Anticholinergic Burden and Dry Mouth Problems Among Older Adults (≥ 50 Years) Receiving Dental Care-A Retrospective, Cross-Sectional Analysis.

OBJECTIVES: Anticholinergics cause dry mouth and are highly relevant for dentists, but little is known about the relationships between intake and the occurrence of subjective and objective dry mouth with age. The German anticholinergic burden score (GACB) is a novel anticholinergic score that re-evaluates medications, particularly, those with classification discrepancies. MATERIAL AND METHODS: We retrospectively investigated the GACB in older patients receiving dental care, evaluated whether GACB is related to xerostomia and unstimulated salivary secretion, and determined the influence of increasing age (beginning at 50 years of age). The GACB score quantified cumulative anticholinergic effects: 0 for no effect, 1 for possible, 2 for moderate, and 3 for strong. Cross-sectional data in patients ≥ 50 years were collected, including xerostomia with the visual analog scale, unstimulated salivary flow rates, and the GACB scores. RESULTS: Among 172 patients (mean age 65.67 ± 9.51 years), 23.8% had a GACB score ≥ 1. A moderate negative correlation was observed between GACB and unstimulated salivary flow rates ( r ̅ $\mathop{r}\limits^{̅}$ = -0.51). Patients with GACB ≥ 1 had fewer teeth (mean 21.76 ± 5.41) than those with GACB = 0 (24.07 ± 5.57). Moreover, unstimulated hyposalivation was observed in 61.0% with GACB ≥ 1 versus 6.8% with GACB = 0 (p < 0.001). Escalating chronic systemic conditions and prescribed medications were recorded with increasing age; those aged 76-80 years had the highest burden. CONCLUSIONS: The GACB quickly and reliably assesses anticholinergic exposure and risks for oral health in older patients. Routine use in those aged ≥ 50 years could enable early identification of risks and initiation of preventive dental measures. TRIAL REGISTRATION: German Registry for Clinical Trials: DRKS00032877 (https://www.germanctr.de; date of registration: 17.10.2023).

Oral Risk Factors in Patients with Cancer Undergoing Chemotherapy - A Pilot Study.

BACKGROUND: Treatment modalities for cancer including surgery, radiotherapy and chemotherapy, have some complications even in the oral cavity. The literature describes oral lesions that may arise as a result of chemotherapy. However, information regarding oral symptoms in advanced cancer patients is poor. OBJECTIVE: To identify the oral manifestations like oral mucositis, dry mouth and loss of taste in patients undergoing chemotherapy treatment. METHODS: We evaluated 60 patients affected by malignancy undergoing chemotherapy treatment. The clinical and pathological data such as age, gender, diagnosis of malignancy and types of treatments with anticancer chemotherapeutic drug treatment, were obtained. Patients were routinely evaluated for the presence of oral mucositis based on the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale for adverse effects and graded. Other findings like dry mouth and loss of taste were recorded. RESULTS: Of the 60 patients, 40 (66.6%) were male, and 20 (33.3%) females with a mean age of 53.7 years. Most patients about 63% and 83% were diagnosed with dry mouth and loss of taste, respectively and 71% of patients had mucositis. Chemotherapy drugs like Cyclophosphamide, carboplatin, nanoxel, paclitaxel, oxaliplatin, docetaxel and doxorubicin, were directly associated with oral mucositis. CONCLUSION: Patients treated with chemotherapy for cancer most often suffer from a multitude of intense and debilitating oral dysfunctions. Oral lesions found in patients undergoing chemotherapy were mucositis, dry mouth and loss of taste. These adverse effects and an appropriate symptomatic therapy need to be discussed with the patients. Chemotherapy has a significant but transient effect on the oral symptoms.

Transdermal pilocarpine on the skin over salivary glands to increase salivation: an in vivo study.

