Management of xerostomia in older patients : a randomised controlled trial evaluating the efficacy of a new oral lubricant solution. Efficacy of a new oral lubricant solution in the management of psychotropic drug-induced xerostomia: a randomized controlled trial. Safety and effectiveness of topical dry mouth products containing olive oil, betaine, and xylitol in reducing xerostomia for polypharmacy-induced dry mouth. Subjective and clinical evaluation of oral lubricants in xerostomic patients. Clinical trial of a mucin-containing oral spray for treatment of xerostomia in hospice patients. Salivary stimulation by chewing gum and lozenges in rheumatic patients with xerostomia. Chewing gum and a saliva substitute alleviate thirst and xerostomia in patients on haemodialysis. Comparison between saliva stimulants and a saliva substitute in patients with xerostomia and hyposalivation. Treatment of xerostomia with polymer-based saliva substitutes in patients with Sjögren's syndrome. The cholinesterase inhibitor physostigmine for the local treatment of dry mouth: a randomized study. Use of a mucoadhesive disk for relief of dry mouth: a randomized, double-masked, controlled crossover study. Subjective assessment of a new moisturizing mouth spray for the symptomatic relief of dry mouth. A double-blind, crossover study of Biotène Oralbalance and BioXtra systems as salivary substitutes in patients with post-radiotherapy xerostomia. Different saliva substitutes for treatment of xerostomia following radiotherapy. A prospective crossover study. The effect of a chewing gum on salivary secretion, oral mucosal friction, and the feeling of dry mouth in xerostomic patients. Comparison between saliva stimulants and saliva substitutes in patients with symptoms related to dry mouth. A multi-centre study. Patient preferences in a preliminary study comparing an intra-oral lubricating device with the usual dry mouth lubricating methods. Treatment of xerostomia: a double-blind trial in 108 patients with Sjögren's syndrome. Comparison of the effect of the linseed extract Salinum and a methyl cellulose preparation on the symptoms of dry mouth. Effects of a betaine-containing toothpaste on subjective symptoms of dry mouth: a randomized clinical trial. A comparison of artificial saliva and chewing gum in the management of xerostomia in patients with advanced cancer. Comparison between new saliva stimulants in patients with dry mouth: a placebo-controlled double-blind crossover study. Fluticasone propionate spray and betamethasone sodium phosphate mouthrinse: a randomized crossover study for the treatment of symptomatic oral lichen planus. Evaluation of the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lysozyme and lactoferrin in elderly patients with dry mouth--a pilot study. Enamel matrix proteins in the regenerative therapy of deep intrabony defects. Randomized-controlled trial: effect of a reservoir biteguard on quality of life in xerostomia. Early hyperbaric oxygen therapy for reducing radiotherapy side effects: early results of a randomized trial in oropharyngeal and nasopharyngeal cancer. Dry mouth with conventional and controlled-release oxybutynin in urinary incontinence. The Ditropan XL Study Group. Pentoxifylline therapy: a new adjunct in the treatment of oral submucous fibrosis. A double-blind randomized dose-response study comparing daily doses of 5, 10 and 15 mg controlled-release oxybutynin: balancing efficacy with severity of dry mouth. Oral hygiene regimens, plaque control, and gingival health: a two-month clinical trial with antimicrobial agents. A double-blind crossover trial of Oral Balance gel and Biotene toothpaste versus placebo in patients with xerostomia following radiation therapy. Multicenter randomized trial of chewing gum for preventing oral mucositis in children receiving chemotherapy. Effect of pilocarpine during radiation therapy: results of RTOG 97-09, a phase III randomized study in head and neck cancer patients. Efficacy of a 2-phase oil: water mouthrinse in controlling oral malodor, gingivitis, and plaque. Clinical and microbiologic effects of chemical versus mechanical cleansing in professional supportive implant therapy.
Xerostomia is a subjective sensation of mouth dryness that may frequently occur in older patients.
                To compare the clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray taken five times daily with that of a commercially available saliva substitute Saliveze in the treatment of xerostomia.
                Forty-one institutionalised patients (28 women, 13 men; mean age 84 +/- 7 years) were randomly assigned to receive either OGT or Saliveze in a 2-week, randomised, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness using a self-rated, 10cm long visual analogue scale (VAS), objective assessment of oral tissue condition using a four-point ordinal scale and subjective assessment of symptoms of xerostomia using dichotomous responses to a questionnaire. The primary endpoint was the day (D) 14 patient-based mouth dryness score measured on a self-rated VAS.
                At D14, OGT resulted in significantly greater efficacy with respect to mouth dryness (mean between-treatment difference 2.1 +/- 0.1, 95% CI 1.9, 2.3; p = 0.001), swallowing difficulty (1.8 +/- 0.3, 95% CI 1.5, 2.1; p = 0.001), speech difficulty (1.1 +/- 0.2, 95% CI 1.0, 2.4; p = 0.04) and overall sensation of symptom relief (2.7 +/- 1.2, 95% CI 1.9, 3.8; p = 0.001). Objective assessment of oral tissues also showed significantly better improvement with OGT spray with respect to dryness (p = 0.01), stickiness (p = 0.005) and dullness (p = 0.001) of oral mucosa; severity of mucositis (p = 0.01); and thickening of the tongue (p = 0.03). A significant difference in taste acceptability was also noted in favour of OGT (1.4 +/- 0.6, 95% CI 1.2, 1.9; p = 0.04).
                OGT lubricant oral spray was superior to Saliveze in improving xerostomia and oral tissue condition in older institutionalised patients. Xerostomia is a subjective sensation of mouth dryness often occurring as an unwanted effect of psychotropic drugs.
                The clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray (1 or 2 sprays up to 4 times daily) in the treatment of xerostomia was compared with those of a commercially available artificial saliva substitute (ASS [Saliveze]) in a 2-week, open-labeled, randomized, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness by means of a 10-cm-long visual analog scale, objective blinded assessment of the oral tissue condition by a dental hygienist by means of a 4-point ordinal scale, and subjective patient-based assessment of dry mouth symptoms by means of dichotomous responses to a questionnaire. [Day 14 - baseline] patient-based mouth dryness score was the primary end point.
