Clinical and antimicrobial evaluation of a mouthwash and toothpaste for xerostomia: A randomized, double-blind, crossover study

Clinical and antimicrobial evaluation of a mouthwash and toothpaste for xerostomia: A randomized, double-blind, crossover study

Journal of Dentistry, 2011-11-01, Volume 39, Issue 11, Pages 757-763, Copyright © 2011 Elsevier Ltd

Abstract

Objectives

Specific toothpaste and mouthwash for xerostomia based on triclosan, fluoride, and mineral salts were studied in order to evaluate their efficacy in improving the quality of life as well as their in vitro antimicrobial action.

Materials and methods

30 patients with dry mouth and hyposalivation confirmed by sialometry were included in a randomized, double-blind, crossover study, during two weeks for each experimental phase. Dryness and oral comfort, difficulty in speaking, chewing, swallowing and using dental prostheses, as well as taste and sleep disorders were evaluated. Values of minimal biocidal and minimal inhibitory concentrations of both products against microorganisms that often cause oral disorders in these patients were determined and compared.

Results

The use of the mouthwash and toothpaste studied improved the dry mouth symptoms, whilst no significant differences when compared with the salivary enzyme substitutes were observed. The test products showed, in general, a higher biocidal and inhibitory action than the control products, with particularly noteworthy action against cariogenic bacteria.

Conclusions

The use of a toothpaste and mouthwash based on triclosan, fluoride, gingival revitalizers and mineral salts, improves the quality of life of patients suffering xerostomia.

Introduction

Saliva is essential both for preserving oral health and for correct oral function. Xerostomia is a term used to describe the subjective (feeling) symptoms of a dry mouth. The objective signs of dry mouth have been categorized as salivary gland hypofunction.

The causes of hyposalivation are diverse, amongst them the most common is the use of certain drugs (diuretics, antidepressants, neuroleptics, cytostatics, antiparkinsonians, antihypertensives and antihistaminics). Other causes are: diabetes, Sjögren’s syndrome and head and neck radiotherapy. Patients affected of hyposalivation usually from the sensation of dry mouth or xerostomia, which is often accompanied by functional oral disorders, such as: difficulties in speaking, chewing and swallowing, taste disturbances, and problems with dental prostheses, when used, which entails a deterioration in the quality of life. Multiple organic manifestations also appear, largely determined by the increase in the build-up of microorganisms on the oral surfaces through the loss of the regulating effect of saliva (physical clearance, modification of bacterial adhesion or direct antibacterial action). In addition, it has been reported that people with dry mouth have an altered microflora, including high proportions of cariogenic bacteria as well as Candida .

The cause of hyposecretion should be eradicated whenever possible. This is sometimes difficult, particularly when the destruction of the salivary glands has occurred or when the cause is the administration of drugs essential for the treatment of other pathologies. The use of saliva-inducing drugs as pilocarpine or cevimeline is the basis of the current treatment for xerostomia. Furthermore, in all cases patients with xerostomia should perform scrupulous oral hygiene keeping the growth of dental plaque under control and, therefore, maintaining both the teeth and gums in a satisfactory state of health. The use of toothpastes and mouthwashes not specifically formulated for xerostomia is unadvisable, as they usually include in their composition certain ingredients (sodium lauryl sulphate, strong flavourings, alcohol, etc.) that produce lack of tolerance and exacerbate the symptoms. Besides presenting an excellent tolerance, it is desirable that the oral hygiene products for xerostomia improve oral symptomatology and act on microorganisms that often cause disorders in the mouth of those patients. The authors hypothesize that new products is clinically more effective in relieving the symptoms of xerostomia

Oral hygiene products (toothpaste and mouthwash) for xerostomia have been developed, based on triclosan, fluoride, gingival revitalizers and mineral salts, whilst their formula contains no sodium lauryl sulphate or alcohol that could impair their tolerance. The aim of this study was to evaluate the efficacy of these toothpaste and mouthwash in the quality of life of patients with xerostomia, as well as to evaluate their in vitro antimicrobial action.

Materials and methods

The study consisted in two parts: a clinical phase, in which the symptoms were evaluated, and a laboratory phase to determine the antimicrobial actions of the studied products.

