Salivary gland function, development, and regeneration.

Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.

Comparisons of Non-Oral Immune-Related Adverse Events Among Patients With Cancer With Different Oral Toxicity Profiles.

OBJECTIVES: Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs. METHODS: A retrospective chart review was conducted to identify patients who started ICIT between December 11, 2011, and September 15, 2019 (n = 4683) in the Mass General Brigham Registered Patient Data Registry. Demographic information, cancer diagnosis, ICIT regimen, treatment duration, and time and number of infusions to irAE onset were recorded. Non-oral irAEs were categorized into 13 groups. Patients with melanoma, pulmonary cancer, or head and neck cancer who had oral irAEs were then matched with those without oral irAEs to compare the prevalence of concomitant non-oral irAEs. RESULTS: Three hundred and fourteen patients with oral irAEs with a mean age of 65.9 ±â€…12.6 years (43.3% females) were included. Patients with multiple oral irAEs were more likely to have non-oral irAEs (OR: 2.7, 95% CI, 1.3-3.5), including cutaneous (OR: 1.7, 95% CI, 1.1-3.0), rheumatological (OR: 2.2, 95% CI, 1.1-4.2), thyroid (OR: 2.4, 95% CI, 1.2-4.9), and neurological irAEs (OR: 2.5, 95% CI, 1.0-6.3). Compared to matched patients with non-oral irAEs, patients with oral irAEs were more likely to have cutaneous (OR: 1.7, 95% CI, 1.0-2.8) and thyroid (OR: 2.86, 95% CI, 1.1-7.5) irAEs. The development of oral and non-oral irAEs is often coincidental. CONCLUSION: Patients who have non-oral irAEs should be monitored for development of oral irAEs for prompt management.

PIEZO1 activation may serve as an early tissue biomarker for the prediction of irradiation-induced salivary gland dysfunction.

Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient's medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

A new approach to prevent radiation-induced xerostomia using intraglandular injection of mitochondria-boosting agents.

Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.

Long-term follow-up of protective effects on salivary and swallowing structures and improvement of late xerostomia and dysphagia by level IIb optimisation in clinical target volume of nasopharyngeal carcinoma.

BACKGROUND: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. RESULTS: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. CONCLUSIONS: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.

Impact of low-level laser therapy on the quality of life of patients with xerostomia undergoing head and neck radiotherapy: a systematic review.

PURPOSE: To carry out a systematic review to assess whether low-level laser therapy can improve the quality of life of patients with xerostomia undergoing head and neck radiotherapy. METHODS: A systematic search was performed through Embase, Medline/PubMed, Cochrane, Scopus, Web of Science, nonpeer-reviewed clinicaltrials.gov and LILACS. The strategy included clinical studies were selected that prospectively followed or evaluated the quality of life by directly comparing the use of low-level laser therapy for xerostomia induced by head and neck radiotherapy with alternative therapies without the use of a laser. The risk of bias in the studies was assessed by RoB 2.0 and Robins I. RESULTS: After all application of the predetermined criteria, four studies were included, dated between the years 2014 and 2023. Three studies described as randomized clinical trials were included, one of which was a randomized pilot study and only one was a prospective clinical trial. A total of 126 patients were evaluated, all four studies used the infrared wavelength, with two studies using the combination with the red wavelength. It was observed that low-level laser therapy can change the sensation of dry mouth, improving patients' quality of life. In addition, changes related to increased stimulated and unstimulated salivary flow were also identified. CONCLUSION: The use of low-level laser therapy has promising results on xerostomia, consequently improving the quality of life of patients undergoing radiotherapy in the head and neck region.

Radiation-induced xerostomia and cariogenic dietary habits.