                Seventy-four patients (41 women and 33 men, 44 +/- 15 years) undergoing long-term psychotropic drug treatment were consecutively enrolled. At day 14, OGT resulted in better efficacy than ASS in mouth dryness score (mean difference, 1.2 +/- 0.4; P = 0.006), speech difficulties (mean difference, 1.2 +/- 0.4; P = 0.005), taste (mean difference, 1.1 +/- 0.4; P = 0.02), and overall mouth condition (mean difference, 1.4 +/- 0.9; P = 0.005). Taste of OGT was better than that of ASS (mean difference, 1.4 +/- 0.6; P = 0.04), as was OGT acceptability (mean difference, 1.4 +/- 0.9; P = 0.005).
                Oxygenated glycerol triester lubricant oral spray was superior to a commercially available ASS in improving xerostomia and overall condition of the oral tissue. Polypharmacy is a common cause of salivary hypofunction, producing symptoms of dry mouth or xerostomia, especially among older populations. As the number of older people continues to increase, polypharmacy-induced salivary hypofunction is becoming an increasing problem. Many over-the-counter products are available for relieving symptoms of dry mouth, but few have been tested in controlled clinical investigations. The purpose of this investigation was to evaluate the safety and efficacy of a group of topical dry mouth products (toothpaste, mouth rinse, mouth spray and gel) containing olive oil, betaine and xylitol. Forty adults were entered into this single-blinded, open-label, cross-over clinical study and 39 completed all the visits. Subjects were randomly assigned at baseline to using the novel topical dry mouth products daily for 1 week, or to maintain their normal dry mouth routine care. After 1 week, they were crossed over to the other dry mouth regimen. The results demonstrated that the use of the novel topical dry mouth products increased significantly unstimulated whole salivary flow rates, reduced complaints of xerostomia and improved xerostomia-associated quality of life. No clinically significant adverse events were observed. These data suggest that the daily use of topical dry mouth products containing olive oil, betaine and xylitol is safe and effective in relieving symptoms of dry mouth in a population with polypharmacy-induced xerostomia. The purpose of this investigation was to evaluate and compare four oral lubricants in relation to oral mucosal status, perceived relief of dry mouth symptoms, and patient acceptance. Three commercial oral lubricants--two sprays and one gel--and a home remedy of margarine were evaluated. Twenty-five xerostomic/salivary gland dysfunctional patients demonstrating < 0.20 mL/min of unstimulated whole saliva participated in the randomized, four-phase, cross-over study. Each phase included a ten-day use of oral lubricants, followed by a four-day washout period. On the first and tenth days of use, lip and buccal mucosa dryness and perceived oral dryness were evaluated. Patient acceptance of the oral lubricant was evaluated at the end of each ten-day period. The Wilcoxon matched-pairs signed-rank test was used to analyze data over time and between-group differences. The gel group reported a statistically significant improvement in perceived oral dryness from Day 1 to Day 10. No other significant within-group differences were found. Subjects rated the gel significantly better than margarine for convenience, perceived value, minutes of relief, and in the "overall" rating. No other significant between-group differences were noted. Thirty-five hospice patients complaining of dry mouth entered a double-blind, single-phase placebo-controlled trial of a mucin-containing oral spray (Saliva Orthana) for the relief of xerostomia. The sprays were administered ad libitum for two weeks by the patients themselves, with nursing help as necessary. A detailed history and examination were undertaken, together with collection of microbiological specimens, at entry and after seven and 14 days of spray usage, respectively. Thirty-one patients were available for follow-up at seven days and 26 patients after 14 days. Relief of oral dryness during the day was reported by 9/15 patients on Saliva Orthana and 10/16 patients on placebo by day 7, with a similar degree of improvement maintained to day 14. The corresponding figures by day 7 for relief of dryness at night were 8/15 for Saliva Orthana and 8/16 for placebo. There were no statistically significant differences between those on active and those on placebo spray for any of the oral symptoms recorded. Neither spray had any major impact on the oral microflora. However, the majority of patients in both treatment groups wished to continue using a mouth spray at the end of their involvement in the trial. Whilst the data from this study provide no evidence for increased benefit of a mucin-containing spray over a mucin-free placebo among xerostomic hospice patients, it is clear that both sprays provided worthwhile symptomatic relief of oral dryness for many of the participants. The effect of chewing gum and lozenges in relieving the signs and symptoms of xerostomia was studied in a 2-wk cross-over clinical trial in 18 rheumatic patients with dry mouth symptoms and low salivary flow rates. Resting flow was measured before (PRESTIM) a chewing stimulated flow rate test (STIM), and also 5 min after (POSTSTIM). STIM flow (mean 1.0 ml/min) was not affected by the test regimens. In the lozenge regimen, mean PRESTIM flow in the group increased from 0.11 to 0.14 ml/min and POSTSTIM from 0.10 to 0.13. In the chewing gum regimen, PRESTIM flow (mean 0.13 ml/min) did not change, whereas POSTSTIM flow increased from 0.13 to 0.16 ml/min. In terms of patients' preferences, chewing gum and lozenges were ranked equal. Both these physiologic stimuli had few side-effects. Subjective symptoms were relieved in about one-third of the subjects, but relief was not always verified by improved flow rates. The regimens were not found to influence buffering capacity; salivary counts of mutans streptococci, lactobacilli, and candida; or oral sugar clearance time. Most patients on haemodialysis (HD) have to maintain a fluid-restricted diet to prevent a high interdialytic weight gain (IWG). The prevalence of xerostomia (the feeling of a dry mouth) is higher in HD patients than in controls. Recently, we demonstrated that xerostomia and thirst were positively correlated with IWG in HD patients. Thus, this may play a role as a stimulus for fluid intake between dialysis sessions. The aim of the present study was to investigate the effect of chewing gum or a saliva substitute on xerostomia, thirst and IWG.
                This study was a randomized two-treatment crossover design with repeated measures. After the use of chewing gum or saliva substitute for 2 weeks, a wash-out period of 2 weeks was introduced and hereafter the other regimen was carried out. Xerostomia and thirst were assessed by validated questionnaires as xerostomia inventory (XI) and dialysis thirst inventory (DTI), at baseline and after each treatment period, as were IWG and salivary flow rates.
                Sixty-five HD patients (42 men, 54.6+/-14.1 years; 23 women, 54.7+/-16.3 years) participated in this study. Chewing gum decreased XI from 29.9+/-9.5 to 28.1+/-9.1 (P<0.05). Chewing gum as well as a saliva substitute reduced DTI significantly (P<0.05), but no differences occurred for the average IWG or salivary flow rates.
