WWOM VII: Effectiveness of systemic pharmacotherapeutic interventions in the management of BMS: A systematic review and meta-analysis.

OBJECTIVES: To determine the effectiveness of systemic pharmacotherapeutic interventions compared to placebo in burning mouth syndrome (BMS) randomized controlled trials (RCTs) based on the core outcome domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). METHODS: A systematic literature review of RCTs, concerning systemic pharmacotherapeutic interventions for BMS, published from January 1994 through October 2019, and meta-analysis was performed. RESULTS: Fourteen RCTs (n = 734 participants) were included. Of those, nine were eligible for the quantitative assessment due to the availability/homogeneity of data for at least one of the IMMPACT domains. Pain intensity was the only domain reported in all RCTs. Weighted mean changes in pain intensity, based on visual analogue scale (ΔVAS), were reported in three RCTs at 6 ± 2 weeks and only one RCT at 10+ weeks follow-ups. Quantitative assessment, based on ΔVAS, yielded very low evidence for the effectiveness of alpha-lipoic acid and clonazepam, low evidence for effectiveness of trazodone and melatonin, and moderate evidence for herbal compounds. CONCLUSIONS: Based on the RCTs studied, variable levels of evidence exist that suggest that select pharmacological interventions are associated with improved symptoms. However, the underreporting of IMMPACT domains in BMS RCTs restricts the multidimensional assessment of systemic interventions outcomes. Standardized outcome measures need to be applied to future RCTs to improve understanding of intervention outcomes.

WWOM VII: Effectiveness of topical interventions in the management of burning mouth syndrome: A systematic review.

OBJECTIVES: To assess the effectiveness of topical interventions in the management of burning mouth syndrome (BMS), based on the core outcome domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT). METHODS: A systematic literature review of RCTs on topical interventions for the management of BMS, published in PubMed, Web of Science, PsycInfo, Cochrane Database/Central, and Google Scholar through May 2021 was performed. RESULTS: Eight RCTs (n = 358 study participants) were included in this study. Due to underreporting of IMMPACT domains, publication bias, high degree of heterogeneity between studies, meta-analysis was not undertaken. Based on changes in visual analogue pain scores (ΔVAS), the most reported outcome, the effectiveness of the topical interventions was demonstrated; however, it is low level of evidence. CONCLUSIONS: High levels of variability (interventions, outcomes, outcome measurement tools, and intervention effects evaluated), heterogeneity, publication bias, and underreporting of IMMPACT domains were observed across the RCTs. This systematic review highlights the need for application of standardized outcome measures to future RCTs. At the present time, there is lack of moderate-strong evidence on short- and long-term outcomes to support or refute the use of any particular topical intervention in managing BMS. Future RCTs with standardized outcome measures are needed.

Influence of smoking history on the perception of radiation-induced dysgeusia/hypogeusia in patients with head and neck cancer.

OBJECTIVES: This investigation aimed to assess the effect of smoking on the onset and resolution of dysgeusia/hypogeusia in head and neck cancer (HNC) patients receiving radiotherapy (XRT). MATERIALS AND METHODS: This is a retrospective cohort investigation of HNC patients treated with XRT. Data collected from the patients' medical records included demographics, primary cancer diagnoses, HNC therapeutic modalities, smoking status, and dates of onset/resolution of dysgeusia/hypogeusia. RESULTS: A 103 met inclusion criteria, of which 61.8% developed dysgeusia/hypogeusia. Mean age was 58.3 ± 12.9 and 66% were either former or current smokers. Never smokers seemed to be at higher, but statistically insignificant, the risk for developing dysgeusia/hypogeusia than former or current smokers [HR 1.05 and 1.66; 95% CI (0.60, 1.84) and (0.85, 3.24)]. They were also less likely to recover when compared to former smokers [HR 0.74; 95% CI (0.39, 1.39)]. Although statistically insignificant, never smokers showed rapid dysgeusia/hypogeusia onset after XRT compared to former or current smokers (median 14 days versus 22 and 9 days, respectively; p = 0.25). Never smokers showed quicker but statistically insignificant, recovery time compared to former or current smokers (median 113 days versus 149 and 238 days, respectively; p = 0.57). CONCLUSION: Although results lacked statistical significance, never smokers receiving XRT were prone to higher risk and faster onset of dysgeusia/hypogeusia than former and current smokers.

Comparing the effectiveness and adverse effects of pilocarpine and cevimeline in patients with hyposalivation.