PURPOSE: Despite the availability of various prevention methods, dental caries continue to be diagnosed in patients receiving head and neck radiotherapy (RT). Since conventional approaches do not evaluate posttreatment alterations in dietary behaviors, we aimed to assess the influence of radiation-induced xerostomia on post-RT cariogenic dietary habits in patients. METHODS: Fifty-seven patients completed the Xerostomia Questionnaire (XQ) and answered questions regarding daily cariogenic food and beverage (CFB) intake, daily tooth brushing, fluoride application, and subjective total taste acuity (STTA). They also underwent evaluations to determine the Simplified Oral Hygiene Index (OHI-S) score, Saxon test score, number of decayed-missing-filled teeth (DMFT), and proportion of DMFT to the test teeth (DMFT rate). Clinical records were searched for information regarding RT modalities, including the median of the mean dose to the parotid glands, days after the completion of RT, submandibular gland resection, whole-neck irradiation, and the DMFT value and rate before RT. The patients were divided into low and high XQ score groups based on the median XQ score of 47.5 for the two sample tests. Univariable and multivariable regression analyses were used to identify independent factors for frequent CFB intake. RESULTS: Higher XQ scores were associated with a significantly greater frequency of CFB intake (p = 0.028*). Regression analysis also identified a higher XQ score (p = 0.017*) as an independent risk factor for frequent CFB intake. CONCLUSION: Radiation-induced xerostomia increased the frequency of CFB intake.

Salivary, lacrimal and nasal (SALANS) measure to assess side effects following radioactive iodine treatment: development, psychometric properties, and factor structure.

PURPOSE: This study aimed to develop and psychometrically evaluate a patient-reported outcome measure (PROM), SAlivary, LAcrimal, NaSal (SALANS), to document patients' symptoms after radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC). METHODS: We generated and iteratively revised SALANS items based on expert input, focus group discussions and feedback from cognitive testing (n = 17). We administered an initial SALANS measure with 39 items to patients diagnosed with DTC in the past two years (n = 105). Exploratory factor analysis (EFA) examined the factor structure of the SALANS items. We assessed the consistency reliability and related the total and subscale scores of the final SALANS to existing PROMs to assess validity. RESULTS: The final SALANS consisted of 33 items and six subscales (sialadenitis, taste, xerostomia, dry eyes, epiphora, and nasal) with six factors extracted by EFA. The six subscales demonstrated good internal reliability (α range = 0.87-0.92). The SALANS total score showed good convergent validity with the Xerostomia Inventory (r = 0.86) and good discriminant validity with a measure of spirituality (r = - 0.05). The mean SALANS total score was significantly higher (d = 0.5, p < 0.04) among patients who had RAI compared to those who did not have RAI. CONCLUSION: Preliminary evidence suggests that SALANS is a novel and reliable PROM to assess the type and frequency all symptoms experienced after RAI treatment for DTC. Future work is needed to further validate and develop the scale.

Use of the modified Schirmer test to measure salivary gland hypofunction/hyposalivation: Systematic review and meta-analysis.

Although dry mouth is a relatively common condition, salivary flow is not routinely measured in dental clinical practice. Moreover, existing data regarding the use of the modified Schirmer test (MST) for the screening of dry mouth has not been summarized. This systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, aimed to determine whether the modified Schirmer test can be used to identify dry mouth. The databases of PubMed, Scopus, ScienceDirect, and CENTRAL (CRD42023393843) were systematically searched to retrieve articles published until 9th November 2023. Among the 343 original articles retrieved, six met the inclusion criteria. A total of 1150 patients, comprising 710 (61.7%) women and 440 (38.3%) men (mean age, 47.1 ± 7.3 years), were included. The meta-analysis revealed a weak correlation coefficient of r ¯ $\bar{r}$  = 0.42 (95% Cl: 0.29-0.55) between MST and the unstimulated salivary flow rate. Therefore, while the MST might offer a simple and accessible alternative for initial screening in the future, especially in non-specialized settings, its variability in sensitivity and specificity, along with an actual lack of standardization, necessitates cautious interpretation. Further studies are necessary before recommending the test in clinical routine.

Cross-cultural adaptation of the Thai Xerostomia Inventory and Summated Xerostomia Inventory.