                The use of chewing gum and, to a lesser extent, a saliva substitute may alleviate thirst and xerostomia in some HD patients. The purpose of this study was to assess patient preference and product efficacy of three non-prescription products for the symptomatic relief of xerostomia. The study group consisted of 80 individuals with a complaint of chronic (> six months) xerostomia and an unstimulated salivary flow rate of < 0.1 mL/min. The three products--a sorbitol/xylitol-sweetened chewing gum, a sorbitol-sweetened sour lemon lozenge, and a sorbitol/xylitol-sweetened artificial saliva substitute spray--were assigned in a permuted block randomization scheme. Each product was used for two weeks with an interval of one week between trials. The study did not identify any product to be statistically significant in terms of patient preference. Kruskal-Wallis testing revealed no statistical significance (P > 0.589) among the products. No product demonstrated marked efficacy in stimulating salivary output. ANOVA analysis followed by Tukey HSD testing revealed no significant difference between the baseline paraffin-stimulated mean flow rate and the gum- and lozenge-stimulated flow rates. To determine the efficacy of 3 types of polymer-based saliva substitutes in reducing oral dryness in patients with Sjögren's syndrome (SS).
                Subjective efficacy of 3 different saliva substitutes (determined by self-administered questionnaire) was evaluated in a double-blind, placebo-controlled trial in 43 patients with primary and secondary SS. High-viscosity versus low-viscosity xanthan gum-based saliva substitutes were also compared in 33 SS patients. Salivary flow rates (SFR) were determined to examine correlations between the SFR and the subjective efficacy of the saliva substitute.
                Neither the saliva substitutes nor the placebo was truly effective. Preference for a particular saliva substitute over placebo was equally distributed among the 3 types of substitutes. The SFR of patients who preferred polyacrylic acid-based saliva substitutes was lower than that in patients who preferred the porcine mucin-based substitute (P < 0.05). Patients whose oral dryness was reduced by low-viscoelastic substitutes had a low stimulated SFR ( < 0.20 ml/minute; P < 0.05).
                The optimal properties of a saliva substitute are not the same for all patients with SS, but are dependent on such parameters as the individual SFR. Thus, to determine the best saliva substitute for a particular patient, it is necessary to have the patient try a number of substitutes of different viscoelastic properties. Application of physostigmine to the oromucosal surface with the aim of stimulating underlying mucin-producing glands while reducing cholinergic systemic effects might be a strategy for treating dry mouth. Subjects suffering from dry mouth and with hyposalivation participated in a crossover, double-blind, randomized study. A gel containing physostigmine (0.9, 1.8, 3.6, and 7.2 mg) or placebo was applied to the inside of the lips and distributed with the tongue. The feeling of dryness was assessed using a visual analogue scale (VAS) (where a score of 100 = extremely dry) and systemic effects were registered. Based on assessments of efficacy and safety, the dose of 1.8 mg of physostigmine was selected for use in the second part of the study to make objective measurements of saliva volumes. Physostigmine (1.8 mg) produced long-lasting (120 min) relief (evident as a score reduction of 25 on the VAS) in the feeling of dryness. Judging from AUC values related to baseline over 180 min, the improvement for both mouth and lips in response to physostigmine was six times greater than that to placebo. At higher doses of physostigmine, gastrointestinal discomfort predominantly occurred. The volume of saliva collected in response to physostigmine was five times higher over 180 min than that collected in response to placebo. Physostigmine, applied locally, therefore appears to be a promising modality for dry-mouth treatment. Dry mouth is a frequent complaint of adults worldwide. In those who experience dry mouth, therapeutic options include the use of salivary substitutes and sialogogues.
                The authors compared the efficacy and safety of mucoadhesive disks (OraMoist, Axiomedic, Zurich; distributed by Quantum Health, Eugene, Ore.) applied three times daily with those of placebo mucoadhesive disks in a double-masked, randomized, controlled crossover study. The primary end point of interest was within-participant differences in subjective (visual analog scale) ratings of dry mouth according to the New York University Bluestone Mouthfeel Questionnaire. The secondary end point was within-participant differences in salivary flow rates.
                Twenty-seven participants completed the single-site study. The results showed no significant difference between the two types of mucoadhesive disks, both of which were associated with a statistically significant improvement in the subjective experience of moistness across the 60-minute period after application and compared with baseline measures after two weeks of use. Furthermore, both disks were associated with a statistically significant improvement in salivary flow rates across the 60-minute period after application and compared with baseline measures after one and two weeks of use. The disks were well tolerated, and participants did not report any adverse events.
                The mucoadhesive disks used in this study were safe and provided symptomatic relief from dry mouth. Practice Implications. Patients with dry mouth may benefit from this novel delivery system. A randomized clinical trial (Study 1) and consumer usage test (Study 2) were conducted to evaluate the acceptability and efficacy of OASIS Mouth Moisturizing Spray in subjects experiencing dry mouth.
                Study 1: A randomized, single-blind, four-arm crossover clinical trial was conducted in 24 subjects, ranging from 50-84 years of age, to evaluate OASIS Mouth Moisturizing Spray and two experimental mouth spray formulations, and compare their performance to a reference (marketed) mouth spray, SALIVEZE. Following a three-day acclimatization phase, subjects used all four products at home for three days. Each treatment phase was separated by a three-day washout period. Study 2: One-hundred twenty subjects participated in a three-week home usage consumer test using OASIS Mouth Moisturizing Spray, after which they completed a 52-question online survey exploring sensory, efficacy, and resultant quality of life attributes of the product.
                Study 1: On average, subjects used the four test products 2-3 times per day. OASIS Mouth Moisturizing Spray was found to be effective in relieving dry mouth in the study population, as evidenced by a statistically significant feeling of coating the mouth (p < 0.05), and statistically significantly longer dry mouth relief (p < 0.005) than the commercial control. The OASIS Mouth Moisturizing Spray was statistically significantly (p < 0.05) better and preferred over the other product tested. All the products used in the study were well-tolerated. Study 2: On a five-point scale, 73% of respondents perceived the OASIS Mouth Moisturizing Spray as "very good" or "excellent," and more than 60% gave the product an "excellent" or "very good" rating on sensory, efficacy, and quality of life attributes.
