Acupuncture for Chronic Radiation-Induced Xerostomia in Head and Neck Cancer: A Multicenter Randomized Clinical Trial.

Importance: Patients with head and neck cancer who undergo radiotherapy can develop chronic radiation-induced xerostomia. Prior acupuncture studies were single center and rated as having high risk of bias, making it difficult to know the benefits of acupuncture for treating radiation-induced xerostomia. Objective: To compare true acupuncture (TA), sham acupuncture (SA), and standard oral hygiene (SOH) for treating radiation-induced xerostomia. Design, Setting, and Participants: A randomized, blinded, 3-arm, placebo-controlled trial was conducted between July 29, 2013, and June 9, 2021. Data analysis was performed from March 9, 2022, through May 17, 2023. Patients reporting grade 2 or 3 radiation-induced xerostomia 12 months or more postradiotherapy for head and neck cancer were recruited from community-based cancer centers across the US that were part of the Wake Forest National Cancer Institute Community Oncology Research Program Research Base. Participants had received bilateral radiotherapy with no history of xerostomia. Interventions: Participants received SOH and were randomized to TA, SA, or SOH only. Participants in the TA and SA cohorts were treated 2 times per week for 4 weeks. Those experiencing a minor response received another 4 weeks of treatment. Main Outcomes and Measures: Patient-reported outcomes for xerostomia (Xerostomia Questionnaire, primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General) were collected at baseline, 4 (primary time point), 8, 12, and 26 weeks. All analyses were intention to treat. Results: A total of 258 patients (201 men [77.9%]; mean [SD] age, 65.0 [9.16] years), participated from 33 sites across 13 states. Overall, 86 patients were assigned to each study arm. Mean (SD) years from diagnosis was 4.21 (3.74) years, 67.1% (n = 173) had stage IV disease. At week 4, Xerostomia Questionnaire scores revealed significant between-group differences, with lower Xerostomia Questionnaire scores with TA vs SOH (TA: 50.6; SOH: 57.3; difference, -6.67; 95% CI, -11.08 to -2.27; P = .003), and differences between TA and SA (TA: 50.6; SA: 55.0; difference, -4.41; 95% CI, -8.62 to -0.19; P = .04) yet did not reach statistical significance after adjustment for multiple comparisons. There was no significant difference between SA and SOH. Group differences in Functional Assessment of Cancer Therapy-General scores revealed statistically significant group differences at week 4, with higher scores with TA vs SOH (TA: 101.6; SOH: 97.7; difference, 3.91; 95% CI, 1.43-6.38; P = .002) and at week 12, with higher scores with TA vs SA (TA: 102.1; SA: 98.4; difference, 3.64; 95% CI, 1.10-6.18; P = .005) and TA vs SOH (TA: 102.1; SOH: 97.4; difference, 4.61; 95% CI, 1.99-7.23; P = .001). Conclusions and Relevance: The findings of this trial suggest that TA was more effective in treating chronic radiation-induced xerostomia 1 or more years after the end of radiotherapy than SA or SOH. Trial Registration: ClinicalTrials.gov Identifier: NCT02589938.

[Salivary gland disorder: consider IgG4-related disease]. / Speekselklierafwijking: denk aan IgG4-gerelateerde ziekte.

A 73-year-old man was presented with painless, bilateral swelling of the submandibular salivary glands and unilateral swelling of the parotid gland on the right side, and complaints of dry mouth. A parotid biopsy was taken and a serologic exam was carried out, resulting in the diagnosis of IgG4-related disease. IgG4-related disease is a rare systemic disorder that can cause symptoms in the head and neck region. Usually there are complaints of bilateral, painless swelling of the submandibular, parotid and/or lacrimal glands, with or without complaints of dryness of the mouth and eyes.

Oral health status, related behaviours and perceived stress in xerostomia, Sicca and Sjögren's syndromes patients - a cross-sectional study.

