a study of tooth whitening
Transcription
a study of tooth whitening
Formattato A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND MECHANISM OF ACTION Formattato: Tipo di carattere: (Predefinito) Arial Gerard Kugel Formattato: Inizio sezione: nuova pagina Formattato: Superiore: 50,4 pt, In basso: 50,4 pt, Inizio sezione: nuova pagina, Diversi per la prima pagina A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND MECHANISM OF ACTION Formattato: Centrato 1 A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND MECHANISM OF ACTION Formattato: Tipo di carattere: (Predefinito) Arial Dipartimento di Scienze Odontostomatologiche Università di Siena Viale Bracci 53100 Siena Formattato: Portoghese (Brasile) Prepared for the graduate committee on June 13, 2004 Gerard Kugel Boston, MA, USA Eliminato: 89¶ 2 The present thesis is respectfully submitted to Prof Piero Tosi, Rector of the University of Siena, to Prof Alberto Auteri, Dean of the Faculty of Medicine, University of Siena, to Prof Egidio Bertelli, vice-Dean of the Faculty of Medicine and Director of the Department of Dental Science, and to Prof Marco Ferrari, Pro-Rector for international affairs and President of Dental School, University of Siena. Graduate Committee: Formattato: Inglese (U.S.A.) Promotor Committee Prof. Dr Marco Ferrari Prof. Dr C.L. Davidson Prof. Dr F. Tay Prof. Dr Toledano Prof. Dr Balleri Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial This thesis was prepared at Tufts University School of Dental Medicine, Boston MA, USA and at the School of Dentistry University of Siena, Italy. 3 Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ Contents Formattato: Tipo di carattere: 14 pt Formattato: Tipo di carattere: 13 pt Chapters Formattato: Tipo di carattere: 12 pt 1 Introduction 2 A Novel Low Dose Tooth-Whitening Delivery System Formattato: Tipo di carattere: 12 pt Efficacy and Safety: A Randomized and Controlled Clinical Trial Formattato: Tipo di carattere: 11,5 pt Formattato: Tipo di carattere: 4 pt Formattato: Tipo di carattere: 12 pt 3 Concentration and Dose Response Clinical Trial Evaluating the Peroxide Concentration Response of a Polyethylene strip Delivery System over 28 Day 4 Light activated Tooth Whitening Clinical Evaluation of a 35% Hydrogen Peroxide In-Office Whitening System Formattato: Rientro: Sporgente 36 pt, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:3 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra di: 36 Formattato: Tipo di carattere: 11,5 pt Formattato: Tipo di carattere: 12 pt 5 Chemical Vs Light activated Tooth Whitening Clinical Evaluation of Chemical And Light-Activated Tooth Whitening Systems 6 Tooth whitening and its Effect on Enamel and Dentin Daily Use of Whitening Strips on Tetracycline Stained Teeth: Comparative Results after Two Months 7 Long Term Hydrogen Peroxide Exposure and its Effect on Dentin Comparative Study of 6.5% Hydrogen Peroxide Bleaching Strips on Tetracycline Stain: Clinical Response after Six Months Daily Use 8 Paint on delivery systems A clinical Comparison of two Paint on Whitening Systems 9 Maintenance of Whitening Clinical Study to Evaluate the Maintenance of Whitening after Bleaching Treatment Formattato ... 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[24] Eliminato: 89¶ 4 10 Intrapulpal Temperatures with Light Activated Whitening Effects of a Light Activated Bleaching System on Pulp Chamber Temperature in Vitro Formattato: Tipo di carattere: 8 pt Formattato: Tipo di carattere: 12 pt, Grassetto Formattati: Elenchi puntati e numerati Formattato: Tipo di carattere: 12 pt 11 Effect of Tooth Whitening on Enamel An exploratory study using SEM to evaluate the enamel surface effects in vivo of a 6% hydrogen peroxide strip bleaching system with that of a 2.5% chlorite tray bleaching system 12 Formattato: Tipo di carattere: 12 pt, Grassetto Formattato: Tipo di carattere: 12 pt Formattato: Tipo di carattere: 11,5 pt, Non Grassetto Formattato: Rientro: Sinistro: 39,6 pt, Interlinea singola Summary and Conclusions Formattato: Tipo di carattere: 11,5 pt Formattato: Tipo di carattere: 11,5 pt, Non Grassetto Formattato: Tipo di carattere: 12 pt, Grassetto Formattati: Elenchi puntati e numerati Formattato: Tipo di carattere: (Predefinito) Arial, 11,5 pt, Non Grassetto, Colore carattere: Automatico, Non Tutto maiuscole Formattato: Rientro: Sinistro: 39,6 pt, Interlinea singola Formattato: Tipo di carattere: 11,5 pt, Non Grassetto Formattato: Tipo di carattere: 12 pt Formattati: Elenchi puntati e numerati Formattato: Tipo di carattere: Grassetto Formattato: Normale Eliminato: 89¶ 5 Eliminato: ¶ Chapter 1 Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: 12 pt INTRODUCTION Formattato: Tipo di carattere: (Predefinito) Arial, Grassetto The dental profession has succeeded in reducing caries and periodontal diseases and as a result dental problems have decrease to the point where esthetic improvements are now more Eliminato: ¶ ¶ ¶ ¶ attainable 1. One of the fastest growing areas of esthetic dentistry today is the management of Formattato: Allineato a sinistra the discolored and hypoplastic dentition. The demand for an improved appearance and a whiter Eliminato: TOOTH WHITENING smile has made tooth whitening a very popular dental procedure. Tooth whitening, sometimes Formattato: Tutto maiuscole referred to as “bleaching”, offers a conservative treatment option for discolored teeth in Formattato: Rientro: Prima riga: 0 pt comparison to resin bonded composites, porcelain veneers or crowns 2,3 . Candidates for whitening procedures include patients whose teeth are stained by aging, chromogenic foods, endodontic treatment, tetracycline use and smoking or use of other tobacco products. Success Eliminato: ¶ Eliminato: (Burrell 1997 Formattato: Apice Eliminato: ) Eliminato: (Papathanasiou 2000, 2001) of the treatment depends on type, intensity and location of the discoloration and a careful diagnosis by the practitioner. Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Formattati: Elenchi puntati e numerati History of Tooth Whitening Many attempts to find an effective bleaching method have been made through out the history of dentistry. The desire to have whiter teeth dates back at least 2000 years ago. During the first Eliminato: Bleaching Eliminato: : Formattato: Rientro: Prima riga: 0 pt century the Romans physicians claimed the use of urine, especially Portuguese, to brush the 4 teeth would whiten the teeth . Barber-surgeons used a solution of nitric acid to lighten the teeth after using a course metal file to abrade the enamel 4, practice until late eighteenth century. Eliminato: (Dale, esthetic dentistry Eliminato: ) Eliminato: (Dale, esthetic dentistry Eliminato: ) Eliminato: In 1895 it was reported the combination use of pyrozone 25% and electricity to bleach the 5 Eliminato: (Westlake A, 1895) Eliminato: (Adams, 1987) endodontically treated teeth . Later on, in 1916, it was stated the use of hypochloric acid to treat endemic fluorosis 6. In 1939 it was advocated the use of 30% hydrogen peroxide, ether Eliminato: 89¶ 6 . . 7 and heat to treat fluorosis staining . In 1966, it was promoted the combination use of Eliminato: (Younger, 1939 Eliminato: ) Eliminato: Mcinnes, 1966 hydrochloric acid and hydrogen peroxide to remove “brown stain from mottled teeth” due to a 8 chronic endemic dental fluorosis . The early efforts to whiten teeth relied on the assumption that the process involved the removal of extrinsic enamel stain. The mechanism of action was poorly understood. Eliminato: It is interesting to observe that most of the efforts of tooth whitening at the time were done evolving extrinsic enamel stains. Formattato: Tipo di carattere: Non Grassetto, Colore carattere: Automatico It was only on 1970 that Cohen and Parkins first published a method for bleaching the Formattato: Colore carattere: Automatico Eliminato: discolored dentin of young adults with cystic fibrosis who has undergone tetracycline treatment Eliminato: (Cohen, 1970). T 9 . This publication indicated that the mechanism of tooth whitening using hydrogen peroxide involves penetration to the dentin. In 1976, Nutting and Poe introduced the walking bleach technique, which uses 35% hydrogen peroxide and sodium perborate for nonvital teeth bleaching10. The breakthrough in tooth whitening was in 1989 when Haywood and Heymann published the nightguard vital bleaching technique 11 . This is procedure is still widely used Eliminato: Eliminato: (Nutting, 1976). Eliminato: technique. among the dental community as the take-home bleaching system. Eliminato: ¶ Eliminato: ¶ Formattati: Elenchi puntati e numerati Tooth Whitening Systems Eliminato: Tooth whitening with various concentrations of peroxide has been demonstrated to be safe and effective in a variety of regimens, including in-office procedures, dentist-prescribed and supervised home treatments and over the counter system approaches 12 . Most dental practices in the United States offer some form of tooth whitening system. Eliminato: .( Eliminato: REFERENCE? LI?) M Eliminato: and as many as one out of five patients have their teeth whitened. Eliminato: Eliminato: : A) Take- home System Eliminato: The most common regimen is the at-home use for 2 to 4 weeks, based on the color of the teeth at the start of whitening 13,11 .The use of hydrogen peroxide for removing intrinsic stains from vital teeth has been used for many years. Haywood and Heymann published the first article describing night guard vital bleaching in 1989 11 . A tray is fabricated from a model of the patient’s teeth using a soft plastic nightguard. This tray is the loaded with carbamide peroxide 7 Eliminato: (Kugel 2000 and Haywood). Eliminato: publication Eliminato: The dentist prescribed home-applied technique most commonly between 10% to 22% carbamide peroxide. Eliminato: patients Eliminato: 89¶ gel and seated over the teeth for approximately 2 hours. The most commonly prescribed concentrations are 10% to 22% carbamide peroxide. Eliminato: The advantage of the take-home systems is the decreased cost when compared to the in office bleaching options. The major disadvantages associated with take-home systems are: (a) they Eliminato: (with minimal inoffice time required to fabricate trays and educate the patient on the take-home procedure). require significant patient compliance with the number of applications usually involving 1-2 hours twice a day or overnight wear, and (b) the entire treatment usually takes at least four weeks. Eliminato: ¶ Eliminato: : B) In-Office System Eliminato: The most acceptable applications involve are in-office techniques, dentist prescribed take-home systems or a combination of both. The in-office bleaching technique generally employs a 15%, 30% or 35% hydrogen peroxide bleaching agent (heated or non-heated). Formattato: Rientro: Prima riga: 0 pt The advantages of the in-office procedure are: (a) it requires minimal patient compliance, and (b) immediate results are attainable. The disadvantages to this treatment are: (a) chair-time requirement, and (b) cost to the patient. It is important to note that this procedure usually requires multiple office visits. Eliminato: ¶ Eliminato: : C) Combination Technique By combining the two techniques (in-office and take-home), there is a reduction in the amount of Formattato: Rientro: Prima riga: 0 pt time and the need for repeated office visits as well as the expense associated with in-office bleaching as a stand-alone technique 14 Eliminato: (Garber 1997). . The combined technique increases overall success Eliminato: (Kugel 1997). and patient satisfaction. This procedure involves the use of a high concentration of hydrogen peroxide (35%) delivered chair side for one hour followed by a take home regimen of 5days. This is often followed by an additional chair side application. 15 Eliminato: (Kugel 1997). Eliminato: 89¶ 8 Eliminato: : D) Whitening Strips A new method involves using a 5.3% hydrogen peroxide-impregnated polyethylene strip Formattato: Rientro: Prima riga: 0 pt (Crest®Whitestrips™) for 30 minutes twice daily. This method is recommended for maintaining Eliminato: and for offering treatment…( Kugel, ... [25] already whitened teeth. It can also be a good option to patients who cannot afford the cost of Formattato: Non Apice / Pedice other whitening treatment or who do not have the time for multiple dental visits for tray fabrication 13 . It was published in 2002 the use of the whitening strips for tetracycline stained teeth 13. Eliminato: . Formattato ... [26] Eliminato: (Gerlach et al., 2001). Formattato ... [27] Eliminato: (Harris et al., 2001) … (McMillan et al., 2001). ... [28] Development of this flexible, polyethylene whitening strips allows for consistent bleaching using shorter contact times. Fixing the daily strip regimen at 30 minutes per day, a randomized, double blind, a double placebo-controlled clinical study was conducted to evaluate the effects of Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Eliminato: Formattato ... [29] Eliminato: ¶ increasing the dosing regimen on tooth shade 17 . Also, an in vitro study explored the impact of varying concentration of carbamide peroxide ranging from 0.4% to 10% on bleaching efficacy and the impact of increasing hydrogen peroxide concentration on bleaching strip efficacy and tolerability under clinical conditions 18 . These studies demonstrated that a modest increase in Eliminato: The main drawback is that they are limited to the anterior teeth and cannot be easily adapted to the malposed teeth.¶ Eliminato: ¶ ¶ ¶ Eliminato: : peroxide concentration on a flexible bleaching strip results in increased whitening effectiveness, Eliminato: Technological advances in dentistry make it ... [30] without adversely impacting on overall tolerability. Formattato ... [31] Formattato ... [32] Eliminato: , being promoted ... [33] Eliminato: E) Light Activated Whitening Systems Formattato The introduction of light activated devices such as Plasma arc, Light Emitting Diodes (LED), Argon lasers, metal halide and xenon-halogen lights by dental manufacturers have helped Formattato Eliminato: the … Formattato create a public demand for the light enhanced tooth whitening systems. ... [34] Eliminato: In 2002 one ... article [35] Eliminato: ... [36] , ... [37] ... [38] 3 Formattato ... [39] Eliminato: Reviews of ... these [40] Controversial papers were published evaluating the efficacy of light activated bleaching agents in 2002. The first article reported positive results19. The other articles concluded the opposite findings 20, 21 . These articles either maintained 22 or questioned the results 23 . The dental profession still needs more evidence of its effectiveness in order to provide better and more 4 Eliminato: …in support… ... [41] Formattato Formattato ... [44] Eliminato: It is apparent...that [45] Formattato Eliminato: 89¶ 9 ... [42] Eliminato: discredited ... [43] 5 ... [46] Eliminato: The lack of ... [47] efficient treatment. The high demand for “up to date” dental office by patients and clinicians Eliminato: need for more ... [48] stimulates manufacturers to inundate the dental profession with advertisements emphasizing Eliminato: more important as that light activated tooth whitening is “the state of the art” and should be part of the armamentarium of the office, with not clear evidence of its usefulness. The use of hydrogen peroxide (H202) for bleaching teeth has been evident with use of heat or Eliminato: even Eliminato: “up to date”... dental [49] Eliminato: Formattato ... [50] Formattato ... [51] Formattato ... [52] Eliminato: Bleaching is... the[53] Eliminato: not . In order to gain treatment time, clinicians have attempted to accelerate the degradation of Eliminato: In 1970, H202 by using heat or light. Cohen and Parkins introduced a technique for bleaching discolored Eliminato: 24 teeth using hydrogen peroxide and a hand-held heating source 9. Eliminato: , such as ... [54] 7 Formattato ... [55] Formattato ... [56] Eliminato: Formattato Recent in vitro study has shown that the use of intense lights does elevate temperature of the bleaching material and as a result caused an increase in intrapulpal temperature. This may have an impact on post bleaching tooth sensitivity and pulpal health 25 . Another research in vitro has verified that the use of laser-activated hydrogen peroxide did not produce any perceivable colour change 26. Light-activated chair side bleaching systems probably offer the benefit of being less time-consuming while producing faster results. The assumption is that clinically tolerable levels of heat will speed the breakdown of H2O2 tooth bleaching chemicals and this accelerated H2O2 breakdown will cause teeth to lighten more rapidly per unit time. In a recent study the decomposition of hydrogen peroxide was measured ... [57] Eliminato: ¶ Eliminato: ¶ Eliminato: Most clinicians ... [58] Formattato ... [59] Formattato ... [60] Formattato ... [61] Formattato ... [62] Formattato ... [63] Eliminato: T Formattato ... [64] Formattato ... [65] Formattato ... [66] Eliminato: he introduction of ... [67] Formattato ... [68] Formattato ... [69] Formattato ... [70] Eliminato: by the amount of oxygen released. The data from this study indicated that at temperatures of up to 85º C accelerated decomposition of the 35% H2O2 was minimal when compared to the control gel 20. Formattato ... [71] Formattato ... [72] Formattato ... [73] Eliminato: The use of light activated bleaching system to accelerate the bleaching process is still on question and more evidence needs to be gathered in order to make a more precise assertion of its effectiveness. Formattato ... [74] Formattato ... [75] Formattato ... [76] Eliminato: Research in... vitro [77] Formattato ... [78] Formattato ... [79] Formattato ... [80] Eliminato: 89¶ 10 F) Toothpaste Many types of toothpaste are available in the market as tooth whitening products, but only a small number of them show stain removal ability and effectiveness. Most of these toothpastes do not contain bleaching agents in their formulation. The ones that do have very low bleach concentration and contact times relatively too short to be effective 27 . Whitening toothpastes contain mild abrasives to remove surface stains. The peroxide content in the toothpastes are very low (1% or less), also the exposures of the toothpastes on the tooth is minimal hence any whitening minimal 28. Eliminato: The efficacy of a bleaching treatment can be determined through first or second evaluators or various technical methods. The use of a shade guide, colorimeter, or computer digitization to measure color change over time has been currently included in clinical trials to 13, assure efficacy assessment 14, 15 .¶ Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Formattato: Tipo di carattere: 12 pt, Non Grassetto Formattato: Normale, Giustificato, Non regolare lo spazio tra testo asiatico e in alfabeto latino, Non regolare lo spazio tra testo asiatico e caratteri numerici Eliminato: : Eliminato: G) Over the Counter Products Eliminato: (Sharif 2000). Easy availability of over the counter whitening products has made whitening of teeth more popular amongst people of all ages. There are different types of over the counter products like Eliminato: ( 1 Eliminato: less ) Eliminato: , Eliminato: mi whitening dentifrices, tray based, whitening strips and the recently introduced brush applications. The latest inclusion to OTC products is a Brush technique. This technique is nontray based paint on application. Gingival irritation can be prevented due to the ease in Eliminato: .11 Formattato ... [81] Eliminato: ¶ Eliminato: : Eliminato: application. Over the counter bleaching kit requires the consumer to use either a prefabricated tray or fabricate their own semi-molded tray then fill it with supplied bleaching agents. These types are less than ideal because the trays are not custom fitted and the formulation is not sophisticated as those dispensed by the dentist 29. Eliminato: .10 Formattato ... [82] Eliminato: ¶ [83] ... Formattato ... [84] Formattati: Elenchi puntati e numerati ... [85] Eliminato: a Eliminato: ECHANISM... OF[86] Mechanism of Action Many studies have been conducted to evaluate the effectiveness of various bleaching materials Formattato ... [87] Formattato ... [88] Eliminato: [ and techniques 27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 15, 41, 42 . The brightening effect of the carbamide peroxide and hydrogen peroxide or of both in a combined technique was reported during the Eliminato: Mokhlis et al.... [89] Eliminato: Christensen... 1989, [90] Eliminato: Cibirka et al. 1999 Eliminato: , above investigations. Eliminato: Jones et al. 1999, Eliminato: Haywood et ... al.[91] Eliminato: 89¶ 11 The exact mechanism of action is not completely understood. Hydrogen peroxide diffuses through the organic matrix of the enamel and dentin 43, 44, 45. Because the radicals have unpaired Eliminato: (Bowles et al 1987, 1986, Fuss et al 1989). electrons, they are extremely electrophylic and unstable and will attack most other organic molecules to achieve stability, generating other radicals. These radicals can react with most unsaturated bonds, resulting in disruption of electron conjugation and a change in the absorption energy of the organic molecules in tooth enamel. Simpler molecules that reflect less light are formed, creating a successful whitening action. This process occurs when the oxidizing agent (hydrogen peroxide) reacts with organic material in the spaces between the inorganic Eliminato: (Goldstein and Garber 1995). salts in tooth enamel 46. Eliminato: ¶ Formattato: Rientro: Sinistro: 18 pt Bleaching Penetration Eliminato: ¶ Enamel is the most dense tissue of the body a study conducted by Bartelstone in 1951 showed Formattato: Tipo di carattere: 12 pt the penetration of I-131 through enamel to dentin which diffused to pulp 47 . Carbamide peroxide breaks down into hydrogen peroxide, carbon dioxide urea and ammonia. Some of the by products penetrate the dentinal tubules reaching the pulp causing reversible pulpitis 43, 48 . Some Formattato: Rientro: Prima riga: 0,05 pt, A sinistra -0,01 ch Formattati: Elenchi puntati e numerati Formattato: Rientro: Prima riga: 0 pt of the pulpal enzymes are sensitive to hydrogen peroxide along with heat. However, in vital Eliminato: (Bartelstone 1951) bleaching the amount peroxide reaching pulp compared to amount of H2O2 required to cause Eliminato: . (Gokayo,2000; Bowels, Ugwuneri 1987) this damage is very low Eliminato: in vital 44 . Gokay et al a higher peroxide diffusion was seen in teeth with Eliminato: (Bowels,Thompso n 1986) restorations using a high concentration of carbamide peroxide compared to using a lower Eliminato: (Gokay 2000) concentration 48. In vitro data using extracted human teeth have demonstrated that a 10% carbamide peroxide gel can change the color of dentin over time 49. In this study teeth were sectioned and placed on glass slides. The teeth were sealed at the cut surfaces and bleached for 10 days. Digital photos Formattato: Tipo di carattere: Non Grassetto, Colore carattere: Automatico Formattato: Tipo di carattere: Non Grassetto, Colore carattere: Automatico were taken from marked areas and lightness values determined. Eliminato: 89¶ 12 Sensitivity is generally mild and transient. Sensitivity occurs earlier in treatment and decreases as treatment continues. This might occurs due to the close contact of gel to the tooth and Eliminato: (Michael 2002). disappearance may be due to sensory accommodation 50. Eliminato: ¶ Eliminato: discoloration Tooth Discoloration: External – Internal Staining Formattato: Tipo di carattere: 12 pt Tooth discolorations can be superficial changes that affect the enamel surface, or can be Formattato: Rientro: Prima riga: 0 pt deeper staining which affects the entire tooth structure. It is essential for the dentist to identify the type of discoloration in the patient’s tooth, diagnose the cause and define the appropriate treatment plan. Tooth discoloration in vital teeth can result from aging, tobacco use, Eliminato: (Haywood 1999). chromogenic foods, medications and pulpal pathology 51. Superficial discolorations are usually caused by the staining effects of certain foods, beverages, or tobacco products. Tea, coffee, red wine, cola and smoking or chewing tobacco usually result in yellow, brown or black staining with pits, fissures, grooves and enamel defects retaining even more of the pigmenting effects. Yellow-brown stains are usually external and from accumulation Eliminato: H. Eliminato: A. Eliminato: utero of environmental colorants to an irregularly formed enamel matrix. Conversely, internal staining results from improper calcification and/or hypoplasia. More severe discolorations result from systematically prescribed medication during tooth formation, intake of excessive amount of fluoride during enamel formation and calcification, different systemic conditions, dental conditions and/or treatment and aging. In 1956, Schwachman and Schuster first reported tooth discoloration caused by incorporation of systemic tetracycline into tooth structure 52 . Tetracycline discoloration occurs with the systemic intake of tetracycline during tooth formation (second trimester in uterus to 8 years of age). The discoloration of the permanent dentition depends on the amount and duration of tetracycline use 53 . The portion of the tooth, color and severity of the stains can be determined by the stage of the tooth development at the time of the drug administration. Tetracycline is incorporated into Eliminato: Eliminato: Excessive systemic fluoride during enamel matrix formation and calcification can result in a defective matrix and improper calcification known as endemic enamel fluorosis or mottled enamel (Stewart et al. 1982, Swift 1988). Fluorosis usually presents bilaterally with white chalky spots, yellow or brown staining Eliminato: . Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Colore carattere: Automatico Eliminato: 4 Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Colore carattere: Automatico Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Colore carattere: Automatico Eliminato: 89¶ 13 dentin during tooth calcification intra and post partum, probably through chelation with calcium 54 forming tetracycline orthophosphate . It can be deposited in fetal tooth buds when administered in the third trimester of pregnancy or by a child during the development of the tooth (between ages 3 to 4 months and 7 to 8 years) Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Colore carattere: Automatico Eliminato: 55, 56 . Colors may vary intensity of gray, blue, brown and yellow. The different banding can also be attributed to the variations of the Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Colore carattere: Automatico Eliminato: tetracycline derivates Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital bleaching with professional tray or strip systems can yield an evident improvement in appearance within a few weeks. While non-invasive, treatment may need to continue over an extended period. Some individuals will show favorable response after 3-4 months, after which treatment may be discontinued. Duration may be difficult to predict, given the variable clinical 6 7 Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Colore carattere: Automatico Eliminato: ¶ Eliminato: ¶ Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Colore carattere: Automatico Formattato: Corpo del testo, Allineato a sinistra manifestations of tetracycline staining. Practitioners and patients should be advised that optimal Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt bleaching of tetracycline staining may necessitate extended daily at-home treatment over a Formattato: Rientro: Prima riga: 0 pt period of 3-6 months. The costs, risks, and benefits of the various treatment options must be Eliminato: management( considered as part of overall patient management 57, 58 . Excessive systemic fluoride during enamel matrix formation and calcification can result in a defective matrix and improper calcification known as endemic enamel fluorosis or mottled enamel 59,60 . Fluorosis usually presents bilaterally with white chalky spots, yellow or brown staining Systemic conditions can also cause tooth discolorations. Amelogenesis imperfecta may result in hypoplasia or hypocalcification with yellow or brown stains and dentinogenesis imperfecta with brownish violet, yellowish or gray discolorations 61 . Hypoplasia or hypocalcification can occur with clefting of the lip and palate or with acquired illnesses such as cerebral palsy, serious renal damage and severe allergies 46 . Blue, brownish or green tooth discolorations may be caused by destruction of an excessive number of blood-cell erythrocytes in erythroblastosis fetalis a result of Rh-factor incompatibility between mother and fetus 46, 61. Formattato: Non Apice / Pedice Eliminato: Haywood, Kugel 02) Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital bleaching of tetracycline-stained teeth. J Esthet Dent. 1997;9:13-9. ¶ Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Colore carattere: Automatico Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Formattato: Tipo di carattere: Grassetto Eliminato: (Stewart et al. 1982, Swift 1988) Eliminato: (Shafer et al. 1974) Eliminato: (Goldstein and Garber1995) Eliminato: (Shafer et al. 1974, Goldstein and Garber 1995) Eliminato: 89¶ 14 Patients with porphyria, a rare condition that causes an excess production of pigment, may result in a red, purplish-brown or brownish tooth discoloration 46, 62, 63 . Dental caries, discolored acrylic or restorations (made of composite, amalgam and/or metal), pins, posts and other materials employed in the dental environment can have an adverse effect on tooth coloration resulting in a darkened shade of the patient’s dentition. Aging usually brings thinning of the enamel, loss of the translucent enamel layer, and formation of secondary dentin. The combination of less enamel and more darkened, opaque dentin creates an older-looking darker tooth 46. Tooth Whitening Protocol Tooth whitening, when used with professional supervision, can be safe and effective. A complete oral examination (with a review of the patient’s medical and dental history) and an updated set of periapical radiographs are necessary before planning any bleaching procedure. It is very important to determine the severity and cause of the tooth’s discoloration because it will allow the dental clinician to specify which treatment plan options are to be used. Discolorations due to medications will need longer and more persistent treatment than stains that occurred from aging, smoking or eating habits. Existence of carious lesions, restorations, endodontic treatment, pulpal anatomy and any periapical pathology must be determined during the clinical and radiographic examination before the onset of the bleaching procedure Different pulp size teeth may have different rates of response to bleaching 39 . 64 . Existence of Eliminato: (Jordan et al. 1984, Faunce 1983, Goldstein and Garber 1995) Eliminato: (Goldstein and Garber 1995) Eliminato: Intrinsic Stains: aging, chromatogenic food and drinks, excessive fluoride intake, medication (tetracycline) and others can be the cause of intrinsic stains. Tetracycline stains, though, are considered to be the most difficult types of intrinsic stains to manage clinically. The devastating effect on tooth formation of as little as one gram of tetracycline was 1 recognized in the late 1950s and confirmed by a study of cystic fibrosis patients by 2 Swachman et al . In 1970, Cohen and Parkins published a method for bleaching the discolored dentin of young adults with cystic fibrosis who had undergone tetracycline 3 treatment Eliminato: Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital bleaching with professional tray or strip systems can yield an evident improvement in appearance within a few weeks. While non-invasive, treatment may need to continue over an... [92] Formattato ... [93] Eliminato: Different variations of tetracycline and derivates produce different colors in ... the [94] Formattati: Elenchi puntati e numerati Eliminato: .¶ Eliminato: .¶ ¶ Tooth Whitening Protocol Formattato ... [95] Formattato ... [96] caries, microcracks in enamel, exposed dentin and open margins in existing restorations must Formattato: Rientro: Prima riga: 0 pt also be taken into consideration before treatment. Restorations that are not properly sealed and Eliminato: (Nathanson 1987). Eliminato: untreated carious lesions can lead to extensive sensitivity and should be treated before Eliminato: ( beginning any bleaching treatment 46. Eliminato: Haywood et al. 1994) Eliminato: treatment Formattato: Apice Eliminato: (Goldstein et al. 1995) Eliminato: 89¶ 15 Tooth sensitivity and gingival irritation have always been a concern when tooth whitening is Eliminato: applied used. Both in-office and take-home bleaching procedures have been reported to induce sensitivity to a significant number of patients 65 . Tooth whitening is generally well tolerated. Eliminato: (Nathanson 1997). Eliminato: Some patients may experience tooth sensitivity and mild oral mucosa irritation; however, these symptoms are generally mild and are alleviated at the end of treatment. Tolerability may be impacted by tray design, poor compliance or product ingestion. Tray thickness may contribute to poor compliance by causing occlusal interferences or jaw pain 13. Eliminato: (Kugel 2000 did any other author said this also?). Detailed clinical and radiographic examination, fabrication of a custom-fitted, well- adapted mouth guard, careful selection of the tooth whitening material and proper patient instruction can significantly decrease the possibility of tooth sensitivity or gingival irritation during the take-home treatment. The tray fabrication technique should include “scalloping” of the tray material to the gingival line to reduce the exposure of excess bleaching agent onto the soft tissues. The thickness of the tray material (0.040” is recommended) is also important to prevent patient discomfort and other problems associated with the temporo mandibular joint (TMJ). The design of the tray (with reservoirs or without reservoirs) will be a determinant of the type of tooth whitening material to be used. Selection of the product to be used should be based on the concentration of active ingredient, viscosity and other salient features. Teeth that have composite or amalgam restorations and are being treated with 10% carbamide peroxide demonstrated increased microleakage in the restorations, according to a study which evaluated the microleakage of previously restored Class II restoratives after exposure to 10% carbamide peroxide. Microleakage of previously restored Class II restoratives after exposure to Formattato: Non Apice / Pedice 10% carbamide peroxide 66. Eliminato: 89¶ 16 The immediate placement of composite resin on bleached teeth has been controversial. According to a study evaluating the shear bond strength of composite restorations placed on bleached and non bleached teeth, there was no statistically significant difference when the composites were placed at 24 hours, 48 hours, 4 or 6 days 67 . A different study, evaluating the effects of take home bleaching systems on enamel surfaces, suggests that a period of 4 days must elapse before bonding to a tooth bleached with a peroxide material, while no delay is necessary for a non-peroxide based bleaching system 68. Most authors and tooth whitener manufacturers recommend the use of reservoirs during bleaching tray fabrication, in order to increase the effectiveness of the tooth whitening material 11 . Clinical studies examined the role of reservoirs reveal that the presence or absence bleaching solution reservoirs in the bleaching tray did not increase the success of take-home bleaching with 10% carbamide peroxide gel Eliminato: (D. Bardwell, C. Habib, G. Kugel, N. Mehta, C. Leone Abstract #306, JDR 2000 Special Issue Vol.79.¶ Eliminato: . Eliminato: (Effect of bleaching on Composite Resin Shear Bond Strength In Vitro. P. Yu, A. Aboushala, D. Bardwell JDR 1999 Vol.78 special issue, abstract #1445) Eliminato: Effects of the two home bleaching systems on Enamel surfaces. M. MacKay, R. Perry, E. Swift, M. Varga S JDR 1997 special issue abstract #1405. (Check also two studies I did with Julie O’Quinn and William Dodge showing that bond strength is impaired immediately after bleaching. I believe the studies were published in 1996!).¶ Eliminato: (Haywood & Heymann 1989, Goldstein & Garber 1995, Ultradent Products 1996, Discus Dental 1996, Dentsply 1996) Eliminato: reveal that 69 . Tooth whitening products pH differs in a range of 4.0 to 7.5, with more acidic pH in materials with higher peroxide concentration. It is important that these materials have a relatively neutral pH, because root resorption, enamel demineralization and erosion may occur with pH less than 5.2 70 . Dental lasers have been used for tooth whitening. Currently the argon laser is the most commonly used laser for power Eliminato: ( Eliminato: Javaheri & Janis 2000) Eliminato: products pH differ Eliminato: ( Price et al. 2000) Eliminato: (Sun 2000) Eliminato: (Blankenau et al. 1999) Eliminato: ¶ bleaching 71. There is not enough evidence to support safety and efficacy of laser bleaching 72. Eliminato: ¶ ¶ Formattato: Allineato a sinistra Bleaching Side Effects Eliminato: ¶ Toxicology Formattato: Tipo di carattere: 12 pt, Grassetto FDA has approved hydrogen peroxide and carbamide peroxide to be used for debriding oral Eliminato: ¶ Formattato ... [97] wounds. Even though bleaching is a longer process than debridment, in vitro toxicological Eliminato: Bleaching Adverse Effects¶ ... [98] evaluation of bleaching agents like 10% carbamide peroxide or 4% hydrogen peroxide was Eliminato: : lower or comparable to commonly used dental materials like eugenol, dentifrices ,mouth rinses Eliminato: ¶ <#>Toxicology:¶ and composites 12. Formattato: Rientro: Prima riga: 0 pt Eliminato: . Eliminato: (Li 1997) Eliminato: 89¶ 17 Studies have shown that daily exposure of carbamide peroxide should not exceed 10mg/kg 73 . Li and Matis found that the average amount of bleaching agent used is 502mg per application. Eliminato: (Dahl and Becher 1995) Formattato: Tipo di carattere: Grassetto Eliminato: Y. Even if the patient swallows all the gel, it would not exceed more than 8.37mg /kg 12 . Therefore Eliminato: B Eliminato: . the safety factor of the bleaching agent is high. Eliminato: (Li 1997). Eliminato: ¶ Oral Side Effects Formattati: Elenchi puntati e numerati The mucosal irritation mostly occurs due to ill fitting trays, improper application of bleaching gel Eliminato: side Eliminato: e or using it for longer time than prescribed. Schulte J and others showed that the group with the overnight exposure to the bleaching gel subjects had mucosal irritation 74 . The soft tissue irritation generally is minimal and is resolved either by adjustment of the bleaching tray, or Eliminato: : Formattato: Rientro: Prima riga: 0 pt Eliminato: Eliminato: (Schulte, 1993) Eliminato: ¶ 75 shortly after cessation of the treatment . Eliminato: (Haywood VB 1994) Eliminato: ¶ Tooth Sensitivity Formattati: Elenchi puntati e numerati Studies have shown that sensitivity occurs in 55 to 75% of the treatment groups. The placebo Eliminato: : groups also experienced 20-30% sensitivity. One study reported tooth sensitivity of about 15 % Formattato: Rientro: Prima riga: 0 pt wearing only the bleaching tray 76,77. Eliminato: (Haywood VB 2001 The development of tooth sensitivity can be a multifactorial phenomenon. If the whitening tray is fabricated from a thick material, it can result in an appliance producing minor orthodontic movements 78 . Allergies and chemical sensitivity to the composition of the tray or the bleaching gel. And the free radical formation of the whitening gel tooth brushing during participation in a clinical trial 77 79 .It can also result from overzealous . Glycerine which is used to carry the active ingredient can absorb water therefore can have a dehydration effect, hence resulting in Eliminato: ; Michael 2002) Eliminato: (Pohjola R 2002) Eliminato: (Leonard 1997) Eliminato: ( Eliminato: Michael 2002) Eliminato: ( Eliminato: Pohjola 2002; Leonard 1997 ) Eliminato: ¶ Formattato: Allineato a sinistra Eliminato: ¶ sensitivity. 78,79. Formattato: Tipo di carattere: 12 pt Formattato: Tipo di carattere: 12 pt, Grassetto Summary Eliminato: : In summary, although tooth whitening is one of the most popular dental procedures it is also one Formattato: Tipo di carattere: Grassetto of the least understood. We are still unclear as to its mechanism of action. There is little data of Formattato: Rientro: Prima riga: 0 pt Eliminato: 89¶ 18 the effects of both concentration and dose on outcome. The techniques for measuring color change have been brought into question. The cause(s) of sensitivity are not clear nor are the issues of long tern exposure to hydrogen peroxide. The issue of rebound in color has not been well examined and issues related to maintenance of the whitening effect are also poorly Eliminato: understood Most recently there has been a push to find ways to accelerate as well as improve the delivery of the whitening process. These include the application of a number of different light sources believed to accelerate the breakdown of peroxide and thus speed up the whitening process. The research in this area has been controversial with publications having quite different conclusions as to the efficacy of light activated bleaching. In an effort to improve the delivery systems both polyethylene strips and paint-on whitening products have been introduced. The efficacy of the paint-on products has been questioned and little research on these products can be found Eliminato: 89¶ 19 REFERENCES 1) Burrell KH. ADA supports vital tooth bleaching—but look for the seal. Journal of the American Dental Association. 128 Suppl:3S-5S, Apr. 1997. 2) Papathanasiou A., Bardwell D, Kugel G : Combining In Office and Take Home Whitening Systems. Contemporary Esthetics and Restorative Practrice Vol.4:8; 88-91, September 2000. 3) Papathanasiou A., Bardwell D, Kugel G : A Clinical Study Evaluating a New Chairside and Take Home Whitening System. Compendium of Continuing Education in Dentistry, Vol: 22; 4: 289-298, April 2001. 4) Dale B.G., Aschheim,K.W. Esthetic Dentistry: a clinical approach to techniques and materials. Lea & Febiger 205-206, Philadelphia, London 1993 5) Westlake A. Bleaching teeth by electricity. Am J Dent Sci 29:101, 1895 6) Adams T.C. Enamel color modifications by controlled hydrochloric acid pumice abrasion. A review with case summaries. Indiana dent Assoc J 66;23,1987 7) Younger, H.B. Bleaching fluorine stain from mottled enamel. Texas Dent J 57:380, 1939 8) McInnes J. Removing brown stain from teeth. Ariz Dent J 12:13, 1966 9) Cohen S, Parkins FM. Bleaching tetracycline-stained vital teeth. Oral Surg 1970; 29:465 10) Nutting EB, Poe GS: A new combination for bleaching teeth. Dent Clin North Am 10:655- Eliminato: ¶ ¶ ¶ ¶ ¶ ¶ ¶ Eliminato: ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ¶ ... [99] Eliminato: : 662, 1976 11) Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-6, 1989. Eliminato: S Formattato: Tutto maiuscole 12) Yiming Li, Toxicological Considerations of Tooth bleaching using peroxide containing Formattato: Tipo di carattere: 12 pt, Tutto maiuscole agents. JADA, April 1997; vol.128; 31S-36S Formattato 13) Kugel G: Nontray Whitening. Compendium, Vol.21, No. 6, June 2000. Formattato: Tipo di carattere: Non Grassetto 14) Garber DA: Dentist-monitored bleaching: a discussion of combination and laser Formattato bleaching. Eliminato: <#>Burrell KH. ADA supports vital tooth bleaching—but look for... the[102] J Am Den Assoc 128(Suppl):26S-30S, 1997. 15) Kugel G, Perry RD, Hoang E, Scherer W: Effective tooth bleaching in 5 days: using a combined in-office and at-home bleaching system. Compen Cont Educ Dent 18(4):378-383, 1997. 16) Kugel G, Kastali S. Tooth-whitening efficacy and safety: a randomized and controlled Formattato ... [100] ... [101] ... [103] Eliminato: <#>Haywwod VB, Heymann HO: Nightguard vital bleaching. Quintessence ... Int [104] clinical trial. Compend Contin Educ Dent Suppl. 2000 Jun;(29):S16-21; quiz S42. Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt 17) Gerlach RW, Jeffers ME, Pernik PS, et al: Impact of prior tooth brushing on whitening Eliminato: 1997. strip clinical response [abstract #922]. J Dent Res 80:151, 2001 Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Non Grassetto 18) McMillan DA, Gibb RD, Gerlach RW: Impact of increasing hydrogen peroxide concentration on bleaching strip efficacy and tolerability [Abstract #1102]. J dent Res 80:173, 2001. Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Eliminato: 89¶ 20 19) Tavares M. Stultz J. Newman M. Smith V. Kent R. Carpino E. Goodson JM. Light augments tooth whitening with peroxide.[comment]. Journal of the American Dental Association. 134(2):167-75, 2003 Feb 20) Hein DK. Ploeger BJ. Hartup JK. Wagstaff RS. Palmer TM. Hansen LD. In-office vital tooth bleaching--what do lights add?. Compendium of Continuing Education in Dentistry. 24(4A):340-52, 2003 Apr. 21) Papathanasiou A, Kastali S, Perry RD, Kugel G. Clinical evaluation of a 35% hydrogen peroxide in-office whitening system. Compend Contin Educ Dent. 2002 Apr; 23(4): 335-8, Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Tipo di carattere: (Predefinito) Arial, Tedesco (Germania) Formattato: Tipo di carattere: (Predefinito) Arial 340, 343-4 passim; quiz 348 22) Jones AH, Diaz-Arnold AM, Vargas MA, Cobb DS.Colorimetric assessment of laser and home bleaching techniques. J Esthet Dent. 1999; 11(2): 87-94 23) Anonymous. Laser-assisted bleaching: an update. ADA Council on Scientific Affairs.[comment]. Journal of the American Dental Association. 129(10):1484-7, 1998 Oct 24) Goldstein RE. Esthetics in Dentistry-Principles, Comunications, Treatment Methods. 2nd Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt ed; vol 1. Hamilton-London: B.C Becker-Year Book; 1998:245. 25) Baik JW, Rueggeberg FA, LiewehrFR. Effect of light-enhanced bleaching on in vitro surface and intrapulpal temperature rise. J Esthet Restor Dent. 2001; 13(6): 370-8 Formattato: Tipo di carattere: (Predefinito) Arial, Tedesco (Germania) Formattato: Tipo di carattere: (Predefinito) Arial 26) Jones AH. Diaz-Arnold AM. Vargas MA. Cobb DS. Colorimetric assessment of laser and home bleaching techniques. Journal of Esthetic Dentistry. 11(2):87-94, 1999 27) Sharif N, MacDonald E, Hughes J, Newcombe RG, Addy M: The chemical stain removal properties of “whitening” toothpaste products: studies in vitro. British Dental Journal 188(11):620-4, 2000. 28) Donly KJ, DonlyAS, BaharlooL, et al. Tooth whitening in children. Compend Contin Edu Dent. 2002; 3:22-27 29) Kugel G Over the counter tooth whitening Systems Compendium April 2003; 24;4A 37682 30) Mokhlis GR, Matis BA, Cochran MA, Eckert GJ: A clinical evaluation of carbamide peroxide and hydrogen peroxide whitening agents during daytime use. J Am Dent Ass 131(9): 1269-77, Sept 2000. 31) Christensen GJ: Tooth bleaching, home-use products. Clinical Research Associates Newsletter 13(7):1, 1989. Formattato: Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Allineato a sinistra, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt 32) Cibirka RM, Myers M, Downey MC, Nelson SK, Browning WD, Hawkins IK, Dickinson GL: Clinical study of tooth shade lightening from dentist-supervised, patient-applied treatment with two 10% carbamide peroxide gels. J Esth Den 11(6):325-31, 1999. 21 Eliminato: 89¶ 33) Jones AH, Diaz-Arnold AM, Vargas MA, Cobb DS: Colorimetric assessment of laser and Eliminato: ¶ home bleaching techniques. J Esth Den 11(2):87-94, 1999. Eliminato: ¶ 34) Haywood VB: Nightguard vital bleaching: a history and product update. 1. Esthet Dent Eliminato: Papathanasiou Update 2(4):63-66, 1991. Eliminato: ¶ 35) Haywood VB: Nightguard vital bleaching: a history and product update. II. Esthet Dent Update 2(5):82-85, 1991. 36) Haywood VB, Heymann HO: Nightguard vital bleaching: how safe is it? Quintessence Int 22:515-523, 1991. 37) Haywood VB: Bleaching of vital and nonvital teeth. Current Opin Dent 142-149, March 1992. 38) Haywood VB: The Food and Drug Administration and its influence on home bleaching. Curr Opin Cosm Dent 12-8, 1993. 39) Haywood VB. Considerations and variations of dentist-prescribed, home-applied vital tooth-bleaching techniques. [Review] [27 refs] Compendium. Suppl 17:S616-21, 1994. 40) Nathanson D, Parra C: Bleaching vital teeth: a review and clinical study. Compend Contin Educ Dent 8(7):490-497, 1987. 41) Kugel G, Perry R, Papathanasiou, Kastali S: Combined in-office and at-home bleaching system: An evaluation1. JDR 77:957, abstract #2604, 1998. 42) Deliperi S., Bardwell D.N., Papathanasiou A. Clinical Evaluation of a Combined InOffice and Take-Home Bleaching System. JADA The Journal of the American Dental Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Non Corsivo, Colore carattere: Automatico Formattato: Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt, Non regolare lo spazio tra testo asiatico e in alfabeto latino Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Non Corsivo, Colore carattere: Automatico Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Formattato: Tipo di carattere: 11 pt, Colore carattere: Automatico Formattato: Tipo di carattere: 11 pt, Non Corsivo, Colore carattere: Automatico 43) Bowles WH, Ugwuneri Z: Pulp chamber penetration by hydrogen peroxide following vital Formattato: Tipo di carattere: 11 pt, Colore carattere: Automatico bleaching procedures. J Endod 13:375-377, 1987. Formattato: Tipo di carattere: 11 pt Association, May 2004, vol. 135, no. 5,pp. 628-634 44) Bowles WH, Thompson LR: Vital bleaching: the effect of heat and hydrogen peroxide on pulpal enzymes. J End 12:108-112, 1986. 45) Fuss A, Szajkis S, Tagger M: Tublar permeability to calcium hydroxide and the bleaching agents. J Endod 15:362-364, 1989. 46) Goldstein RE, Garber DA: Complete dental bleaching. Quintessence books 1995. 47) Bartelstone HJ. Radioiodine Penetration through Intact Enamel with Uptake by Bloodstream and Thyroid Gland. Journal of Dental Research October 1951; 728-733 48) Gokay O, Tuncbilek M,Ertan R. Penetration of the pulp chamber by carbamide peroxide Eliminato: <#>Bardwell D, Papathanasiou A, Deliperi S: In vitro evaluation of tooth color modifications utilizing ... [105] Formattato: Tipo di carattere: Grassetto Formattato ... [106] Eliminato: hydrogen peroxide Eliminato: ¶ Formattato: Tedesco (Germania) bleaching agents on teeth restored with composite resin. J of Endodontics 2000; 27; 92-94 Eliminato: <#>Fuss A, Szajkis S, Tagger M: Tublar ... [107] 49) McCaslin A.J., Haywood V.B., Potter B.J., Dickinson G.L., Russell C.M. Assessing Formattato Dentin Color Changes From Nightguard Vital Bleaching .JADA. The Journal of the American Formattato: Tipo di carattere: Non Grassetto Dental Association, October 1999, vol. 130, no. 10,pp. 1485-1490 Formattato ... [109] Formattato ... [110] Eliminato: 89¶ 22 ... [108] 50) Michael G Jorgensen, William B. Carroll. Incidence of tooth sensitivity after home whitening treatment. JADA vol.133 August 2002 ;1076-1082 51) Blankenau R. Goldstein RE. Haywood VB. The current status of vital tooth whitening techniques. Compendium of Continuing Education in Dentistry. 20(8):781-4, 786, 788 passim; quiz 796, 1999 Aug. 52) Schwachman H, Schuster A: The tetracyclines applied pharmacology. Pediat Clin North Am 3:295, 1956. 53) Christensen GJ: Bleaching vital tetracycline stained teeth. 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Philadelphia, Saunders, 1974. 62) Jordan RE, Boksman L: Conservative vital bleaching treatment of discolored dentition. Comp Cont Ed Dent 5(10):803-808, 1984. 63) Faunce F. Management of discolored teeth. [Review] [30 refs] Dental Clinics of North America.27(4):657-70, Oct. 1983 . 64) Nathanson D, Parra C. Bleaching vital teeth: a review and a clinical study. Compendium 1987; 8:490-8 65) Nathanson D: Vital tooth bleaching: sensitivity and pulpal considerations. J Am Dent Assoc., 128(Suppl): 41S-44S, 1997. 66) Bardwell D, Habib C, Kugel G, Mehta N, Leone L: Microleakage of previously restored Class II restoratives after exposure to 10% carbamide peroxide. JDR 2000 Special Issue Vol.79, abstract 306. Formattato: Tedesco (Germania) Formattato: Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Tedesco (Germania) Formattato: Giustificato, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Non Corsivo Formattato: Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Interlinea 1,5 righe Formattato: Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Formattato: Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Eliminato: 89¶ 23 67) P. Yu, A. Aboushala, D. Bardwell. Effect of bleaching on Composite Resin Shear Bond Strength In Vitro. JDR 1999 Vol.78 special issue, abstract #1445 Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt 68) MacKay M., Perry R., Swift E., Varga M. S. Effects of the two home bleaching systems on Enamel surfaces. JDR 1997 special issue abstract #1405. Formattato: Tipo di carattere: (Predefinito) Arial 69) Javaheri DS, Janis JN: The efficacy of reservoirs in bleaching trays. Operative Dentistry, 2000, 25, 149-151. 70) Price RBT, Sedarous M, Hiltz G: The pH of tooth-whitening products. J Can Den Ass, Sept. 2000, Vol. 66, No. 8, 421-426. 71) Sun G: The role of lasers in Cosmetic Dentistry Dental Clinics of North America, Vol. 44, No 4, Oct. 2000, 831-849. 72) Blankenau R, Goldstein R, Haywood V: The current status of vital tooth whitening techniques. Compendium of Continuing Education in Dentistry, Aug 1999, Vol. 20, No 8, 781794. 