Association between rheumatoid arthritis and pulpal-periapical pathology: a systematic review.

OBJECTIVES: Rheumatoid arthritis (RA) is a debilitating disease where numerous pro-inflammatory cytokines have a proven role in its pathology. These cytokines are also involved in the pathogenesis of apical periodontitis (AP) where they have a pro-inflammatory role and induce bone resorption. Patients with RA may therefore be more prone to develop pulpal-periapical pathology (PPP). This study systematically reviewed the existing literature evaluating the association between RA and PPP. MATERIALS AND METHODS: Studies including human participants with both RA and PPP were included. The search was performed in PubMed, Web of Science, and The Cochrane Library databases using keywords and Medical Subject Headings (MeSH) search terms. The risk of bias was assessed using Newcastle-Ottawa Quality Assessment Scale. The following parameters were extracted and analyzed by the reviewers; author, journal, year, design of the study, diagnostic criteria for periapical pathology, the association between rheumatoid arthritis and periapical pathology, and the evidence level. RESULTS: The search identified 142 records. Inclusion criteria were as follows; studies in the English language, including human participants only, including patients with RA and PPP, cohort studies, cross-sectional studies, clinical trials, and case-control studies. According to the inclusion criteria, 5 studies were included in this systematic review. Three of the five studies reported significant association between RA and PPP. CONCLUSIONS: Existing evidence suggests there may be an association between RA and PPP. CLINICAL RELEVANCE: Clinicians should be aware that RA patients can be more prone to develop PPP which may result in a reduced quality of life.

Point-of-care HbA1c Measurements in Oral Cancer and Control Patients in Hungary.

BACKGROUND/AIM: This study aimed to investigate the link between preoperative glycated hemoglobin (HbA1c) levels and oral cancer patients and diabetes mellitus (DM). We aimed to highlight the importance of point-of-care HbA1c measurements in oral cancer patients. PATIENTS AND METHODS: A total of 214 patients were admitted to the Department of Inpatient Care at Semmelweis University's Department of Oromaxillofacial Surgery and Stomatology between 1 September 2020 and 21 May 2021; individuals, who had undergone maxillofacial surgery under general anesthesia, were included in the study. RESULTS: There was a significant difference between the oral cancer group and the control group in terms of smoking (p=0.009) and alcohol intake (p=0.003). There was no statistically significant difference regarding sex (p=0.132) and DM (p=0.147) between the two groups. The tumor group had an 8.52% greater prevalence of DM, which was not significant. In the oral cancer group, twenty individuals (17.69%) had a higher HbA1c level than the upper level of the optimal metabolic value (6.9%). Nine participants (8.91%) in the control group had an HbA1c value greater than 6.9%, which means that their metabolic level was poor. The oral cancer group did not have higher blood glucose levels than those of the control group. CONCLUSION: No direct connection between high blood glucose levels and oral cancer was found. However, point-of-care HbA1c measurement can be a diagnostic tool to detect DM in the dental office.

Impact of Gingivitis on Circulating Neutrophil Reactivity and Gingival Crevicular Fluid Inflammatory Proteins.

Gingivitis is an extremely common oral inflammatory condition and can be induced in humans using an acute 21-day experimental gingivitis model. Neutrophils are known to be highly prevalent in the gingival crevice during gingival inflammation; however, the effect of gingivitis and the associated biofilm on peripheral blood neutrophils (PBN) is not well characterised. Thus, the aim of this study was to examine the impact of inflammation induced by experimental gingivitis and its resolution upon the function of PBN. Fifteen systemically healthy volunteers undertook a split-mouth 21-day experimental gingivitis study followed by a resolution phase of 14 days. PBN function, including reactive oxygen species (ROS) production, neutrophil extracellular trap (NET) release, directional chemotactic accuracy and expression of host mediators in gingival crevicular fluid (GCF), were measured at baseline (day 0), on day 21 and on day 35. NET formation and ROS production were significantly elevated at day 21. Chemotactic speed was also elevated in response to bacterial peptide fMLP at day 21. At day 35, ROS production in response to an Fcgamma stimulant, opsonised Staphylococcus aureus, remained elevated. The data presented suggest a lasting biological impact of the experimental gingivitis on PBN function even after clinical symptoms have abated.