OBJECTIVE: To cross-culturally adapt and validate the Thai version of the Xerostomia Inventory (XI) and Summated Xerostomia Inventory (SXI) for subjective evaluation of oral dryness in Thai middle-aged and older adults. METHODS: The original English versions of the XI and SXI were cross-culturally translated into Thai. Content validity was examined by the expert panel and 30 pilot subjects. The XI/SXI-Thai were then administered to 200 Thai adults (aged 50 years or older) for further assessment of psychometric properties. The standard question, the Bother Index, and the Xerostomia Questionnaire were used as comparator instruments for the evaluation of criterion and construct validity, respectively. Internal consistency reliability was assessed using Cronbach's alpha. RESULTS: The final XI/SXI-Thai were found to have good content validity. Both scales were able to distinguish between xerostomia and non-xerostomia groups. We observed moderate to strong correlation between the XI/SXI-Thai and other comparator instruments, reflecting good criterion and construct validity. Cronbach's alpha values were 0.875 and 0.847 for the XI-Thai and SXI-Thai, respectively. CONCLUSIONS: The XI-Thai and SXI-Thai were found to be valid, reliable, and easily administrable instruments for xerostomia assessment in Thai middle-aged and older individuals in both clinical and research settings.

A real-life experience of long-term use of pilocarpine in irradiated head and neck cancer patients.

AIMS: To assess long-term efficacy and side effects of pilocarpine on irradiated head and neck cancer (HNC) patients in both for prevention and treatment of radiation-induced xerostomia (RIX). METHODS: Retrospective observational study was conducted. Eligibility criteria included irradiated HNC patients who received pilocarpine at least 12 weeks either for prevention (group A) or for treatment (group B) of RIX. We collected the documented Late Effect Normal Tissue Task Force-Subjective, Objective, Management, Analytics subjective/objective grades of RIX before (only group B) and the latest visit for pilocarpine prescription, dosage, side effects, duration of treatment, and the cause of discontinuation. RESULTS: Between December 2007 and June 2022, 182 patients were enrolled including 95 patients (52%) in group A and 87 patients (48%) in group B. Group A patients reported grades 1, 2, 3, and 4 objective RIX in 0%, 7%, 93%, and 0%. Grade 1, 2, and 3 subjective RIX were 57%, 28%, and 15%. All patients in group B had grade 3 both objective/subjective RIX. The overall improvement of objective/subjective RIX was found in 40%/83%. Discontinuation was found in 51% of patients due to tolerable symptoms or deterioration of the patient's status. CONCLUSIONS: Based on this retrospective analysis, long-term use of pilocarpine in irradiated HNC appears feasible for both prevention and treatment of RIX.

Oral conditions are associated with salt taste disability among American adults.

AIM: To explore the association between oral conditions and their interaction with salt taste disability among American adults. METHODS: Data from the 2013-2014 NHANES cycle were used (n = 2373). The exposures were periodontitis, defined by the 2017 EFP-AAP classification, dental caries, missing teeth, and edentulism, as per the DMF-T index, and xerostomia. The outcome was salt taste disability, objectively assessed. Covariates included sex, age, educational level, poverty index, obesity, diabetes, smoking, alcohol consumption, and medications related to mouth dryness. Weighted multivariable logistic regression modeling was used to evaluate the relationship between oral conditions and their interaction and salt taste disability. RESULTS: Participants who reported xerostomia were more likely to have salt taste disability (OR 2.42; 95%CI 1.44-4.07), especially those older than 60 years (OR 3.63; 95%CI 1.72-7.63). Among participants aged 40-59, xerostomia increased the chance of salt taste disability; however, the confidence interval included the null value. The interactions between xerostomia and edentulism increased the chance of salt taste disability. CONCLUSION: Oral conditions seem to influence the ability to taste salt. Dental professionals may help identify individuals with taste alterations and raise their awareness of the risk of systemic diseases that require the reduction of salt intake.

Oral Candida in post-radiotherapy patients with xerostomia/hyposalivation: A narrative review.

