Hairy leukoplakia; lessons learned: 30-plus years.

Well into the fourth decade of the HIV/AIDS pandemic, we can look back on the early years, the initial discoveries, and the broad sweep of the progress of our understanding of the nature, causes, and significance of the oral lesions seen in those infected with the virus. Prominent among these is oral hairy leukoplakia (HL), a previously unknown lesion of the mouth associated with Epstein-Barr virus (EBV) and initially seen only in people with AIDS, in the then-recognized risk groups, or those shown to be HIV positive. Subsequently, it became clear that the distribution of HL extends well beyond the HIV spectrum. In this brief review, we consider the clinical and histological features of HL, discuss how it was discovered, explore its cause, diagnosis, relationship with AIDS, pathogenesis, significance in EBV biology, options for management, and how it changes with HIV/AIDS therapy.

Physical and chemical characterization of dentin surface following treatment with NovaMin technology.

OBJECTIVE: The aim of this study was to characterize, in vitro, the mode of action of calcium sodium phosphosilicate (NovaMin) in occluding dentin tubules for the purpose of treating dentin hypersensitivity. METHODS: Calcium sodium phosphosilicate (CSPS) was combined with artificial saliva on surfaces of prepared dentin discs. The layer formed was initially examined by a scanning electron microscope (SEM). Focused ion beam (FIB) milling was used to make bulk cross-sections and thin film lamellae. Low kV scanning transmission electron microscopy (STEM), energy dispersive x-ray spectroscopy (EDS), and selected area electron diffraction were then used to characterize, chemically and structurally, the layer formed and the material occluding the tubules. Experiments were also performed to assess the suitability of using an environmental scanning electron microscope (ESEM) in wet mode to follow the transition from CSPS to hydroxyapatite. RESULTS: SEM imaging showed that a layer was formed on the treated dentin samples, and that this layer occluded tubules. Chemical and structural analysis of this material showed that it was hydroxyapatite-like. The wet mode ESEM experiments demonstrated that this technique has the potential to follow the transition from CSPS to the crystalline hydroxyapatite material. CONCLUSION: The use of modern imaging and analysis techniques has demonstrated, in vitro, the reaction of CSPS from an amorphous material to a crystalline hydroxyapatite-like material. These experiments confirmed an occlusion mode of action for CSPS for the treatment of dentin hypersensitivity.

Physical and chemical characterization of the surface layers formed on dentin following treatment with a fluoridated toothpaste containing NovaMin.

OBJECTIVE: To characterize in vitro the formation and robustness of a layer formed on dentin following treatment with a fluoridated toothpaste containing calcium sodium phosphosilicate (NovaMin) using modem imaging and analysis techniques. METHODS: Calcium sodium phosphosilicate (CSPS)-containing toothpaste was brushed on to etched dentin specimens twice daily for up to five days. In between applications the samples were stored in artificial saliva. Additionally, certain samples underwent a chemical challenge in the form of a dietary acid, whereby samples were exposed to a cola or grapefruit juice beverage for five minutes on day 4 of the five-day study. The ability of the CSPS-containing formulation to occlude tubules was assessed visually by scanning electron microscope (SEM) imaging and compared to a water control. In a second experiment, the mechanical resistance of the layer was assessed using profilometry after controlled brushing for 200 brush strokes with a wet medium-bristled toothbrush. To visualize the layer and characterize the tubule occlusion, longitudinal cross-sections were prepared using a focused ion beam scanning electron microscope (FIB SEM), and analysis performed by energy dispersive x-ray spectroscopy (EDS) and electron diffraction. Owing to the complexity of the mixed material deposited after application of the toothpaste, material from inside a dentin tubule was selectively removed after five days of treatment, and the morphologically different materials imaged and analyzed by electron diffraction in the transmission electron microscope (TEM). RESULTS: SEM inspection showed significant coverage of the dentin samples after application of CSPS toothpaste for all five days, in contrast to the water control where the majority of tubules remained open after all five days. Exposure of the NovaMin-treated samples to common dietary acids did not lead to re-exposure of the tubules. Profilometry measurements demonstrated an intact layer covering the dentin surface after one and five days. EDS analysis and electron diffraction indicated the layer and the material plugging the tubule to be a calcium phosphate material with a crystallographic structure similar to hydroxyapatite. CONCLUSION: CSPS contained in toothpaste formulations adhered to exposed dentin surfaces. The layer formed was resistant to acid and mechanical challenges. Characterization of this layer indicated it was hydroxyapatite-like in nature.