Randomised methodology development study to investigate plaque removal efficacy of manual toothbrushes.

OBJECTIVES: This study aimed to evaluate plaque removal efficacy of toothbrushes to guide clinical model development. METHODS: This single-centre, randomised, controlled, examiner-blind, method development study included 80 healthy participants. Over 28 days, participants brushed twice-daily using a fluoride toothpaste and one of four marketed toothbrushes: Toothbrushes A (compact head) and B (regular head): medium-hard; flat trim; end-rounded bristles; Toothbrush C: medium-hard; end-rounded bristles; silky, tapered filaments; compact head; Toothbrush D: soft; tapered filaments; compact head. Supra-gingival plaque removal was evaluated immediately after single brushing events (Days 0, 7, 28, at study centre) and following 7- and 28-days' home use via Rustogi modified Navy Plaque Index (RPI) and Turesky modified Quigley Hein Plaque Index (TPI). RESULTS: All toothbrushes provided significant plaque removal after single-brushing events with change from Day 0 pre-brushing scores on RPI ranging from -0.10 to -0.16 (p<.0001) and on TPI ranging from -0.61 to -0.89 (p<.0001). Toothbrushes A and B showed significant (p<.05) pre-brushing RPI/TPI plaque reductions after 7- (-0.04/-0.06, respectively for RPI; -0.16/-0.20, respectively for TPI) and 28-days (-0.04/-0.03, respectively for RPI; -0.20/-0.11, respectively for TPI) use versus Day 0 pre-brushing (except Toothbrush B, Day 28, non-significant TPI). There were no significant differences with Toothbrush C. Toothbrush D TPI was significantly lower at both timepoints versus Day 0 pre-brushing (p<.05). Study toothbrushes were generally well-tolerated. CONCLUSION: The observations from this study showed how various aspects of a study design could impact toothbrushes performance. These data will inform the design of future clinical studies of plaque removal efficacy using manual toothbrushes. CLINICAL SIGNIFICANCE STATEMENT: Regular effective oral hygiene can help prevent and treat gingivitis, principally via twice-daily mechanical cleaning with a toothbrush. Data generated from this methodology development study will help to identify the key aspects which impact toothbrushes' performance and understand which one would be more suitable to answer questions of scientific interest. This study provides useful information for the design of future clinical trials to assess plaque removal efficacy of manual toothbrushes and generate results to inform clinical recommendations.

Prognostic performance of the 2017 World Workshop classification on staging and grading of periodontitis compared with the British Society of Periodontology's implementation.

BACKGROUND: The British Society of Periodontology (BSP) implemented a simplified version of the 2017 World Workshop Classification (WWC) on staging and grading of periodontitis, for use in UK clinical practice. The aim of this study was to assess the long-term (>10 years) prognostic capability of BSP's implementation (BSP-i) compared with the 2017 WWC, using periodontal-related tooth loss (TLP) as a disease outcome. METHODS: Data on medical history, smoking status, and clinical periodontal parameters were retrieved from 270 patients who received non-surgical and surgical periodontal therapy from 1966 to 2007. Each patient received a baseline diagnosis according to the 2017 WWC and the BSP-i guidelines for implementation. Univariate multilevel Cox regression frailty models were performed to analyze the association between variables with TLP. A post-hoc comparison with Bonferroni correction was performed to analyze interclass comparisons. The prognostic performance of both systems was analyzed using Harrell C index. RESULTS: The prognostic performance of both systems was very similar (0.922 for the 2017 WWC and 0.925 for the BSP-i). The singular prognostic performance of BSP stage was slightly higher than that of 2017 WWC stage (0.9212 versus 0.9188), while the 2017 WWC grade showed a slightly better performance than BSP grade (0.9175 versus 0.9155). BSP-i's extent performed better than the 2017 WWC extent (0.9203 versus 0.9098); however, in the 2017 WWC extent, the class "localized" was associated with a better prognosis than "generalized." CONCLUSION: The overall prognostic performance of the two systems was excellent, with both systems having a Harrell C index score of >0.92.