                These studies show that OASIS Mouth Moisturizing Spray helped provide dry mouth relief and was well liked by the study population. This study assessed the efficacy of the Bioxtra (BX) and Biotène Oralbalance (OB) systems in the treatment of post-radiotherapy xerostomia. In a double-blind, crossover study, 20 patients with post-radiotherapy xerostomia were randomly allocated to receive either OB then BX, or vice versa, each product for 2 weeks, with a 1 week wash-out period in between. Subject-based dry mouth scores derived from 100-mm visual analogue scales were recorded at days 0 and 14 of each 2-week period, together with subjective perception of changes in dry mouth symptoms. Both treatments were effective, resulting in reduction of visual analogue scale scores from day 0-14. Between-groups comparisons identified that BX achieved significantly better improvements compared with OB for the perception of dry mouth and improvements in speech and was also rated as more pleasant to use than OB (P < 0.05). In conclusion, both treatments were effective in alleviating the symptoms of post-radiotherapy xerostomia, although BX achieved superiority in some of the outcomes assessed compared with OB. Xerostomia is an important chronic side effect of radiotherapy in the head and neck area. The authors investigated the efficacy of different artificial saliva compounds in patients with postirradiation xerostomia.
                In 120 patients with xerostomia after radiotherapy for head and neck cancer, four different saliva substitute compounds (gel, carmellose spray, oil, mucin spray) were tested in a prospective crossover design. Xerostomia at baseline and under treatment with each compound was measured with a questionnaire approved in a pilot trial.
                All compounds significantly improved xerostomia when compared to baseline situation (p < 0.0001). The gel was rated best, the carmellose spray was rated worst by the patients, but the single compounds did not differ significantly in their effects. In spite of this result, most patients chose the carmellose spray as their favorite compound. This is due to its good taste and easy handling, which play an important role for the acceptance of the products. Big individual differences in the preference of the single compounds were found.
                For most patients considerable relief from xerostomia can be reached by saliva substitutes. Thus, every patient with xerostomia should be given different artificial saliva compounds for a test period. This will help to find the individually best way to cope with the dry mouth. A new chewing gum (PTC) with the ability to release flavoring substances for a rather long time was tested for its ability to stimulate saliva secretion. The chewing gum is mildly flavored and contains non-cariogenic sweeteners (xylitol and sorbitol). Measurements of saliva secretion rate and oral mucosal sliding friction and subjective evaluations on visual analog scales were made in relation to chewing and compared with those when chewing a commercially available gum (V6). The study was a randomized, crossover comparison with blind evaluation. Both chewing gums stimulated saliva secretion and decreased oral mucosal friction. The PTC gum gave consistently higher mean values of saliva secretion rate and lower oral mucosal friction values than V6. The difference was statistically significant for the saliva secretion rate and most pronounced after 5-10 min of chewing. There was also a statistically significant difference between the subjective evaluations of V6 and PTC with regard to saliva-stimulating ability and taste in favor of the PTC gum. Five saliva stimulants (Salivin, V6, Mucidan, Ascoxal-T and Nicotinamide) and three saliva substitutes (Saliment, Salisynt and an ex témpore solution) were evaluated in 106 patients with a low salivay flow rate and a long history of dry mouth. The study was carried out as a multi-centre study in collaboration with ten different hospital dental clinics. The participants were interviewed about their complaints related to dry mouth. Each patient was then asked to use the eight saliva stimulants and substitutes for 14 days in a randomized order with one week intervals. After the 14-day-periods, the patients were interviewed about the effect of the various products by a dentist using a standardized questionnaire. Paraffin-stimulated whole saliva samples were collected after each test period. The most serious complaints among the patients were, besides dryness of the mouth, difficulty to talk and difficulty to swallow. The results showed that all eight tested saliva stimulants and substitutes relieved the symptoms of dry mouth to some extent. However, V6 chewing gum and Salivin lozenge were ranked as the two best products by the patients. No long-term effect was found with any of the eight products on the flow rate of paraffin-stimulated whole saliva. To compare an intra-oral device to relieve oral dryness with the other methods of lubricating the mouth at night.
                Multidisciplinary single blind randomised cross over study.
                The subjects were drawn from patients attending a dry mouth clinic.
                Thirty-four dentate subjects attended on five occasions at intervals of 4 weeks. At the first visit the teeth were scaled and impressions were recorded. The device was fitted either on the second or the fourth visit. At all visits samples were taken of the resting and stimulated saliva for volumetric analysis and the dry mouth score recorded. Data were collected from the lubrication timings and the questionnaire.
                Ten water, nine saliva substitute and ten sugar-free chewing gum lubricators completed the study. There were 27 female and two male subjects with an average age of 62 years. Nine out of 10 of those lubricating with chewing gum preferred wearing the device (P = 0.037). After the device wearing period the subjects' self assessment of mouth dryness (P = 0.056), speech (P = 0.009) and swallowing (P = 0.031) were more favourable when compared with the alternative lubrication with 66% preferring the intra-oral device to their alternative method of lubrication.