BACKGROUND: Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats. METHODS: Pilocarpine was administered to rats orally (0.5 mg/kg) or topically on the salivary gland skin (5 mg/body). Saliva volume, the number of sweat dots, and fecal weight were measured along with pilocarpine concentration in plasma and submandibular gland tissues. RESULTS: Saliva volume significantly increased 0.5 h after oral administration and 0.5, 3, and 12 h after topical administration. Fecal weight and sweat dots increased significantly 1 h after oral administration; however, no changes were observed after topical application. The pilocarpine concentration in the submandibular gland tissues of the topical group was higher than that in the oral group at 0.5, 3, and 12 h of administration. CONCLUSIONS: Pilocarpine application to salivary gland skin persistently increased salivary volume in rats without inducing sweating or diarrhea. Transdermal pilocarpine applied to the skin over the salivary glands may be an effective and safe treatment option for hyposalivation.

Assessment of taste alteration and its correlation with nutritional status and quality of life among cancer patients undergoing chemotherapy.

BACKGROUND: Chemotherapy is the most commonly utilized therapeutic strategy among the numerous cancer treatments. These chemotherapeutic agents have a variety of adverse reactions, one of which is taste alteration (TA), which substantially influences the patient's nutritional status and quality of life (QoL). OBJECTIVE: The study aims to assess TAs, associated factors, and the nutritional status and QoL of cancer patients undergoing chemotherapy. METHODS: An observational cross-sectional study was carried out for 6 months, among cancer patients diagnosed with TA. Data was collected using a chemotherapy-induced taste alteration scale (CiTAS). Demographic details of the patients, factors associated with TA, details regarding chemotherapeutic agent used, number of current chemotherapy cycles etc, were recorded using a self-designed data collection form. Nutritional status and QoL on cancer patients were collected using Mini nutritional assessment - short form (MNA-SF) and EuroQol 5 dimension 5 levels (EQ5D5L), respectively, and statistical package for the social sciences (SPSS) software version 29 was used for the analysis of data. RESULTS: A significant association was observed between TA and QoL. There was also a significant association between TA and predisposing factors such as nausea and dry mouth, which was obtained from the Chi-square test. Male patients were found to have higher TA than female patients. TA has also affected various aspects of QoL, such as mobility, pain, and discomfort. Patients experiencing mouth dryness or xerostomia had higher TA than others. A negative association was seen between TAs and nutritional status. CONCLUSION: This study shows a significant relationship between gender and TA, dry mouth, nausea, and TA. Several QoL factors like mobility, pain/discomfort, and TA were also observed. Despite this study not observing any statistical association between nutritional status and TA, clinically, most of the patients with higher TA were malnourished. This study concluded that there was a relationship between TA and QoL and that nausea and dry mouth are the predisposing factors for TA.

Effect of cevimeline and different concentration of gum arabic on parotid salivary gland function in methotrexate-induced xerostomia: a comparative study.

OBJECTIVE: This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate. METHODS: One hundred twenty-five rats were divided into five equal groups of twenty-five each. The rats in Group I received basic diets, while those in Groups II, III, IV, and V received 20 mg/kg MTX as a single intraperitoneal dose on day one. Group III received 10 mg/kg CVM dissolved in saline orally and daily, and the other two groups received a 10% W/V aqueous suspension of GA. Therefore, Group IV received 2 ml/kg suspension orally and daily, while Group V received 3 ml/kg suspension orally and daily. After 9 days, the parotid glands were dissected carefully and prepared for hematoxylin and eosin (H&E) staining as a routine histological stain and caspase-3 and Ki67 immunohistochemical staining. Quantitative data from α-Caspase-3 staining and Ki67 staining were statistically analysed using one-way ANOVA followed by Tukey's multiple comparisons post hoc test. RESULTS: Regarding caspase-3 and Ki67 immunohistochemical staining, one-way ANOVA revealed a significant difference among the five groups. For Caspase-3, the highest mean value was for group II (54.21 ± 6.90), and the lowest mean value was for group I (15.75 ± 3.67). The other three groups had mean values of 31.09 ± 5.90, 30.76 ± 5.82, and 20.65 ± 3.47 for groups III, IV, and V, respectively. For Ki67, the highest mean value was for group I (61.70 ± 6.58), and the lowest value was for group II (18.14a ± 5.16). The other three groups had mean values of 34.4 ± 9.27, 48.03 ± 8.40, and 50.63 ± 8.27 for groups III, IV, and V, respectively. CONCLUSION: GA, rather than the normally used drug CVM, had a desirable effect on the salivary glands of patients with xerostomia.