OBJECTIVE: Head and Neck Cancer (HNC) patients receiving radiotherapy (RT) often suffer from xerostomia and/or hyposalivation. As saliva plays an important antimicrobial and cleansing roles, these patients are at higher risks of opportunistic infections. This narrative review aims to provide an overview of current evidence on oral Candida colonisation and infection in these patients. METHODS: A literature review of clinical studies on oral Candida colonisation and candidiasis in HNC patients receiving radiotherapy/chemoradiotherapy was conducted. RESULTS: Many clinical studies found high levels of Candida colonisation and a substantial proportion of post-RT HNC patients suffering from oropharyngeal candidiasis (OPC). Importantly, oral Candida could be a reservoir for life-threatening systemic infection in immunocompromised patients. The rising prevalence of non-albicans Candida species and drug-resistant infections has made identification of Candida species and antifungal susceptibility more important. Recent advances in oral microbiome and its interactions with Candida are discussed. This review also offers perspectives on limitations of current evidence and suggestions for future research. CONCLUSION: Further research to better understand Candida carriage, microbiome, OPC, and xerostomia/hyposalivation post-RT would aid in devising a more comprehensive long-term management plan and novel therapeutic approaches for HNC patients to achieve the full benefits of RT while minimising side effects.

Validation of the Korean version of the Summated Xerostomia Inventory among older adults residing in nursing homes.

BACKGROUND: Xerostomia is commonly experienced by older individuals. We sought to develop and evaluate the reliability and validity of the Korean version of the Summated Xerostomia Inventory (K-SXI) among older adults residing in long-term care facilities (LTCFs) in Korea. METHODS: In this secondary data analysis study using cross-sectional data, a cross-cultural adaptation process was conducted for the Korean version before data collection. Data collection was conducted from July 2021 to January 2022, targeting 544 older adults in 16 LTCFs. Data analysis included intraclass correlation coefficient (ICC) for test-retest reliability, and Cronbach's α for internal consistency reliability. Exploratory and confirmatory factor analyses were used to verify construct and convergent validity. Test-retest analysis was performed 6 weeks after baseline. Convergent and concurrent validities were assessed with age group and the xerostomia standard single question, respectively. RESULTS: A total of 544 older adults participated in this study. The mean of total K-SXI score was 11.70 (standard deviation, 4.96) points. The ICC value was calculated to be 0.90, and Cronbach's α of K-SXI was 0.92. Exploratory factor analysis revealed a single factor, explaining 74.8% of the total variance, however, some goodness-of-fit indices of the single factor model were found to be unsuitable in confirmatory factor analysis. The convergent and concurrent validity were supported. CONCLUSION: The present study provides evidence supporting the validity and reliability of the K-SXI for measuring xerostomia in institutionalized older adults in Korea.

Age related impairments in ingestion from a large population based-sample.

OBJECTIVES: Epidemiological data regarding the evolution of problems related to mastication and swallowing with age are lacking. This study aims to (i) describe changes in oral function with age, using data from a large French population, (ii) validate online, self-report uses of an ICF questionnaire in older persons, and (iii) assess whether impairment is related to avoidance of certain foods, xerostomia, body mass index (BMI) and oral health related quality of life (OHRQoL). METHODS: Volunteers aged ≥18 years with internet access completed a series of questionnaires on sociodemographic, anthropometric and oral health characteristics (oral function, Xerostomia Index (XI), OHRQoL, reasons for avoidance of certain food). Oral function was assessed using items derived from the International Classification of Functioning (ICF). Five ICF items related to ingestion function and six items related to activities and participation were used. A validation study was undertaken to identify those with poor chewing ability and low salivary flow amongst older participants reporting impairment. FINDINGS: 39 597 individuals were included. The prevalence of individuals with impairment for ICF items related to ingestion function and oral activity (eating, drinking and speaking), and the percentage of participants with poor OHRQoL increased significantly with age (p < 0.001). Each ICF item was significantly associated with OHRQoL (p < 0.001), XI (p < 0.001), BMI (p < 0.001) and avoidance of certain food due to chewing or swallowing difficulties. CONCLUSION: Overall, 21.5% and 13.5% of the study population had chewing and/or biting impairments respectively, which might affect food selection and consumption. These findings raise individual and population-based issues. Further studies are needed to assess whether impairment in oral function might increase frailty in older individuals, and also to compare data with those from other countries.