                The majority of the subjects preferred wearing the device at night compared with their normal method of lubrication. Subjects' perception of dryness, speech and swallowing became closer to the clinician's assessment after wearing the device. The first-ever controlled study of a therapeutic modality for xerostomia is reported. A recently described formulation for saliva substitute (SS) has been tested against a glycerine mouthwash as a control saliva substitute (placebo) in a double-blind clinical trial in 108 patients with varying grades of xerostomia of Sjögren's syndrome. The results indicate that SS offered significant relief of nocturnal oral discomfort (p less than 0.02) and more patients reported "excellent" improvement (p less than 0.01) on a five-point graded response. In all other respects, the SS was not significantly better than the placebo. Significant adverse effects were not reported. It is suggested that any such current and future therapeutic modalities for Sjögren's syndrome be subjected to similar critical appraisal of their worth. The effect of a linseed extract Salinum and a sodium carboxymethyl cellulose preparation called MAS-84 was compared with regard to its effect on the symptoms of dry mouth. Twenty patients with xerostomia, who had been treated for cancer in the head and neck by radiation were recruited from the clinic for maxillofacial surgery, Malmo University Hospital. Following radiation treatment the salivation was severely reduced. The symptoms of a general feeling of a dry mouth, difficulties in chewing and swallowing, taste disturbances, problems with speech and mouth burning were registered on a subjective verbal rating scale. In addition plaque index and gingival bleeding were determined. The study design was crossover and performed single blind. The experimental period was 7 weeks. The patients were randomly divided into 2 groups. One group used Salinum and the other MAS-84 for 3 weeks. The fourth week was a wash out period and for the next three weeks the patients shifted preparation. Each of the preparations was used ad libitum. Registrations of the various parameters were undertaken on days 0, 7 and 21 of the respective period. At the initial examination all patients reported considerable disturbances from mouth-dryness. These symptoms were reduced in 15 patients during the Salinum period and in 9 during the MAS-84 period. The relief was significantly more pronounced during the use of Salinum compared to that during the use of the methyl cellulose preparation. On day 21 plaque and gingival bleeding were significantly reduced during the Salinum period but not during the MAS-84 period. The results of the present study confirm those of a previous pilot study and indicate that the linseed mucilage significantly reduced the symptoms of dry mouth. This effect increased with increasing time of saliva substitute use. The linseed mucilage Salinum appeared to be a suitable saliva replacement in mouth dry patients. Our aim was to study the effects of mildly flavoured sodium lauryl sulphate (SLS)-containing and detergent-free toothpastes with and without betaine (BET) on subjective symptoms of dry mouth in a randomised clinical trial. BET is an osmoprotectant that reacts with molecules to supply the surface with a water coating that protects cells from surfactants. Twenty-seven xerostomic patients and 18 healthy controls took part in the randomised, double-blind clinical trial with a crossover design. Three mildly flavoured toothpastes: (1) 4% BET, (2) 1% SLS and 4% BET, and (3) 1% SLS were used for six weeks each. The reference or washout paste contained neither SLS nor BET. The subjects' dental appointments were at the beginning of the trial and before and after the use of each toothpaste. At each appointment, the subjects were interviewed about subjective sensations of dry mouth (Visual Assessment Scoring (VAS) Index). The subjects did not report any adverse effects in connection with the use of the toothpastes. The VAS scores for lip dryness and eating difficulties were significantly lower for the BET paste (lip dryness: BET<BET+SLS; p < 0.005 and eating difficulties: BET<BET+SLS; p = 0.02; BET<reference; p = 0.003). The BET paste relieved dry mouth symptoms in 44% of the xerostomic patients, the corresponding figures for the other pastes being BET+SLS 22% (p = 0.002 as compared with BET), SLS 18% (p = 0.022), and reference 7% (p = 0.000). In conclusion, all the mildly flavoured toothpastes used in this study were well accepted by the xerostomic subjects. Thus, other toothpaste components may be more mucosa-irritating than just SLS, or else they enhance the effect of SLS. The detergent-free, BET-containing toothpaste appeared to be associated with relief of some symptoms of dry mouth. This was a prospective, randomized, open, crossover study comparing a mucin-based artificial saliva (Saliva Orthana) with a low-tack, sugar-free chewing gum (Freedent) in the management of xerostomia in patients with advanced cancer. The conclusions of this study were that both Saliva Orthana and Freedent are effective in the management of xerostomia in patients with advanced cancer, that both Saliva Orthana and Freedent cause some side-effects in this group of patients, and that patients with cancer think that chewing gum is an acceptable treatment. Sixty-nine per cent of the patients preferred the chewing gum to the artificial saliva. Furthermore, the chewing gum scored better than the artificial saliva on every measure of efficacy. However, none of these results reached statistical significance. Two new saliva stimulants: V6 and a mucin containing chewing gum were tested in this placebo-controlled double-blind crossover study. Forty-three patients (mean age 63 yr) complaining of dry mouth participated. The products were administered in a randomized order, and used for 2 wk each. The effect was evaluated by interviews and by determining changes in stimulated and unstimulated saliva flow rates. A positive effect was reported by 64%, 44%, and 26% of the patients using the mucin chewing gum, V6, and the placebo, respectively. More than 2/3 of the patients found the mucin chewing gum efficient at various times and situations. Sixty-one percent of the patients preferred the mucin chewing gum, 21% V6, and 5% the placebo product. Fifty percent of the patients had an increase in unstimulated salivary secretion rate from all products after 14 days regular use indicating a long-term effect. Symptomatic oral lichen planus (OLP) has been palliated with a wide spectrum of topical and systemic therapies. Although the majority of management strategies include corticosteroids, few have been evaluated in randomized controlled trials.
                We investigated the acceptability and efficacy of topical fluticasone propionate spray (FP) and betamethasone sodium phosphate mouthrinse (BSP) upon the signs and symptoms of OLP, assessing patient quality of life changes as a consequence of these therapies.
                We implemented a randomized, crossover study in which each drug was administered for a period of 6 weeks with an intervening washout period of 2 weeks at an outpatient oral medicine unit in London, United Kingdom. We treated 48 patients with biopsy-proven symptomatic OLP, and 44 patients (92%) completed the study. The dosage was 50 microg two dose unit sprays and BSP 500 microg, each 4 times daily. Symptomatic improvement was evaluated by means of a visual analogue scale (VAS), the McGill pain score, the Oral Health Impact Profile (OHIP), and Oral Health Quality of Life (OHQoL) questionnaires. The total surface area of the lesions, including all white, erythematous, and ulcerative lesions was measured at each visit. The efficacy, ease of application, and adverse effects associated with each medication were recorded.
                Both FP and BSP mouthwash caused both a statistically significant reduction in painful symptoms as measured by the VAS and improvement in quality of life as measured by the OHIP and OHoQL indices. There was no significant difference between the two corticosteroids in their efficacy in reducing painful symptoms (measured by the VAS) or in their effect on patient quality of life. Both FP and BSP significantly reduced the surface area of oral lesions. However, FP was statistically significantly better than BSP in reducing lesion surface area. There was no statistically significant difference between the patient-assessed effects of the 2 therapies.
                FP and BSP are both effective in the short-term clinical management of symptomatic OLP. FP is more acceptable to patients than BSP because of the convenience of the spray form. To evaluate the clinical efficacy of a mouthwash and oral gel containing the antimicrobial proteins lactoperoxidase, lactoferrin and lysozyme, in a sample of elderly individuals with dry mouth.