Orally dissolving buprenorphine for opioid use disorder linked to caries.

BACKGROUND: Buprenorphine is under scrutiny because of the development of xerostomia and caries. The purpose of this article was to inform dental care professionals about the oral effects of buprenorphine and to increase knowledge and awareness of medication-assisted treatment in the management of opioid use disorder (OUD). CASE DESCRIPTION: In 2022, the US Food and Drug Administration issued a warning about xerostomia and caries associated with the use of transmucosal (sublingual and buccal formulations) buprenorphine. Dental health care professionals should instruct patients taking buprenorphine on how to prevent these dental issues by means of rinsing with water and swallowing once the drug has been completely dissolved, followed by toothbrushing at least 1 hour after taking the drug. In addition, a fluoride supplement should be prescribed. PRACTICAL IMPLICATIONS: It is imperative for dentists to recognize buprenorphine as medication-assisted treatment and to recognize a patient as having an OUD. While taking buprenorphine, the patient should have more frequent oral health care appointments, including home care instructions and caries risk assessment to monitor for caries and xerostomia so that treatment, if indicated, could be initiated as soon as possible. In addition, the dentist's role in OUD is to make sure patients follow the treatment recommendations and use the buprenorphine and to not have them discontinue because of potential caries risk.

Polymorphisms in ERBB4 and TACR1 associated with dry mouth in clozapine-treated patients.

BACKGROUND: Sialorrhea is a common and uncomfortable adverse effect of clozapine, and its severity varies between patients. The aim of the study was to select broadly genes related to the regulation of salivation and study associations between sialorrhea and dry mouth and polymorphisms in the selected genes. METHODS: The study population consists of 237 clozapine-treated patients, of which 172 were genotyped. Associations between sialorrhea and dry mouth with age, sex, BMI, smoking, clozapine dose, clozapine and norclozapine serum levels, and other comedication were studied. Genetic associations were analyzed with linear and logistic regression models explaining sialorrhea and dry mouth with each SNP added separately to the model as coefficients. RESULTS: Clozapine dose, clozapine or norclozapine concentration and their ratio were not associated with sialorrhea or dryness of mouth. Valproate use (p = 0.013) and use of other antipsychotics (p = 0.015) combined with clozapine were associated with excessive salivation. No associations were found between studied polymorphisms and sialorrhea. In analyses explaining dry mouth with logistic regression with age and sex as coefficients, two proxy-SNPs were associated with dry mouth: epidermal growth factor receptor 4 (ERBB4) rs3942465 (adjusted p = 0.025) and tachykinin receptor 1 (TACR1) rs58933792 (adjusted p = 0.029). CONCLUSION: Use of valproate or antipsychotic polypharmacy may increase the risk of sialorrhea. Genetic variations in ERBB4 and TACR1 might contribute to experienced dryness of mouth among patients treated with clozapine.

Oral Toxicities of PSMA-Targeted Immunotherapies for The Management of Prostate Cancer.