Patient acceptability of targeted risk-based detection of non-communicable diseases in a dental and pharmacy setting.

BACKGROUND: Non-communicable diseases [NCDs] are the major cause of mortality globally and are increasing in prevalence. Different healthcare professionals' access different population groups; and engaging allied healthcare professionals in risk-driven early case detection of certain NCDs may be beneficial, especially those who have not been tested for NCDs within the previous 12 months. The objectives of this study were to determine: whether NCD case finding in dental/community pharmacy settings is feasible in terms of patient acceptability, barriers to recruitment, impact on the existing service. Determine time taken to test for: type 2 diabetes risk [T2DM], chronic obstructive pulmonary disease [COPD], hypertension, vitamin D deficiency and chronic kidney disease [CKD]. Determine whether there is added benefit of point of care testing [POCT] to identify diabetes risk compared to a validated screening questionnaire alone. METHODS: An exploratory study was undertaken to explore issues associated with NCD assessment in one dental practice and one community pharmacy within the West-Midlands, UK. Fifty patients > 40 years-of-age were recruited per site. Participants undertook: a questionnaire providing demographic data, any previous NCD diagnosis or positive family history. Validated questionnaires for determining NCD risk [T2DM/COPD]. Chair-side capillary blood [finger-prick] samples for HbA1C, creatinine/eGFR, Vitamin-D. Prior work had been undertaken to measure the agreement between point of care testing [POCT] devices and a central laboratory method, and to gauge the opinions of participants regarding discomfort experienced using venous (antecubital fossa) and capillary (finger-prick) blood collection, via a 10 cm Visual-Analogue-Scale. The POCT devices demonstrated good concordance with laboratory testing and were acceptable methods of blood collection for participants. RESULTS: Recruitment rates demonstrated that 8 days were needed to recruit 50 participants and 60% of those approached opted to participate. The principal barrier to participation was time, with average time taken to test being 19mins. Utilising dental and pharmacy settings identified potential cases of previously undiagnosed disease. CONCLUSIONS: Risk-targeted testing for NCDs in high street dental and community pharmacies is both attractive and acceptable to patients.

Predicted salivary human protease activity in experimental gingivitis revealed by endoProteo-FASP approach.

Gingivitis is a highly prevalent oral condition that can be studied in humans via the 21-d experimental gingivitis model, which allows for investigations into the induction and resolution of gingivitis. In this study, we used the autolysis of saliva as a source of peptides to predict the activity of human proteases in saliva during induction and resolution of inflammation. Healthy volunteers, with no remarkable oral or systemic conditions, were recruited into the study and stimulated saliva samples were collected at days 0, 21, and 35 of experimental gingivitis. Plaque and gingival indices were recorded to ensure clinical induction and resolution. Saliva was auto-digested at 37°C for 18 h before identification of peptides by mass spectrometry. Protease prediction was carried out using Proteasix in silico with the identified peptides. A comparison of day 0 to days 21 and 35 showed changes in predicted protease activity. Correlation network analysis revealed that at day 21 the proteases became less connected and showed a potential for a dysregulated system; by day 35 the connectivity was returning towards similar conditions at day 0. This study demonstrates that changes in predicted proteases are apparent even in saliva collected from donors experiencing inflammation around three teeth.

The clinical and inflammatory relationships between periodontitis and chronic obstructive pulmonary disease.