                Twenty elderly institutionalised subjects with dry mouth and with a certain degree of independence for daily life activities were included in this pilot study. A randomised, double blind and cross-over design was used. The study variables comprised subjective dry mouth sensation, the severity of discomfort assessed by means of a visual analogical scale (VAS), the Oral Health Impact Profile (OHIP), the presence of signs and symptoms of dry mouth, sialometry and Candida albicans culture. All the variables were recorded before and after each of the two periods of the study.
                The 20 selected subjects we made up of 16 women and four men, with a mean age of 81.3 years. Improvement was observed on analysing the data between the first and second intervention period in terms of the OHIP values, the presence of dry mouth, and the need to drink fluids to swallow. However, the improvement in certain variables before and after treatment did not take a positive course in all cases, and some subjects even improved with placebo.
                The evaluated mouthwash and oral gel improved some subjective and clinical aspects in elderly individuals with dry mouth, though a placebo effect cannot be entirely discarded. This prospective multicentre randomized controlled clinical trial was designed to compare the clinical outcomes of papilla preservation flap surgery with or without the application of enamel matrix proteins (EMD).
                172 patients with advanced chronic periodontitis were recruited in 12 centers in 7 countries. All patients had at least one intrabony defect of > or =3mm. Heavy smokers (> or =20 cigarettes/day) were excluded. The surgical procedures included access for root instrumentation using either the simplified or the modified papilla preservation flap in order to obtain optimal tissue adaptation and primary closure. After debridement, roots were conditioned for 2 min with a gel containing 24% EDTA. EMD was applied in the test subjects, and omitted in the controls. Postsurgically, a strict plaque control protocol was followed. At baseline and 1 year following the interventions, clinical attachment levels (CAL), pocket probing depths (PPD), recession (REC), full-mouth plaque scores and full-mouth bleeding scores were assessed. A total of 166 patients were available for the 1-year follow-up.
                At baseline, 86 test and 86 control patients presented with similar subject and defect characteristics. On average, the test defects gained 3.1+/-1.5 mm of CAL, while the control defects yielded a significantly lower CAL gain of 2.5+/-1.5 mm. Pocket reduction was also significantly higher in the test group (3.9+/-1.7 mm) when compared to the controls (3.3+/-1.7 mm). A multivariate analysis indicated that the treatment, the clinical centers, cigarette smoking, baseline PPD, and defect corticalisation significantly influenced CAL gains. A frequency distribution analysis of the studied outcomes indicated that EMD increased the predictability of clinically significant results (CAL gains > or =4 mm) and decreased the probability of obtaining negligible or no gains in CAL (CAL gains <2 mm).
                The results of this trial indicated that regenerative periodontal surgery with EMD offers an additional benefit in terms of CAL gains, PPD reductions and predictability of outcomes with respect to papilla preservation flaps alone. To assess the effect of a reservoir biteguard for artificial saliva on the oral health-related quality of life of patients with xerostomia.
                Double-blind randomized placebo-controlled trial among 86 adults with xerostomia. Study group received the trial biteguard. Control group received a conventional biteguard. Outcomes were number of impacts and total scores as recorded by oral impacts on daily performances (OIDP).
                At 1-month follow up 84 people remained in the trial. The median number of impacts in the study and control groups was 3 and 4 respectively. The median total score was 6 and 12 respectively. In ANCOVA receipt of the reservoir biteguard reduced the number of impacts recorded by OIDP but there was no difference in the total score.
                Reservoir biteguards improved the quality of life of people with xerostomia by reducing the number of impacts on daily life. Comparison of quality of life (QoL) and side effects in a randomized trial for early hyperbaric oxygen therapy (HBOT) after radiotherapy (RT).
                From 2006, 19 patients with tumor originating from the tonsillar fossa and/or soft palate (15), base of tongue (1), and nasopharynx (3) were randomized to receive HBOT or not. HBOT consisted of 30 sessions at 2.5 ATA (15 msw) with oxygen breathing for 90 min daily, 5 days per week, applied shortly after the RT treatment was completed. As of 2005, all patients received validated questionnaires (i.e., the European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ Head and Neck Cancer Module (H&N35), Performance Status Scale): before treatment; at the start of RT treatment; after 46 Gy; at the end of RT treatment; and 2, 4, and 6 weeks and 3, 6, 12, and 18 months after follow-up.
                On all QoL items, better scores were obtained in patients treated with hyperbaric oxygen. The difference between HBOT vs. non-HBOT was significant for all parameters: EORTC H&N35 Swallowing (p = 0.011), EORTC H&N35 Dry Mouth (p = 0.009), EORTC H&N35, Sticky Saliva (p = 0.01), PSS Eating in Public (p = 0.027), and Pain in Mouth (visual analogue scale; p < 0.0001).
                Patients randomized for receiving hyperbaric oxygen after the RT had better QoL scores for swallowing, sticky saliva, xerostomia, and pain in mouth. To compare the efficacy and safety of controlled-release oxybutynin with conventional, immediate-release oxybutynin and determine rates of dry mouth.
                Patients (n = 226) who were known to be responsive to anticholinergic therapy and who had seven or more urge incontinence episodes per week were randomized to receive controlled-release oxybutynin or immediate-release oxybutynin. After an initial placebo run-in period, dosing in each began at 5 mg per day and increased weekly by 5 mg per day to a maximum of 20 mg per day or when a balance between improvement of incontinence symptoms and tolerability of side effects was achieved. Rates of urge incontinence and dry mouth were compared. Post hoc Kaplan-Meier survival analysis was used to describe elimination of incontinence episodes by dose and to analyze dry mouth risk by dose.
                Reductions in urge urinary incontinence episodes from baseline to the end of treatment were 18.6 to 2.9 per week (83% mean decrease) and 19.8 to 4.4 per week (76% mean decrease) in the controlled- and immediate-release oxybutynin groups (P =.36), respectively. At equal doses, comparable proportions of patients in both groups reported the absence of urge incontinence (P =.85). The incidence of dry mouth increased with dose in both groups, but there was no difference in dry mouth rates between the groups: 47.7% and 59.1% for the controlled- and immediate-release oxybutynin (P =.09), respectively. However, Kaplan-Meier analysis to examine first report of dry mouth at a given dose revealed that a significantly lower proportion of patients taking controlled-release oxybutynin had moderate to severe dry mouth (P =.007) or any dry mouth (P =.003) compared with those taking immediate-release oxybutynin.