The Oral HIV/AIDS Research Alliance: updated case definitions of oral disease endpoints.

The Oral HIV/AIDS Research Alliance (OHARA) is part of the AIDS Clinical Trials Group (ACTG), the largest HIV clinical trials organization in the world. Its main objective is to investigate oral complications associated with HIV/AIDS as the epidemic is evolving, in particular, the effects of antiretrovirals on oral mucosal lesion development and associated fungal and viral pathogens. The OHARA infrastructure comprises: the Epidemiologic Research Unit (at the University of California San Francisco), the Medical Mycology Unit (at Case Western Reserve University) and the Virology/Specimen Banking Unit (at the University of North Carolina). The team includes dentists, physicians, virologists, mycologists, immunologists, epidemiologists and statisticians. Observational studies and clinical trials are being implemented at ACTG-affiliated sites in the US and resource-poor countries. Many studies have shared end-points, which include oral diseases known to be associated with HIV/AIDS measured by trained and calibrated ACTG study nurses. In preparation for future protocols, we have updated existing diagnostic criteria of the oral manifestations of HIV published in 1992 and 1993. The proposed case definitions are designed to be used in large-scale epidemiologic studies and clinical trials, in both US and resource-poor settings, where diagnoses may be made by non-dental healthcare providers. The objective of this article is to present updated case definitions for HIV-related oral diseases that will be used to measure standardized clinical end-points in OHARA studies, and that can be used by any investigator outside of OHARA/ACTG conducting clinical research that pertains to these end-points.

Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: To determine the impact of highly active antiretroviral therapy (HAART) on salivary gland function in human immunodeficiency virus (HIV) positive women from the Women's Interagency HIV Study (WIHS). DESIGN: Longitudinal cohort study. SUBJECTS AND METHODS: A total of 668 HIV positive women from the WIHS cohort with an initial and at least one follow-up oral sub-study visit contributed 5358 visits. Salivary gland function was assessed based on a dry mouth questionnaire, whole unstimulated and stimulated salivary flow rates, salivary gland enlargement or tenderness and lack of saliva on palpation of the major salivary glands. MAIN OUTCOME MEASURES: Changes in unstimulated and stimulated flow rates at any given visit from that of the immediate prior visit (continuous variables). The development of self-reported dry mouth (present/absent), enlargement or tenderness of salivary glands (present/absent), and absence of secretion on palpation of the salivary glands were binary outcomes (yes/no). RESULTS: Protease Inhibitor (PI) based HAART was a significant risk factor for developing decreased unstimulated (P = 0.01) and stimulated (P = 0.0004) salivary flow rates as well as salivary gland enlargement (P = 0.006) as compared with non-PI based HAART. CONCLUSIONS: PI-based HAART therapy is a significant risk factor for developing reduced salivary flow rates and salivary gland enlargement in HIV positive patients.

Differential effects of bone graft substitutes on regeneration of bone marrow.

BACKGROUND: This study used a rat tibial marrow ablation model to test the hypothesis that bone remodeling within the medullary canal varies with bone graft materials of different chemical compositions and structural properties, impacting marrow cavity restoration. Bone graft materials were selected based on their relative resorption or degradation in vivo and their osteogenic properties. METHODS: Following ablation of the right tibial marrow in male Sabra-strain rats, materials were implanted in the proximal marrow cavity: poly-D,L-lactide-co-glycolide 75 : 25 (PLGA); coralline-hydroxyapatite (HA), calcium-sulfate (CaSO4), collagen-HA-tricalcium phosphate granules, anorganic bovine bone mineral, demineralized bone matrix (DBM), 45S5 Bioglass (BG), PLGA with BG 50 : 50, PLGA : BG 80 : 20, and PLGA and PLGA:BG 50 : 50 plus bone marrow (BM). Control tibias were ablated but received no implants. At 2 (endosteal bone healing), 4 (marrow cavity remodeling) and 8 weeks (marrow restoration), six to eight animals per group were euthanized and tibias processed for histomorphometry of proximal and distal medullary canals. RESULTS: Control tibias showed primary bone in proximal and distal medullary canals at 2 weeks, with trabeculae surrounded by cellular marrow. At 4 and 8 weeks, control trabeculae were thinned and marrow had more fat cells. In the treated tibias, trabecular bone volume (TBV) varied with time and was material specific. Most implants supported comparable TBV at 2 weeks. Sites with CaSO4 or DBM exhibited decreased TBV with time whereas trabecular bone was retained in proximal tibias containing other materials, closely juxtaposed to the implants. TBV did not always correlate directly with implant volume, but changes in BM volume were correlated inversely with TBV. Addition of BM increased marrow restoration in sites containing PLGA; however, BM reduced restoration of marrow when added to PLGA : BG. Although the presence of implants in the proximal tibia resulted in retention of trabecular bone, there was a time-dependent reduction in TBV in distal canals; the rate and extent of the distal TBV reduction were implant dependent. CONCLUSIONS: Thus, although many materials can support bone formation in the marrow cavity, bone quality, quantity, and physical relationship to the implant, and its rate of resorption differ in a material-dependent manner, resulting in differences in the restoration of marrow. CLINICAL RELEVANCE: Bone graft materials should be selected not only for their ability to support new bone formation but also for their impact on the remodeling phase of bone healing.