INTRODUCTION: Prostate Specific Membrane Antigen (PSMA)-targeted radionucleotide therapy has been shown to cause dry mouth, but the oral manifestations of PSMA-targeted immunotherapy have not been extensively studied. The aim of this study was to describe and quantify the oral manifestations of PSMA-targeted immunotherapies (bispecific antibodies or Chimeric Antigen Receptor T cell therapies) in the management of metastatic castration resistant prostate cancer. PATIENTS AND METHODS: We performed a retrospective analysis of the oral toxicities of PSMA-targeted immunotherapies of the patients seen at a single institution's cancer center between 2020 and 2023. Descriptive statistics were used to summarize the data. RESULTS: In a total of 19 patients treated with PSMA-targeted immunotherapies between 2020 and 2023, 9 patients (47%) experienced the following oral toxicities: xerostomia (n = 6; 32%), mucositis (n = 2; 10%), dysgeusia, dry throat and teeth sensitivity in (n = 1 each; 5%), respectively. Oral infections, such as candidiasis and herpes simplex, were not observed in any patients. Mucositis was managed with salt rinses and resolved within few months from onset. Xerostomia persisted in all the patients (median: 306 days, range: 98-484 days) among those who reported dry mouth at the time of data collection, despite treatment with salivary stimulants (n = 5; 83%). Dysgeusia was also persistent, although it was not specifically treated. CONCLUSIONS: Patients treated with PSMA-targeted immunotherapies for prostate cancer can present with various short-term and long-term off-tumor on-target oral toxicities including xerostomia and dysgeusia that may affect quality of life. This study serves as a foundation to future prospective studies with a larger sample size and also helps oncologists managing prostate cancer patients with targeted immunotherapies to familiarize common oral toxicities. Furthermore, we emphasize the importance of oral medicine consultation for a comprehensive oral examination and management of oral complications.

Actinium-225-PSMA radioligand therapy of metastatic castration-resistant prostate cancer (WARMTH Act): a multicentre, retrospective study.

BACKGROUND: Actinium-225 (225Ac) prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) is a novel therapy for metastatic castration-resistant prostate cancer (mCRPC). We aimed to report the safety and antitumour activity of 225Ac-PSMA RLT of mCRPC in a large cohort of patients treated at multiple centres across the world. METHODS: This retrospective study included patients treated at seven centres in Australia, India, Germany, and South Africa. We pooled data of consecutive patients of any age and Eastern Cooperative Oncology Group performance status with histopathologically confirmed adenocarcinoma of the prostate who were treated with one or more cycles of 8 MBq 225Ac-PSMA RLT administered intravenously for mCRPC. Previous lines of mCRPC treatment included taxane-based chemotherapy, androgen-receptor-axis inhibitors, lutetium-177 (177Lu) PSMA RLT, and radium-223 dichloride. The primary outcomes were overall survival and progression-free survival. FINDINGS: Between Jan 1, 2016, and May 31, 2023, 488 men with mCRPC received 1174 cycles of 225Ac-PSMA RLT (median two cycles, IQR 2-4). The mean age of the patients was 68·1 years (SD 8·8), and the median baseline prostate-specific antigen was 169·5 ng/mL (IQR 34·6-519·8). Previous lines of treatment were docetaxel in 324 (66%) patients, cabazitaxel in 103 (21%) patients, abiraterone in 191 (39%) patients, enzalutamide in 188 (39%) patients, 177Lu-PSMA RLT in 154 (32%) patients, and radium-223 dichloride in 18 (4%) patients. The median follow-up duration was 9·0 months (IQR 5·0-17·5). The median overall survival was 15·5 months (95% CI 13·4-18·3) and median progression-free survival was 7·9 months (6·8-8·9). In 347 (71%) of 488 patients, information regarding treatment-induced xerostomia was available, and 236 (68%) of the 347 patients reported xerostomia after the first cycle of 225Ac-PSMA RLT. All patients who received more than seven cycles of 225Ac-PSMA RLT reported xerostomia. Grade 3 or higher anaemia occurred in 64 (13%) of 488 patients, leukopenia in 19 (4%), thrombocytopenia in 32 (7%), and renal toxicity in 22 (5%). No serious adverse events or treatment-related deaths were recorded. INTERPRETATION: 225Ac-PSMA RLT shows a substantial antitumour effect in mCRPC and represents a viable therapy option in patients treated with previous lines of approved agents. Xerostomia is a common side-effect. Severe bone marrow and renal toxicity are less common adverse events. FUNDING: None.

Goji Berry Juice Prevents Tumor Necrosis Factor Alpha-Induced Xerostomia in Human Salivary Gland Cells.