Clinical study

Study population

Thirty patients were recruited from the Dental Clinic at the University of Murcia (Spain), with the following inclusion criteria: continual symptoms of xerostomia with over 3 months’ evolution; age >18 years; non-stimulated sialometry <0.2 ml/min and sialometry stimulated with 4% citric acid <1 ml/min and >0, both performed with the drainage technique. All the patients signed the informed consent. Individuals who were receiving systemic medication to treat their xerostomia as well as being treated by drugs having some effect on salivation which was planned to be concluded during the patient’s participation in the trial, were excluded. Patients having known hypersensitivity to any of the components of the medications used in the study; pregnant or breastfeeding women; edentulous patients; patients who needed oral inhalants for the treatment of respiratory pathologies; patients who were under treatment with radiotherapy or who expected to initiate this treatment during the conduct of the study and patients with oral mucosa lesions were also excluded.

This investigation conformed to the principles outlined in the Declaration of Helsinki .The study was authorized by the Clinical Research Ethics Committee of Hospital Universitario Virgen de la Arrixaca of Murcia (Spain).

Study design

A double-blind crossover study with randomized treatment distribution was performed ( Fig. 1 ). The study consisted in two experimental phases lasting two weeks each. The test products were used in one of the two phases and the control in the other. The test treatment was a toothpaste d

d Xerolácer ® Toothpaste (Lácer, S.A., Barcelona, Spain).

and a mouthwash e

e Xerolácer ® Mouthwash (Lácer, S.A., Barcelona, Spain).

based on triclosan, fluoride, gingival revitalizers and mineral salts (toothpaste: triclosan 0.3%, fluoride ion 2500 ppm, vitamin E acetate 0.2%, dipotassium glycyrrhicinate 0.15%, panthenol 0.2%, aloe vera 0.05% and mineral salts; mouthwash: triclosan 0.15%, fluoride ion 1500 ppm, vitamin E acetate 0.2%, dipotassium glycyrrhicinate 0.03%, panthenol 0.2%, aloe vera 0.05% and mineral salts). A toothpaste f

f Biotène ® Toothpaste (Laclede International, Brussels, Belgium).

and a mouthwash g

g Biotène ® Mouthwash (Laclede International, Brussels, Belgium).

with salivary enzyme substitutes were used as the control treatment (toothpaste: glucose oxidase 10,000 units, lactoperoxidase 15,000 units, lysozyme 16 mg, lactoferrin 16 mg, fluoride ion 100 ppm; mouthwash: lactoperoxidase 0.002%, lysozyme 0.006%, lactoferrin 0.006%, glucose oxidase 0.002% and xylitol 7.77%). The different products were masked and packed in anonymous bottles in order to preserve the blind during the study. The toothpastes were used twice a day followed by rinses with 10 ml of mouthwash. They were instructed to use the same amount of toothpaste (0.5 g/day). In addition, they were provided with a spray bottle refillable with mouthwash for use ad libitum (four squirts each time). Prior to each experimental phase a washout period was performed in which the patients used a placebo toothpaste (with no active ingredients except fluoride ion 2500 ppm) and a placebo mouthwash (with no active ingredients) for one week. All patients included were provided of a soft toothbrush h

h Lácer ® Soft Toothbrush (Lácer, S.A., Barcelona, Spain).

to be used throughout the study and they were informed that the use of any oral hygiene or treatment product (toothpastes, mouthwashes, sprays) other than those supplied for the study should be avoided. Consumption of treatment chewing gums or sweets was also prohibited, whereas no limit was placed on the amount of liquids imbibed.
Study design.
Fig. 1
Study design.

Five control visits (baseline, to confirm the selection criteria, one at the outset of each experimental period and another at the end) were made. Unstimulated salivary flow was measured by means of the drainage technique. Additionally, the patients filled a modified standard xerostomia quality of life questionnaire at the outset and end of each experimental phase. This questionnaire comprised seven questions on the following symptoms: oral dryness (main symptom defining xerostomia), oral comfort, night time oral dryness, difficulty in speaking, difficulty in chewing and swallowing, taste disturbance and difficulty in wearing dental prostheses, when used. The symptoms were evaluated by using 10 cm visual analogue scales, with the lowest score corresponding to the severest degree of the symptoms. In addition, a mouth examination was performed during all visits and the possible adverse effects of the therapies were investigated ( Fig. 2 ).

Xerostomia questionnaire.
Fig. 2
Xerostomia questionnaire.