BMP1 and TLL1 Are Required for Maintaining Periodontal Homeostasis.

Mutations in bone morphogenetic protein 1 (BMP1) in humans or deletion of BMP1 and related protease tolloid like 1 (TLL1) in mice lead to osteogenesis imperfecta (OI). Here, we show progressive periodontal defects in mice in which both BMP1 and TLL1 have been conditionally ablated, including malformed periodontal ligament (PDL) (recently shown to play key roles in normal alveolar bone formation), significant loss in alveolar bone mass ( P < 0.01), and a sharp reduction in cellular cementum. Molecular mechanism studies revealed a dramatic increase in the uncleaved precursor of type I collagen (procollagen I) and a reduction in dentin matrix protein 1 (DMP1), which is partially responsible for defects in extracellular matrix (ECM) formation and mineralization. We also showed a marked increase in the expression of matrix metallopeptidase 13 (MMP13) and tartrate-resistant acid phosphatase (TRAP), leading to an acceleration in periodontal breakdown. Finally, we demonstrated that systemic application of antibiotics significantly improved the alveolar bone and PDL damage of the knockdown phenotype, which are thus shown to be partially secondary to pathogen-induced inflammation. Together, identification of the novel roles of BMP1 and TLL1 in maintaining homeostasis of periodontal formation, partly via biosynthetic processing of procollagen I and DMP1, provides novel insights into key contributions of the extracellular matrix environment to periodontal homeostasis and contributes toward understanding of the pathology of periodontitis.

Oral lesions of HIV disease and HAART in industrialized countries.

The epidemiology of HIV-related oral disease in industrialized nations has evolved following the initial manifestations described in 1982. Studies from both the Americas and Europe report a decreased frequency of HIV-related oral manifestations of 10-50% following the introduction of HAART (highly active antiretroviral therapy). Evidence suggests that HAART plays an important role in controlling the occurrence of oral candidosis. The effect of HAART on reducing the incidence of oral lesions, other than oral candidosis, does not appear as significant, possibly as a result of low lesion prevalence in industrialized countries. In contrast to other oral manifestations of HIV, an increased prevalence of oral warts in patients on HAART has been reported from the USA and the UK. HIV-related salivary gland disease may show a trend of rising prevalence in the USA and Europe. The re-emergence of HIV-related oral disease may be indicative of failing therapy. A range of orofacial iatrogenic consequences of HAART has been reported, and it is often difficult to distinguish between true HIV-related oral disease manifestations and the adverse effects of HAART. A possible association between an increased risk of oral squamous cell carcinoma and HIV infection has been suggested by at least three epidemiological studies, with reference to the lip and tongue. These substantial and intensive research efforts directed toward enhancing knowledge regarding the orofacial consequences of HIV infection in the industrialized nations require dissemination in the wider health care environment.

Oral candidiasis in HIV infection: pseudomembranous and erythematous candidiasis show similar rates of progression to AIDS.

Candidiasis is the most common oral fungal infection seen in association with HIV infection. It may present in a number of clinical forms, including pseudomembranous and erythematous candidiasis. To determine whether erythematous candidiasis, like the pseudomembranous form, is predictive of the development of AIDS, we reviewed the records of 169 HIV-seropositive patients seen at clinic of the Oral AIDS Center, University of California, San Francisco who were diagnosed with pseudomembranous or erythematous (or both) forms of oral candidiasis at their first examination. Kaplan-Meier analysis showed a rapid rate of progression to AIDS (median, 25 months) and to death (median, 43.8 months) in all three groups. We conclude that erythematous candidiasis is as serious a prognostic indicator as pseudomembranous candidiasis. Because the erythematous form is more difficult to recognize and hence is underdiagnosed, efforts should be made to teach non-dental clinicians who care for HIV-infected patients to diagnose and treat this lesion.