Sjögren's syndrome (SS) is an autoimmune disorder characterized by oral dryness that is primarily attributed to tumor necrosis factor alpha (TNF-α)-mediated reduction in saliva production. In traditional Chinese medicine, goji berries are recognized for their hydrating effect and are considered suitable to address oral dryness associated with Yin deficiency. In the present study, we used goji berry juice (GBJ) to investigate the potential preventive effect of goji berries on oral dryness caused by SS. Pretreatment of human salivary gland cells with GBJ effectively prevented the decrease in aquaporin-5 (AQP-5) mRNA and protein levels induced by TNF-α. GBJ also inhibited histone H4 deacetylation and suppressed the generation of intracellular reactive oxygen species (ROS). Furthermore, GBJ pretreatment reserved mitochondrial membrane potential and suppressed the upregulation of Bax and caspase-3, indicating that GBJ exerted an antiapoptotic effect. These findings suggest that GBJ provides protection against TNF-α in human salivary gland cells and prevents the reduction of AQP-5 expression on the cell membrane. Altogether, these results highlight the potential role of GBJ in preventing oral dryness caused by SS.

Medication impact on oral health in schizophrenia.

BACKGROUND: Patients with schizophrenia constitute a particularly vulnerable group for oral diseases. Among the different factors involved, we aimed to examine the evidence of how drugs could contribute to the poorer oral health of this population. MATERIAL AND METHODS: An overview of the potential impact of medication on dental/oral health among people with schizophrenia was proposed focusing on selected literature. RESULTS: Studies show a higher dental caries and degree of periodontal diseases in this population and point to drug-induced xerostomia as an important risk factor for oral health deterioration. The risk of dry mouth depends on not only antipsychotics, but also drugs with anticholinergic activity. We hypothesize that antipsychotic induced glycaemic alterations might contribute to reduced oral health, and that the antimicrobial activity of certain antipsychotics could have an impact on oral microbiota affecting oral condition. Pharmacovigilance data show that involuntary movements are caused by typical and some atypical antipsychotics. Dry mouth is most frequently reported for quetiapine and olanzapine, while clozapine is more frequently associated with sialorrhea. CONCLUSIONS: Literature clearly shows higher caries and periodontal disease in schizophrenic patients. However, overall, there is scarce literature about the potential influence of drugs in these disorders. Health professionals should be aware of this issue in order to implement adequate preventive measures in this vulnerable population.

Xerostomia and prevention of dryness with a Pycnogenol® mouth spray: a pilot study.

BACKGROUND: The aim of this pilot, supplement study was the evaluation of primary, idiopathic mucosal mouth dryness (xerostomia or dry mouth) in subjects without systemic diseases. METHODS: Subjects with xerostomia were managed either with standard management (SM) or with SM and a Pycnogenol® mouth spray (Hankintatukku Oy, Karkkila, Finland), at the dosage of 60 mg/day in 30 spurts, for 2 weeks. RESULTS: A total of 50 subjects were included in the study: 25 controls using only standard management (SM) and 25 subjects using the Pycnogenol® mouth spray. No side effects and no tolerability problems were observed with the Pycnogenol® mouth spray. The groups were comparable for characteristics and symptoms at baseline. These otherwise healthy subjects had a BMI<26. After 2 weeks, salivary flow and salivary oxidative stress (in Carr Units) were improved significantly with Pycnogenol® mouth spray as compared to controls (P<0.05), whereas minimal improvements in salivary flow were seen with SM. The subjective symptomatic dry mouth score and the number of mucosal breaks and ulcerations (all minimal, <1 mm in length or diameter) were significantly decreased with the Pycnogenol® mouth spray supplement compared to SM controls (P<0.05). The Pycnogenol® mouth spray led to significant improvement in salivary lysozyme levels, compared to controls (P<0.05). CONCLUSIONS: Based on these preliminary results, Pycnogenol® mouth spray could be a new supplementary option for the management of primary xerostomia.

Characterization of dysgeusia and xerostomia in patients with multiple myeloma treated with the T-cell redirecting GPRC5D bispecific antibody talquetamab.