OBJECTIVES: Pilocarpine (PILO) and cevimeline (CEV) are muscarinic acetylcholine receptor agonists that stimulate salivary gland function. The aim of this investigation was to retrospectively run a head-to-head comparison for their effectiveness and frequency of adverse effects in patients with hyposalivation. METHODS: A retrospective chart review was conducted for patients seen at the Oral Medicine Clinic at Tufts University School of Dental Medicine (TUSDM) and was prescribed PILO or CEV. Patients' demographics, medical history/medication, stimulated salivary (SS), and unstimulated salivary (US) flow recorded at the initial visit and at 3- and 6-month follow-ups were collected. Changes in dosage/frequency, side effects, and drug discontinuation were also reported. RESULTS: A total of 110 patients' charts were reviewed. The majority of subjects (91%) were females with an average age of 61. At 3-month follow-up, the use of CEV showed significant improvement in SS compared to PILO (p = .033) but not in US (p = .10). At 6-month follow-up, there was no significant difference in SS or US between the two groups (SS: p = .09; US: p = .71). The use of PILO was associated with a higher proportion of adverse effects compared to CEV (p = .04). The overall adherence rate was significantly higher in the CEV group (p = .0056). CONCLUSIONS: The effectiveness of CEV and PILO is comparable. However, PILO seems to be associated with more reporting of side effects.

World Workshop on Oral Medicine VII: Burning mouth syndrome: A systematic review of disease definitions and diagnostic criteria utilized in randomized clinical trials.

OBJECTIVE: To conduct a systematic review analyzing disease definitions and diagnostic criteria used in randomized controlled trials (RCTs) involving burning mouth syndrome (BMS). METHODS: A systematic search conducted in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar that included RCTs on BMS published between 1994 and 2017 was performed. RESULTS: Considerable variability in BMS disease definitions and diagnostic criteria used created substantial heterogeneity in the selection of participants and weakened the rigor of the 36 RCTs identified. The analyzed RCTs routinely under-reported the methods used to rule in or out study participants and the number of individuals excluded from BMS RCTs. CONCLUSIONS: Our findings indicate that a large proportion of participants enrolled in these studies may have had an underlying condition that could have explained their BMS symptoms. Thus, outcomes of therapeutic interventions from these BMS RCTs should be interpreted with caution due to heterogeneous disease definitions and diagnostic criteria. In order to improve the quality of clinical trials, future research should focus on establishing consensus for a single definition of BMS that includes specific inclusion and exclusion criteria that should be used to select study participants for clinical trials.

World Workshop in Oral Medicine VII: Reporting of IMMPACT-recommended outcome domains in randomized controlled trials of burning mouth syndrome: A systematic review.

OBJECTIVES: To determine the frequency of use of the core outcome domains published by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) in burning mouth syndrome (BMS) randomized controlled trials (RCTs). METHODS: This systematic review, conducted as part of the World Workshop on Oral Medicine VII (WWOM VII), was performed by searching the literature for studies published in PubMed, Web of Science, PsycINFO, Cochrane Database/Cochrane Central, and Google Scholar from January 1994 (when the first BMS definition came out) through October 2017. RESULTS: A total of 36 RCTs (n = 2,175 study participants) were included and analyzed. The overall reporting of the IMMPACT core and supplemental outcome domains was low even after the publication of the IMMPACT consensus papers in 2003 and 2005 (mean before IMMPACT consensus publication = 2.6 out of 6; mean after IMMPACT publication = 3.8 out of 6). Use of validated assessment tools recommended by the IMMPACT consensus was scarce (1.9 out of 6). None of the RCTs reviewed cited the IMMPACT consensus papers. CONCLUSIONS: The underreporting of IMMPACT outcome domains in BMS RCTs is significant. Raising awareness regarding the existence of standardized outcome domains in chronic pain research is essential to ensure more accurate, comparable, and consistent interpretation of RCT findings that can be clinically translatable.

World Workshop on Oral Medicine VIII: Barriers to research in oral medicine: results from a global survey.

