and treatment protocols for dry mouth patients are b. provide relief from dry mouth aimed at ______. c. help manage oral mucositis a. relieving dry mouth and the associated discomfort d. all of the above b. r educing the risk of, and managing, associated diseases and conditions 16. Home use of 5,000 ppm fluoride prescription paste once or twice c. improving the patient’s quality of life daily is one of the ways to help to increase protection against d. all of the above ______. a. dental caries b. abrasion c. oral irritations d. hyposalivation

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*E-mail: AGD Code: 149,730 *Telephone: License Renewal Date: EDUCATIONAL OBJECTIVES QUIZ ANSWERS 1. Review salivary production and the functions of saliva; Fill in the circle of the appropriate 2. List and describe etiologies for dry mouth; answer that corresponds to the 3. Describe common oral complications, signs and symptoms associated with dry mouth; and, question on previous pages. 4. Review options for the prevention, management and treatment of oral complications. 1. A B C D COURSE EVALUATION 2. A B C D Please evaluate this course using a scale of 3 to 1, where 3 is excellent and 1 is poor. 3. A B C D 1. Clarity of objectives ...... 3 2 1 4. A B C D 2. Usefulness of content ...... 3 2 1 5. A B C D 3. Benefit to your clinical practice...... 3 2 1 6. A B C D 4. Usefulness of the references...... 3 2 1 7. A B C D 5. Quality of written presentation...... 3 2 1 8. A B C D 6. Quality of illustrations...... 3 2 1 9. A B C D 7. Clarity of quiz questions...... 3 2 1 10. A B C D 8. 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