AIM: To investigate associations between periodontitis and chronic obstructive pulmonary disease (COPD) with and without alpha-1 antitrypsin deficiency (AATD), including neutrophil functions implicated in tissue damage. METHODS: The presence and severity of periodontitis (using two international criteria) and lung disease were assessed in 156 COPD patients with and without AATD accounting for common confounding factors. Saliva and systemic inflammatory markers were measured by ELISA together with neutrophil migration. RESULTS: COPD and AATD patients exhibited higher prevalence of periodontitis (COPD 95%; AATD 88%) than reported in unselected community-dwelling populations even when risk factors (age, smoking history, socio-economic status and dental habits) were considered. Periodontitis severity associated with lung disease severity (AATD, periodontitis versus no periodontitis; FEV1 = 56% versus 99% predicted; TLCO = 59% versus 81% predicted, p < .0001 for both). Neutrophil migratory accuracy declined in stage II-IV periodontitis patients with COPD or AATD compared to COPD or AATD with no or stage I periodontitis. Improved dental habits appeared to be associated with a reduction in exacerbation frequency in COPD. CONCLUSION: The results support shared pathophysiology between periodontitis and COPD, especially when associated with AATD. This may reflect an amplification of neutrophilic inflammation and altered neutrophil functions, already described in periodontitis, COPD and AATD.

Free light chains as an emerging biomarker in saliva: Biological variability and comparisons with salivary IgA and steroid hormones.

BACKGROUND: Salivary free light chains (FLCs) are an emerging biomarker in health and behavioural research. However, little is known regarding biological variability of salivary FLCs and how they relate to other established salivary biomarkers. This study aimed to investigate the diurnal and day-to-day variation of salivary FLCs and their relationship with salivary IgA and steroid hormones. METHODS: A total of 46 healthy adults participated in studies exploring the biological variability of FLCs. Diurnal variation was investigated by collecting saliva samples immediately upon waking, 0.5 h, 3 h, 6 h, 9 h and 14 h post-waking. Saliva samples were assessed for FLCs, IgA, cortisol and dehydroepiandrosterone (DHEA). Between-day variation in FLCs and IgA was assessed by collecting saliva samples immediately upon waking for seven consecutive days. Participants underwent a dental examination to exclude oral health as a potential confounding variable. Within and between-person day-to day variation was explored in relation to a range of different factors: awakening time, sleep, exercise, well-being and alcohol consumption. RESULTS: Salivary secretion rates of FLCs decreased following waking and up to 3 h post-waking and then plateaued. This same pattern was observed for IgA. DHEA was stable upon waking and higher levels were seen in the morning with significantly lower levels thereafter. Cortisol levels significantly increased 0.5 h post-waking then continued to decline across the day. FLCs were significantly correlated with IgA but not cortisol or DHEA. Both FLCs and IgA parameters showed day-to-day variability, with coefficients of variation ≥ 40%. Earlier waking time was significantly correlated with higher FLC and IgA secretion rates. Inter-person differences in saliva parameter variability were observed but the degree of variation in FLCs and IgA was related within person. Inter-person day-to-day variation appeared to be uninfluenced by lifestyle or behavioural factors. CONCLUSIONS: Saliva FLCs secretion exhibits diurnal fluctuation that mirrors IgA fluctuation. Findings strongly indicate salivary FLC secretion is orchestrated by local plasma cells. FLCs and IgA both showed notable variability day-to-day, which was similar within person and influenced by awakening time. FLCs offer a promising adjunct to IgA in the measurement of oral immune activation.

Use of Dental Practices for the Identification of Adults With Undiagnosed Type 2 Diabetes Mellitus or Nondiabetic Hyperglycemia: Protocol for a Systematic Review.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a growing global health burden and is expected to affect more than 590 million people by the year 2035. Evidence exists to demonstrate that dental settings have been used for risk assessment and identification of individuals who may be at high risk for T2DM or who may already unknowingly have the condition. OBJECTIVE: This protocol aims to outline the methodology that will be undertaken to synthesize the literature relating to the use of primary care (nonhospital-based) dental services for the identification of undiagnosed T2DM or prediabetes-often termed nondiabetic hyperglycemia-in adult patients. METHODS: This paper outlines the protocol that will be followed to conduct a systematic review and meta-analysis of the available literature. The protocol outlines the aims, objectives, search strategy, data extraction and data management methods, as well as the statistical analysis plan. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines were followed in developing the protocol as were elements of the Cochrane handbook. RESULTS: We expect the systematic review to be completed within 18 months of publication of this protocol and expect to see a high degree of heterogeneity in the existing literature. CONCLUSIONS: This review is of importance as it will synthesize the existing evidence base and inform future studies in the field. Following the publication of the protocol, the review will be registered on Prospective Register of Systematic Reviews. Following the completion of the review, results will be published in a suitable peer-reviewed journal. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11843.