PURPOSE: In recent years, various immunotherapies have improved the survival of patients with multiple myeloma (MM). However, there remains an unmet need for novel agents. Talquetamab is the first-in-class GPRC5D-targeting T-cell redirecting bispecific antibody, which has substantial activity in advanced MM. Rapidly after the start of talquetamab treatment, patients reported taste changes (dysgeusia; 60% of patients), and a feeling of dry mouth (xerostomia; 30-57% of patients), which may be related to expression of the target antigen in healthy tissues, such as taste buds. Here, we aimed at better characterizing these oral toxicities. METHODS: We measured salivary flow and the ability to taste (objectively and patient-reported), assessed the feeling of dry mouth, and evaluated quality of life before and 8 weeks after the start of talquetamab therapy in eight heavily pretreated MM patients. RESULTS: Talquetamab treatment led to the rapid and significant decrease in objectively measured taste scores (total score 8.8 ± 2.0 vs 4.9 ± 2.5). All patients reported moderate to severe taste changes. Moreover, patients experienced severe xerostomia after the initiation of talquetamab treatment, in the absence of changes in unstimulated and stimulated salivary flow. Because of these oral toxicities a significant impairment in global health status/(oral health related) quality of life was reported. CONCLUSION: Studying taste changes in patients treated with talquetamab following up on the described leads provides a new and unique opportunity to further unravel the pathophysiology of taste changes after cancer treatment.

Anticholinergic burden of medications is associated with dry mouth and reflected in minor labial gland secretion.

OBJECTIVE: Medications with anticholinergic potential inhibit saliva secretion. Polypharmacy potentiates anticholinergic burden, causing dry mouth symptoms and chronic deterioration of oral health. Patients of any age can be affected by anticholinergic medication-triggered hyposalivation (the objective measure of dry mouth); therefore, seeking predictions of hyposalivation to screen dry mouth is needed. DESIGN: In our prospective, cross-sectional clinical study, 55 middle-aged adult patients participated. We examined whether the anticholinergic burden calculated from anticholinergic medications (anticholinergic drug score; ADS) and blood serum anticholinergic activity (SAA; the gold standard measure of anticholinergic burden) is associated with hyposalivation. As no prior studies measured minor salivary glands regarding the quantifiable anticholinergic burden, we assessed hyposalivation by the minor saliva flow (MSF) and unstimulated whole saliva (UWS) secretion. RESULTS: Our data showed a negative linear relationship between SAA and UWS (p < 0.05); when SAA increases by one pmol/ml unit, the saliva flow decreases by 0.058 ml/min. MSF showed a linear correlation (p < 0.005) with UWS. In a multivariate logistic regression model (including age, gender, race, smoking status, xerostomia severity, ADS, and BMI), we identified SAA and age as predictors of hyposalivation (p < 0.05). CONCLUSIONS: We provide evidence for the significant relationship between measurable anticholinergic burden and saliva flow. The correlation between UWS and MSF suggests that both saliva flow rate measurement methods could reflect anticholinergics-induced changes in salivary health.

Anticholinergic Burden and Xerostomia in Critical Care Settings.

BACKGROUND: Although previous studies have established the association of medications with anticholinergic adverse effects and xerostomia, anticholinergic burden and xerostomia in critical care settings are poorly characterized. The objective of this study was to determine the impact of medication burdens associated with anticholinergic adverse effects, particularly the occurrence of xerostomia (dry mouth) in a critical care setting. In addition, this study explored the correlation between the timing of the first instance of xerostomia and the administration timing of medication known to have anticholinergic adverse effects. METHODS: A retrospective case-control study was used with the MIMIC (Medical Information Mart for Intensive Care) III database. The MIMIC-III clinical database is a publicly available, deidentified, health-related database with more than 40 000 patients in critical care units from 2001 to 2012. Cases of xerostomia (n = 1344) were selected from clinical notes reporting "dry mouth," "xerostomia," or evidence of pharmacological treatment for xerostomia; control (n = 4032) was selected using the propensity analysis with 1:3 matching on covariates (eg, age, sex, race, ethnicity, and length of stay). The anticholinergic burden was quantified as the cumulative effect of anticholinergic activities using the Anticholinergic Burden Scale. RESULTS: Anticholinergic burden significantly differed between xerostomia patients and control subjects (P = .04). The length of stay was a statistically significant factor in xerostomia. The probability of developing the symptom of xerostomia within 24 hours was .95 (95%) for patients of xerostomia. CONCLUSIONS: Anticholinergic Burden Scale is associated with xerostomia in the critical care setting, particularly within 24 hours after admission. It is crucial to carefully evaluate alternative options for medications that may have potential anticholinergic adverse effects. This evaluation should include assessing the balance between the benefits and harms, considering the probability of withdrawal reactions, and prioritizing deprescribing whenever feasible within the initial 24-hour period.