OBJECTIVES: To explore factors influencing research interest and productivity and perceived barriers to conducting research in Oral Medicine (OM). METHODS: Invitations to participate in an online survey were e-mailed to a network of international OM practitioners and related professional organizations. Questions captured respondents' demographic/professional variables and gauged research interest, productivity, and perceived barriers to conducting research specifically in OM. Statistical analysis was conducted via descriptive, logistic regression, and multivariate modeling. RESULTS: Five hundred and ninety-three OM practitioners from 55 countries completed the survey, with 54%, 25%, and 21% practicing in high, upper-middle, and lower-middle-income countries, respectively. Eighty-six percent of respondents were interested in conducting research. Age (less interest with an increase in age), working in academia, and practicing in a lower-middle vs high-income country were significant predictors of research interest. Self-reported research productivity was significantly greater among males, those working in academia, and those who graduated from programs that mandated research presentation/publication. Obtaining research funding was a significant barrier among respondents from lower and upper-middle-income countries, whereas finding time for research was a reported barrier by respondents from high-income countries. CONCLUSION: The results of this survey identified perceived barriers to conducting research in OM and highlighted solutions to address such barriers.

Conservative Management of Chronic Suppurative Parotitis in Patients with Sjögren Syndrome: A Case Series.

BACKGROUND Parotitis is an inflammation of the parotid gland, which can be caused by factors including infection, radiation, and hyposalivation secondary to systemic conditions, such as Sjögren syndrome, rheumatoid arthritis, or medication. Bacterial parotitis is a rare complication that can be observed in patients with hyposalivation. However, it is also observed in elderly and immunocompromised patients. Lack of continuous flushing of salivary glands and their ducts due to decreased salivary flow renders the glands prone to retrograde colonization with oral microflora. Several microorganisms have been associated with bacterial infections of the parotid glands; Staphylococcus aureus is the most common, accounting for 80% of cases, followed by mixed bacterial communities, including streptococci, anaerobes, and gram-negative bacilli. Bacterial parotitis presents as tenderness, swelling, and purulent sialorrhea from the salivary gland's duct. Immediate administration of broad-spectrum antibiotics, based on the results of the patient's culture and sensitivity test, has shown success in treating these cases. CASE REPORT We report 3 cases of chronic suppurative parotitis secondary to dry mouth and due to Sjögren syndrome that did not respond to oral or intravenous antibiotics and was successfully managed using conservative methods, such as the local application of superficial moist heat and periodic pus drainage by manipulating the parotid glands at dental clinics. CONCLUSIONS We concluded that conservative approaches, such as massaging the glands, local application of superficial moist heat, and periodic pus drainage without using antibiotics, should be considered as the first-line management of bacterial infection of the parotid glands.

Chronic Oral Lesions.

Chronic oral mucosal lesions can be associated with several mucocutaneous diseases. This article reviews the autoimmune and immune-mediated, reactive, genetic, and infectious diseases that may present with chronic oral and/or cutaneous manifestations and provides a rational approach to diagnosis and management.

The effectiveness of acupuncture in the management of persistent regional myofascial head and neck pain: A systematic review and meta-analysis.

Persistent head and neck myofascial pain is among the most frequently reported pain complaints featuring major variability in treatment approaches and perception of improvement. Acupuncture is one of the least invasive complimentary modalities that can optimize conventional treatment. The aim of this review was to determine the evidence for the effectiveness of acupuncture in the management of localized persistent myofascial head and neck pain. Only randomized controlled clinical trials (RCTs) were included. The search was conducted in PubMed, Ovid Medline, Embase, Google Scholar, and Cochrane Library in addition to manual search. The main outcome measure was the comparison of the mean pain intensity score on VAS between acupuncture and sham-needling/no intervention groups. Safety data and adherence rate were also investigated. Six RCTs were identified with variable risk of bias. All included studies reported reduction in VAS pain intensity scores in the groups receiving acupuncture when compared to sham needling/no intervention. Meta-analysis, using a weighted mean difference as the effect estimate, included only 4 RCTs, revealed a 19.04 point difference in pain intensity between acupuncture and sham-needling/no intervention (95 %CI: -29.13 to -8.95). High levels of safety were demonstrated by the low rates of side effects/withdrawal. Inconsistency in reporting of outcomes was a major limitation. In conclusion, moderate-quality evidence suggests that acupuncture may be an effective and safe method in relieving persistent head and neck myofascial pain. Optimizing study designs and standardizing outcome measures are needed for future RCTs.

Assessment of the anti-CD40 antibody iscalimab in patients with primary Sjögren's syndrome: a multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study.

