The value-for money of preventing and managing periodontitis: Opportunities and challenges.

This article gives an overview of the societal and economic aspects of periodontitis and periodontal care. Despite its largely preventable nature, periodontitis is highly prevalent worldwide and imposes a substantial health and economic burden on individuals and society as a whole. The worldwide estimated direct treatment costs and productivity losses due to periodontitis (including for periodontitis-related tooth loss) amounted to US$ 186 billion and US$ 142 billion in 2019, respectively. The burden of periodontitis is particularly evident in low and disadvantaged populations. Smoking, dietary habits, and presence of systemic diseases along with social and commercial determinants are considered as risk factors for the periodontal diseases. The cost-effectiveness of preventing and managing periodontitis has been explored in several studies but it has been highlighted that there is scope for improvement in defining the methodology and quality of reporting of such studies. A recent report by The Economist Intelligence Unit examined the cost-effectiveness of interventions to prevent and manage periodontal diseases, suggesting that prevention of periodontitis through prevention of gingivitis by means of individual home care would be more cost-efficient than four other examined approaches. Future research in this field is recommended to further decipher the economic burden of periodontitis to society and to assess the value for money of alternative approaches to address periodontitis with particular emphasis on public health preventive strategies and intersectoral care approaches that address the common risk factors of periodontitis and other non-communicable diseases simultaneously.

Consensus report of the second European Consensus Workshop on Education in Periodontology.

BACKGROUND: The second European Consensus Workshop on Education in Periodontology was commissioned, as a result of the changes in the discipline and the advances in educational methods/technology, to update the 2009 Consensus report of the first European Federation of Periodontology (EFP) Workshop on the same topic that was jointly authored by the Association for Dental Education in Europe. AIM: To identify and propose changes necessary in periodontal education at three levels, namely undergraduate, specialist and continuing professional development (CPD), with respect to learning outcomes, competencies and methods of learning/training and evaluation. METHODS: Four working groups (WGs) considered education in periodontology at the undergraduate, specialist and CPD levels, and education methods. Four commissioned position papers, one per WG, summarized the relevant information. Workshop participants gathered at an in-person consensus meeting to discuss the individual reviews, and this consensus report summarizes the conclusions. RESULTS: The learning outcomes for undergraduate and specialist education in periodontology have been updated, and a proposal for learning outcomes for CPD programmes was made. Learning/teaching/training and evaluation methods were proposed for each level of education, which included face-to-face, virtual and blended learning methods. CONCLUSION: Developments in oral/dental medicine and in contemporary educational technologies have been translated into updated learning outcomes and learning/teaching/ training/evaluation methods relevant to education in periodontology.

How to recognise a Behçet's ulcer from other types of oral ulceration? Defining Behçet's ulceration by an International Delphi Consultation.

OBJECTIVES: To define the clinical characteristics of oral ulceration (OU) in Behçet's disease (BD), to allow differentiation from other causes of OU, including aphthous ulcers, by an International Delphi consultation. To develop a clinical guideline on how to recognise BD ulcers. METHODS: Round 1. 40 clinical images of OU in BD, recurrent aphthous stomatitis (RAS), inflammatory bowel disease (IBD) and mucous membrane pemphigoid (MMP) were shown. Participants answered, independently, which images would be consistent with a BD ulcer. Round 2. The results from marking independently were shown. The panel remarked the questions through iteration process. The images not agreed to be a possible BD ulcer were discarded. Round 3. 10 clinical descriptors that may define BD ulcers were suggested. Participants ranked the level of importance for each descriptor on each image presented. Round 4. Participants re-ranked their level of agreement for each descriptor through iteration process. Whether the clinical pictures would be different from RAS was also explored. A final agreement was reached. RESULTS: This study has shown clear differentiation between BD, IBD and MMP ulcers when defining them by phenotype through clinical images only. On the other hand, no differentiation between RAS and BD ulcers was found. The most important clinical descriptors that define BD ulcers have been agreed. CONCLUSIONS: New clinical guidance for Health Care Professionals (HCP) on how to recognise a BD ulcer has been proposed. This should elucidate an earlier diagnosis, quicker access to treatment and control of the disease enhancing patient's quality of life.

The role of the host-Neutrophil biology.