Antimicrobial study

The antimicrobial action of test and control toothpastes and mouthwashes was evaluated by means of determining the Minimum Biocidal and Inhibitory Concentrations (MBC and MIC) of these products on different microorganisms. These were selected on the basis of two criteria: on the one hand the microorganisms mostly present in the altered microflora of patients with xerostomia were selected, but also, as the second criterion, the microorganisms that are normally involved in caries, periodontal disease and in mucosal infections were included in the study, though being organic alterations common in cases of hyposalivation. We selected the following microorganisms:

  • cariogenic : Lactobacillus spp., S. mutans , S. salivarius and S. mitis ;

  • periodontogenic : P. intermedia , P. gingivalis , F. nucleatum and A. actinomycetemcomitans ;

  • involved in mucosal infections : Candida albicans , S. aureus and E. coli

Statistical analysis

The number of subjects necessary to detect a significant difference between the two groups by chi-square test (two sided significance level of 5% and power of 80%) was calculated to be 30 per group. Non-parametric Kruskal–Wallis test was performed to determine statistically significant differences between treatments at the beginning and the end of each experimental period. This test was also used to analyse the evolution (difference between the final and baseline score) of the variables in each treatment group. The mixed model for fixed and random effects was used to compare the evolution of the different variables between treatments, as well as to evaluate possible sequence and period effects.

Results

Clinical study

Of the 30 patients included in the trial (27 women, 3 men), 29 completed it. The reason why one patient dropped out has nothing to do with the therapies. The mean age was 60.30 ± 11.56 years. Unstimulated salivary flow increased from 0.04 to 0.08 ml/min and from 0.02 to 0.07 ml/min in patients treated with test and control products, respectively. These differences were not statistically significant. Both treatments significantly improved the main symptom, i.e. oral dryness ( Table 1 ) (test treatment p = 0.0086; control treatment p = 0.0036), although no significant differences between them were observed.

Table 1
Evolution of the symptoms after two weeks’ treatment.
Symptoms Test treatment Control treatment
Before treatment After treatment p -Value Before treatment After treatment p -Value
Oral dryness 4.54 6.28 0.0086 4.07 5.87 0.0036
Oral comfort 4.78 5.99 NS 4.18 6.08 0.0011
Night time oral dryness 7.29 7.88 NS 6.36 7.77 0.0085
Difficulty speaking 5.68 6.88 0.0255 5.74 6.23 NS
Difficulty chewing and swallowing 5.33 6.64 0.0224 5.95 6.85 NS
Distortion of taste 8.08 8.21 NS 8.26 8.31 NS
Difficulty in wearing dental prosthesis 7.56 8.43 NS 7.61 7.96 NS
Global symptoms a 5.95 6.98 0.0123 5.76 6.85 0.0126
NS: not statistically significant.

a Except difficulty in wearing prosthesis.

As regards the rest of symptoms ( Table 1 ), the test treatment reduced the difficulties in speaking ( p = 0.0255), chewing and swallowing ( p = 0.0224). The control treatment improved oral comfort ( p = 0.0011) and night time oral dryness ( p = 0.0085). No statistically significant differences between treatments were found. We use a coefficient representing oral dryness, oral comfort, night time oral dryness, difficulty in speaking without drinking liquids, difficulty chewing and swallowing foods and taste disturbance. The scale of difficulty in wearing prostheses was not included, since its use was not general in the population studied. The improvement measured as the mentioned coefficient was statistically significant in both therapies (test treatment p = 0.0123; control treatment p = 0.0126), although again no statistically significant differences were observed between them.

Antimicrobial study

Values of minimal biocidal concentration are presented in Table 2 . Minimal inhibitory concentrations are shown in Table 3 . All values are indicated as level of dilution of the product able to kill or completely inhibit the visible growth, respectively.