BACKGROUND: Primary Sjögren's syndrome is an autoimmune disease that presents as dryness of the mouth and eyes due to impairment of the exocrine glands. To our knowledge, no systemic therapies for primary Sjögren's syndrome have shown efficacy. CD40-CD154-mediated T cell-B cell interactions in primary Sjögren's syndrome contribute to aberrant lymphocyte activation in inflamed tissue, leading to sialadenitis and other tissue injury. Therefore, we investigated the safety and preliminary efficacy of iscalimab (CFZ533), a novel anti-CD40 monoclonal antibody, in patients with primary Sjögren's syndrome. METHODS: This multicentre, randomised, double-blind, placebo-controlled, proof-of-concept study took place at ten investigational sites across Europe (UK, n=4; Germany, Switzerland, and Hungary, n=1 each) and the USA (n=3). Eligible patients were aged 18-75 years and fulfilled the 2002 American European consensus group diagnostic classification criteria for primary Sjögren's syndrome. In the double-blind phase of the trial, patients were randomly assigned (2:1) via computer-generated unique randomisation numbers to receive subcutaneous iscalimab (3 mg/kg) or placebo at weeks 0, 2, 4, and 8 (cohort 1) or intravenous iscalimab (10 mg/kg) or placebo at weeks 0, 2, 4, and 8 (cohort 2). Randomisation was stratified according to baseline intake of oral corticosteroids. At week 12, patients in both cohorts received open-label iscalimab (same dose and route) for 12 weeks. The primary objectives of the study were to assess the safety, tolerability, and efficacy of multiple doses of iscalimab in the two sequential dose cohorts. Safety and tolerability were assessed by adverse events and efficacy of iscalimab versus placebo was assessed by clinical disease activity, as measured by the change in European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI) score after 12 weeks of treatment. Analyses were done on a per-protocol basis. The trial was registered with ClinicalTrials.gov, NCT02291029. FINDINGS: Between Oct 22, 2014, and June 28, 2016, we assessed 82 patients for eligibility (25 for cohort 1 and 57 for cohort 2). 38 patients were excluded because of ineligibility. In cohort 1, 12 patients were randomly assigned to receive either 3 mg/kg doses of iscalimab (n=8) or placebo (n=4), and in cohort 2, 32 patients were randomly assigned to receive either intravenous 10 mg/kg doses of iscalimab (n=21) or placebo (n=11). Adverse events were similar between iscalimab treatment groups and placebo groups, with adverse events occurring in all patients in cohort 1, and in 52% and 64% of the iscalimab and placebo groups, respectively, in cohort 2. Two serious adverse events were reported (one case of bacterial conjunctivitis in cohort 1 and one case of atrial fibrillation in cohort 2), which were unrelated to treatment with iscalimab. Intravenous treatment with iscalimab resulted in a mean reduction of 5·21 points (95% CI 0·96-9·46; one-sided p=0·0090) in ESSDAI score compared with placebo. There was no signficiant difference in ESSDAI score between subcutaneous iscalimab and placebo. INTERPRETATION: To our knowledge, this is the first randomised, placebo-controlled proof-of-concept study of a new investigational drug for primary Sjögren's syndrome that indicates preliminary efficacy. Our data suggest a role of CD40-CD154 interactions in primary Sjögren's syndrome pathology and the therapeutic potential for CD40 blockade in this disease should be investigated further. FUNDING: Novartis Pharma.

Utilizing the concept of geste antagoniste for conservative management of oro-mandibular tardive dyskinesia: a case report and mini-review.

OBJECTIVE: This case report highlights the implication of the concept of "geste antagoniste" in conservatively managing oromotor dysfunction and its complications. CLINICAL PRESENTATION: A 66-year-old female with a 1-year history of tardive dyskinesia (TD) was referred to the Craniofacial Pain Department (CPC) at Tufts University School of Dental Medicine for management of sore labial/lingual mucosa secondary to excessive daytime involuntary activity of the tongue, lips, and mandible. A detailed head/neck examination revealed excessive involuntary movements of the tongue, lips, and mandible with generalized tenderness of her masticatory muscles. No TMJ or bone pathology was evident in a panoramic radiograph. INTERVENTION: A lower daytime appliance with bilateral posterior contacts was fabricated to protect her oral mucosa. On reevaluation, excessive movement of the jaw/tongue was significantly reduced with the presence of the appliance in her mouth. Face/neck muscle tenderness was also greatly reduced. CONCLUSION: The use of oral appliance therapy in TD patients plays an important role in protecting the teeth/oral mucosa. The subsequent inhibition of excessive motor activity is proposed and should be further investigated.