Xerostomia: An easily ignored symptom induced by induction chemotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND: To investigate the prevalence and predictive factors of xerostomia during induction chemotherapy (IC) in patients with nasopharyngeal carcinoma (NPC). METHODS: We prospectively enrolled NPC patients who received IC between October 2020 and October 2021. The Visual Analogue Scale (VAS) and Xerostomia Inventory (XI) were used to evaluate the condition of xerostomia. The volume of the submandibular gland (SMG) was also calculated before and after IC. RESULTS: Fifty-two patients were enrolled in this study. Of these patients, 32.7% (n = 17) experienced xerostomia before IC. There were 32 (61.5%) patients suffered from xerostomia after IC, including 21 (40.4%) patients with newly diagnosed xerostomia after IC and 11 (21.1%) patients complained their xerostomia aggravated in those with xerostomia before IC. The median XI scores increased from 11 (standard deviation [SD], 2.930) to 18 (SD 3.995), 16 (SD 3.605), and 17 (SD 4.331) after the first, second, and third cycles of IC, respectively. The median score of VAS also increased from 0 to 4 during the following three cycles of IC. In those with IC-related xerostomia, the SMG volume after IC was significantly decreased compared with those without IC-related xerostomia (P = 0.001). The reduction of the SMG volume after IC was the independent risk factor for xerostomia (P = 0.002). CONCLUSION: Approximately two-thirds of NPC patients suffered from IC-related xerostomia and patients with a reduction of SMG volume after IC had a higher risk of xerostomia.

Protective Effect of Electroacupuncture on Chemotherapy-Induced Salivary Gland Hypofunction in a Mouse Model.

Radiotherapy and chemotherapy can impair salivary gland (SG) function, which causes xerostomia and exacerbate other side effects of chemotherapy and oral infection, reducing patients' quality of life. This animal study aimed to assess the efficacy of electroacupuncture (EA) as a means of preventing xerostomia induced by 5-fluorouracil (5-FU). A xerostomia mouse model was induced via four tail vein injections of 5-FU (80 mg/kg/dose). EA was performed at LI4 and LI11 for 7 days. The pilocarpine-stimulated salivary flow rate (SFR) and salivary glands weight (SGW) were recorded. Salivary immunoglobulin A (SIgA) and lysozyme were determined via enzyme-linked immunosorbent assay (ELISA). SG was collected for hematoxylin and eosin staining to measure acini number and acinar cell size. Tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and aquaporin 5 (AQP5) mRNA expressions in SG were quantified via RT-qPCR. 5-FU caused significant decreases in SFR, SGW, SIgA, lysozyme, AQP5 expression, and acini number, while TNF-α and IL-1ß expressions and acinar cell size were significantly increased. EA treatment can prevent 5-FU damage to the salivary gland, while pilocarpine treatment can only elevate SFR and AQP5 expression. These findings provide significant evidence to support the use of EA as an alternative treatment for chemotherapy-induced salivary gland hypofunction and xerostomia.

Association between medication-induced xerostomia and orofacial pain: a systematic review.