Table 2
Comparison of minimum biocidal concentration values for test and control products against oral microorganisms.
Microorganisms Products
Test mouthwash Control mouthwash Test toothpaste Control toothpaste
Lactobacillus spp. 1/128 1/8 1/128 1/4
S. mutans 1/128 1/8 1/128 1/4
S. salivarius 1/128 1/8 1/128 1/4
S. mitis 1/128 1/8 1/128 1/4
P. intermedia 1/8 1/16 1/2 1/8
P. gingivalis 1/32 1/2 1/8 1/2
F. nucleatum 1/32 1/2 1/8 1/2
A. actinomycetemcomitans 1/8 1/4 1/8 1/2
S. aureus 1/16 1/16 1/16 1/2
E. coli 1/8 1/4 1/8 1/2
C. albicans 1/2 1/2 1/2 1/2
Table 3
Comparison of minimum inhibitory concentration values for test and control products against oral microorganisms.
Microorganisms Products
Test mouthwash Control mouthwash Test toothpaste Control toothpaste
Lactobacillus spp. 1/512 1/64 1/256 1/8
S. mutans 1/512 1/64 1/256 1/16
S. salivarius 1/512 1/64 1/256 1/16
S. mitis 1/512 1/64 1/256 1/16
P. intermedia 1/16 1/64 1/4 1/32
P. gingivalis 1/128 1/4 1/32 1/4
F. nucleatum 1/128 1/4 1/32 1/4
A. actinomycetemcomitans 1/32 1/8 1/32 1/8
S. aureus 1/64 1/32 1/32 1/8
E. coli 1/32 1/8 1/32 1/8
C. albicans 1/8 1/4 1/4 1/4

For the majority of the microorganisms evaluated, the test products showed greater antimicrobial activity that their respective control products, being particularly noteworthy on cariogenic bacteria.

Discussion

The present study is a double-blind crossover study with randomized treatment to evaluate the efficacy of the use of a toothpaste and mouthwash based on triclosan, fluoride, gingival revitalizers and mineral salts, with positive clinical results improving the quality of life of the patients suffering xerostomia. Clinical trials are important methods for evaluating treatment modalities and their impact on current and future clinical practice is great.

Xerostomia is usually accompanied by a series of symptoms, such as oral soreness, difficulty in speaking, chewing and swallowing as well as distortion of taste and sleep, which impair the quality of life of the subjects who suffer from it. In addition, patients with xerostomia present a high prevalence of organic oral alterations, such as: caries, periodontal disease and mucosal infections. One of the methods to reduce the incidence of these alterations is based on oral hygiene.

It is well established that females have much better plaque control than the males. The use of products containing sodium lauryl sulphate (a detergent commonly added to toothpastes and mouthwashing solutions) can worsen xerostomia symptoms. For this reason it is advisable to promote the use of specific products for the oral hygiene of individuals with xerostomia. Such products should be free of irritating substances (sodium lauryl sulphate, strong aromas, alcohol), and include ingredients that will improve the symptoms.

Treatments based on salivary enzyme substitutes have been proved to be effective in patient symptomatology improvement but ineffective in reducing oral cariogenic flora, which is increased in these patients. The results herein presented are in agreement with these. Short-term use of products containing salivary enzyme substitutes improved the quality of life of patients with xerostomia, but their low antimicrobial power and the demineralizing effect of the mouthwash due to its low pH, besides the lack of fluoride, lead to the suspicion that they are not effective in preventing oral diseases such as caries and periodontal diseases.

New specific products, based on triclosan, fluoride, gingival revitalizers and mineral salts, for the oral hygiene of patients with xerostomia have been evaluated. Triclosan is an antiseptic used in products for oral use due to its high antiplaque and antimicrobial efficacies, low toxicity, and because it not causes staining.

In relation to the results of the clinical phase of the study, they have shown that the test treatment improves the oral symptoms of patients with dry mouth, besides presenting an excellent tolerance. Overall, the symptomatology improves with both treatments and was statistically significant with the test treatment for the main symptom or sensation of oral dryness, as well as for difficulty in speaking, difficulty chewing and swallowing and the symptomatology considered as a whole .The reason why the evolution of other symptoms was not statistically significant could be due to the high baseline score of those symptoms, i.e. the absence of severity at the outset of the treatment. Furthermore, the improvement in the oral symptoms did not match up with a significant increase in salivary flow with either of the treatments, although it has been widely established that salivary flow measured at different intervals for the same individual may vary considerably and that the levels of salivary flow do not always correlate with the symptoms.

Optimal oral hygiene and regular oral screening is necessary in individuals with hyposalivation due to an increased risk for caries and periodontal diseases. Saliva substitutes should not only relieve the symptoms of oral dryness, but also provide protection against demineralization.