BACKGROUND: Mouth dryness increases the risk of some oral health-related conditions. Furthermore, it is unclear if patients with dry mouth engage in appropriate oral health-related behaviours. The study examined oral health, related behaviours, and perceived stress in dry-mouth patients and compared them to matched controls without mouth dryness. METHODS: Information about 182 dry-mouth patients and 302 age- and sex-matched subjects was retrieved. Three dry mouth groups: xerostomia, Sicca syndrome and Sjögren's syndrome, were formed based on patient self-reported and objectively assessed symptoms. The World Health Organization's Oral Health for Adults and Perceived Stress Scale (PSS-10) questionnaires inquired about sociodemographic characteristics, oral health-related behaviours, and self-perceived stress. Clinical oral health assessments included: caries experience measured as total numbers of decayed (DS), missing (MS), filled surfaces (FS), number of remaining teeth, erosive tooth wear and extent of periodontal pocketing. Data were analyzed using bivariate and multivariable tests. RESULTS: The dry-mouth participants had higher mean (SD) DMFS scores than their matched controls: xerostomia patients vs. controls: 74.6 (34.4) and 66.3 (35.4), Sicca syndrome patients vs. controls: 88.3 (34.0) and 70.1 (33.9), and Sjögren's syndrome patients vs. controls: 95.7 (31.5) and 74 (33.2). In comparison to controls, individuals with Sicca and patients with Sjögren's syndromes had lower mean (SD) number of remaining teeth, 15.9 (10.1) vs. 21.7 (8.4) and 13.8 (10.0) vs. 20.1 (9.2), and a lower mean (SD) extent of periodontal pocketing, 20.7 (28.6) vs. 41.1 (31.0), and 21.2 (24.1) vs. 34.8 (34.2), respectively. Xerostomia, Sicca syndrome and Sjögren's syndrome patients had higher odds of using fluoridated toothpaste; OR 1.8 (95%CI 1.1-2.9), OR 5.6 (95%CI 1.7-18.3) and OR 6.9 (95%CI 2.2-21.3), respectively. Participants with Sjögren's syndrome had lower odds of the last dental visit being within the last year; OR 0.2 (95%CI 0.1-0.8). CONCLUSIONS: Dry-mouth patients had higher caries experience and fewer teeth than comparison groups but a lower extent of periodontal pocketing. Even though more participants with dry mouth used fluoridated toothpastes, their oral health-related behaviours were not optimal.

Factors associated with age-related changes in oral diadochokinesis and masticatory function in healthy old adults.

BACKGROUND: This cross-sectional study aimed to identify factors associated with age-related changes in masticatory performance (MP) and oral diadochokinesis (ODK) and to provide normal values in healthy old adults for the diagnosis of oral frailty. METHODS: A total of 385 participants were divided into three age groups (Gr1-3): 20-64 years, 65-74 years, and ≥ 75 years. To investigate tongue-lip motor function, ODK was assessed as the number of repetitions of the monosyllables /pa/ta/ka/. Four questionnaires were used to assess subjective masticatory ability, cognitive ability, and psychological status. MP, bite force, and occlusal area were tested to assess dynamic objective masticatory function, and the number of remaining teeth and functional tooth pairs were determined to assess static objective masticatory function. Handgrip strength (HG), oral dryness, and tongue pressure (TP) were assessed to identify influencing factors. Intergroup differences were evaluated by ANOVA and the Kruskal‒Wallis test, and correlations between ODK and orofacial factors were evaluated. RESULTS: This study revealed significant age-related declines in TP, HG, and ODK, especially after 65 years of age. Factors affecting MP were posterior teeth, the Eichner index, bite force, occluding area, the Korean Mini-Mental State Examination (KMMSE) score, and ODK. Each ODK syllable was associated with different factors, but common factors associated with ODK were MP, HG, and PHQ-9 score. For the syllables /pa/ta/, the Eichner Index, TP, and oral dryness were also associated. For the syllable /ka/ in Gr3, MP, TP, HG, oral dryness, and the KMMSE score were associated. CONCLUSIONS: These results could provide practical guidelines for oral rehabilitation in old adults and contribute to improving the understanding of age-related changes in oral function and the multidimensional nature of masticatory dynamics.

Assessment of oral hypofunction and its association with age among Korean community-dwelling older adults.