Neutrophilic polymorphonuclear leukocytes (neutrophils) are myeloid cells packed with lysosomal granules (hence also called granulocytes) that contain a formidable antimicrobial arsenal. They are terminally differentiated cells that play a critical role in acute and chronic inflammation, as well as in the resolution of inflammation and wound healing. Neutrophils express a dense array of surface receptors for multiple ligands, ranging from integrins to support their egress from bone marrow into the circulation and from the circulation into tissues, to cytokine/chemokine receptors that drive their navigation to the site of infection or tissue damage and also prime them for a second stimulus, to pattern recognition receptors and immunoglobulin receptors to facilitate the destruction and removal of infective agents or debridement of damaged tissues. When afferent neutrophil signals are proportionate and coordinated they will phagocytose opsonized and unopsonized bacteria, activating the nicotinamide adenine dinucleotide phosphate oxidase (respiratory burst) to generate reactive oxygen species, which augment the proteolytic destruction of microbes secured within the phagosome. A highly orchestrated process of apoptosis follows, forming membrane-bound substructures that are removed by macrophages. Neutrophils are capable of various other forms of programmed cell death, such as NETosis and pyroptotic cell death, as well as nonprogrammed cell death by necrosis. In recent years, research has revealed that neutrophils are capable of far more subtle cell-cell interactions than previously thought possible. This includes synthesis of various inflammatory mediators and also myeloid cell training within bone marrow, where epigenetic and metabolic signals associated with returning neutrophils that undergo reverse egress from tissues into the vasculature and back to bone marrow program a hyperreactive subset of neutrophils during myelopoiesis that are capable of hypersensitive reactions to microbial aggressors. These characteristics are evident in various neutrophil subsets/subpopulations, creating broad heterogeneity in the behavior and biological repertoire of these seemingly schizophrenic immune cells. Moreover, neutrophils are critical effector cells of adaptive and innate immunity, binding to opsonized bacteria and destroying them by extracellular and intracellular methods. The former creates substantial collateral host tissue damage, as they are less specific than T-cytotoxic cell-killing mechanisms, and in conditions such as peri-implantitis, where plasma cells and neutrophils dominate the immune infiltrate, bone and tissue destruction are rapid and appear relentless. Finally, the role of neutrophils as conduits for periodontal-systemic disease connections and for oxidative damage to act as a causal link between the two has only recently been realized. In this chapter, we attempt to expand on these issues, emphasizing the contributions of European scientists throughout a detailed appraisal of the benefits and side effects of neutrophilic inflammation and immune function.

Pre-conditioning of gingival epithelial cells with sub-apoptotic concentrations of curcumin prevents pro-inflammatory cytokine release.

BACKGROUND AND OBJECTIVE: Plaque-induced gingival inflammation (gingivitis) is ubiquitous in humans. The epithelial barrier reacts to the presence of oral bacteria and induces inflammatory cascades. The objective of this study was to investigate the mechanism by which the small molecule micronutrient curcumin could decrease inflammatory response in vitro to oral bacterium heat-killed Fusobacterium nucleatum as curcumin could be a useful compound for combatting gingivitis already consumed by humans. METHODS: H400 oral epithelial cell line was pre-conditioned with curcumin and the production of cytokines was measured by enzyme-linked immunosorbent assay (ELISA) and translocation of transcription factors was used to monitor inflammatory responses. Haem oxygenase (HO-1) expression and molecules that HO-1 releases were evaluated for their potential to reduce the quantity of cytokine production. Immunofluorescence microscopy and Western blotting were used to evaluate changes in transcription factor and enzyme location. RESULTS: Pre-conditioning of H400 cells with a sub-apoptotic concentration of curcumin (20 µM) attenuated secretion of Granulocyte-Macrophage - Colony-Stimulating Factor (GM-CSF) and reduced NFkB nuclear translocation. This pre-conditioning caused an increase in nuclear Nrf2; an initial drop (at 8 h) followed by an adaptive increase (at 24 h) in glutathione; and an increase in haem oxygenase (HO-1) expression. Inhibition of HO-1 by SnPPIX prevented the curcumin-induced attenuation of GM-CSF production. HO-1 catalyses the breakdown of haem to carbon monoxide, free iron and biliverdin: the HO-1/CO anti-inflammatory pathway. Elevations in carbon monoxide, achieved using carbon monoxide releasing molecule-2 (CORM2) treatment alone abrogated F. nucleatum-induced cytokine production. Biliverdin is converted to bilirubin by biliverdin reductase (BVR). This pleiotropic protein was found to increase in cell membrane expression upon curcumin treatment. CONCLUSION: Curcumin decreased inflammatory cytokine production induced by Fusobacterium nucleatum in H400 oral epithelial cells. The mechanism of action appears to be driven by the increase of haem oxygenase and the production of carbon monoxide.

Periodontal health and patient-reported outcomes: A longitudinal analysis of data from non-specialist practice settings.