We may conclude that the use of a toothpaste and a mouthwash based on triclosan, fluoride, gingival revitalizers and mineral salts, improves the quality of life of patients with xerostomia and, in addition, thanks to its antimicrobial action, mainly against cariogenic bacteria, could prove beneficial in preventing caries and other oral disorders that often appear in cases of hyposalivation.

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Clinical and antimicrobial evaluation of a mouthwash and toothpaste for xerostomia: A randomized, double-blind, crossover study M.P. López-Jornet , G. García-Teresa , M. Viñas and T. Vinuesa Journal of Dentistry, 2011-11-01, Volume 39, Issue 11, Pages 757-763, Copyright © 2011 Elsevier Ltd Abstract Objectives Specific toothpaste and mouthwash for xerostomia based on triclosan, fluoride, and mineral salts were studied in order to evaluate their efficacy in improving the quality of life as well as their in vitro antimicrobial action. Materials and methods 30 patients with dry mouth and hyposalivation confirmed by sialometry were included in a randomized, double-blind, crossover study, during two weeks for each experimental phase. Dryness and oral comfort, difficulty in speaking, chewing, swallowing and using dental prostheses, as well as taste and sleep disorders were evaluated. Values of minimal biocidal and minimal inhibitory concentrations of both products against microorganisms that often cause oral disorders in these patients were determined and compared. Results The use of the mouthwash and toothpaste studied improved the dry mouth symptoms, whilst no significant differences when compared with the salivary enzyme substitutes were observed. The test products showed, in general, a higher biocidal and inhibitory action than the control products, with particularly noteworthy action against cariogenic bacteria. Conclusions The use of a toothpaste and mouthwash based on triclosan, fluoride, gingival revitalizers and mineral salts, improves the quality of life of patients suffering xerostomia. 1 Introduction Saliva is essential both for preserving oral health and for correct oral function. Xerostomia is a term used to describe the subjective (feeling) symptoms of a dry mouth. The objective signs of dry mouth have been categorized as salivary gland hypofunction. The causes of hyposalivation are diverse, amongst them the most common is the use of certain drugs (diuretics, antidepressants, neuroleptics, cytostatics, antiparkinsonians, antihypertensives and antihistaminics). Other causes are: diabetes, Sjögren's syndrome and head and neck radiotherapy. Patients affected of hyposalivation usually from the sensation of dry mouth or xerostomia, which is often accompanied by functional oral disorders, such as: difficulties in speaking, chewing and swallowing, taste disturbances, and problems with dental prostheses, when used, which entails a deterioration in the quality of life. Multiple organic manifestations also appear, largely determined by the increase in the build-up of microorganisms on the oral surfaces through the loss of the regulating effect of saliva (physical clearance, modification of bacterial adhesion or direct antibacterial action). In addition, it has been reported that people with dry mouth have an altered microflora, including high proportions of cariogenic bacteria as well as Candida . The cause of hyposecretion should be eradicated whenever possible. This is sometimes difficult, particularly when the destruction of the salivary glands has occurred or when the cause is the administration of drugs essential for the treatment of other pathologies. The use of saliva-inducing drugs as pilocarpine or cevimeline is the basis of the current treatment for xerostomia. Furthermore, in all cases patients with xerostomia should perform scrupulous oral hygiene keeping the growth of dental plaque under control and, therefore, maintaining both the teeth and gums in a satisfactory state of health. The use of toothpastes and mouthwashes not specifically formulated for xerostomia is unadvisable, as they usually include in their composition certain ingredients (sodium lauryl sulphate, strong flavourings, alcohol, etc.) that produce lack of tolerance and exacerbate the symptoms. Besides presenting an excellent tolerance, it is desirable that the oral hygiene products for xerostomia improve oral symptomatology and act on microorganisms that often cause disorders in the mouth of those patients. The authors hypothesize that new products is clinically more effective in relieving the symptoms of xerostomia Oral hygiene products (toothpaste and mouthwash) for xerostomia have been developed, based on triclosan, fluoride, gingival revitalizers and mineral salts, whilst their formula contains no sodium lauryl sulphate or alcohol that could impair their tolerance. The aim of this study was to evaluate the efficacy of these toothpaste and mouthwash in the quality of life of patients with xerostomia, as well as to evaluate their in vitro antimicrobial action. 