OBJECTIVE: Xerostomia (or oral dryness) is most commonly caused by medications that affect saliva secretion, and is often accompanied by symptoms of orofacial pain. Medication-induced xerostomia may or may not be associated with objectively demonstrable hyposalivation. The present study attempted to systematically identify an association between medication-induced xerostomia and orofacial pain. METHOD AND MATERIALS: A systematic search was conducted using the following databases: WoS, PubMed, SCOPUS, and MEDLINE. The search terms used were: xerostomia OR "dry mouth" AND medication AND ("oral pain" OR "orofacial pain" OR "craniofacial pain" OR "burning mouth" OR "glossodynia") NOT Sjögren's NOT cancer. Inclusion criteria were medication-induced xerostomia and reported symptoms of orofacial pain. Four researchers performed the selection process and quality assessment and two researchers conducted data extraction. RESULTS: Seven studies with a total of 1,029 patients were included. These studies were conducted between 2009 and 2022 and consisted of cross-sectional studies, case-control studies, and one randomized crossover trial. The studies consisted of a total of 1,029 participants. All studies included male and female participants whose mean ages ranged from 43 to 100 years. CONCLUSIONS: A positive association was found between medication-induced xerostomia and orofacial pain. No associations were found between salivary flow measurements (hyposalivation) and medication use. Future research should focus on saliva flow measurements, standardized assessment of medication-induced xerostomia, as well as the inclusion of accompanying orofacial pain diagnosis in the medical history to allow for higher level of evidence in establishing reliable predictors of medication-induced oral health damage to facilitate clinical prevention and management.

Dysfunction of the Salivary and Lacrimal Glands After Radioiodine Therapy for Thyroid Cancer: Results of the START Study After 6-Months of Follow-Up.

Background: Understanding of changes in salivary and lacrimal gland functions after radioactive iodine therapy (131I-therapy) remains limited, and, to date, no studies have evaluated dose-response relationships between absorbed dose from 131I-therapy and dysfunctions of these glands. This study investigates salivary/lacrimal dysfunctions in differentiated thyroid cancer (DTC) patients six months after 131I-therapy, identifies 131I-therapy-related risk factors for salivary/lacrimal dysfunctions, and assesses the relationships between 131I-therapy radiation dose and these dysfunctions. Methods: A cohort study was conducted involving 136 DTC patients treated by 131I-therapy of whom 44 and 92 patients received 1.1 and 3.7 GBq, respectively. Absorbed dose to the salivary glands was estimated using a dosimetric reconstruction method based on thermoluminescent dosimeter measurements. Salivary and lacrimal functions were assessed at baseline (T0, i.e., immediately before 131I-therapy) and six months later (T6) using validated questionnaires and salivary samplings, with and without stimulation of the salivary glands. Statistical analyses included descriptive analyses and random-effects multivariate logistic and linear regressions. Results: There was no difference between T0 and T6 in the level of parotid gland pain, nor was there difference in the number of patients with hyposalivation, but there were significantly more patients with dry mouth sensation and dry eyes after therapy compared with baseline. Age, menopause, depression and anxiety symptoms, history of systemic disease, and not taking painkillers in the past three months were found to be significantly associated with salivary or lacrimal disorders. Significant associations were found between 131I-exposure and salivary disorders adjusted on the previous variables: for example, per 1-Gy increase in mean dose to the salivary glands, odds ratio = 1.43 [CI 1.02 to 2.04] for dry mouth sensation, ß = -0.08 [CI -0.12 to -0.02] mL/min for stimulated saliva flow, and ß = 1.07 [CI 0.42 to 1.71] mmol/L for salivary potassium concentration. Conclusions: This study brings new knowledge on the relationship between the absorbed dose to the salivary glands from 131I-therapy and salivary/lacrimal dysfunctions in DTC patients six months after 131I-therapy. Despite the findings of some dysfunctions, the results do not show any obvious clinical disorders after the 131I-therapy. Nevertheless, this study raises awareness of the risk factors for salivary disorders, and calls for longer follow-up. Clinical Trials Registration: Number NCT04876287 on the public website (ClinicalTrials.gov).