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.

Rates of oropharyngeal cancer continue to rise steeply amongst Australian men.

OBJECTIVE: The objective was to analyse the trends in the incidence of oropharyngeal cancers (OPC) across Australia from 1982 to 2017 with implications for prevention. METHODS: Data were obtained from the Australian Cancer Database (ACD) compiled at the Australian Institute of Health and Welfare (AIHW). Joinpoint analyses are presented. RESULTS AND DISCUSSION: There was a striking increase of age-standardised incidence rate (ASIR) of OPC by over 1.5 times; the most significant rise was between 2007 and 2017 with an annual percentage change (APC) of +5.24% (p < 0.001). Slow but gradual growth of ASIR was observed amongst women with a statistically significant APC of +1.02% (p < 0.001). Statistically significant bimodal increasing trends of APC were also observed in total ASIR of OPC. These rising trends are widely attributed to increased oral sex practices. The highest number of incident cases was found in patients aged 55-69 years attributable to continued alcohol and tobacco exposure. The most common subsites affected were base of the tongue (BOT) and 'oropharynx' from 1982 to 2017. CONCLUSION: Oropharyngeal cancer is rising rapidly across Australia, particularly in men. Whilst the national proportion of cases driven by HPV is not known, it is evident that vaccination is yet to have an impact.

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.

Consensus agreement to rename burning mouth syndrome and improve International Classification of Diseases-11 disease criteria: an international Delphi study.

ABSTRACT: The International Classification of Diseases (ICD-11) proposes revisions in the nomenclature, disease definition, and diagnostic criteria for "burning mouth syndrome" (BMS). This process could benefit from additional systematically collected expert input. Thus, the purpose of this study was to use the Delphi method to (1) determine whether revision in nomenclature and alternative names for "BMS" are warranted and (2) identify areas of consensus among experts for changes to the disease description and proposed diagnostic criteria of "BMS," as described in the ICD-11 (World Health Organization). From 31 international invited experts, 23 who expressed interest were sent the survey. The study used 4 iterative surveys, each with a response rate of ≥82%. Consensus was predefined as 70% of participants in agreement. Data were summarized using both descriptive statistics and qualitative thematic analysis. Consensus indicated that BMS should not be classified as a syndrome and recommended instead renaming to "burning mouth disorder." Consensus included deletion of 2 diagnostic criteria: (1) emotional distress or functional disability and (2) the number of hours symptoms occur per day. Additional items that reached consensus clarified the disease definition and proposed more separate diagnostic criteria, including a list of local and systemic factors to evaluate as potential secondary causes of oral burning. Experts in this study recommended and came to consensus on select revisions to the proposed ICD-11 BMS nomenclature, diagnostic criteria, and disease definition. The revisions recommended have the potential to improve clarity, consistency, and accuracy of diagnosis for this disorder.

MASCC/ISOO clinical practice guidelines for the management of mucositis: sub-analysis of current interventions for the management of oral mucositis in pediatric cancer patients.

OBJECTIVE: The aim of this sub-analysis was to highlight the MASCC/ISOO clinical practice guidelines for the management of oral mucositis (OM) in pediatric patients and to present unique considerations in this patient population. METHODS: This sub-analysis of the pediatric patient population is based on the systematic review conducted by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISSO) published in 2019/2020. Studies were scored and assigned a level of evidence based on previously published criteria. Data regarding adverse effects and compliance was collected from the original publications. RESULTS: A total of 45 papers were included and assessed in this sub-analysis, including 21 randomized controlled trials (RCTs). Chewing gum was demonstrated to be not effective in preventing OM in pediatric cancer patients in 2 RCTs. The efficacy of all other interventions could not be determined based on the available literature. CONCLUSION: There is limited or conflicting evidence about interventions for the management of OM in pediatric cancer patients, except for chewing gum which was ineffective for prevention. Therefore, currently, data from adult studies may need to be extrapolated for the management of pediatric patients. Honey and photobiomodulation therapy in this patient population had encouraging potential. Implementation of a basic oral care protocol is advised amid lack of high level of evidence studies.

MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy.