2 Materials and methods The study consisted in two parts: a clinical phase, in which the symptoms were evaluated, and a laboratory phase to determine the antimicrobial actions of the studied products. 2.1 Clinical study 2.1.1 Study population Thirty patients were recruited from the Dental Clinic at the University of Murcia (Spain), with the following inclusion criteria: continual symptoms of xerostomia with over 3 months’ evolution; age >18 years; non-stimulated sialometry <0.2 ml/min and sialometry stimulated with 4% citric acid <1 ml/min and >0, both performed with the drainage technique. All the patients signed the informed consent. Individuals who were receiving systemic medication to treat their xerostomia as well as being treated by drugs having some effect on salivation which was planned to be concluded during the patient's participation in the trial, were excluded. Patients having known hypersensitivity to any of the components of the medications used in the study; pregnant or breastfeeding women; edentulous patients; patients who needed oral inhalants for the treatment of respiratory pathologies; patients who were under treatment with radiotherapy or who expected to initiate this treatment during the conduct of the study and patients with oral mucosa lesions were also excluded. This investigation conformed to the principles outlined in the Declaration of Helsinki .The study was authorized by the Clinical Research Ethics Committee of Hospital Universitario Virgen de la Arrixaca of Murcia (Spain). 2.1.2 Study design A double-blind crossover study with randomized treatment distribution was performed ( Fig. 1 ). The study consisted in two experimental phases lasting two weeks each. The test products were used in one of the two phases and the control in the other. The test treatment was a toothpaste d d Xerolácer ® Toothpaste (Lácer, S.A., Barcelona, Spain). and a mouthwash e e Xerolácer ® Mouthwash (Lácer, S.A., Barcelona, Spain). based on triclosan, fluoride, gingival revitalizers and mineral salts (toothpaste: triclosan 0.3%, fluoride ion 2500 ppm, vitamin E acetate 0.2%, dipotassium glycyrrhicinate 0.15%, panthenol 0.2%, aloe vera 0.05% and mineral salts; mouthwash: triclosan 0.15%, fluoride ion 1500 ppm, vitamin E acetate 0.2%, dipotassium glycyrrhicinate 0.03%, panthenol 0.2%, aloe vera 0.05% and mineral salts). A toothpaste f f Biotène ® Toothpaste (Laclede International, Brussels, Belgium). and a mouthwash g g Biotène ® Mouthwash (Laclede International, Brussels, Belgium). with salivary enzyme substitutes were used as the control treatment (toothpaste: glucose oxidase 10,000 units, lactoperoxidase 15,000 units, lysozyme 16 mg, lactoferrin 16 mg, fluoride ion 100 ppm; mouthwash: lactoperoxidase 0.002%, lysozyme 0.006%, lactoferrin 0.006%, glucose oxidase 0.002% and xylitol 7.77%). The different products were masked and packed in anonymous bottles in order to preserve the blind during the study. The toothpastes were used twice a day followed by rinses with 10 ml of mouthwash. They were instructed to use the same amount of toothpaste (0.5 g/day). In addition, they were provided with a spray bottle refillable with mouthwash for use ad libitum (four squirts each time). Prior to each experimental phase a washout period was performed in which the patients used a placebo toothpaste (with no active ingredients except fluoride ion 2500 ppm) and a placebo mouthwash (with no active ingredients) for one week. All patients included were provided of a soft toothbrush h h Lácer ® Soft Toothbrush (Lácer, S.A., Barcelona, Spain). to be used throughout the study and they were informed that the use of any oral hygiene or treatment product (toothpastes, mouthwashes, sprays) other than those supplied for the study should be avoided. Consumption of treatment chewing gums or sweets was also prohibited, whereas no limit was placed on the amount of liquids imbibed. Fig. 1 Study design. Five control visits (baseline, to confirm the selection criteria, one at the outset of each experimental period and another at the end) were made. Unstimulated salivary flow was measured by means of the drainage technique. Additionally, the patients filled a modified standard xerostomia quality of life questionnaire at the outset and end of each experimental phase. This questionnaire comprised seven questions on the following symptoms: oral dryness (main symptom defining xerostomia), oral comfort, night time oral dryness, difficulty in speaking, difficulty in chewing and swallowing, taste disturbance and difficulty in wearing dental prostheses, when used. The symptoms were evaluated by using 10 cm visual analogue scales, with the lowest score corresponding to the severest degree of the symptoms. In addition, a mouth examination was performed during all visits and the possible adverse effects of the therapies were investigated ( Fig. 2 ). Fig. 2 Xerostomia questionnaire. 