                At the same daily dose, controlled- and immediate-release oxybutynin demonstrated comparable efficacy in reduction of urge incontinence episodes. The incidence of dry mouth was dose dependent but equal in both groups; first report of moderate to severe dry mouth was significantly lower in the controlled-release group. This study was designed to determine the effect of pentoxifylline (Trental) on the clinical and pathologic course of oral submucous fibrosis. This drug is a methylxanthine derivative that has vasodilating properties and was envisaged to increase mucosal vascularity.
                This investigation was conducted as a randomized clinical trial incorporating a control group (Standard drug group SDG, multivitamin, and local heat therapy) in comparison to pentoxifylline test cases (Experimental drug group EDG, 400mg 3 times daily, as coated, sustained release tablets). The stipulated treatment period was 7 months and a total of 29 cases of advanced fibrosis (14 test subjects and 15 age and sex matched diseased controls) were included in this study and 100% compliance was reported at the end ofthe test period.
                Mild gastric irritation that could be managed by diet protocols was the only untoward symptom reported during this trial. Review of the patients and controls was done at an interval of 30 days and subjective and objective measurements were recorded. The follow up data at each visit with respect to each other and to base-line values was calibrated using a nonparametric test of Mann-Whitney (Kruskal-Wallis test). Significant comparisons with regard to improvement were recorded as objective criteria of mouth opening (t=11.285, p= 0.000), tongue protrusion (t= 3.898, p = 0.002), and relief from perioral fibrotic bands (p = 0.0001554). Subjective symptoms of intolerance to spices (p = 0.0063218), burning sensation of mouth (p = 0.0005797), tinnitus (p=0.000042), difficulty in swallowing (p=0.0000714). and difficulty in speech (p=0.0000020) were also recorded significant improvement at the end of the trial period.
                This pilot investigation points to the effectiveness of pentoxifylline as an adjunct therapy in the routine management of oral submucous fibrosis. To assess the efficacy, incidence of dry mouth and overall satisfaction with initial doses of 5, 10 and 15 mg of a new, once-daily, controlled-release (CR) form of oxybutynin for treating urge urinary incontinence (UUI).
                Patients who reported urinary incontinence (UI) (one or more episodes/diary) and voiding frequency (eight or more voids/day) or urgency (one or more episodes/diary) during a 2-week baseline were randomized to once-daily 5, 10 or 15 mg CR oxybutynin for 4 weeks. Daily episodes of UI, voids, urgency, adverse events, dry mouth and satisfaction were recorded in a 3-day diary at baseline and after 4 weeks of treatment. In all, 237 patients were randomized and evaluated.
                Episodes of UI, voids and urgency were significantly reduced over the study period at all doses. Daily UI episodes were significantly lower with 15 mg/day than 5 and 10 mg/day. Dry mouth symptoms were similar in the 10 and 15 mg/day groups, and higher than in the 5 mg/day group. However, significantly greater overall satisfaction was reported with 15 than 5 mg/day.
                There were significant dose-response relationships with CR oxybutynin for both UI episodes and dry mouth. The greatest satisfaction was with 15 mg/day, and the severity of dry mouth was comparable at 10 mg/day, indicating that greater efficacy at the higher dose did not compromise tolerability. The purpose of this study was to examine the effects of various product combinations involving brush, paste, rinse, and floss on the prevention of plaque regrowth and gingivitis.
                In this randomized, parallel-group, examiner-blind, eight-week study, 179 subjects with gingivitis had a dental prophylaxis and were randomly assigned to one of six product combinations: 1) Colgate Wave manual toothbrush + Colgate Total dentifrice (0.3% triclosan/copolymer dentifrice); 2) Wave + Total + Listerine (essential oils rinse); 3) Oral-B CrossAction manual toothbrush + Crest Pro-Health dentifrice (0.454% stannous fluoride/sodium hexametaphosphate); 4) CrossAction + Pro-Health dentifrice + Crest Pro-Health Rinse (0.07% cetylpyridinium chloride rinse); 5) Oral-B ProfessionalCare Series 8000 power toothbrush + Pro-Health dentifrice; or 6) ProfessionalCare power brush + Pro-Health dentifrice + Oral-B Hummingbird power flosser. Subjects used their test products for the duration of the study. Whole mouth plaque, gingivitis, and product-related adverse events were assessed. Treatments were compared at a 0.05 level of significance.
                One-hundred and seventy-four subjects completed the study and were included in the data analysis. At Week 8, the overnight adjusted whole mouth plaque scores were statistically significantly lower in all other groups relative to the Wave + Total group (p < or = 0.030). Plaque scores were also statistically significantly lower (approximately 20%) in both groups where a therapeutic rinse was added to a manual brush and therapeutic paste relative to scores for the brush plus paste without a rinse (p < or = 0.034). All groups showed a reduction in gingivitis at Week 4, and mean scores remained stable or increased slightly at Week 8. The power toothbrush groups were directionally better at preventing gingivitis than the manual groups at Weeks 4 and 8.