Efficacy of lemon mouthwash in improving dry mouth symptoms and salivary flow in hemodialysis patients.

BACKGROUND/AIMS: Gargling mouthwash is a safe and convenient oral care intervention; it rinses the mouth and increases salivary flow rate. The effectiveness of lemon mouthwash in relieving xerostomia and increasing the salivary flow rate among hemodialysis patients has not been studied. Our study sought to analyze the effectiveness of varying concentrations of lemon in mouthwash solutions on xerostomia and salivary flow rate. METHODS: A multi-concentration test was used to assess lemon mouthwash at 20%, 15%, 10%, 5%, and 2.5% concentrations to determine the optimal concentration for relieving dry mouth and increasing salivary flow rate. Generalized estimating equations were used to analyze the differences between various concentrations of lemon mouthwash and bassline values. RESULTS: In total, 44 patients were recruited. The 10% lemon concentration mouthwash was the most effective for increasing salivary flow rate, but the 5% and 2.5% were better accepted by the participants. Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients. CONCLUSIONS: Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients.

The supportive use of photobiomodulation on salivary glands: a narrative review and meta-analysis.

PURPOSE: Radiotherapy is one of the main strategies used in the treatment of cancer patients and it can cause early or late xerostomia and/or hyposalivation. Therapeutic management of xerostomia includes oral hygiene, sialogenic agents among others. METHODS: This study reviews the use of extra-oral salivary glands photobiomodulation in treating xerostomia and/or hyposalivation after radiotherapy and performs a meta-analysis of this data. RESULTS: After a broad search of the literature, eight clinical studies were selected. DISCUSSION: In a safe way, the studies found that extra-oral stimulation of the salivary glands has benefits in the hyposalivation and changes in salivary flow resulting from lesions by radiotherapy. A meta-analysis found significant values in pain comparing the pre- and post-treatment moments (MD - 3.02, I2 95%, IC - 5.56; - 0.48) and for stimulated salivary flow at 30 days after the end of radiotherapy (MD 2.90, I2 95%, IC 1.96; 3.84). CONCLUSION: The most promising parameters comprise wavelengths between 630 and 830 nm, radiant exposure from 2 to 10 J/cm2, two-to-three times a week, before the radiotherapy damage, and homogeneously in the glands. Therefore, Light-Emitting Diode (LED) stimulation of larger areas than the punctual stimulation of small millimeters of the Low-Level Laser Therapy (LLLT) appears to be promising.

Does lower dose pilocarpine have a role in radiation-induced xerostomia in the modern radiotherapy era? A single-center experience based on patient-reported outcome measures.

PURPOSE: This study aims to investigate the efficacy of lower dose pilocarpine in alleviating late dry mouth symptoms in head and neck cancer patients received radiotherapy. METHODS: Eighteen head and neck cancer patients experiencing persistent dry mouth were enrolled in this study. All participants started pilocarpine treatment a median of 6 months post-radiotherapy. Initially, patients received pilocarpine at 5 mg/day, with a gradual increase to the recommended dose of 15 mg/day. A Patient-Reported Outcome Measurement (PROMs) questionnaire assessed symptoms' severity related to hyposalivation. RESULTS: All patients reported symptomatic dry mouth above grade 2 before starting the medication. Pilocarpine treatment continued based on patients' self-assessment, with a median duration of 12 months (range, 3-36 months). The median daily maintenance dose was 10 mg (range, 5 to 20 mg). Total PROMs scores significantly decreased following medication, from 13 points (range 7-18 points) to 7 points (range 4-13 points) (p = 0.001). Significant improvements were observed in questions related to dry mouth (p < 0.001), water intake during eating (p = 0.01), carrying water (p = 0.01), taste (p < 0.001), and water intake during speech (p < 0.001). Initial and maintenance doses of pilocarpine were lower, and the duration of pilocarpine usage was shorter in patients treated with intensity-modulated radiation therapy compared to conformal radiotherapy (12 months vs. 25 months, p = 0.04). CONCLUSION: Pilocarpine may be considered at doses lower for late-term dry mouth. With modern radiotherapy techniques effectively preserving the parotid gland, short-term use may be recommended in these patients. Future studies may enhance the development of a more robust patient selection criteria model.