BACKGROUND: Due to the increasing proportion of older adults in Korea and growing interest in aging, the concepts of oral aging and oral hypofunction have recently been introduced. Thus, it is necessary to investigate the age-specific oral function levels of Korean older adults and develop expert intervention methods for healthy aging. METHODS: Dysphagia, independence of daily living, and oral hypofunction were assessed in 206 older adults living in Wonju, Gangwon State, South Korea. Subjective dysphagia was assessed through self-report questionnaires using the Dysphagia Handicap Index (DHI), the Korean version of Eating Assessment Tool-10, and the Korean version of the Modified Barthel Index. In addition, the oral hypofunction assessment items included decreased chewing ability, occlusal pressure, tongue pressure, oral dryness, and oral cleanliness. RESULTS: DHI increased significantly with age, with those in their 80 s reporting the most difficulty swallowing. Oral function in terms of chewing ability (maximum occlusal pressure and number of remaining teeth), maximum occlusal pressure, and maximum tongue pressure also declined with increasing age. While there was no significant difference in oral dryness by age, those in their 80 s had dry mouth according to the criteria of the oral moisture checking device. CONCLUSIONS: In an assessment of oral function in community-dwelling, independent Korean older adults, the number of items that were assessed as oral hypofunction increased with age. The findings can be used to standardize the oral hypofunction assessment item and develop age-based individualized intervention plans for the early management of oral health and individual oral myofunctional rehabilitation in Korean community-dwelling older adults.

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.

Evaluation of Oral Mucosal Lesions in Iranian Smokers and Non-smokers.

BACKGROUND: Tobacco smoking statistics are alarming and the oral mucosa is the first human part of the body that is exposed to the toxic substances of smoking. AIMS: Considering the high prevalence rate of tobacco-associated problems in the oral cavity and few studies on the Iranian population regarding the effects of smoking on the oral cavity, this study aimed to evaluate the relationship between smoking and oral lesions in the Iranian population. MATERIALS AND METHODS: Observational study. In this observational study, the oral cavities of 200 participants (smokers = 100 and non-smokers = 100) were examined by a trained dental student under the supervision of an oral and maxillofacial medicine expert, and the presence of coated tongue, leukoedema, leukoplakia, smoker's palate, smoker's melanosis, erythroplakia, frictional hyperkeratosis, acute pseudomembranous candidiasis, and erythematous candidiasis were recorded. Xerostomia was evaluated based on participants' self-reporting through a questionnaire. All data were analyzed using T-test, Chi-square test, odd ratio, 95% confidence interval, Fisher's exact test, and Spearman's rank correlation coefficient. RESULTS: The results of this study showed smoking is significantly associated with an increased risk of coated tongue (OR: 1.80, 95% CI: 1.32-3.54, P = 0.005), smoker's melanosis (OR: 6.176, 95% CI: 3.28-11.62, P = 0.00002), and frictional hyperkeratosis (OR: 1.33, 95% CI: 0.68-2.60, P = 0.005). However, no significant association was observed between smoking and leukoedema (OR: 1, 95% CI: 0.51-1.94, P = 1). None of the participants presented smoker's palate, erythroplakia, and candidiasis. CONCLUSIONS: This study's results showed that smokers exhibited a greater chance of developing oral lesions compared to non-smokers.

Reducing Salivary Toxicity with Adaptive Radiotherapy (ReSTART): A Randomized Controlled Trial Comparing Conventional IMRT to Adaptive IMRT in Head and Neck Squamous Cell Carcinomas.

BACKGROUND: The utility of Adaptive Radiotherapy (ART) in Head and Neck Squamous Cell Carcinoma (HNSCC) remains to be ascertained. While multiple retrospective and single-arm prospective studies have demonstrated its efficacy in decreasing parotid doses and reducing xerostomia, adequate randomized evidence is lacking. METHODS AND ANALYSIS: ReSTART (Reducing Salivary Toxicity with Adaptive Radiotherapy) is an ongoing phase III randomized trial of patients with previously untreated, locally advanced HNSCC of the oropharynx, larynx, and hypopharynx. Patients are randomized in a 1:1 ratio to the standard Intensity Modulated Radiotherapy (IMRT) arm {Planning Target Volume (PTV) margin 5 mm} vs. Adaptive Radiotherapy arm (standard IMRT with a PTV margin 3 mm, two planned adaptive planning at 10th and 20th fractions). The stratification factors include the primary site and nodal stage. The RT dose prescribed is 66Gy in 30 fractions for high-risk PTV and 54Gy in 30 fractions for low-risk PTV over six weeks, along with concurrent chemotherapy. The primary endpoint is to compare salivary toxicity between arms using salivary scintigraphy 12 months' post-radiation. To detect a 25% improvement in the primary endpoint at 12 months in the ART arm with a two-sided 5% alpha value and a power of 80% (and 10% attrition ratio), a sample size of 130 patients is required (65 patients in each arm). The secondary endpoints include acute and late toxicities, locoregional control, disease-free survival, overall survival, quality of life, and xerostomia scores between the two arms. DISCUSSION: The ReSTART trial aims to answer an important question in Radiation Therapy for HNSCC, particularly in a resource-limited setting. The uniqueness of this trial, compared to other ongoing randomized trials, includes the PTV margins and the xerostomia assessment by scintigraphy at 12 months as the primary endpoint.