73) DahlJE, Becher R. Acute Toxicity of carbamide peroxide and commercially available tooth bleaching agent in rats; Journal of dental Research 1995; 74: 710-714 74) Schulte J,Morrissette D,Gasior E,Czajewski,M. Clinical Changes on the Gingiva as a result of at-home bleaching. Compendium 1993, VolXIV, no.11; 1362-1371 75) Haywood VB, Leonard RH, Chauncy NF, Brunson WD. Effectiveness, Side Effects and Long Term Status of Nightguard Vital Bleaching. JADA, September 1994 ,vol.125pg 12191226 76) Haywood VB, Caughman FW,Frazier KB,Myers ML. Tray delivery of potassium nitratefluoride to reduce bleaching sensitivity. Quintessence International ,vol32,no.2,2001;105-108 77) Michael G Jorgensen, William B. Carroll. Incidence of tooth sensitivity after home whitening treatment. JADA vol.133 August 2002 ;1076-1082 78) Pohjola R,Browning WD, Hackman ST, Michael ML, Downey MC. Sensitivity and Tooth Whitening Agents. Journal of esthetic and Restorative dentistry 2002; vol2, no.2; 85-91, 2002 79) Leonard RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and gingival irritation associated with nightguard vital bleaching. Quintessence International; 1997 vol. 28 no. 8; 527-534 Formattato: Tipo di carattere: Non Grassetto Formattato: Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Tipo di carattere: Non Grassetto Formattato: Allineato a sinistra, Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Eliminato: Eliminato: 2001 Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Tedesco (Germania) Formattato: Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Eliminato: 89¶ 24 Chapter 2 Eliminato: ¶ A Novel Low Dose Tooth-Whitening Delivery System Efficacy and Safety: A Randomized and Controlled Clinical Trial Abstract A randomized, single-center, double-blind, parallel-group, placebo controlled trial evaluated the whitening efficacy and safety of 2-week, twice daily use of a 5.3% hydrogen peroxide toothbleaching gel delivered on polyethylene film. Efficacy was based on change in Vita® shade scores from baseline to the end of treatment. Thirty-three patients in each group completed treatment. Use of the peroxide-containing gel led to a mean change in baseline Vita® shade score of –3.70 ± 0.35, compared with a change of –0.87± 0.24 after use of a placebo gel. After adjustment for baseline scores, the mean difference in shade change between the peroxide gel–treated group and placebo-treated group was –2.85 ± 0.41 (P < 0.0001). Both treatments were generally well tolerated. The strips offer ease of use, comfort, and shorter duration of wear compared with other at-home bleaching systems. Introduction Tooth whitening is one of the most widely accepted esthetic procedures today, with treatment options that include in-office procedures, dentist prescribed home-applied systems, over-thecounter (OTC) bleaching kits, and a host of whitening dentifrices. Peroxides have been used for tooth bleaching for more than 100 years, and at-home nightguard vital bleaching, which involves use of a 10% carbamide peroxide gel in a custom-fitted tray, has met with much success since its introduction in 1989.1 The safety and efficacy of carbamide peroxide bleaching agents is well documented, and currently six products have been approved by the American Dental Association for home whitening.2 Eliminato: 89¶ 25 Tooth discoloration in vital teeth can result from chromogenic foods, tobacco products, medications such as tetracycline and fluoride, pulp pathology, and aging.2 Concentrations of up to 35% peroxide have been used to resolve discoloration. The most research has been conducted on 10% carbamide peroxide, which produces substantial lightening of treated teeth after 2 to 6 weeks of treatment, 3, 4 although a period as long as 6 months may be required for stubborn stains, such as those caused by tetracycline or nicotine.5 After treatment, the whitening effect may persist for 3 or more years. Tooth-whitening agents are remarkably well tolerated; the main adverse events are generally mild and transient tooth sensitivity and gingival irritation.6 Nevertheless, poor compliance and product ingestion are problems that are encountered with whitening therapy. Many of these are associated with the delivery trays, even custom-fitted ones, used in most at-home regimens. Tray insertion and removal can lead to sensitivity and gum irritation, and tray thickness is believed to contribute to poor compliance and development of occlusal interferences. One alternative to the rigid delivery tray is a polyethylene strip with a hydrogen peroxide (H2O2)– containing tooth-whitening gel (Crest® Whitestrips™, a). In this article we report preliminary results from a randomized, placebo-controlled clinical trial that evaluated the whitening efficacy and safety of the 2-week, twice-daily use of a peroxide tooth-whitening gel delivered on a polyethylene film. Materials and Methods Formattato: Tipo di carattere: 12 pt Study Population Seventy adults in good general health were selected for the study. To be included, participants had to have (1) a minimum of 16 natural teeth, including 4 maxillary anterior teeth; and (2) at least 3 maxillary teeth gradable at Vita®,b shade A2 or darker. Patients with obvious periodontal Eliminato: 89¶ 26 disease (as evidenced by purulent exudate, tooth mobility, or other signs), oral pathoses requiring prompt treatment, active untreated dental caries, dentinal hypersensitivity, or who had tetracycline stain, dental fluorosis, or atypical non uniform stain were excluded from the study. Previous participation in a professional or home-use vital bleaching trial, participation in a dentifrice-whitening trial in the past year, or having fixed orthodontic appliances on the anterior teeth were further reasons for exclusion. All participants provided written informed consent and agreed to delay any elective dentistry (including dental prophylaxis) and to refrain from using any other than the assigned dentifrices or toothbrushes during the study. Formattato: Tipo di carattere: 12 pt Study Design The study was a randomized, placebo-controlled, double-blind, parallel-group trial. Subject eligibility and an average Vita® shade score for each participant were determined at the screening visit (visit 1). At the baseline visit (visit 2), participants were stratified on the basis of their screening Vita® shade average score and gender, and randomized to either the placebo or the active treatment group with a block-randomization protocol. Baseline tooth color and safety assessments (described below) were performed. These assessments were repeated at the end of the 2-week treatment period (visit 3). Formattato: Tipo di carattere: 12 pt Treatment The active treatment product consisted of a polyethylene film with a tooth-whitening gel containing 5.3% H2O2, supplied as strips for anterior teeth. Polyethylene film with a placebo tooth-whitening gel served as the control. Except for the presence of peroxide, test products were identical in composition and packaging. Study participants applied the strips twice daily to the maxillary anterior teeth for 30 minutes at home and brushed normally twice a day with Crest®,a toothpaste and provided toothbrushes. Eliminato: 89¶ 27 Efficacy Assessment Efficacy was assessed as the change in Vita® shade tooth color between baseline and end-oftreatment visits. Up to six teeth from among the maxillary incisors and cuspids were selected at baseline on the basis of shade (minimum Vita® shade score of A2) and access for grading. At a minimum, the four maxillary incisor teeth were graded at baseline for each subject. The Vita® shade guide has been used successfully in clinical studies to gauge the efficacy of tooth whitening products.7,8 All assessments were made by a standardized, trained, and calibrated examiner, and performed in the same operatory throughout the study. All examinations were performed blinded as to treatment assignment. Safety Assessment Extensive safety evaluations were performed to establish the absence of irreversible side effects associated with the use of the tooth-whitening gel. Assessments were performed at baseline and at the end of treatment and included the following: 1. Oral soft-tissue (OST) examination—this consisted of a visual examination of the oral Formattati: Elenchi puntati e numerati cavity and perioral area, including gingiva (free and attached), hard and soft palate, oropharynx/uvula, buccal mucosa, tongue, floor of mouth, labial mucosa, mucobuccal/mucolabial folds, and lips. 2. Oral hard-tissue examination—a visual and tactile examination was performed of the dentition and restorations. 3. Dentinal hypersensitivity—this parameter was assessed by questioning participants about tooth hypersensitivity to thermal, air, or other stimuli. 4. Löe and Silness gingival index (GI)—the GI was an assessment of periodontal health that evaluated the severity of gingivitis on the basis of color, consistency, and bleeding on probing (BOP). Six gingival areas on each Ramfjord tooth (tooth Nos. 3, 9, 12, 19, 25, and 28) were scored from 0 to 3, and an average score for each participant was derived Eliminato: 89¶ 28 by dividing the sum of individual scores by the number of evaluable sites. Scoring criteria were as follows: 0—normal gingiva; 1—mild inflammation (slight color changes and edema; no BOP); 2—moderate inflammation (redness, edema, and glazing; BOP); 3— severe inflammation (marked redness, edema, ulceration; tendency toward spontaneous bleeding); 8—ungradable site; 9—missing tooth. 5. Silness and Löe plaque index (PI)—the PI was an assessment of the plaque deposit at the gingival area of the tooth. Dental plaque was scored on the facial, lingual, mesial, and distal surfaces of the Ramfjord teeth at 6 sites per tooth, in both arches (with a maximum of 36 sites). An average PI score was obtained for each participant, by dividing the sum of individual scores by the number of gradable sites. Scoring criteria were as follows: 0—no plaque/debris; 1—film of plaque adherent to free gingival margin and adjacent tooth area and seen in situ only after probing; 2—gingival area visibly covered with a thin to moderately thick layer of plaque; 3—abundant soft matter within the gingival pocket or on the tooth and gingival margin; 8—ungradable site; 9—missing tooth. Formattato: Tipo di carattere: 12 pt Analysis Effectiveness was determined by measuring the change in Vita® shade codes from baseline to end of treatment for each evaluable tooth for the active group (Figures 2A and 2B). Shade scores were ordered from 1 to 16 according to the brightness grouping recommended by the manufacturer. Using this ranking, B-1 represented a score of “1,” while C-4 represented a score of “16.” A decrease in Vita®shade numeric code represented an increase in tooth whiteness. All adverse events related to OST, hard tissue, and dentinal hypersensitivity were summarized. Analysis of covariance was used to compare the mean Vita® shade score change from baseline between the active and placebo groups at the end of the 2-week treatment period. Baseline Vita® shade score was included as a covariate in the model. Eliminato: 89¶ 29 Formattato: Tutto maiuscole RESULTS Demographic and Baseline Characteristics The peroxide-treated and placebo groups were comparable with respect to age, sex, and race distribution (Table 1). Baseline Vita® shade scores were similar for the two treatment groups. Scores were 8.18 (D-4 to A-3) and 8.28 (D-4 to A-3), and, on average, ranged from A-2 to C-4 and from A-2 to A-4 in the active and placebo groups, respectively. Sixty four percent of teeth treated in the active group started at scores of C-2 or whiter. Efficacy Table 2 summarizes the Vita® shade scores in the 2 treatment groups at the end of the 2- week treatment period. Data were evaluated for 33 participants in each group. After treatment with the peroxide-containing gel, the average score declined from 8.18 at baseline to 4.55, which was a change of –3.7 ± 0.35, representing an average increase in tooth whiteness of approximately 4 Vita® shades. By contrast, the placebo group experienced a Vita® shade score change of only – 0.87 ± 0.24. After adjustment for baseline scores, the mean difference in shade change between the peroxide gel–treated group and placebo-treated group was –2.85 ± 0.41 (P < 0.0001). Safety Abnormal soft-tissue findings were noted at baseline and after completion of treatment. There were no new notable findings, nor was there any exacerbation of baseline pathology in any soft tissue for the 66 participants evaluated at the end of treatment. In the placebo group, one patient had slight cervical inflammation over one tooth. After treatment with peroxide-containing gel, one patient developed a minor superficial distal cervical lesion on one tooth and a second patient showed a swollen papilla between two adjacent teeth. The hard-tissue examination and dentinal hypersensitivity assessment were unremarkable. 30 Both groups experienced a Eliminato: 89¶ significant reduction (P < 0.0001) in gingivitis and plaque scores over the 2-week evaluation period (Table 3). After adjusting for baseline, there were no significant differences (P > 0.70) between the treatment groups in either the gingivitis or plaque scores after 2 weeks. Discussion This study demonstrates the efficacy and safety of a simple at-home tooth-whitening technique consisting of 5.3% H2O2 gel applied to disposable polyethylene strips. Twice-daily, 30-minute applications of the whitening strips for 2 weeks lightened discolored teeth by more than 3 Vita® shades, compared with a change of less than 1 Vita® shade in teeth treated with placebo gel. This treatment difference was highly significant after adjusting for baseline. Adverse effects after treatment were minimal and were observed in less than 10% of subjects in either treatment group. The main findings in these participants were papillary swelling, minor cervical inflammation, and a superficial cervical lesion. Growing public interest in whiter, brighter teeth has increased demand for tooth-whitening procedures and products. More than 90% of dentists now offer an at-home whitening procedure, and 50% to 60% offer an in-office technique. 9,10 Despite their proven efficacy, these systems suffer from certain drawbacks. In-office treatments are rarely successful in just a single visit, and 3 to 5 visits are usually needed to achieve reasonable results, making this an expensive procedure.11 Also, the higher concentrations of H2O2 (30% to 35%) used for in-office bleaching can cause chemical trauma to gingival tissue and also hold the risk of cervical root resorption.12 Home-whitening systems provide a relatively inexpensive way to lighten discolored teeth but require patient compliance and discipline. The nightguard system, which requires patients to wear a custom-fabricated tray all night or for several hours during the day to achieve optimal results, is cumbersome and requires an average of 2 to 6 weeks of treatment.2 Stubborn stains may require extended treatment periods of 2 to 6 months. Patient compliance with such lengthy Eliminato: 89¶ 31 regimens is therefore a problem; in a 6-month nightguard vital bleaching study, the rate of compliance was only 60%.5 To encourage compliance, some offices recall patients on a weekly basis, which is not an efficient use of office time and also adds to the cost of the procedure. Many patients may therefore elect to have the procedure completed in the dentist’s office and will pay the extra cost.13 Thermal tooth sensitivity and gingival irritation, two common adverse effects that may occur in as many as two thirds of patients undergoing nightguard treatment, have been ascribed to tray rigidity, multiple changes of the whitening solution in a 24-hour period, soft-tissue coverage of the guard, and leakage of fluid from the guard.14 Furthermore, the system may not be favorable for use in certain patient groups. For example, patients with temporo-mandibular joint disorders can wear trays only during the day, and patients with bruxism may wear through several trays over the course oftreatment.11 A strong market also exists for OTC products, despite the fact that advertised claims for the efficacy and safety of these products remain unsubstantiated.11 Additional drawbacks of OTC systems include lack of professional supervision and poorly adapted bleaching trays, which can cause occlusal problems, joint and muscle pain, increased salivation, and discomfort during sleep with extended treatment times.2,11 The treatment described here provides an attractive alternative to current at-home whitening procedures. The polyethylene film with peroxide gel is supplied as ready-to-use strips and is easily applied by patients. This ease of use contrasts with the nightguard system, which must be custom fabricated, precisely fitted, and filled with the bleaching product at each use. In addition, successful tooth lightening with the film is observed with a much shorter duration of daily wear, and the thin film is more comfortable and better tolerated by patients. These factors favor patient acceptance of the procedure and encourage compliance with the whitening regimen. Eliminato: 89¶ 32 Table 1—Demographic Characteristics at Baseline PeroxideContaining Gel (n = 35) Placebo Gel (n = 35) Overall (n = 70) 32.3 (18-66) 33.8 (22-56) 33.0 (18-66) Male Female 15 20 17 18 32 38 Asian Black White Hispanic 5 2 27 1 2 2 30 1 7 4 57 2 Demographic Characteristic Age (years) mean range Tabella formattata Sex Race S19 Formattato: Tipo di carattere: (Predefinito) Arial Table 2—Average Shade Scores by Treatment Tabella formattata 5.3% Peroxide Strip Placebo Strip Baseline (n = 35) End of Treatment (n = 33) Change from Baseline (n = 33) Baseline (n = 35) End of Treatment (n = 33) Change from Baseline (n = 33) Mean 8.18 4.55 -3.70 8.28 7.49 -0.87 Standard Deviation 2.72 2.56 1.99 2.51 3.00 1.35 Median 7.00 3.67 -4.00 7.33 6.67 0 Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ 33 Table 3—Gingival (GI) and Plaque Index (PI) Scores at Baseline and 2 weeks Tabella formattata Baseline End Of Treatment (2 weeks) Change (BaselineEnd of Treatment ) n Mean SD Range n Mean SD Range Mean 5.3% Peroxide Strip 35 0.75 0.405 (0, 1.6) 33 0.23 0.331 (0, 1) -0.52 Placebo Strip 35 0.65 0.436 (0, 1.5) 33 0.16 0.323 (0, 1) -0.49 5.3% Peroxide Strip 35 0.85 0.437 (0, 1.6) 33 0.24 0.407 (0, 1) -0.61 Placebo Strip 35 0.76 0.450 (0, 1.3) 33 0.18 0.380 (0, 1) -0.59 GI PI Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ 34 Formattato: Tutto maiuscole REFERENCES 1. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20:173-176, 1989. 2. Haywood VB: Current status and recommendations for dentist-prescribed, at-home tooth whitening. Contemp Esthet 3(suppl 1):2-9, 1999. 3. Haywood VB, Leonard RH, Nelson CF, et al: Effectiveness, side effects, and long-term status of nightguard vital bleaching. J Am Dent Assoc 125:1219-1226, 1994. 4. Matis BA, Cochran MA, Eckert G, et al: The efficacy and safety of a 10% carbamide peroxide bleaching gel. Quintessence Int 29:555-563, 1998. 5. Haywood VB, Leonard RH, Dickinson GL: Efficacy of 6 months of nightguard vital bleaching of tetracycline stained teeth. J Esthet Dent 9:13-19, 1997. 6. Li Y: Biological properties of peroxide-containing tooth whiteners. Food Chem Toxicol 34:887-904, 1996. 7. Croll TP, Sasa IS: Carbamide peroxide bleaching of teeth with dentinogenesis imperfecta discoloration: report of a case. Quintessence Int 26:683-686, 1995. 8. Small BW: The application of and integration of at-home bleaching into private dental practice. Compend Contin Educ Dent 19:810-813, 1998. 9. Christensen GJ: Bleaching teeth: practitioner trends. J Am Dent Assoc 128:16S-18S, 1997. 10. Christensen GJ: Bleaching teeth: report of a survey. 1997. J Esthet Dent 10:16-20, 1998. 11. Blankenau R, Goldstein RE, Haywood VB: The current status of vital tooth whitening techniques. Compend Contin Educ Dent 20:781-794, 1999. 12. Barghi N: Making a clinical decision for vital tooth bleaching: at-home or in-office? Compend Contin Educ Dent 19:831-838, 1998. 13. Nash RW: In-office bleaching system for quick esthetic change. Compend Contin Educ Dent 20:986-1000, 1999. 14. Leonard RH: Efficacy, longevity, side effects, and patient perceptions of nightguard vital bleaching. Compend Contin Educ Dent 19:766-781, 1998. Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ 35 Chapter 3 Concentration and Dose Response Clinical Trial Evaluating the Peroxide Concentration Response of a Polyethylene strip Delivery System over 28 Day Formattato: Tutto maiuscole ABSTRACT Formattato: Allineato a sinistra OBJECTIVES: The research evaluated the peroxide concentration whitening response Formattato: Tipo di carattere: Non Corsivo, Tutto maiuscole following self-directed use of whitening strips over a 28-day period. Formattato: Tipo di carattere: Grassetto, Tutto maiuscole MATERIALS AND METHODS: A randomized, double-blind, parallel group clinical study was conducted. 37 healthy adult volunteers were randomly assigned to one of three groups based Formattato: Tipo di carattere: Non Corsivo, Tutto maiuscole on tooth color at screening – 1.8% hydrogen peroxide strips (HPS), 3.3% HPS or 5.3% HPS. Subjects applied the assigned maxillary strips twice per day for 30 minutes over 28 days. Tooth color was evaluated at day 7, 14 & 28 from digital images of the maxillary 6 anterior teeth using a standard method. Treatments were compared using analysis of covariance (adjusting for baseline), or analysis of variance at a 0.05 level of significance. RESULTS: Hydrogen peroxide at concentrations ranging from 1.8-5.3% resulted in significant (p < 0.05) color improvement versus baseline as early as Day 7. There was a clear concentration-response for all color parameters (Δb*, ΔL* and ΔE*) at all timepoints, favoring the higher concentrations. While the concentration-whitening relationship approached a linear response at Day 7, continued treatment resulted in incremental color improvement. All three peroxide concentrations were well tolerated, and no subjects discontinued early due to a treatment-related adverse event. Formattato: Tipo di carattere: Non Corsivo, Tutto maiuscole Formattato: Tipo di carattere: Grassetto, Tutto maiuscole Formattato: Tipo di carattere: Grassetto, Corsivo Formattato: Tipo di carattere: Arial, 11 pt, Grassetto, Non Corsivo, Colore carattere: Automatico, Inglese (U.S.A.), Tutto maiuscole Formattato: Tipo di carattere: Arial, 11 pt, Inglese (U.S.A.) Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Inglese (U.S.A.) CLINICAL SIGNIFICANCE: Digital image analysis demonstrated a concentration gradient for whitening response following use of a low peroxide dose strip whitening system. 36 Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Eliminato: 89¶ INTRODUCTION Formattato: Tipo di carattere: (Predefinito) Arial, Tutto maiuscole Discoloration of the natural dentition may occur as a result of exposure to various chemicals or Formattato: Corpo del testo 2 medicines, disease processes, and other factors.1 Much of this staining is intrinsic in nature, and Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto a likely product of the aging process that can be readily measured as increased yellowness and decreased brightness in tooth color.2 Treatment typically involves peroxide-based vital Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto bleaching, sometimes in combination with other esthetic dental procedures. In practice, Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto peroxide-containing gels may be applied using a tray, strip or other barrier system, at-home Formattato: Tipo di carattere: Arial over time, or in-office with gingival isolation, to assure necessary contact time for peroxide Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto diffusion through enamel to the underlying stain. Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Practiced widely since the late 1980s, vital bleaching is recognized as safe and effective. There Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto are several contemporary reviews that support tooth whitening using peroxide-containing gels in combination with barrier systems.3-5 Some cases with extensive staining, from tetracycline or other agents, have been treated daily with peroxide for several weeks or months without significant adverse response.6,7 Post-treatment follow-up, which has now exceeded a decade in some instances, provides further evidence of safety with vital bleaching. 8,9 Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Peroxide concentration and contact time with tooth surfaces are recognized as playing a prominent role in the clinical response seen with vital bleaching.10 Since the 1980s, use of higher peroxide concentration gels has become more commonplace, in turn, lowering recommended treatment times from several weeks to only a few days. At the extreme, very high concentrations of hydrogen peroxide in the range of 35-38% provide a basis for tooth whitening as an in-office procedure.11,12 Research on peroxide degradation in vivo, and in vitro shade measurements on extracted teeth further support a relationship between peroxide concentration and whitening. 13,14 Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato ... [111] Formattato ... [112] Formattato ... [113] Formattato ... [114] Formattato ... [115] Formattato ... [116] Formattato ... [117] Formattato ... [118] Formattato ... [119] Formattato ... [120] Formattato ... [121] Formattato ... [122] Formattato ... [123] Eliminato: 89¶ 37 Although widely-accepted and plausible, there are surprisingly few peroxide concentration ranging studies in the clinical trials literature. Such evidence is largely confined to the traybased, professional bleaching systems at hydrogen peroxide-equivalent concentrations of 37%.7,15 Formattato: Tipo di carattere: Arial, 11 pt, Non Apice / Pedice Concentration ranging studies provide important evidence, not only of product response, but Formattato: Tipo di carattere: Arial, 11 pt also of measurement validity in clinical trials applications. New clinical research was conducted Formattato: Tipo di carattere: Arial, 11 pt to evaluate the effects of peroxide concentration on clinical response using one of the new selfdirected strip-based bleaching systems. Digital image analysis was used to extend the dose ranging evidence from older tray-based research to the newer strip delivery system.15 Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial, 11 pt MATERIALS AND METHODS Formattato: Tipo di carattere: 12 pt, Grassetto, Colore carattere: Nero, Tutto maiuscole A randomized, double-blind, parallel group clinical trial was conducted to evaluate the impact of Formattato: Colore carattere: Nero, Tutto maiuscole peroxide concentration and treatment duration on whitening effectiveness. The research was Formattato: Normale conducted within a private dental practice located in western Tuscany, Italy. Following informed consent, 37 healthy adult volunteers underwent vital bleaching of the maxillary anterior teeth using a flexible polyethylene strip coated on one side with an experimental, hydrogen peroxide bleaching gel. After balancing for baseline tooth color, subjects were randomly assigned to one of three experimental groups: 1.8% hydrogen peroxide strips, 3.3% hydrogen peroxide strips or 5.3% hydrogen peroxide strips (The Procter & Gamble Company, Cincinnati, OH USA). Maxillary strips carried 0.200 mg of hydrogen peroxide gel distributed uniformly across the 9.9 cm2 strip surface. In this double-blind study, treatment groups differed only in peroxide concentration, and otherwise, were identical in appearance, aesthetics, packaging, and labeling. Usage was twice daily for 30 minutes over a 28-day period, at-home and unsupervised. Study participants returned for efficacy and safety evaluations at day 7, day 14, and day 28. Efficacy and safety assessments were conducted at baseline and subsequent visits blind as to treatment assignment. Efficacy was assessed as change in tooth color as measured from 38 Eliminato: 89¶ standard digital images of the maxillary anterior teeth. This objective and instrumental color measurement method had previously been used to demonstrate a peroxide concentration response for tray-based professional bleaching systems.15 Using this method, subjects were first positioned in a chin rest, retractors were inserted, and standard bilateral illumination of the arch was obtained from two 150-watt lights and linear polarizers. Images were then captured using a photographic system using a HC1000 CCD high resolution digital camera manufactured by Fuji a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens, and a personal computer. Color measurements were calibrated to known standards daily prior to use and hourly thereafter to assure proper operation. Safety was assessed by interview and clinical examination at each visit. The interview focused on tooth sensitivity or oral irritation during treatment, since these have been recognized as the most common adverse events associated with vital bleaching.16 The clinical examination, using a standard dental light, dental mirror, and gauze, evaluated the oral and perioral regions, including the gingiva (free and attached), hard and soft palate, oropharynx/uvula, buccal mucosa, tongue, floor of the mouth, labial mucosa, mucobuccal/mucolabial folds, and lips to assess any changes in oral status with treatment. For analysis, red-green-blue values for the 6 maxillary teeth were derived with reference to calibration standards, and then, these average values were transformed to yield CIELAB tooth color values for b* (yellow – blue), L* (lightness), and a* (red – green).17 Change values were calculated for any given post-baseline visit as: Δb* = b*visit - b*baseline, ΔL* = L*visit - L*baseline, Δa* = a*visit - a*baseline. In addition, a composite parameter, ΔE*, was derived from the square root of the sum of the squares of the individual L*a*b* changes. Reduction in yellowness (Δb*) was selected a priori as the primary endpoint, because this parameter has been previously shown to correlate with subjective perception of whitening following vital bleaching.18 A paired difference t-test was used to evaluate absolute color improvement (change from baseline). Between-group efficacy comparisons were made at each time point using analysis of Eliminato: 89¶ 39 covariance with the baseline value as the covariate. A separate model was fit for Δb* and ΔL*. Treatment comparisons for ΔE* used analysis of variance methods. All testing was two-sided at a 5% significance level without adjusting for multiple comparisons. Tolerability outcomes were tabulated by treatment. Formattato: Tutto maiuscole RESULTS Of the 37 subjects randomized, one had a baseline image that was not evaluable, one had extensive facial anterior restorations, and one had heavy, atypical extrinsic stain. Of the 34 remaining subjects, 32, 29 and 28 were present and evaluable at Days 7, 14 and 28, respectively. This sample ranged in age from 21-66 years, with mean (SD) age of 37.2 (11.4). Males (53%) and females (47%) were similarly represented in the population. Study subjects exhibited considerable diversity with respect to tooth color. At baseline, b* (yellowness) ranged from 16.2 to 22.7, L* (brightness) ranged from 66.3 to 77.2, and a* (redness) ranged from 5.9 to 9.1. Treatment groups were balanced (p > 0.18) with respect to age, gender, and tooth color at baseline. All three treatments resulted in significant whitening, with color improvement evident as early as Day 7. For the primary response parameter, the Day 7 mean (SD) Δb* values were –0.44 (0.558), –0.86 (0.509), and –1.41 (0.690) in the 1.8%, 3.3% and 5.3% hydrogen peroxide strip groups, respectively, with each group differing significantly from baseline (p < 0.05) at this initial timepoint. Outcomes were generally similar for ΔL*, as well as the composite parameter ΔE*, with each differing significantly (p < 0.05) from baseline at Day 7. Continued use past Day 7 resulted in incremental color improvement. This was evident for the individual parameters Δb* and ΔL*, as well as the composite parameter, ΔE*. Between-group comparisons generally favored the higher concentration groups (Table 1-3). At Day 7, the 5.3% strips exhibited significant (p < 0.05) reduction in yellowness versus the other 40 Eliminato: 89¶ two groups, while at Day 14, both the 5.3% and 3.3% groups differed significantly (p < 0.03) from the lowest concentration 1.8% strips. These outcomes generally held (directionally or significantly) for ΔL*, and for the composite parameter ΔE*. At Day 7, mean (SE) ΔE* was 1.01 (0.204), 1.66 (0.204) and 2.30 (0.214) for the 1.8%, 3.3% and 5.3% groups, respectively. All three treatments differed significantly (p < 0.05), with increasing concentration contributing to greater composite color change. Results were similar over time, though by Day 28, the composite ΔE* for the intermediate concentration approached that seen with the higher concentration. Mean (SE) ΔE* was 3.23 (0.272) and 3.26 (0.246) for the 3.3% and 5.3%, respectively, with these higher concentration strips not differing significantly (p = 0.944). Figure 1 illustrates the concentration response for the primary whitening parameter Δb* over time. (Because yellowness is removed during bleaching, negative change in b* is representative of color improvement. The graph illustrates –Δb* in order to be consistent with ΔL*, where positive change represents improvement.) The linear concentration response is most evident at Day 7 across the concentration ranges tested in this research. Similar results are evident for ΔL*, and the mathematical composite parameter ΔE* (Figures 2-3). Overall, twice-daily use of 5.3% strips for 14 days yielded generally similar whitening (Δb*, ΔL and ΔE*) to the 3.3% strips used for 28 days. Transient oral irritation represented the most common side effect associated with treatment. Oral irritation was reported only in the lower concentration group (25% of subjects), and the higher concentration group (36% of subjects). One subject (in the 5.3% hydrogen peroxide group) had an aphthous ulcer during treatment. Other safety findings were generally unremarkable. Most (75%) oral soft tissue findings were judged “mild” in severity, with only two events (in the higher concentration group) scored as moderate. All peroxide concentrations were well tolerated overall, and none of the study participants discontinued strip use due to a product-related adverse event. Eliminato: 89¶ 41 Formattato: Tipo di carattere: (Predefinito) Arial, 12 pt DISCUSSION This double-blind clinical trial evaluated the effect of peroxide concentration on whitening Formattato: Tipo di carattere: (Predefinito) Arial, Tutto maiuscole response following repeated daily use of a self-directed bleaching system. In this research, Formattato: Corpo del testo 2 hydrogen peroxide at concentrations ranging from 1.8-5.3% resulted in significant color Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Automatico improvement compared to baseline. This was evident for all individual L*a*b* color parameters measured in the study, as well as the mathematical composite parameter ΔE*, beginning as early as Day 7. Formattato: Tipo di carattere: Arial Extended treatment duration past Day 7 contributed to greater observed whitening response for each of the strip concentrations. This was evident for all parameters (Δb*, ΔL* and ΔE*) Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Automatico measured in this study. Such results are consistent with previous research which demonstrated a favorable impact of treatment duration on tooth color in head-to-head testing comparing a popular tray and strip-based system.19 Use of hydrogen peroxide under barrier conditions at lower concentrations (~2%) is likely to require a much greater treatment duration. In this research, the observed whitening response at Day 7 with the 5.3% strips (Δb*, ΔL* and ΔE*) Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Automatico exceeded that achieved with the 1.8% strips at Day 28. Clinical implications with respect to compliance and other factors may suggest use of higher concentrations where possible. Formattato: Tipo di carattere: Arial The research provides clear evidence of a peroxide concentration whitening response. Whitening efficacy was greatest for the highest concentration group (5.3% hydrogen peroxide), Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Automatico while the intermediate concentration group had an intermediate response. Not surprisingly, this effect most approached linearity at the earliest time point (Day 7). At that time, adjusted mean Δb* for was –1.43, –0.84, and –0.44 in the higher, intermediate and lower concentration groups, respectively. Relative to the lowest concentration strip, this represented a 225% improvement in whitening for the 5.3% strip (a 194% increase in concentration), and a 91% improvement in whitening for the 3.3% strip (a 83% increase in concentration). As such, peroxide concentration Eliminato: 89¶ 42 alone likely contributed the measured differences in response at that time point, results that are completely consistent with the physical chemical bleaching process. Formattato: Tipo di carattere: Arial With extended treatment, the concentration response curve flattened out especially at the two higher peroxide concentrations. At Day 28, the adjusted mean Δb* was 20% higher in the 5.3% Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Automatico group compared to the 3.3% group (a 61% difference in concentration). While sample sizes were small, there were no statistically significant differences in Δb*, ΔL* or ΔE* between the higher and intermediate concentrations at Day 28. This flattening with extended treatment may be expected in dose ranging, especially where the response substrate (intrinsic stain) is nonrenewal or slowly renewable, as it is with vital bleaching. Formattato: Tipo di carattere: Arial Despite the concentration differences (there was nearly a three-fold difference between the lowest and highest concentration tested in this research), all three strips tested in this research Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Automatico carried a low total amount of peroxide. The total amount of hydrogen peroxide on each predispensed strip ranged only from 3.6-10.6 mg. Relative to some tray-based systems, which may deliver up to 2 grams of bleaching gel, total peroxide delivered with any of these strips was remarkably low. This likely contributed to the low overall adverse event rate seen in this trial. All three treatments were well tolerated, with no subjects reducing or discontinuing treatment due to bleaching-related adverse events. Formattato: Tipo di carattere: Arial This new clinical research provides evidence of a concentration gradient for whitening response following use of a low peroxide dose strip whitening system. As such, this may represent a first Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Automatico example of concentration ranging for one of the self-directed bleaching systems. More importantly, the research also provides evidence of the sensitivity and robustness of the measurement method – in this instance – digital imaging. While previous concentration ranging research was conducted in the US on tray-based systems, this work was done in Italy, in a private dental practice using strips for peroxide delivery.15 The authors are unaware of any other Eliminato: 89¶ 43 method (whether subjective shade assessment or objective colorimetry) that has demonstrated similar measurement sensitivity under such diverse clinical research conditions. Formattato: Tipo di carattere: Arial Concentration ranging trials, like this one, represent one of the most complex and difficult Formattato: Tipo di carattere: Arial, 11 pt studies types in the clinical research arena. Research of this nature may be particularly Formattato: Normale, Interlinea doppia exemplary of the measurement sensitivity (or lack thereof) of the clinical method used in the study. By design, the goal of this research was to distinguish both the effect of increased peroxide concentration (three treatment groups) and increased treatment duration (three posttreatment timepoints) within the constraints and variability seen with unsupervised human testing. Moreover, the research involved a degree of blinding, both with respect to the test products (identical appearing peroxide-containing strips), and clinical methods (instrumental color measurement from digital images) greater than that seen in most vital bleaching clinical trials. Despite these complexities, the research adequately differentiated multiple concentrations from low to high over time. With Δb* as an endpoint, the study demonstrated a nearly linear concentration response relationship, with measured efficacy differences at Day 7 that reasonably modeled the real concentration differences between groups. As such, the research provides important evidence of the validity of this method and endpoint for practicerelevant evaluation of vital bleaching technologies. Eliminato: 89¶ 44 Tables and Figures Table 1 Adjusted Mean Δb* and ANCOVA Treatment Comparisons Table 2 Adjusted Mean ΔL* and ANCOVA Treatment Comparisons Table 3 Mean ΔE* and ANOVA Treatment Comparisons Figure 1 Peroxide Concentration on Strip and Adjusted Mean –Δb* at 7, 14 & 28 Days Figure 2 Peroxide Concentration on Strip and Adjusted Mean ΔL* at 7, 14 & 28 Days Figure 3 Peroxide Concentration on Strip and Adjusted Mean ΔE*at 7, 14 & 28 Days Eliminato: 89¶ 45 Formattato Table 1 Adjusted Mean Δb* and ANCOVA Treatment Comparisons Evaluable Subjects (N=34) Visit/Group Day 7 1.8% H2O2 3.3% H2O2 5.3% H2O2 Day 14 1.8% H2O2 3.3% H2O2 5.3% H2O2 Day 28 1.8% H2O2 3.3% H2O2 5.3% H2O2 a Adjusted Mean Change From Baseline (SE)a Two-Sided p-Value 3.3% H2O2 5.3% H2O2 -0.44 (0.181) -0.84 (0.182) -1.43 (0.195) 0.122 0.001 0.041 -1.02 (0.203) -1.77 (0.245) -1.99 (0.240) 0.026 0.006 0.525 -1.23 (0.284) -1.91 (0.272) -2.30 (0.251) 0.094 0.010 0.308 Means adjusted for baseline b* Eliminato: 89¶ 46 Table 2 Adjusted Mean ΔL* and ANCOVA Treatment Comparisons Evaluable Subjects (N=34) Visit/Group Day 7 1.8% H2O2 3.3% H2O2 5.3% H2O2 Day 14 1.8% H2O2 3.3% H2O2 5.3% H2O2 Day 28 1.8% H2O2 3.3% H2O2 5.3% H2O2 a Adjusted Mean Change From Baseline (SE)a Two-Sided p-Value 3.3% H2O2 5.3% H2O2 0.74 (0.281) 1.07 (0.287) 1.31 (0.297) 0.423 0.175 0.580 1.20 (0.203) 1.32 (0.249) 1.86 (0.240) 0.717 0.051 0.140 1.28 (0.318) 2.03 (0.302) 2.15 (0.275) 0.100 0.051 0.776 Means adjusted for baseline L* Eliminato: 89¶ 47 Table 3 Mean ΔE* and ANOVA Treatment Comparisons Evaluable Subjects (N=34) Visit/Group Day 7 1.8% H2O2 3.3% H2O2 5.3% H2O2 Day 14 1.8% H2O2 3.3% H2O2 5.3% H2O2 Day 28 1.8% H2O2 3.3% H2O2 5.3% H2O2 Mean Change From Baseline (SE) Two-Sided p-Value 3.3% H2O2 5.3% H2O2 1.01 (0.204) 1.66 (0.204) 2.30 (0.214) 0.031 <0.001 0.041 1.83 (0.182) 2.39 (0.223) 2.84 (0.211) 0.061 0.001 0.158 2.00 (0.289) 3.23 (0.272) 3.26 (0.246) 0.005 0.003 0.944 Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Normale, Interlinea singola Eliminato: 89¶ 48 Formattato: Tipo di carattere: Arial, Italiano (Italia) Figure 1 Eliminato: 89¶ 49 Figure 2 Eliminato: 89¶ 50 Figure 3 Eliminato: 89¶ 51 Formattato: Tutto maiuscole REFERENCES 1. Watts A, Addy M. Tooth discolouration and staining: a review of the literature. Br Dent J 2001;190:309-16. 2. Odioso LL, Gibb RD, Gerlach RW. Impact of demographic, behavioral and utilization parameters on tooth color and personal satisfaction. Compend Contin Educ Dent 2000;21:S3541. 3. Niederman R, Tantraphol MC, Slinin P, Hayes C, Conway S. Effectiveness of dentistprescribed, home-applied tooth whitening. A meta analysis. J Contemp Dent Pract 2000;15:2036. 4. Haywood VB. Current status of nightguard vital bleaching. Compend Contin Educ Dent 2000;28:S10-7. 5. Gerlach RW, Zhou X. Vital bleaching with whitening strips: Summary of clinical research on effectiveness and tolerability. J Contemp Dent Pract 2001;2:1-16. 6. Kugel G, Aboushala A, Zhou X, Gerlach RW. Daily use of whitening strips on tetracyclinestained teeth: comparative results after 2 months. Compend Contin Educ Dent 2002;23:29-34. 7. Matis BA, Wang Y, Jiang T, Eckert GJ. Extended at-home bleaching of tetracycline-stained teeth with different concentrations of carbamide peroxide. Quintessence Int 2002;33:645-55. 8. Ritter AV, Leonard RH Jr, St Georges AJ, Caplan DJ, Haywood VB. Safety and stability of nightguard vital bleaching: 9 to 12 years post-treatment. J Esthet Restor Dent 2002;14:275-85. 9. Leonard RH Jr, Van Haywood B, Caplan DJ, Tart ND. Nightguard vital bleaching of tetracycline-stained teeth: 90 months post treatment. J Esthet Restor Dent. 2003;15:142-52. 10. Matis BA. Tray whitening: what the evidence shows. Compend Contin Educ Dent 2003;24:354-62. 11. Gallagher A, Maggio B, Bowman J, Borden L, Mason S, Felix H. Clinical study to compare two in-office (chairside) whitening systems. J Clin Dent 2002;13:219-24. 12. Papathanasiou A, Kastali S, Perry RD, Kugel G. Clinical evaluation of a 35% hydrogen peroxide in-office whitening system. Compend Contin Educ Dent 2002;23:335-44. 13. Matis BA, Yousef M, Cochran MA, Eckert GJ. Degradation of bleaching gels in vivo as a function of tray design and carbamide peroxide concentration. Oper Dent 2002;27:12-8. 14. Leonard RH, Sharma A, Haywood VB. Use of different concentrations of carbamide peroxide for bleaching teeth: an in vitro study. Quintessence Int 1998;29:503-7. 15. Gerlach RW, Gibb RD, Sagel PA: A randomized clinical trial comparing a novel 5.3% hydrogen peroxide bleaching strip to 10%, 15% and 20% carbamide peroxide tray-based bleaching systems. Compend Contin Educ Dent 2000;21:S22-28. 16. Leonard RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and gingival irritation associated with nightguard vital bleaching. Quintessence Int 1997;28:527-34. 17. Commission Internationale de L’Eclairage: Recommendations on uniform color spaces. Color difference equations. Psychometric color terms. Suppl 2 to CIE pub 15 (E-13.1)1971/(TC1.3), Paris, France: Bureau Central de la CIE, 1978. 18. Gerlach RW, Barker ML, Sagel PA. Objective and subjective whitening response of two self-directed bleaching systems. Am J Dent 2002;15:7-12A. 19. Karpinia KA, Magnusson I, Sagel PA, Zhou X, Gerlach RW. Vital bleaching with two athome professional systems. Am J Dent 2002;15:13-18A. Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Eliminato: 89¶ 52 Chapter 4 Light activated Tooth Whitening Clinical Evaluation of a 35% Hydrogen Peroxide In-Office Whitening System Formattato: Tutto maiuscole ABSTRACT This study evaluated the effectiveness of light-curing (heat conversion) vs no light-curing (no Formattato: Tipo di carattere: 11 pt heat conversion) of a 35% hydrogen peroxide in-office tooth whitening system. Twenty patients with sound medical history (without tooth sensitivity) participated in this randomized, parallel clinical evaluation. Only six maxillary anterior teeth with discoloration and a tooth shade of A3 or darker were selected. Patients received a complete prophylaxis and were evaluated for initial (baseline) shade by three independent evaluators, precalibrated at 85% rater reliability in determining shades before the experiment began. Participants received a 20-minute chairside whitening treatment with a 35% hydrogen peroxide agent using a reflective resin barrier for gingival isolation. During the whitening treatment, the 35% hydrogen peroxide agent was light activated with a halogen curing light on teeth Nos. 6 through 8 (Group I), but was not lightactivated on teeth Nos. 9 through 11 (Group II). All patients returned 24 hours after the whitening application for shade evaluation. Although there were isolated instances (7 out of 20 patients) of greater degrees of lightening in the light-curing group, there was no statistically significant difference using the Mann-Whitney U test (P > .05). This study indicates that lightcuring is optional with this 35% tooth whitening system. Eliminato: 89¶ 53 Learning Objectives After reading this article, the reader should be able to: describe an in-office whitening technique using 35% hydrogen peroxide. Formattato: Tipo di carattere: 11 pt discuss tooth color modifications produced using a 35% hydrogen peroxide. recognize the effectiveness of tooth color modifications produced with 35% hydrogen peroxide in-office technique. Tooth whitening has become one of the most popular esthetic dental procedures. The management of the discolored dentition is not new to the dental profession—it was first reported 1 in 1877. Whitening offers a conservative, simplified, and economical approach to changing the color of one’s teeth. Candidates for whitening include patients whose teeth have been stained over time by aging, chromogenic foods, endodontic treatment, tetracycline use, and smoking or 2 the use of other tobacco products. Acceptable whitening techniques include the in-office procedure, the dentist-prescribed homeapplied technique, or a combination of the two. Recently, whitening strips have been introduced 3 as an alternative whitening method. In the 1970s, vital tooth whitening was being performed with in-office treatments using different concentrations of liquid hydrogen peroxide solutions and 4 (sometimes) a heat lamp. In 1989, the first article on nightguard vital bleaching using carbamide peroxide was published by Haywood and Heymann after evaluation at the University 5 of North Carolina. Currently, the in-office whitening technique uses a 15% to 35% hydrogen peroxide whitening agent (heated or nonheated); the dentist-prescribed home-applied technique most commonly uses a 10% to 15% carbamide peroxide gel. The advantage of the in-office procedure is that it does not require patient compliance and results may be seen immediately. The disadvantage is the chair time, cost to the patient, and the possibility of multiple visits. A light-activated chairside whitening system has the potential advantages of taking less time and providing quicker results. Eliminato: 89¶ 54 The purpose of this study was to evaluate: 1. The effectiveness of a 35% hydrogen peroxide in-office system Formattato: Tipo di carattere: 11 pt ® ®,a ®,a (Opalescence Xtra and OpalDam ) in tooth color modifications. 2. The effect of light when compared to no-light activation (light-to-heat activator and light-to-nonheated activator). 3. The incidence of soft tissue irritation related to the active whitening chemical, hydrogen peroxide. 4. Patient responses to the whitening treatment. Formattato: Tutto maiuscole METHODS AND MATERIALS Formattato: Tabulazioni: 0 pt, Allineato a sinistra Before participating in this blinded, parallel tooth whitening study, all patients were asked to sign an informed consent form. Both the form and the research protocol were reviewed Formattato: Normale, Interlinea doppia, Tabulazioni: 0 pt, Allineato a sinistra + 54 pt, Allineato a sinistra and approved by the Human Investigational Review Committee at Tufts University. A total of 20 patients (with no medically compromised history or tooth sensitivity) were recruited from the Tufts University dental clinic to participate in this randomized, parallel clinical evaluation. The criteria used to recruit participants for this investigation included: Formattato: Tipo di carattere: 11 pt No active caries. 18 years of age or older. Formattato: Tipo di carattere: 11 pt Maxillary and mandibular teeth with the same color. Formattato: Tipo di carattere: 11 pt Formattato: Rientro: Prima riga: 36 pt The exclusion criteria were: Intrinsic dental staining (ie, tetracycline or fluorosis). Nonvital teeth. Patients that had previous tooth whitening procedures. Extended composite restorations at the teeth that would be included in this study. Eliminato: 89¶ 55 Only 6 maxillary anterior teeth with minor uniform staining or discoloration with a shade no Formattato: Tipo di carattere: 11 pt lighter than A3 were selected. The six mandibular anterior and contralateral maxillary, non–lightcured teeth were used as the control group. At the initial appointment, all necessary consent forms were signed before any treatment was Formattato: Normale, Interlinea doppia rendered. Then, a thorough clinical and medical evaluation was taken for each patient. All patients received a complete oral prophylaxis (cleaning and polishing) 2 weeks before beginning the whitening process. At the next appointment, all of the subjects underwent a baseline periodontal evaluation, which included color, size, shape, and consistency of the involved gingival tissue. Each patient was evaluated for initial (baseline) shade by three independent evaluators. The evaluators consisted of the subject, the dentist treating the subject, and a second dentist. All evaluators were calibrated at 85% rater reliability in determining shades before the onset of this project. A consensus method (two of the three evaluators) was used Formattato: Tipo di carattere: 12 pt to record the shades of the 6 test anterior maxillary teeth and 6 lower anterior teeth as the control group. Shades were assessed using the Standard Vita Shade Guideb. All shade measurements were recorded at baseline and an initial photograph was taken of the maxillary and mandibular teeth. At this appointment, the 20 participants received a 20-minute chairside whitening treatment with a 35% hydrogen peroxide whitening agent (Opalescence Xtra), using OpalDam for gingival Formattato: Tipo di carattere: 12 pt, Tedesco (Germania), Non Alzato/ Abbassato Formattato: Tipo di carattere: 12 pt Formattato: Tipo di carattere: 12 pt, Non Alzato/ Abbassato Formattato: Tipo di carattere: 12 pt isolation. Before the hydrogen peroxide application, all teeth were cleaned using pumice and a slow-speed rotary brush/prophy cup. Teeth Nos. 6 through 11 were whitened using the 35% hydrogen peroxide whitening agent, but only teeth Nos. 6 through 8 were light activated with a curing light. A questionnaire was provided to the patients for recording any comments. All participants were able to contact any of the principle investigators if any side effects such Formattato: Tipo di carattere: 12 pt as tooth sensitivity, gum tissue irritation, or bad taste were experienced. All patients were required to return 24 hours after the day of the second appointment for a recall appointment. A final periodontal evaluation was taken for all patients, which consisted of visual gingival recordings using standardized Löe and Silness Gingival Index: 56 Eliminato: 89¶ Formattato: Tipo di carattere: 11 pt 0 = No inflammation 1 = Slight inflammation 2 = Moderate inflammation 3 = Severe inflammation In addition, recordings of loss of sensation, change in gingival texture, spontaneous bleeding, Formattato: Normale, Interlinea doppia and the sloughing of gingival tissue were noted. A final shade was then selected and a final intraoral photograph was taken at the 24-hour recall appointment. Data (degree of color change from baseline) were analyzed using statistical tests to determine Formattato: Tipo di carattere: 11 pt the significance of the light activation when using the 35% hydrogen peroxide tooth whitening agent. Formattato: Tutto maiuscole RESULTS The 35% hydrogen peroxide in-office tooth whitening system was effective in lightening teeth. Formattato: Tipo di carattere: 11 pt However, the purpose of this study was to evaluate the effectiveness of light-curing vs no lightcuring of this whitening system. Although there were isolated instances (7 out of 20 patients) of greater degrees of lightening in the light-curing group (median for Group I was 7.21 and Group II was 6.78) (Table 1), there was no statistical significant difference using the Mann-Whitney U test (P > .05). Both whitening protocols were effective in the lightening of teeth with no adverse effects. All shade evaluations using the Vita Shade Guide were recorded with the guide arranged in value order, where they are assigned a number from 1 through 16. This order is shown at the bottom of Table 1. Patients were given questionnaires to record tooth sensitivity, gingival irritation, bad taste, and noticeable shade change. One patient experienced slight tooth sensitivity (only at one tooth) at the end of the whitening procedure, which subsided before the 24-hour recall visit. No bad taste and no gingival irritation were reported and OpalDam appeared to be effective in isolating the tissues against any caustic behavior. All participants in the study expressed satisfaction with the whitening process and the results (Table 2). Formattato: Tipo di carattere: 11 pt Eliminato: 89¶ 57 Formattato: Tutto maiuscole DISCUSSION Traditionally, in-office whitening products have been used to give a patient a head start in the whitening process, to touch-up postwhitening cases if they should regress in shade, and to 6 function solely as a whitening product. Opalescence Xtra is a commonly used 35% hydrogen peroxide tooth whitening agent for in-office treatment. After gingival isolation with OpalDam , the whitening material was applied to each facial enamel surface on the six maxillary anterior teeth, but was light-cured only on teeth Nos. 6 through 8. This light-activated material is contained in a carotene base to absorb light, providing an increased whitening 7 effect. The results of this study revealed that the use of the halogen light improved the effectiveness of the whitening material in some cases. However, in those cases, the difference between light-cured vs non–light-cured teeth was 1 to 3 shades, which was not noticeable to the patients. Shade evaluation determined Vita ® shade B1 for teeth Nos. 6 through 8 (light-cured) and A1 for teeth Nos. 9 through 11 (non–light-cured). As stated earlier, the purpose of this study was to determine if the use of a light in the in-office whitening process would increase the effect of whitening on the teeth. Of the 20 patients in this Formattato: Tipo di carattere: 11 pt Formattato: Corpo del testo 3, Tabulazioni: 36 pt, Allineato a sinistra study, 7 patients experienced an increase in lightening of the split arch protocol. The increase was an average lightened increase of 1.714 shades as compared to the non–light-cured side. This was not a significant clinical change. Any shade difference as noted by the light-activated side was most likely a result of dehydration resulting from heat generated by the halogen curing light. Statistically, there was no significant difference between the light-activated side when compared to non–light-activated side. The results contradict other studies, which have indicated that light activation causes an increased whitening effect as used with hydrogen peroxide whitening agents. 8,9 Formattato: Tipo di carattere: 11 pt Based on the Clinical Research Associates’ report, the use of a curing light in addition to the manufacturerrecommended exposure times, does not produce sufficient heat generation was to significantly 58 Formattato: Tipo di carattere: 11 pt Eliminato: 89¶ increase the breakdown of H2O2. 