2.2 Antimicrobial study The antimicrobial action of test and control toothpastes and mouthwashes was evaluated by means of determining the Minimum Biocidal and Inhibitory Concentrations (MBC and MIC) of these products on different microorganisms. These were selected on the basis of two criteria: on the one hand the microorganisms mostly present in the altered microflora of patients with xerostomia were selected, but also, as the second criterion, the microorganisms that are normally involved in caries, periodontal disease and in mucosal infections were included in the study, though being organic alterations common in cases of hyposalivation. We selected the following microorganisms: - cariogenic : Lactobacillus spp., S. mutans , S. salivarius and S. mitis ; - periodontogenic : P. intermedia , P. gingivalis , F. nucleatum and A. actinomycetemcomitans ; - involved in mucosal infections : Candida albicans , S. aureus and E. coli 2.2.1 Statistical analysis The number of subjects necessary to detect a significant difference between the two groups by chi-square test (two sided significance level of 5% and power of 80%) was calculated to be 30 per group. Non-parametric Kruskal–Wallis test was performed to determine statistically significant differences between treatments at the beginning and the end of each experimental period. This test was also used to analyse the evolution (difference between the final and baseline score) of the variables in each treatment group. The mixed model for fixed and random effects was used to compare the evolution of the different variables between treatments, as well as to evaluate possible sequence and period effects. 3 Results 3.1 Clinical study Of the 30 patients included in the trial (27 women, 3 men), 29 completed it. The reason why one patient dropped out has nothing to do with the therapies. The mean age was 60.30 ± 11.56 years. Unstimulated salivary flow increased from 0.04 to 0.08 ml/min and from 0.02 to 0.07 ml/min in patients treated with test and control products, respectively. These differences were not statistically significant. Both treatments significantly improved the main symptom, i.e. oral dryness ( Table 1 ) (test treatment p = 0.0086; control treatment p = 0.0036), although no significant differences between them were observed. Table 1 Evolution of the symptoms after two weeks’ treatment. Symptoms Test treatment Control treatment Before treatment After treatment p -Value Before treatment After treatment p -Value Oral dryness 4.54 6.28 0.0086 4.07 5.87 0.0036 Oral comfort 4.78 5.99 NS 4.18 6.08 0.0011 Night time oral dryness 7.29 7.88 NS 6.36 7.77 0.0085 Difficulty speaking 5.68 6.88 0.0255 5.74 6.23 NS Difficulty chewing and swallowing 5.33 6.64 0.0224 5.95 6.85 NS Distortion of taste 8.08 8.21 NS 8.26 8.31 NS Difficulty in wearing dental prosthesis 7.56 8.43 NS 7.61 7.96 NS Global symptoms a 5.95 6.98 0.0123 5.76 6.85 0.0126 NS: not statistically significant. a Except difficulty in wearing prosthesis. As regards the rest of symptoms ( Table 1 ), the test treatment reduced the difficulties in speaking ( p = 0.0255), chewing and swallowing ( p = 0.0224). The control treatment improved oral comfort ( p = 0.0011) and night time oral dryness ( p = 0.0085). No statistically significant differences between treatments were found. We use a coefficient representing oral dryness, oral comfort, night time oral dryness, difficulty in speaking without drinking liquids, difficulty chewing and swallowing foods and taste disturbance. The scale of difficulty in wearing prostheses was not included, since its use was not general in the population studied. The improvement measured as the mentioned coefficient was statistically significant in both therapies (test treatment p = 0.0123; control treatment p = 0.0126), although again no statistically significant differences were observed between them. 3.2 Antimicrobial study Values of minimal biocidal concentration are presented in Table 2 . Minimal inhibitory concentrations are shown in Table 3 . All values are indicated as level of dilution of the product able to kill or completely inhibit the visible growth, respectively. Table 2 Comparison of minimum biocidal concentration values for test and control products against oral microorganisms. Microorganisms Products Test mouthwash Control mouthwash Test toothpaste Control toothpaste Lactobacillus spp. 1/128 1/8 1/128 1/4 S. mutans 1/128 1/8 1/128 1/4 S. salivarius 1/128 1/8 1/128 1/4 S. mitis 1/128 