Mesenchymal Stromal/Stem Cell Therapy Improves Salivary Flow Rate in Radiation-Induced Salivary Gland Hypofunction in Preclinical in vivo Models: A Systematic Review and Meta-Analysis.

BACKGROUND: Mesenchymal stromal/stem cells (MSCs) have been suggested for salivary gland (SG) restoration following radio-induced salivary gland damage. This study aimed to determine the safety and effectiveness of MSC therapy on radio-induced SG damage and hypofunction in preclinical in vivo studies. METHODS: PubMed and EMBASE were systematically searched for preclinical in vivo interventional studies evaluating efficacy and safety of MSC treatment following radio-induced salivary gland damage published before 10th of January 2022. The primary endpoint was salivary flow rate (SFR) evaluated in a meta-analysis. The study protocol was published and registered on PROSPERO ( www.crd.ac.uk/prospero ), registration number CRD42021227336. RESULTS: A total of 16 preclinical in vivo studies were included for qualitative analysis (858 experimental animals) and 13 in the meta-analysis (404 experimental animals). MSCs originated from bone marrow (four studies), adipose tissue (10 studies) and salivary gland tissue (two studies) and were administered intravenously (three studies), intra-glandularly (11 studies) or subcutaneously (one study). No serious adverse events were reported. The overall effect on SFR was significantly increased with a standardized mean difference (SMD) of 6.99 (95% CI: 2.55-11.42). Studies reported improvements in acinar tissue, vascular areas and paracrine factors. CONCLUSION: In conclusion, this systematic review and meta-analysis showed a significant effect of MSC therapy for restoring SG functioning and regenerating SG tissue following radiotherapy in preclinical in vivo studies without serious adverse events. MSC therapy holds significant therapeutic potential in the treatment of radio-induced xerostomia, but comprehensive, randomized, clinical trials in humans are required to ascertain their efficacy in a clinical setting.

Mesenchymal Stem/Stromal Cell Therapy for Radiation-Induced Xerostomia in Previous Head and Neck Cancer Patients: A Phase II Randomized, Placebo-Controlled Trial.

PURPOSE: No effective treatment exists for radiation-induced xerostomia. The objective of this study was to compare the effect of adipose-derived mesenchymal stem/stromal cell (ASC) injection, relative to placebo, on salivary gland function in patients with radiation-induced xerostomia. PATIENT AND METHODS: In this single-centre, double-blind, placebo-controlled trial, patients with hyposalivation were randomised to receive ultrasound-guided injections of allogeneic ASCs or placebo into the submandibular glands. Patients were followed for 4 months. We evaluated unstimulated whole salivary flow rate (UWS), stimulated salivary flow rate, and patient-reported outcomes. Adverse events were recorded and immune response determined in blood samples. RESULTS: We enrolled 120 patients. ASC treatment resulted in a statistically significant UWS increase of 0.04 [95% confidence interval (CI), 0.02-0.06] mL/min (38%) compared with pretreatment baseline whereas placebo treatment did not cause a significant increase [0.01 (95% CI, -0.01 to 0.04) mL/min (21%)]. Both the ASC and placebo treatment yielded notable symptom reductions, with dry mouth decreasing by 13.6 and 7.7 units, sticky saliva decreased by 14.8 and 9.3 units, swallowing difficulties decreased by 7.9 and 8.0 units, and the summary score of the Xerostomia Questionnaire decreased 5.9 and 5.1 units for the ASC and placebo arms, respectively. We found no statistically significant group difference between the ASC and placebo arms for any of the outcomes. CONCLUSIONS: We could not confirm superiority of the ASC relative to placebo. ASC therapy significantly improved UWS in previous patients with head and neck cancer, whereas placebo resulted in an insignificant increase.

Common Oral Conditions: A Review.