10 It is this activation of H2O2 that results in the increased whitening effect. A transient whitening effect may be the result of dehydration. To potentiate the Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: 11 pt effect of H2O2, high temperatures must be reached, which could potentially cause damage to the tooth. This report also states that Opalescence Xtra experiences a relatively low rate 10 increase in H2O2 even when temperatures are raised as high as 100° C. This would also support our findings that the addition of light does not increase the effect of the whitening Formattato: Tipo di carattere: 11 pt process. Formattato: Tutto maiuscole CONCLUSION This study evaluated the effectiveness of light-curing vs no light-curing of a 35% hydrogen Formattato: Tipo di carattere: 11 pt peroxide in-office tooth whitening system. Tweny patients with sound medical history (without tooth sensitivity) participated in this randomized, parallel clinical evaluation. The outcome of this study leads to the conclusion that the use of a halogen curing light to increase the activation of 35% hydrogen peroxide is of no benefit to the dentist or the patient. Eliminato: 89¶ 59 Table 1 Tooth Color Modifications as Ascertained by The Consensus Method Subject Light Cured) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Initial Final (Light Cured) Final (No A3 A3 A3.5 A3 A3 D3 A3 D3 C3 A3 A3 A3 A3 D3 A3 A3 D3 A3 A3 A3 B1 A1 A2 A1 A1 B1 A1 A1 C1 A2 A1 A2 D2 A1 D2 A1 A1 B1 D2 B1 A1 A2 A2 A1 D2 A1 A1 A1 C1 A2 A1 A2 D2 A2 D2 A1 A1 A1 A2 B1 (8) (7) (7) (7) (7) (9) (7) (8) (8) (4) (7) (4) (5) (8) (5) (7) (8) (8) (5) (8) Formattato: Tipo di carattere: Arial (7) (4) (7) (7) (5) (8) (7) (8) (8) (4) (7) (4) (5) (5) (5) (7) (8) (7) (4) (8) Totals: Group I:137, Group II:125. Median Group I: 7.21 Median Group II: 6.78 The numbers in parentheses show how many shade changes were accomplished with the use ® ® of Opalescence Xtra during the study, from the initial to the final appointment. ® Vita Shade Guide arranged in value order: B1 A1 B2 1 2 3 D2 A2 C1 C2 D4 A3 4 5 6 7 8 9 D3 10 B3 11 A3.5 12 B4 13 C3 14 A4 C4 15 16 Table 2—Tooth Sensitivity, Gingival Irritation, Bad Taste, and Noticeable Shade Change Evaluation by Each Subject in the Exit Questionnaire Eliminato: 89¶ 60 Subject Tooth Sensitivity Gingival Irritation Bad Taste Noticeable 1 No No No Yes 2 No No No Yes 3 No No No Yes 4 No No No Yes 5 No No No Yes 6 No No No Yes 7 No No No Yes 8 No No No Yes 9 No No No Yes 10 No No No Yes 11 Yes No No Yes 12 No No No Yes 13 No No No Yes 14 No No No Yes 15 No No No Yes 16 No No No Yes 17 No No No Yes 18 No No No Yes 19 No No No Yes 20 No No No Yes Shade Change Eliminato: 89¶ 61 Formattato: Tutto maiuscole PRODUCT REFERENCES a Ultradent Products, Inc., South Jordan, UT 84095; (800) 552-5512 b Vita Zahnfabrik, Germany, distributed in US by Vident, Brea, CA 92621; (800) 828-3839). Formattato: Tutto maiuscole REFERENCES 1. Fasanaro TS: Bleaching teeth: history, chemicals and methods used for common tooth discoloration. J Esthet Dent 4: 71-78, 1992. 2. Kugel G: Nontray whitening. Compend Contin Educ Dent 21(6):524-528, 2000. 3. Kugel G, Kastali S: Tooth whitening eficacy and safety: randomized and control clinical trial. Compend Contin Educ Dent 21(Suppl 28): 2000. 4. Nathanson D: Vital bleaching sensitivity and pulpal considerations. J Am Dent Assoc 128(Suppl):41S-44S, 1997. 5. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-176, 1989. 6. Kugel G, Perry RD, Hoang E, et al: Effective tooth bleaching in 5 days: using a combined inoffice and at-home bleaching system. Compend Contin Educ Dent 18(4):378-383, 1997. 7. Gultz J, Kaim J, Scherer W, et al: Two in-office bleaching systems: a scanning electron microscope study. Compend Contin Educ Dent 20(10):965-970, 1999. 8. Li Y, Cartwright S, Lezama M, et al: Effect of light application on an in-office bleaching gel [abstract]. J Dent Research 80(147), 2001. Abstract 895. 9. Tavares M, Goodson JM, Stutz J, et al: A randomized single blind clinical trial of tooth whitening with peroxide and light [abstract]. J Dent Research 80(182):2001. Abstract 1171. 10. CRA Newsletter August, 2000. Eliminato: 89¶ 62 CHAPTER 5 CHEMICAL VS LIGHT ACTIVATED TOOTH WHITENING Clinical Evaluation of Chemical and Light-Activated Tooth Whitening Systems ABSTRACT BACKGROUND Formattato: Tipo di carattere: 11 pt, Tutto maiuscole Tooth whitening has become one of the most popular of dental treatments. There are many Formattato: Tipo di carattere: 11 pt options available. The paper attempts to compare the efficacy of two in-office whitening Formattato: Tipo di carattere: 11 pt systems. Formattato: Tipo di carattere: 11 pt, Tutto maiuscole METHODS In this split-arch, randomized, parallel, blinded clinical evaluation six maxillary anterior teeth (N=60) A-2 or darker were selected using the value order Vita Shade Guide. Patients received one-hour light-activated chairside treatment using 15% H2O2 teeth 6-8 (Group I), teeth 9-11 received a 38% H2O2 system for 1 hr without a light (Group II). Before and after treatment images were taken. L*, a* and b* and Vita shades were measured. Patients returned after 2 weeks for final shade evaluation. Formattato: Tipo di carattere: 11 pt, Tutto maiuscole Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: 11 pt RESULTS Formattato: Tipo di carattere: 11 pt Both in-office tooth whitening systems were effective. Group I averaged 5.9 ± 2.5 and Group II 3.97 ± 2.33 shade changes immediately after treatment. At the 2-week recall, Group I scored an average of 4.6 ± 2.14 and Group II 4.6 7± 2.3 shade changes, compared to the pre-bleaching Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: 11 pt shades. A paired sample t-test revealed statistically significant difference (p<0.0001) between Formattato: Tipo di carattere: 11 pt, Tutto maiuscole Groups I and II immediately after bleaching, with Group I performing better. At the 2-week recall, Formattato: Tipo di carattere: 11 pt however, only Group I showed a significant rebound (p=0.0002). At the completion of the study, there was no significant difference between Groups I and II (p=0.7826). 63 Formattato: Tipo di carattere: 11 pt Eliminato: 89¶ CONCLUSION Formattato: Tipo di carattere: 11 pt, Tutto maiuscole This study indicated that both chairside tooth whitening systems are effective and that no Formattato: Tipo di carattere: 11 pt statistically significant differences were observed over the 2-week period of observation. Formattato: Tipo di carattere: 11 pt CLINICAL IMPLICATIONS Both systems were effective in whitening teeth. The use of light did Formattato: Tipo di carattere: 11 pt, Tutto maiuscole not demonstrate an increase in the effectiveness of Britesmile after a two-week recall. Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: Arial INTRODUCTION Technological advances in dentistry make it possible for the practitioner to deliver the highest level of care in an efficient and often economical way. With the introduction of light activated devices such as Plasma arc, Light Emitting Diodes (LED), Argon lasers, metal halide and xenon-halogen lights, being promoted as “the future of dentistry,” dental manufacturers have helped create a public awareness and demand for the so-called: “ Light enhanced tooth whitening systems”. In 2002 one article and more recently two papers were published evaluating the efficacy of light Formattato: Tipo di carattere: 11 pt activated bleaching agents. One study reported positive results1, whereas the other articles concluded the opposite 2,3. Reviews of these articles were either in support 4 or discredited the findings5. It is apparent that the dental profession needs more evidence in order to provide for better and more efficient treatment. The lack of knowledge is to the detriment of the dentist and patient alike. The need for more knowledge becomes even more important as manufacturers inundate the dental profession with advertisements emphasizing that light activated tooth whitening is “the state of the art” and should be part of the armamentarium of the “up to date” dental office. Bleaching is the most conservative treatment for discolored teeth when compared to resin bonded composites, porcelain veneers or crowns. It offers a simple and economical approach to changing the color of teeth. Success of the treatment depends on a careful diagnosis by the Eliminato: 89¶ 64 practitioner. Candidates for whitening procedures include patients whose teeth are stained by aging, chromogenic foods, endodontic treatment, tetracycline use and smoking or use of other tobacco products. Acceptable tooth whitening techniques include the in-office technique, dentist-prescribed homeapplied technique, or a combination of the two. The use of hydrogen peroxide (H202) for bleaching teeth dates back to 1995 6. To reduce treatment time, clinicians attempted to accelerate the degradation of H202 by heat or light. In 1970, Cohen and Parkins introduced a technique for bleaching discolored teeth, such as tetracycline stained-teeth, using hydrogen peroxide and a hand-held heating source 7. Most clinicians know that hydrogen peroxide is a bleaching agent that can attain a desired whitening effect. Bleaching can also be accomplished with Carbamide Peroxide, a lower concentration of hydrogen peroxide and urea, which breaks down to 3.6% hydrogen peroxide 8,9 .The degree of whitening correlates directly with the amount of contact time and concentration of the active ingredient, the pH and viscosity 9. The side effects are usually diminished when lower concentrations are used. The in-office bleaching treatment using hydrogen peroxide and an accelerating source (heat or light) were predominant until 1989 when Haywood published the first article on nightguard vital Formattato: Tipo di carattere: 11 pt bleaching using carbamide peroxide 10. Currently, the in-office bleaching technique employs a 15 - 40% hydrogen peroxide bleaching agent (heat activated or not), while the dentist prescribed home-applied technique most commonly uses a 10 - 15% carbamide peroxide gel. The advantages of an in-office procedure are twofold. It does not require patient compliance and immediate results can be accomplished. The disadvantages are the chair side time involved and the cost to the patient, as the procedure usually requires multiple visits. Lightactivated chair side bleaching systems potentially offer the benefit of being less time-consuming while producing faster results. The introduction of very high intensity Plasma Arc lights and Argon Lasers meets the need of an Formattato: Tipo di carattere: 11 pt ever increasing demand for whiter teeth. Research in vitro has demonstrated that the use of Eliminato: 89¶ 65 laser-activated hydrogen peroxide did not produce any perceivable color change 11. Another recent in vitro study, and one which should be of concern to the practitioner, has shown that the use of these intense lights does elevate temperature of the bleaching material and as a result caused an increase in intrapulpal temperature. This may have an impact on post bleaching tooth sensitivity and pulpal health 12. The efficacy of a bleaching treatment can be determined through first or second evaluators or Formattato: Tipo di carattere: 11 pt various technical methods. The use of a shade guide, colorimeter, or computer digitization to measure color change over time has been currently included in clinical trials to assure efficacy Formattato: Tipo di carattere: 11 pt assessment 13, 14, 15. The purpose of this study was to compare the efficacy of color changes of two in-office tooth whitening systems, Brite Smile, a 15% Hydrogen peroxide system a and Opalescence Xtra Boost, a 38% Hydrogen Peroxide system b. In addition, feed back from the participants allowed for an evaluation of their satisfaction with the results of the treatment and the occurrence of sensitivity during and after the bleaching treatment. Formattato: Tipo di carattere: Arial MATERIALS AND METHODS Ten patients with no medical contraindications to treatment and an absence of tooth sensitivity Formattato: Tipo di carattere: 11 pt were asked to participate in this split-arch, randomized, parallel, blinded clinical evaluation. Only six to eight upper anterior teeth with minor uniform intrinsic staining or discoloration with a shade no lighter than A-3 were selected. The six lower anterior teeth and contra lateral upper incisors were used as control groups. All patients had received a prophylaxis (cleaning and polishing) less than 3 months before starting the experiment. Each patient was evaluated for initial (baseline) shade by two evaluators. The evaluators consisted of the dentist treating the subject and a second dentist. Both evaluators were calibrated at 85% rater reliability in determining shades before the onset of this project. Calibration was conducted pre and post study to ensure inter and intra rater reliability. Eliminato: 89¶ 66 At the initial appointment shades were assessed using a Standard Vita Shade Guide c. All shade measurements were recorded at baseline and an initial photograph was taken of the upper and lower teeth. At the same appointment the patient received a one-hour chair side bleaching treatment for teeth 5-8 using Brite Smile according to manufacturer’s recommendations; 3 applications of 20 minutes each in one visit. Opal Dam b was used for gingival isolation. Teeth 9-12 were isolated from the Brite Smile material and light source during treatment by means of a custom made poly vinylsiloxane (PVS) block. Teeth were also kept moist using wet gauze under the PVS block. Upon completion, teeth 5-8 were isolated as descrived above and teeth # 9-12 were treated with Opalescence Xtra Boost without the use of a curing light (3 applications of 20 minutes each in one visit), following the manufacturer’s recommendations. Three measurements were recorded from each side before and immediately after treatment. In addition 35mm transparencies, as well as digital photos were taken before and after treatment. All patients were scheduled to return 2 weeks after the day of the tooth whitening treatment for a recall appointment. Once more post bleaching records by means of transparencies and digital photography were taken. In addition a determination of the final shade was made. As a service to the patient the mandibular teeth were whitened after final recording at the end of the study using Opalescence 10% carbamide peroxide take-home system. b A. Efficacy Assessment The efficacy of the whitening system was evaluated with the use of a Digital Imaging Camera d, Formattato: Tipo di carattere: 11 pt a 35 mm camera e and Standard Vita Shade Guidec15,16. The Olympus C2500L high resolution digital camera is utilized for sampling. To ensure proper color analysis an extended procedure of sampling nine locations on the central incisor, lateral incisors of the maxillary and mandibular arches was completed. This data is then averaged to find a mean color and standard deviation of color on each tooth. A Gaussian blur filter was Eliminato: 89¶ 67 applied during post processing which does an averaging of color over the digitally sampled photo. All digital images were then analyzed to yield L*, a* and b* data 15. All individuals are located in the same position in a single operatory with the camera positioned 9 inches and perpendicular from the tooth surface of the left central incisor. Patients are presented edge to edge with retractors and asked to touch the tip of their tongue to their soft palate. This allows light to readily pass through the tooth surface and reduce reflectance from their tongue. A polarized filter is used on the camera to reduce the gloss that occurs from the Formattato: Tipo di carattere: 11 pt flash further ensuring the reduction of hot spots and increase consistent color accuracy. The camera flash is used to ensure the consistency of light source due to its great influence on value data. The camera is plugged in to a 120-volt source to ensure no fluctuation of flash intensity between subjects and maintain stability of the light source. A Standard Vita Shade Guide, arranged in order of value, was used for subjective evaluation of the shades. Furthermore, 35mm transparencies were taken as part of the shade evaluation protocol. Each participant was asked to brush with water and an extra-soft toothbrush, according to Brite Smile recommendations, to remove any debris that could interfere with shade evaluation and photography. To standardize the photography, cheek retractors were used to retract the cheeks and lips and the patient was instructed to line-up the lower incisal edges with the upper front teeth. Additional photos were taken positioning the baseline shade tab next to the teeth to be evaluated. All digital photos and analysis were performed by a blinded evaluator. B. Safety Assessment Formattato: Tipo di carattere: 11 pt This clinical study assessed the efficacy and patient tolerance of two different in-office tooth Formattato: Tipo di carattere: 11 pt whitening systems after a single visit one-hour application. Clinical safety data information indicated that the use of these systems, when used according to the protocol specified in this clinical trial, did not present any undue risks to the participants. Eliminato: 89¶ 68 This was a randomized, blinded, parallel group study with 10 healthy participants, which approved by the Institutional Review Board of the University where the study was conducted. Subjects that met inclusion criteria were asked to report whether they had any teeth that were sensitive. During the initial visit an informed consent form and an explanation of the eligibility criteria were presented. The health of the oral soft tissues was examined and recorded and a shade determination made. Photography as described previously was also done at this visit. Both whitening systems were used for each patient. The Brite Smile System for teeth #5-8 and Opalescence Xtra Boost for teeth # 9-12. The application lasted for 60 minutes, according to the protocol and instructions provided by the manufacturers. An evaluation of the oral soft tissues, tooth sensitivity and change in shade was completed after the tooth whitening treatment and two weeks after application. The mandibular teeth were whitened after the end of the study using Opalescence, a 10% carbamide peroxide tray-delivered home bleaching system. Safety and comfort was determined by an absence of irreversible effects associated with the use of the systems and included assessment of oral soft tissues and the degree of tooth hypersensitivity. Oral soft tissue examination was conducted visually utilizing a standard dental light, dental mirror and gauze. Abnormal soft tissue findings were noted after the tooth whitening treatment had been completed. The Brite Smile System consists of a 15% hydrogen peroxide gel, Opalescence Xtra Boost of Formattato: Tipo di carattere: 11 pt 38% hydrogen peroxide gel and Opalescence is 10% carbamide peroxide. All three whitening systems have undergone previous clinical safety testing 17,18. Two types of adverse reactions have been reported, i.e. oral soft tissue irritation and tooth sensitivity 17,18. The occurrence of these reactions were carefully evaluated and recorded following completion of the bleaching treatment. RESULTS During the in-office treatment, soft tissue irritation was usually avoided with the appropriate Formattato: Justified para, Rientro: Prima riga: 0 pt, Spazioprima 6 pt, Tabulazioni: 468 pt, Allineato a sinistra placement of a gingival isolation gel recommended and included in each in-office tooth Eliminato: 89¶ 69 whitening system. Soft tissue irritation was typically of mild severity and was usually observed at the gingival margin. The irritation resolved while the subject were still undergoing tooth whitening treatment or within 1-3 days after discontinuation of use. Baseline values were confirmed using the lower teeth as a control group. Tooth sensitivity was experienced and Formattato: Tipo di carattere: (Predefinito) Arial recorded and was of mild severity, which resolved usually within 1-2 days after discontinuation Formattato: Tipo di carattere: 11 pt of the product. Formattato: Normale, Rientro: Prima riga: 0 pt, Interlinea singola A. Shade Guide Evaluation Formattato: Non Tutto maiuscole Both in-office whitening systems were effective in making teeth lighter. The Vita Shade Guide scores from the lightest to the darkest shade in numeric code order (Table I). The recorded shades utilizing the Vita Shade Guide showed that Brite Smile averaged 5.9 ± 2.5 and Opalescence Xtra Boost averaged 3.97 ± 2.33 shade changes immediately after the whitening procedure. At the 2 week recall, Brite Smile’s effect was reduced to an average of 4.6 ± 2.14 while Opalescence Xtra Boost increased to 4.67 ± 2.3 shade changes (Table II and Table III). Patients were given a questionnaire to record tooth sensitivity, gingival irritation, bad taste and noticeable shade changes. Six patients experienced tooth sensitivity in which four patients reported sensitivity in both sides; one patient reported sensitivity on the Britesmile side and the other patient reported sensitivity on the Opalescence Xtra Boost side. One patient reported gingival irritation at the end of the whitening procedure, observed in both sides, which subsided in less than 24 hour. No bad taste was reported and all participants in the study expressed satisfaction with the whitening process and the results. Formattato: Tipo di carattere: Arial, Non Maiuscoletto B. Digital Photography Evaluation The digital photography revealed the following results (Table IV): Whitening benefit is defined as tooth color change from baseline assessed by the digital imaging measurements b* (yellow – blue), L* (light – dark), and a* (red – green). For a given Eliminato: 89¶ 70 post-baseline visit: Δb* = b*visit - b*baseline, ΔL* = L*visit - L* baseline, Δa* = a* visit - a* baseline. Preoperative vs. Immediate Post Bleaching There was a significant difference in b∗ (p=0.01) for the BriteSmile compared to Opalescence Xtra Boost immediately post bleaching, while Opalescence Xtra Boost had a significant decrease in the a∗ score (p=0.01) post bleaching compared to BriteSmile. The other values showed no significant differences between the two products. The data indicates that BriteSmile had a greater whitening effect when evaluated immediately post bleaching based on L* and b* which are directly linked to bleached dentition (citation). Both products show statistical difference (P=.01) before and after treatment for L* and b*. Immediate Postoperative vs. 2 Weeks Post Bleaching BriteSmile demonstrated a significant rebound by a positive b∗ value (p<0.001). This signifies that the BriteSmile subjects had an increase in yellow coloration. This may be attributed to dehydration of the tooth from the application of the light or it may be a normal response of rebound. The Opalescence Xtra Boost may not have displayed this rebound due to the prolonged activity of the bleaching material after the sample readings were taken immediately post bleaching. The a* values showed no statistical change in either group. The L* displayed no significant change for the Britesmile yet the Ultra Boost showed the mean L* increase in value by 1.7 units. Preoperative vs. 2 Weeks Post Bleaching (Overall) The data indicates that both BriteSmile and Opalescence Xtra Boost whitened teeth to statistically significant level (P=.01) for L* 3.6 (BriteSmile), 3.8 (Xtra Boost) and b* -6.0 (BriteSmile), -5.0 (Xtra Boost) equivalent to between 3 and 6 shades as determined on a Vita shade guide (cite). The two whitening systems were not statistically significantly different from pre-bleaching to two weeks post bleaching. All patients reported to be satisfied with the results 71 Eliminato: 89¶ at the end of the treatment. Sensitivity appeared not to be an issue and none of the patients expressed concern or complained about this side effect. DISCUSSION The question as to whether to use light activation during chair side bleaching or not and the Formattato: Tipo di carattere: 11 pt purported benefits are still an issue of debate. The use of two blinded and calibrated evaluators in this study set it apart it from other publications evaluating this technology 1. In this study, the direct in-office whitening system using a gas plasma light for three twenty minute applications in conjunction with 15%hydrogen peroxide gel, was compared to a chemically activated system using 38% hydrogen peroxide. Either heat or a chemical reaction can cause the peroxide to break down into oxygen radicals and water more quickly. The more oxygen is liberated, the more oxydation can take place. In the absence of heat, lowering the pH is one such mechanism, by which, when Opal Xtra Boost is chemically activated, oxygen and water are liberated. The clinical observation using a value ordered Vita Shade Guide was confirmed using digital analysis of L*, a*, b* color values 15 . In addition the digital camera was calibrated for each image. Unlike other studies, the teeth of the one side were kept moist during bleaching, thus minimizing the effect of dehydration that can occur while the other lateral side was being bleached. This might explain why our data does not show the dramatic results reported in another paper 1. The use of light activation using the Britesmile in-office bleaching system resulted in increased whitening compared to Opalescence Xtra Boost, which does not require light activation. This is believed to be the result of dehydration of the tooth caused by the generation of heat from the curing light 2. This increase, however, was of temporary nature, as after 2 weeks no differences were recorded between the two systems. The initial improvement in tooth whitening observed with the Britesmile system is therefore most probably the result of dehydration. The Britesmile system incorporates the use of “hydrogel” and it has been suggested that this hydrogel (the company does not volunteer the composition), prevents the teeth from dehydrating. Prevention 72 Eliminato: 89¶ of dehydration of any light activated in office bleaching procedure is virtually impossible, however. Opalescence Xtra Boost did not demonstrate significant rebound and actually showed a slight improvement after 2 weeks. This is possibly due to the fact that there was less dehydration since no light and /or heat are required to activate the system. Furthermore, it is also possible that a prolonged exposure and activity after the gel took place after it was rinsed off. It is believed that continued oxydation can take place over time with the chemically activated system, as activated hydrogen peroxide in water is able to penetrate deeper and/or reside in the tooth longer, since it is not driven out by evaporation due the application of heat. It is reasonable to conclude that with the increase in temperature, dehydration did occur, which was subsequently followed by rehydration. Therefore in spite of the initial perception that an increase in whitening took place, the 2-week post-operative evaluation did not demonstrate a difference, which was confirmed by an absence of a statically significant difference between the two materials. We realize that this study represents a small sample size. This was due in part to the difficulty in obtaining a Bristesmile unit. More independent research evaluating a larger sample size is recommended. Factors such as cost of the light, operatory space, and maintenance should be entered in the equation when purchasing a light. Advantages and disadvantages of light activated whitening systems should be carefully considered. CONCLUSIONS 1. BriteSmile and Opalescence Xtra Boost whitened teeth between 3 and 6 shades and Formattati: Elenchi puntati e numerati were not statistically significantly different from pre-bleaching to two weeks post bleaching, 2. BriteSmile had a greater whitening effect when evaluated immediately post bleaching, Formattato: Tipo di carattere: 11 pt but demonstrated a significant rebound of the b∗ score (p<0.001). This may be attributed Eliminato: 89¶ 73 to dehydration of the tooth from the application of the light (heat) or it may be a normal response of rebound, 3. Opalescence Xtra Boost did not display this rebound effect, probably due to a more prolonged activity of the bleaching material after the sample readings were taken immediately post bleaching, 4. All patients reported to be satisfied with the results at the end of the treatment; 5. Sensitivity appeared not to be an issue and none of the patients expressed concern or complained about this side effect. a BriteSmileTM,Inc., Walnut Creek, CA 94598;(925) 941-6260 b Ultradent Products Inc., South Jordan, UT USA c VITA Zahnfabrik, Bad Säckingen, Germany d Olympus Camedia C2500L-SLR, Olympus America Inc., Melville, NY USA e Dental Eye III, Yashica-kyocera, Somerset, New Jersey USA Tables: Vita Shade Guide c scores from the lightest to the darkest shade in numeric code order. Mean Shade Change from Baseline Mean Shade Change from Baseline Results showed from digital photography analysis Table I: Table II: Table III: Table IV: Formattato: Tipo di carattere: 12 pt TABLE I Lightest Darkest Tabella formattata B1 A1 B2 D2 A2 C1 C2 D4 A3 D3 B3 A3.5 B4 C3 A4 C4 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Corresponding Numeric Code Formattato: Centrato Eliminato: 89¶ 74 TABLE II Patient Teeth 1 central lateral canine central lateral canine central 2 3 lateral canine 4 6 8 9 10 A3.5 A3.5 A2 A2 A3.5 central lateral canine central lateral 7 C1 A2 B3 B4 B4 A4 A3 central lateral canine 5 Initial Shade (# 6-11) A2 A2 A3 D3 A3.5 canine central lateral canine central lateral canine central lateral canine central lateral canine A4 A2 A2 B3 A2 A2 A3 D3 A3 A3.5 A2 A2 A3.5 A1 (4) B1 (4) A1 (9) A2 (8) A1 (11) A3 (6) B1 (8) Opal. Xtra Boost (#9-11) Postoper. A1 (4) A1 (3) A3 (2) A2 (8) D2 (9) A3 (6) B2 (6) A1 (4) A1 (3) A2 (6) C2 (6) C1 (7) A3 (6) A1 (7) Opal. Xt. Boost (#9-11) 2 w. rec. A1 (4) A1 (3) A2 (6) C2 (6) C1 (7) A3 (6) A1 (7) B1 (11) A2 (7) A2 (7) A2 (7) A2 (7) A3 (3) A2 (7) A2 (7) A1 (3) A1 (3) A1 (3) A1 (3) A1 (3) A1 (3) A1 (3) A1 (3) A2 (7) A2 (7) A2 (7) A2 (7) B1 (4) A1 (3) A1 (7) A1 (8) B1 (4) A1 (3) D2 (5) B2 (7) D2 (1) D2 (1) D2 (5) A1 (8) D2 (1) D2 (1) D2 (5) A1 (8) A1 (10) A2 (7) A2 (7) A2 (7) A3 (6) A1 (3) A1 (3) A2 (6) A1 (3) A1 (3) B2 (6) A1 (8) D2 (5) A2 (7) A1 (3) B1 (4) A3.5 (3) B2 (2) A1 (3) A3 (2) A2 (0) A2 (0) A3 (0) A2 (5) A2 (4) A3 (3) A1 (3) B1 (4) A3 (6) A1 (3) A1 (3) A2 (6) A1 (3) A1 (3) A3 (0) A2 (5) A2 (4) A3 (3) A1 (3) B1 (4) A2 (10) B2 (2) A1 (3) A3 (2) B2 (2) A1 (3) A2 (4) A2 (5) A2 (4) A3 (3) A1 (3) B1 (4) A2 (7) A3 (3) A2 (7) A2 (7) Brite Smile (# 6-8) Postoper. Brite Smile (# 6-8) 2 w. recall Eliminato: 89¶ 75 Formattato: Tipo di carattere: 12 pt TABLE III Formattato: Tipo di carattere: (Predefinito) Arial Mean Shade Change from Baseline Formattato: Tipo di carattere: Arial 12 10 8 6 4 2 0 -2 Brite Smile - Brite Smile - 2 Opal Boost - Opal Boost - 2 After bleaching week recall After bleaching week recall n Mean SD SE 95% CI of Mean Median IQR 95% CI of Median Brite Smile After bleaching 30 5.900 2.524 0.461 4.958 to 6.842 6.000 4.000 4.000 to 7.000 Brite Smile 2 week recall 30 4.600 2.143 0.391 3.800 to 5.400 4.500 3.250 3.000 to 6.000 Opal Boost After bleaching 30 3.967 2.327 0.425 3.098 to 4.835 3.000 2.250 3.000 to 5.000 Opal Boost 2 week recall 2.294 0.419 3.810 to 5.523 4.000 4.000 3.000 to 6.000 30 4.667 TABLE IV Pre Post 2 Week Brite Smile Ultradent Boost Brite Smile Ultradent Boost L* a* b* L* a* b* L* a* b* L* a* b* L* a* b* Mean 70.4 -2.8 7.3 73.6 -2.6 0.2 72.5 -1.9 3.2 74.0 -2.4 1.6 74.2 -1.9 2.0 St.Dev. 7.4 1.9 4.4 6.0 0.7 2.3 6.1 1.2 3.0 5.4 0.9 1.8 5.3 1.3 2.4 Tabella formattata Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 12 pt Formattato: Tipo di carattere: Arial Eliminato: 89¶ 76 Formattato: Tutto maiuscole REFERENCES 1. Tavares M. Stultz J. Newman M. Smith V. Kent R. Carpino E. Goodson JM. Light augments tooth whitening with peroxide.[comment]. Journal of the American Dental Association. 134(2):167-75, 2003 Feb 2. Hein DK. Ploeger BJ. Hartup JK. Wagstaff RS. Palmer TM. Hansen LD. In-office vital tooth bleaching--what do lights add?. Compendium of Continuing Education in Dentistry. 24(4A):34052, 2003 Apr. 3. Papathanasiou A, Kastali S, Perry RD, Kugel G. Clinical evaluation of a 35% hydrogen peroxide in-office whitening system. Compend Contin Educ Dent. 2002 Apr; 23(4): 335-8, 340, 343-4 passim; quiz 348 4. Jones AH, Diaz-Arnold AM, Vargas MA, Cobb DS.Colorimetric assessment of laser and home bleaching techniques. J Esthet Dent. 1999; 11(2): 87-94 5. Anonymous. Laser-assisted bleaching: an update. ADA Council on Scientific Affairs.[comment]. Journal of the American Dental Association. 129(10):1484-7, 1998 Oct nd 6. Goldstein RE. Esthetics in Dentistry-Principles, Comunications, Treatment Methods. 2 ed;vol 1. Hamilton-London: B.C BeckerYear Book; 1998:245. 7. Cohen S, Parkins FM. Bleaching tetracycline-stained vital teeth. Oral Surg 1970 Mar; 29:46571 8. Goldstein RE, Garber DA. Complete dental bleaching. Chicago: Quintessence, 1995 9. Clinical Research Associates. Tooth Bleaching, state-of-art ’97. CRA Newsletter. April, 1997 10. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence Int 1989;20: 173-6. 11. Jones AH. Diaz-Arnold AM. Vargas MA. Cobb DS. Colorimetric assessment of laser and home bleaching techniques. Journal of Esthetic Dentistry. 11(2):87-94, 1999 12. Baik JW, Rueggeberg FA, LiewehrFR. Effect of light-enhanced bleaching on in vitro surface and intrapulpal temperature rise. J Esthet Restor Dent. 2001; 13(6): 370-8 Formattato: Inglese (U.S.A.) 13. Haywood VB. Historical development of whiteners: clinical safety and efficacy. Dent Update. 1997;24:98-104. 14. Gegauff AG, Rosenstiel SF, Langhout KJ, Johnston WM.Evaluating tooth color change from carbamide peroxide gel. J Am Dent Assoc. 1993;124:65-72 15. Kugel G, Aboushala A, Sharma S, Ferreira S, Anderson C. Maintenance of Whitening with Sonicare Advance Toothbrush after bleaching treatment. Compend Contin Educ Dent. 2004 Feb; 25(2): 17-24; quiz 25 16. Anderson C, Kugel G. Rebound evaluation of tetracycline stained subjects treated with a 6.5% hydrogen peroxide gel; quantitative assessment by standard digital photography[abstract]. J Dent Res. 2002;81(special issue):A-429.Abstract 3488. 17. Deliperi S, Bardwell D, Papathanasiou A, Kim M-J. Effectiveness of a Combined In-office and Take-home Bleaching System. AADR Abstract. March 2003 18. Papathanasiou A, Deliperi S, Bardwell D, Wegley C. In vitro Evaluation of a Combined In-office and Take-home Bleaching System. AADR Abstract. March 2003. Eliminato: 89¶ 77 Chapter 6 Tooth whitening and its Effect on Dentin Daily Use of Whitening Strips on Tetracycline Stained Teeth: Formattato: Tipo di carattere: Arial Formattato: Centrato Formattato: Centrato, Destro 80,3 pt Comparative Results After Two Months ABSTRACT Formattato: Tipo di carattere: Arial, Tutto maiuscole This clinical article reviews the efficacy of a new 6.5% hydrogen peroxide tooth-whitening gel Formattato: Tipo di carattere: Arial strip for bleaching teeth that have been intrinsically stained from tetracycline. Given the severity of the staining in the cases presented during a recently conducted clinical trial, the resulting efficacy is dramatic. Additionally, the continuous use of these strips for 30 minutes per day, twice daily for 4 months with no adverse effects—unlike many previously prescribed whitening alternatives—is also noteworthy. INTRODUCTION Formattato: Tipo di carattere: Arial, Tutto maiuscole In cases requiring esthetic enhancement of discolored dentition, those involving tetracycline Formattato: Tipo di carattere: Arial stains are among the most challenging. These intrinsic stains, which cannot be removed with polishing or abrasive mechanisms, may result from the administration of tetracycline during Formattato: Tabulazioni: 432 pt, Allineato a sinistra + 450 pt, Allineato a sinistra + 468 pt, Allineato a sinistra childhood for the treatment of disease. The color and severity of stains vary and are influenced by the duration of tetracycline use, and the stage of tooth development at the time the medication was prescribed. While some patients may select veneers or full-coverage crown Formattato: Tipo di carattere: Arial restorations as the method with which to brighten their smile, still others may desire a more Formattato: Tipo di carattere: Arial conservative approach. To that end, tooth whitening offers a conservative, simplified, and economical alternative for changing tooth color. Eliminato: 89¶ 78 When clinicians are faced with the prospect of whitening a patient’s intrinsically stained teeth, considerations for treatment include shade and location of discoloration,1 as well as which formulation of whitening solutions to use. Whether whitening should take place in the office or at home under the dentist’s supervision, along with the longevity of the whitening protocol, must also be decided. It has been suggested that when discoloration appears at the neck of the tooth, the whitening results may be poorest; when the stain is dark gray or blue, the prognosis is similarly unimpressive. When whitening tetracycline-stained teeth, patients may need to commit to a course of treatment lasting several weeks or months.2-4 Treatment commonly involves the use of at-home vital bleaching kits, which were first introduced in 1989.5 According to some reports, tetracycline-stained teeth have been shown to demonstrate a favorable prognosis dependent upon the treatment considerations, even though they are the most resistant to bleaching.6 Specifically, one report showed that 97% of patients with tetracycline stains experienced successful tooth lightening when a carbamide peroxide whitening solution was used in a nightguard.1 A recently introduced 6.5% hydrogen peroxide whitening delivery system (Crest® Professional Whitestrips)a shows promise for use in whitening tetracycline-stained dentition when used at home for two months and under a dentist’s supervision. The hydrogen peroxide-impregnated polyethylene strips represent a treatment alternative for patients who cannot afford the cost of other whitening treatments and/or do not have time for multiple dental visits.7 This article presents the recent research findings of a clinical trial designed to evaluate the efficacy of two at-home vital bleaching systems on tetracycline-stained teeth. METHODS Formattato: Tipo di carattere: Arial, Tutto maiuscole A randomized clinical trial compared the efficacy of two at-home vital bleaching systems on Formattato: Tipo di carattere: Arial tetracycline-stained teeth. Daily bleaching was conducted over two months. Eligibility was Eliminato: 89¶ 79 limited to healthy adult volunteers who had 16 or more natural teeth, including at least 3 gradable maxillary incisors with significant tetracycline staining. Individuals demonstrating tooth sensitivity or an immediate need for dental treatment were excluded from participation in this trial. The study protocol, informed consent, and advertising were reviewed and approved by the Institutional Review Board. Written and verbal informed consent was received prior to study initiation. After informed consent and baseline measurements, subjects were randomized 3:1 to a strip-based, hydrogen peroxide tooth-whitening system (Crest® Professional Whitestrips) or a marketed tray-based, carbamide peroxide whitening system control (Opalescence® 10%)b. Subjects in both groups were supplied with a standard dentifrice (Crest® Cavity Protection Regular Paste)a, and soft toothbrush (Crest® Complete)a, for use throughout the study. All test products were overpackaged in 1-month product kits, and all labeling was identical except for a unique subject identification number. The 40 randomized subjects included 30 assigned to the strip group and 10 assigned to Formattato: Tipo di carattere: Arial, Non Grassetto the tray group. The study population ranged from 22 to 70 years of age. Approximately half of the sample presented with moderate to severe tetracycline staining (levels II through IV), one third of who had the more severe banding that is occasionally reported Formattato: Tipo di carattere: Arial, Non Grassetto following childhood antibiotic use. While tobacco use was uncommon (15% of the sample), 95% of the study participants consumed coffee, tea, or cola beverages daily. Treatment groups were generally well balanced with respect to demographic and behavioral parameters and tetracycline stain levels. Formattato: Tipo di carattere: Arial Eliminato: 89¶ 80 The first product application was supervised for instructional purposes, but all other treatment was unsupervised. Only the maxillary arch was treated. Participants in the strip group were instructed to wear a whitening strip for 30 minutes twice daily. Individuals in the tray group had a custom soft, full-arch bleaching tray fabricated with gingival scalloping and gel reservoirs using materials supplied by the manufacturer. Subjects in that group were instructed to place one half to three quarters of the contents of a bleaching syringe into the custom tray and wear the device for two hours daily. Clinical response was evaluated at entry and again each month after treatment. First, the level of tetracycline staining on the maxillary anterior teeth was assessed using a modified standard 3-point index.8 This modification recognized the possibility of successfully bleaching teeth with relatively severe tetracycline stain (Table 1). These baseline values, along with age, were used for balance and assignment during treatment randomization. Efficacy was assessed using a standard 16-step value-oriented tooth shade guidec used in dentistry to match artificial crowns to the natural dentition. Shade assessments were performed in a neutral-colored dental operatory under color-balanced lighting conditions by a trained and calibrated examiner. Tolerability was assessed by intraoral examination and subject report at each study visit (Table 1). Individual shade scores were determined by ordering the 16 shades arranged from dark to light Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto according to the rank ordering suggested by the manufacturer. To account for unusually dark colors (often seen with tetracycline stain) or white colors (often seen postbleaching), this 16step guide was supplemented by 2 additional values (C4+ and B1-) representing shades darker than C4 or lighter than B1. Effectiveness was determined by calculating the change in shade scores from baseline at each posttreatment visit. Using this method, a decrease in numeric shade score represented an increase in tooth whiteness. Treatment groups were compared Eliminato: 89¶ 81 using analysis of covariance with the baseline shade as the covariant. Comparisons to baseline were 1-sided, while between-group comparisons were 2-sided using a 5% significance level. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, Grassetto, Colore carattere: Automatico, Tutto maiuscole RESULTS Both treatments were effective overall in improving the shade of tetracycline-stained teeth (Table 2). Relative to baseline, the 2 groups averaged approximately 4 to 6.5 units of shade Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto improvement after 2 months of treatment. Observed changes were greater on average after 2 months as compared to 1 month. Response was faster in the strip group. During the first month’s treatment, individuals in the strip group averaged greater than a 4-unit reduction in tooth shade, which represented a highly statistically significant (P < .0001) improvement vs baseline. In contrast, subjects in the tray group averaged less than a 1-shade reduction during the first month, not differing statistically from baseline (P > .10). Adjusting for baseline, the strip group averaged 2.6 to 3.2 units more shade reduction compared with the tray group control. With respect to between-group comparisons, the strip group experienced statistically significantly superior reductions (P < .01) in shade compared with the tray group at both the 1- Formattato: Tipo di carattere: Arial, 11 pt and 2-month time points (Table 3). Formattato: Tipo di carattere: Arial Both treatments were generally well tolerated. Mild and transient tooth sensitivity and oral Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto irritation were the most common adverse events associated with daily bleaching (Table 4). All such events were typically reported early in the treatment regimen, and there were no clinical manifestations present at the Month 1 or Month 2 clinical examinations. Six subjects discontinued treatment during the first 2 months (3 in each treatment group). Of these, 2 individuals in the tray group reported the regimen was inconvenient and withdrew after the Month 1 visit. No one withdrew early or reported modifying their treatment regimen because of an adverse event. Formattato: Tipo di carattere: Arial Eliminato: 89¶ 82 Formattato: Tipo di carattere: Arial, Grassetto, Colore carattere: Automatico, Tutto maiuscole DISCUSSION This study was designed to evaluate clinical response following longer-term, daily use of 6.5% hydrogen peroxide whitening strips. The researchers elected to test extended treatment in Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto individuals with tetracycline staining, because this clinical condition is reported to require extended treatment of several weeks or months in order to achieve meaningful whitening.9 A marketed 10% carbamide peroxide, tray-based system was selected as the control group, because this agent has been previously used and reported to be effective in longer-term studies of tetracycline staining.10,11 Formattato: Tipo di carattere: Arial Both the strip and tray-bleaching systems were effective, with both groups differing significantly Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto from baseline at the end of the 2-month monitoring period. Color response in the strip group was superior to the tray group, as evidenced by the significant (P < .01) between-group treatment differences at both Months 1 and 2, favoring the “trayless” whitening strip system. Onset of these clinical benefits was more rapid in the strip group. After 1 month of treatment, the strip group averaged more than a 4-shade improvement compared to less than 1 shade in the tray group, with only the strip group experiencing statistically significant improvements in tooth color after 1 month. After 2 months, the strip group averaged a 67% greater shade improvement overall compared to the tray control group. While overnight tray use may improve clinical response in that group, such daily treatment conducted during the long term could also affect Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Non Corsivo Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto subject compliance. Treatment response in some individuals was impressive (Figures 1 and 2). However, this study confirms early observations of the need for extended contact time in many tetracycline-stained patients. After 2 months of daily treatment, involving approximately 60 hours of strip use or 120 hours of tray use, no subjects had yet reached the predetermined bleaching cutoff (B1-). In these subjects, additional time may be necessary to affect maximum color change. Previous Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto reports suggest a minimum of 2 months of treatment, hence the time point elected in this Eliminato: 89¶ 83 study.12 The researchers expect to continue treatment and observation of this study population for up to 6 months to further assess the effectiveness and tolerability of these agents with even longer-term exposure. Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Non Apice / Pedice Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Twice-daily use of the 6.5% hydrogen peroxide whitening strips was well tolerated over the 2month treatment period. The side effects in this study—transient tooth sensitivity and gingival irritation—were generally similar in nature and severity to the primary events reported in other longitudinal trials using the at-home tray-bleaching systems.9 In the current study, where the whitening strips were used for a total of 60 contact hours over a 2-month period, no subject in the strip group discontinued treatment due to an adverse event. This extended exposure associated with long-term, daily treatment of tetracycline stain corroborates and extends the safety of strip-based tooth whitening as reported in earlier, shorter-duration clinical trials.13-20 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Non Apice / Pedice Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Non Apice / Pedice Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto CONCLUSION The use of whitening strips has been proposed as a viable option for longer-term whitening because of favorable compliance, lower systemic exposure, and other factors associated with this easy-to-use bleaching system.14 New clinical research involving extended treatment of tetracycline stain over 2 months confirms this proposition. In the current study, daily treatment Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, Grassetto, Colore carattere: Automatico, Tutto maiuscole Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto for 1 month with a 6.5% hydrogen peroxide whitening strip provided similar efficacy as 2 months of treatment with a 10% carbamide peroxide tray system. Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ 84 Tables Formattato: Tipo di carattere: (Predefinito) Arial, Sottolineato Table 1—Tetracycline Stain Classification Formattato: Tipo di carattere: Arial Table 2—Baseline Demographic and Behavioral Information Table 3—Tooth Shade by Treatment and Time Table 4—Tooth Sensitivity and Oral Irritation Table 1—Tetracycline Stain Classification* Score Clinical Presentation 0 No tetracycline staining evident I Uniform light yellow, brown, or grey stain confined to incisal three-quarters of Formattato: Tipo di carattere: Arial the crown II Deep yellow, brown, or grey stain, without banding III Dark grey or blue stain with marked banding IV More severe or extreme staining *Modified from Boksman and Jordan, 1983. Formattato: Tipo di carattere: Arial Eliminato: 89¶ 85 Table 2—Baseline Demographic, Behavioral and Tooth Shade Information Demographic Strip Characteristic/Statistic Tray Overall Two-Sided (n =30) (n =10) (n =40) .7591 P-value Age (Years) Mean (SD) 37.7 (9.46) 38.9 (14.72) 38 (10.81) Minimum - Maximum 22 - 58 25 - 70 22 - 70 Female 19 (63.3%) 3 (30%) 22 (55%) Male 11 (36.7%) 7 (70%) 18 (45%) Asian (Oriental) 6 (20%) 4 (40%) 10 (25%) Caucasian 24 (80%) 6 (60%) 30 (75%) No 25 (83.3%) 9 (90%) 34 (85%) Yes 5 (16.7%) 1 (10%) 6 (15%) Sex .1401 Race .2323 Tobacco Use 1.0000 Daily Coffee/Tea/Cola Consumption No 2 (6.7%) 0 (0.0%) 2 (5%) Yes 28 (93.3%) 10 (100%) 38 (95%) 1.0000 Tetracycline Stain Levels I 15 (50%) 4 (40%) 19 (47.5%) II 7 (23.3%) 1 (10%) 8 (20%) III 8 (26.7%) 4 (40%) 12 (30%) IV 0 (0.0%) 1 (10%) 1 (2.5%) Mean 11.1 13.5 11.7 Minimum-Maximum 6-17 7-17 6-17 .3176 Tooth Shade .0823 Eliminato: 89¶ 86 Formattato: Tipo di carattere: Arial Table 3—Tooth Shade by Treatmemt and Time Comparison to Baseline Between-Group Comparisons N Mean Change (S.E.) P-Value Mean P-Value Treatment Difference (S.E.) Month 1 Strip 26 -4.05 (0.397) <. 0001 Tray 9 -0.9 (0.696) 0.1014 Strip 26 -6.6 (0.418) <. 0001 Tray 7 -3.96 (0.835) <. 0001 -3.15 (0.852) .0005 -2.63 (0.993) .0097 Month 2 Table 4—Tooth Sensitivity and Oral Irritation Formattato: Tipo di carattere: Arial, Portoghese (Brasile) Strip Tray Overall (n=30)(n=10)(n=40) No. % No. % No. % Subj. Subj. Subj. Subj. Subj. Subj. Gingival Irritation 10 33.3 1 10 11 27.5 Tooth Sensitivity 13 43.3 4 40 17 42.5 0 0 0 0 0 0 Formattato: Tipo di carattere: Arial Reported Observed Gingival Irritation Formattato: Tipo di carattere: Arial Eliminato: 89¶ 87 Formattato: Tipo di carattere: Arial, Tutto maiuscole PRODUCT REFERENCES a The Procter & Gamble Co, Cinncinati, OH 45202; 800-492-7378 b Ultradent Products, Inc, South Jordan, UT 84095; 800-552-5512 c Vita Zahnfabrik, Germany; distributed in the US by Vident™, Brea, CA 92621; 800-828-3839 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial REFERENCES 1. Haywood VB, Leonard RH, Nelson CF, et al: Effectiveness, side effects and long-term status of nightguard vital bleaching. J Am Dent Assoc 125(9):1219-1226, 1994. 2. Haywood VB, Leonard RH, Dickinson GL: Efficacy of six months of nightguard vital bleaching of tetracycline-stained teeth. J Esthet Dent 9(1):13-19, 1997. 3. Haywood VB: Extended bleaching of tetracycline-stained teeth. Contemporary Esthetics and Restorative Practice 1(1):14-21, 1997. 4. Haywood VB: Bleaching tetracycline-stained teeth. Esthet Dent Update 7(1):25-26, 1996. 5. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-176, 1989. 6. Haywood VB, Leonard RH, Nelson CF: Efficacy of 6-months nightguard vital bleaching of tetracycline-stained teeth. J Dent Res 73 1994. 7. Kugel G: Nontray whitening. Compend Contin Educ Dent 21(6):524-528, 2000. 8. Boksman L, Jordan RE: Conservative treatment of the stained dentition: vital bleaching. Aust Dent J 28(2):67-72, 1983. 9. Leonard RH: Nightguard vital bleaching: Dark stains and long-term results. Compend Contin Educ Dent 21(suppl 28):S18-S27, 2000. 10. Leonard RH, Haywood VB, Eagle JC, et al: Nightguard vital bleaching of tetracyclinestained teeth: 54 months post treatment. J Esthet Dent 11(5):265-77, 1999. 11. Matis BA, Wang Y, Jiang T, et al: Six-month evaluation of bleaching agents in patients with tetracycline staining (abs). J Dent Res 80:182, 2001. 12. Haywood VB: Current status of nightguard vital bleaching. Compend Contin Educ Dent 21(suppl 28):S10-S17, 2000. 13. Gerlach RW: Shifting paradigms in whitening: introduction of a novel system for vital tooth bleaching. Compend Contin Educ Dent 21(suppl 29):S4-S9, 2000. 14. Kugel G, Kastali S: Tooth whitening efficacy and safety: a randomized and controlled clinical trial. Compend Contin Educ Dent 21(suppl 29):S16-S21, 2000. 15. Gerlach RW, Jeffers MJ, Pernik PS, et al: Impact of prior tooth brushing on whitening strip clinical response (abs). J Dent Res 80:151, 2001. 16. Gerlach RW, Campolongo KL, Hoke PD, et al: Use of peroxide-containing polyethylene strips: effect of dosing duration on initial and sustained shade change (abs). J Dent Res 80:150, 2001. 17. Gerlach RW, Gibb RD, Sagel PA: A randomized clinical trial comparing a novel 5.3% hydrogen peroxide whitening strip to 10%, 15% and 20% carbamide peroxide tray-based bleaching systems. Compend Contin Educ Dent 21(suppl 29):S22-S28, 2000. 18. McMillan DA, Gibb RD, Gerlach RW: Impact of increasing hydrogen peroxide concentration on bleaching strip efficacy and tolerability (abs). J Dent Res 80:173, 2001. 