Does HIV cause salivary gland disease?

HIV-associated salivary gland disease (HIV-SGD) is characterized by enlargement of the major salivary glands and/or xerostomia. HIV does not appear to play a direct role in this disease since it was detected by immunohistochemistry in only occasional lymphocytes in labial salivary glands in two out of six patients; it was not found in the salivary gland epithelial cells. Moreover, HIV was not found in any of 21 saliva samples from seven patients. We conclude that HIV-SGD is not caused by direct infection of the salivary glands with HIV.

Prevalence of HIV-associated periodontitis and gingivitis in HIV-infected patients attending an AIDS clinic.

We investigated the prevalence of HIV-associated periodontal disease in an AIDS clinic in San Francisco. Patient recruitment occurred over 6 months with 90% patient participation. In 136 patients, three forms of periodontal disease were recorded: HIV-associated gingivitis (HIV-G), HIV-associated periodontitis (HIV-P), and conventional non-HIV-associated periodontal disease. Diagnosis was based on defined clinical criteria established before the study began. For the HIV-associated diseases, two sets of diagnostic criteria were used. One consisted of clinical signs that included bleeding on probing, pocket depth, and attachment loss; and the other consisted of the same signs but did not require probing (the measurement of the depth of the gingival sulcus). Using the first set of these criteria, HIV-G was diagnosed in 42 patients [31%; 95% confidence interval (CI) 23 to 39%] and HIV-P in 5 (4%; 95% CI 1 to 7%). Using the second set, 68 patients were diagnosed with HIV-G (50%; 95% CI 42 to 58%) and 8 with HIV-P (6%; 95% CI 2 to 10%). All other categories of periodontal disease that were non-HIV-associated were diagnosed in 60 (44%) of patients. These results indicate that while the prevalence of HIV-P is low, the prevalence of HIV-G and conventional periodontal disease among HIV-infected individuals is high and should be considered in the dental care of these patients.

Randomized trial of itraconazole oral solution for oropharyngeal candidiasis in HIV/AIDS patients.

PURPOSE: Oropharyngeal candidasis (thrush) is the most common opportunistic infection in individuals who are positive for the human immunodeficiency virus (HIV) and those who have progressed to AIDS. Itraconazole has a broad in vitro spectrum of activity, including a wide variety of Candida species. Our study determined the relative efficacy of a new oral solution formulation of itraconazole and fluconazole tablets in the treatment of oropharyngeal candidiasis. PATIENTS AND METHODS: This was a prospective randomized, third-party-blind, multicenter trial conducted at 12 centers in the United States. One hundred seventy-nine HIV-positive patients with mycologically documented oropharyngeal candidiasis were treated with itraconazole oral solution 200 mg/ day for 7 or 14 days, or fluconazole tablets 100 mg/day for 14 days. Severity of disease was scored clinically before treatment and at clinical evaluations on days 3, 7, 14, 21, 35, and 42. Semi-quantitative cultures of mouth washings were also obtained on these days. RESULTS: Both 14-day and 7-day regimens of itraconazole oral solution were equivalent to fluconazole for most efficacy parameters. The clinical response rate was 97% after 14 days of itraconazole and 87% after 14 days of fluconazole. Itraconazole oral solution given for 7 days was also equivalent to fluconazole treatment for 14 days. Approximately one half of patients in all three groups relapsed by 1 month after completion of treatment. There were few adverse reactions to either drug. CONCLUSION: Itraconazole oral solution is well tolerated and offers an alternative at least as effective as fluconazole in the treatment of oropharyngeal candidiasis.

Osteoblast response to bioactive glasses in vitro correlates with inorganic phosphate content.