BACKGROUND: Mucositis is a significant toxicity of cancer therapy with numerous systemic sequelae. The goal of this systematic review was to update the Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) Clinical Practice Guidelines for the management of mucositis. METHODS: The literature was reviewed systematically to identify interventions for mucositis. Studies were rated according to the presence of major and minor flaws according to previously published criteria. The body of evidence for each intervention and in each treatment setting was assigned a level of evidence based on previously published criteria. Guidelines were developed based on the level of evidence, with 3 possible guideline determinations: recommendation, suggestion, or no guideline possible. RESULTS: The guideline covers evidence from 1197 publications related to oral or gastrointestinal mucositis. Thirteen new guidelines were developed for or against the use of various interventions in specific treatment settings, and 11 previous guidelines were confirmed after aa review of new evidence. Thirteen previously established guidelines were carried over because there was no new evidence for these interventions. CONCLUSIONS: The updated MASCC/ISOO Clinical Practice Guidelines for mucositis provide professional health caregivers with a clinical setting-specific, evidence-based tool to help with the management of mucositis in patients who have cancer.

Systematic review of natural and miscellaneous agents, for the management of oral mucositis in cancer patients and clinical practice guidelines - part 2: honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents.

OBJECTIVE: To update the clinical practice guidelines for the management of oral mucositis (OM) that were developed by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO). This part focuses on honey, herbal compounds, saliva stimulants, probiotics, and miscellaneous agents. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The body of evidence for each intervention, in each clinical setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, one of the following guidelines were determined: Recommendation, Suggestion, No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, of which 49 were included in this review and merged with nine publications that were reported in the previous guidelines update. A new Suggestion was made for honey (combined topical and systemic delivery) for the prevention of OM in head and neck cancer patients receiving radiotherapy with or without chemotherapy. A new Suggestion clarified that chewing gum is not effective for the prevention of OM in pediatric patients with hematological or solid cancer treated with chemotherapy. No guideline was possible for other interventions. CONCLUSIONS: Numerous natural products and herbal remedies were studied for the management of OM. Of the agents reviewed in this systematic review, a guideline in favor was made for honey (combined topical and systemic), while a guideline against was made for chewing gum. Additional research is warranted to clarify the potential of other interventions.

Efficacy of gabapentin in the treatment of trigeminal neuralgia: A systematic review of randomized controlled trials.

The aim of this systematic review was to determine the efficacy of gabapentin (GBP) in the treatment of pain of  idiopathic trigeminal neuralgia (TN). A comprehensive literature search was conducted using the Cumulative Index of Nursing and Allied Health Literature (EBSCO Industries), Emcare (Ovid), Medline (Ovid), Medline (PubMed), Scopus (Elsevier) and Web of Science (Clarivate Analytics). The inclusion criteria comprised randomized controlled trials of GBP as a monotherapy in the treatment of idiopathic TN in adult participants and publications in English. All other study methodologies were excluded. The search yielded 1472 articles, and after exclusion, 11 full-text articles were eligible for full-text analysis. Only two studies met the inclusion criteria. There is insufficient evidence either to support or refute the efficacy of GBP in the management of idiopathic TN. Therefore, further well-designed placebo-controlled trials are required to confirm the efficacy of GBP in managing TN pain as a single therapy.

Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines-part 1: vitamins, minerals, and nutritional supplements.

PURPOSE: To update the clinical practice guidelines for the use of natural and miscellaneous agents for the prevention and/or treatment of oral mucositis (OM). METHODS: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer / International Society of Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the 2014 MASCC/ISOO clinical practice guidelines. Based on the evidence level, the following guidelines were determined: Recommendation, Suggestion, and No Guideline Possible. RESULTS: A total of 78 papers were identified within the scope of this section, out of which 29 were included in this part, and were analyzed with 27 previously reviewed studies. A new Suggestion was made for oral glutamine for the prevention of OM in head and neck (H&N) cancer patients receiving radiotherapy with concomitant chemotherapy. The previous Recommendation against the use of parenteral glutamine for the prevention of OM in hematopoietic stem cell transplantation (HSCT) patients was re-established. A previous Suggestion for zinc to prevent OM in H&N cancer patients treated with radiotherapy or chemo-radiotherapy was reversed to No Guideline Possible. No guideline was possible for other interventions. CONCLUSIONS: Of the vitamins, minerals, and nutritional supplements studied for the management of OM, the evidence supports a Recommendation against parenteral glutamine in HSCT patients and a Suggestion in favor of oral glutamine in H&N cancer patients for the management of OM.

Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: The aim of this systematic review was to update the clinical practice guidelines for the use of anti-inflammatory agents in the prevention and/or treatment of oral mucositis. METHODS: A systematic review was conducted by the Multinational Association of Supportive Care in Cancer/ International Society of Oral Oncology (MASCC/ISOO) subcommittee on mucositis guideline update. The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. The findings were added to the database used to develop the clinical practice guidelines published in 2014. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guidelines. RESULTS: A total of 11 new papers across five interventions were examined. The recommendation for the use of benzydamine mouthwash for the prevention of radiotherapy-induced mucositis remained unchanged. New suggestion for the use of the same for prevention of mucositis associated with chemoradiotherapy was made. No guideline was possible for any other anti-inflammatory agents due to inadequate and/or conflicting evidence. CONCLUSIONS: Of the anti-inflammatory agents studied for oral mucositis, the evidence supports the use of benzydamine mouthwash in the specific populations listed above. Additional well-designed research is needed on other (class of agents) interventions and in other cancer treatment settings.

Effect of submucosal dexamethasone injections in the prevention of postoperative pain, trismus, and oedema associated with mandibular third molar surgery: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to determine whether there are clinically effective reductions in postoperative pain, oedema, and trismus following submucosal dexamethasone administration during impacted mandibular third molar surgery. An electronic database search was conducted up to and including June 2018. Randomized and quasi-randomized trials assessing the effects of submucosal dexamethasone in adult patients undergoing mandibular third molar surgery were included. The mean differences or standardized mean differences were extracted and pooled using the fixed-effects or random-effects model. Seventeen trials were included and independently assessed for risk of bias. There was low quality evidence that submucosal dexamethasone reduces early postoperative pain, early and late postoperative trismus, and late postoperative oedema after mandibular third molar extraction. Moderate quality evidence was found for the reduction of late postoperative pain and early postoperative oedema. The greatest clinical effect of submucosal dexamethasone injection during impacted mandibular third molar surgery was a reduction of early postoperative pain (number needed to treat (NNT) = 4) and early postoperative oedema (NNT = 5). The reduction in trismus was not clinically significant (<5 mm). Further research focusing on strengthening the quality of evidence, investigating potential harms and a definitive protocol for submucosal administration during mandibular third molar surgery is required.

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.

Nonneoplastic diseases and disorders of the oral mucosa: A contemporary overview.

Oral mucosal diseases encompass a diverse array of conditions and disorders arising from malignant, potentially malignant, and nonneoplastic processes. Considerable attention has been paid to the former in recent years, much less to the wide range of nonneoplastic disease processes, which constitute a sizeable proportion of the oral disease burden globally. Many nonneoplastic disease processes of the oral mucosa significantly affect the patient's quality of life. Fortunately, timely identification and intervention can reduce the associated morbidity and, sometimes, mortality. As such, it is of utmost importance that dentists are familiar with early identification and management of this wide range of oral mucosal diseases. This volume of Periodontology 2000 provides a comprehensive contemporary review of such diseases and disorders through 15 chapters. We cover all relevant disease categories: developmental anomalies, infections, white and red lesions, vesiculo-bullous diseases, oral dermatoses, oral ulcerative conditions, dysplastic lesions, and mucosal diseases as manifestations of systemic disease or oral lesions as a part of systemic diseases. Each chapter discusses epidemiology, etiopathogenesis, clinical features, diagnosis, and management. Controversies and many significant gaps in knowledge are exposed, with suggestions for research to address limitations in current understandings. We take a look at the 2017 classification of the periodontal diseases and discuss the importance of close liaison between the specialties of oral medicine and of periodontology in the management of the many oral diseases, apart from the common forms primarily related to oral biofilm, affecting the gingivae and other parts of the periodontium.

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.

Malignant transformation of actinic cheilitis: A systematic review of observational studies.

The aim of the present systematic review was to determine the malignant transformation rate of actinic cheilitis (AC). A comprehensive literature search was conducted using Medline/PubMed, Cumulative Index of Nursing and Allied Health Literature, Scopus, OvidSP, and Google Scholar. The inclusion criteria comprised of observational human studies involving the malignant transformation of AC and publications in English. Studies included in this review were clinical follow-up, cohort, retrospective, or prospective investigations. The search yielded 1126 articles, and after exclusion, 34 full-text articles were eligible for full-text analysis. Only one article met the inclusion criteria. Based on the included article, it was determined that the malignant transformation rate of AC to squamous cell carcinoma (SCC) was 3.07%. Excluded articles focused on the clinicopathological characteristics and treatment efficacies of AC, and no malignant transformation rate was assessed. There is a need for more clinical studies on the malignant transformation of AC, as lip cancer is a public health concern. High-risk populations, including those living in tropical regions, have excessive exposure to UV radiation, and have older aged males, fair-skinned people, and smokers should be identified to prevent AC and its malignant change. Health practitioners should facilitate early intervention to prevent the progression of AC to SCC of the lip.