Patients' attendance patterns to different healthcare settings and perceptions of stakeholders regarding screening for chronic, non-communicable diseases in high street dental practices and community pharmacy: a cross-sectional study.

OBJECTIVE: Non-communicable diseases (NCDs) impose a significant health and economic burden. This study aimed to assess the differential attendance patterns of public to different healthcare professionals and gauge the opinions of key stakeholders towards screening of NCDs by allied healthcare professionals. DESIGN: Questionnaires were designed piloted and subsequently completed by key stakeholders. The results were analysed descriptively. SETTING: Public questionnaires were undertaken in a West Midlands transport station and Public Markets. High street dental and community pharmacy settings were selected via local clinical and research networks. Healthcare professionals were identified using professional networks and were emailed a web link to an online survey. PARTICIPANTS: 1371 members of the public, 1548 patients and 222 healthcare professionals (doctors general practitioner (GP), dentists general dental practitioner (GDP) and pharmacists) completed the questionnaires. OUTCOME MEASURES: The outcome was to compare attendance patterns at GDP and GP practices to determine whether different populations were more likely to access different healthcare professionals, this included determining when patients were last screened for NCDs by their GP. Additionally, the willingness of patients to undergo the required intervention and the opinions of stakeholders regarding the concept of screening for the specified NCDs in general dental and community pharmacy settings were also explored. RESULTS: 12% of patients who reported seeing a GDP biannually reported that they had not had contact with a GP in the last year. Over 61% of the public reported attending a GDP biannually, of this group 48% reported having never had a check-up at the GP. All stakeholders surveyed were in broad support of the concept of allied health professionals undertaking screening for specific general health conditions. CONCLUSIONS: This study has established that allied healthcare professionals may have access to different cohorts of the population to GPs. If GDPs and pharmacists have access to patients who are not using healthcare services elsewhere, they may be ideally placed to risk assess, and where appropriate offer preventative advice and test for NCDs.

Association between periodontal health status and patient-reported outcomes in patients managed in a non-specialist, general dental practice.

AIMS: To explore the associations between periodontal status and patient-reported outcomes (PROs) in a large cohort of patients based in non-specialist general dental practice. MATERIALS AND METHODS: Analysis was conducted using data from 14,620 patients, in 233 non-specialist dental practices across the UK. As part of routine clinical care, data on periodontal probing depths (PPD), alveolar bone loss (ABL), bleeding on probing (BoP) as well as PROs (oral pain/discomfort, dietary restrictions and dental appearance) were recorded using an online database. The associations between periodontal status and PROs were investigated using logistic regression analysis, adjusting for confounders. RESULTS: We found a positive association between worse periodontal health and the prevalence of PROs. After adjustment for confounders, 13.8% of patients in the healthiest category (PPD < 5 mm, ABL < 2 mm, no BoP) reported pain/discomfort, compared to 20.7% of patients in the worst category (PPD > 7 mm, ABL > 4 mm). A similar trend was seen with reporting a restricted diet and unhappiness with appearance. CONCLUSION: This study provides novel insights into the associations between periodontal status and PROs in a non-specialist, general dental practice, highlighting the benefits of prevention and management of periodontitis.

Dysbiotic Subgingival Microbial Communities in Periodontally Healthy Patients With Rheumatoid Arthritis.