Inorganic phosphate (Pi) is a physiological regulator of osteoblasts and chondrocytes, suggesting that phosphate may contribute to the biological response of these cells to bioactive glasses like Bioglass 45S5, which is composed of 45% SiO2, 24.5% CaO, 24.5% Na2O, and 6% P2O5. We investigated the effect of varying the Pi content of bioactive glass disks (0%, 3%, 6% and 12% P2O5) using human osteoblast-like MG63 cells as the model. Cell number on 6% Pi disks was comparable to cultures on tissue culture plastic, but was reduced at higher and lower Pi concentrations. Alkaline phosphatase specific activity of isolated cells and cell layer lysates, as well as PGE2, TGF-beta1 and NO levels in conditioned media, were elevated in cultures grown on bioactive glass and varied with the Pi content. The greatest effects were observed in cultures grown on disks with the lowest Pi concentrations. Thus, growth on the bioactive glasses enhances cell function in comparison with tissue culture plastic and lower Pi content favors osteoblast differentiation.

The prevalence of xerostomia and salivary gland hypofunction in a cohort of HIV-positive and at-risk women.

The association of xerostomia and salivary gland hypofunction with HIV infection has been established for men but not for women. We investigated the prevalence of these conditions in a national cohort (n = 733) of HIV-positive and at-risk HIV-negative women. Participants in this prospective cross-sectional study were recruited from the Women's Interagency HIV Study (WIHS) at five outpatient USA clinics. Xerostomia was assessed based on "yes" responses to a dry-mouth questionnaire. Samples of unstimulated whole and chewing-stimulated whole saliva were collected under standardized conditions. The major salivary glands were also evaluated clinically. The prevalence of dry-mouth complaint, the absence of saliva upon palpation, and zero unstimulated whole saliva (flow rate = 0 mL/min) were significantly (p = 0.001) higher in HIV-positive women. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher in HIV-positive women vs. HIV-negative women (OR = 2.86; 95% CI, 1.23 to 6.63). Significant (p = 0.03) univariate association was found between zero unstimulated whole saliva and CD4 counts. Adjusted odds of zero unstimulated whole saliva were significantly (p = 0.02) higher for HIV-positive women with CD4 < 200 compared with those with CD4 > 500 (OR = 2.61; 95% CI, 1.17 to 5.85). Chewing-stimulated flow rates were not significantly different between seropositive and seronegative women. The prevalence of xerostomia and salivary gland hypofunction appears to be significantly higher in HIV-positive women relative to a comparable group of at-risk seronegative women. Immunosuppression levels measured by CD4 cell counts are significantly associated with xerostomia and salivary gland hypofunction in a population of HIV-positive women.

Dental caries in HIV-seropositive women.

Reports that compare dental caries indices in HIV-seropositive (HIV+) subjects with HIV-seronegative (HIV-) subjects are rare. The objective of this study was to determine if there was an association between HIV infection and dental caries among women enrolled in the Women's Interagency HIV Study. Subjects included 538 HIV+ and 141 HIV- women at baseline and 242 HIV+ and 66 HIV- women at year 5. Caries indices included DMFS and DFS (coronal caries) and DFSrc (root caries). Cross-sectional analysis of coronal caries data revealed a 1.2-fold-higher caries prevalence among HIV+ women compared with HIV- women. Longitudinally, DMFS increased with increasing age and lower average stimulated salivary volume. Root caries results were not significant except for an overall increased DFSrc associated with smoking. Anti-retroviral therapy was not identified as a risk factor for dental caries.

A new quantitative method to evaluate the in vitro bioactivity of melt and sol-gel-derived silicate glasses.

Two melt-derived glasses (45S5 and 60S) and four sol-gel glasses (58S, 68S, 77S, and 91S) have been synthesized. The activation energy for the silicon release was determined, and a very close correlation was observed between this value and published results of the bioactive behavior of the glasses. This relationship can be explained in terms of the influence of chemical composition, textural properties, and structural density on the silanol group formation and silicon dissolution. These measurements provide a quantitative method to evaluate the in vitro bioactivity of SiO(2)-based glasses. Preliminary studies suggest an activation energy gap (Ea) of 0.35-0.5 eV as a boundary between bioactive and nonbioactive glasses.

Xerostomia: diagnosis and management.

Xerostomia, or dry mouth, is a common complaint that may be caused by several conditions, which include side effects of a wide variety of drugs, such as antidepressants, therapeutic radiation to the head and neck, dehydration, diabetes, and diseases involving salivary glands, such as Sjögren's syndrome. The complaint of dry mouth may or may not be associated with decreased salivary gland function. Individuals with xerostomia complain of problems with eating, speaking, swallowing, and wearing dentures. Some people also complain of salivary gland enlargement or changes in taste. Lack of saliva may predispose one to oral infections, such as candidiasis, and increase the risk of dental caries. Management of the individual patient with xerostomia includes assessment of salivary gland function, replacement therapy, and prevention of caries and oral candidiasis. Early recognition and management of xerostomia may prevent devastating dental disease and help to improve the quality of life.