1/8 1/128 1/4 P. intermedia 1/8 1/16 1/2 1/8 P. gingivalis 1/32 1/2 1/8 1/2 F. nucleatum 1/32 1/2 1/8 1/2 A. actinomycetemcomitans 1/8 1/4 1/8 1/2 S. aureus 1/16 1/16 1/16 1/2 E. coli 1/8 1/4 1/8 1/2 C. albicans 1/2 1/2 1/2 1/2 Table 3 Comparison of minimum inhibitory concentration values for test and control products against oral microorganisms. Microorganisms Products Test mouthwash Control mouthwash Test toothpaste Control toothpaste Lactobacillus spp. 1/512 1/64 1/256 1/8 S. mutans 1/512 1/64 1/256 1/16 S. salivarius 1/512 1/64 1/256 1/16 S. mitis 1/512 1/64 1/256 1/16 P. intermedia 1/16 1/64 1/4 1/32 P. gingivalis 1/128 1/4 1/32 1/4 F. nucleatum 1/128 1/4 1/32 1/4 A. actinomycetemcomitans 1/32 1/8 1/32 1/8 S. aureus 1/64 1/32 1/32 1/8 E. coli 1/32 1/8 1/32 1/8 C. albicans 1/8 1/4 1/4 1/4 For the majority of the microorganisms evaluated, the test products showed greater antimicrobial activity that their respective control products, being particularly noteworthy on cariogenic bacteria. 4 Discussion The present study is a double-blind crossover study with randomized treatment to evaluate the efficacy of the use of a toothpaste and mouthwash based on triclosan, fluoride, gingival revitalizers and mineral salts, with positive clinical results improving the quality of life of the patients suffering xerostomia. Clinical trials are important methods for evaluating treatment modalities and their impact on current and future clinical practice is great. Xerostomia is usually accompanied by a series of symptoms, such as oral soreness, difficulty in speaking, chewing and swallowing as well as distortion of taste and sleep, which impair the quality of life of the subjects who suffer from it. In addition, patients with xerostomia present a high prevalence of organic oral alterations, such as: caries, periodontal disease and mucosal infections. One of the methods to reduce the incidence of these alterations is based on oral hygiene. It is well established that females have much better plaque control than the males. The use of products containing sodium lauryl sulphate (a detergent commonly added to toothpastes and mouthwashing solutions) can worsen xerostomia symptoms. For this reason it is advisable to promote the use of specific products for the oral hygiene of individuals with xerostomia. Such products should be free of irritating substances (sodium lauryl sulphate, strong aromas, alcohol), and include ingredients that will improve the symptoms. Treatments based on salivary enzyme substitutes have been proved to be effective in patient symptomatology improvement but ineffective in reducing oral cariogenic flora, which is increased in these patients. The results herein presented are in agreement with these. Short-term use of products containing salivary enzyme substitutes improved the quality of life of patients with xerostomia, but their low antimicrobial power and the demineralizing effect of the mouthwash due to its low pH, besides the lack of fluoride, lead to the suspicion that they are not effective in preventing oral diseases such as caries and periodontal diseases. New specific products, based on triclosan, fluoride, gingival revitalizers and mineral salts, for the oral hygiene of patients with xerostomia have been evaluated. Triclosan is an antiseptic used in products for oral use due to its high antiplaque and antimicrobial efficacies, low toxicity, and because it not causes staining. In relation to the results of the clinical phase of the study, they have shown that the test treatment improves the oral symptoms of patients with dry mouth, besides presenting an excellent tolerance. Overall, the symptomatology improves with both treatments and was statistically significant with the test treatment for the main symptom or sensation of oral dryness, as well as for difficulty in speaking, difficulty chewing and swallowing and the symptomatology considered as a whole .The reason why the evolution of other symptoms was not statistically significant could be due to the high baseline score of those symptoms, i.e. the absence of severity at the outset of the treatment. Furthermore, the improvement in the oral symptoms did not match up with a significant increase in salivary flow with either of the treatments, although it has been widely established that salivary flow measured at different intervals for the same individual may vary considerably and that the levels of salivary flow do not always correlate with the symptoms. Optimal oral hygiene and regular oral screening is necessary in individuals with hyposalivation due to an increased risk for caries and periodontal diseases. Saliva substitutes should not only relieve the symptoms of oral dryness, but also provide protection against demineralization. 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