Efficacy of natural enzymes mouthwash: a randomised controlled trial.

OBJECTIVES: Natural enzymes mouthwash has been proposed as salivary substitutes to treat xerostomia. This study aims to evaluate the efficacy of the mouthwash to treat xerostomia. MATERIALS AND METHODS: A double-blind, parallel group randomised control clinical trial involving N = 49 adult participants with xerostomia was carried out. Intervention group received natural enzymes moisturising mouthwash (with active ingredients lactoferrin, lysozyme, lactoperoxidase and glucose oxidase); while control group received benzydamine mouthwash. Mouthwashes were repacked, labelled with specific code, and were given to participants by third-party. Subjects were instructed to rinse with the mouthwash 4 times per day at a specific period, for 2 weeks. Symptoms of xerostomia were assessed using Xerostomia Inventory at day 0 and 14; together with the assessment of Clinical Oral Dryness Score (CODS), and measurement of resting and stimulated salivary flow rate. RESULTS: 48 participants completed the clinical follow-up, and n = 1 had lost of follow-up. From the 48 participants, n = 23 received natural enzymes mouthwash, while n = 25 received benzydamine mouthwash. Intervention group achieved reduction in symptoms of xerostomia from baseline. Intervention group also showed significantly better improvements in the cognitive perception of dry mouth and oromotor function such as chewing, swallowing and speech of the participants; and reduction in waking up at night to drink water (p < 0.05). The CODS and resting salivary flow rate were also significantly improved in intervention group (p < 0.05). CONCLUSION: Use of natural enzymes mouthwash improved signs and symptoms of xerostomia. CLINICAL RELEVANCE: Natural enzymes mouthwash is potentially effective to treat xerostomia, well-tolerated and safe to be used by xerostomia patients. CLINICAL TRIAL REGISTRATION NUMBER: This study was retrospectively registered in ClinicalTrials.gov ID NCT05640362 on 7 December 2022.

A novel test for hyposalivation using a sugar cube.

BACKGROUND: Hyposalivation is a highly prevalent condition in old persons. OBJECTIVES: The aim of this study was to assess a novel tool for the diagnosis of hyposalivation using a sugar cube and to compare its reliability to other validated test methods. METHODS: Five tests were performed: unstimulated salivary flow test by draining method (USFT), oral moisture device Mucus® (MCS), sugar cube test (SCT), stimulated salivary flow test by chewing gum (CG) and Saxon test (SX). The sugar cube test consisted in measuring the time needed to disintegrate a standard-sized sugar cube N°4 (5.6 g) placed beneath the tongue. Bivariate correlation analyses were performed. ROC curve analysis and the Youden Index were used to determine the cut-off value. Sensitivity and specificity were calculated according to the determined cut-off point. RESULTS: A total of 121 participants were recruited, with an average age of 49.8 ± 18.2 years. The USFT was best correlated with the SCT. No correlation was found between SCT and the stimulated saliva tests (CG, SX) as well as the MCS test. According to the Youden index, 140 s is appropriate to diagnose hyposalivation. Sensitivity of .64 and specificity of .91 were found for SCT using USFT as gold standard. The mean subjective evaluation score of the SCT was 3.1 ± 1, significantly higher than USFT 2.6 ± 1.1 (p < .05). CONCLUSIONS: The sugar cube test proved to be a useful method for assessing unstimulated salivation, reducing test execution time and causing less participant discomfort than the gold standard unstimulated salivary flow test.