AIM: To explore the associations between periodontal health and patient-reported outcomes (PROs), accounting for changes over time, in a large, non-specialist dental practice patient cohort. MATERIALS AND METHODS: This longitudinal study used data from 13,162 dentate patients, collected by 162 dentists at routine appointments between May 2013 and April 2020, in 238 non-specialist dental practices across the United Kingdom. Dentists collected data, as part of routine clinical care, on periodontal probing pocket depths, alveolar bone loss, bleeding on probing, as well as a range of covariates. Patients inputted data on outcomes (oral pain/discomfort, dietary restrictions, and dental appearance). Mixed-effects logistic regression analysis was used to investigate the associations between periodontal health and PROs. Models accounted for clustering at the patient and dentist level and were adjusted for time and variables which were thought to confound these associations. RESULTS: The odds of all PROs tended to increase with worsening periodontal parameters. For example, the odds of reporting pain in the worst periodontal health category were 1.99 (95% confidence interval: 1.57-2.53) times higher than in the best periodontal health category. CONCLUSIONS: This study confirms, using a large longitudinal dataset from a unique non-specialist setting, the associations between poorer periodontal health and poorer PROs.

Outcomes of periodontal therapy in rheumatoid arthritis: The OPERA feasibility randomized trial.

AIM: Periodontitis is independently associated with rheumatoid arthritis (RA); however, there is limited data on whether periodontal treatment improves overall RA disease activity. We conducted a pilot feasibility randomized controlled clinical trial to test whether intensive periodontal therapy reduces RA disease activity in patients with active RA and periodontitis. MATERIALS AND METHODS: The following inclusion criteria were applied: patients with RA and periodontitis, aged 18+, stable on treatment with disease-modifying anti-rheumatic drugs for ≥3 months, disease activity score (DAS28) ≥3.2, and DAS28 >5.1 only if patient unwilling to take biologics. Participants meeting the inclusion criteria were randomized to immediate intensive periodontal therapy or to delayed therapy (control group) administered by a dental hygienist in a secondary care setting. Data were collected at baseline and at 3 and 6 months of follow-up. Participants randomized to the control group (delayed therapy) received the standard of care for the duration of the trial, including oral hygiene instructions delivered by a dental hygienist, and the same periodontal therapy as the intervention group after study completion (i.e., 6 months after randomization). The periodontal inflammation surface area was calculated using clinical attachment loss (CAL), periodontal probing pocket depth, and bleeding on probing. Cumulative probing depth was also measured. We examined the effect of periodontal therapy on periodontal outcomes and on clinical markers of disease activity in RA, as measured by the DAS28-C-reactive protein score as well as musculo-skeletal ultrasound grey scale and power Doppler scores. RESULTS: A total of 649 patients with RA were invited to participate in the study. Of these, 296 (46%) consented to participate in the screening visit. A sample of 201 patients was assessed for eligibility, of whom 41 (20%) did not meet the RA inclusion criteria and 100 (50%) did not meet the periodontal disease criteria. Among the 60 (30%) eligible participants, 30 were randomized to immediate periodontal therapy and 30 were allocated to the control group. The loss to follow-up was 18% at the end of the trial. There were no major differences with regard to baseline characteristics between the groups. Periodontal therapy was associated with reduced periodontal inflamed surface area, cumulative probing depths, RA disease activity scores, and ultrasound scores over the course of the trial. There was no change in CAL. CONCLUSIONS: Overall, the trial was feasible and acceptable to the study participants. Recruitment to and satisfactory retention in a randomized controlled trial on the effect of periodontal treatment on RA patients is possible, albeit challenging. In this feasibility study of patients with RA and periodontitis, periodontal treatment resulted in significant improvements in periodontal disease outcomes and overall RA disease activity, although complete resolution of periodontal inflammation was difficult to achieve in some cases.

Prevention and treatment of peri-implant diseases-The EFP S3 level clinical practice guideline.

BACKGROUND: The recently published Clinical Practice Guidelines (CPGs) for the treatment of stages I-IV periodontitis provided evidence-based recommendations for treating periodontitis patients, defined according to the 2018 classification. Peri-implant diseases were also re-defined in the 2018 classification. It is well established that both peri-implant mucositis and peri-implantitis are highly prevalent. In addition, peri-implantitis is particularly challenging to manage and is accompanied by significant morbidity. AIM: To develop an S3 level CPG for the prevention and treatment of peri-implant diseases, focusing on the implementation of interdisciplinary approaches required to prevent the development of peri-implant diseases or their recurrence, and to treat/rehabilitate patients with dental implants following the development of peri-implant diseases. MATERIALS AND METHODS: This S3 level CPG was developed by the European Federation of Periodontology, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations, and a structured consensus process involving leading experts and a broad base of stakeholders. RESULTS: The S3 level CPG for the prevention and treatment of peri-implant diseases culminated in the recommendation for implementation of various different interventions before, during and after implant placement/loading. Prevention of peri-implant diseases should commence when dental implants are planned, surgically placed and prosthetically loaded. Once the implants are loaded and in function, a supportive peri-implant care programme should be structured, including periodical assessment of peri-implant tissue health. If peri-implant mucositis or peri-implantitis are detected, appropriate treatments for their management must be rendered. CONCLUSION: The present S3 level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to maintain healthy peri-implant tissues, and to manage peri-implant diseases, according to the available evidence at the time of publication.