OBJECTIVE: Studies that demonstrate an association between rheumatoid arthritis (RA) and dysbiotic oral microbiomes are often confounded by the presence of extensive periodontitis in these individuals. This study was undertaken to investigate the role of RA in modulating the periodontal microbiome by comparing periodontally healthy individuals with RA to those without RA. METHODS: Subgingival plaque was collected from periodontally healthy individuals (22 with RA and 19 without RA), and the 16S gene was sequenced on an Illumina MiSeq platform. Bacterial biodiversity and co-occurrence patterns were examined using the QIIME and PhyloToAST pipelines. RESULTS: The subgingival microbiomes differed significantly between patients with RA and controls based on both community membership and the abundance of lineages, with 41.9% of the community differing in abundance and 19% in membership. In contrast to the sparse and predominantly congeneric co-occurrence networks seen in controls, RA patients revealed a highly connected grid containing a large intergeneric hub anchored by known periodontal pathogens. Predictive metagenomic analysis (PICRUSt) demonstrated that arachidonic acid and ester lipid metabolism pathways might partly explain the robustness of this clustering. As expected from a periodontally healthy cohort, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were not significantly different between groups; however, Cryptobacterium curtum, another organism capable of producing large amounts of citrulline, emerged as a robust discriminant of the microbiome in individuals with RA. CONCLUSION: Our data demonstrate that the oral microbiome in RA is enriched for inflammophilic and citrulline-producing organisms, which may play a role in the production of autoantigenic citrullinated peptides in RA.

The Role of the Dental Team in the Prevention of Systemic Disease: the Importance of Considering Oral Health As Part of Overall Health.

The global burden of non-communicable disease (NCD) is significant and the World Health Organization highlighted tackling non-communicable diseases (NCDs) as a key strategic objective in their 'Global action plan for the prevention and control of noncommunicable diseases, 2013-2020'. Dental teams see a large proportion of the UK population at regular intervals, including when patients deem themselves to be in good dental health. Given that many NCDs have shared risk factors, often behavioural with implications for oral and general health, dental teams are ideally placed to provide preventative advice for diseases beyond the oral environment. This article aims to assess the key risk factors for NCDs and oral diseases as well as assess the potential for dental care professionals (DCPs) to provide patients with general health advice based on their individual risk factors.

Defining Over-Sedation: Literature Review and National Survey of Dental Hospitals Within the United Kingdom.

AIMS: To review the literature, to investigate whether there was aconsensus on what encompasses over-sedation, and to determine the guidance employed for the administration of flumazenil. METHODS: A literature search was performed following which a self-designed questionnaire was emailed to 14 sedation leads within UK Dental Hospitals. RESULTS: 10 documents in the literature review met the inclusion criteria. In their definitions of over-sedation, loss of consciousness and respiratory depression were the main terms used; but a variety of terms were also seen, indicating a lack of agreement. Fourteen dental institutes were contacted of which nine (64%) responded. Thirty-seven per cent of sedation leads who responded stated they were unaware of a definition for over-sedation. Seventy-seven percent stated that when flumazenil was used this was recorded in a drugs book, with a broad range of justifications given. CONCLUSION: This study shows that there is a lack of uniformity both from clinicians and the literature, in what encompasses over-sedation. This makes formulating an accepted definition of over-sedation difficult. In order to ensure accurate reporting, monitoring and auditing of such events, a clear definition for over-sedation is required and can be used to provide clarity when flumazenil is to be administered.

Juvenile Hyaline Fibromatosis: Impact of Periodontal Care on Quality of Life and a Patient Perspective.

Juvenile hyaline fibromatosis (JHF) is a rare autosomal recessive inherited condition presenting early in life and characterized by the accumulation of hyaline-like tissue in the skin as well as various organs. Gingival overgrowth is a significant oral manifestation. This paper highlights how early and essential periodontal intervention may be necessary to improve mastication and subsequent weight gain, and to eliminate pain and improve the patient's quality of life. Here we highlight the key features of this condition and demonstrate how appropriate surgical management can have a significant impact on a patient's wellbeing. CPD/CLINICAL RELEVANCE: Juvenile hyaline fibromatosis has a significant impact on patient wellbeing and it is therefore important that clinicians are able to recognize the condition and ensure that patients receive appropriate care and management.