19. Swift EJ, Heymann HO, Ritter AV, et al: Clinical evaluation of a novel “trayless” tooth whitening system. J Dent Res 80:151, 2001 Formattato: Tipo di carattere: Arial, Tutto maiuscole Formattato: Tipo di carattere: Arial Eliminato: 89¶ 88 Chapter 7 Long Term Hydrogen Peroxide Exposure and its Effect on Dentin Comparative Study of 6.5% Hydrogen Peroxide Bleaching Strips On Tetracycline Stain: Clinical Response After Six Months Daily Use Formattato: Tutto maiuscole ABSTRACT BACKGROUND A variety of indications exist for bleaching single or multiple teeth, including Formattato: Tipo di carattere: Grassetto, Non Corsivo, Tutto maiuscole tetracycline staining. The primary objective of this study was to evaluate clinical response following extended daily use of a trayless 6.5% hydrogen peroxide tooth bleaching gel (Crest® Professional Whitestrips, The Proctor & Gamble, Cincinnati, OH USA) on tetracycline stain. In this research, 10% carbamide peroxide in an at-home daytime tray delivery system (Opalescence® 10%, Ultradent Products, Inc., South Jordan, UT, USA) was used for comparison purposesas an experimental control. MATERIALS AND METHODS In this single-blind clinical trial, subjects were randomly Formattato: Tipo di carattere: 11 pt, Non Corsivo, Tutto maiuscole assigned to a Strip group (30 subjects) or a Tray group (10 subjects) following screening for tetracycline staining. Subjects used their respective products for approximately 6 months, with clinical safety and efficacy measurements taken at the end of each month. The strip product was used for 30 minutes, twice daily (maxillary arch only). The tray product was used for 2 hours daily (maxillary arch only). Treatment efficacy was determined by the tooth color change from baseline using an expanded Vita Shade guide. RESULTS The Strip group averaged greater shade reduction compared to the day wear Tray Formattato: Tipo di carattere: 11 pt, Non Corsivo, Tutto maiuscole group at the Months 1, 2, and 3 visits, respectively. After Month 3, there were no significant between-group differences in shade. Of the subjects in the Strip group, 65 % reached B1 tooth color by Month 6, while 43% of subjects in Tray group obtained this result after 6 months. Both treatments were generally well tolerated. Mild and transient tooth sensitivity (40-47%) and oral irritation (30-47%) were the most common adverse events associated with daily bleaching, yet Eliminato: 89¶ 89 neither affected study participation. Conclusions: Both the 6.5% H2O2 experimental bleaching strip (Crest Professional Whitestrips) and daywear marketed tray-based carbamide peroxide system (Opalescence 10%) provided significant tooth whitening in subjects with tetracycline stain. The Strip group obtained the results in a shorter pproximately half the time compared to the day wear Tray group. Formattato: Tutto maiuscole CLINICAL SIGNIFICANCE When used daily for 6 months, a 6.5% H2O2 bleaching strip and the 10% carbamide peroxide tray system can be effective in whitening tetracycline stain. Both the professional strip and tray systems were well tolerated throughout the 6-month usage period. This extended use provides additional evidence of clinical safety associated with use of these products for vital bleaching. Formattato: Tipo di carattere: Arial, 12 pt Formattato: Titolo 1, Interlinea doppia INTRODCUTION Formattato: Tutto maiuscole Aging, chromatogenic food and drinks, excessive fluoride intake, medication (tetracycline) and others can be the cause of intrinsic stains. Tetracycline stains, though, are considered to be the most difficult types of intrinsic stains to manage clinically. The devastating effect on tooth Formattato: Tipo di carattere: Arial, Tutto maiuscole Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Nero formation of as little as one gram of tetracycline was recognized in the late 1950s1 and confirmed by a study of cystic fibrosis patients by Swachman et al 2. In 1970, Cohen and Parkins published a method for bleaching the discolored dentin of young adults with cystic fibrosis who had undergone tetracycline treatment 3. Different variations of tetracycline and derivates produce different colors in the tooth. When the Formattato: Normale, Giustificato teeth are exposed to the sunlight, they become darker, with a distinct gray/blue tinge. It is Formattato: Tipo di carattere: Arial suggested that the reason that the front incisor teeth darken while the molars remain yellow longer is the different exposure to light 3. The discoloration of the permanent dentition depends Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Nero on the amount and duration of tetracycline use4. The portion of the tooth, color and severity of the stains can be determined by the stage of the tooth development at the time of the drug administration. Tetracycline is incorporated into dentin during tooth calcification intra and post Eliminato: 89¶ 90 partum, probably through chelation with calcium forming tetracycline orthophosphate 5. It can be deposited in fetal tooth buds when administered in the third trimester of pregnancy or by a child during the development of the tooth (between ages 3 to 4 months and 7 to 8 years) 6, 7. Colors may vary intensity of gray, blue, brown and yellow. The different banding can also be attributed to the variations of the tetracycline derivates. Clinicians are aware of the results from the use of tetracycline in pregnancy and young children. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto, Colore carattere: Nero Even though physicians and dentists should seek other sources of treatment, tetracycline is still the drug of choice for treatment of Rocky Mountain spotted fever and it is also the most prescribed medication for acne. Tetracycline stained teeth may respond to bleaching treatments but in a different rate from the other types of stains 8,9. Treatment is usually achieved by at-home vital bleaching kits, which were first introduced in 1989 10. The most common regimen in the literature involves overnight application of the bleaching tray for periods of several months8. Even with this extended treatment, clinical outcomes may be mixed. Recently, a strip-based system was developed to deliver peroxide topically without fabrication of a custom tray 11,12 Formattato: Tipo di carattere: (Predefinito) Arial . This trayless approach may be particularly relevant where professionally-directed long term use is indicated, and where compliance with trays may be problematic12. This new research was conducted to extend strip treatment over a much longer duration than heretofore in order to evaluate clinical safety and effectiveness of vital bleaching in patient’s longer treatment. Formattato: Tutto maiuscole MATERIALS AND METHODS Clinical research was conducted to evaluate clinical safety and effectiveness of a hydrogen peroxide-based tooth whitening system under conditions of extended (long term) daily use. The research was a randomized, examiner-blind, parallel group clinical trial comparing two peroxide systems that differed with respect to delivery, and peroxide source. The experimental group Eliminato: 89¶ 91 was 6.5% hydrogen peroxide whitening strips (Crest® Professional Whitestrips, The Procter & Gamble Co., Cincinnati, OH USA). The comparison group positive control was a 10% carbamide peroxide gel (Opalescence® 10%, Ultradent Products, Inc., South Jordan, UT, USA) delivered in a custom bleaching tray. This system, which carries the American Dental Association “Seal of Acceptance”13 for tooth whitening products, has been shown to be safe and effective in numerous clinical trials14,15,16,17. Bleaching was conducted each day over a 6 month period. The target population was individuals with tetracycline staining, because these case types are widely recognized to require several months of treatment 18 . Eligibility was limited to healthy adult volunteers who had a minimum of 16 natural teeth, including all 4 maxillary central and lateral incisors, and at least 3 gradable maxillary incisors having clinical evidence of tetracycline-related staining. Individuals with untreated periodontal disease or dental caries, or dentinal hypersensitivity were excluded from participation. The study protocol, informed consent, and advertising were reviewed and approved by Tufts University Institutional Review Board. Written and verbal informed consent was received prior to initiating the study. Because the tray system had been used for an extended period, and shown to be safe, this research was specifically designed to thoroughly evaluate the clinical safety and effectiveness of the strip system under extended usage conditions. Because of the difficulty in identifying patients who would participate in long term research, and to assure an adequate sample size in the strip group, subjects were randomized 3:1 to the whitening strips or tray control group. A dental impression was taken of the maxillary arch of those subjects assigned to the tray group to make custom bleaching trays. Subjects in that group received a custom, soft, fullarch bleaching tray fabricated with gingival scalloping and gel reservoirs using materials 92 Eliminato: 89¶ supplied by the manufacturer (Ultradent Products, Inc. South Jordan, UT USA). Each strip kit contained one carton of 56 upper strips in pouches. Each tray kit contained 24 unit-dose syringes and 1 pocket tray case for the custom maxillary bleaching tray. In addition to the test products (and custom tray where appropriate), all subjects were supplied with an anticavity dentifrice (Crest® Cavity Protection, The Procter & Gamble Co., Cincinnati, OH USA), and 2 soft toothbrushes (Crest® Complete, The Procter & Gamble Co., Cincinnati, OH USA). All study-related products and materials were dispensed every four weeks in nonidentifiable kits with. For blinding purposes, kit labeling was identical, except for a unique subject identification numbers. Only the maxillary arch was treated. Strip use was 30 minutes twice daily. Subjects in the tray group were instructed to place half to three quarters of the contents of a bleaching syringe into the custom tray and wear the device for 2 hours daily. Because both groups were assigned to a peroxide-containing product, and because only the maxillary arch was treated, all subjects were offered a marketed, peroxide-based tooth whitening system for “compassionate use” on the mandibular arch after study completion. Clinical response was evaluated at baseline and again every 4 weeks after treatment. The level of tetracycline stain on the maxillary anterior teeth was assessed using a modified standard index (Jordan and Boksman Tetracycline Stain Classification) that recognized the possibility of successfully bleaching teeth with relatively severe tetracycline stain 19,9 . Tetracycline stain (I or II versus III or IV) and age were used for balancing during treatment randomization. Efficacy was assessed using a standard 16-steptab value-oriented tooth shade guide (Vita Lumin, Vita Zahhnfabrik, Bad Sackingen, Germany). Shade examinations were performed Eliminato: 89¶ 93 under color-balanced lighting conditions by a trained and calibrated examiner. Safety was assessed at baseline and each subsequent visit. Subjects were interviewed at each visit to ascertain the occurrence of any tooth hypersensitivity and/or oral irritation anytime during treatment. All adverse events were collected irrespective of causality. For subjects with findings, severity and duration were assessed, along with any interventions (rescue medications, treatment alteration, and the like) in accordance with pharmaceutical research standards. Where banding was present, shade measurements were based on the predominant shade scored ofn the tooth outside of the banded zone. All shades were collected by an examiner who was blind to treatment assignment. Individual shade scores were determined by ranking the 16 shade tabs, arranged from light to dark, according to the rank order suggested by the manufacturer. This value-ordered ranking assigned “B1” as the first (lowest) step, and “C4” as the last (highest) step of the 16 possible outcomes. To account for exceedingly light or dark tooth colors, shade scores were expanded to include two additional categories representing colors lighter or darker than those available using this value-oriented system: shade “B1–“ (whiter than “B1”) with a numerical code “0”, and shade “C4+” (darker than “C4”) with numerical code “17”. Effectiveness was determined by calculating the change in shade scores from baseline at each post-treatment visit. Using the expanded 18-tabstep rank order, a decrease in numeric shade score represented an increase in tooth whiteness. Anticipating the effectiveness of long term peroxide treatment, any subject who reached the lowest numerical shade (B1 or lower) before end-of-treatment was withdrawn from active treatment by the investigator. For those subjects who were withdrawn from treatment (< or = B1 before Month 6), the “last observation carried forward” method was used to compute shade improvement at Eliminato: 89¶ 94 subsequent visits. Tobit censored regression models were used to adjust for possible bias attributable to effectiveness-related early withdrawals20,21. Treatment groups were compared using analysis of covariance with the baseline shade as the covariant. Comparisons to baseline were 1-sided, while between-group comparisons were 2-sided using a 5% significance level. Formattato: Tutto maiuscole RESULTS Age at baseline ranged from 22 years to 70 years, with mean (SD) age of 38 (10.8) years (Table 1). Females accounted for 55% of the population. 25% of subjects reported Southeast Asian origin. There was considerable variation in tetracycline staining, with 52% of subjects presenting with moderate-to-severe tetracycline staining (levels II-IV). Only one subject in the tray group exhibited the most severe staining/banding (level IV) at baseline. Shade scores ranged from 6 (corresponding to the “C1” tab) to 17 (“C4+”). While tobacco use was uncommon (15% of the sample), 95% of study participants consumed coffee, tea, or cola beverages daily. Treatment groups were balanced (p > 0.14) with respect to demographics, behavioral parameters and tetracycline stain levels. Formattato: Tipo di carattere: Arial Both treatments were effective overall in improving the shade of tetracycline-stained teeth, as Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto evidenced by the significant (p < 0.05) improvement in shade after 1-2 months depending on treatment. After 1-month treatment, the strip group averaged more than a 4-shade improvement compared to a less than 1 shade in the tray group. The strip group exhibited a statistically significant (p<0.0001) improvement in tooth shade after 1 month (Table 2). Both groups experienced incremental shade improvement with continued use after Month 1. This incremental benefit was more apparent in the tray group, such that, by Month 4, there were no significant (p > 0.48) differences between groups with respect to mean shade improvement from baseline. After 6-months daily use, the groups averaged a 10-11 shade improvement from baseline. Eliminato: 89¶ 95 Formattato: Tipo di carattere: Arial During the first 2 months of continuous daily treatment, no subjects in either treatment group Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto reached or exceeded the minimum shade level. By Month 3, only 2 subjects (both in the strip group reached) reached “B1” or lighter and were withdrawn from treatment. After 6 months daily treatment, 40% of study subjects still had not reached or exceeded this minimal shade cutoff. Use of Tobit (censored regression) models, which adjusted for the biases in the treatment difference at Month 3, 4, 5 and 6 visits, yielded treatment differences ranging from 1.3 to 0.6 shades favoring of the strip group (Table 3). Groups differed significantly (p = 0.04) with respect to this “carry-forward” response only at the Month 3 time point. Formattato: Tipo di carattere: Arial Mild and transient tooth sensitivity and oral irritation were the most common adverse events Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto associated with treatment (Table 4). Findings were symptomatic in nature, as there were no product-related clinical manifestations present at any of the monthly clinical examinations. Occurrence of tooth sensitivity and oral irritation, which ranged from 30-47%, was somewhat higher in the strip group compared to the tray group. Onset was generally during the first month of treatment, and transitory, resolving fully concurrent with treatment. Six subjects discontinued treatment during the first 2 months (3 in each treatment group). Two individuals (both in the tray group) found the daily treatment regimen to be inconvenient and withdrew after the Month 1 visit. The other 4 were “lost-to-follow-up”. There were no systemic or non-oral adverse events (nausea or others) relating to product usage anytime during the 6month treatment period. No subjects reported using any “rescue medication” such as analgesics because of treatment-related sensitivity. There were no reports of early withdrawal due to a product-related adverse event, and none of the study subjects reported modifying usage because of treatment-related irritation or sensitivity. Formattato: Tipo di carattere: Arial Eliminato: 89¶ 96 Formattato: Tutto maiuscole DISCUSSION This study evaluated clinical response following longer-term, daily use of hydrogen peroxide- Formattato: Tipo di carattere: Arial, 11 pt, Non Grassetto containing whitening strips relative to thea carbamide peroxide day wear tray-based group.control. The target population consisted of individuals with tetracycline staining, because clinical research repeatedly has demonstrated the need for extended treatment over several months to achieve meaningful whitening with these cases 220 . A marketed 10% carbamide peroxide, tray-based system was selected for as the comparisoncontrol group, because this agent has been previously reported to be safe and effective on tetracycline stain when used overnight over a 6 month period.(1144) .. Subjects used their assigned treatment regimen throughout the 6-month test period unless they reached an average Vita Shade score of “B1” or lighter prior to last evaluation. Those attaining this degree of whiteness were withdrawn from additional bleaching but were followed through the remainder of the trial for efficacy and safety outcomes. In this research, both the strip and tray bleaching systems were effective, yielding a highly significant (p < 0.001) and similar 10-11 mean shade improvement from baseline after 6 months use. That both systems were comparable with respect to end-of-treatment efficacy may be expected given certain overt similarities between treatments. The 6.5% hydrogen peroxide strip system was used twice daily for 30 minutes, a 1-hour total daily contact time. The 10% carbamide peroxide tray system (equivalent to ~3.5% hydrogen peroxide) was used once daily for 2-hours. In this study, onset of shade improvement was earlier, and the magnitude of the change was greater with strips compared to trays. Through Month 3, the strip group exhibited a statistically significant (p < 0.05) 1.3 to 3.2 shade improvement relative to the tray control. What accounteds for the significant between-group differences in shade improvement seen early in treatment? One likely explanation is that tTwice a day use of a strip for 30 minutes applied a Eliminato: 89¶ 97 higher concentration of peroxide more frequently , which allows for episodic treatment, could represent an easier regimen for some individuals when compared to 2-hours of continuous tray use of the lower concentration carbamide peroxide gel. Other factors could have contributed to these findings, including the small sample size in the tray group, differences in the tetracycline staining at baseline, and/or compliance (strips versus the day wear regimen used for the trays). The portability and flexibility of strips may aid in treatment compliance, especially early in the treatment regimen. However, shade guides represent an imperfect measure of efficacy, especially for complex clinical presentations like those seen with tetracycline staining. As such, the comparative effectiveness of outcomes must be evaluated with caution because causality cannot be assessed from multi-factorial research like this clinical trial. This study provides new evidence of an expanded safety in-use with strip-based tooth whitening. Both bleaching systems in this trial were well tolerated with daily use over a 6-month treatment period. No subjects in either group discontinued treatment early due to productrelated adverse events. For the tray system, these findings corroborate other reports of safe continuous daytime use of 10% carbamide peroxide on tetracycline stain 231,242 . The research provides additional assurance of the clinical safety of this 10% carbamide peroxide tray system with conventional use over a few weeks, and longer term use for treatment of tetracycline staining. For the strip system, the findings provide first evidence of in-use clinical safety with extended treatment. The research, which expands on an earlier report establishing clinical safety at concentrations up to 6.5% hydrogen peroxide on strips for periods of up to 2 months daily use, extends treatment duration through 6-months 9. Twice-daily use of the 6.5% hydrogen peroxide whitening strips was well tolerated over that period, with the principal side effects being —ttransient tooth sensitivity and gingival irritation. These events were observed to occur more frequently in the strip group. Differences in occurrence rates between groups could be attributable to the higher peroxide concentration in the strip versus the day wear tray group, or other factors, including random chance. —being similar in nature and severity to the carbamide Eliminato: 89¶ 98 peroxide, tray-based control group. Compared to the earlier 2-month findings, extended use resulted in only a few additional reports of sensitivity/irritation, with no increasing severity or persistence. Longer-term use through Month 6 showed no evidence of any cumulative toxicity. While the sample size is small, (n=7) this research also suggests that a 10% carbamide peroxide tray based system can result a meaningful reduction in tetracycline stain with day-time use. Previous research showed the effectiveness of 10% carbamide peroxide used overnight in a tray based system 8. This new research suggests day-time use may be a viable option where indicated due to compliance, patient preference or other factors. Long term clinical trials of this duration may be particularly relevant in establishing clinical safety associated with routine treatment, as a research model that evaluates extreme (intentional or unintentional) use. Such research may only be appropriate with populations such as this one, where long-term treatment is common and/or necessary to achieve a desired endpoint, where ethical and experimental controls are adequate to interpret outcomes, and where rigorous and sufficient exit criteria are established to assure in-use safety. Under these conditions, longer duration trials represent a “torture test” of sorts, offering additional insight on short-term clinical safety. This extended duration research, wherein whitening strips were professionally- dispensed following clinical examination, and used for 180 contact hours over a 6-month period to treat tetracycline stain, corroborates and extends the safety of strip-based tooth whitening as reported in earlier, shorter duration clinical trials 9,253-27,24. Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital bleaching with professional tray or strip systems can yield an evident improvement in appearance within a few weeks. While this non-invasive, treatment may need to continue over an extended period. Some individuals will show favorable response after 3-4 months, after which treatment may be discontinued. Duration may be difficult to predict, given the variable Eliminato: 89¶ 99 clinical manifestations of tetracycline staining. Practitioners and patients should be advised that optimal bleaching of tetracycline staining may necessitate extended daily at-home treatment over a period of 3-6 months. The costs, risks, and benefits of the various treatment options must be considered as part of overall patient management. Formattato: Tutto maiuscole CONCLUSION Both the 6.5% hydrogen peroxide bleaching strip (Crest Professional Whitestrips) and the daytime tray-based carbamide peroxide tray systems (Opalescence 10%) provided significant tooth whitening of tetracycline stain. While shade improvement generally occurred earlier with the strips compared to the trays, by Month 4, groups did not differ significantly in this whitening end point. Both groups demonstrated similar results after 6 months. Daily use of strips or daytime tray bleaching for an extended 6-month period (approximately 180 contact hours) was generally well-tolerated, with no subjects discontinuing treatment early due to an adverse event, and with the principal adverse events—mild tooth sensitivity or and oral irritation—being similar to that seen with the at-home carbamide peroxide tray system. Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Rientro: Sinistro: 9 pt Eliminato: 89¶ 100 Tables and Figures Table 1. BASELINE DEMOGRAPHIC CHARACTERISTICS Table 2. Treatment Comparisons, Mean Shade Change at Months 1-3 Figure 1. Mean Shade Change by Group Figure 2. Percent of Subjects Who Reached Minimum (“B1”) Shade by Group Table 3. Treatment Comparisons, Percent of Subjects Who Reached Minimum Shade at AND TETRACYCLINE STAINING Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt, Non Grassetto Months 3-6 Table 4. Occurrence of Oral Irritation and Tooth Sensitivity TABLE 1 BASELINE DEMOGRAPHIC CHARACTERISTICS AND TETRACYCLINE STAINING CHARACTERISTIC STATISTIC STRIP GROUP (n =30) TRAY GROUP (n =10) OVERALL (n =40) TWO-SIDED p-VALUE 37.7 (9.46) 38.9 (14.72) 38.0 (10.81) 0.7591 22 - 58 25 - 70 22 - 70 19 (63.3%) 11 (36.7%) 3 (30%) 7 (70%) 22 (55%) 18 (45%) 0.1401 e 15 (50%) 7 (23.3%) 8 (26.7%) 0 (0.0%) 4 (40%) 1 (10%) 4 (40%) 1 (10%) 19 (47.5%) 8 (20%) 12 (30%) 1 (2.5%) 0.3176 e AGE (YEARS) Mean (SD) Minimum Maximum Sex Female Male TETRACYLINE STAIN LEVEL I II III IV Eliminato: 89¶ 101 Table 2 Treatment Comparisons Shade Change from Baseline at Months 1-3 CHANGE FROM BASELINE N ADJ. (S.E.) MEAN ADJUSTED MEAN CHANGE (P-VALUE ) 95% C. I. ADJUSTED MEAN TREATMENT DIFFERENCE (S.E.) Strip Group 26 8.13(0.397) -4.05 (<0.001) (-4.83,3.27) -3.15 (0.852) <0.001 Tray Group 9 11.28(0.696) -0.9 (0.101) Strip Group 26 5.49(0.417) -6.61 (<0.001) (-7.43,5.79) -2.64 (0.991) 0.010 Tray Group 7 8.13(0.833) -3.98 (<0.001) (-5.61,2.34) Strip Group 26 3.52 (0.267) -8.59 (<0.001) (-9.11,8.07) -1.26 (0.634) 0.048 Tray Group 7 4.77 (0.533) -7.33 (<0.001) (-8.38,6.29) Strip Group 24 2.37 (0.309) -9.84 (<.0001) (-10.45,9.24) -0.41 (0.713) 0.5484 Tray Group 7 2.78 (0.592) -9.43 (<.0001) (-10.59,8.27) Strip Group 23 2.04 (0.262) -10.35 (<.0001) (-10.86,9.83) -0.31 (0.593) 0.5876 Tray Group 7 2.35 (0.49) -10.04 (<.0001) (-11,-9.08) Strip Group 23 1.71 (0.285) -10.67 (<.0001) (-11.23,10.12) -0.18 (0.645) 0.7764 Tray Group 7 1.89 (0.532) -10.5 (<.0001) (-11.54,9.45) PVALUE Month 1 (-2.27,0.46) Month 2 Month 3 Month 4 Month 5 Month 6 Eliminato: 89¶ 102 Table 3 Treatment Comparisons Percent of Subjects Who Reached Minimum Shade at Months 3-6 Subjects who Reached B1/B1- Treatment Difference N # (%) SUBJECTS P-VALUE ADJUSTED MEAN TREATMENT DIFFERENCE (S.E.) P-VALUE Strip Group 26 2 (7.7%) 1.00 -1.26 (0.61) 0.039 Tray Group 7 0 (0%) Strip Group 24 11 (45.8%) 0.202 -0.63 (0.96) 0.511 Tray Group 7 1 (14.3%) Strip Group 23 12 (52.2%) 0.103 -0.60 (0.85) 0.481 Tray Group 7 1 (14.3%) Strip Group 23 15 (65.2%) 0.394 -0.55 (1.25) 0.657 Tray Group 7 3 (42.9) Formattato: Tipo di carattere: (Predefinito) Arial Month 3 Month 4 Month 5 Month 6 Eliminato: 89¶ 103 Formattato: Tipo di carattere: (Predefinito) Arial, Grassetto, Non Corsivo Table 4 Formattato: Centrato OCCURRENCE OF ORAL IRRITATION AND TOOTH SENSITIVITY STRIP (n =30)a AE SOURCE/AE CLASSIFICATION Formattato: Tipo di carattere: (Predefinito) Arial GROUP TRAY (n =10)a GROUP OVERALL (n =40)a No. Subj. % Subj. No. Subj. % Subj. No. Subj. % Subj. 13 14 43.3 46.7 3 4 30 40 16 18 40.0 45.0 0 0 0 0 0 0 Reported Oral Discomfort Tooth Sensitivity Observed Oral Irritation Figure 1 Eliminato: 89¶ 104 Figure 2 Eliminato: 89¶ 105 REFERENCES 1. Arens D. The role of bleaching in esthetics. Dent Clin North Am 1989; 33:319-36 2. Swachman H, Fekete E, Kulezychi L, Foley T. The effect of long-term antibiotic therapy in patients with cystic fibrosis of the pancreas. Antibiot Annu 1958; 9:622-9 3. Cohen S, Parkins FM. Bleaching tetracycline-stained vital teeth. Oral Surg 1970; 29:465 4. Christensen GJ: Bleaching vital tetracycline stained teeth. Quintessence Int.1978 Jun: 9(6): 13-9 5. Mello HS. The mechanism of tetracycline staining in primary and permanent teeth. J Dent Child 1967; 34(6): 478 6. Moffitt JM, Cooley RO, Olsen NH, et al. Prediction of tetracycline-induced tooth discoloration. J Am Dent Assoc 1974; 88:547-552 7. Mull MM. The tetracycline and the teeth. Dent Abstr 1967; 12:346-350 8. Haywood VB, Leonard RH. Six-and 12-month color stability after 6 months bleaching tetracycline teeth [abstract 2891]. J Dent Res 1996; 75(special issue): 379 9. Kugel G, Aboushala A, Zhou X, Gerlach RW. Daily use of strips on tetracycline-stained teeth: comparative results after 2 months. Comp of Cont Edu in Dent. Jan 2002; 23 (1A): 2934 10. Haywood VB, Heymann HO:Nightguard vital bleaching . Quintessence Int 20(3):173176,1989. Kugel G. Nontray whitening. Compend Contin Educ Dent 2000;6:524-528. 11. Gerlach RW. Whitening paradigms 1 year later: Introduction of a novel professional tooth-bleaching system. Compend Contin Educ Dent 2002;23:4-8. 12. Siew C. American Dental Association. ADA Guidelines for the acceptance of tooth-whitening products. Compend Contin Educ Dent. Supplem (28): S44-7, 2000 Jun. 13. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital bleaching of tetracycline-stained teeth. J Esthet Dent. 1997;9:13-9. 14. Matis BA, Cochran MA, Eckert G, Carlson TJ. The efficacy and safety of a 10% carbamide peroxide bleaching gel. Quintessence Int. 1998;29:555-63. 15. Gerlach RW, Gibb RD, Sagel PA. A randomized clinical trial comparing a novel 5.3% hydrogen peroxide bleaching strip to 10%, 15% and 20% carbamide peroxide tray-based bleaching systems. Compend Contin Educ Dent 2000;21:S22-S28. 16. Matis BA. Tray whitening: What the evidence shows. Compend Contin Educ Dent 2003;24:354-362. 17. Haywood VB. Frequently asked questions about bleaching. Compend Contin Educ Dent 2003;24:324-338. 18. Boksman L, Jordan RE. Conservative treatment of the stained dentition: vital bleaching. Aust Dent J 1983;28:67-72. 19. Tobin, J. Estimation of Relationships for Limited Dependent Variables. Econometrica, 1958;26, 24 -36. 20. Green, W.H. Econometric Analysis, 2nd Edition, New York: Cambridge University Press, 1993. 21. Leonard RH. Long-term treatment results with nightguard vital bleaching. Compend Contin Educ Dent. 2003;24:364-74. 22. Leonard RH Jr, Haywood VB, Caplan DJ, Tart ND. Nightguard vital bleaching of tetracycline-stained teeth: 90 months post treatment. J Esthet Restor Dent. 2003;15:142-52 23. Matis BA, Wang Y, Jiang T, Eckert GJ. Extended at-home bleaching of tetracyclinestained teeth with different concentrations of carbamide peroxide. Quintessence Int. 2002;33:645-55. 24. Gerlach RW. Zhou X. Comparative clinical efficacy of two professional bleaching systems. Compend Contin Educ Dent 2002;23:35-41. Formattato: Tipo di carattere: (Predefinito) Arial, Tutto maiuscole Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Inglese (U.S.A.) Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Eliminato: 89¶ 106 25. Karpinia KA, Magnusson I, Sagel PA, Zhou X, Gerlach RW. Vital bleaching with two athome professional systems. Am J Dent 2002;15:13-18A. 1. Li Y, Lee SS, Cartwright SL, Wilson AC. Comparison of clinical efficacy and safety of three professional at-home tooth whitening systems. Compend Contin Educ Dent 2003;24(5):357-64. Formattato: Tedesco (Germania) Formattati: Elenchi puntati e numerati Formattato: Inglese (U.S.A.) Formattato: Tipo di carattere: Arial Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Eliminato: 89¶ 107 Chapter 8 Paint on delivery systems A Clinical Comparison of Two Paint on Whitening Systems Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial INTRODUCTION Formattato: Tipo di carattere: (Predefinito) Arial, Non Corsivo The use of peroxide to whiten teeth dates back over 100 years. The advent of patient-applied kits, bleaching has become both common and popular, and use of peroxide is now generally Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt recognized as a safe and effective method for tooth whitening1-3. There are a variety of indications for bleaching single or multiple teeth, including staining from chromagenic foods or other sources, dental fluorosis, tetracycline staining and devital discolored teeth4-7. Delivery is via in-office, at-home regimens, such as polyethylene strips and paint-on, or combination regimens with or without professional supervision8-9. Easy availability of over the counter whitening products has made whitening of teeth more popular amongst people of all ages. There are different types of over the counter products like whitening dentifrices, tray based, whitening strips and the recently introduced brush Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt applications. Over the counter bleaching kit requires the consumer to use either a prefabricated tray or fabricate their own semi-molded tray then fill it with supplied bleaching agents. These types are less than ideal because the trays are not custom fitted and the formulation is not sophisticated as those dispensed by the dentist.10 Whitening toothpastes contain mild abrasives to remove surface stains. The peroxide content in the toothpastes are very low ( 1% or less ), also the exposures of the toothpastes on the tooth is minimal hence any whitening minimal.11 Eliminato: 89¶ 108 Formattato: Tipo di carattere: (Predefinito) Arial Whitening Strips is an alternative to rigid tray system for vital tooth whitening. The strip Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt technology uses same peroxide chemistry used in tray systems. The main drawback is that they are limited to the anterior teeth and cannot be easily adapted to the malposed teeth. The latest inclusion to OTC products is a Brush technique. This technique is non-tray based paint on application. These products include a 19% sodium percarbonate film (5.3% hydrogen Formattato: Tipo di carattere: Arial, 11 pt peroxide) along with an 18% carbamide peroxide paint-on gel. The advantages to the paint- on Formattato: Tipo di carattere: Arial, 11 pt products is ease of use as well as the elimination of the need for a tray. These systems also Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt limit gingival exposure. There is little data on efficacy of these products. Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Study Objectives The objective of this trial was to compare the safety and whitening efficacy of an experimental liquid strip (four weeks of use) to Colgate Simply White (three weeks of use). Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial Study Design This was a randomized, controlled, double-blind, parallel, single-center study. Fifty (50) Formattato: Tipo di carattere: Arial, 11 pt generally healthy subjects who desired to have their teeth whitened were enrolled in the study. Subjects who qualified for the study based on the results of their Baseline visit were randomly assigned to one of two treatment groups. The first product use was supervised at the Product Distribution visit. All product use followed the labeled use instructions. Digital imaging and oral tissue examinations were conducted at Baseline, Week 2, Week 3, and Week 4. Subjects Formattato: Tipo di carattere: Arial assigned to Simply White discontinued product use after the Week 3 visit and returned one Formattato: Tipo di carattere: Arial, 11 pt week later for digital imaging and oral tissue examinations. Subjects assigned to the experimental product continued product use for all four weeks of the study. During the entire Eliminato: 89¶ 109 study period (treatment and post-treatment), subjects brushed with Crest® Cavity Protection Formattato: Tipo di carattere: Arial, 11 pt, Non Apice / Pedice dentifrice and an extra-soft toothbrush. Formattato: Tipo di carattere: Arial, 11 pt . Formattato: Tipo di carattere: Arial Selection of Study Population Formattato: Allineato a sinistra Fifty (50) generally healthy adults with a Vita Shade score of B2 or darker who met all study Formattato: Tipo di carattere: Arial, 11 pt entrance criteria were enrolled. Subjects who withdrew from the study were not replaced. INCLUSION CRITERIA Formattato: Tipo di carattere: Arial, 11 pt To be included in this study, each subject must have: Formattato: Tipo di carattere: Arial, 11 pt a. presented with a Vita Shade score of B2 or darker on Teeth 8 and 9; Formattati: Elenchi puntati e numerati Formattato: Tipo di carattere: Arial, 11 pt b. provided written informed consent prior to their participation and be given a copy of the Formattati: Elenchi puntati e numerati signed consent form; Formattato: Tipo di carattere: Arial, 11 pt c. been at least 18 years of age at the time of enrollment; Formattati: Elenchi puntati e numerati Formattato: Tipo di carattere: Arial, 11 pt d. agreed not to participate in any other oral/dental product clinical studies during the course of Formattati: Elenchi puntati e numerati this study; Formattato: Tipo di carattere: Arial, 11 pt e. agreed to return for the scheduled visits and follow the study procedures; and Formattati: Elenchi puntati e numerati Formattato: Tipo di carattere: Arial f. agreed to refrain from the use of any non-study dentifrices and tooth whitening products for Formattati: Elenchi puntati e numerati the study duration. EXCLUSION CRITERIA Formattato: Tipo di carattere: Arial, 11 pt The subjects were excluded from this study if they: Formattato: Tipo di carattere: Arial, 11 pt Eliminato: 89¶ 110 a. had dental crowns or clinically meaningful malocclusion involving the maxillary or mandibular anterior dentition (also confirmed by Investigator at Baseline visit); b. reported having teeth previously bleached by a professional treatment, over-the-counter bleaching kit, or clinical trial test product; c. presented with any pre-existing oral or medical condition that the examiner or Investigator determined may have placed the subject at increased health risk from study participation; Formattato: Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: a, b, c, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra di: 36 pt, Tabulazioni: Non a 36 pt Formattato: Tipo di carattere: Arial Formattato: Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: a, b, c, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra di: 36 pt, Tabulazioni: Non a 36 pt Formattato: Tipo di carattere: Arial d. had any dental care planned during the duration of the study that may have: • impacted the general health of the subject, • impacted the ability of the subject to bleach teeth according to the protocol, • required a dental prophylaxis, or Formattato: Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: a, b, c, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra di: 36 pt, Tabulazioni: Non a 36 pt Formattato: Tipo di carattere: Arial Formattato • ... [124] Formattati: Elenchi puntati e numerati involved the anterior dentition; Formattato: Tipo di carattere: Arial e. were undergoing current treatment for gingivitis, periodontitis, or caries; Formattati: Elenchi puntati e numerati Formattato: Tipo di carattere: Arial f. were currently using a chlorhexidine mouth rinse or Listerine® mouth rinse; Formattati: Elenchi puntati e numerati Formattato: Tipo di carattere: Arial g. had teeth with clinically meaningful intrinsic staining due to tetracycline, fluorosis or Formattati: Elenchi puntati e numerati hypocalcification; Formattato: Tipo di carattere: Arial Formattati: Elenchi puntati e numerati h. had self-reported dentinal sensitivity, or Formattato: Tipo di carattere: Arial Eliminato: 89¶ 111 i. Formattati: Elenchi puntati e numerati had teeth that could not be imaged. CONTINUANCE CRITERIA Formattato: Tipo di carattere: Arial, 11 pt Subjects may have been discontinued from the study or been excluded from the efficacy Formattato: Tipo di carattere: Arial, 11 pt analysis if they: a. used a chlorhexidine mouth rinse and/or Listerine® mouth rinse; b. received a dental prophylaxis; or c. used any tooth whitening products other than assigned study products. Removal of Subjects from the Study Formattato: Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: a, b, c, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 54 pt + Tabulazione dopo: 72 pt + Rientra di: 72 pt, Tabulazioni: Non a 72 pt Formattato: Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: a, b, c, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 54 pt + Tabulazione dopo: 72 pt + Rientra di: 72 pt, Tabulazioni: Non a 72 pt Formattato: Tipo di carattere: Arial subjects from the study for medical reasons and where, in his judgment, there was significant Formattato: Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: a, b, c, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 54 pt + Tabulazione dopo: 72 pt + Rientra di: 72 pt, Tabulazioni: Non a 72 pt lack of compliance at any time. Formattato: Tipo di carattere: Arial Subjects were encouraged to complete the full course of the study; however subjects may have withdrawn from the study at any time or for any reason. The reason for withdrawal was documented on the appropriate case report form (CRF). The Investigator may have removed Formattato: Allineato a sinistra Formattato: Tipo di carattere: Arial Formattato: Normale Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial Formattato: Allineato a sinistra, Destro 16,55 pt, Interlinea singola Formattato: Tipo di carattere: Arial Study Procedures Formattato: Normale Eliminato: 89¶ 112 There were 5 study visits. A table detailing the procedures performed at each visit is provided in Formattato: Tipo di carattere: Arial, 11 pt Table 1. Formattato: Tipo di carattere: Arial, 11 pt, Grassetto SCHEDULE OF EVENTS Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Study No. 2002147 Table 1 Schedule of Events PreTreatment Treatment Visit 2 Procedures Visit 1 Product Visit 3 Visit 4 Visit 5 Baseline Distribution Week 2 Week 3 Week 4 Informed Consent X Inclusion/Exclusion Criteria X Demographics X Balance & Assignment X Supervised Product X Application Product Distribution X Product Return X Oral Status Interview X X X X Oral Hard & Soft Tissue X X X X X X X Examination Continuance Criteria X Eliminato: 89¶ 113 Study No. 2002147 Table 1 Schedule of Events PreTreatment Treatment Visit 2 Procedures Digital Imaging Visit 1 Product Visit 3 Visit 4 Visit 5 Baseline Distribution Week 2 Week 3 Week 4 X X X X X X X Adverse Events Subject Accountability X Formattato: Tipo di carattere: Arial BASELINE VISIT Written informed consent was obtained from each subject following review of the study design Formattato: Tipo di carattere: Arial, 11 pt and test regimen. Demographic information and inclusion/exclusion criteria were obtained and documented on the appropriate CRF. Each subject was given an oral status interview prior to receiving an oral soft tissue (OST) examination that included a self-reported tooth sensitivity assessment. Digital images of the facial anterior dentition were collected. PRODUCT DISTRIBUTION/BALANCE & ASSIGNMENT VISIT The b* and L* digital imaging scores obtained at the Baseline visit, along with age, were arrayed Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt to balance and assign subjects to treatment groups. Test product (kit boxes plus Crest) was distributed and written instructions were reviewed. Subjects completed their first product use under supervision. Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ 114 WEEK 2 VISIT Formattato: Tipo di carattere: Arial, 11 pt Approximately 2 weeks after beginning test product use, subjects returned to the clinical site. Formattato: Tipo di carattere: Arial, 11 pt Continuance criteria were assessed. An oral status interview and an oral exam were conducted. Self-reported, clinical OST and tooth sensitivity abnormal findings not present at Baseline were documented on the AE CRF. Digital images of the facial anterior dentition were collected. Formattato: Tipo di carattere: Arial WEEK 3 VISIT Formattato: Tipo di carattere: Arial, 11 pt Approximately 3 weeks after beginning test product use, subjects returned to the clinical site. Formattato: Tipo di carattere: 11 pt Continuance criteria were assessed. An oral status interview and an oral tissue exam were conducted. Self-reported, clinical OST and tooth sensitivity abnormal findings not present at Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial, 11 pt Baseline were documented on the AE CRF. Digital images of the facial anterior dentition were collected. Subjects assigned to Simply White discontinued product use at this time (per labeling), but continued to brush with the provided toothbrush and dentifrice. Formattato: Tipo di carattere: (Predefinito) Arial WEEK 4 VISIT Formattato: Tipo di carattere: Arial, 11 pt Continuance criteria were assessed. An oral status interview and an OST exam were Formattato: Tipo di carattere: Arial, 11 pt conducted. Self-reported, clinical OST, and tooth sensitivity abnormal findings not present at Formattato: Tipo di carattere: Arial, 11 pt Baseline were documented on the AE CRF. Digital images of the facial anterior dentition were collected. All test product was returned. Subjects were exited from the study Formattato: Tipo di carattere: Arial EFFICACY ASSESSMENTS DIGITAL IMAGING CAMERA The photographic system consisted of a HC2500 CCD high resolution digital camera Formattato: Tipo di carattere: Arial, 11 pt manufactured by Fuji. It was equipped with a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens and a linear polarizer to permit cross-polarized light. Two 150-watt lights located on each side of a CCD camera provided the lighting. The unit was connected to a personal computer which 115 Formattato: Tipo di carattere: Arial, 11 pt Eliminato: 89¶ recorded and analyzed the images. Prior to daily use, the system was calibrated to assure proper operation. Additionally, a color standard was centered and imaged every hour, then was removed prior to imaging subjects. Maxillary anterior facial surfaces were measured for tooth color using the digital image technology. One color value (L* a* b*) was generated from the complete surface of the measured teeth. Formattato: Tipo di carattere: Arial For each examination period, lighting in the exam room was background or ambient. Each Formattato: Tipo di carattere: Arial, 11 pt subject was asked to brush with water and an extra-soft toothbrush to dislodge any debris that Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt may have interfered with photography. The subject sat on a stool in front of a chin rest used to Formattato: Tipo di carattere: Arial, 11 pt hold the head still. The subject placed his/her chin on the chin rest, then positioned two plastic retractors into the mouth to retract his/her lips and cheeks. Formattato: Tipo di carattere: Arial It was also acceptable for the subject to position the retractors, then place their chin on the chin Formattato: Tipo di carattere: Arial, 11 pt rest. The subject was instructed to use the retractors to retract his/her lips and cheeks (toward their ears) as far as possible. The incisal edges of the front teeth were placed together and centered in the camera. The chin rest may have been adjusted to bring the teeth into the plane of focus and ensured the image was centered. Prior to exposure, the subject was instructed to draw air through their teeth and to position their tongue away from the teeth so that the tongue was not visible. By proper positioning of the camera, frontal images of each subject were taken at each visit. Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial SAFETY ASSESSMENTS In this study, an AE was defined as any negative oral cavity health effect, either reported by the Formattato: Tipo di carattere: Arial, 11 pt subject or noted by the Investigator. Serious adverse events (SAEs), which occurred during the course of the study and were reported to or observed by the study Investigator/examiner, were documented on the appropriate CRF. All SAEs were to be followed until resolution or until Eliminato: 89¶ 116 discharge from follow-up was warranted based on consultation between the Sponsor and the Investigator. Serious AEs were defined as one or more of the following: a) death, b) life-threatening, c) required in-patient hospitalization, and d) resulted in persistent or significant disability. When the Investigator was notified of an SAE, the Investigator must have promptly (within 24 hours) notified Procter & Gamble (P&G, the CRA or the Medical Monitor) of the SAE, regardless of causality. Within 5 working days, a written report describing the circumstances of the event must have been submitted to P&G. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 12 pt ORAL SOFT TISSUE (OST) EXAMINATION Assessment of the OST was conducted via a visual examination of the oral cavity and perioral Formattato: Tipo di carattere: Arial, 11 pt area utilizing a standard dental light, dental mirror, and gauze. The structures examined included the gingiva (free and attached), hard and soft palate, oropharynx/uvula, buccal mucosa, tongue, floor of the mouth, labial mucosa, mucobuccal/mucolabial folds, lips, and perioral area. All abnormal OST findings noted after test product assignment which were not documented at Baseline, or were present at Baseline but had worsened during test product usage, were recorded as AEs on the AE CRF. Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial TREATMENTS Method of Assigning Subjects to Treatment Groups Formattato: Tipo di carattere: (Predefinito) Arial After the Baseline visit, digital images were processed and subjects were randomly assigned in Formattato: Tipo di carattere: Arial, Tutto maiuscole approximately equal numbers to one of the two treatment groups. The randomization balanced Formattato: Allineato a sinistra for Baseline b* and L* scores, as well as age. Subjects who resided in the same household Formattato: Tipo di carattere: Arial, 11 pt were assigned to identical marketed products. A statistician that was not a member of the project team carried out the assignment procedure. Formattato: Tipo di carattere: Arial, 11 pt Eliminato: 89¶ 117 Formattato: Tipo di carattere: Arial TREATMENTS ADMINISTERED Formattato: Tipo di carattere: Arial, Non Maiuscoletto Experimental Whitening Product Formattato: Non Maiuscoletto Subjects were instructed to follow their customary brushing regimen for the study duration using Formattato: Tipo di carattere: Arial the Crest Cavity Protection dentifrice and toothbrush provided. Prior to using the test product, Formattato: Tipo di carattere: Arial, 11 pt subjects were instructed to brush and dry their teeth. Subjects applied the liquid strip to the facial surfaces of the maxillary anterior teeth once daily just prior to bedtime. Subjects were instructed not to eat, drink, or smoke for 90 minutes following treatment application. The test product was removed each morning by thoroughly brushing the teeth. Subjects were supplied with written instructions and shown pictures on how to apply the product. The first product use was completed under supervision at the Product Distribution visit. All other uses were unsupervised at-home. Formattato: Tipo di carattere: Arial Colgate Simply White Formattato: Tipo di carattere: Arial, Non Maiuscoletto Subjects followed the manufacturer directions for product use, and followed their customary Formattato: Tipo di carattere: Arial, 11 pt brushing regimen for the study duration using Crest Cavity Protection dentifrice and the toothbrush provided. Prior to using the test product, subjects were instructed to brush and dry their teeth. Subjects applied the whitening product to the facial surfaces of the maxillary anterior teeth twice per day. Subjects were instructed not to eat or drink for 30 minutes following treatment application. Subjects were supplied with the marketed instructions for use and shown pictures on how to apply the product. The first product use is completed under supervision at the Product Distribution visit. All other uses are unsupervised at-home. Formattato: Tipo di carattere: Arial, 11 pt IDENTITY OF INVESTIGATIONAL PRODUCTS • Experimental tooth whitener (19.0% sodium percarbonate, equivalent to 5.3% hydrogen Formattato: Tipo di carattere: Arial Formattati: Elenchi puntati e numerati peroxide), manufactured by The Procter & Gamble Company. Packaged in individual sachets / stick packs. Eliminato: 89¶ 118 • Colgate Simply White (commercial product) Formattato: Tipo di carattere: Arial Experimental Whitening Product Formattato: Tipo di carattere: Arial, Non Maiuscoletto Each kit contained a four-week supply of single unit doses (sachets), 20 micro brushes for Formattato: Tipo di carattere: Arial, 11 pt product application, one tube of toothpaste (Cavity Protection Crest, The Procter & Gamble Co., Cincinnati, OH, USA) one extra-soft toothbrush (Crest Complete, The Procter & Gamble Co., Cincinnati, OH, USA), and one instruction sheet. The sachets were labeled with study number, product number, applicable caution and warning statements, usage directions and other information as dictated by internal regulatory requirements and clinical standard operating procedures (SOPs). Formattato: Tipo di carattere: Arial Colgate Simply White Formattato: Tipo di carattere: Arial, Non Maiuscoletto Product was supplied in subject kit boxes. Each kit contained one 0.34 oz polypropylene bottle Formattato: Tipo di carattere: Arial, 11 pt with applicator, one tube of toothpaste (Cavity Protection Crest, The Procter & Gamble Co., Cincinnati, OH, USA) one extra-soft toothbrush (Crest Complete, The Procter & Gamble Co., Cincinnati, OH, USA), and one instruction sheet. The kits were labeled with study number, product number, applicable caution and warning statements, labeled usage directions and other information as required by internal regulatory and clinical SOPs. Formattato: Tipo di carattere: Arial Supplemental product was provided to the Investigator if additional product was needed, and Formattato: Tipo di carattere: Arial, 11 pt was dispensed only after consulting with the Sponsor for correct treatment group identification. The shipping containers were labeled with the "ship to" clinical site address and a "content statement" listing study number and subject numbers contained within. Eliminato: 89¶ 119 Formattato: Tipo di carattere: Arial BLINDING This was a double-blind study. Product use was conducted in an area where the examiner was Formattato: Tipo di carattere: Arial, 11 pt not present. Subjects were instructed not to discuss product appearance or physical qualities with the examiner. Formattato: Tipo di carattere: Arial TREATMENT COMPLIANCE Subjects received verbal and written instructions on dentifrice usage. Subjects used their Formattato: Tipo di carattere: Arial, 11 pt product for the first time on site under supervision as part of the instructions. Subjects were queried regarding compliance at each visit. Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial STATISTICAL ANALYSIS PLANS The primary assessment compared the treatment groups for yellowness reduction (Δb*) at the Formattato: Tipo di carattere: Arial, 11 pt end-of-treatment visit. The secondary assessment compared the treatment groups for yellowness reduction (Δb*) at the Week 2 visit. The tertiary assessment compared the treatment groups for yellowness reduction (Δb*) at the end-of-study visit. The mean whitening benefit for each treatment group was assessed at the post-baseline visits. The safety profile of each treatment group was characterized. Formattato: Tipo di carattere: Arial, Non Corsivo Operational Trial Hypotheses Tooth color was assessed by the digital imaging measurements b* (yellow – blue), L* Formattato: Tipo di carattere: Arial, 11 pt (lightness), and a* (red – green). For a given post-baseline visit: Δb* = b*visit - b*baseline, ΔL* = L*visit - L*baseline, Δa* = a*visit - a*baseline, and ΔE* = (ΔL*2 + Δa*2 + Δb*2) ½. In the case of tooth color, whitening benefit resulted primarily from negative Δb* (yellowness reduction). Additionally, positive ΔL* (increasing lightness) and negative Δa* (redness reduction) may have been observed. Changes in Δb*, ΔL*, and Δa* resulted in increased ΔE* (overall color change). Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial Eliminato: 89¶ 120 An additional color quantity was computed from the L*a*b* color values for each subject and Formattato: Tipo di carattere: Arial, 11 pt visit: W* = (b*visit2 + a*visit2 + (L*visit - 100)2) ½ which represented the distance to pure white for a given visit. One may have defined ΔW* = (b*visit2 + a*visit2 + (L*visit - 100)2) ½ – (b*baseline2 + a*baseline2 + (L*baseline - 100)2) ½ as the distance to pure white at a given visit minus the distance to pure white at Baseline. In the equations above, pure whiteness was achieved when b* = 0, a* = 0, and L* = 100. Primary Hypotheses Formattato: Tipo di carattere: Arial, Non Maiuscoletto The following hypothesis was tested at the end-of-treatment visit. Formattato: Tipo di carattere: Arial, 11 pt Null: The mean level of Δb* in the experimental group is equal to the mean level of Δb* in the Simply White group. Alternative: The mean level of Δb* in the experimental is not equal to the mean level of Δb* in the Simply White group. Formattato: Tipo di carattere: Arial Secondary Hypotheses Formattato: Tipo di carattere: Arial, Non Maiuscoletto The following hypothesis was tested at the Week 2 visit. Formattato: Tipo di carattere: Arial, 11 pt Null: The mean level of Δb* in the experimental group is equal to the mean level of Δb* in the Simply White group. Alternative: The mean level of Δb* in the experimental is not equal to the mean level of Δb* in the Simply White group. Formattato: Tipo di carattere: Arial Eliminato: 89¶ 121 Tertiary Hypotheses Formattato: Tipo di carattere: Arial, Non Maiuscoletto The following hypothesis was tested at the end-of-study visit. Formattato: Tipo di carattere: Arial, 11 pt Null: The mean level of Δb* in the experimental group is equal to the mean level of Δb* in the Simply White group. Alternative: The mean level of Δb* in the experimental is not equal to the mean level of Δb* in the Simply White group. The following hypothesis was tested for each treatment group and post-baseline visit. Null: The mean level of Δb* is equal to zero. Alternative: The mean level of Δb* is not equal to zero. The hypotheses above were investigated for other color parameters as well. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, Non Corsivo Efficacy Analysis Plans Summary statistics (e.g., means, standard deviations, frequencies, etc.) of the demographic Formattato: Tipo di carattere: Arial, 11 pt characteristics, b*, L*, a*, W*, and ΔE* were calculated for each treatment group and visit. The treatment groups were compared using analysis of covariance (ANCOVA) methods. The response was color change from Baseline and the covariate was the color at Baseline. Age was used as a covariate. Treatment comparisons were tested at the 0.05 level of significance. Formattato: Tipo di carattere: Arial Whitening benefit at each post-baseline visit was investigated using the mean color change Formattato: Tipo di carattere: Arial, 11 pt from Baseline within each treatment group and then performing one-sample t-tests. Comparisons to Baseline were tested using a two-sided 0.05 level of significance. Eliminato: 89¶ 122 Formattato: Tipo di carattere: Arial, Non Corsivo Safety Analysis Plans The safety data were summarized with respect to tooth sensitivity and oral irritation. Following Formattato: Tipo di carattere: Arial, 11 pt the end-of-study visit, all AEs, including OST-related AEs and dentinal hypersensitivity AEs were summarized overall and by treatment group. The safety data were also summarized through the Week 2 visit. Formattato: Tipo di carattere: Arial, 11 pt POWER AND SAMPLE SIZE CONSIDERATIONS At least 23 subjects per treatment group completing the study ensured at least 80% power to Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt detect a difference of 0.7 b* units between the treatment groups with a common standard deviation of 0.7, in two-sided testing at a 0.05 significance level. A target of up to 25 subjects was recruited per group (total of up to 50). Formattato: Tipo di carattere: Arial CHANGES TO THE ANALYSIS PLANS All planned analyses were performed. In addition, efficacy comparisons were made between Formattato: Tipo di carattere: Arial, 11 pt Week 2 for the Experimental Film group and Week 3 for the Colgate Simply White group. Also, the treatment groups were compared at the Week 3 visit as well. Safety data was also summarized through the Week 2 visit of the study. RESULTS Formattato: Tipo di carattere: Arial, Nessuna sottolineatura, Tutto maiuscole DISPOSITION OF SUBJECTS Formattato: Tipo di carattere: Arial Fifty-one subjects were screened, however, Subject 3021 was dropped from the study at Baseline due to investigator recommendation. Fifty subjects were randomized to treatment, and 47 subjects received product. Three subjects failed to present for product distribution visit: Formattato: Tipo di carattere: Arial Formattato: Normale, Interlinea singola Formattato: Tipo di carattere: Arial, 11 pt Subject 3007 voluntarily withdrew from the study, Subjects 3013 and 3041 were lost to follow- Eliminato: 89¶ 123 up. Thirty-nine subjects completed the study. Eight subjects 3024, 3025, 3027, 3032, 3033, 3045, 3057, 3016 were lost to follow-up (Table 3). Formattato: Tipo di carattere: Arial DATA SETS ANALYZED Demographic, digital imaging and adverse event data were all analyzed for this study. Three Formattato: Tipo di carattere: Arial, 11 pt subjects failed to present for the product distribution visit: Subject 3007 voluntarily withdrew Formattato: Tipo di carattere: Arial, 11 pt from the study, Subjects 3013 and 3041 were lost to follow-up. In the Colgate Simply White group, one subject (3045) was lost follow-up starting at the Week 2 visit and six subjects (3024, 3025, 3027, 3032, 3033, and 3057) were lost to follow-up at the Week 4 visit, two subjects (3002 and 3015) each missed one visit. In the Experimental Film group, one subject (3016) was lost follow-up starting at the Week 2 visit, two subjects (3008 and 3022) each missed one visit (Table 3). Formattato: Tipo di carattere: Arial DEMOGRAPHIC AND BASELINE CHARACTERISTICS Subjects ranged in age from 21 to 70 years with an average of 35 years. Sixty-four percent of Formattato: Tipo di carattere: Arial, 11 pt the subjects were female. Twenty-eight subjects (59.6%) were Caucasian, 12 subjects (25.5%) were Black, 3 subjects (6.4%) were Asian, 2 subjects (4.3%) were Asian and 2 subjects (4.3%) were Multi-racial. Cigarette and cigar smokers accounted for 10.6% of the subjects. Coffee, tea, and dark cola drinkers accounted for 89.4% of the subjects with a median of 2 drinks per day. Treatment groups were relatively balanced in demographic characteristics and behavioral parameters (Table 4-5). Formattato: Tipo di carattere: Arial Formattato: Allineato a sinistra Efficacy Results PRIMARY EFFICACY The end-of-treatment comparison compared the Experimental Film group at Week 4 relative to the Colgate Simply White group at Week 3. At the end-of-treatment visit, the Experimental Film group provided more than 7.9 times greater reduction in yellowness (Δb*) when compared to the 124 Eliminato: 89¶ Colgate Simply White group with estimated means and standard errors of –0.782 ± 0.137 and – 0.098 ± 0.131, respectively. The treatment comparison for Δb* was statistically significant (pvalue = 0.0009 from Table 16). Formattato: Tipo di carattere: Arial SECONDARY EFFICACY At Week 2 visit, the Experimental Film group provided more than 3.0 times greater reduction in Formattato: Tipo di carattere: Arial, 11 pt yellowness (Δb*) when compared to the Colgate Simply White group with estimated means and standard errors of –0.691 ± 0.124 and –0.230 ± 0.116, respectively. The treatment comparison for Δb* was statistically significant (p-value = 0.0109 from Table 11). Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial TERTIARY EFFICACY At the end-of-study visit (Week 4), the Experimental Film group provided more than 4.4 times Formattato: Tipo di carattere: Arial, 11 pt greater reduction in yellowness (Δb*) when compared to the Colgate Simply White group with estimated means and standard errors of –0.788 ± 0.140 and –0.177 ± 0.152, respectively. The treatment comparison for Δb* was statistically significant (p-value = 0.006 from Table 11). Formattato: Tipo di carattere: Arial For the whitening benefit measured by mean change in b* (yellowness) from Baseline, the Formattato: Tipo di carattere: Arial, 11 pt Experimental Film group was effective at each post-baseline visit (p-values ≤ 0.0003 from Table 6), while the Colgate Simply White group was only statistically significant at the Week 2 visit (pvalue = 0.0305 from Table 6). Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial ADDITIONAL EFFICACY Summary statistics were calculated for b*, L*, a*, ΔW* and ΔE* (Tables 6-10). The treatment groups were well balanced on b* (yellowness), L* (lightness), and a* (redness) at Baseline. Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial, 11 pt Figure 1 displays the adjusted means of Δb* for each treatment group at each visit. Figure 2 displays the adjusted means of ΔL* for each treatment group at each visit. Eliminato: 89¶ 125 Formattato: Tipo di carattere: Arial Formattato: Tutto maiuscole END-OF-TREATMENT (Experimental Film at Week 4 versus Colgate Simply White at Week 3) At the end-of-treatment visit, the Experimental Film group provided more than 7.3 times greater Formattato: Tipo di carattere: Arial, 11 pt improvement in lightness (ΔL*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.061± 0.124 and 0.145 ± 0.118, respectively. The treatment comparison for ΔL* was statistically significant (p-value < 0.0001 from Table 16). The Experimental Film group provided more than 39 times greater improvement in redness (Δa*) when compared to the Colgate Simply White group with estimated means and standard errors of –0.394 ± 0.073 and –0.010 ± 0.070, respectively. The treatment comparison for Δa* was statistically significant (p-value = 0.0005 from Table 16). The Experimental Film group provided more than 8 times greater improvement in composite whiteness (ΔW*) when compared to the Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt Colgate Simply White group with estimated means and standard errors of –1.377 ± 0.149 and –0.172 ± 0.142, respectively. The treatment comparison for ΔW* was statistically significant (pvalue < 0.0001 from Table 16). The Experimental Film group provided more than 2.3 times greater overall color change (ΔE*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.526 ± 0.137 and 0.670 ± 0.131, respectively. The treatment comparison for ΔE* was statistically significant (p-value < 0.0001 from Table 16). Formattato: Tipo di carattere: Arial ADDITIONAL TREATMENT COMPARISONS Formattato: Tipo di carattere: Arial, Tutto maiuscole (Experimental Film at Week 2 versus Colgate Simply White at Week 3) Formattato: Tipo di carattere: Arial The Experimental Film group at Week 2 provided more than 6.3 times greater reduction in Formattato: Tipo di carattere: Arial, 11 pt yellowness (Δb*) when compared to the Colgate Simply White group at Week 3 with estimated means and standard errors of –0.691 ± 0.122 and –0.108 ± 0.114, respectively. The treatment comparison for Δb* was statistically significant (p-value = 0.0014 from Table 17). The Experimental Film group at Week 2 provided more than 4.5 times greater improvement in Eliminato: 89¶ 126 lightness (ΔL*) when compared to the Colgate Simply White group at Week 3 with estimated means and standard errors of 0.690 ± 0.114 and 0.152 ± 0.106, respectively. The treatment comparison for ΔL* was statistically significant (p-value = 0.0015 from Table 17). The Experimental Film group at Week 2 provided more than 29.9 times greater improvement in redness (Δa*) when compared to the Colgate Simply White group at Week 3 with estimated means and standard errors of –0.419 ± 0.067 and –0.014 ± 0.062, respectively. The treatment comparison for Δa* was statistically significant (p-value < 0.0001 from Table 17). The Experimental Film group provided more than 5.5 times greater improvement in composite whiteness (ΔW*) when compared to the Colgate Simply White group with estimated means and standard errors of –1.028 ± 0.138 and –0.185 ± 0.129, respectively. The treatment comparison Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt for ΔW* was statistically significant (p-value < 0.0001 from Table 17). The Experimental Film group provided more than 1.7 times greater overall color change (ΔE*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.183 ± 0.114 and 0.683 ± 0.106, respectively. The treatment comparison for ΔE* was statistically significant (pvalue = 0.0032 from Table 17). Formattato: Tipo di carattere: Arial Week 2 Comparisons Formattato: Tipo di carattere: 11 pt At the Week 2 visit, only Experimental Film group was effective in whitening teeth as measured Formattato: Tipo di carattere: Arial, 11 pt by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7). The Experimental Film group provided more than 13 times greater improvement in lightness (ΔL*) when compared to the Colgate Simply White group with estimated means and standard errors of 0.693 ± 0.132 and 0.053 ± 0.123, respectively. The treatment comparison for ΔL* was statistically significant (p-value = 0.0012 from Table 12). Both treatments were effective in whitening teeth as measured by mean change in a* (redness) from Baseline: the Experimental Film group had a p-value < 0.0001 and the Colgate Simply White group had a p-value equal to 0.0163 (Table 8). The Experimental Film group provided more than 3.4 times greater improvement in redness (Δa*) when compared to the Colgate Simply White group with 127 Eliminato: 89¶ estimated means and standard errors of –0.430 ± 0.062 and –0.124 ± 0.058, respectively. The treatment comparison for Δa* was statistically significant (p-value = 0.0010 from Table 13). Only the Experimental Film group was effective in whitening teeth as measured by mean change in W* (composite whiteness) from Baseline with p-value < 0.0001 (Table 9). The Experimental Film provided more than 5.3 times greater improvement in composite whiteness (ΔW*) when compared to the Colgate Simply White group with estimated means and standard errors of –1.034 ± 0.148 and –0.193 ± 0.138, respectively. The treatment comparison for ΔW* Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt was statistically significant (p-value = 0.0002 from Table 14). Both treatments were effective at increasing overall color change (ΔE*) with p-values < 0.0001 (Table 10). The Experimental Film group provided more than 1.5 times greater overall color change (ΔE*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.199 ± 0.120 and 0.773 ± 0.112, respectively. The treatment comparison for ΔE* was statistically significant (pvalue = 0.0154 from Table 15). Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial Week 3 Comparisons Formattato: Tipo di carattere: 11 pt At the Week 3 visit, the Experimental Film group provided more than 6.3 times greater reduction Formattato: Tipo di carattere: Arial, 11 pt in yellowness (Δb*) when compared to the Colgate Simply White group with estimated means and standard errors of –0.705 ± 0.129 and –0.111 ± 0.123, respectively. The treatment comparison for Δb* was statistically significant (p-value = 0.0021 from Table 11). Only the Experimental Film group was effective in whitening teeth as measured by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7). The Experimental Film group provided more than 7 times greater improvement in lightness (ΔL*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.071± 0.137 and 0.149 ± 0.131, respectively. The treatment comparison for ΔL* was statistically significant (pvalue < 0.0001 from Table 12). Only the Experimental Film group effective in whitening teeth as measured by mean change in a* (redness) from Baseline (p-value = 0.0025 from Table 8). The Experimental Film provided more than 15.7 times greater improvement in redness (Δa*) 128 Eliminato: 89¶ when compared to the Colgate Simply White group with estimated means and standard errors of –0.268 ± 0.069 and –0.017 ± 0.066, respectively. The treatment comparison for Δa* was statistically significant (p-value = 0.0126 from Table 13). Only the Experimental Film group was effective in whitening teeth as measured by mean change in W* (composite whiteness) from Baseline with p-value < 0.0001 (Table 9). The Experimental Film group provided more than 6.9 times greater improvement in composite whiteness (ΔW*) when compared to the Colgate Simply White group with estimated means and standard errors of –1.313 ± 0.159 and –0.188 ± 0.152, respectively. The treatment comparison for ΔW* was statistically significant (p-value < 0.0001 from Table 14). Both treatments were effective at increasing overall color change (ΔE*) with p-values < 0.0001 (Table 10). The Experimental Film provided more than 1.9 times greater overall color change (ΔE*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.464 ± 0.136 and 0.692 ± 0.129, respectively. The treatment comparison for ΔE* was statistically significant (p-value = 0.0002 from Table 15). End-of-Study (Week 4) Comparisons Formattato: Tipo di carattere: 11 pt At the Week 4 visit, only the Experimental Film group was effective in whitening teeth as Formattato: Tipo di carattere: Arial, 11 pt measured by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7). The Experimental Film group provided more than 4 times greater improvement in lightness (ΔL*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.065± 0.135 and 0.263 ± 0.146, respectively. The treatment comparison for ΔL* was statistically significant (p-value = 0.0003 from Table 12). Only the Experimental Film group effective in whitening teeth as measured by mean change in a* (redness) from Baseline (pvalue = 0.0003 from Table 8). The Experimental Film group provided more than 3.8 times greater improvement in redness (Δa*) when compared to the Colgate Simply White group with estimated means and standard errors of –0.397 ± 0.072 and –0.104 ± 0.078, respectively. The treatment comparison for Δa* was statistically significant (p-value = 0.0099 from Table 13). Both treatments were effective in whitening teeth as measured by mean change in W* 129 Eliminato: 89¶ (composite whiteness) from Baseline with p-values ≤ 0.0029 (Table 9). The Experimental Film group provided more than 4.2 times greater improvement in composite whiteness (ΔW*) when compared to the Colgate Simply White group with estimated means and standard errors of –1.385 ± 0.146 and –0.325 ± 0.158, respectively. The treatment comparison for ΔW* was statistically significant (p-value < 0.0001 from Table 14). Both treatments were effective at increasing overall color change (ΔE*) with p-values < 0.0001 (Table 10). The Experimental Film group provided more than 1.9 times greater overall color change (ΔE*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.534 ± 0.147 and 0.788 ± 0.160, respectively. The treatment comparison for ΔE* was statistically significant (pvalue = 0.0020 from Table 15). Formattato: Tipo di carattere: Arial, Colore carattere: Automatico, Tutto maiuscole SAFETY RESULTS For Adverse Events Through Week 4 (End-of-Study) Only the Experimental Film group had reported or observed tooth sensitivity and oral irritation. Eight subjects (36.4%) reported oral irritation and four subjects (18.2%) reported tooth Formattato: Allineato a sinistra Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: Arial, 11 pt sensitivity. Two subjects (9.1%) had both tooth sensitivity and oral irritation (Table 18.1). Overall, there were a total of 14 adverse events involving 11 different study subjects: Ten subjects in the Experimental Film group and one subject in the Colgate Simply White group (Table 19.1). By type, the most frequently reported AEs were gingivitis and hyperesthesia which accounted for 50% and 36%, respectively, of all events (Table 18). One hundred percent of all events were “mild” in severity. No subjects discontinued treatment early “for cause” – that is – due to a treatment-related adverse events (Table 3). Formattato: Tipo di carattere: Arial, 11 pt Eliminato: 89¶ 130 For Adverse Events Beginning On or Before Week 2 Formattato: Tipo di carattere: 11 pt Only the Experimental Film group had reported or observed tooth sensitivity and oral irritation. Formattato: Tipo di carattere: Arial, 11 pt Two subjects (9.1%) reported oral irritation and two subjects reported tooth sensitivity. No subjects reported both tooth sensitivity and oral irritation (Table 18.2). Overall, there were a total of 5 adverse events involving 5 different study subjects who were all in the Experimental Film group. One hundred percent of all events were “mild” in severity (Table 19.2). Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial, Nessuna sottolineatura, Tutto maiuscole CONCLUSIONS Formattato: Tipo di carattere: Arial • • The Experimental Film provided significant whitening improvement from Baseline as Formattato: Tipo di carattere: Arial, 11 pt measured by all color parameters at all post-baseline visits. Formattati: Elenchi puntati e numerati In general, the Colgate Simply White did not differ statistically from Baseline with the exception of Δb* at the Week 2 visit. • The Experimental Film provided significant whitening improvement relative to Colgate Simply White for all comparisons of interest and all color parameters. Whitening benefit for the Experimental Film group improved slightly after 2 weeks of treatment, in contrast, whitening benefit for the Colgate Simply White relapsed by Week 3 and rebounded for subjects completing the study at 1 week post-treatment (Week 4). • Both products were generally well tolerated overall. Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ 131 Formattato: Tipo di carattere: Arial Tables and Figures Formattato: Tipo di carattere: (Predefinito) Arial TABLE 1 SUBJECT DISPOSITION a,b NUMBER OF SUBJECTS ENROLLED AT EACH VISIT a b c VISIT COLGATE SIMPLY WHITE EXPERIMENTAL FILM OVERALL Baseline 25 25 50 Week 2 25 22 47 Week 3 25 22 47 Week 4 25 22 47 See Appendices 2.1 for data listing and evaluability memo for details. Randomization to treatment occurred after the Baseline visit and prior to product distribution. Fifty-one subjects were screened, however, Subject 3021 was dropped from the study at Baseline due to investigator recommendation. Fifty subjects were enrolled and randomized to treatment, and 47 subjects received product. Eliminato: 89¶ 132 TABLE 2 a SUMMARY OF EVALUABLE SUBJECT POPULATION EVALUABLE VISIT/ TREATMENT GROUP NO. SUBJ. NO. SUBJ. % SUBJ.b NON-EVALUABLE NO. SUBJ. % SUBJ.b Formattato: Tipo di carattere: (Predefinito) Arial BASELINE Colgate Simply White 25 25 100.0 0 0.0 Experimental Film 22 22 100.0 0 0.0 Overall 47 47 100.0 0 0.0 Colgate Simply White 25 23 92.0 2 8.0 Formattato: Tipo di carattere: (Predefinito) Arial Experimental Film 22 20 90.9 2 9.1 Overall 47 43 91.5 4 8.5 Formattato: Tipo di carattere: Arial Colgate Simply White 25 23 92.0 2 8.0 Formattato: Tipo di carattere: Arial Experimental Film 22 21 95.5 1 4.5 Formattato: Tipo di carattere: (Predefinito) Arial Overall 47 44 93.6 3 6.4 Formattato: Tipo di carattere: Arial WEEK 2 WEEK 3 WEEK 4 a b Colgate Simply White 25 18 72.0 7 28.0 Experimental Film 22 21 95.5 1 4.5 Overall 47 39 83.0 8 17.0 See Appendices 3.1 and 4.1 for the statistical analysis program and output, respectively. Percent of subjects evaluable or non-evaluable out of the number of subjects treated. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Eliminato: 89¶ 133 Formattato: Tipo di carattere: (Predefinito) Arial TABLE 3 LISTING OF SUBJECTS EXCLUDED FROM EVALUABLE POPULATIONa,b TREATMENT/ SUBJECT NO. COLGATE SIMPLY WHITE 3002 3015 3024 3025 3027 3032 3033 3045 3057 EXPERIMENTAL FILM 3008 3016 3022 a b c NON-EVALUABLE c VISIT(S) REASON(S) Week 3 Week 2 Week 4 Week 4 Week 4 Week 4 Week 4 Week 2+ Week 4 Missed Visit Missed Visit Lost to Follow-up Lost to Follow-up Lost to Follow-up Lost to Follow-up Lost to Follow-up Lost to Follow-up Lost to Follow-up Week 3 Week 2+ Week 2 Missed Visit Lost to Follow-up Missed Visit See Appendix 2.1 for the data listing and evaluability memo for details. Three subjects failed to present for product distribution visit: Subject 3007 voluntarily withdrew from the study, Subjects 3013 and 3041 were lost to follow-up. “+” indicates that the subject was excluded from the evaluable population at the indicated visit and all subsequent visits. Eliminato: 89¶ 134 Formattato: Tipo di carattere: (Predefinito) Arial TABLE 4 BASELINE DEMOGRAPHIC CHARACTERISTICSa,b ALL SUBJECTS TREATED BASELINE CHARACTERISTIC/ STATISTIC AGE (YEARS) Mean (SD) Minimum-Maximum COLGATE SIMPLY WHITE c (n = 25) EXPERIMENTAL FILM c (n = 22) OVERALL c (n = 47) TWOSIDED p-VALUE 36.9 (13.02) 21 - 65 32.6 (11.72) 22 - 70 34.9 (12.48) 21 - 70 0.2446 f 15 (60.0%) 10 (40.0%) 15 (68.2%) 7 (31.8%) 30 (63.8%) 17 (36.2%) 0.7617 g 1 (4.0%) 7 (28.0%) 15 (60.0%) 1 (4.0%) 1 (4.0%) 2 (9.1%) 5 (22.7%) 13 (59.1%) 1 (4.5%) 1 (4.5%) 3 (6.4%) 12 (25.5%) 28 (59.6%) 2 (4.3%) 2 (4.3%) 0.9463 g 22 (88.0%) 3 (12.0%) 20 (90.9%) 2 (9.1%) 42 (89.4%) 5 (10.6%) 1.0000 g 5 (10.6%) 42 (89.4%) g SEX Female d Male d RACE Asian d Black d Caucasian d Hispanic d Multi - racial d COFFEE/TEA/COLA e DRINKER No d Yes d NUMBER OF DRINKS PER DAY Median Minimum-Maximum a b c d e f g h 2 (8.0%) 23 (92.0%) 3 (13.6%) 19 (86.4%) Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial SMOKER No d Yes d Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial 0.6536 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial 2.0 0-8 2.0 0 - 14 2.0 0 - 14 0.7502 h See Appendices 2.1, 3.2, and 4.2 for the data listing, statistical analysis program, and output, respectively. Demographics were collected at the baseline visit. n = number of treated subjects in each treatment group and overall. Number and percent of subjects in each category. A drink consists of a cup for coffee or tea or a 12 ounce can of dark cola. Two-sided p-value for the treatment comparison from a two-sample t-test. Two-sided p-value for the treatment comparison from Fisher's Exact test. Two-sided p-value for the treatment comparison from an exact Wilcoxon rank-sum test. Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ 135 Formattato: Tipo di carattere: (Predefinito) Arial Tabella formattata TABLE 5 a DESCRIPTIVE SUMMARY BASELINE COLOR VALUES ALL SUBJECTS TREATED COLOR VALUE / TREATMENT N Colgate Simply White 25 MINIMUM MEDIAN MAXIMUM MEAN (SD) P-VALUEb Formattato: Tipo di carattere: (Predefinito) Arial b* Experimental Film 13.79 17.57 21.58 22 15.27 17.63 20.64 Colgate Simply White 25 66.94 73.68 77.43 Experimental Film 22 68.10 73.91 78.73 17.89 (2.059) 17.67 (1.598) 0.6825 Experimental Film a b 73.14 (2.932) 73.67 (2.382) 25 5.30 6.70 9.57 6.78 (0.919) 22 4.88 6.61 7.79 6.52 (0.814) 25 27.58 32.18 40.25 22 26.95 32.67 37.60 33.01 (3.417) 32.42 (2.406) See Appendices 2.1, 3.3, and 4.3 for the data listing, statistical analysis program, and output, respectively. Two-sided p-value for the treatment comparison from a two-sample t-test. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial L* a* Colgate Simply White Experimental Film W* Colgate Simply White Formattato: Tipo di carattere: Arial 0.5026 Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial 0.3052 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial 0.5017 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Eliminato: 89¶ 136 Formattato: Tipo di carattere: (Predefinito) Arial TABLE 6 a DESCRIPTIVE SUMMARY b* EVALUABLE SUBJECTS CHANGE FROM BASELINE COLOR VALUE / TREATMENT N MEAN (SD) MINI MEDIA MAXI MUM N MUM MEAN (SD) PVALU b E Formattato: Tipo di carattere: Arial WEEK 2 Colgate Simply White Experimental Film 23 20 17.69 (2.097) 17.14 (1.484) 1.21 4 1.93 5 -0.370 1.15 3 2.17 4 -0.270 1.30 3 2.07 4 -0.529 0.67 2 -0.257 (0.532) 0.030 5 Formattato: Tipo di carattere: (Predefinito) Arial 0.11 7 -0.660 (0.592) < 0.000 1 Formattato: Tipo di carattere: (Predefinito) Arial WEEK 3 Colgate Simply White Experimental Film 23 21 17.84 (2.094) 16.95 (1.466) 0.86 0 -0.135 (0.516) 0.221 1 0.77 5 -0.677 (0.682) 0.000 2 -0.260 0.68 5 -0.232 (0.587) 0.111 5 -0.771 0.72 7 -0.741 (0.765) 0.000 3 -0.636 WEEK 4 Colgate Simply White Experimental Film a b Formattato: Tipo di carattere: Arial 18 17.93 (2.006) 21 17.03 (1.422) See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively. Two-sided p-value for the mean color change from screening using the one-sample t-test. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Normale Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 137 Tabella formattata TABLE 7 DESCRIPTIVE SUMMARYa L* EVALUABLE SUBJECTS Formattato: Tipo di carattere: Arial CHANGE FROM BASELINE COLOR VALUE / TREATMENT N MEAN (SD) MINIMU MAXIMU MEDIAN M M MEAN (SD) Formattato: Tipo di carattere: Arial Pb VALUE WEEK 2 Colgate Simply White Experimental Film WEEK 3 Colgate Simply White Experimental Film WEEK 4 a b 23 20 23 21 Colgate Simply White 18 Experimental Film 21 73.14 (3.142) 74.19 (2.124) -1.242 0.058 0.864 -0.126 0.869 1.554 73.15 (3.145) 74.65 (2.430) -0.886 0.137 1.071 -0.172 1.149 3.019 73.74 (3.286) 74.49 (2.111) -1.291 0.420 1.081 0.160 0.903 2.463 0.046 (0.600) 0.702 (0.534) 0.7189 < 0.0001 Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial 0.141 (0.452) 1.079 (0.745) 0.1477 < 0.0001 Formattato: Tipo di carattere: Arial 0.264 (0.550) 1.064 (0.638) 0.0575 Formattato: Tipo di carattere: Arial < 0.0001 Formattato: Tipo di carattere: (Predefinito) Arial See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively. Two-sided p-value for the mean color change from screening using the one-sample t-test. Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 138 Formattato: Tipo di carattere: (Predefinito) Arial TABLE 8 DESCRIPTIVE SUMMARYa a* EVALUABLE SUBJECTS Tabella formattata CHANGE FROM BASELINE COLOR VALUE / TREATMENT MINIMU N MEAN (SD) M P- MAXIMU MEDIAN M MEAN (SD) b VALUE WEEK 2 Colgate White Simply Experimental Film WEEK 3 Colgate White Simply Experimental Film WEEK 4 Colgate White Simply Experimental Film a b 23 20 23 21 18 21 6.71 (0.846) 6.15 (0.786) -0.943 -0.084 0.356 -0.871 -0.472 0.125 6.82 (0.913) 6.25 (0.790) -0.715 -0.062 0.558 -0.666 -0.315 0.533 6.80 (0.926) 6.18 (0.790) -1.026 -0.094 0.287 -1.132 -0.428 0.290 -0.151 (0.279) -0.398 (0.310) 0.0163 < 0.0001 Formattato: Tipo di carattere: (Predefinito) Arial -0.031 (0.293) -0.252 (0.333) 0.6119 Formattato: Tipo di carattere: Arial 0.0025 Formattato: Tipo di carattere: (Predefinito) Arial -0.136 (0.314) -0.370 (0.382) 0.0836 Formattato: Tipo di carattere: (Predefinito) Arial 0.0003 Formattato: Tipo di carattere: Arial See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively. Two-sided p-value for the mean color change from screening using the one-sample t-test. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 139 Tabella formattata TABLE 9 a DESCRIPTIVE SUMMARY W* EVALUABLE SUBJECTS CHANGE FROM BASELINE COLOR VALUE / TREATMENT MINIMU P- MAXIMU b N MEAN (SD) M MEDIAN M MEAN (SD) VALUE 23 32.88 (3.638) 31.64 (2.060) -1.234 -0.270 0.927 0.0992 -2.280 -0.833 -0.128 -0.212 (0.591) -1.012 (0.694) 32.98 (3.637) 31.18 (2.447) -1.145 -0.227 0.744 0.0724 -3.530 -1.232 -0.026 -0.199 (0.505) -1.302 (0.879) WEEK 2 Colgate White Simply Experimental Film 20 < 0.0001 WEEK 3 Colgate White Simply Experimental Film 23 21 < 0.0001 WEEK 4 Colgate White Simply Experimental Film a b 18 21 32.54 (3.737) 31.33 (2.077) -1.471 -0.384 0.351 -2.704 -1.221 -0.090 -0.367 (0.449) -1.348 (0.825) See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively. Two-sided p-value for the mean color change from screening using the one-sample t-test. 0.0029 < 0.0001 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 140 Tabella formattata TABLE 10 a DESCRIPTIVE SUMMARY ΔE* EVALUABLE SUBJECTS CHANGE FROM BASELINE COLOR VALUE / TREATMENT N MINIMUM MEDIAN MAXIMUM MEAN (SD) b P-VALUE WEEK 2 Colgate Simply White Experimental Film 23 0.107 0.759 1.706 20 0.238 1.099 2.371 0.796 (0.392) 1.172 (0.656) < 0.0001 0.693 (0.309) 1.463 (0.809) < 0.0001 Formattato: Tipo di carattere: (Predefinito) Arial < 0.0001 Formattato: Tipo di carattere: Arial 0.827 (0.415) 1.501 (0.825) < 0.0001 Formattato: Tipo di carattere: Arial < 0.0001 Formattato: Tipo di carattere: (Predefinito) Arial < 0.0001 Experimental Film 23 0.168 0.672 1.247 21 0.342 1.353 3.534 Experimental Film a b 18 0.358 0.688 2.102 21 0.271 1.272 2.815 See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively. Two-sided p-value for the mean color change from screening using the one-sample t-test. Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial WEEK 4 Colgate Simply White Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 3 Colgate Simply White Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 141 Formattato: Tipo di carattere: (Predefinito) Arial TABLE 11 TREATMENT COMPARISONS a ANALYSIS OF COVARIANCE MEAN b* ADJUSTED FOR BASELINE AND AGE EVALUABLE SUBJECTS TREATMENT COMPARISON VISIT/ TREATMENT GROUP N BASELINE MEAN (SE) ADJUSTED MEAN CHANGE FROM b BASELINE (SE) TREATMENT DIFFERENCE (SE) p-VALUEc WEEK 2 Colgate Simply White 23 17.948 (0.446) -0.230 (0.116) Experimental Film 20 17.805 (0.356) -0.691 (0.124) Colgate Simply White 23 17.974 (0.443) -0.111 (0.123) Experimental Film 21 17.629 (0.355) -0.705 (0.129) 0.462 (0.173) 0.0109 0.594 (0.180) 0.0021 c Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 4 b Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 3 a Formattato: Tipo di carattere: (Predefinito) Arial Colgate Simply White 18 18.161 (0.489) -0.177 (0.152) Experimental Film 21 17.775 (0.340) -0.788 (0.140) 0.610 (0.209) See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively. 0.0060 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Means adjusted for baseline b* value and age. Two-sided p-value for the treatment comparison of the difference in mean change of Δb*. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 142 Formattato: Tipo di carattere: (Predefinito) Arial TABLE 12 TREATMENT COMPARISONS a ANALYSIS OF COVARIANCE MEAN L* ADJUSTED FOR BASELINE AND AGE EVALUABLE SUBJECTS TREATMENT COMPARISON VISIT/ TREATMENT GROUP N BASELINE MEAN (SE) ADJUSTED MEAN CHANGE FROM b BASELINE (SE) TREATMENT DIFFERENCE (SE) p-VALUEc WEEK 2 Colgate Simply White 23 73.092 (0.638) 0.053 (0.123) Experimental Film 20 73.490 (0.489) 0.693 (0.132) Colgate Simply White 23 73.004 (0.627) 0.149 (0.131) Experimental Film 21 73.566 (0.522) 1.071 (0.137) -0.640 (0.183) 0.0012 -0.922 (0.192) < 0.0001 c Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 4 b Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 3 a Formattato: Tipo di carattere: (Predefinito) Arial Colgate Simply White 18 73.473 (0.711) 0.263 (0.146) Experimental Film 21 73.428 (0.469) 1.065 (0.135) -0.802 (0.201) See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively. 0.0003 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Means adjusted for baseline L* value and age. Two-sided p-value for the treatment comparison of the difference in mean change of ΔL*. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 143 TABLE 13 TREATMENT COMPARISONS a ANALYSIS OF COVARIANCE MEAN a* ADJUSTED FOR BASELINE AND AGE EVALUABLE SUBJECTS TREATMENT COMPARISON VISIT/ TREATMENT GROUP N BASELINE MEAN (SE) ADJUSTED MEAN CHANGE FROM b BASELINE (SE) TREATMENT DIFFERENCE (SE) p-VALUE WEEK 2 Colgate Simply White 23 6.865 (0.189) -0.124 (0.058) Experimental Film 20 6.552 (0.188) -0.430 (0.062) Colgate Simply White 23 6.847 (0.192) -0.017 (0.066) Experimental Film 21 6.506 (0.181) -0.268 (0.069) 0.307 (0.086) 0.0010 0.251 (0.096) 0.0126 c Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 4 b Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial WEEK 3 a c Colgate Simply White 18 6.940 (0.223) -0.104 (0.078) Experimental Film 21 6.553 (0.179) -0.397 (0.072) 0.293 (0.108) See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively. 0.0099 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Means adjusted for baseline a* value and age. Two-sided p-value for the treatment comparison of the difference in mean change of Δa*. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 144 TABLE 14 TREATMENT COMPARISONS a ANALYSIS OF COVARIANCE MEAN W* ADJUSTED FOR BASELINE AND AGE EVALUABLE SUBJECTS TREATMENT COMPARISON VISIT/ TREATMENT GROUP N BASELINE MEAN (SE) ADJUSTED MEAN CHANGE FROM b BASELINE (SE) TREATMENT DIFFERENCE (SE) p-VALUE c WEEK 2 Colgate Simply White 23 33.096 (0.741) -0.193 (0.138) Experimental Film 20 32.647 (0.486) -1.034 (0.148) Colgate Simply White 23 33.178 (0.730) -0.188 (0.152) Experimental Film 21 32.477 (0.535) -1.313 (0.159) 0.841 (0.205) 0.0002 1.125 (0.222) < 0.0001 c Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 4 b Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 3 a Formattato: Tipo di carattere: (Predefinito) Arial Colgate Simply White 18 32.910 (0.842) -0.325 (0.158) Experimental Film 21 32.681 (0.463) -1.385 (0.146) 1.060 (0.217) See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively. < 0.0001 Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Means adjusted for baseline W* value and age. Two-sided p-value for the treatment comparison of the difference in mean change of ΔW*. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 145 TABLE 15 TREATMENT COMPARISONS a ANALYSIS OF COVARIANCE MEAN ΔE* ADJUSTED FOR BASELINE AND AGE EVALUABLE SUBJECTS TREATMENT COMPARISON VISIT/ TREATMENT GROUP MEAN CHANGE FROM BASELINE N (SE) TREATMENT DIFFERENCE (SE) p-VALUEb Formattato: Tipo di carattere: (Predefinito) Arial WEEK 2 Colgate Simply White 23 0.773 (0.112) Experimental Film 20 1.199 (0.120) Colgate Simply White 23 0.692 (0.129) Experimental Film 21 1.464 (0.136) -0.426 (0.168) 0.0154 Formattato: Tipo di carattere: Arial WEEK 3 -0.772 (0.190) 0.0002 b c Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial WEEK 4 a Formattato: Tipo di carattere: Arial Colgate Simply White 18 0.788 (0.160) Experimental Film 21 1.534 (0.147) -0.746 (0.222) 0.0020 See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively. Means adjusted for baseline b*, L*, and a* values as well as age. Two-sided p-value for the treatment comparison of the difference in mean change of ΔE * . Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 146 Formattato: Distanza piè di pagina dal bordo: 57,6 pt TABLE 16 END-OF-TREATMENT COMPARISONS – ANALYSIS OF COVARIANCE a EXPERIMENTAL FILM AT WEEK 4 VS COLGATE SIMPLY WHITE AT WEEK 3 ADJUSTED FOR BASELINE AND AGE EVALUABLE SUBJECTS TREATMENT COMPARISON ADJUSTED MEAN TREATMENT CHANGE FROM DIFFERENCE VISIT/ BASELINE BASELINE (SE)b p-VALUEc TREATMENT GROUP MEAN (SE) (SE) N Δb* Colgate Simply White 23 17.974 (0.443) -0.098 (0.131) Experimental Film 21 17.775 (0.340) -0.782 (0.137) 0.684 (0.191) 0.0009 23 73.004 (0.627) 0.145 (0.118) Experimental Film 21 73.428 (0.469) 1.061 (0.124) Colgate Simply White 23 6.847 (0.192) -0.010 (0.070) Experimental Film 21 6.553 (0.179) -0.394 (0.073) -0.916 (0.173) < 0.0001 0.384 (0.102) 0.0005 ΔW* 23 33.178 (0.730) -0.172 (0.142) Experimental Film 21 32.681 (0.463) -1.377 (0.149) 1.205 (0.208) < 0.0001 ΔE* a b c Colgate Simply White 23 0.670 (0.131) Experimental Film 21 1.526 (0.137) Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Δa* Colgate Simply White Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial ΔL* Colgate Simply White Formattato: Tipo di carattere: (Predefinito) Arial -0.855 (0.193) See Appendices 2.1, 3.6, and 4.6 for the data listing, statistical analysis program, and output, respectively. Means adjusted for baseline color and age. Two-sided p-value for the treatment comparison of the difference in mean color change from baseline. < 0.0001 Formattato ... [125] Formattato ... [126] Formattato ... [127] Formattato ... [128] Formattato ... [129] Formattato ... [130] Formattato ... [131] Formattato ... [132] Formattato ... [133] Formattato ... [134] Formattato ... [135] Formattato ... [136] Formattato ... [137] Formattato ... [138] Formattato ... [139] Formattato ... [140] Formattato ... [141] Formattato ... [142] Formattato ... [143] Formattato ... [144] Formattato ... [145] Formattato ... [146] Formattato: Centrato 147 Formattato: Tipo di carattere: (Predefinito) Arial TABLE 17 ADDITIONAL TREATMENT COMPARISONS – ANALYSIS OF COVARIANCE a EXPERIMENTAL FILM AT WEEK 2 VS COLGATE SIMPLY WHITE AT WEEK 3 ADJUSTED FOR BASELINE AND AGE EVALUABLE SUBJECTS TREATMENT COMPARISON ADJUSTED MEAN TREATMENT CHANGE FROM DIFFERENCE VISIT/ BASELINE BASELINE (SE)b p-VALUEc TREATMENT GROUP MEAN (SE) (SE) N Δb* Colgate Simply White 23 17.974 (0.443) -0.108 (0.114) Experimental Film 20 17.805 (0.356) -0.691 (0.122) 0.583 (0.170) 0.0014 Colgate Simply White 23 73.004 (0.627) 0.152 (0.106) Experimental Film 20 73.490 (0.489) 0.690 (0.114) Colgate Simply White 23 6.847 (0.192) -0.014 (0.062) Experimental Film 20 6.552 (0.188) -0.419 (0.067) -0.538 (0.157) 0.0015 Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Colgate Simply White 23 33.178 (0.730) -0.185 (0.129) Experimental Film 20 32.647 (0.486) -1.028 (0.138) 0.405 (0.093) < 0.0001 23 0.683 (0.106) Experimental Film 20 1.183 (0.114) Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial 0.843 (0.192) < 0.0001 ΔE* Colgate Simply White Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial ΔW* c Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Δa* b Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial ΔL* a Formattato: Tipo di carattere: (Predefinito) Arial -0.501 (0.159) See Appendices 2.1, 3.7, and 4.7 for the data listing, statistical analysis program, and output, respectively. Means adjusted for baseline color and age. Two-sided p-value for the treatment comparison of the difference in mean color change from baseline. 0.0032 Formattato ... [147] Formattato ... [148] Formattato ... [149] Formattato ... [150] Formattato ... [151] Formattato ... [152] Formattato ... [153] Formattato ... [154] Formattato ... [155] Formattato ... [156] Formattato ... [157] Formattato ... [158] Formattato ... [159] Formattato ... [160] Formattato ... [161] Formattato ... [162] Formattato ... [163] Formattato ... [164] Formattato ... [165] Formattato: Centrato 148 TABLE 18.1 POSSIBLE OR PROBABLE TREATMENT RELATED (BY WEEK 4) a ORAL IRRITATION OR TOOTH SENSITIVITY ALL SUBJECTS TREATED COLGATE SIMPLY EXPERIMENTAL WHITE FILM b b (n = 25) (n = 22) AE SOURCE/AE CLASSIFICATION Formattato: Superiore: 108 pt, In basso: 108 pt, Larghezza 612 pt, Altezza: 792 pt, Distanza piè di pagina dal bordo: 57,6 pt Formattato: Tipo di carattere: (Predefinito) Arial Tabella formattata OVERALL (n = 47)b NO. SUBJ. (% SUBJ.)c NO. SUBJ. (% SUBJ.)c NO. SUBJ. (% SUBJ.)c Oral Irritation 0 (0) 8 (36.4) 8 (17.0) Formattato: Tipo di carattere: Arial Tooth Sensitivity 0 (0) 4 (18.2) 4 (8.5) Formattato: Tipo di carattere: Arial 0 (0) 2 (9.1) 2 (4.3) Formattato: Tipo di carattere: Arial 0 (0) 10 (45.5) 10 (21.3) Formattato: Tipo di carattere: Arial SELF REPORTED Oral Irritation and Tooth Sensitivity Oral Irritation or Tooth Sensitivity Formattato: Tipo di carattere: Arial OBSERVED Oral Irritation EITHER OBSERVED SELF REPORTED 0 (0) b c 1 (2.1) OR Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Oral irritation 0 (0) 8 (36.4) 8 (17.0) Tooth Sensitivity 0 (0) 4 (18.2) 4 (8.5) 0 (0) 2 (9.1) 2 (4.3) Formattato: Tipo di carattere: Arial 0 (0) 10 (45.5) 10 (21.3) Formattato: Tipo di carattere: Arial Oral irritation and Tooth Sensitivity Oral irritation or Tooth Sensitivity a 1 (4.5) See Appendices 2.1, 3.8, and 4.8 for the data listing, statistical analysis program, and output, respectively. Formattato: Tipo di carattere: Arial Tabella formattata Number of subjects randomized in each group and overall. Number (Percent) of randomized subjects with the indicated AE (out of the number reported in each group). Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 149 Tabella formattata Formattato: Tipo di carattere: Arial TABLE 18.2 POSSIBLE OR PROBABLE TREATMENT RELATED (BY WEEK 2) a ORAL IRRITATION OR TOOTH SENSITIVITY ALL SUBJECTS TREATED AE SOURCE/AE CLASSIFICATION Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial COLGATE SIMPLY WHITE (n = 25)b EXPERIMENTAL FILM (n = 22)b OVERALL b (n = 47) NO. SUBJ. (% SUBJ.)c NO. SUBJ. (% c SUBJ.) NO. SUBJ. (% c SUBJ.) SELF REPORTED Formattato: Tipo di carattere: Arial 2 (9.1) 2 (4.3) Formattato: Tipo di carattere: (Predefinito) Arial Tooth Sensitivity 0 (0) 2 (9.1) 2 (4.3) Formattato: Tipo di carattere: Arial 0 (0) 0 (0) 0 (0) Formattato: Tipo di carattere: Arial 0 (0) 4 (18.2) 4 (8.5) EITHER OBSERVED REPORTED 0 (0) OR Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Oral Irritation 1 (4.5) 1 (2.1) Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial SELF Oral irritation 0 (0) 2 (9.1) 2 (4.3) Formattato: Tipo di carattere: (Predefinito) Arial Tooth Sensitivity 0 (0) 2 (9.1) 2 (4.3) Formattato: Tipo di carattere: Arial 0 (0) 0 (0) 0 (0) Formattato: Tipo di carattere: (Predefinito) Arial 0 (0) 4 (18.2) 4 (8.5) Formattato: Tipo di carattere: (Predefinito) Arial Oral irritation and Tooth Sensitivity Oral irritation or Tooth Sensitivity c Formattato: Tipo di carattere: (Predefinito) Arial 0 (0) OBSERVED b Formattato: Tipo di carattere: Arial Oral Irritation Oral Irritation and Tooth Sensitivity Oral Irritation or Tooth Sensitivity a Formattato: Tipo di carattere: (Predefinito) Arial See Appendices 2.1, 3.9, and 4.9 for the data listing, statistical analysis program, and output, respectively. Formattato: Tipo di carattere: Arial Number of subjects randomized in each group and overall. Formattato: Tipo di carattere: (Predefinito) Arial Number (Percent) of randomized subjects with the indicated AE (out of the number reported in each group). Formattato ... [166] Formattato ... [167] Formattato ... [168] Formattato: Centrato 150 Tabella formattata TABLE 19.1 a SUMMARY OF ADVERSE EVENTS (BY WEEK 4) ALL SUBJECTS TREATED COLGATE SIMPLY WHITE b (n = 25) NO. AES (% AES)d NO. SUBJ. (% c SUBJ.) NO. AES (% AES)d Serious AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Formattato: Tipo di carattere: Arial Mild AEs 1(4) 1(100) 10(45) 13(100) 11(23) 14(100) Formattato: Tipo di carattere: Arial Moderate AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Severe AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Formattato: Tipo di carattere: Arial Not Related 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Doubtful Related 1(4) 1(100) 1(5) 1(8) 2(4) 2(14) Formattato: Tipo di carattere: Arial Possibly Related 0(0) 0(0) 7(32) 8(62) 7(15) 8(57) Formattato: Tipo di carattere: Arial Probably Related 0(0) 0(0) 4(18) 4(31) 4(9) 4(29) Formattato: Tipo di carattere: Arial 1(4) 1(100) 10(45) 13(100) 11(23) 14(100) Formattato: Tipo di carattere: Arial Mean number of AEs per subject (all subjects) Mean number of AEs per subject (only subjects with AEs) b c d OVERALL (n = 47)b NO. SUBJ. (% c SUBJ.) Total a EXPERIMENTAL FILM (n = 22)b NO. SUBJ. NO. AES d (% (% AES) c SUBJ.) 0.04 0.59 0.3 1 1.3 1.27 See Appendices 2.1, 3.10, and 4.10 for the data listing, statistical analysis program, and output, respectively. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial n = number of subjects within the specified treatment group or overall. Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group). Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group). Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 151 Tabella formattata Formattato: Tipo di carattere: Arial TABLE 19.2 a SUMMARY OF ADVERSE EVENTS (BY WEEK 2) ALL SUBJECTS TREATED COLGATE SIMPLY WHITE b (n = 25) c d OVERALL (n = 47)b Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Tipo di NO. AEFormattato: S carattere: (Predefinito) Arial d (% AES) NO. AES (% AES)d NO. SUBJ. (% c SUBJ.) NO. AES (% AES)d NO. SUBJ. (% SUBJ.)c Serious AEs 0(0) 0(0) 0(0) 0(0) 0(0) Mild AEs 0(0) 0(0) 5(23) 5(100) 5(11) Moderate AEs 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Severe AEs Formattato: Tipo di carattere: (Predefinito) Arial 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Not Related 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Formattato: Tipo di carattere: Arial Doubtful Related 0(0) 0(0) 1(5) 1(20) 1(2) 1(20) Possibly Related 0(0) 0(0) 0(0) 0(0) 0(0) 0(0) Probably Related 0(0) 0(0) 4(18) 4(80) 4(9) 4(80) carattere: (Predefinito) Arial 0(0) 0(0) 5(23) 5(100) 5(11) Mean number of AEs per subject (all subjects) Mean number of AEs per subject (only subjects with AEs) b EXPERIMENTAL FILM (n = 22)b NO. SUBJ. (% SUBJ.)c Total a Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial 0(0) Formattato: Tipo di 5(100)carattere: Arial 0.11 0 1 1 Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group). Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group). Formattato: Tipo di carattere: Arial Tipo di 5(100)Formattato: carattere: Arial 0.23 See Appendices 2.1, 3.11, and 4.11 for the data listing, statistical analysis program, and output, respectively. Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di 0 n = number of subjects within the specified treatment group or overall. Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: (Predefinito) Arial Formattato ... [169] Formattato ... [170] Formattato ... [171] Formattato: Centrato 152 TABLE 20 ADVERSE EVENTS IN DECREASING ORDER OF INCIDENCE a BY COSTART PREFERRED TERM AND TREATMENT GROUP ALL SUBJECTS TREATED COSTART PREFERRED TERM COLGATE SIMPLY WHITE b (n = 25) EXPERIMENTAL FILM b (n = 22) NO. SUBJ. (% SUBJ.)c NO. AES (% AES)d GINGIVITIS 1(4) 1(100) 6(27) HYPERESTHESIA 0(0) 0(0) CHEILITIS 0(0) STOMATITIS TOTAL a b c d NO. SUBJ. NO. AES (% SUBJ.)c (% AES)d OVERALL b (n = 47) NO. SUBJ. (% SUBJ.)c NO. AES (% AES)d 6(46) 7(15) 7(50) Formattato: Tipo di carattere: Arial 5(23) 5(38) 5(11) 5(36) Formattato: Tipo di carattere: Arial 0(0) 1(5) 1(8) 1(2) 1(7) 0(0) 0(0) 1(5) 1(8) 1(2) 1(7) 1(4) 1(100) 10(45) 13(100) 11(23) 14(100) See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively. n = number of subjects within the specified treatment group or overall. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group). Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group). Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 153 TABLE 21 MILD ADVERSE EVENTS a BY COSTART PREFERRED TERM AND TREATMENT GROUP ALL SUBJECTS TREATED COSTART PREFERRED TERM COLGATE SIMPLY WHITE b (n = 25) EXPERIMENTAL FILM b (n = 22) NO. SUBJ. (% SUBJ.)c NO. AES (% AES)d GINGIVITIS 1(4) 1(100) 6(27) HYPERESTHESIA 0(0) 0(0) CHEILITIS 0(0) STOMATITIS TOTAL a b c d NO. SUBJ. NO. AES (% SUBJ.)c (% AES)d OVERALL b (n = 47) NO. SUBJ. (% c SUBJ.) NO. AES (% AES)d 6(46) 7(15) 7(50) Formattato: Tipo di carattere: Arial 5(23) 5(38) 5(11) 5(36) Formattato: Tipo di carattere: Arial 0(0) 1(5) 1(8) 1(2) 1(7) 0(0) 0(0) 1(5) 1(8) 1(2) 1(7) 1(4) 1(100) 10(45) 13(100) 11(23) 14(100) See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively. n = number of subjects within the specified treatment group or overall . Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group). Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group). Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 154 TABLE 22 NOT OR DOUBTFUL TREATMENT RELATED ADVERSE EVENTS a BY COSTART PREFERRED TERM AND TREATMENT GROUP ALL EVALUABLE SUBJECTS COSTART PREFERRED TERM COLGATE SIMPLY WHITE (n = 25)b EXPERIMENTAL FILM b (n = 22) NO. SUBJ. c (% SUBJ.) NO. AES d (% AES) GINGIVITIS 1(4) 1(100) 0(0) HYPERESTHESIA 0(0) 0(0) TOTAL 1(4) 1(100) a b c d NO. SUBJ. NO. AES c d (% SUBJ.) (% AES) OVERALL b (n = 47) NO. SUBJ. c (% SUBJ.) NO. AES d (% AES) 0(0) 1(2) 1(7) Formattato: Tipo di carattere: Arial 1(5) 1(8) 1(2) 1(7) Formattato: Tipo di carattere: Arial 1(5) 1(8) 2(4) 2(14) See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial n = number of subjects within the specified treatment group or overall. Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group). Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group). Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Normale Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 155 TABLE 23 POSSIBLE OR PROBABLE TREATMENT RELATED ADVERSE EVENTS a BY COSTART PREFERRED TERM AND TREATMENT GROUP ALL SUBJECTS TREATED COSTART PREFERRED TERM COLGATE SIMPLY WHITE b (n = 25) EXPERIMENTAL FILM b (n = 22) NO. SUBJ. (% SUBJ.)c NO. AES (% AES)d GINGIVITIS 0(0) 0(0) 6(27) HYPERESTHESIA 0(0) 0(0) CHEILITIS 0(0) STOMATITIS TOTAL a b c d NO. SUBJ. NO. AES (% SUBJ.)c (% AES)d OVERALL b (n = 47) NO. SUBJ. (% SUBJ.)c NO. AES (% AES)d 6(46) 6(13) 6(43) Formattato: Tipo di carattere: Arial 4(18) 4(31) 4(9) 4(29) Formattato: Tipo di carattere: Arial 0(0) 1(5) 1(8) 1(2) 1(7) 0(0) 0(0) 1(5) 1(8) 1(2) 1(7) 0(0) 0(0) 10(45) 12(92) 10(21) 12(86) See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively. n = number of subjects within the specified treatment group or overall. Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group). Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group). Formattato: Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Formattato: Centrato 156 Figure 1: Adjusted Mean Yellowness Improvement (–Δb*) 1 0.8 0.6 0.4 0.2 0 Week 2 Week 3 C olgate Sim ply White Week 4 Experim ental Film Figure 2: Adjusted Mean Lightness Improvement (ΔL*) 1.2 1 0.8 0.6 0.4 0.2 0 Week 2 Week 3 C olgate Sim ply White Week 4 Experim ental Film Formattato: Centrato Eliminato: 214¶ 156 Formattato: Tutto maiuscole REFERENCES 1. HaywoodVB, Heymann HO. Nightguard vital bleaching. Quintessence Int. 1989; 20:173-6 2. Goldstein RE.In-office bleaching: where we came from, where we are today. Jam Dent Assoc1997;128:11S-15S 3. BurrellKH.ADA supports vital tooth bleaching –but look for the seal. J Am Dent Assoc1997 128:3S-5S. 4. CrollTP, SasaIS.Carbemide peroxide of teeth with dentiogenisis imperfecta discoloration: report of a case. Quintessence Int. 1995; 26:683-6 5. Haywood VB. Night guard bleaching to lighten a restored, nonvital discolored tooth. Compend Continuing Education Dent 1998;19:810-3 6. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth. Compend Contin Educ Dent 1998; 19:810-3 7. Small BW. The application and integration of at-home bleaching into private dental practice. Compend Contin Educ Dent 1998;19:799-806 8. HaywoodVB, Robinson FG.Vital tooth bleaching with nightgaurd vital bleaching. Curr.Opin CosmeticDent1997;4:45-52 9. KugelG,PerryRD, Hoang E,Scherer W.Effective tooth bleaching in 5days: using a combined in office and at home bleaching system . Comp contin Educ Dent 1997 ;18:378-83 10. Kugel G Over the counter tooth whitening Systems Compendium April 2003; 24;4A 376-82 11. Donly KJ, DonlyAS, BaharlooL, et al. Tooth whitening in children, Compend Contin Edu Dent. 2002; 3:22-27. Formattato: Centrato Eliminato: 214¶ 157 Chapter 9 Maintenance of Whitening Clinical Study to Evaluate the Maintenance of Whitening after Bleaching Treatment Abstract Formattato: Interlinea doppia A randomized, parallel, examiner-blind clinical study was conducted to examine the ability of 2 toothbrushes to maintain teeth whitening after at-home bleaching. Forty subjects used a 15% carbamide peroxide tray bleaching system at home for 2 weeks per the manufacturer’s instructions and then were randomly assigned to use either the Sonicare® Advance power toothbrush or a manual toothbrush as part of their home oral hygiene routine for 6 months. The color of the labial surfaces of the subjects’ maxillary anterior dentition was assessed before bleaching and immediately, 2 months, 3 months, and 6 months after bleaching. Color was assessed by comparison with Vita® Classical shade tabs and by digital image analysis in the CIE L*a*b* color space. Both groups demonstrated a rebound effect at the 2-month visit and beyond, with mean Vita shade scores significantly higher than immediately after bleaching. At the 6-month evaluation, there was a significant difference in the amount of rebound in each group. Specifically, the rebound of the Sonicare brush group was on average 1.12 Vita shades less than that of the manual brush group. The 6-month difference was confirmed through digital image analysis, with the Sonicare brush group 4.8 L* units lighter, corresponding to 2 Vita shades, and 2.1 b* units less yellow than the manual brush group. This clinical trial demonstrates that the Sonicare Advance toothbrush better maintains whitening after bleaching treatment than a manual toothbrush. Formattato: Centrato Eliminato: 214¶ 158 Learning Objectives Formattato: Normale After reading this article, the reader should be able to: • Understand maintenance of whitening after bleaching using an electric toothbrush. • To demonstrate that significant rebound can occur post bleaching. • To demonstrate the use of digital photography in determining L* a* b* values Formattato: Interlinea doppia Formattato: Puntato + Livello:1 + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra di: 36 pt Formattato: Interlinea doppia The use of peroxide to whiten teeth has a lengthy history dating to the early 20th century. With the advent of patient-applied kits, bleaching has become both common and popular, and use of peroxide is now generally recognized as a safe and effective method for tooth whitening.1-3 There are a variety of indications for bleaching single or multiple teeth, including staining from chromogenic foods, dental fluorosis, tetracycline staining, and devital discolored teeth.4-7 Up to 90% of U.S. dental practices offer vital tooth bleaching, and in some dental practices, up to one-fifth of patients undergo bleaching.8-9 Concentrations of up to 35% peroxide are used alone or in combination with various agents for tooth bleaching. Delivery is via in-office, at-home, or combination regimens, with or without professional supervision.10,11 Of these, bleaching is most commonly accomplished at home over a period of a few weeks.12 Treatment duration may vary based on the degree of staining because whitening is reported to be a product of peroxide concentration and contact time.13 For some difficult stains like tetracycline, daily bleaching for up to 6 months may be indicated.14 Formattato: Interlinea doppia Treatment is generally effective, with 90% or more of clinical trial subjects experiencing initial whitening.15,16 The efficacy of a bleaching treatment may be established through first or second person observation or various technical methods. Clinical trials most commonly include the use of a shade guide, colorimeter, or computer digitization to measure color change over time.17,18 In these studies, efficacy is commonly monitored for 6 months.13,16 While there may be some shade deterioration over time, most patients experience a whitening effect that may persist, to at least 159 Formattato: Centrato Eliminato: 214¶ some degree, 3 years or more after initial treatment.13,15 In addition to the cosmetic benefits, bleaching is believed to contribute to various intangibles, including heightened patient involvement and increased interest in dentistry and oral health.7,8 Some patients who have undergone bleaching are concerned with the stability of their newly bleached teeth. Practitioners often have no real answer for the patient concerning the stability of bleached dentition. Rebound, the re-coloring of bleached teeth, is assumed to be a multifactor process. The factors may include the structure and composition of an individual’s dentin and enamel, the types of food and drink he or she consumes, and the oral hygiene routine. In the current study, we examined the impact of the oral hygiene routine. Specifically, we assessed the ability of the Sonicare® Advance powered toothbrusha to prevent rebound compared with a standard manual toothbrush. Formattato: Interlinea doppia The Sonicare Advance toothbrush operates with high-frequency bristle movement (260 Hz; 31,000 brush strokes per minute). In addition to cleaning by direct bristle contact, the Sonicare Advance generates significant fluid activity, which has been hypothesized as the reason for the brush’s ability to clean beyond the reach of the bristles as demonstrated in several laboratory studies.19-22 The Sonicare Advance also has been shown to remove stains in clinical and laboratory studies, removing more stain in vivo than a manual toothbrush.23, 24 A study of the brush’s ability to inhibit rebound after bleaching, a natural extension of this earlier work, was the focus of the current study. Formattato: Allineato a sinistra, Interlinea doppia, Non mantenere con successivo Methods and Materials Formattato: Interlinea doppia Population Selection Potential subjects were screened and enrolled in this clinical trial at Tufts University, Boston, Massachusetts, after meeting the inclusion/exclusion criteria. At screening, written informed consent was obtained from each subject after review of the study design and test regimen. Using the Vita® Classical shade guideb, Vita shade scores were recorded for each subject on labial Formattato: Centrato Eliminato: 214¶ 160 surfaces of the maxillary anterior teeth. Subjects with individual tooth scores of A2 or darker were eligible for enrollment. Dentinal sensitivity, use of tobacco products, the presence of tetracycline stain, dental fluorosis, atypical nonuniform stain, fixed orthodontic appliances, and large intake of stain-inducing beverages were all reasons for exclusion. Subjects who qualified and agreed to participate were enrolled in the study. At the postbleaching evaluation, subjects exhibiting a decrease of at least 2 Vita shades were allowed to continue in the study; all subjects met this requirement. Formattato: Tutto maiuscole STUDY DESIGN This was an examiner blind, parallel-group, 6-month study with clinical evaluations both before (prebleaching baseline) and after (postbleaching baseline) a two-week bleaching treatment and at one, 2, 3, and 6 months after the end of bleaching. At each visit, oral soft and hard tissues were examined, subjects were questioned about presence or absence of tooth hypersensitivity to thermal, air, or other such stimuli, and a Vita shade assessment of the labial surfaces of the anterior maxillary teeth was recorded. A subset of 14 subjects, 7 per treatment group, was randomly selected for digital image analysis. For subjects in this subset, digital images of the maxillary anterior teeth also were captured at each visit. At the screening appointment, impressions of the maxillary teeth were taken and used to fabricate the bleaching trays. The trays were distributed at the first study visit, baseline prebleaching, along with a standard home bleaching system of 15% carbamide peroxide (Opalescencec). All subjects were given a standard manual toothbrush (Crest® Extra Softd) and sodium fluoride dentifrice (Crest Cavity Protectiond) for use during the bleaching period. Subjects received oral and written instructions on the bleaching system’s recommended use and the Bass brushing technique.25 Subjects were asked to use the bleaching trays twice per day for 60 minutes at each use and to brush with the manual toothbrush twice per day for 2 minutes at each brushing. At the postbleaching baseline appointment 2 weeks later, bleaching trays were collected and study Formattato: Centrato Eliminato: 214¶ 161 toothbrushes were distributed according to a stratified randomization designed to foster similar shade distributions at prebleaching baseline (low / medium / high Vita shade score means) in each brush group. Subjects exhibiting a mean Vita shade score improvement of at least 2.0 were permitted to continue in the study. Subjects in one group were asked to continue using the manual toothbrush as previously instructed. Subjects in the other group were given a Sonicare Advance toothbrush, instructed in its use according to the manufacturer’s instructions, and asked to use the toothbrush with the same study dentifrice twice daily for 2 minutes at each brushing. Formattato: Tutto maiuscole Formattato: Interlinea doppia EFFICACY ASSESSMENTS Vita Shade Guide Assessment Assessments of tooth color with the Vita Classical shade guide included the maxillary incisors. The Vita shade guide is a standard scale of multiple tooth-shaped tabs, each having a different color. Commonly used in dentistry to match artificial crowns to the natural dentition, the Vita shade guide has been successfully applied in clinical studies to assess the efficacy of tooth whitening products.4,7-9 All examinations were performed under color balanced lighting conditions using diffused lighting, with color temperature approximately 5500 K. To reduce variation, all examinations were performed in the same operatory—and thus under the same lighting conditions—whenever possible. The operatory colors were neutral, and both the evaluator and subject were instructed to avoid wearing bright clothing. A blue bib was draped over all subjects, and they were instructed to remove jewelry, eyeglasses, lipstick, and anything else that could interfere with shade selection. Without drying the teeth, the evaluators judged tooth color by selecting the closest shade tab on the guide. Between individual observations, the evaluators looked at a light blue card for a few seconds. Assessment of brushing treatment efficacy was performed by a rank ordering of shade tabs arranged from dark to light according to the rank ordering suggested by the manufacturer (Table 1). To ensure maximum integrity of the data, only 2 evaluators performed Vita shade assessments in the study. Before the screening visit, the clinical evaluators examined a subset of subjects for tooth 162 Formattato: Centrato Eliminato: 214¶ color using the Vita shade guide to establish intra-evaluator repeatability. Intra-examiner kappa statistics at 3 months were 1.00 (95% confidence interval (CI): 0.73, 1.00) and 0.88 (95% CI: 0.62, 1.00) for the examiners, and the inter-examiner kappa for the 2 examiners was 0.88. Formattato: Tutto maiuscole DIGITAL IMAGING Using existing technologies of digital photography and photographic analysis software used in the printing industry, it is possible to assess the color of teeth that currently cannot be matched by Formattato: Interlinea doppia, Non regolare lo spazio tra testo asiatico e in alfabeto latino existing shade guides, making it possible to assess differences as small as one-eighth of a Vita shade.26 In recent years the CIE L*a*b* color space has been accepted as the benchmark for assessing color.27 This space covers the entire range of color seen by the human eye. The L*a*b* color model consists of a luminance component, L* (black to white), and 2 chromatic components, a* (green to red) and b* (blue to yellow). Figure 1 presents the CIE L*a*b* scale as a 3-dimensional visualization. The subjects’ baseline post bleaching and 6-month rebound images were photographed using the same standard digital camera under lighting conditions identical to those used during the Vita shade assessments. Subjects were positioned with the central incisal edge 9 inches from the lens of the camera, which was mounted on an axis perpendicular to the facial surface of the central incisors. Patients were presented edge-to-edge with retractors and were asked to touch the tip of their tongue to their soft palate. This allowed light to readily pass through the tooth surface and reduce reflectance from the tongue. The camera’s flash unit was used to ensure the consistency of light source and an ultraviolet filter was used on the camera to reduce glossing, which may occur with flash usage, thereby reducing the likelihood of hot spots and increasing the consistency of color accuracy between images. The camera was plugged into a 120volt power source to ensure a constant flash intensity between images. Vita Classical and 3D Master shade guides were photographed as well, providing controls to ensure maintenance of Formattato: Centrato Eliminato: 214¶ 163 photographic settings and quality and to establish a guideline for comparison between the L*a*b* and Vita shade guide subject data collected. Adobe Photoshop softwaree was used to generate the L*a*b* scores. To ensure accuracy, 9 Formattato: Interlinea doppia locations were sampled on each of the central incisors, lateral incisors and canines of the maxillary arch, and L*a*b* scores were generated at these points. These data were then averaged to find a mean color and standard deviation of color on each tooth. A Gaussian blur filter set at 13 units, which averages color over an entire photo, was then applied to the original digital image. Using this filtering technique, 4 sampling locations were identified as optimal—the incisal-middle third and the middle-middle third of the maxillary left central and lateral incisors—because they provided the same information obtained from sampling the 9 locations without a filter. This allowed for faster sampling and decreased variability in the data by moderating the color extremes. Efficacy of the brushing treatment was made by comparison of L*a*b* scores derived from images captured at the first post bleaching clinical visit (post bleaching baseline) and 3 and 6 months thereafter. L* and b* are the 2 components of L*a*b* scores most recognized as being influenced by bleaching treatment, with an increase in L* indicating lightening and a decrease in b* indicating decreasing yellow and thus decreasing stain. Formattato: Tutto maiuscole STATISTICAL ANALYSIS The primary analysis used linear mixed effect models appropriate for a repeated measures design. This type of analysis supports the use of incomplete cases and allows for the testing of overall differences between brushes, overall change over time, and differences in brushes over time. The primary Vita shade analysis focused on comparing mean Vita shade scores between treatment groups over time. Secondary Vita shade analysis included comparisons between mean Vita shade scores of individual teeth over time. The luminance component of the L*a*b* scores generated from the digital images collected on the subset of 14 subjects was analyzed with 2-sample Student tFormattato: Centrato Eliminato: 214¶ 164 tests, comparing differences in L* and b* (post bleaching baseline to 6 months post bleaching) between groups. Formattato: Allineato a sinistra, Interlinea doppia Formattato: Tutto maiuscole RESULTS Formattato: Interlinea doppia A total of 43 subjects 18 years of age or older and in good health were enrolled in the study. At the pre-bleaching baseline examination, the groups were comparable in terms of Vita shade scores and Formattato: Interlinea doppia, Non regolare lo spazio tra testo asiatico e in alfabeto latino age (Tables 2 and 3). Three subjects did not return after the bleaching treatment and were dropped from the study, making the total sample size 40. The study sample was composed of 23 women and 17 men. Thirty-one subjects, 18 from the Sonicare group and 13 from the manual toothbrush group, returned for all clinical evaluations over the course of the 6-month study. Twelve subjects, 3 from the Sonicare group and 9 from the manual toothbrush group, missed at least 1 visit over the course of the 6-month study. The mean Vita shade scores over time overall and by individual tooth are presented in FiFigure 2 and Figure 3, respectively. Formattato: Interlinea doppia After completion of the bleaching treatment, the average shade score in the manual toothbrush group was approximately 1.3 Vita shades lower than that of the Sonicare group. Clearly the 2 groups responded differently to the bleaching treatment, though both were using the same dentifrice and manual toothbrush during the bleaching process. To assess the statistical significance of the observed difference, a 2-sample Student t-test was used to test the null hypothesis of no difference in mean Vita score between groups after bleaching. Because the result was not statistically significant (P = .06), the null hypothesis of no difference in mean post bleaching shade scores between brush groups was accepted. Results of the linear mixed effects model using the complete case data indicate a statistically significant effect per visit. With the exception of the 1-month evaluation, all visits were found to have significantly different mean Vita scores (1 month P = .14; 2 months P < .001; 3 months P = .013; 6 Formattato: Centrato Eliminato: 214¶ 165 months P < .001), relative to the first post bleaching exam. That is, for both brush groups at the 2month visit and beyond, mean Vita shade scores were significantly higher (darker) than immediately after bleaching. This indicates a rebound effect after 2 months. No statistically significant effect between groups, or brush type, was found (P = .07). This is not surprising because the groups were designed to have similar shade levels and this tests the combined group averages across all visits. To determine if rebound was affected over time by brush type, the interaction of brush type and visit was tested. A statistically significant difference was found at the 6-month evaluation (P = .04), indicating that the brush groups rebounded differently after 6 months of brushing. On average, the manual brush group rebound was 1.12 Vita shades greater than that of the Sonicare brush group. The 2-sample Student t-test assessing the mean change in luminance L* between brush groups (post bleaching baseline to 6 months post bleaching) returned a statistically significant result (P < .001), indicating teeth darkened with the use of the manual toothbrush compared with the use of the Sonicare toothbrush. The difference was estimated at –4.8 (95% CI: –6.5, –3.1); that is, after 6 months of toothbrush use, the manual toothbrush group mean was 4.8 L* units darker than the Sonicare toothbrush group mean. This difference in luminance was equivalent to 2 Vita Classical shades. The mean change in the blue-yellow axis b* also was assessed with a 2-sample Student ttest (post bleaching baseline to 6 months post bleaching). Again, the Sonicare toothbrush group showed a statistically significant difference from the manual toothbrush group (P < .001), indicating less of the yellow component for the Sonicare toothbrush group. The difference between groups was estimated at 2.1 b* units (95% CI: 0.9 to 3.2). (Table 4) Three subjects showed signs of gingival sensitivity associated with the bleaching treatment; all subsequently resolved with the completion of the bleaching treatment. Both brushes had excellent Formattato: Centrato safety records with no adverse events or abnormal intraoral exams reported after bleaching. 166 Eliminato: 214¶ Photographs representing the type of changes observed in each group are presented in Figure 4 and Figure 5. Formattato: Interlinea doppia, Non regolare lo spazio tra testo asiatico e in alfabeto latino Formattato: Interlinea doppia Formattato: Tutto maiuscole DISCUSSION The analyses of the digital images and the Vita shade data both show the Sonicare toothbrush to be superior to a manual toothbrush at maintaining whitening 6 months after bleaching. While this is the first study examining the effect of Sonicare on maintaining whitening, there are other data on the effect of a manual toothbrush. Matis and colleagues,28 for example, report an increase of 5.2 L* units and 2.9 shade guide units only 6 weeks after a 2-week bleaching regimen using 15% carbamide peroxide. Our results show a more modest but still measurable rebound effect for manual brushing. The estimated 6-month Vita shade difference between groups was larger in the digital analysis (2 Vita shades) than in the Vita shade analysis (1.12 Vita shades). This difference in estimates may be Formattato: Interlinea doppia, Non regolare lo spazio tra testo asiatico e in alfabeto latino the result of the varying precision and accuracy of the 2 efficacy measures. We additionally note that the ordering of the Vita Classical shade guide does not follow the order suggested by digital image analysis of the shade tabs. In particular, ranking the tabs by decreasing luminance L*, that is the pure value axis of the L*a*b* color sphere, suggests not only that the color tabs are incorrectly ordered but also that the color change between tabs is nonlinear (Figure 6). Similar observations have been reported by O’Brien and colleagues29 and Paravina and colleagues.30 These factors also may contribute to the difference in estimates between the 2 efficacy measures. Formattato: Interlinea doppia The choice of randomization based on pre-bleaching mean Vita scores was made after considering the alternative of basing the randomization on the post bleaching mean Vita scores. The use of the former generated treatment groups with similar color shade distribution before bleaching. It was Formattato: Centrato Eliminato: 214¶ 167 believed that the method would produce groups with similar rebound patterns because the 2 groups were comparable before bleaching. The latter method would have produced comparable groupings after bleaching, but would have ignored the initial, pre-bleaching color distributions. This could have lead to groups with different rebound responses if their initial shade colors were very different. Formattato: Tutto maiuscole CONCLUSIONS The demand for tooth bleaching products and their use by professionals and patients is increasing every day. Treatment options include in-office bleaching, take-home bleaching, or a combination of the 2, with or without professional supervision. The take-home system is the most convenient for patients and professionals alike and proves to be very effective over a period of a few weeks. Studies have shown that there is some shade rebound over time. The clinician should keep in mind that the patient’s eating and drinking habits are likely to affect rebound as extrinsic staining can be caused by the use of coffee, tea, tobacco, red wine, and red grapes. The patients’ main concern after a successful bleaching treatment remains maintaining the bleached color over a period of time. In the current study the Sonicare Advance toothbrush was proven more effective than a manual toothbrush in maintaining the color of bleached teeth for 6 months. This finding, added to the established record of safety, superior plaque removal, and gingivitis reduction31-33 and extrinsic stain removal for this device, make Sonicare an excellent choice for patients interested in overall oral health and specifically tooth whitening maintenance. Formattato: Centrato Eliminato: 214¶ 168 Table 2—Ranking and Scoring of Vita Classical Shades Shade Score B1– 1 B1 2 A1 3 B2 4 D2 5 A2 6 C1 7 C2 8 D4 9 A3 10 D3 11 B3 12 A3.5 13 B4 14 C3 15 A4 16 C4 17 Formattato: Allineato a sinistra, Interlinea doppia, Non mantenere con successivo Lightest Formattato: Allineato a sinistra, Interlinea doppia Darkest Formattato: Interlinea doppia Formattato: Centrato Eliminato: 214¶ 169 Table 3—Number of Subjects per Group by Visit Manual Sonicare Screening 22 21 Baseline prebleaching 22 21 Baseline postbleaching 19 21 1 Month 18 19 2 Months 17 19 3 Months 14 18 6 Months 13 18 Formattato: Centrato Eliminato: 214¶ 170 Table 4—Study Demographics (Age) Statistic Manual Sonicare Minimum 20 21 1st quartile 26 27 Mean 34.0 Median 29 32 3rd quartile 44 46 Maximum 51 66 N 22 21 Missing 1 0 Standard deviation 10.6 Formattato: Allineato a sinistra, Interlinea doppia, Non mantenere con successivo Formattato: Allineato a sinistra, Interlinea doppia 36.7 13.3 Table 5—L*a*b* Mean Differences (postbleaching baseline to 6 months) Difference in Mean (SD) L* a* b* Manual Sonicare Manual Sonicare Manual Sonicare –3.3 (3.5) 1.5 (2.9) 0.9 (1.5) 0.3 (1.4) 2.3 (2.6) 0.2 (1.6) Formattato: Centrato Eliminato: 214¶ 171 Figures +L* –a* –b* CIE L*a*b* Color Space +b* +a* –L* Figure 1—CIE L*a*b* Color Space Formattato: Centrato Eliminato: 214¶ 172 Mean Vita Scores All Teeth 6 4 5 Fi 3 Mean (All Teeth) Vita Score 7 8 Manual Sonicare 0 5 10 15 20 25 # Weeks Post-Bleaching Figure 2—Overall mean Vita scores over time. Formattato: Centrato Eliminato: 214¶ 173 Mean Vita Scores Tooth 8 10 15 20 7 6 0 5 10 15 Mean Vita Scores Tooth 9 Mean Vita Scores Tooth 10 10 15 20 25 4 5 6 7 Manual Sonicare 0 # Weeks Post-Bleaching 25 3 Mean (Tooth 10) Vita Score 7 6 5 4 5 20 8 # Weeks Post-Bleaching 3 Mean (Tooth 9) Vita Score 5 25 # Weeks Post-Bleaching Manual Sonicare 0 4 Mean (Tooth 8) Vita Score 8 5 8 0 Manual Sonicare 3 4 5 6 7 Manual Sonicare 3 Mean (Tooth 7) Vita Score 8 Mean Vita Scores Tooth 7 5 10 15 20 25 # Weeks Post-Bleaching Figure 3—Mean Vita scores by tooth over time. Formattato: Centrato Eliminato: 214¶ 174 Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt (a) Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt (b) Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt (c) Figure 4—Images of a representative subject from the manual toothbrush group (a) at screening, (b) at post bleaching baseline, (c) at 6 months after the end of bleaching. Formattato: Centrato Eliminato: 214¶ 175 Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt (a) Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt (b) Formattato: Tipo di carattere: (Predefinito) Arial, 11 pt (c) Figure 5—Images of a representative subject from the Sonicare toothbrush group (a) at screening, (b) at post bleaching baseline, (c) at 6 months after the end of bleaching. Formattato: Centrato Eliminato: 214¶ 176 80 Luminance L* 70 60 50 C 4 C 3 A4 A3 .5 B4 D 3 B3 C 1 C 2 D 4 A3 B2 D 2 A2 B1 A1 40 Vita Classical shades in manufacturer's order Figure 6—Luminance component of CIE L*a*b* color (middle-middle third of tab) vs manufacturer’s order for Vita Classical shade tabs. Acknowledgments This work was supported by Philips Oral Healthcare, Inc. Formattato: Centrato Eliminato: 214¶ 177 PRODUCT REFERENCES Formattato: Tutto maiuscole 1 Formattato: Tipo di carattere: (Predefinito) Arial Philips Oral Healthcare, Inc, Snoqualmie, WA 98065; (800) 676-SONIC b Vita Zahnfabrik, Bad Säckingen, Germany; distributed in the USA by Vident, Brea, CA 92621; (800) 828-3839 c Ultradent Products, Inc, South Jordan, UT 84095; (800) 496-8337 d The Procter & Gamble Company, Cincinnati, OH 45202; (800) 492-7378 e Adobe Systems, Inc, San Jose, CA 95110; (800) 833-6687 Formattato: Tutto maiuscole REFERENCES 1. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence Int. 1989;20:173-176. 2. Goldstein RE. In-office bleaching: where we came from, where we are today. J Am Dent Assoc. 1997;128(suppl):11S-15S. 3. Burrell KH. ADA supports vital tooth bleaching—but look for the seal. J Am Dent Assoc. 1997;128(suppl):3S-5S. 4. Croll TP, Sasa IS. Carbamide peroxide bleaching of teeth with dentinogenesis imperfecta discoloration: report of a case. Quintessence Int. 1995;26:683-686. 5. Haywood VB. Current status of nightguard vital bleaching. Compend Cont Educ Dent. 2000;21(suppl 28):S10-S17. 6. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth [published erratum appears in Compend Contin Educ Dent. 1998;19:864]. Compend Contin Educ Dent. 1998;19:810-813. 7. Small BW. The application and integration of at-home bleaching into private dental practice. Compend Contin Educ Dent. 1998;19:799-808. 8. Christensen GJ. Bleaching teeth: practitioner trends. J Am Dent Assoc. 1997;128(suppl):16S18S. 9. Christensen GJ. Bleaching teeth: report of a survey, 1997. J Esthet Dent. 199810:16-20. 10. Haywood VB, Robinson FG. Vital tooth bleaching with Nightguard vital bleaching. Curr Opin Cosmet Dent. 1997;4:45-52. 11. Kugel G, Perry RD, Hoang E, Scherer W. Effective tooth bleaching in 5 days: using a combined in-office and at-home bleaching system. Compend Contin Educ Dent. 1997;18:378-383. 12. Li Y. Toxicological considerations of tooth bleaching using peroxide-containing agents. J Am Dent Assoc. 1997;128(suppl):31S-36S. 13. Leonard RH Jr. Efficacy, longevity, side effects, and patient perceptions of nightguard vital bleaching. Compend Contin Educ Dent. 1998;19:766-774. 14. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital bleaching of tetracycline-stained teeth. J Esthet Dent. 1997;9: 13-19. 15. Haywood VB, Leonard RH, Nelson CF, Brunson WD. Effectiveness, side effects and long-term status of nightguard vital bleaching. J Am Dent Assoc. 1994;125:1219-1226. 16. Matis BA, Cochran MA, Eckert G, Carlson TJ. The efficacy and safety of a 10% carbamide peroxide bleaching gel. Quintessence Int. 1998;29:555-563. 17. Haywood VB. Historical development of whiteners: clinical safety and efficacy. Dent Update. 1997;24:98-104. 18. Gegauff AG, Rosenstiel SF, Langhout KJ, Johnston WM. Evaluating tooth color change from carbamide peroxide gel. J Am Dent Assoc. 1993;124:65-72. Formattato: Centrato Eliminato: 214¶ 178 19. Stanford CM, Srikantha R, Wu CD. Efficacy of the Sonicare® toothbrush fluid dynamic action on removal of human supragingival plaque. J Clin Dent. 1997;8(1 Spec No):10-14. 20. Stanford CM, Srikantha R, Kirchner HL, Wu CD. Removal of supragingival plaque in an intraoral model by use of the Sonicare® toothbrush. J Int Acad Periodontol. 2000;2:115-119. 21. Wu-Yuan CD, Anderson RD, McInnes C. Ability of the Sonicare® electronic toothbrush to generate dynamic fluid activity that removes bacteria. J Clin Dent. 1994;5:89-93. 22. Hope CK, Petrie A, Wilson M. In vitro assessment of the plaque-removing ability of hydrodynamic shear forces produced beyond the bristles by two electric toothbrushes. J Periodontol. In press. 23. McInnes C, Johnson B, Emling RC, Yankell SL. Clinical and computer-assisted evaluations of the stain removal ability of the Sonicare® electronic toothbrush. J Clin Dent. 1994;5:13-18. 24. Zammitti S, Habib C, Kugel G. Use of environmental scanning electron microscopy to evaluate dental stain removal. J Clin Dent. 1997;8(1 Spec No):20-25. 25. Bass CC. An effective method of personal oral hygiene; part II. J La State Med Soc. 1954;106:100-112. 26. Anderson C, Kugel G. Rebound evaluation of tetracycline stained subjects treated with a 6.5% hydrogen peroxide gel; quantitative assessment by standard digital photography [abstract]. J Dent Res. 2002;81(spec iss):A-429. Abstract 3488. 27. Commission Internationale de l’Eclairage. Colorimetry Official Recommendation of the International Commission on Illumination. Paris: Bureau Central de la CIE; 1971.CIE Publication 15 (E-13.1). 28. Matis BA, Mousa HN, Cochran MA, Eckert GJ. Clinical evaluation of bleaching agents of different concentrations. Quintessence Int. 2000;31:303-310. 29. O'Brien WJ, Groh CL, Boenke KM. A new, small-color-difference equation for dental shades. J Dent Res. 1990;69:1762-1764. 30. Paravina RD, Powers JM, Fay RM. Dental color standards: shade tab arrangement. J Esthet Restor Dent. 2001;13:254-263. 31. Tritten CB, Armitage GC. Comparison of a sonic and a manual toothbrush for efficacy in supragingival plaque removal and reduction of gingivitis. J Clin Periodontol. 1996;23:641-648. 32. Johnson BD, McInnes C. Clinical evaluation of the efficacy and safety of a new sonic toothbrush. J Periodontol. 1994;65:692-697. 33. O’Beirne G, Johnson RH, Persson GR, Spektor MD. Efficacy of a sonic toothbrush on inflammation and probing depth in adult periodontitis. J Periodontol. 1996;67:900-908. Formattato: Portoghese (Brasile) Formattato: Inglese (U.S.A.) Formattato: Inglese (U.S.A.) Formattato: Centrato Eliminato: 214¶ 179 Chapter 10 Intrapulpal Temperatures with Light Activated Whitening Formattato: Tipo di carattere: 14 pt Formattato: Centrato Effects of a Light Activated Bleaching System on Pulp Chamber Temperature in Vitro Formattato: Tipo di carattere: 12 pt, Grassetto Formattato: Tipo di carattere: 12 pt ABSTRACT Several new techniques and materials for in-office bleaching have been introduced recently. The aim of this in vitro study was to measure the temperature increase in pulp chamber produced by Zoom light and to investigate the influence of this light in conjunction with the application of bleaching gel on temperature rise. Ten extracted caries-free, unrestored human maxillary anterior teeth were used for the study. Each tooth was exposed three times in both groups (n=30 per group). The root of each tooth was cut about approximately 2-3mm apically to the CEJ and the apical orifice of the root canal was enlarged. The remaining pulp tissue was removed and the empty pulp chamber was filled with a heat sink compound which replaced the pulp tissue as a heat conducting medium. A thin K-type thermocouple was inserted to the pulp chamber through the cut root area. The root surfaces of the tooth were partially submerged in a water bath during the testing procedure at 37.5oC . In the first group, whitening gel, 25% hydrogen peroxide was applied to the buccal surfaces of teeth, approximately 1-2mm thick. Then the light was positioned at ~2.50 inches. The material was applied according to manfacturers instrutions. In the second group, the same teeth were exposed with the Zoom light without application of bleaching gel. The temperature at the pulp before treatment (baseline) and temperature increase during exposing the light were measured for both treatment modalities. There was a 5 minutes interval between the end of one measurement and begining of the next. The mean temperature rise for group I (light and bleaching gel) was 1.11oC(0.18 ). The mean temperature use for group II (light alone) was 1.01 oC (0.12 ). 180 Formattato: Centrato Eliminato: 214¶ There was a statistically significant difference between two groups (p= 0.003). Application of Zoom light in conjuction with the application of bleaching gel produced greater temperature rise than did the light alone. The maximum temperature rise was seen in the first 5 minutes of the treatment for both groups then the temperature decreased. Although a difference was noticed between the group receiving light and gel (group I) versus the group receiving light (group II), neither group showed significant increase in the intrapulpal temperature of teeth when used for the recommended Formattato: Inglese (U.S.A.) exposure time. INTRODUCTION Tooth Whitening has become one of dentistry’s most popular esthetic procedures as it is a conservative treatment for discolored teeth 1. Power bleaching is an in-office whitening technique developed to bleach teeth in a single visit. It’s done by the combination of a whitening agent, such as, peroxide, and an auxiliary, such as light 2, 3 . Currently, the in-office whitening technique uses a 15% to 35% hydrogen peroxide whitening agent (heated or non-heated); the dentist-prescribed home-applied technique most commonly uses a 10% to 15% carbamide peroxide gel. The advantage of the in-office procedure is that it does not require patient compliance and results may be seen immediately. The disadvantage is the chair time, cost to the patient, and the possibility of multiple visits. A light-activated chairside whitening system has the potential advantages of taking less time and providing quicker results. Recently, several new techniques and materials for in-office bleaching have been introduced. The Zoom Chairside teeth whitening system is one of the power bleaching systems that consists of a mercury Halide lamp filtered to emit light in the 350-400nm range. Tooth sensitivity is the most common side effect of whitening4 .Concerns have been raised with the use of in-office whitening system energy sources like lasers, plasma arc lights and infrared lamps. It’s believed that these systems activate peroxide formulations and may induce a temperature rise Formattato: Centrato Eliminato: 214¶ 181 that could cause sensitivity. Additionally, it has been reported that the light by itself might have a bleaching effect 2. Lately, one study article reported the efficacy of the light whitening system whereas another study publication accomplished the opposite1, 2. In a recent investigation done in our lab employing a mercury halide light activated bleaching system significant sensitivity was reported. In this study 30 patients received treatment with the light & 25% hydrogen peroxide gel, gel alone or light alone. The gel and light group reported a 90 % severe to moderate tooth sensitivity rate. This was significantly higher than the other groups. (submitted to IADR, 2004).Therefore the aim of this in vitro study was to measure the temperature increase in pulp chamber produced by Zoom light and to investigate the influence of this light in conjunction with the application of bleaching gel on the temperature rise. EXPERIMENTAL DESIGN Ten extracted caries-free, unrestored human maxillary anterior teeth were used for the study. Teeth were randomized and used for three separate temperature recordings for a total of thirty readings per group. Two groups were designed Group 1 was treated with bleaching gel and ZOOM light was applied for three cycles of 20 minutes .Group 2 was treated only with ZOOM light for three cycles of 20 minutes. Every 5 minutes temperatures were measured for each group using K-type thermocouple. The mean temperature and p-value for group 1 and group 2 were calculated. MATERIALS AND METHODS Ten extracted caries-free, unrestored human maxillary anterior teeth were used for the study. After the teeth were polished with pure pumice to remove any surface debris or contaminants, they were stored in distilled water until used. The root of each tooth was cut about 2-3mm apically to the CEJ and the apical orifice of the root canal was enlarged. The remaining pulp tissue was removed and Formattato: Centrato Eliminato: 214¶ 182 the empty pulp chamber was filled with heat sink compound (American Oil and Supply Co., Newark, NJ, USA) which replaced the pulp tissue as a heat conducting medium. A thin K-type thermocouple was inserted to the pulp chamber through the cut root area. The root surfaces of the tooth were partially submerged in a water bath during the testing procedure. This method effectively stabilized the internal baseline temperature at 37.5°C This also minimized the effects of ambient temperature changes and provided a consistent initial temperature for each data set. In the first group, whitening gel, 25% hydrogen peroxide was applied to the buccal surfaces of teeth, approximately 1-2mm thick. Then the light was positioned according to the manufacturer’s instructions using the integral bite appliance guide to set the distance between the teeth and the light source approximately 2.50 inches. The teeth were exposed with the Zoom light for 20 minutes. After each 20minute session the whitening gel was rinsed off, and reapplied. In the second group, the same teeth were exposed with the Zoom light without application of bleaching gel. The temperature at the pulp before treatment (baseline) and temperature increase during exposing the light were used for both treatment modalities. There was a 5 minute interval between the end of one measurement and the beginning of the next. RESULTS The mean temperature rise was 1.11ºC(0.18) in the first group where the light was used with bleaching gel and 1.01ºC(0.12) in the second group at 5 minutes (graph 1). According to ANOVA test, there was a statistically significant difference between two groups (p= 0.003). Application of Zoom light in conjuction with the application of bleaching gel produced greater temperature rise than did light alone at the 5 minute exposure time. The maximum temperature rise was seen in the first 5 minutes of the treatment for both groups. Temperature slowly decreased for the 10, 15 and 20 minute recordings (table1). Formattato: Centrato Eliminato: 214¶ 183 During the 20 minute exposure time temperatures slowly decreased to 0.43ºC for the light and 0.53ºC for the gel and light system. None of the samples returned to the baseline level during the 20 minute application (table 1). DISCUSSION Tooth whitening lights lights may emit heat. The effects of heat on the pulp tissue has been welldocumented. Due to its low compliance nature, lights may cause a temperature increase within the pulp chamber that may harm the pulp and/or cause tooth sensitivity 5. Zach and Cohen found that a temperature rise of 5,5 C in a healthy pulp resulted in necrosis in 15% of the Macaca rhesus monkey teeth 6. However in our study the maximum temperature rise was 1,01. Therefore the zoom light was found to cause only a slight increase in the temperature. However temperature was increaed when the light was used in conjunction with the 25% hydroge peroxide bleaching agent. Since these results were obtained in vitro, long-term clinical trials are needed to fully understand the reasons of hyersensitivity and performance of this new whitening sytem. SUMMARY This study concluded the mean temperature rise was 1.11°C for the gel & light when samples are maintained at body temperature ( table 1). Recently an article published by Hein 4 showed that in vivo gel temperature change, Zoom! Light bleach gel reached 5°C on the tooth surface during its 20 minute exposure time. The Zoom! Light was designed specifically for tooth bleaching. The results achieved by this study indicate that although previous reports showed significant temperature rise on the tooth surface our results demonstrate that the intrapulpal temperature increases only slightly during the exposure time. Therefore the Zoom light was found to cause only a slight increase in intrapulpal temperature. The use of the light and gel demonstrated a significantly higher temperature increase than the light alone. However, this increase is still lower than the necessary to cause pulpal damage (5.5 °C). The sensitivity noted during light activated bleaching is most Formattato: Centrato Eliminato: 214¶ 184 probably increase dehydration on the surface of the tooth. This may relate to 5°C surface temperature change previously reported on the enamel surface. Since these results were obtained in vitro, long-term clinical trials are needed to fully understand the reasons of hypersensitivity and performance of these new whitening systems. The effects of light activated bleaching systems on temperature rise in the pulp are not clinically significant. Hanning and Bott have shown that temperatures exceeding 42.5 °C can result in irreversible damage to pulp tissue 7. The distance between the light and tooth could affect the temperature rise in the pulp chamber. It is interesting to comment that normally hot liquids are consumed with short term temperatures at 60 °C to 70° C. It’s believed that the pulp only increases a few degrees due to the thermal insulting properties of the dental hard tissue, when using a regular halogen curing light 7 .Our study would indicate no long term pulpal damage from this light activated bleaching system. Graph 1: Zoom Light Zoom Light + Bleaching Gel 1.2 Mean Temperature Rise 1 0.8 0.6 0.4 0.2 0 0 10 5 Time of Exposure 15 20 Formattato: Centrato Eliminato: 214¶ 185 Table 1: Mean Temperature Rise Time in Minutes Zoom Light Zoom Light + Bleaching Gel Baseline 0 OC(37.5ºC) 0 OC(37.5ºC) 5 1.01OC 1.11 OC 10 0.82 OC 0.98 OC 15 0.60 OC 0.77 OC 20 0.43 OC 0.53 OC Formattato: Centrato Eliminato: 214¶ 186 REFERENCES: 1. Papathanasiou A, Bardwell D, Kugel G. A clinical study evaluating a new chairside and takehome whitening system. Compendium 2001; 22: 289-297. 2. Tavares M, Stultz J, Newman M, Smith V, Kent R, Carpino E, Goodson JM. Light augments tooth whitening with peroxide. JADA 2003; 134: 167-175. Formattato: Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra di: 36 pt, Tabulazioni: 18 pt, Tabulazione elenco + Non a 36 pt 3. Nathanson D. Vital tooth bleaching: sensitivity and pulpal considerations. JADA 1997; 128: suppl: 41S-44S. 4. Hein DK. Ploeger BJ. Hartup JK. Wagstaff RS. Palmer TM. Hansen LD. In-office vital tooth bleaching--what do lights add?. Compend of Contin Educ Dent. 2003 Apr; 24(4A):340-52. 5. Blankenau R, Goldstein R, Haywood VB. The current status of vital tooth whitening techniques. Compendium 1999; 20: 781-794. 6. Zach L, Cohen G. Pulp response to externally applied heat. Oral Surg Oral Med Oral Pathol 1965; 19: 515-530. 7. Hannig M, Bott B. In-vitro pulp chamber temperature rise during composite resin polymerization with various light-curing sources. Dent Mater. 1999 Jul;15(4):275-81 Formattato: Tipo di carattere: Arial, Turco Formattato: Tipo di carattere: Arial Formattato: Centrato Eliminato: 214¶ 187 Chapter 11 Formattato: Tipo di carattere: 14 pt Effect of Tooth Whitening on Enamel Formattato: Centrato Formattato: Tipo di carattere: 12 pt, Grassetto An exploratory study using SEM to evaluate the enamel surface effects in vivo of a 6% hydrogen peroxide strip bleaching system with that of a 2.5% chlorite tray bleaching system Formattato: Tipo di carattere: Arial Formattato: Allineato a sinistra INTRODUCTION Tooth whitening has become both common and popular, and use of peroxide is now generally recognized as a safe and effective method for tooth whitening 1-3 . There are a variety of indications for bleaching single or multiple teeth, including staining from chromagenic foods or other sources, dental fluorosis, tetracycline staining and devital discolored teeth 4-6 . Concentrations of up to 35% peroxide are used alone or in combination with various agents for tooth bleaching. Delivery is via in-office, at-home regimens or combination regimens with or without professional supervision 7, 8 . Of these, bleaching is most commonly accomplished at-home over a period of a few weeks 9. Treatment duration may vary based on the degree of staining, since whitening is reported to be a product of peroxide concentration and contact time 10 . For some difficult stains like tetracycline, daily bleaching for periods of up to 6 months may be indicated 11. Efficacy may be established through first or second person observation or various technical methods. Clinical trials most commonly include use of a shade guide, colorimeter, or computer digitization to measure color change over time. Of these, methods that assess three-direction (dimension) color space are reported to be more objective and linear, and as such, may be preferred for clinical trials research 12,13. A comprehensive literature review found tooth bleaching agents to be remarkably well-tolerated. The principal adverse events — tooth sensitivity to temperature changes and local oral mucosal irritation — were generally mild and transient. Patients with pre-existing sensitivity may be at Formattato: Centrato Eliminato: 214¶ 188 highest risk for after-bleaching sensitivity. Several factors are reported to contribute to hard and soft tissue events, including tray design, formulation, and others 10. Tolerability may be impacted by poor compliance, overuse, unnecessary product ingestion, and others 5,. Many of these factors may be associated with the delivery trays (either custom or stock) which are commonly used in most at-home regimens. Rapid innovation, especially with the advent of new in-office options for immediate care and the emerging popularity of the direct-to-consumer systems, challenges many of the basic tray-based precepts of the previous decade. One of the most prominent of these is the whitening strip (Crest®, Blend-a-Med® or AZ® Whitestrips™), a novel system that uses a flexible polyethylene strip to deliver a hydrogen peroxide bleaching gel to the anterior dentition. These whitening strips are reported to offer specific advantages vs the more conventional custom tray-based systems, with respect to total peroxide dose, contact time, and ease of use. Evidence of safe and effective use has been established in clinical and pre-clinical studies comparing whitening strips to various negative and positive controls. The application of such bleaching agents to whiten vital-teeth is less well-characterized with little research published in the scientific literature. There have been a number of studies evaluating the effect of bleaching on the hardness and morphology of enamel. The results from these studies have varied. One study concluded that the use of bleaching agents resulted in a significant reduction in Calcium/Phosphate ratio in enamel 14 and they concluded that bleaching materials may adversely affect the dental hard tissue. Other authors state that surface hardness and tooth morphology are not deleteriously affected by Eliminato: 15 , 16 bleaching . Eliminato: This clinical trial evaluated the safety of a recently introduced 2.5% sodium chlorite tray-based ¶ Formattato: Tipo di carattere: Arial whitening system, Odol-med 3 Beauty Kurr, versus a currently marketed 6% hydrogen peroxide Formattato: Centrato Eliminato: 214¶ 189 strip system. Sodium chlorite is the only chlorite salt produced commercially in significant quantities. Formattato: Tipo di carattere: Arial It is used mainly for the generation of chlorine dioxide in situ for bleaching textiles, in pulp and paper processing, and for disinfection. Scanning Electron Micrographs from replicas were used to observe surface effects/ morphological changes in teeth enamel after treatment with bleaching agents. The observations included any changes in the porosity, precipitations, erosive process, destruction and depression areas, with the formation of craters and exposure of enamel rods. Formattato: Tipo di carattere: Arial, 8 pt Formattato: Tipo di carattere: Arial OBJECTIVE The aim of this exploratory study was to assess any surface morphological changes in tooth enamel after treating with a currently marketed hydrogen peroxide strip bleaching system and a currently marketed sodium chlorite tray-based system using an SEM Investigation. Formattato: Tipo di carattere: Arial MATERIAL AND METHODS Formattato: Giustificato This was a parallel, examiner-blind, single-center study. Approximately 10 generally healthy subjects (5 per treatment group) were randomly selected from a pool of subjects undergoing a 3 week regimen of vital tooth bleaching with either a 6% whitening strip (Group I) or 2.5% sodium chlorite tray system (Group II). The Test Products were: • AZ Whitestrips (Polyethylene strips containing 6% Hydrogen Peroxide gel). Formattati: Elenchi puntati e numerati Manufactured by The Procter & Gamble Company. • Odol-med 3 Beauty Kur (Tooth Whitening System including the Activator containing 2.5% Sodium Chlorite). Manufactured by Glaxo Smithkline. Subjects assigned to Crest Whitestrips treated their anterior maxillary tooth surfaces for a period of Formattato: Tipo di carattere: Arial three weeks. The product was used twice a day for 30 minutes each. Subjects assigned to Odolmed 3 also treated their maxillary surfaces for three-week duration, as per the manufacturer’s Eliminato: was supervised instructions. This product was used twice a day for 10 minutes. The first product use was Formattato: Centrato Eliminato: 214¶ 190 supervised at the Product Distribution visit. All other uses were completed at home and were Formattato: Tipo di carattere: Arial unsupervised. Formattato: Tipo di carattere: Arial, 8 pt Subjects on the Group I brushed twice daily with AZ Protezione Caries toothpaste (currently Formattato: Tipo di carattere: Arial marketed cavity protection toothpaste). It contains 0.32% Sodium Fluoride (Procter & Gamble Eliminato: I brushed Company). Subjects on the Group II had whitening toothpaste provided to them with their test Formattato: Tipo di carattere: Arial product. All subjects were assigned an Oral B40 Soft Bristle toothbrush (Braun Oral B Company). Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: 8 pt Formattato: Tipo di carattere: Arial Inclusion Criteria The subjects were included if they: 1. provided written informed consent prior to their participation and be given a copy of the signed Formattati: Elenchi puntati e numerati consent form, 2. were at least 18 years of age at the time of enrolment, 3. had a minimum of 16 natural teeth, specifically all 4 maxillary anterior central and lateral incisors. 4. agreed to return for the scheduled visits and follow the study procedures, 5. agreed not to participate in any other oral /dental product clinical studies during the course of this study, 6. agreed to refrain from the use of any non-study dentifrices and tooth whitening products for the study duration and 7. had teeth sufficiently free of caries Formattato: Tipo di carattere: 8 pt Formattato: Tipo di carattere: Arial Exclusion Criteria The subjects were excluded from the 2003088 study if they: 1. had restorations or dental crowns, generalized gingival recession or clinically meaningful malocclusion involving the maxillary or mandibular anterior dentition, Formattati: Elenchi puntati e numerati Eliminato: generalised Formattato: Tipo di carattere: Arial Formattato: Centrato Eliminato: 214¶ 191 2. presented with any pre-existing oral or medical condition that the examiner or investigator determines may place the subject at increased health risk from study participation, 3. had any dental care planned during the duration of the study that may: • impact the general health of the subject • impact the ability of the subject to bleach teeth according to the protocol • require a dental prophylaxis • involve the anterior dentition 4. were undergoing current treatment for gingivitis, periodontitis, or caries, 5. reported having teeth previously bleached by a professional treatment, over-the-counter bleaching kit, or clinical trial test product, 6. were currently using a chlorhexidine mouth rinse or Listerine mouth rinse, 7. had teeth with clinically meaningful intrinsic staining due to tetracycline, fluorosis or hypocalcification, 8. had self-reported dentinal sensitivity, or 9. had teeth that cannot be imaged. Formattato: Sottolineato Continuance Criteria Eliminato: Subjects were discontinued for the following reasons: Formattato: Allineato a sinistra 1. use of dentifrices or mouthrinses or tooth whitening products other than those assigned; Formattato: Tipo di carattere: Arial 2. elective dentistry prior to study completion, including dental prophylaxis; Formattati: Elenchi puntati e numerati 3. Inability or unwillingness to comply with study procedures including test product regimen. The same continuance criteria were governing the subject’s eligibility to continue participation in this study. An SEM Investigation was done on Baseline, Day 14 and Day 21. Subjects discontinued product use at the Day 21 visit. During the entire study period subjects brush with their assigned toothbrush Formattato: Centrato Eliminato: 214¶ 192 and toothpaste. An impression of the dentition and SEM investigation was conducted and used as the post treatment assessment. A rubber impression of both the maxillary and the mandibular anterior teeth was taken for each of the selected subject. These were done both at the baseline (pre-treatment) and after completing the product usage (post treatment). The impressions were poured with epoxy resin material. The buccal surfaces of the two upper central incisors were evaluated. The buccal surfaces of central incisors were gold sputtered and Eliminato: labelled then mounted in metallic stubs. All the study material was labeled with the subject number, tooth Formattato: Tipo di carattere: Arial number and the evaluation day. Observations under the SEM were made on changes in porosity, precipitations, erosive process, destruction and depression areas, with the formation of craters and exposure of enamel rods. Photographs of the scans were taken. Two different evaluators who were blinded to the test product did the observations and scoring. The scoring was done independent of one another. The scoring was done at constant magnifications (x500, x2000 and x5000). Four readings were made on each tooth, dividing the surface into four quadrants (figure 1). The reading was performed in the centre of each quadrant. All the scores were collected and evaluated according with the scores (figure 2) and the location. The SEM scores were done by two independent graders using a scoring system of 0-4. Due to small sample size, non-parametric methods were used to explore the data (figures 3-6). In addition to the visual observation models were poured in epoxy die and 3D laser profilometry was done on all samples. Delta Ra data was obtained and statistical differences from baseline were determined. Formattato: Tipo di carattere: Arial Formattato: Centrato Eliminato: 214¶ 193 RESULTS Scores from the visual evaluation of the SEM data indicated that there was little evidence of any increased surface roughness in either group following treatment (Table 1). This is based on the visual evaluation of two independent calibrated evaluators. Evaluations were based on a comparison between baseline (no treatment) and after 21 days of exposure. It should be noted that all evaluations indicated that the roughness noted was superficial with no deep roughness observed. The profilometry data (table 2) shows a good biological diversity with both products producing a similar but insignificant change in surface roughness. Differences between groups showed no statistical significance using a nonparametric analysis, the Wilson rank sum test. This produces a P-value =0.69 which indicates that neither treatment had any adverse effects on the surface morphology the teeth examined. These results confirm the data presented in table 1. Formattato: Tipo di carattere: Arial DISCUSSION Eliminato: ¶ This study represents the first paper to evaluate enamel following tooth whitening using both visual Eliminato: o analysis and laser profilometry. There have been other studies to evaluate the hard tissue effects of tooth whitening. These have employed microhardness and SEM analysis of the enamel surfaces 15 14, . In this study the use of a visual scoring system for changes on enamel morphology indicated that there were no significant changes from the baseline in either the 6% Hydrogen Peroxide gel group or the 2.5% Sodium Chlorite group. It is important to note that in all evaluations the roughness Formattato: Tipo di carattere: Arial Eliminato: 20 Formattato: Tipo di carattere: Arial Eliminato: 21 Formattato: Tipo di carattere: Arial observed was superficial in nature and that all teeth varied slightly at baseline. This is expected given the variability of enamel clinically and these observations are only relevant when compared within the sample. In order to confirm our SEM visual evaluation Laser profilometry was done for both groups. Measurements were compared using baseline (before treatment) and following 21 days of Formattato: Centrato Eliminato: 214¶ 194 Eliminato: analysed exposure. Samples were analyzed for differences from baseline for both the 6% hydrogen peroxide Formattato: Tipo di carattere: Arial and the 2.5% Sodium Chlorite groups. There is no statistical difference between the baseline and 21 day samples. This is true for both tooth whitening systems. In both groups the 21 day dosing Eliminato: ¶ has no effect on surface roughness of the exposed teeth. In conclusion this study indicates that 21 day exposure to two different tooth whitening systems had no observable or measurable adverse Formattato: Tipo di carattere: Arial Eliminato: n effects on enamel. Formattato: Tipo di carattere: Arial, 8 pt Tables and figures: Formattato: Tipo di carattere: Arial Figure 1 Four readings were made on each tooth, dividing the surface into four quadrants Figure 2: Scoring scales for SEM evaluation Figure 3: Samples of SEM 2,000X with roughness score 0 Figure 4: Samples of SEM 2,000X with roughness score 1 Figure 5: Samples of SEM 2,000X with roughness score 2 Figure 6: Samples of SEM 2,000X with roughness score 3 Table 1: Average scores per group by quadrant Table 2: Laser profilometry Ra analysis Figure 1: A B C D Formattato: Tipo di carattere: Arial Formattato: Centrato Eliminato: 214¶ 195 Figure 2: SEM Scores Score 0 no visible surface roughness Score 1 5-25% of the surface displays roughness Score 2 25-50% of the surface displays roughness Score 3 50-75% of the surface displays roughness Score 4 75-100% of the surface displays roughness Figure 3: Formattato: Tipo di carattere: Arial Eliminato: ¶ Formattato: Tipo di carattere: Arial Formattato: Centrato Eliminato: 214¶ 196 Figure 4: Formattato: Tipo di carattere: Arial Figure 5: Formattato: Centrato Eliminato: 214¶ 197 Figure 6: Eliminato: ¶ Formattato: Tipo di carattere: Arial Table 1: Eliminato: ¶ Formattato: Tipo di carattere: Arial Quadrant A Average per Group 500X 2000X Baseline 14-Day 21-Day Baseline 14-Day 21-Day GROUP I 0 0.4 0.2 1.4 1.6 0.8 GROUP II 0 0 0.2 1.6 1.6 0.4 Formattato: Tipo di carattere: Arial Formattato: Centrato Eliminato: 214¶ 198 Quadrant B Average per Group 500X 2000X Baseline 14-Day 21-Day Baseline 14-Day 21-Day GROUP I 0.2 0.4 0 1.6 1.8 1 Formattato: Tipo di carattere: Arial, 11 pt GROUP II 0.2 0.2 0 1.6 1.6 0.6 Formattato: Tipo di carattere: Arial, 11 pt Quadrant C Average per Group 500X 2000X Baseline 14-Day 21-Day Baseline 14-Day 21-Day GROUP I 0.4 0.4 0 2 1.8 0.6 GROUP II 0.4 0.6 0 2 1.4 0.6 Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial, 11 pt Eliminato: ¶ Formattato: Tipo di carattere: Arial Quadrant D Average per Group 500X 2000X Baseline 14-Day 21-Day Baseline 14-Day 21-Day GROUP I 0.8 0.4 0 2.2 1.6 0.6 GROUP II 0.6 0.2 0 1.2 1.6 0.6 Formattato: Tipo di carattere: Arial, 11 pt Formattato: Tipo di carattere: Arial, 11 pt Formattato: Centrato Eliminato: 214¶ 199 Eliminato: ¶ Table 2: Specimen Treatment 5 Group I 12 Group I 20 Group I 24 Group I 32 Group I Mean Value Specimen Treatment 1 Group II 3 Group II 4 Group II 25 Group II 27 Group II Mean Value Baseline 0.5192 0.2458 0.1815 0.2189 0.3545 0.30398 21 day 0.7154 0.3715 0.2208 0.2034 0.2613 0.35448 Delta Ra 0.1962 0.1257 0.0393 -0.0155 -0.0932 0.0505 Baseline 0.1305 0.2588 0.2792 0.3158 0.3365 0.26416 21 day 0.1976 0.2505 0.2748 0.3244 0.3 0.26946 Delta Ra 0.0671 -0.0083 -0.0044 0.0086 -0.0365 0.0053 Formattato: Tipo di carattere: Arial, Grassetto Formattato: Tipo di carattere: Arial, Grassetto Formattato: Tipo di carattere: Arial Formattato: Tipo di carattere: Arial, Grassetto Formattato: Tipo di carattere: Arial, Grassetto Formattato: Tipo di carattere: Arial REFERENCE 1. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence Int 1989;20: 173-6. 2. Goldstein RE. In-office bleaching: where we came from, where we are today. J Am Dent Assoc 1997; 128: 11S – 15S 3. Burrell KH. ADA supports vital tooth bleaching – but look for the seal. J Am Dent Assoc 1997 128:3S-5S. Formattato: Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra di: 36 pt, Tabulazioni: 18 pt, Tabulazione elenco + Non a 36 pt 4. Croll TP, Sasa IS. Carbamide peroxide bleaching of teeth with dentinogenisis imperfecta discoloration: report of a case. Quintessence Int 1995; 26:683-6 5. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth. Compend Contin Educ Dent 1998; 19:810-3 6. Small BW. The application and integration of at-home bleaching into private dental practice. Compend Contin Educ Dent 1998;19:799-806 Formattato: Centrato Eliminato: 214¶ 200 7. Kugel G, Perry RD, Hoang E, Scherer W. Effective tooth bleaching in 5 days: using a combined in-office and at-home bleaching system. Comp Contin Educ Dent 1997; 18:378-83. 8. Li Y. Toxicological considerations of tooth bleaching using peroxide-containing agents. J Am Dent Assoc 1997; 128:31S-36S 9. Leonard RH. Efficacy, longevity, side effects, and patient perceptions of nightguard vital bleaching. Compend Contin Educ Dent 1998; 19: 177-780 10. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital bleaching of tetracycline-stained teeth. J Esthet Dent 1997;9: 13-9 11. Haywood VB, Leonrd RH, Nelson CF, Brunson WD. Effectiveness, side effects, and long-term status of nightguard vital bleaching. J Am Dent Assoc 1994; 125 1219-26 12. Gegauff AG, Rosenstiel SF, Langout KJ, Johnston WM. Evaluation of tooth color change from carbamide peroxide gel. J Am Dent Assoc 1993;124:65-72. 13. Rotstein I. Dankner E. Goldman A. Heling I. Stabholz A. Zalkind M. Histochemical analysis of Formattato: Tipo di carattere: Arial, Tedesco (Germania) Formattato: Tipo di carattere: Arial dental hard tissues following bleaching. Journal of Endodontics. 22(1):23-5, 1996 Jan. 14. White DJ. Kozak KM. Zoladz JR. Duschner HJ. Gotz H. Effects of Crest Whitestrips bleaching on surface morphology and fracture susceptibility of teeth in vitro. Journal of Clinical Dentistry. 14(4):82-7, 2003. 15. Spalding M. Taveira LA. de Assis GF. Scanning electron microscopy study of dental enamel surface exposed to 35% hydrogen peroxide: alone, with saliva, and with 10% carbamide peroxide. Journal of Esthetic & Restorative Dentistry: Official Publication of the American Formattato: Tipo di carattere: Arial, Portoghese (Brasile) Formattato: Tipo di carattere: Arial Academy of Esthetic Dentistry. 15(3):154-64; discussion 165, 2003. Summary and Discussion In Chapter 1, as an introduction to the main topic of this study, a major aspect of modern dentistry was presented. The area of tooth whitening, although one of the fastest growing and affecting millions of patients, it relies on a weak base of scientific evidence. The actual mechanism of action of hydrogen peroxide on enamel and dentin is presumed to be an oxidation process that affects both enamel and dentin. The assumption is that because the radicals have unpaired electrons, they are extremely electrophylic and unstable and will attack most other organic molecules to achieve stability, generating other radicals. These radicals can react with most unsaturated bonds, resulting in disruption of electron conjugation and a change in the absorption energy of the organic 201 Formattato: Centrato Eliminato: 214¶ molecules in tooth enamel. Simpler molecules that reflect less light are formed, creating a successful whitening action. This process occurs when the oxidizing agent (hydrogen peroxide) reacts with organic material in the spaces between the inorganic salts in tooth enamel. This assumption is difficult to prove. Our data supports the idea that there must be significant penetration of the peroxide into dentin and that once it reaches the dentin it is in a form that is able to oxidize the organic material causing a lightening effect. The early work on tetracycline staining supports the idea that there is a penetration of the free radical. These studies relied on small sample sizes and incorporated high dose delivery systems. The causes of both intrinsic and extrinsic staining were reviewed following the section on penetration of hydrogen peroxide. This was done to support the belief that these intrinsic stains require significant penetration in order for these to be lightened. It is interesting that so little is known about the concentration and dose response during the whitening process. The assumption has been that the higher the concentration the better the effect. It has also been assumed that a dose of 30-50 mg was required to whiten teeth. We examine in this thesis the use of a novel low dose delivery system using 9-11 mg of carbamide peroxide on a polyethylene strip. A review of the evolution of tooth whitening demonstrates the field is not new. The review of the literature also shows that there a number of systems available for tooth whitening. The most common bring the night guard vital bleaching method. Other systems have been more recently introduced such as the polyethylene strip and paint-on products. The area of light activated bleaching as indicated in the introduction remains one of the most controversial areas in this field. This is due to the poor quality of many of these studies the results have been questioned. The mechanism of action of these light (and heat) activated systems is addressed along with the evidence that the assumed increased breakdown of the hydrogen peroxide and thus increased Formattato: Centrato efficacy would require temperatures the would be detrimental to vital teeth. 202 Eliminato: 214¶ Finally; the issue of adverse events and possible side effects were reviewed. The toxicological side effects seem to be minimal however tooth sensitivity can be quite significant. Studies have shown that sensitivity occurs in 55 to 75% of the treatment groups. The placebo groups also experienced 20-30% sensitivity. The causes of tooth sensitivity are poorly understood. It is most often seen as the result of tooth dehydration. In Chapter 2 a randomized, single-center, double-blind, parallel-group, placebo controlled trial evaluating the whitening efficacy and safety of 2-week, twice daily use of a 5.3% hydrogen peroxide tooth-bleaching gel delivered on polyethylene film. This system employed a low dose delivery of 9-11 mg of carbamide peroxide gel. Efficacy was based on change in Vita® shade scores from baseline to the end of treatment. Baseline Vita® shade scores were similar for the two treatment groups. Scores were 8.18 (D-4 to A-3) and 8.28 (D-4 to A-3), and, on average, ranged from A-2 to C-4 and from A-2 to A-4 in the active and placebo groups, respectively. Sixty-four percent of teeth treated in the active group started at scores of C-2 or whiter. Thirty-three patients in each group completed treatment. Use of the peroxide-containing gel led to a mean change in baseline Vita® shade score of –3.70 ± 0.35, compared with a change of –0.87± 0.24 after use of a placebo gel. After adjustment for baseline scores, the mean difference in shade change between the peroxide gel–treated group and placebo-treated group was –2.85 ± 0.41 (P < 0.0001). Both treatments were generally well tolerated. Adverse effects after treatment were minimal and were observed in less than 10% of subjects in either treatment group. The main findings in these participants were papillary swelling, minor cervical inflammation, and a superficial cervical lesion. This was the first study to examine the use of such a thin film of hydrogen peroxide gel in tooth whitening. Prior to the research dentist would us a night guard fabricated to a stone model of the patient and contoured at the margins Spacer was routinely used on the facings of the teeth to insure that a high dose of material could be delivered to the teeth with the assumption that this was Formattato: Centrato necessary to have a significant amount of material in contact with the teeth for tooth whitening to 203 Eliminato: 214¶ occur. This study was the first to demonstrate that a low dose (9-11 mgs) but higher concentration 5.3 % hydrogen peroxide applied for 30 minutes twice daily resulted in significant lightening when compared to placebo control. This study was controversial since this delivery system was easy to apply, effective, minimal adverse events and did not require the fabrication of a tray and therefore had the potential to be used as over-the-counter product. In Chapter 3 the question of concentration response using a low dose (4-11 mg) delivery system was addressed employing digital image analysis of treatment groups in order to analyze the CIELAB tooth color values for b* (yellow – blue), L* (lightness), and a* (red – green).17 Change values were calculated for any given post-baseline visit. The objective of this study was to evaluate the peroxide concentration whitening response following self-directed use of whitening strips over a 28-day period. A randomized, double-blind, parallel group clinical study was conducted. Thirty-seven healthy adult volunteers were randomly assigned to one of three groups based on tooth color at screening – 1.8% hydrogen peroxide strips (HPS), 3.3% HPS or 5.3% HPS. Subjects applied the assigned maxillary strips twice per day for 30 minutes over 28 days. Tooth color was evaluated at day 7, 14 & 28 from digital images of the maxillary 6 anterior teeth using a standard method. Treatments were compared using analysis of covariance (adjusting for baseline), or analysis of variance at a 0.05 level of significance. The results of this study demonstrated hydrogen peroxide at concentrations ranging from 1.85.3% resulted in significant (p < 0.05) color improvement versus baseline as early as Day 7. There was a clear concentration-response for all color parameters (Δb*, ΔL* and ΔE*) at all time points, favoring the higher concentrations. While the concentration-whitening relationship approached a linear response at Day 7, continued treatment resulted in incremental color improvement. All three Formattato: Centrato Eliminato: 214¶ 204 peroxide concentrations were well tolerated, and no subjects discontinued early due to a treatmentrelated adverse event. The research provides clear evidence of a peroxide concentration whitening response. Whitening efficacy was greatest for the highest concentration group (5.3% hydrogen peroxide), while the intermediate concentration group had an intermediate response. Not surprisingly, this effect most approached linearity at the earliest time point (Day 7). At that time, adjusted mean Δb* for was – 1.43, –0.84, and –0.44 in the higher, intermediate and lower concentration groups, respectively. Relative to the lowest concentration strip, this represented a 225% improvement in whitening for the 5.3% strip (a 194% increase in concentration), and a 91% improvement in whitening for the 3.3% strip (a 83% increase in concentration). Despite the concentration differences (there was nearly a three-fold difference between the lowest and highest concentration tested in this research), all three strips tested in this research carried a low total amount of peroxide. The total amount of hydrogen peroxide on each pre-dispensed strip ranged only from 3.6-10.6 mg. Relative to some tray-based systems, which may deliver up to 2 grams of bleaching gel, total peroxide delivered with any of these strips was remarkably low. This likely contributed to the low overall adverse event rate seen in this trial. This new clinical research provides evidence of a concentration gradient for whitening response following use of a low peroxide dose strip whitening system. As such, this may represent a first example of concentration ranging for one of the self-directed bleaching systems. More importantly, the research also provides evidence of the sensitivity and robustness of the measurement method – in this instance – digital imaging. The study in Chapter 3 compliments the earlier work done in Chapter 2. In Chapter 2 we discussed the introduction of a low dose novel delivery system and we demonstrate its effectiveness vs contro Formattato: Centrato Eliminato: 214¶ 205 using a value-ordered shade guide. In Chapter 3 we determine that there is a concentration response when measured digitally using this low dose system. This research adequately differentiated multiple concentrations from low to high over time. With Δb* as an endpoint, the study demonstrated a nearly linear concentration response relationship, with measured efficacy differences at Day 7 that reasonably modeled the real concentration differences between groups. As such, the research provides important evidence of the validity of this method and endpoint for practice-relevant evaluation of vital bleaching technologies. In Chapter 4 we evaluated the effectiveness of light-curing (heat conversion) vs. no light- curing (no heat conversion) of a 35% hydrogen peroxide in-office tooth whitening system. Heat conversion is used as a means of speeding up the breakdown and thus increasing the efficacy of the hydrogen peroxide oxidation process. This was one of the first controlled studies to evaluate light activated bleaching. Twenty patients with sound medical history (without tooth sensitivity) participated in this randomized, parallel clinical evaluation. Only six maxillary anterior teeth with discoloration and a tooth shade of A3 or darker were selected. Patients received a complete prophylaxis and were evaluated for initial (baseline) shade by three independent evaluators, precalibrated at 85% rater reliability in determining shades before the experiment began. Participants received a 20-minute chairside whitening treatment with a 35% hydrogen peroxide agent using a reflective resin barrier for gingival isolation. During the whitening treatment, the 35% hydrogen peroxide agent was light activated with a halogen curing light on teeth Nos. 6 through 8 (Group I), but was not light-activated on teeth Nos. 9 through 11 (Group II). All patients returned 24 hours after the whitening application for shade evaluation. Although there were isolated instances (7 out of 20 patients) of greater degrees of lightening in the light-curing group, there was no statistically significant difference using Formattato: Centrato Eliminato: 214¶ 206 the Mann-Whitney U test (P > .05). This study indicates that light-curing is optional with this 35% tooth whitening system. Of the 20 patients in this study, 7 patients experienced an increase in lightening of the split arch protocol with an average lightened increase of 1.714 shades as compared to the non–light-cured side. This was not a significant clinical change. Any shade difference as noted by the light-activated side was most likely a result of dehydration resulting from heat generated by the halogen curing light. Statistically, there was no significant difference between the light-activated side when compared to non–light-activated side. The results contradict other studies, which have indicated that light activation causes an increased whitening effect as used with hydrogen peroxide whitening agents The study in Chapter 5 is complimentary to that in Chapter 4. The purpose of this study was to compare the efficacy of color changes of two in-office tooth whitening systems, a 15% Hydrogen peroxide light activated system and a 38% non-light activated hydrogen peroxide system. In this split-arch, randomized, parallel, blinded clinical evaluation six maxillary anterior teeth (N=60) A-2 or darker were selected using the value order Vita Shade Guide. Patients received one-hour light-activated chair side treatment using 15% H2O2 teeth 6-8 (Group I), teeth 9-11 received a 38% H2O2 system for 1 hr without a light (Group II). Before and after treatment images were taken. L*, a* and b* and Vita shades were measured. The Olympus C2500L high resolution digital camera is utilized for sampling. To ensure proper color analysis an extended procedure of sampling nine locations on the central incisor, lateral incisors of the maxillary and mandibular arches was completed. This data is then averaged Formattato: Centrato Eliminato: 214¶ 207 to find a mean color and standard deviation of color on each tooth. A Gaussian blur filter was applied during post processing which does an averaging of color over the digitally sampled photo. All digital images were then analyzed to yield L*, a* and b* data Patients returned after 2 weeks for final shade evaluation. The L*, a* and b* data indicates that both BriteSmile and Opalescence Xtra Boost whitened teeth to statistically significant level (P=.01) for L* 3.6 (BriteSmile), 3.8 (Xtra Boost) and b* -6.0 (BriteSmile), -5.0 (Xtra Boost) equivalent to between 3 and 6 shades as determined on a Vita shade guide. The two whitening systems were not statistically significantly different from pre-bleaching to two weeks post-bleaching. The Vita Shade Guide results showed that both in-office tooth whitening systems were effective. Group I averaged 5.9 ± 2.5 and Group II 3.97 ± 2.33 shade changes immediately after treatment. At the 2-week recall, Group I scored an average of 4.6 ± 2.14 and Group II 4.6 7± 2.3 shade changes, compared to the pre-bleaching shades. A paired sample t-test revealed statistically significant difference (p<0.0001) between Groups I and II immediately after bleaching, with Group I performing better. At the 2-week recall, however, only Group I showed a significant rebound (p=0.0002). At the completion of the study, there was no significant difference between Groups I and II (p=0.7826). The clinical observation using a value ordered Vita Shade Guide was confirmed using digital analysis of L*, a*, b* color values 15 . In addition the digital camera was calibrated for each image. Unlike other studies, the teeth of the one side were kept moist during bleaching, thus minimizing the effect of dehydration that can occur while the other lateral side was being bleached. This might explain why our data does not show the dramatic results reported in another paper. It is reasonable to conclude that with the increase in temperature, dehydration did occur, which was subsequently followed by rehydration. Therefore, in spite of the initial perception that an increase in whitening Formattato: Centrato Eliminato: 214¶ 208 took place, the 2-week post-operative evaluation did not demonstrate a difference, which was confirmed by an absence of a statistically significant difference between the two materials. This data is particularly relevant since the use of light activated bleaching has been gaining in popularity in the US. This is partially due to the fact that there are few well controlled, independent studies in the field. In a study that we just completed at our University but the (data yet unpublished) we used a metal halide (Zoom) light N=30 patients and we once again found no value to use of a light in bleaching. In Chapter 6 we address the issue of hydrogen peroxide penetration as well as mechanism of action by examining the efficacy of a low dose delivery system on bleaching tetracycline-stained teeth. We incorporate a patient population with documented intrinsic staining so that we could evaluate the ability of the low dose gel to penetrate to the dentin. This clinical article reviews the efficacy of a new 6.5% hydrogen peroxide tooth-whitening gel strip for bleaching teeth that have been intrinsically stained from tetracycline. Given the severity of the staining in the cases presented during this conducted clinical trial, the resulting efficacy is dramatic. A randomized clinical trial compared the efficacy of two at-home vital bleaching systems on tetracycline-stained teeth. Daily bleaching was conducted over two months. Eligibility was limited to healthy adult volunteers who had 16 or more natural teeth, including at least 3 gradable maxillary incisors with significant tetracycline staining. Individuals demonstrating tooth sensitivity or an immediate need for dental treatment were excluded from participation in this trial. The 40 randomized subjects included 30 assigned to the strip group and 10 assigned to the tray group. The study population ranged from 22 to 70 years of age. Approximately half of the sample presented with moderate to severe tetracycline staining (levels II through IV), one third of whom had the more severe banding that is occasionally reported following childhood antibiotic use. While Formattato: Centrato tobacco use was uncommon (15% of the sample), 95% of the study participants consumed coffee, 209 Eliminato: 214¶ tea, or cola beverages daily. Treatment groups were generally well balanced with respect to demographic and behavioral parameters and tetracycline stain levels. Efficacy was assessed using a standard 16-step value-oriented tooth shade guidec used in dentistry to match artificial crowns to the natural dentition. Shade assessments were performed in a neutral-colored dental operatory under color-balanced lighting conditions by a trained and calibrated examiner. Tolerability was assessed by intraoral examination and subject report at each study visit. Individual shade scores were determined by ordering the 16 shades arranged from dark to light according to the rank ordering suggested by the manufacturer. To account for unusually dark colors (often seen with tetracycline stain) or white colors (often seen post-bleaching), this 16-step guide was supplemented by 2 additional values (C4+ and B1-) representing shades darker than C4 or lighter than B1. Effectiveness was determined by calculating the change in shade scores from baseline at each post-treatment visit. Using this method, a decrease in numeric shade score represented an increase in tooth whiteness. Treatment groups were compared using analysis of covariance with the baseline shade as the covariant. Comparisons to baseline were 1-sided, while between-group comparisons were 2-sided using a 5% significance level. Both treatments were effective overall in improving the shade of tetracycline-stained teeth. Relative to baseline, the 2 groups averaged approximately 4 to 6.5 units of shade improvement after 2 months of treatment. Observed changes were greater on average after 2 months as compared to 1 month. Response was faster in the strip group. During the first month’s treatment, individuals in the strip group averaged greater than a 4-unit reduction in tooth shade, which represented a highly statistically significant (P < .0001) improvement vs. baseline. In contrast, subjects in the tray group averaged less than a 1-shade reduction during the first month, not differing statistically from baseline (P > .10). Adjusting for baseline, the strip group averaged 2.6 to 3.2 units more shade reduction compared with the tray group control. With respect to between-group comparisons, the strip group experienced statistically significantly superior reductions (P < .01) in shade compared Formattato: Centrato with the tray group at both the 1- and 2-month time points. 210 Eliminato: 214¶ This study confirms early observations of the need for extended contact time in many tetracyclinestained patients. After 2 months of daily treatment, involving approximately 60 hours of strip use or 120 hours of tray use, no subjects had yet reached the predetermined bleaching cutoff (B1-). In these subjects, additional time may be necessary to affect maximum color change. Previous reports suggest a minimum of 2 months of treatment, hence the time point elected in this study. This data demonstrates the difficulty, regardless of the delivery system, in bleaching tetracyclinestained teeth. This confirms that the peroxide does penetrate to the dentin and that the oxidation process affects the color of the stained dentin. It also confirms that this is a slow process and requires extended exposure. Chapter 7 is the continuation of the 2 month study described in Chapter 6. Chapter 6 was the published data from the first 2 month of this 6 month study. A variety of indications exist for bleaching single or multiple teeth, including tetracycline staining. The primary objective of this study was to evaluate clinical response following extended daily use of a trayless 6.5% hydrogen peroxide tooth bleaching gel on tetracycline stain. In this research, 10% carbamide peroxide in an at-home daytime tray delivery system was used for comparison purposes. As in Chapter 6 this is a single-blind clinical trial, subjects were randomly assigned to a Strip group (30 subjects) or a Tray group (10 subjects) following screening for tetracycline staining. Subjects used their respective products for approximately 6 months, with clinical safety and efficacy measurements taken at the end of each month. The strip product was used for 30 minutes, twice daily (maxillary arch only). The tray product was used for 2 hours daily (maxillary arch only). Treatment efficacy was determined by the tooth color change from baseline using an expanded Vita Shade guide. The Strip group averaged greater shade reduction compared to the day wear Tray group at the Months 1, 2, and 3 visits, respectively. After Month 3, there were no significant between-group differences in shade. Of the subjects in the Strip group, 65% reached B1 tooth color by Month 6, while 43% of subjects in Tray group obtained Formattato: Centrato this result after 6 months. Both treatments were generally well tolerated. Mild and transient tooth 211 Eliminato: 214¶ sensitivity (40-47%) and oral irritation (30-47%) were the most common adverse events associated with daily bleaching, yet neither affected study participation. Both the 6.5% H2O2 experimental bleaching strip and daywear marketed tray-based carbamide peroxide system provided significant tooth whitening in subjects with tetracycline stain. The Strip group obtained the results in a shorter time compared to the daywear tray group. In this study, onset of shade improvement was earlier, and the magnitude of the change was greater with strips compared to trays. Through Month 3, the strip group exhibited a statistically significant (p < 0.05) 1.3 to 3.2 shade improvement relative to the tray control. What accounted for the significant between-group differences in shade improvement seen early in treatment? One likely explanation is that twice a day use of a strip for 30 minutes applied a higher concentration of peroxide more frequently compared to 2-hours of continuous tray use of the lower concentration carbamide peroxide gel. Other factors could have contributed to these findings, including the small sample size in the tray group, differences in the tetracycline staining at baseline, and/or compliance (strips versus the day wear regimen used for the trays). However, shade guides represent an imperfect measure of efficacy, especially for complex clinical presentations like those seen with tetracycline staining. As such, the comparative effectiveness of outcomes must be evaluated with caution because causality cannot be assessed from multi-factorial research like this clinical trial. This study provides new evidence of an expanded safety in-use with strip-based tooth whitening. Both bleaching systems in this trial were well tolerated with daily use over a 6-month treatment period. No subjects in either group discontinued treatment early due to product-related adverse events. For the tray system, these findings corroborate other reports of safe continuous daytime use of 10% carbamide peroxide on tetracycline stain 23,24 . The research provides additional assurance of the clinical safety of this 10% carbamide peroxide tray system with conventional use over a few weeks, and longer term use for treatment of tetracycline staining. For the strip system, the findings provide first evidence of in-use clinical safety with extended treatment. Long term Formattato: Centrato clinical trials of this duration may be particularly relevant in establishing clinical safety associated 212 Eliminato: 214¶ with routine treatment, as a research model that evaluates extreme (intentional or unintentional) use. Such research may only be appropriate with populations such as this one, where long-term treatment is common and/or necessary to achieve a desired endpoint, where ethical and experimental controls are adequate to interpret outcomes, and where rigorous and sufficient exit criteria are established to assure in-use safety. Under these conditions, longer duration trials represent a “torture test” of sorts, offering additional insight on short-term clinical safety. Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital bleaching with professional tray or strip systems can yield an evident improvement in appearance within a few weeks. This non-invasive treatment may need to continue over an extended period. Some individuals will show favorable response after 3-4 months, after which treatment may be discontinued. Duration may be difficult to predict, given the variable clinical manifestations of tetracycline staining. This study confirms that hydrogen peroxide will penetrate enamel and oxidize dentin. Even with long term exposure to these various whitening regimens no adverse results were noted. In Chapter 8 we explore a new delivery system for tooth whitening. This is one of the first studies to do a direct comparison of two paint-on delivery systems. The latest inclusion to OTC products is a Brush technique. This technique is non-tray based paint on application. These products include a 19% sodium percarbonate film (5.3% hydrogen peroxide) along with an 18% carbamide peroxide paint-on gel. The advantages to the paint- on products are ease of use as well as the elimination of the need for a tray. These systems also limit gingival exposure. There is little data on efficacy of these products. The objective of this trial was to compare the safety and whitening efficacy of an experimental liquid strip (four weeks of use) to Colgate Simply White (three weeks of use). This was a randomized, controlled, double-blind, parallel, single-center study. Fifty (50) generally healthy subjects who desired to have their teeth whitened were enrolled in the study. Subjects who qualified for the study based on the results of their Baseline visit were randomly assigned to one of Formattato: Centrato Eliminato: 214¶ 213 two treatment groups. Data was obtained using a HC2500 CCD high resolution digital camera manufactured by Fuji. It was equipped with a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens and a linear polarizer to permit cross-polarized light. Two 150-watt lights located on each side of a CCD camera provided the lighting. The unit was connected to a personal computer which recorded and analyzed the images. Prior to daily use, the system was calibrated to assure proper operation. Additionally, a color standard was centered and imaged every hour, and then was removed prior to imaging subjects. Maxillary anterior facial surfaces were measured for tooth color using the digital image technology. One color value (L* a* b*) was generated from the complete surface of the measured teeth. At the Week 4 visit, only the Experimental Film group was effective in whitening teeth as measured by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7). The Experimental Film group provided more than 4 times greater improvement in lightness (ΔL*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.065± 0.135 and 0.263 ± 0.146, respectively. The treatment comparison for ΔL* was statistically significant (p-value = 0.0003 from Table 12). Only the Experimental Film group effective in whitening teeth as measured by mean change in a* (redness) from Baseline (p-value = 0.0003 from Table 8). The Experimental Film group provided more than 3.8 times greater improvement in redness (Δa*) when compared to the Colgate Simply White group with estimated means and standard errors of –0.397 ± 0.072 and –0.104 ± 0.078, respectively. The treatment comparison for Δa* was statistically significant (p-value = 0.0099 from Table 13). Both treatments were effective in whitening teeth as measured by mean change in W* (composite whiteness) from Baseline with p-values ≤ 0.0029 (Table 9). The Experimental Film group provided more than 4.2 times greater improvement in composite whiteness (ΔW*) when compared to the Colgate Simply White group with estimated means and standard errors of –1.385 ± 0.146 and –0.325 ± 0.158, respectively. The treatment comparison for ΔW* was Formattato: Centrato Eliminato: 214¶ 214 statistically significant (p-value < 0.0001 from Table 14). Both treatments were effective at increasing overall color change (ΔE*) with p-values < 0.0001 (Table 10). The Experimental Film group provided more than 1.9 times greater overall color change (ΔE*) when compared to the Colgate Simply White group with estimated means and standard errors of 1.534 ± 0.147 and 0.788 ± 0.160, respectively. The treatment comparison for ΔE* was statistically significant (p-value = 0.0020 from Table 15). This study indicated that the 19% sodium percarbonate film (5.3% hydrogen peroxide) paint-on whitening product was affective in whitening teeth, however neither system tested was as affective as the tray or strip systems previously tested. In Chapter 9 we explore the rebound that occurs post bleaching as well as methods to limit its affect. A randomized, parallel, examiner-blind clinical study was conducted to examine the ability of 2 toothbrushes to maintain teeth whitening after at-home bleaching. Forty subjects used a 15% carbamide peroxide tray bleaching system at home for 2 weeks per the manufacturer’s instructions and then were randomly assigned to use either the Sonicare® Advance power toothbrush or a manual toothbrush as part of their home oral hygiene routine for 6 months. The color of the labial surfaces of the subjects’ maxillary anterior dentition was assessed before bleaching and immediately, 2 months, 3 months, and 6 months after bleaching. Color was assessed by comparison with Vita® Classical shade tabs and by digital image analysis in the CIE L*a*b* color space. Both groups demonstrated a rebound effect at the 2-month visit and beyond, with mean Vita shade scores significantly higher than immediately after bleaching. At the 6-month evaluation, there was a significant difference in the amount of rebound in each group. Specifically, the rebound of the Sonicare brush group was on average 1.12 Vita shades less than that of the manual brush group. The 6-month difference was confirmed through digital image analysis, with the Sonicare brush group 4.8 L* units lighter, corresponding to 2 Vita shades, and 2.1 b* units less yellow than the manual brush group. This clinical trial demonstrates that the Sonicare Advance toothbrush better maintains whitening after bleaching treatment than a manual toothbrush. Formattato: Centrato Eliminato: 214¶ 215 The analyses of the digital images and the Vita shade data both show the Sonicare toothbrush to be superior to a manual toothbrush at maintaining whitening 6 months after bleaching. While this is the first study examining the effect of Sonicare on maintaining whitening, there are other data on the effect of a manual toothbrush. Matis and colleagues, for example, report an increase of 5.2 L* units and 2.9 shade guide units only 6 weeks after a 2-week bleaching regimen using 15% carbamide peroxide. Our results show a more modest but still measurable rebound effect for manual brushing. The estimated 6-month Vita shade difference between groups was larger in the digital analysis (2 Vita shades) than in the Vita shade analysis (1.12 Vita shades). This difference in estimates may be the result of the varying precision and accuracy of the 2 efficacy measures. We additionally note that the ordering of the Vita Classical shade guide does not follow the order suggested by digital image analysis of the shade tabs. In particular, ranking the tabs by decreasing luminance L*, that is the pure value axis of the L*a*b* color sphere, suggests not only that the color tabs are incorrectly ordered but also that the color change between tabs is nonlinear. Similar observations have been reported by O’Brien and colleagues and Paravina and colleagues. These factors also may contribute to the difference in estimates between the 2 efficacy measures. This study is important in a number of ways. It confirms that post bleaching rebound occurs as soon as 1 month after bleaching and this rebound continues at a slower rate up to 6 month. Secondly this data questions the degree of rebound reported in other studies. Finally this study brings in question the adequacy of the value ordered shade guide in its present form for bleaching studies. In Chapter 10 an in vitro study was performed to measure the temperature increase in pulp Formattato: Tipo di carattere: Non Grassetto chamber produced by Zoom light (mercury halide) and to investigate the influence of this light in Formattato: Tipo di carattere: Grassetto conjunction with the application of bleaching gel on the intrapulpal temperature. The Zoom! Light Formattato: Tipo di carattere: (Predefinito) Arial was designed specifically for tooth bleaching. The results achieved by this study indicate that although previous reports showed significant temperature rise on the tooth surface our results demonstrate that the intrapulpal temperature increases only slightly during the exposure time. Formattato: Centrato Therefore the Zoom light was found to cause only a slight increase in intrapulpal temperature. The 216 Eliminato: 214¶ use of the light and gel demonstrated a significantly higher temperature increase than the light alone. However, this increase is still lower than the necessary to cause pulpal damage (5.5 °C). The sensitivity noted during light activated bleaching is most probably increase dehydration on the surface of the tooth. This may relate to 5°C surface temperature change previously reported on the enamel surface. Finally this study supports the clinical observation that light activated bleaching does not result in long term pulp damage and it suggests that the sensitivity noted during light activated tooth whitening may be the result of dehydration and not pulpal irritation. In Chapter 11 an exploratory study was done to assess any surface morphological changes in Formattato: Tipo di carattere: Grassetto tooth enamel after treating with a currently marketed hydrogen peroxide strip bleaching system and Formattato: Tipo di carattere: Non Grassetto a currently marketed sodium chlorite tray-based system using an SEM Investigation. This study Formattato: Tipo di carattere: Arial represents the first paper to evaluate enamel following tooth whitening using both visual analysis and laser profolometry. In this study the use of a visual scoring system for changes on enamel morphology indicated that there were no significant changes from the baseline in either the 6% Hydrogen Peroxide gel group or the 2.5% Sodium Chlorite group. It was also noted that in all evaluations the roughness observed was superficial in nature and that all teeth varied slightly at baseline. The laser profilometry data indicated that there is no statistical difference between the baseline and 21 day samples. This is true for both tooth whitening systems. In both groups the 21 day dosing has no effect on surface roughness of the exposed teeth. Using two different measurement techniques the results from both tests have the same conclusion that 21 day exposure to two different tooth whitening systems had no observable or measurable adverse effects on enamel. Formattato: Tipo di carattere: 12 pt Formattato: Centrato Conclusions and Recommendations Eliminato: 214¶ 217 The following conclusions and recommendations may be drawn from our studies on tooth whitening: 1. The use of a low dose delivery system is adequate to get significant whitening. Formattati: Elenchi puntati e numerati 2. The use of a polyethylene strip containing 5.3% hydrogen peroxide 30 minutes twice per day results in significant whitening. 3. This research provides clear evidence of a peroxide concentration whitening response. Whitening efficacy was greatest for the highest concentration group while the intermediate concentration group had an intermediate response. This effect most approached linearity at the earliest time point (Day 7). 4. This clinical research provides evidence of a concentration gradient for whitening response following use of a low peroxide dose whitening system. As such, this may represent a first example of concentration ranging for one of the self-directed bleaching systems. There is a measurable concentration affect during bleaching. 5. The use of a light and/or heat to speed up the oxidation process in tooth whitening is of no benefit. This was tested using the Halogen. Gas Plasma and Metal Halide light sources. Dehydration appears to cause the initial improvement that is noted immediately post bleaching. 6. The use of a mercury halide light for tooth whitening does not result in pulpal temperatures that would cause irreversible pulp damage but might be able to result in dehydration of exposed teeth. 7. Our data demonstrates the difficulty, regardless of the delivery system, in bleaching tetracycline stained teeth. This confirms that the peroxide does penetrate to the dentin and that the oxidation process affects the color of the stained dentin. It also confirms that this is a slow process and requires extended exposure. 8. Long term exposure (6 month continuous use) to either 10% carbamide peroxide in a tray system or 6.5% hydrogen peroxide strip resulted in no serious adverse events. This study Formattato: Centrato Eliminato: 214¶ 218 represents the largest sample size for this type of study and the first to use the strip delivery system. 9. Paint-on whitening systems vary in effectiveness and none of those tested equal the efficacy found with the tray or strip systems. 10. Post bleaching rebound occurs as soon as 1 month after bleaching and this rebound continues at a slower rate up to 6 month. 11. The adequacy of the value ordered shade guide in its present form for bleaching studies is inadequate. This ordering on the shades is incorrect when checked using digital L*a*b* analysis. The ADA needs to re-evaluate its requirement for this method of evaluation in order to obtain ADA approval for tooth whitening systems. 12. Tooth whitening systems tested had no observable or measurable adverse effects on Formattato: Tipo di carattere: Arial enamel. Acknowledgements I wish to express my sincere gratitude to all who contributed to this work. Prof. Dr Marco Ferrari who has supported me in many ways both as a friend and fellow researcher. He has encouraged me to complete this thesis and pushed me to become a better scientist, as he pushes himself. He has always been there when I have needed advise and I value him dearly. Prof. Dr C.L. Davidson who has inspired me as a researcher and who I am always trying to emulate in both my research and in my life. Dr. Robert Gerlach, my good friend and fellow researcher. We have spent many hours discussing our projects and he is a constant source of advice and friendship. Dr’s Ferreria and Sharma who are wonderful young investigators always willing to help and always wanting to learn. Formattato: Centrato Eliminato: 214¶ 219 Isabella Desir, my staff assistant, who is willing to put in long hours and always with a smile. To my family that has always been there when I need them and support me in every way. To my wife, Karen, who has been with me through it all and is a constant source of inspiration to me. My children, Kurt and Chrissy; they put life in perspective. My family is most important to me and I apologize to all of them for the hours of travel and study that have kept me from them. I would also to thank the members of the committee, Prof Piero Tosi, Rector of the Formattato: Tipo di carattere: Non Grassetto University of Siena, to Prof Alberto Auteri, Dean of the Faculty of Medicine, University of Siena, to Prof Egidio Bertelli, vice-Dean of the Faculty of Medicine and Director of the Department of Dental Science, and to Prof Marco Ferrari, Pro-Rector for international affairs and President of Dental School, University of Siena for their support with this thesis. CURRICULUM VITAE Gerard Kugel, D.M.D., M.S., F.A.C.D., F.I.C.D., F.A.G.D., F.A.D.M. 171 Burlington Street Lexington, MA 02173 (781) 861-1935 EDUCATION Tufts University School of Dental Medicine Boston, Massachusetts D.M.D., Ph.D. Program, 1981-1985 D.M.D., 1985 Sackler School of Graduate Biomedical Sciences Department of Anatomy and Cellular Biology Tufts University Boston, Massachusetts M.S., 1993 Formattato: Tipo di carattere: 11 pt Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial, Non Grassetto Formattato: Tipo di carattere: (Predefinito) Arial, 9 pt Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial, Grassetto Formattato: Allineato a sinistra, Rientro: Sinistro: 3,6 pt Tabella formattata Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial, 8 pt Formattato: Centrato Eliminato: 214¶ 220 Cornell University Graduate School of Medical Sciences Department of Neurobiology New York, NY Ph.D. candidate, 1977-1979 (transferred) WORK EXPERIENCE Rutgers University New Brunswick, NJ B.S. Biology and Psychology 1976 Associate Dean for Research Tufts University School of Dental Medicine Boston, Massachusetts March 2001 – Present Visiting Professor, Restorative Dentistry University of Siena, Siena, Italy 1993 - Present Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tabulazioni: 62,1 pt, Allineato a sinistra + Non a 67,5 pt Formattato: Rientro: Sinistro: 0 pt Head of the Division of Operative Dentistry Tufts University School of Dental Medicine Boston, Massachusetts April 1988 – Present Private Practice Boston Center for Oral Health 400 Commonwealth Avenue Boston, Massachusetts 02115 September 1988 – Present Formattato: Centrato Eliminato: 214¶ 221 PUBLICATIONS Kugel G, PapathanasiouA, Williams III A J, Anderson C, Clinical Evaluation of Chemical And Light-Activated Tooth Whitening Systems, Compendium Accepted July 2004. Ferrari M, Kugel G, Cagidiaco M C, Barker M L, Gerlach R W, Clinical Trial Evaluating the Peroxide Concentration Response of Whitening Strips Over 28 Days, Am J Dent. In Press Formattato: A destra 0 ch Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial Kugel G, Gerlach R W, Aboushala A, Susana Ferreira-Martin, Marco Ferrari,The Long term use of 6.5% Hydrogen Peroxide Bleaching Strips on Tetracycline Stain: A controlled Clinical Study, J of Esth and Rest Dent, May-04. Accepted Kugel G, What You Need to Know When Choosing a Material, Dentist’s Money Digest, pages 24-25, April 2004 Kugel G, Aboushala A, Sharma S, Ferreira S, Anderson C, Maintenance of Whitening with a Power Toothbrush After Bleaching Treatment, Compendium, Vol. 25, No. 2, pages 119131, February 2004. Ferreira S, Kugel G, A Simple Review of LED Curing Lights, Contemporary Esthetics and Restorative Practice, pages 52-56, November 2003. Aboushala A, Kugel G, Meta N, Using a Novel Bite Plate to Alleviate Chronic Bruxism Symtoms, Contemporary Esthetics and Restorative Practice, Vol 7, No. 10 Pages 72-78, October 2003 Zhang Q, Rosenberg M, Kugel G, Agarwal R, Phillips j, Kumar S, Effect of Nitrous Oxide on Intracellular Events of GT1-7 GnRHsecreting Neurons, Anesth Prog 50:53-61, 2003 Zhang Q, Bratton G, Agarwal R, Calise D, Kugel G, Wan Y, Kumar A, Lead-induced cell singnaling cascades in GT1-7 cells, Brain Research Bulletin, 61, pages 207-217, 2003 Kugel G, Perry R, Restoring Anterior Maxillary Dentition Using Alumina and Zirconia –Based, Compendium, Vol. 24, No. 8, pages 569-580, August 2003. Zhang Q, Bratton G, Agarwal R, Calise D, Kugel G, Wan Y, Kumar A. Lead-induced cell signaling cascades in GT1-7 cells, Brain Research Bulletin Vol. 61, No. 207-217, April 2003 Formattato: Centrato Eliminato: 214¶ 222 Kugel G, Over-the-Counter Toothwhitening Systems, Compendium Vol. 24, No 4A. April 2003 Fabianelli A, Kugel G, Ferrari Marco, Efficacy of self-etching primer on sealing margins of Class II restorations, American Journal of Dentistry Vol 16, No.1, pages 37-41, February 2003. Kugel G, Perry R, Direct Composite Resins: An Update, Compendium. Vol. 23, No. 7. July 2002. Kugel G, Boghosian A. Impact of the Sonicare® Toothbrush on Plaque and Gingivitis, Compendium. Vol. 23, No. 7. July 2002. Suppl. 1 Kugel G, Boghosian A. Effects of the Sonicare® Toothbrush for Specific Indications, Compendium. Vol. 23, No. 7. July 2002. Suppl. 1 Papathanasiou A, Kastali S, Perry R, Kugel G, Clinical Evaluation of a 35% Hydrogen Peroxide In-Office Whitening System, Compendium. Vol. 23, No. 4. April 2002. Perry R, Kugel G, Success with Inlays/Onlays: The Seven Essentials, Compendium. Vol 23, No. 3. March 2002. Gheewalla E, Perry R., Kugel G, Effects of Three Electric Toothbrushes on Orthodontic Bracket Retention, Journal of Clinical Orthodontics, Volume XXXVI No. 2, January 2002 Fabianelli A, Kugel G, Ferrari M. Efficacy of self-etching primer on sealing margins of CI II restorations. American Journal of Dentistry. Accepted 2002. Formattato: Corpo del testo, Allineato a sinistra, Destro 0 pt Ferrari M, Cagidiaco M, Kugel G, Dolci G. Evaluation concentration response after 4 weeks treatment with a flexible, polyethylene whitening strips. Compendium/Special Issue Volume 22, No. 2, 2001. Kugel G, Aboushala A, Zhou X, Gerlach R. Daily Use of Whitening Strips on Tetracycline-Stained Teeth: Comparative Results After 2 Months. Compendium Volume 22, No. 2, 2001. Formattato: Centrato Eliminato: 214¶ 223 Kugel, G., Garcia-Godoy F., Direct Esthetic Adhesive Restorative Materials A Review. The Indian Dentist, No. 7-13, 21, April – June 2001 Papathanasiou A., Bardwell D, Kugel G., A Clinical Study Evaluation a New Chairside and Take-Home Whitening System. Compendium of Continuing Education in Dentistry, Volume 22, No. 4:289-300, April 2001 Goracci C., Gheewalla R., Kugel G., Ferrari M., Orthodonticrestorative treatment of chipped or worn incisors. American Journal of Dentistry, Volume 14, No. 50-55, February, 2001 Kugel G., Provisional Esthetic Enhancements Following Initial Treatment to Correct Anterior Wear, Esthetic Technique, Volume 1, No. 1:3-7, April 2001 Leinfelder K, Kugel G., Flowable Compomers, Dialogues in Esthetic Dentistry, Volume 2, No. 1:7-8, April 2001 Javaheri DS, Kugel G., Janis JN. Current Status of At-Home Bleaching. Practical Procedures and Aesthetic Dentistry, Volume 13, No. 1:10-13, January/February 2001 Perry R, Kugel G. Two-Year Clinical Evaluation of a HighDensity Posterior Restorative Material. Compendium of Continuing Education in Dentistry, Volume 21,No. 12:10671080, December 2000 Weinstock E, Skoulas A, Kugel G, Aboushala A. The Myth of Dentist-Patient Confidentiality. Compendium of Continuing Education in Dentistry, Volume 21, No. 12:1056-1064, December 2000 Kugel G. Direct and Indirect Adhesive Restorative Materials: A Review. American Journal of Dentistry, Volume 13, Special Issue, No. 35-40, November, 2000. Formattato: Centrato Eliminato: 214¶ 224 Kugel G, Garcia-Godoy F. Direct and Indirect Esthetic Adhesive Restorative Materials: A Review. Dental News, Volume VII, Number 3:29-39, 2000 Perry R, Kugel G, Kunzelmann KH, Flessa HP, Estafan D. Composite Restoration Wear Analysis: Conventional Methods vs. Three-Dimensional Laser Digitizer. JADA, Vol. 131, No. 10:, p.1472-1477, October 2000. Papathanasiou A, Bardwell D, Kugel G. Combining In-Office and Take-Home Whitening Systems. Contemporary Esthetics and Restorative Practice. Vol. 4. No. 8: 88, September 2000 Kugel G, Garcia-Godoy, F. Direct Esthetic Adhesive Restorative Materials: A Review. Contemporary Esthetics and Restorative Practice. Vol. 4. No. 9: 6-10, September 2000. Kugel G, Kastali S. Tooth-Whitening Efficacy and Safety: A Randomized and Controlled Clinical Trial. Compendium 21, S29, 16-21, July 2000 Kugel G. Nontray Whitening. Chairside: Compendium. Vol. 21, No. 6, 524-528, June 2000. Kugel G, Ferrari M. The Science of Bonding: From First to Sixth Generation. JADA, Vol. 131:20S-25S, June 2000. Kugel G, Perry R, Ferrari M, Lalicata P. Disinfection and Communication Practices: A Survey of U.S. Dental Laboratories. JADA, Vol. 131:786-792, June 2000. Zervou C, Kugel G, Leone C, Zavras A, Doherty E. Enameloplasty Effects on Microleakage of Pit and Fissure Sealants Under Load: an In-Vitro Study. The Journal of Clinical Pediatric Dentistry. 24(4): 279285, April 2000 Ferrari M, Mannocci F, Mason PN, Kugel G, In vitro leakage of resin-bonded all-porcelain crowns. Journal of Adhesive Dentistry, 1:3:233-242, 1999. Kugel G, Swift EJ, Sorenson JA, Dunne JT, Tucker JH. A prospective clinical evaluation of electronically mixed polyvinyl siloxane impression materials. Compendium, S24:2-22, 1999. Formattato: Centrato Eliminato: 214¶ 225 Petridis H, Hirayama H, Kugel G, Habib C, Garefis P. Shear bond strength of techniques for bonding esthetic veneers to metal. Journal of Prosthetic Dentistry, 82:5:608-614, 1999. Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Clinical evaluation of a one-bottle bonding system for desensitizing exposed roots. American Journal of Dentistry, 12:5:243-249, 1999. Kugel G, Perry R, Hoang E, Hoang T, Ferrari M. Dyract Compomer: Comparison of Total Etch vs. No Etch Technique. Journal of the Academy of General Dentistry, Volume 46, Number 6:604-606, Nov-Dec 1998. Kugel G. Clinical Testing of Surefil. Journal of International Dental Symposia, 5:7, 1998. Ferrari M, Mason PN, Fabranelli A, Mannocci F, Kugel G, Davidson CL. Influence of Tissue Characteristics at Margins on Leakage of Class II Indirect Restorations, Accepted, American Journal of Dentistry, 1998. Ferrari M, Kugel G. Handling of Composites in Posterior Teeth, Compendium, 19:879-892, 1998. Kugel G, Ferrari M. AelitefloTM. To Base or Not to Base, There Is No Question!, Restorative Quarterly, 1:7, April 1998. Karuri AR, Kugel G, Engelking LR, Kumar MSA. Alterations in Catecholamine Turnover Rate in Specific Regions of the Rat Brain Following Acute Exposure to Nitrous Oxide, Brain Research Bulletin, 45:557-561, 1998. Kugel G, Minimale Präpartion für Frontzahnrestaurationen (Minimal Preparation for Anterior Restorations), Phillip Journal, 14:383-384, 1997. Donly K, Vargas M, Meckes M, Sharma A, Kugel G, Hurley E. InVitro Comparison of Restoration Wear and Tensile Strength Following Extended Brushing with Sonicare and Manual Toothbrushes, Journal of Clinical Dentistry, 8:1:30-35, 1997. Zammitti S, Habib C, Kugel G. Use of Environmental Scanning Electron Microscopy to Evaluate Dental Stain Removal, Journal of Clinical Dent, 8:1: 20-25, Winter 1997. Formattato: Centrato Eliminato: 214¶ 226 Samadzadeh A, Aboushala A, Hurley E, Kugel G. A Comparison of Fracture Strength Between PMMA and Resin-Based Provisional Restorations Reinforced with Plasma-Treated Woven Polyethylene Fiber, Journal of Prosthetic Dentistry, 78:5:447-450, November 1997. Kugel G, Perry R, Putignamo A, Ferrari M. Valutazione clinica a due anni dello spectrumTPH nel restauro di lesioni cariose in cavità di classe II in denti permanenti.. Quintessence International, Settembre/Ottobre 1997. Ferrari M, Kugel G. Handling of Composites in Posterior Teeth, Compendium, 19:879-892, 1998. Kugel G. Buying Right, Journal of the Massachusetts Dental Society, 46:2:12-14, October 1997. Perry RD, Kugel G, Habib CM, McGarry P, Settembrini L. A Two Year Clinical Evaluation of TPH for Restoration of Class II Carious Lesions in Permanent Teeth, General Dentistry, 45: 4:344-349, July/August 1997. Ferrari M, Mannocci F, Cagidiaco MC, Kugel G. Short-Term Assessment of Leakage of Class V Composite Restorations Placed In Vivo, Clinical Oral Investigation, 1:2:61-64, June 1997. Kugel G, Perry R, Hoang E. Effective Tooth Bleaching in 5 Days: Using a Combined In-Office and At-Home Bleaching System, Compendium, 18:4:378-383, April 1997. Abdel-Latif M, Kugel G, Norris L, Kabani S. Nd: Yag Laser and Conventional Techniques in Bone Surgery, Cairo Dental Journal, 13:1:225-230, 1997. Kugel G. Classification and Application of Cementation Alternatives, Signature: The Art and Science of Modern Dentistry, Fall 1997. Ferrari, M, Cagidiaco, Kugel G, Davidson CL. Dentin Infiltration by Three Adhesive Systems in Clinical and Laboratory Conditions, American Journal of Dentistry, 9:6:240-244, December 1996. Weiner RS, Weiner LK, Kugel G. Teaching the Use of Bases and Liners: A Survey of North American Dental Schools, JADA, 127:11:1640-1645, November 1996. Formattato: Centrato Eliminato: 214¶ 227 Kugel G, Perry RD, Habib CM, McGarry P. A Two Year Clinical Evaluation of Pertac Hybrid for Restoration of Class II Carious Lesions in Permanent Teeth, Compendium, November 1996. Ferrari M, Cagidiaco MC, Kugel G. Leakage of Class V Resin Composite Restorations Placed in Vivo, American Journal of Dentistry, October 1996. Aboushala A, Kugel G, Hurley E. Class II Composite Resin Restorations Using Glass-Ionomer Liners: Microleakage Studies, Journal of Clinical Pediatric Dentistry, 21:1:67-70, Fall 1996. Agawal RK, Kugel G, Karuri A, Gwosdow AR, Kumar, MSA. Effects of Low and High Doses of Nitrous Oxide on Preproenkephalin on RNA and Its Peptide Methionine Enkephalin Levels In the Hypothalamus, Brain Research, 730:1,2:47-51, August 1996. Ferrari M, Cagidiaco MC, Kugel G. All -Ceramic Fixed Restorations: A Preliminary Clinical Evaluation, Practical Periodontics Aesthetic Dentistry, 8:1:73-80, Jan-Feb 1996. Habib C, Smith S, Kugel G, Aboushala A. Dimensional Stability of Elastomeric Impressions After Long-Term Disinfection, Journal of Prosthetic Dentistry, January 1996. Ferrari M, Kugel G. IPS - Empress Crowns: Clinical Reports, Practical Periodontics and Aesthetic Dentistry, 1996. Kugel G, Bardwell DN. Restoration of a Class V Lesion Using a New Compomer Material, Signature: The Art and Science of Modern Dentistry, 14-17, November 1995. Kugel G. The Changing Face of Oral Health Care, Feature Article, Tuftonia, 27, Spring 1994. Ferrari M, Dalloca L, Kugel G, Bertelli E. An Evaluation of the Effect of the Adhesive Luting on Microleakage of the IPS Empress Crowns, Practical Periodontics and Aesthetic Dentistry, 6:4:15-24, May 1994. Fischman SL, Kugel G, Truelove RB, Nelson BJ, Cancro LP. The Motivational Benefits of a Dentifrice Containing Baking Soda and Hydrogen Peroxide Used, The Journal of Clinical Dentistry, 3:3 8892, 1992. Formattato: Centrato Eliminato: 214¶ 228 Russell DA, Kugel G. Preceptor Program: An Alternative Mode of Instruction for the Slowly Progressing Dental Student, Journal of Dental Education, 55:1:36-37, January 1991. Champion MA, Kugel G, Gruskowski C. Evaluation of a New Intraoral Isolation Device, Operative Dentistry, 16:181-185, 1991. Kugel G, Zive M, Agawal RK, Beumer JR, Kumar AM. Effects of Nitrous Oxide on the Concentration of Opioid Peptides, Substance P, and LHRH in Brain and β-Endorphin in the Pituitary, Anesthesia Progress, 38:206-211, 1991. Kugel G, Letelier M, Zive H, King JC. Nitrous Oxide and Infertility, Anesthesia Progress, 37:4:176-180, July 1990. Kugel G, Zive M, Norris L. Nitrous Oxide and Occupational Exposure, Journal of the Society for the Advancement of Anesthesia in Dentistry, 7:10:266-276, May 1990. Kugel G, Zive M, Norris L. N2O/O2 - It's No Laughing Matter, Review Article, Journal of the American Analgesia Society, 24:1:14-16, March 1990. Kugel G, Norris L, Zive M. Nitrous Oxide; Occupational Exposure: It's Time to Stop Laughing. Anesthesia Progress, 36:6:252-257, 1989. King J C, Kugel G, Zahniser D, Wooledge K, Damassa D, Alexsavich B. 3-D Analyses Reveal Changes in Populations of LHRH Cell Bodies Following Gonadectomy, Peptides, 8:721-735, August 1987. King JC, Lechan RM, Kugel G, Anthony ELP. Acrolein: A Fixative for - Immunocyto-chemical Localization of Peptides in the Central Nervous System, The Journal of Histo-chemistry and Cytochemistry, 31:1:62-68, January 1983. Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Centrato Eliminato: 214¶ 229 ABSTRACTS Perry R, Kugel G, Shrama S, Ferreira S, Clinical Evaluation of a LED Curing Light, Journal of Dental Research, 83: 540 March 2004 Kugel G, Ferreira S, Sharma S, Barker M L, Garlach R W, Comparison of Daytime and Nighttime Brush-Applied Whitening Systems, Journal of Dental Research, 83:1912 March 2004 Formattato: Tipo di carattere: (Predefinito) Arial Papathanasiou A, Kastali S, Clinical Evaluation of a New AdhesiveComposite System, Journal of Dental Research, 83:538 March 2004 Petkevis J, Alfaro M, Doherty E H, Kugel G, Kanca J, Self-etch adhesive bond strength at two time intervals, Journal of Dental Research, 83: 465 March 2004 Bedi A, Hirayama H, Kugel G, Forgione A G, Surface Roughness and Irregularities of Castings using Different Iinvestment Techniques, Journal of Dental Research, 83: 1680 March 2004 Kugel G, Papathanasiou, Clinical Evaluation of Two Different In-office Tooth Whitening Systems, Journal of Dental Research, 28: 897 March 2003 Formattato: Tipo di carattere: (Predefinito) Arial, Non Corsivo Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial, Non Corsivo Aboushala, A, Kugel G, Sharma S, Ferreira S, SonicareToothbrush Whitening Effect after Bleaching Treatment, Journal of Dental Research, 82: 614, March 2003 Formattato: Tipo di carattere: (Predefinito) Arial Anderson C, Kugel G, Aboushala, A, Sharma S, Ferreira S, Rebound Evaluation of Post-Bleaching Maintenance Utilizing Manual and Electric Toothbrushes; Quantitative Assessment by Digital Photography, Journal of Dental Research, 82: 605, March 2003 Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: (Predefinito) Arial, Corsivo Kugel G, Aboushala, A, Zhou X, Gerlach R Six-month Continuous Use of Two At-home Professional Bleaching Systems on Tetracycline Stain, Journal of Dental Research, 82: 32, March 2003 Anderson C, Kugel G, Ferreira S, Aboushala, A, Sharma S, Six-month Rebound Evaluation of Subjects Treated with a 15% Carbamide Peroxide Gel; Quantitative Assessment by Standard Digital Photography, Journal of Dental Research, 82: 1303, March 2003 Perry R, Papathanasiou A, Kugel G, Davidiian E, A Comparison of Two Flowable Composite Materials in Posterior Restorations Journal of Dental Research, 82: 256, March 2003 Formattato: Centrato Eliminato: 214¶ 230 Watts R, Joffre E, Doherty E, Kugel G, Shear Bond Strength Investigation of an Experimental Self-etching Bonding System, Journal of Dental Research, 82: 566, March 2003 Anderson C, Kugel G, Perry R, Garcia-Godoy F, Evaluation of an Experimental One-Step Composite Polishing System, Journal of Dental Research, 81: 1267, March 2002 Anderson C, Sethi S, Kugel G, Perry R, Garcia-Godoy F, Comparison of Surface Gloss and Time by Three Composite Polishing Systems, Journal of Dental Research, 81: 1273, March 2002 Kugel G, Aboushala A, Zhou X, Gerlach R W, Use of Whitening Strips on etracycline: Results after four months, Journal of Dental Research, 81: 2442, March 2002 Kim M S, Reusch B, Hoffmann H, Doherty E H, Kugel G, Surface Wettability of Saliva and Blood Plasma During Setting of Impression Materials, Journal of Dental Research, 81: 2660, March 2002 Nguyen T, Doherty E H, Aboushala A, Kugel G, Perry R, Effect of Chemomechanical Caries Removal System on Microleakage of Composite Resin Restorations, Journal of Dental Research, 81: 3391, March 2002 Anderson C, Kugel G, Rebound Evaluation of Tetracycline Stained Subjects Treated with a 6.5% Hydrogen Peroxide Gel; Quantitative Assessment by Standard Digital Photography, Journal of Dental Research, 81: 3488, March 2002 Perry R, Gheewalla E, Kugel G, A Comparison of Three Electric Toothbrushes on Orthodontic Bracket Retention, Journal of Dental Research, 80: 590, 2001 Kim MS, Doherty EH, Kugel, G, Flow Under Pressure of Four Impression Materials Using Shark-Fin Device, Journal of Dental Research, 80: 624, 2001 Kastali S, Papathanasiou A, Perry R, Kugel G, Clinical Evaluation Of A Light To Heat Activated Bleaching System, Journal of Dental Research, 80: 926, 2001 Formattato: Centrato Eliminato: 214¶ 231 Kugel G, Kastali S, Sagel P, Gerlach R, Six-Month Clinical Response with Whitening Strips: Comparison to Placebo, Journal of Dental Research, 80: 1174, 2001 Lokko NN, Kugel G, Habib C, Doherty E, Rand W, In Vitro Bond Strength Evaluation of Resin, Modified Glass Ionomer Cements, Journal of Dental Research, 80: 1304, 2001 Verdier A, Kugel G, Habib C, Comparison of Surface Finish Produced on Resin Composites following Extended Brushing With A Manual Toothbrush and Sonicare, Journal of Dental Research, 80: 1337, 2001 Perry R, Kugel G, Aboushala A, Two-Year Clinical Evaluation of a HighDensity Posterior Restorative, Journal of Dental Research, 79:158, 2000. Fabianelli A, Vichi A, Kugel G, Ferrari M, Influence of Self-etching Priming Bonding Systems on Sealing Ability of Class II Restorations: Leakage and SEM Evaluation, Journal of Dental Research, 79:305, 2000. Bardwell D, Habib C, Kugel G, Mehta N, Leone C, Microleakage of Previously Restored Class II Restoratives After Exposure to 10% Carbamide Peroxide, Journal of Dental Research, 79:306, 2000. Kastali S, Papathanasiou K, Perry R, Kugel G, Clinical Evaluation of a New Hybrid Composite, Journal of Dental Research, 79:333, 2000. Zervou C, Kugel G, Leone C, Zavras A, Doherty E, White G.E., Enameloplasty and Load Effects on Microleakage of Sealants (in vitro), Journal of Dental Research, 79:1688, 2000. Papathanasiou K, Kastali S, Perry R, Kugel G, Clinical Evaluation of Light Cured Flowable Compomere in Class V Restorations, Journal of Dental Research, 79:1735, 2000. Rassovsky M, Hirayama H, Habib C, Kugel G, The Expansion of Various Luting Agents Used to Cement Post & Core: An in vitro study, Journal of Dental Research, 79:2327, 2000. Naidu K, Kugel G, Habib C, Class II Composite Restorations: Microleakage Using Three Different Curing Systems, Journal of Dental Research, 79:2466, 2000. Formattato: Centrato Eliminato: 214¶ 232 Habib C, Kugel G, Effect of Aging on Three Enamel Dentin Adhesive Systems, Journal of Dental Research, 79:2475, 2000. Aboushala A, Kugel G, Efthimiadis N, Korchak M, Efficacy of a Computer-controlled Injection System of Local Anesthesia, in vivo, Journal of Dental Research, 79:2775, 2000. Aboushala A, Mehta N, Forgione A, Kugel G, Chapman R. Vertical Dimension and Electromyography of Masseters in Complete Denture Patients, Journal of Dental Research, 78:2911, 1999. Nam C, Kugel G, Habib C. Changes in Enamel Surfaces After Take Home Bleaching Treatment in vitro, Journal of Dental Research, 78:1695, 1999. Perry R, Kugel G. One-Year Clinical Evaluation of a High-Density Posterior Restorative, Journal of Dental Research, 78:1628, 1999. Lalsingh C, Hurley E, Hassan M, Trushkowsky R, Kugel G, Leone C. Effects of Curing Lights on Microleakage in Class V Composite Restorations, Journal of Dental Research 78:1601, 1999. Papathanasiou A, Kastali G, Kugel G, Bardwell D, Hurley E. Microleakage Evaluation of Three Class II Composite Restorative Techniques in vitro, Journal of Dental Research 78:1600, 1999. Hurley E, Aboushala A, Perry R, Kugel G. Microleakage in Class II Restorations Using a New Posterior Composite, Journal of Dental Research 77:487, June 1998. Drukteinis S, Hurley E, Perry R, Kugel G. The Performance of Aluminum Oxide and Cojet Microetchant Systems, Journal of Dental Research 77:506, June 1998. Gheewalla E, Perry R, Kugel G. Effect of Powered Toothbrushes on Orthodontic Bracket Adhesion in vivo, Journal of Dental Research, 77:506, June 1998. Formattato: Centrato Eliminato: 214¶ 233 Kugel G, Karuri A, Kumar MSA. Alterations in the Cathecholamine Turnover Rate in Specific Regions of Rat Brain Following Acute Exposure to Nitrous Oxide, Journal of Dental Research 77:921, June 1998. Ferrari M, Mason PN, Fabianelli A, Kugel G, Davidson CL. Influence of Different Margin Substrates on Leakage of Class II Indirect Restorations, Journal of Dental Research 77:2248, June 1998. Aboushala A, Kugel G, Perry R, Leone C. Resin-Ionomer Restoration of Molar Furcations in Humans, Journal of Dental Research 77:2573, June 1998. Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Clinical Evaluation of SB1 Root Desensitization with/without Acid Etching. Journal of Dental Research 77:2586, June 1998. Ferrari M, Mannocci F, Innocenti M, Kugel G, Davidson CL. Clinical Evaluation of Dyract AP and Fuji IX to Build up Abutments for Porcelain Crowns, Journal of Dental Research 77:2598, June 1998. Kastali S, Kugel G, Perry R, Papathanassiou A. Combined In-Office and At-Home Bleaching Systems: An Evaluation, Journal of Dental Research 77:2604, June 1998. Perry R, Kugel G, Kastali S. Evaluation of a Non-Hydrogen Peroxide At-Home Bleaching System, Journal of Dental Research 77:2605, June 1998. Kugel G, Squier C. Fact vs. Fiction: The Transfer of Scientific Knowledge into the Dental Curriculum, Journal of Dental Research 77:4, March 1998. Aboushala A, Mehta N, Forgione A, Kugel G, Chapman R, Clark RE. Vertical Dimension and Electromyography of Sternocliedomastoids in Complete Denture Patients, Journal of Dental Research, 77:456, March 1998. Chafka A, Mehta N, Kugel G, Hayes C, Forgione A. Effect of Graded Increases in Vertical Dimension on Cervical Flexor Strength, Journal of Dental Research 77:735, March 1998. Kugel G, Lalicata PJ, Perry R. Survey of U.S. Dental Impression Materials and Techniques, Journal of Dental Research, 76:1343, March 1997. Formattato: Centrato Eliminato: 214¶ 234 Daryabegi Y, Perry R, and Kugel G. Differences Shear Bond Strength of Three Dentin Bonding System, Journal of Dental Research, 76:1387, March 1997. Fu A, Mehta N, Forgione A, Clark E, Hayes C, Kugel G. Abdallah E. Maxillomandibular Relationship in TMD Patients Before and After Short Term Bite Plate Therapy, Journal of Dental Research, 76:2363, March 1997. Hoang E, Kugel G. and Perry R. Combined in Office and Home Applied Bleaching System, Journal of Dental Research, 76:2476, March 1997. Perry R, Kugel G, McGarry P, Hurley E. An In Vivo Subcutaneous Investigation of a Resin-Ionomer, Journal of Dental Research, 76:2499, March 1997. Aboushala A, Mehta N, Forgione A, Kugel G. Chapman R. and Clark RE. Vertical Dimension Effects on Strenocleidomastoid Strength in Complete Denture Patients, Journal of Dental Research, 76:3185, March 1997. Bahram R, Aboushala A, Kugel G, Perry R. Compomer Effects on Microleakage in Class II Composite Resin Restorations, Journal of Dental Research, 76:3236, March 1997. Druktenis S, McGarry P, Aboushala A, Kugel G, Habib C. Effect of Adhesives on Microleakage Between Dentin and Light Cured Glass Ionomer Liners, Journal of Dental Research, 76:3238, March 1997. Yau L, Perry R, Kugel G. Three Body Wear of Light Cured Flowable Composites, Journal of Dental Research, 76:3276, March 1997. McSweeney T, Perry R, Aboushala A. Kugel G. Different Liners in Class II Composite Resin Restorations, Journal of Dental Research, 76:3283, March 1997. Vaughn V, Kugel G, Perry R, Noonan ST. Measuring Flow of Elastomeric Impression Materials Using the Shark Fin Device, Journal of Dental Research, 76:3292, March 1997. Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Dentin Infiltration by Three Adhesive Systems in Clinical and Laboratory Conditions, American Journal of Dentistry, 9:6, December 1996. 235 Formattato: Centrato Eliminato: 214¶ Habib C, Smith C, Kugel G, Aboushala A. Comparison of Dimensional Stability of Elastomeric Impression After Immersion Disinfection, Journal of Dental Research, 75:357, March 1996. Sharma A, Kugel G, Hurley E. Evaluation of the Effect of Sonic and Manual Toothbrushes on Cemented Crowns, Journal of Dental Research, 75:361, March 1996. Samadzadeh A, Aboushala A, Kugel G. A Comparison of Fracture Strengths Between PMMA and Resin-Based Provisional Restorations Reinforced with Plasma-Treated Woven Polyethylene Fiber, Journal of Dental Research, 75:369, March 1996. Marcus A, Bender G, McGarry P, Kugel G. Comparison of Dental Cements Shear Bond Strength to a Semi-Precious Alloy Surface In Vitro, Journal of Dental Research, 75:398, March 1996. Vaughn V, Bardwell D, Kugel G, Perilli. Follow-Up Comparing Three Polishing Systems to Glazed Porcelain Utilizing Profilometry, Journal of Dental Research, 75:1038, March 1996. McSweeney T, Perry R, Kugel G. Profilometry Comparison of Polished Porcelain. Journal of Dental Research, 75:1039, March 1996. Bhatt A, Gheewalla E, Perry R, Kugel G. Comparison of a Compomer and Resin Cement for Bonding of Orthodontic Bracket, Journal of Dental Research, 75:1259, March 1996. Perry R, Kugel G, Kunzelmann KH, Flessa HP, Mehi A, Hickel R. A Composite Study of Wear Analysis Methods of In-Vivo Posterior Composite Restorations, Journal of Dental Research, 75:1910, March 1996. Lee K, Aboushala A, Kugel G. Microleakage of Class II Composite Resin Restorations Using Different Placement and Light Cure Techniques In Vitro, Journal of Dental Research, 75:2168, March 1996. Formattato: Centrato Eliminato: 214¶ 236 Perry R, Kugel G, Kunzelmann KH, McGarry P. Two-Year Evaluation of a Hybrid Composite for Posterior Restorations. Journal of Dental Research, 75:2181, March 1996. Prezioso A, Kugel G, Perry R. Microleakage: A Comparison of Three Chairside Ceramic Repair Kits In Vitro. Journal of Dental Research, 75:2965, March 1996. Hoang E, Perry R, Aboushala A, Kugel G. Comparison of Microleakage Using Etched and Non-Etched Techniques in Class V Restorations, Journal of Dental Research, 75:2966, March 1996. Vaughn V, Aboushala A, Habib C, Kugel G. Comparison Between Two Sealants for Reducing Class II Composite Resin Microleakage In Vitro, Journal of Dental Research, 75:3017, March 1996. Beaber W, Arbree N, Kugel G. Pilot study: A Skin Protectant for Latex-Glove-Induced Dermal Sensitivity Reaction, Journal of Dental Research, 75:3185, March 1996. Smith N, Sharma A, Habib C, Perry R, Kugel G. Comparison of a Cordless Curing Light and a Single Unit Curing Light, Journal of Dental Research, 74:495, March 1995. Vaughn V, Bardwell D, Kugel G, Perilli R. Comparing Three Polishing Systems to Glazed Porcelain Utilizing Profilometry, Journal of Dental Research, 74:220, March 1995. Resnick S, Prezioso A, Kugel G, Smith C, McGarry P. Effect of Surface Treatments on Microleakage of Composite - Ceramic Repair, Journal of Dental Research,. 74:228, March 1995. Joseph A, Perry R, Kugel G, Smith C. Effects of Varying Concentrations of 4-META on Tensile Strength on Bonding Composite to Dentin, Journal of Dental Research, 74:495, March 1995. Morrill F, Galburt R, Kugel G, Habib CM. Comparison of Bond Strength Formed Between Amalgam and Composite by Varying the Ratio of Spherical to Lathe Cut Particle, Journal of Dental Research, 74: 743, March 1995. Zammitti S, Kugel G, Habib C. Environmental Scanning Electron Microscope Study Evaluating the Efficacy of a Sonic Toothbrush, Journal of Dental Research, 74:970, March 1995. Formattato: Centrato Eliminato: 214¶ 237 Mehta N, Kugel G, Lamkin J, Bansal S, Forgione A. Effectiveness of Electronic Anesthesia in Controlling Pain During Periodontal Scaling, Journal of Dental Research, 74:972, March 1995. McSweeney T, Perry R, Kugel G. Tensile Strength of Dentin Bonding Agents With Different Acid Etch Preparations, Journal of Dental Research, 74:1107, March 1995. Supnet L, Bhatt A, Aboushala A, Bardwell D, Smith C, Kugel G. Microleakage of Three Experimental Dentin Primers With Altered HEMA Concentrations, Journal of Dental Research, 74:1112, March 1995. Perry R, Kugel G, Habib C, McGarry P, Champion M. TwoYear Evaluation of a Hybrid Composite for Posterior Restorations, Journal of Dental Research, 74:1224, March 1995. Kugel G, Court MH, Agarwal RK, Kumar MSA. Effects of Nitrous Oxide on Preproenkephalia mRNA and Methionine Enkephalin, Journal of Dental Research, 74:1309, March 1995. Bahram R, Kugel G, Mclure T, Habib C. Comparison of Polishability of Three Composite Materials, Journal of Dental Research, 74:1386, March 1995. Aboushala A, Kugel G, Habib C. Microleakage Class II Composite Restorations Using Glass Ionomer Liner, Journal of Dental Research, 74:1398, March 1995. Shayegan A, Aboushala A, Kugel G. Microleakage of Class II Composite Restoration Using a Glass Ionomer, Liner and Base, Journal of Dental Research, 74:1399, March 1995. Smith N, Gheewalla E, Kugel G, Habib C. Evaluation of Effects of a Sonic Toothbrush on the Bond Strength of Bonded Orthodontic Appliances, Journal of Dental Research, 74:1414, March 1995. Ferrari M, Kugel G, Davidson CL. In Vivo and In Vitro Hybrid Layer Formation, IADR-CED Meeting, Lubiana, 1995. Habib C, Smith C, Kugel G, Aboushala A. Dimensional Stability of Elastomeric Impressions After Long Term Disinfection, Journal of Dental Research, 73:409, 1994. Formattato: Centrato Eliminato: 214¶ 238 Morrill F, Galburt R, Kugel G, Zive M, Habib C. Comparison of Different Shaped Particles of Amalgam Alloy Bonded to Composite and Dentin with 4-Methacryloxyethyl Trimellitate Anhydride, Journal of Dental Research, 73:221, 1994. Bahram R, Kugel G, Zive M, Habib C, Golden M. Comparison of Bond Strength of Two Dentin Bonding Systems to Radicular Dentin, Journal of Dental Research, 73:199, 1994. Mehta N, Kugel G, Al Shuria A, Sands M, Forgione A. Effect of Electronic Anesthesia T.E.N.S. on T.M.J. and Orofacial Pain, Journal of Dental Research, 73:358, 1994. Kugel G, Smith N, Sharma A, Habib C, Perry R. A Comparison of a Cordless Curing Light and a Single Unit Curing Light, Journal of Dental Research, 73:406, 1994. Zive M, Champion M, Kugel G. Marginal Microleakage Around Tooth-Colored Inlay Systems, Journal of Dental Research, 72:307, 1993. Ghazinouri R, Zammitti S, Zive M, Kugel G, Habib C. Microleakage Using a New Technique for Posterior Composite Restorations, Journal of Dental Research, 72:308, 1993. McGarry P, Kugel G, Habib C, Perry R. Clinical Evaluation of a Small Particle Composite to Treat Root Caries & Cervical Erosions, Journal of Dental Research, 72:349, 1993. Bellucci A, Kugel G, Habib C, Zive M. Adhesion Strengths of Four Luting Agents with Various Core Buildup Materials, Journal of Dental Research, 72:361, 1993. Habib C, Kugel G, Herr K. Two-Year Evaluation of Composite Restoration of Root Surface Caries After Chemo-Mechanical Excavation, Journal of Dental Research, 72:381, 1993. Kugel G, Habib C, Zammitti S. Enamel and Dentin Surfaces After Treatment With Adhesion Conditioners Using the Environmental SEM, Journal of Dental Research, 72:387, 1993. Agarwal R, Zive M, Kugel G, Gwosdow A, Kraytsberg G, Kilpatrick D, Kumar A. Nitrous Oxide Effects on the Expression of Brain Opiate System, Journal of Dental Research, 71:913A, March 1992. Formattato: Centrato Eliminato: 214¶ 239 Jong G, Zive M, Kugel G, Habib C. Surface Treatment Effects on Porcelain Composite Bonding, Journal of Dental Research, 71:1372, March 1992. Thomas K, Kugel G, Habib CM. Comparison of Dentin Surfaces after Treatment with Dentin Bonding Primers Using the Environmental Scanning Electron Microscope, Journal of Dental Research, 71:1390, March 1992. Habib C, Kronman J, Kugel G. One-year Evaluation of Composite Restoration for Root Surface Caries after ChemoMechanical Excavation, Journal of Dental Research, 71:795, March 1992. Kugel G, Achour A, Zive M. A Comparison of Marginal Microleakage Around Porcelain and Resin Inlay Systems, Journal of Dental Research, 70:990, April 1991. Habib C, Kronman J, Kugel G, Tutin, R. Dentinal Bonding and Composite Restoration of Root Surface Caries after ChemoMechanical Excavation, Journal of Dental Research, 70:1025, April 1991. Bellucci A, El Alfy H, Kugel G, Chapman R. Fracture Resistance of Porcelain Related to Polishing and Glazing. Journal of Dental Research, 70:638, April 1991. Latif M, Kugel G, Chapman R, Norris L, Kabani S, Washburn B. Techniques in Bone Surgery. Journal of Dental Research, 70:1956, April 1991. Kugel G, Rider C, Angelopoulos A, Fakitsas A. Evaluation of the Nd:YAG Contact Laser in Oral Surgery. Journal of Dental Research, 69:1172, March 1990. Zive MA, Kugel G, Beumer J, Kumar MSA. Brain Neuropeptide Changes in Rats Exposed to N20, Journal of Dental Research, 69:314, March 1990. Geshnizgani A, Kugel G, Onderdonk A, Delaney M, McDonough P, Habib C, Cisneros R. Effect of Nitrous Oxide on Oral Microorganisms, 89th Annual Meeting, American Society for Microbiology, May 1989. Kugel G, Letelier C, Atallah H, Zive M. Chronic Low Level Nitrous Oxide Exposure and Infertility, Journal of Dental Research, 68:1057, March 1989. Formattato: Centrato Eliminato: 214¶ 240 Kugel G, Norris L, Zive M. Nitrous Oxide: Occupational Exposure, Journal of Dental Research, 68:1058, March 1989. Kugel G, Letelier C, Atallah H, King JC, Gilmore WC. Nitrous Oxide and Infertility, Journal of Dental Research, 67:380, March 1988. Kugel G, Rosenberg L. Effects of Nitrous Oxide Exposure on the Central Nervous System Control of Reproduction in Female Rats, Journal of Dental Research, 66:394, March 1987. King JC, Kugel G, Zahniser D, Wooledge K, Damassa D, Alexsavich B. Sex Differences in the Response of LHRH Neurons to Gonadectomy in the Rat: Three-Dimensional Computer Analyses, Society for Neuroscience, 87, May 1984. King JC, Lechan RM, Kugel G, Anthony ELP. A Fixative for Immunocyto-Chemical Localization of Peptides, Greater New York Dental Meeting, New York, New York, November 1983. Eliminato: Blankenau R. Goldstein RE. Haywood VB. The current status of vital tooth whitening techniques [interview].¶ Compendium of Continuing Education in Dentistry (Jamesburg, NJ). 20(8):781-4, 786, 788 passim; quiz 796, 1999.¶ Caughman WF. Frazier KB. Haywood VB. Carbamide peroxide whitening of nonvital single discolored teeth: case reports. Quintessence International. 30(3):155-61, Mar 1999.¶ Schwachman H, Schuster A: The tetracyclines applied pharmacology. Pediat Clin North Am 3:295, 1956.¶ Mello HS: The mechanism of tetracycline staining in primary and permanent teeth. J Dent Child 34:478, 1967.¶ Albert A, Rees CW: Avidity of the tetracyclines for the cations of metals. Nature 177:433, 1956.¶ Finerman GAM, Milch RA: In vitro binding of tetracyclines to calcium. Nature 198:486, 1963.¶ Stewart DJ: The effects of tetracyclines upon the dentition. Br J Dermat 76:374, 1964. ¶ Stewart RE et al: Pediatric Dentistry. St Louis, CV Mosby Co., p.87, 1982.¶ Swift EJ: A method for bleaching discolored vital ... [172] Formattato: Tipo di carattere: 12 pt Formattato: Tipo di carattere: 12 pt Formattato: Tipo di carattere: 12 pt, Grassetto Formattato: Allineato a sinistra Formattato: Tipo di carattere: 12 pt, Grassetto Formattato: Tipo di carattere: 12 pt, Grassetto Formattato: Tipo di carattere: 12 pt Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Tipo di carattere: 12 pt Formattato: Tipo di carattere: (Predefinito) Arial Formattato: Centrato Eliminato: 214¶ 241 Pagina 4: [1] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 idesir01 08/11/2004 11.38.00 Tipo di carattere: 12 pt Pagina 4: [2] Formattato Tipo di carattere: 11,5 pt Pagina 4: [3] Formattato Tipo di carattere: 11,5 pt Pagina 4: [4] Formattato Tipo di carattere: 12 pt Pagina 4: [5] Formattato Tipo di carattere: 12 pt Pagina 4: [6] Formattato Tipo di carattere: 12 pt Pagina 4: [7] Formattato Rientro: Sporgente 54 pt, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:6 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 54 pt + Rientra di: 54 pt, Tabulazioni: 0 pt, Tabulazione elenco + Non a 18 Pagina 4: [8] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 15/06/2004 10.26.00 gkugel01 28/10/2004 12.00.00 gkugel01 15/06/2004 10.26.00 Tipo di carattere: 12 pt Pagina 4: [9] Formattato Tipo di carattere: 11,5 pt Pagina 4: [10] Formattato Tipo di carattere: 12 pt Pagina 4: [11] Formattato Tipo di carattere: 12 pt Pagina 4: [12] Formattato Tipo di carattere: 12 pt Pagina 4: [13] Formattato Tipo di carattere: 11,5 pt Pagina 4: [14] Formattato Tipo di carattere: 11,5 pt Pagina 4: [15] Formattato Tipo di carattere: 12 pt Pagina 4: [16] Formattato Tipo di carattere: 11,5 pt Pagina 4: [17] Formattato Tipo di carattere: 8 pt Pagina 4: [18] Formattato Tipo di carattere: 12 pt Pagina 4: [19] Formattato Interlinea minima 12 pt Pagina 4: [20] Formattato Tipo di carattere: (Predefinito) Arial Pagina 4: [21] Formattato Normale, Rientro: Sinistro: 0 pt, Interlinea doppia Pagina 4: [22] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 Tipo di carattere: (Predefinito) Arial, 11,5 pt Pagina 4: [23] Formattato Tipo di carattere: 11 pt Pagina 4: [24] Formattato gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.04.00 tufts 08/06/2004 17.16.00 tufts 07/06/2004 11.05.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 tufts 08/06/2004 17.27.00 tufts 08/06/2004 17.28.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.27.00 Tipo di carattere: (Predefinito) Arial Pagina 9: [25] Eliminato and for offering treatment Pagina 9: [25] Eliminato ( Kugel, 2000) Pagina 9: [25] Eliminato also Pagina 9: [26] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [26] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [27] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [27] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [28] Eliminato (Harris et al., 2001) Pagina 9: [28] Eliminato (McMillan et al., 2001). Pagina 9: [29] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [29] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [29] Formattato Tipo di carattere: 11 pt Pagina 9: [30] Eliminato Technological advances in dentistry make it possible for the practitioner to deliver the highest level of care in an efficient and often economical way. With t Pagina 9: [31] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 11/06/2004 9.35.00 Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [32] Formattato Rientro: Prima riga: 0 pt Pagina 9: [33] Eliminato tufts 07/06/2004 11.28.00 tufts 07/06/2004 11.28.00 , being promoted as “the future of dentistry,” Pagina 9: [33] Eliminato awareness and Pagina 9: [33] Eliminato tufts 07/06/2004 11.28.00 Pagina 9: [33] Eliminato tufts 07/06/2004 11.28.00 Pagina 9: [33] Eliminato tufts 07/06/2004 11.28.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.29.00 tufts 07/06/2004 11.29.00 tufts 07/06/2004 11.31.00 tufts 07/06/2004 11.31.00 tufts 07/06/2004 11.31.00 tufts 07/06/2004 11.31.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.31.00 tufts 08/06/2004 17.29.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 so-called: “ L ” Pagina 9: [34] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [35] Eliminato In 2002 one article and more recently Pagina 9: [35] Eliminato two Pagina 9: [35] Eliminato One Pagina 9: [35] Eliminato study Pagina 9: [35] Eliminato reported Pagina 9: [35] Eliminato , whereas Pagina 9: [36] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [37] Eliminato the , Pagina 9: [37] Eliminato Pagina 9: [38] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [39] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [39] Formattato gkugel01 28/10/2004 12.00.00 tufts 08/06/2004 17.28.00 Pagina 9: [41] Eliminato tufts 07/06/2004 11.37.00 Pagina 9: [41] Eliminato tufts 07/06/2004 11.37.00 tufts 08/06/2004 17.29.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.34.00 tufts 07/06/2004 11.33.00 tufts 08/06/2004 17.29.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.39.00 Pagina 9: [45] Eliminato tufts 07/06/2004 11.39.00 Pagina 9: [45] Eliminato tufts 07/06/2004 11.39.00 tufts 07/06/2004 11.39.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.40.00 Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [40] Eliminato Reviews of these articles were in support 4 Pagina 9: [41] Eliminato Pagina 9: [42] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [43] Eliminato discredited Pagina 9: [43] Eliminato findings 5 Pagina 9: [43] Eliminato Pagina 9: [44] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 9: [45] Eliminato It is apparent that t needs Pagina 9: [45] Eliminato for Pagina 9: [46] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 10: [47] Eliminato The lack of knowledge is to the detriment of the dentist and patient alike. Pagina 10: [48] Eliminato need for more knowledge becomes tufts 07/06/2004 11.40.00 Pagina 10: [49] Eliminato tufts 07/06/2004 11.41.00 gkugel01 28/10/2004 12.00.00 gkugel01 11/06/2004 9.35.00 “up to date” dental office Pagina 10: [50] Formattato Tipo di carattere: (Predefinito) Arial Pagina 10: [51] Formattato Allineato a sinistra, Rientro: Prima riga: 0 pt, Spazioprima 0 pt Pagina 10: [52] Formattato gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.38.00 Tipo di carattere: (Predefinito) Arial Pagina 10: [53] Eliminato Bleaching is the most conservative treatment for discolored teeth when compared to resin bonded composites, porcelain veneers or crowns. It offers a simple and economical approach to changing the color of teeth. Success of the treatment depends on a careful diagnosis by the practitioner. Candidates for whitening procedures include patients whose teeth are stained by aging, chromogenic foods, endodontic treatment, tetracycline use and smoking or use of other tobacco products. Acceptable tooth whitening techniques include the in-office technique, dentist-prescribed homeapplied technique, or a combination of the two. The use of hydrogen peroxide (H202) for bleaching teeth dates back to 1995 6. To reduce Pagina 10: [54] Eliminato tufts 07/06/2004 12.04.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 11.49.00 , such as tetracycline stained-teeth, Pagina 10: [55] Formattato Tipo di carattere: (Predefinito) Arial Pagina 10: [56] Formattato Tipo di carattere: (Predefinito) Arial Pagina 10: [57] Formattato Tipo di carattere: (Predefinito) Arial Pagina 10: [58] Eliminato Most clinicians know that hydrogen peroxide is a bleaching agent that can attain a desired whitening effect. Bleaching can also be accomplished with Carbamide Peroxide, a lower concentration of hydrogen peroxide and urea, which breaks down to 3.6% hydrogen peroxide 8,9 .The degree of whitening correlates directly with the amount of contact time and concentration of the active ingredient, the pH and viscosity 9. The side effects are usually diminished when lower concentrations are used. The in-office bleaching treatment using hydrogen peroxide and an accelerating source (heat or light) were predominant until 1989 when Haywood published the first article on nightguard vital bleaching using carbamide peroxide 10. Currently, the in-office bleaching technique employs a 15 40% hydrogen peroxide bleaching agent (heat activated or not), while the dentist prescribed homeapplied technique most commonly uses a 10 - 15% carbamide peroxide gel. The advantages of an in-office procedure are twofold. It does not require patient compliance and immediate results can be accomplished. The disadvantages are the chair side time involved and the cost to the patient, as the procedure usually requires multiple visits. Light-activated chair side bleaching systems potentially offer the benefit of being less time-consuming while producing faster results. Pagina 10: [59] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 12.07.00 Tipo di carattere: (Predefinito) Arial Pagina 10: [60] Formattato Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 10: [61] Formattato Tipo di carattere: (Predefinito) Arial Pagina 10: [62] Formattato Tipo di carattere: 11 pt Pagina 10: [63] Formattato Tipo di carattere: 11 pt Pagina 10: [64] Formattato Tipo di carattere: (Predefinito) Arial Pagina 10: [65] Formattato Tipo di carattere: 11 pt Pagina 10: [66] Formattato Tipo di carattere: 11 pt Pagina 10: [67] Eliminato he introduction of very high intensity Plasma Arc lights and Argon Lasers meets the need of an ever increasing demand for whiter teeth. Pagina 10: [68] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 12.01.00 Tipo di carattere: (Predefinito) Arial Pagina 10: [69] Formattato Tipo di carattere: (Predefinito) Arial Pagina 10: [70] Formattato Normale, Giustificato, Spazioprima 0 pt, Non regolare lo spazio tra testo asiatico e in alfabeto latino, Non regolare lo spazio tra testo asiatico e caratteri numerici, Tabulazioni: Non a 22,5 pt Pagina 10: [71] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 11/06/2004 9.36.00 Tipo di carattere: 11 pt, Non Grassetto Pagina 10: [72] Formattato Tipo di carattere: 11 pt Pagina 10: [73] Formattato Tipo di carattere: 11 pt, Non Grassetto Pagina 10: [74] Formattato Tipo di carattere: 11 pt Pagina 10: [75] Formattato Tipo di carattere: 11 pt, Inglese (U.S.A.) Pagina 10: [76] Formattato Rientro: Prima riga: 0 pt, Spazioprima 0 pt Pagina 10: [77] Eliminato tufts 07/06/2004 12.03.00 Research in vitro has demonstrated that the use of laser-activated hydrogen peroxide did not produce any perceivable color change 11. Another recent in vitro study, and one which should be of concern to the practitioner, has shown that the use of these intense lights does elevate temperature of the bleaching material and as a result caused an increase in intrapulpal temperature. This may have an impact on post bleaching tooth sensitivity and pulpal health 12. Pagina 10: [78] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 tufts 07/06/2004 10.26.00 gkugel01 28/10/2004 12.00.00 gkugel01 04/06/2004 7.01.00 Tipo di carattere: (Predefinito) Arial Pagina 10: [79] Formattato Tipo di carattere: 11 pt Pagina 10: [80] Formattato Tipo di carattere: (Predefinito) Arial Pagina 11: [81] Formattato Non Apice / Pedice Pagina 11: [82] Formattato Non Apice / Pedice Pagina 11: [83] Eliminato Pagina 11: [84] Formattato Tipo di carattere: 12 pt Pagina 11: [85] Cambia Elenchi puntati e numerati formattati Pagina 11: [86] Eliminato tufts 08/06/2004 18.30.00 gkugel01 28/10/2004 12.00.00 ECHANISM OF ACTION Pagina 11: [87] Formattato Tipo di carattere: 12 pt Pagina 11: [88] Formattato gkugel01 11/06/2004 9.36.00 Rientro: Prima riga: 0 pt Pagina 11: [89] Eliminato tufts 08/06/2004 17.42.00 tufts 08/06/2004 17.42.00 tufts 08/06/2004 17.44.00 Mokhlis et al. 2000, Pagina 11: [90] Eliminato Christensen 1989, Sharif et al. 2000, Pagina 11: [91] Eliminato Haywood et al. 1991, 1992, 1993, 1994, Nathanson et al. 1987, Kugel et al. 1997, Kugel et al. 1998 (abstract), Bardwell et al. 2000 (abstract or unpublished data), Papathanasiou et al. 2000 (abstract or unpublished data)] Pagina 15: [92] Eliminato tufts 07/06/2004 10.27.00 Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital bleaching with professional tray or strip systems can yield an evident improvement in appearance within a few weeks. While non-invasive, treatment may need to continue over an extended period. Some individuals will show favorable response after 3-4 months, after which treatment may be discontinued. Duration may be difficult to predict, given the variable clinical manifestations of tetracycline staining. Practitioners and patients should be advised that optimal bleaching of tetracycline staining may necessitate extended daily athome treatment over a period of 3-6 months. The costs, risks, and benefits of the various treatment options must be considered as part of overall patient management Pagina 15: [93] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 04/06/2004 12.57.00 Tipo di carattere: (Predefinito) Arial, 11 pt Pagina 15: [94] Eliminato Different variations of tetracycline and derivates produce different colors in the tooth. When the teeth are exposed to the sunlight, they become darker, with a distinct gray/blue tinge. It is suggested that the reason that the front incisor teeth darken while the molars remain yellow longer is the different exposure to light 3. The discoloration of the permanent dentition depends on the amount and duration of tetracycline use4. The portion of the tooth, color and severity of the stains can be determined by the stage of the tooth development at the time of the drug administration. Tetracycline is incorporated into dentin during tooth calcification intra and post partum, probably through chelation with calcium forming tetracycline orthophosphate 5. It can be deposited in fetal tooth buds when administered in the third trimester of pregnancy or by a child during the development of the tooth (between ages 3 to 4 months and 7 to 8 years) 6, 7 . Colors may vary intensity of gray, blue, brown and yellow. The different banding can also be attributed to the variations of the tetracycline derivates. Clinicians are aware of the results from the use of tetracycline in pregnancy and young children. Even though physicians and dentists should seek other sources of treatment, tetracycline is still the drug of choice for treatment of Rocky Mountain spotted fever and it is also the most prescribed medication for acne. Pagina 15: [95] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 tufts 08/06/2004 18.32.00 Tipo di carattere: 12 pt, Non Tutto maiuscole Pagina 15: [96] Formattato Tipo di carattere: 12 pt, Non Tutto maiuscole Pagina 17: [97] Formattato Rientro: Prima riga: 0,05 pt, A sinistra -0,01 ch Pagina 17: [98] Eliminato tufts 08/06/2004 18.32.00 tufts 08/06/2004 18.38.00 Bleaching Adverse Effects Pagina 20: [99] Eliminato Pagina 20: [100] Formattato gkugel01 15/06/2004 14.44.00 Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Pagina 20: [101] Formattato gkugel01 15/06/2004 14.44.00 Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Pagina 20: [102] Eliminato tufts 08/06/2004 10.02.00 Burrell KH. ADA supports vital tooth bleaching—but look for the seal. Journal of the American Dental Association. 128 Suppl:3S-5S, Apr. 1997. Papathanasiou A., Bardwell D, Kugel G : Combining In Office and Take Home Whitening Systems. Contemporary Esthetics and Restorative Practrice Vol.4:8; 88-91, September 2000. Papathanasiou A., Bardwell D, Kugel G : A Clinical Study Evaluating a New Chairside and Take Home Whitening System. Compendium of Continuing Education in Dentistry, Vol: 22; 4: 289298, April 2001. Pagina 20: [103] Formattato gkugel01 15/06/2004 14.44.00 Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Pagina 20: [104] Eliminato tufts 08/06/2004 10.03.00 Haywwod VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-6, 1989. Pagina 22: [105] Eliminato tufts 08/06/2004 15.41.00 Bardwell D, Papathanasiou A, Deliperi S: In vitro evaluation of tooth color modifications utilizing differing hydrogen peroxide concentrations. Unpublished data 2000. Papathanasiou A, Bardwell D, Kastali S: A clinical study evaluating the efficiency of a new chairside and take home bleaching system. Unpublished data 2000. Pagina 22: [106] Formattato gkugel01 15/06/2004 14.44.00 Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Pagina 22: [107] Eliminato tufts 08/06/2004 17.57.00 Fuss A, Szajkis S, Tagger M: Tublar permeability to calcium hydroxide and the bleaching agents. J Endod 15:362-364, 1989. Goldstein RE, Garber DA: Complete dental bleaching. Quintessence books 1995. Pagina 22: [108] Formattato gkugel01 15/06/2004 14.44.00 Interlinea 1,5 righe, Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Pagina 22: [109] Formattato gkugel01 15/06/2004 14.44.00 Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt Pagina 22: [110] Formattato gkugel01 15/06/2004 14.44.00 Numerazione automatica + Livello:1 + Stile numerazione: 1, 2, 3, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 14,4 pt + Tabulazione dopo: 14,4 pt + Rientra di: 14,05 pt, Non regolare lo spazio tra testo asiatico e in alfabeto latino Pagina 37: [111] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 14/06/2004 10.34.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 idesir01 08/11/2004 11.38.00 Tipo di carattere: Arial, 11 pt, Non Grassetto Pagina 37: [112] Formattato Tipo di carattere: Arial Pagina 37: [113] Formattato Tipo di carattere: Arial, 11 pt Pagina 37: [114] Formattato Corpo del testo 3 Pagina 37: [115] Formattato Tipo di carattere: Arial, 11 pt Pagina 37: [116] Formattato Tipo di carattere: Arial, 11 pt Pagina 37: [117] Formattato Tipo di carattere: Arial, 11 pt Pagina 37: [118] Formattato Tipo di carattere: Arial, 11 pt Pagina 37: [119] Formattato Tipo di carattere: Arial Pagina 37: [120] Formattato Tipo di carattere: Arial, 11 pt Pagina 37: [121] Formattato Tipo di carattere: Arial, 11 pt Pagina 37: [122] Formattato Tipo di carattere: Arial, 11 pt, Apice Pagina 37: [123] Formattato Tipo di carattere: Arial, 11 pt Pagina 111: [124] Formattato Rientro: Sinistro: 0 pt, Numerazione automatica + Livello:1 + Stile numerazione: a, b, c, … + Comincia da:1 + Allineamento: A sinistra + Allinea a: 18 pt + Tabulazione dopo: 36 pt + Rientra di: 36 pt, Tabulazioni: Non a 36 pt Pagina 147: [125] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 15/06/2004 13.21.00 Tipo di carattere: Arial Pagina 147: [126] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [127] Formattato Tipo di carattere: Arial Pagina 147: [128] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [129] Formattato Tipo di carattere: Arial Pagina 147: [130] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [131] Formattato Tipo di carattere: Arial Pagina 147: [132] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [133] Formattato Tipo di carattere: Arial Pagina 147: [134] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [135] Formattato Tipo di carattere: Arial Pagina 147: [136] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [137] Formattato Tipo di carattere: Arial Pagina 147: [138] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [139] Formattato Tipo di carattere: Arial Pagina 147: [140] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [141] Formattato Tipo di carattere: Arial Pagina 147: [142] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [143] Formattato Tipo di carattere: Arial Pagina 147: [144] Formattato Tipo di carattere: (Predefinito) Arial Pagina 147: [145] Formattato Tipo di carattere: (Predefinito) Arial Pagina 137: [146] Formattato Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Pagina 148: [147] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 15/06/2004 13.21.00 Tipo di carattere: (Predefinito) Arial Pagina 148: [148] Formattato Tipo di carattere: Arial Pagina 148: [149] Formattato Tipo di carattere: (Predefinito) Arial Pagina 148: [150] Formattato Tipo di carattere: Arial Pagina 148: [151] Formattato Tipo di carattere: (Predefinito) Arial Pagina 148: [152] Formattato Tipo di carattere: Arial Pagina 148: [153] Formattato Tipo di carattere: (Predefinito) Arial Pagina 148: [154] Formattato Tipo di carattere: Arial Pagina 148: [155] Formattato Tipo di carattere: (Predefinito) Arial Pagina 148: [156] Formattato Tipo di carattere: Arial Pagina 148: [157] Formattato Tipo di carattere: (Predefinito) Arial Pagina 148: [158] Formattato Tipo di carattere: Arial Pagina 148: [159] Formattato Tipo di carattere: (Predefinito) Arial Pagina 148: [160] Formattato Tipo di carattere: Arial Pagina 148: [161] Formattato Tipo di carattere: (Predefinito) Arial Pagina 148: [162] Formattato Tipo di carattere: Arial Pagina 148: [163] Formattato Tipo di carattere: (Predefinito) Arial Pagina 148: [164] Formattato Tipo di carattere: (Predefinito) Arial Pagina 137: [165] Formattato Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Pagina 150: [166] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 28/10/2004 12.00.00 gkugel01 15/06/2004 13.21.00 Tipo di carattere: Arial Pagina 150: [167] Formattato Tipo di carattere: (Predefinito) Arial Pagina 137: [168] Formattato Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Pagina 152: [169] Formattato Tipo di carattere: Arial gkugel01 28/10/2004 12.00.00 Pagina 152: [170] Formattato gkugel01 28/10/2004 12.00.00 gkugel01 15/06/2004 13.21.00 Tipo di carattere: (Predefinito) Arial Pagina 137: [171] Formattato Posizione: Orizzontale: 288 pt, Rispetto a: Pg, Verticale: 2,15 pt, Rispetto a: Paragrafo Pagina 241: [172] Eliminato gkugel01 15/06/2004 10.57.00 Blankenau R. Goldstein RE. Haywood VB. The current status of vital tooth whitening techniques [interview]. Compendium of Continuing Education in Dentistry (Jamesburg, NJ). 20(8):781-4, 786, 788 passim; quiz 796, 1999. Caughman WF. Frazier KB. Haywood VB. Carbamide peroxide whitening of nonvital single discolored teeth: case reports. Quintessence International. 30(3):155-61, Mar 1999. Schwachman H, Schuster A: The tetracyclines applied pharmacology. Pediat Clin North Am 3:295, 1956. Mello HS: The mechanism of tetracycline staining in primary and permanent teeth. J Dent Child 34:478, 1967. Albert A, Rees CW: Avidity of the tetracyclines for the cations of metals. Nature 177:433, 1956. Finerman GAM, Milch RA: In vitro binding of tetracyclines to calcium. Nature 198:486, 1963. Stewart DJ: The effects of tetracyclines upon the dentition. Br J Dermat 76:374, 1964. Stewart RE et al: Pediatric Dentistry. St Louis, CV Mosby Co., p.87, 1982. Swift EJ: A method for bleaching discolored vital teeth. Quint Int 19:607, 1988. Shafer WG, Hine MK, Levy BL: A textbook of Oral Pathology, 3rd Ed. Philadelphia, Saunders, 1974. Jordan RE, Boksman L: Conservative vital bleaching treatment of discolored dentition. Comp Cont Ed Dent 5(10):803-808, 1984. Faunce F. Management of discolored teeth. [Review] [30 refs] Dental Clinics of North America.27(4):657-70, Oct. 1983 . Nathanson D: Vital tooth bleaching: sensitivity and pulpal considerations. J Am Dent Assoc., 128(Suppl): 41S-44S, 1997. Bardwell D, Habib C, Kugel G, Mehta N, Leone L: Microleakage of previously restored Class II restoratives after exposure to 10% carbamide peroxide. JDR 2000 Special Issue Vol.79, abstract 306. P. Yu, A. Aboushala, D. Bardwell. Effect of bleaching on Composite Resin Shear Bond Strength In Vitro. JDR 1999 Vol.78 special issue, abstract #1445 M. MacKAY, R. PERRY, E. SWIFT, M. VARGAS Effects of two home bleaching systems on Enamel surfaces. JDR 1997 special issue abstract #1405 Ultradent Products Opalescence Instructions (1996), Ultradent Products, Inc, South Jordan, UT 84095. Discus Dental Nite White Instructions (1996), Discus Dental Inc, Los Angeles, CA 90064. Dentsply Nupro Gold Instructions, Dentsply Preventive Care, York, PA 17405. Javaheri DS, Janis JN: The efficacy of reservoirs in bleaching trays. Operative Dentistry, 2000, 25, 149-151. Price RBT, Sedarous M, Hiltz G: The pH of tooth-whitening products. J Can Den Ass, Sept. 2000, Vol. 66, No. 8, 421-426. Sun G: The role of lasers in Cosmetic Dentistry Dental Clinics of North America, Vol. 44, No 4, Oct. 2000, 831-849. Blankenau R, Goldstein R, Haywood V: The current status of vital tooth whitening techniques. Compendium of Continuing Education in Dentistry, Aug 1999, Vol. 20, No 8, 781-794. Haywood VB: Nightguard bleaching: current concepts and research. J Am Den Assoc 128(Suppl):19S-25S, 1997. Seals NS, McIntosh JE, Taylor AN: Pulpal reaction to bleaching of teeth in dog. J Dent Res 60:948-953, 1981. Yiming Li, Toxicological Considerations of Tooth bleaching using peroxide containing agents. JADA, April 1997; vol.128; 31S-36S DahlJE, Becher R. Acute Toxicity of carbamide peroxide and commercially available tooth bleaching agent in rats; Journal of dental Research 1995; 74: 710-714 Schulte J,Morrissette D,Gasior E,Czajewski,M. Clinical Changes on the Gingiva as a result of at-home bleaching. Compendium 1993, VolXIV, no.11; 1362-1371 Haywood VB, Leonard RH, Chauncy NF, Brunson WD. Effectiveness, Side Effects and Long Term Status of Nightguard Vital Bleaching. JADA, September 1994 ,vol.125pg 1219-1226 Haywood VB History, safety and effectiveness of current bleaching techniques and applications of the vital bleaching technique. Qunitessence Int 1992; 23:471-488 Michael G Jorgensen, William B. Carroll. Incidence of tooth sensitivity after home whitening treatment. JADA vol.133 August 2002 ;1076-1082 Pohjola R,Browning WD, Hackman ST, Michael ML, Downey MC. Sensitivity and Tooth Whitening Agents. Journal of esthetic and Restorative dentistry 2002; vol2, no.2; 85-91, 2002 Leonard RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and gingival irritation associated with nightguard vital bleaching. Quintessence International; 1997 vol. 28 no. 8; 527-534 Bartelstone HJ. Radioiodine Penetration through Intact Enamel with Uptake by Bloodstream and Thyroid Gland. Journal of Dental Research October 1951; 728-733 Gokay O, Tuncbilek M,Ertan R. Penetration of the pulp chamber by carbamide peroxide bleaching agents on teeth restored with composite resin. J of Endodontics 2000; 27; 92-94 Bowels WH and Ugwuneri Z . Pulp Chamber Penetration by Hydrogen Peroxide Following Vital Bleaching Procedures. J of Endodontics Aug. 1987vol.13 375-377 Jorgensen MG, Caroll WB.Incidence of tooth sensitivity after home Whitening treatment, JADA, 2002 Sep; 133(9):1174 Over the Counter 1.HaywoodVB, Heymann HO. Nightguard vital bleaching. Quintessence Int. 1989; 20:173-6 2.Goldstein RE.In-office bleaching: where we came from, where we are today. Jam Dent Assoc1997;128:11S-15S 3.BurrellKH.ADA supports vital tooth bleaching –but look for the seal. J Am Dent Assoc1997 128:3S-5S. 4.CrollTP, SasaIS.Carbemide peroxide of teeth with dentiogenisis imperfecta discoloration: report of a case. Quintessence Int. 1995; 26:683-6 5.Haywood VB. Night guard bleaching to lighten a restored, nonvital discolored tooth. Compend Continuing Education Dent 1998;19:810-3 6. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth. Compend Contin Educ Dent 1998; 19:810-3 7. Small BW. The application and integration of at-home bleaching into private dental practice. Compend Contin Educ Dent 1998;19:799-806 8.HaywoodVB, Robinson FG.Vital tooth bleaching with nightgaurd vital bleaching. Curr.Opin CosmeticDent1997;4:45-52 9.KugelG,PerryRD, Hoang E,Scherer W.Effective tooth bleaching in 5days: using a combined in office and at home bleaching system . Comp contin Educ Dent 1997 ;18:378-83 10. Kugel G Over the counter tooth whitening Systems Compendium April 2003; 24;4A 376-82 11.Donly KJ, DonlyAS, BaharlooL, et al. Tooth whitening in children, Compend Contin Edu Dent. 2002; 3:22-27