                Reductions in overnight plaque were seen when therapeutic rinses were added to manual brush plus therapeutic dentifrice regimens above that observed with a manual brush and therapeutic dentifrice alone. Following therapeutic irradiation of the head and neck, patients with profound xerostomia have complaints associated with oral dryness, effects upon use of oral prosthesis, speech, and taste. In addition, xerostomia may lead to risk of oral infections and rampant demineralization of teeth. The use of topical Oral Balance gel and Biotene toothpaste (Laclede Professional Products, Gardena, CA) versus carboxymethylcellulose gel and commercial toothpaste applications was assessed in a 2-week double-blind, crossover design. The palliative effects of Oral Balance gel and Biotene toothpaste were superior to the effects of a placebo. No effect on oral colonization by Candida species and cariogenic oral microflora was seen with use of the topical agents. The properties of saliva led us to hypothesize that the salivary flow increase induced by gum chewing might protect the oral mucosa from lesions due to cancer chemotherapy. We conducted a multicenter randomized trial to evaluate the efficacy of chewing gum in preventing oral mucositis in 145 children receiving chemotherapy regimens expected to induce WHO grade 3-4 oral mucositis in at least 30% of patients. Patients were allocated at random to standard oral care with or without 5 gum pieces per day. No overall reduction in severe oral mucositis occurred in the gum arm (51%) compared with the standard arm (44%). VIDE, COPADM, and multidrug intensive chemotherapy caused severe oral mucositis in 75% of patients in both arms. In patients receiving less toxic regimens, a decrease in WHO grade 1-4 oral mucositis was noted in the gum arm compared with the standard arm (49% vs. 72%, P=0.03). In the multivariate analysis, the risk of oral mucositis was related only to the type of chemotherapy regimen, suggesting that further strategies for preventing oral mucositis could be mainly based on these criteria. Radiation therapy is an important curative modality in the treatment of patients with head and neck cancer. However, radiation-induced changes in the oral cavity, such as xerostomia and mucositis, are among the most debilitating treatment sequelae experienced by patients undergoing radiation therapy, and attempts at ameliorating these side effects have been poor at best. Pilocarpine has been approved for post-radiation xerostomia, and the effect of its use during radiation therapy on salivary flow, xerostomia, mucositis, and quality of life (QOL) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group (RTOG 97-09). In total, 245 evaluable patients were randomized to pilocarpine or placebo. Selected patients were required to have > or = 50% of the volume of the major salivary glands receive > or = 50Gy; to agree to provide stimulated and unstimulated samples of saliva (measured in g) before treatment, at the end of treatment, and 3 and 6 months after completion of radiation therapy; and to complete the University of Washington Head and Neck Symptom Scale. Following the completion of radiation therapy, the average unstimulated salivary flow was statistically greater in the pilocarpine group, whereas no difference was noted following parotid stimulation. There was no effect on the amelioration of mucositis. The results of the QOL scales did not reveal any significant difference between the pilocarpine and placebo groups with regard to xerostomia and mucositis. The significant difference in unstimulated salivary flow supports the concomitant use of oral pilocarpine to decrease radiation-associated xerostomia. However, the absent correlation between improved salivary flow and QOL scores is of some concern (though not a new finding) and may be related to the existence of comorbidities and the lack of effect on mucositis. The purpose of the study was to examine the anti-malodor, anti-gingivitis, and plaque reducing properties of a 2 phase oil:water mouthrinse compared with a control mouthrinse. Fifty subjects rinsed with one of the two rinses for 30 seconds twice a day over 6 weeks, while continuing their normal oral hygiene habits. Measurements were made at time zero (prior to beginning the rinsing regimen), and > or = 9 hours following rinsing, at intervals of 1, 3, and 6 weeks. Malodor of whole mouth, as well as tongue dorsum anterior and posterior, was assessed on a 0 to 5 semi-integer scale by two odor judges. Volatile sulphide compounds (VSC) were determined using a sulphide monitor. Gingival, plaque, and bleeding indices were recorded for Ramfjord teeth. Oral microbial levels were assessed using the oratest. Salivary levels of diamines (putrescine and cadaverine) were analyzed by HPLC. Results were analyzed by 2-tailed covariant ANOVA, with the time zero value as covariant. Dramatic improvements were observed in parameters associated with malodor, periodontal health, plaque accumulation, and microbial levels in both groups. As compared to time zero scores, whole mouth odor, tongue dorsum anterior and posterior odors decreased continuously over time, attaining 80%, 79% and 70%, reductions, respectively following 6 weeks, in the 2-phase mouthrinse group, versus 70%, 77% and 59% for the control group. For whole mouth and tongue dorsum posterior, the reductions observed in the 2-phase mouthrinse group were significantly greater than those obtained with the control mouthrinse (P = 0.026 and P = 0.025, respectively), suggesting that the 2-phase mouthrinse is superior to the control mouthrinse in long-term reduction of oral malodor. For bleeding index, gingival index, oral microbial levels, and VSC, differences between the groups were not significant. Diamine levels were not significantly reduced in either group. The control mouthrinse reduced plaque index more significantly than the 2-phase mouthrinse (P < 0.005). The results of this randomized clinical trial suggest that the 2-phase oil:water mouthrinse formulation is superior to the control mouthrinse in long-term reduction of oral malodor. The aim of the present study was to compare the cleansing properties of mechanical supportive care for dental implants with the use of an etching gel. Sixteen patients underwent a 5-month clinical trial with monthly recalls. These patients, wearing maxillary complete dentures and mandibular overdentures supported by a bar device on 4 implants, were treated in a split-mouth study design. Test and control therapy were randomly assigned to left and right sides of the mandible. At the test side, 35% phosphoric etching gel (pH 1) was applied in the peri-implant sulcus. After 1 minute, the sulcus was thoroughly rinsed with a water spray for approximately 15 seconds per implants. Control therapy consisted of supra- and subgingival debridement using carbon fiber curettes and a rubber cup. Plaque, calculus, probing pocket depth, and modified Gingival Index were determined before each treatment. Microbiologic evaluation was performed at baseline, 1 month later, and 5 months later, just before and immediately after each treatment. Per treatment and per assessment, the mean scores of all clinical parameters were calculated for each patient. The number of colony-forming units was used as the primary efficacy variable in the analysis of microbiologic data. At baseline, no differences between test and control sites were observed for any of the clinical parameters. The mean Gingival Index and the mean probing pocket depth were reduced over the 5-month period. The mean reduction in Gingival Index at the test sites proved to be significantly larger at the control sites (P = .03). Both treatment modalities resulted in an instant reduction of the number of colony-forming units, where the reduction by chemical cleaning was larger (P < .05). This short-term study employing a high recall frequency indicates that local application of 35% phosphoric acid gel can be as effective as conventional mechanical supportive therapy.
There is no strong evidence from this review that any topical therapy is effective for relieving the symptom of dry mouth. OGT spray is more effective than an aqueous electrolyte spray (SMD 0.77, 95% CI 0.38 to 1.15) which is approximately equivalent to a mean difference of 2 points on a 10-point VAS scale for mouth dryness. Chewing gums appear to increase saliva production in those with residual secretory capacity and may be preferred by patients, but there is no evidence that gum is better or worse than saliva substitutes. Integrated mouthcare systems and oral reservoir devices may be helpful but further research is required to confirm this. Well designed, adequately powered randomised controlled trials of topical interventions for dry mouth, which are designed and reported according to CONSORT guidelines, are required to provide evidence to guide clinical care. For many people the symptom of dry mouth is a chronic problem and trials should evaluate whether treatments are palatable, effective in reducing xerostomia, as well as the long-term effects of treatments on quality of life of those with chronic dry mouth symptoms.