Importance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are 3 of the most common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. Observations: In a meta-analysis of 26 population-based cohort and cross-sectional studies, the global prevalence of dry mouth symptoms was 23% (95% CI, 18% to 28%), placing individuals at risk of oral candidiasis, dental caries, dysgeusia, masticatory/speech impairment, and oropharyngeal dysphagia. Dry mouth is associated with using more than 3 oral medications per day (odds ratio [OR], 2.9 [95% CI, 1.4 to 6.2]), head and neck radiation, and Sjögren disease. Symptoms may include difficulty swallowing and speaking, thirst, and halitosis. Dry mouth is associated with an 11.5% (95% CI, 3.6% to 27%) higher risk of oral candidiasis, based on a meta-analysis of 6 observational cohorts. Management of dry mouth includes mechanical salivary stimulants, oral moisturizers, and/or systemic sialagogues. Oral candidiasis is an opportunistic fungal infection caused by overgrowth of the Candida genus with C albicans, which accounts for 76.8% of infections. The prevalence of oral candidiasis is higher in patients who are immunosuppressed, for example, those with HIV (35% [95% CI, 28% to 42%]) and those with salivary gland hypofunction (OR, 3.02 [95% CI, 1.73 to 5.28]). Common risk factors associated with oral candidiasis include use of antibiotics (P = .04) and oral mucosal disorders such as lichen planus. Oral burning and dysgeusia are common symptoms of oral candidiasis. Treatment includes addressing risk factors and use of topical and/or systemic antifungal medications. Recurrent aphthous stomatitis is characterized by symptomatic round or oval oral ulcers, which are covered by a gray-white fibrin layer and encircled by an erythematous ring. A meta-analysis of 10 case-controlled studies revealed an increased risk of recurrent aphthous stomatitis associated with polymorphism of IL-1ß (+3954C/T) (OR, 1.52 [95% CI, 1.07 to 2.17]) and IL-1ß (-511C/T) (OR, 1.35 [95% CI, 1.09 to 1.67]). Another meta-analysis of 9 case-control studies reported that patients with recurrent aphthous stomatitis had a higher frequency of nutritional deficiencies, including vitamin B12 (OR, 3.75 [95% CI, 2.38 to 5.94]), folic acid (OR, 7.55 [95% CI, 3.91 to 14.60]), and ferritin (OR, 2.62 [95% CI, 1.69 to 4.06]). Recurrent aphthous stomatitis can be associated with systemic diseases. A meta-analysis of 21 case-control studies revealed that celiac disease is associated with a higher incidence of recurrent aphthous stomatitis (25% vs 11%; OR, 3.79 [95% CI, 2.67 to 5.39]; P <.001). Topical corticosteroids are first-line agents to manage recurrent aphthous stomatitis; however, systemic medications may be necessary in more severe cases. Conclusions and Relevance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. First-line treatment includes over-the-counter sialagogues for dry mouth, topical antifungals for oral candidiasis, and topical corticosteroids for aphthous ulcers. Oral conditions that do not improve with first-line treatment may require treatment with systemic medications.

[Questionnaire Survey on Oral Care and Oral Troubles for Patients with Gastric Cancer Received Chemotherapy].

BACKGROUND: The actual situation of oral care and oral troubles for patients with gastric cancer received chemotherapy is not clear. METHODS: Questionnaire survey in the form of oral questions was performed for patients with gastric cancer who received chemotherapy from December 2021 to February 2022. The relevance between the survey results and background factors was examined using the χ2 test. RESULTS: We performed the questionnaire survey for 36 patients. Of the 36 patients, 29 patients received dental check-up before starting chemotherapy. Fourteen of the 29 patients(48%)continued the dental check-up. Of 14 patients who continued the dental check-up, 9 patients were 65 years or older, while 14 of 15 patients who discontinued the dental check-up were 65 years or older. Continuity of dental check-up was low among the elderly patients. The rate of dysgeusia were 78 vs 30% in the patients who adopted and who did not adopt oral care other than toothbrushing(p=0.01). The frequency of oral troubles was dysgeusia(47%), stomatitis(42%), and dry mouth(36%). The severity of the oral troubles was, in order, dysgeusia, dry mouth, and pain. The most common side effect due to chemotherapy causing decreased food intake was dysgeusia. CONCLUSIONS: Dysgeusia was the most frequent and severe oral trouble.

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.