Accuracy of diagnoses of HIV-related oral lesions by medical clinicians. Findings from the Women's Interagency HIV Study.

OBJECTIVE: To determine if medical clinicians are as accurate as dental clinicians in recognizing diagnostic characteristics of HIV-related oral lesions. METHODS: In 355 HIV-infected participants at five Women's Interagency HIV Study sites, we paired oral examinations conducted within 7 days of each other by dental and medical clinicians. We used the former as a gold standard against which to evaluate the accuracy of the latter. We assessed the accuracy of the medical clinicians' findings based both on their observations of abnormalities and on their descriptions of these abnormalities. RESULTS: Dental clinicians diagnosed some oral abnormality in 38% of participants. When "abnormality" was used as the medical clinicians' outcome, sensitivities were 75% for pseudomembranous candidiasis and 58% for erythematous candidiasis, but only 40% for hairy leukoplakia. When a precise description of the abnormality was used as their outcome, sensitivities were 19%, 12% and 20%, respectively. CONCLUSIONS: Medical clinicians recognize that HIV-related oral abnormalities are present in 40-75% of cases, but less often describe them accurately. Low sensitivity implies that the true associations of specific oral lesions with other HIV phenomena, such as time until AIDS, must be stronger than the literature suggests.

The PRO-SELF Mouth Aware program: an effective approach for reducing chemotherapy-induced mucositis.

Many oncology patients receive chemotherapy drugs that have the potential to induce oral mucositis. If mucositis is not prevented, patients will have to manage the problems associated with mucositis: pain, local infection, and decreased ability to take fluids or food. At the time of this writing, clinical approaches for mucositis management are variable and generally ineffective. The mouth care program, PRO-SELF: Mouth Aware (PSMA), presented in this article, was found to be a significant component of a self-care program that may have reduced the incidence of chemotherapy-induced mucositis. The PSMA program has three dimensions: (a) didactic information, (b) development of self-care exercises (skills), and (c) supportive interactions with a nurse in the setting where the patients are receiving their treatment. This program focuses on decreasing the direct (i.e., incidence and severity of mucositis) and indirect morbidities of oral mucositis (i.e., number of local infections, level of discomfort/pain, and disruption in fluid and/or food intake). It provides the critical dimensions (i.e., specific information, self-care exercises, and nurse support) to promote the prevention of mucositis. The PSMA program is designed to provide patients with a definitive self-care repertoire to manage chemotherapy-induced mucositis in the home without the direct supervision of a health care provider.

Randomized clinical trial of chlorhexidine versus placebo for prevention of oral mucositis in patients receiving chemotherapy.

PURPOSE/OBJECTIVES: To test the effectiveness of a nurse-initiated systematic oral hygiene teaching program-PRO-SELF: Mouth Aware (PSMA)-in conjunction with two mouthwashes (0.12% chlorhexidine or sterile water) in preventing chemotherapy-induced oral mucositis. DESIGN: Randomized, double-blind, placebo-controlled, clinical trial. SETTINGS: 23 outpatient clinics and office practices in California. SAMPLE: 222 patients who were starting a cycle of mucositis-inducing chemotherapy. METHOD: Participants were followed over three chemotherapy cycles. All patients were provided the PSMA program. Random assignment to a mouthwash occurred prior to the development of oral mucositis. Researchers used the Oral Assessment Guide to assess the patients oral cavities monthly (with the patients cycles of chemotherapy) and when patients reported any oral changes between cycles. MAIN RESEARCH VARIABLES: Type of mouthwash, incidence, days to onset, and severity of chemotherapy-induced oral mucositis. FINDINGS: No significant differences existed between the two mouthwashes in regard to incidence, days to onset, and severity of mucositis. CONCLUSIONS: Because chlorhexidine (S20 per pint) was no more effective than water, a substantial cost savings can be realized by rinsing with water. Interestingly, the PSMA program appeared to reduce the incidence of mucositis from on a prior estimate of 44% to less than 26%. IMPLICATIONS FOR NURSING PRACTICE: A nursing prescription of a systematic oral hygiene program using water as a mouth rinse is cost efficient and may be effective in preventing oral mucositis.