Serotonin norepinephrine reuptake inhibitors in managing neuropathic pain following spinal and non-spinal surgery: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: While serotonin norepinephrine reuptake inhibitors (SNRIs) offer promise in managing Post-surgical neuropathic pain (PSNP), uncertainties remain. This study aims to evaluate the effectiveness and adverse events of SNRIs in managing PSNP. METHODS: Systematic searches of PubMed, Embase, and Cochrane databases up to January 1st 2023 identified randomized controlled trials (RCTs) comparing SNRIs to placebo for PSNP. The primary outcome measures were pain at rest and adverse events post-surgery. Subgroup analyses were conducted based on surgical type and specific SNRIs. RESULTS: A total of 19 RCTs, encompassing 1440 participants (719 in the SNRI group vs 721 in the placebo group), met the inclusion criteria and were included. The pooled results demonstrated that pain scores were significantly lower in patients treated with SNRIs at 2 hours (MD:-0.26; 95%CI: -0.47 to -0.04; p=0.02), 6 hours (MD:-0.68; 95%CI: -1.01 to -0.34; p<0.0001), 24 hours (MD:-0.54; 95%CI: -0.99 to -0.09; p=0.02), and 48 hours (MD:-0.66; 95%CI: -1.23 to -0.10; p=0.02) post-surgery. In terms of adverse events, dizziness (OR:2.53; 95%CI: 1.34-4.78; p=0.004) and dry mouth (OR:2.21; 95%CI: 1.25-3.92; p=0.007) were significantly higher in the SNRIs group. Subgroup analysis showed that SNRI was found to significantly lower the 24-hour pain score after spinal surgery (MD:-0.45; 95%CI: -0.84 to -0.05; p=0.03). Duloxetine (MD:-0.63; 95%CI: -1.15 to -0.11; p=0.02) had a significant effect in lowering the 24-hour pain score at rest compared to placebo, whereas venlafaxine did not. CONCLUSIONS: SNRIs yielded considerable pain score reductions across multiple post-surgical intervals, although accompanied by an increased incidence of dizziness and dry mouth.

Cost-effectiveness of weekly adaptive radiotherapy versus standard IMRT in head and neck cancer alongside the ARTIX trial.

BACKGROUND AND PURPOSE: We performed a cost-effectiveness analysis (CEA) comparing an adaptive radiotherapy (ART) strategy, based on weekly replanning, aiming to correct the parotid gland overdose during treatment and expecting therefore to decrease xerostomia, when compared to a standard IMRT. MATERIALS AND METHODS: We conducted the ARTIX trial, a randomized, parallel-group, multicentric study comparing a systematic weekly replanning ART to a standard IMRT. The primary endpoint was the frequency of xerostomia at 12 months, measured by stimulating salivary flow with paraffin. The CEA was designed alongside the ARTIX trial which was linked to the French national health data system (SNDS). For each patient, healthcare consumptions and costs were provided by the SNDS. The reference case analysis was based on the primary endpoint of the trial. Sensitivity and scenario analyses were performed. RESULTS: Of the 129 patients randomly assigned between 2013 and 2018, only 2 records were not linked to the SNDS, which provides a linkage proportion of 98.4%. All of the other 127 records were linked with good to very good robustness. On the intent-to-treat population at 12 months, mean total costs per patient were €41,564 (SD 23,624) and €33,063 (SD 16,886) for ART and standard IMRT arms, respectively (p = 0.033). Incremental cost effectiveness ratio (ICER) was €162,444 per xerostomia avoided. At 24 months, ICER was €194,521 per xerostomia avoided. For both progression-free and overall survival, ART was dominated by standard IMRT. CONCLUSION: The ART strategy was deemed to be not cost-effective compared with standard IMRT for patients with locally advanced oropharyngeal cancer.

Neighborhood Deprivation and Changes in Oral Health in Older Age: A Longitudinal Population-Based Study.

The aim of this study was to examine the extent to which neighborhood-level socioeconomic factors (objective and perceived) are associated with poor oral health in older adults over time, independent of individual socioeconomic position. Data for this cross-sectional and longitudinal observation study came from a socially and geographically representative cohort of men aged 71 to 92 y in 2010-12 (n = 1,622), drawn from British general practices, which was followed up in 2018-19 (aged 78-98 y; N = 667). Dental measures at both times included number of teeth, periodontal pocket depth, self-rated oral health, and dry mouth. Neighborhood deprivation was based on Index of Multiple Deprivation (IMD) and a cumulative index measuring perceptions about local environment. Individual-level socioeconomic position was based on longest-held occupation. Multilevel and multivariate logistic regressions, adjusted for relevant sociodemographic, behavioral, and health-related factors, were performed to examine the relationships of dental measures with IMD and perceived neighborhood quality index, respectively. Cross-sectionally, risks of tooth loss, periodontal pockets, and dry mouth increased from IMD quintiles 1 to 5 (least to most deprived); odds ratios (ORs) for quintile 5 were 2.22 (95% confidence interval [CI], 1.41-3.51), 2.82 (95% CI, 1.72-4.64), and 1.51 (95% CI, 1.08-2.09), respectively, after adjusting for sociodemographic, behavioral, and health-related factors. Risks of increased pocket depth and dry mouth were significantly greater in quintile 5 (highest problems) of perceived neighborhood quality index compared to quintile 1. Over the 8-y follow-up, deterioration of dentition (tooth loss) was significantly higher in the most deprived IMD quintiles after full adjustment (OR for quintile 5 = 2.32; 95% CI, 1.09-4.89). Deterioration of dentition and dry mouth were significantly greater in quintile 5 of perceived neighborhood quality index. Neighborhood-level factors were associated with poor oral health in older age, both cross-sectionally and longitudinally, particularly with tooth loss, and dry mouth, independent of individual-level socioeconomic position.

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.

The changes on salivary flow rates, buffering capacity and chromogranin A levels in adults after bariatric surgery.

OBJECTIVES: This study aimed to investigate changes in salivary flow rates, buffering capacity, and salivary chromogranin A (CHGA) levels in adults undergoing bariatric surgery (BS) compared with a non-obese control group. MATERIALS AND METHODS: Salivary analyses were performed on 62 participants aged over 50 years, stratified into two groups matched for age and gender-individuals who had undergone bariatric surgery (BS) (n = 31) and a corresponding healthy control group (n = 31). Before saliva collection, participants completed a comprehensive 11-point visual numerical rating scale (NRS 0-10) xerostomia questionnaire, assessing subjective perceptions of two key aspects: dryness of the oral mucosa and resultant impact on oral functional ability. Three distinct saliva measurements were obtained: unstimulated whole saliva (UWS), stimulated whole saliva (SWS), and unstimulated upper labial saliva (ULS). The buffering capacity of unstimulated saliva was assessed using pH indicator strips, and concentrations of salivary Chromogranin A (CHGA) were quantified in stimulated saliva via enzyme-linked immunosorbent assay (ELISA). RESULTS: After BS, more than 40% of BS group patients reported xerostomia, with 16.1% experiencing only mild symptoms without significant functional impact (p = 0.009). The prevalence of xerostomia and tongue dryness was higher in the BS group compared to the control group (p = 0.028 and p = 0.025, respectively). The comparative analysis unveiled no statistically significant differences in flow rates of unstimulated upper labial saliva (ULS), unstimulated whole saliva (UWS), and stimulated whole saliva (SWS) between the control group and patients who underwent bariatric surgery. However, in patients undergone BS with xerostomia, both ULS and UWS flow rates were significantly lower than in controls with xerostomia (p = 0.014 and p = 0.007, respectively). The buffering capacity was significantly lower in patients undergone BS than in controls (p = 0.009). No differences were found between groups regarding CHGA concentration and output values, nevertheless, higher values of CHGA concentrations were significantly correlated to lower flow rates. CONCLUSION: According to the results, this study suggests that individuals undergoing BS may exhibit altered salivary buffering capacity and reduced unstimulated salivary flows in the presence of xerostomia. Additionally, the findings suggest that elevated concentration of salivary CHGA might be associated, in part, with salivary gland hypofunction. CLINICAL RELEVANCE: The clinical significance of this study lies in highlighting the changes in salivary functions after BS. The identified salivary alterations might be attributed to adverse effects of BS such as vomiting, gastroesophageal reflux, and dehydration. Understanding these changes is crucial for healthcare professionals involved in the care of post-BS patients, as it sheds light on potential oral health challenges that may arise as a consequence of the surgical intervention. Monitoring and managing these salivary alterations can contribute to comprehensive patient care and enhance the overall postoperative experience for individuals undergoing BS.