Association between periodontal diseases and cardiovascular diseases, diabetes and respiratory diseases: Consensus report of the Joint Workshop by the European Federation of Periodontology (EFP) and the European arm of the World Organization of Family Doctors (WONCA Europe).

AIM: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles. MATERIALS AND METHODS: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors. CONCLUSIONS: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated.

Under pressure-mechanisms and risk factors for orthodontically induced inflammatory root resorption: a systematic review.

BACKGROUND: The application of orthodontic forces causes root resorption of variable severity with potentially severe clinical ramifications. OBJECTIVE: To systematically review reports on the pathophysiological mechanisms of orthodontically induced inflammatory root resorption (OIIRR) and the associated risk factors based on in vitro, experimental, and in vivo studies. SEARCH METHODS: We undertook an electronic search of four databases and a separate hand-search. SELECTION CRITERIA: Studies reporting on the effect of orthodontic forces with/without the addition of potential risk factors on OIIRR, including (1) gene expression in in-vitro studies, the incidence root resorption in (2) animal studies, and (3) human studies. DATA COLLECTION AND ANALYSIS: Potential hits underwent a two-step selection, data extraction, quality assessment, and systematic appraisal performed by duplicate examiners. RESULTS: One hundred and eighteen articles met the eligibility criteria. Studies varied considerably in methodology, reporting of results, and variable risk of bias judgements.In summary, the variable evidence identified supports the notion that the application of orthodontic forces leads to (1) characteristic alterations of molecular expression profiles in vitro, (2) an increased rate of OIIRR in animal models, as well as (3) in human studies. Importantly, the additional presence of risk factors such as malocclusion, previous trauma, and medications like corticosteroids increased the severity of OIIRR, whilst other factors decreased its severity, including oral contraceptives, baicalin, and high caffeine. CONCLUSIONS: Based on the systematically reviewed evidence, OIIRR seems to be an inevitable consequence of the application of orthodontic forces-with different risk factors modifying its severity. Our review has identified several molecular mechanisms that can help explain this link between orthodontic forces and OIIRR. Nevertheless, it must be noted that the available eligible literature was in part significantly confounded by bias and was characterized by substantial methodological heterogeneity, suggesting that the results of this systematic review should be interpreted with caution. REGISTRATION: PROSPERO (CRD42021243431).

Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK).

BACKGROUND: Risk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. METHODS: We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19. RESULTS: We recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0-30.0 kg/m2 and 1.39 (1.06 to 1.84) for BMI >30.0 kg/m2 versus BMI <25.0 kg/m2). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use. CONCLUSIONS: After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04330599).

Investigating the utility of saliva immunoglobulins for the detection of myeloma and using myeloma proteins to clarify partition between oral and systemic immunity.

OBJECTIVES: Myeloma is characterised by the presence of monoclonal immunoglobulin (M-protein) and the free light chain (FLC) in blood. We investigated whether these M-proteins and FLC are detectable in myeloma patients' saliva to evaluate its utility for non-invasive screening and monitoring of haematological malignancies. METHODS: A total of 57 patients with monoclonal gammopathy and 26 age-matched healthy participants provided paired serum and saliva samples for immunoglobulin characterisation and quantification. RESULTS: Myeloma patients had IgG or IgA M-protein levels ranging up to five times and FLC levels up to a thousand times normal levels of polyclonal immunoglobulins. Despite these highly elevated levels, only two IgG and no IgA M-proteins or FLC could be detected in paired saliva samples. Most patients had reduced levels of serum polyclonal immunoglobulins, but all had normal levels of salivary IgA. CONCLUSIONS: Immunoglobulin transfer from blood is not determined by levels in the systemic circulation and more likely dictated by periodontal inflammation and the integrity of the oral epithelium. Immunoglobulins secreted by bone marrow plasma cells do not substantially enter saliva, which represents a poor medium for myeloma diagnosis. These findings, along with normal salivary IgA levels despite systemic immunoparesis, support a strong partitioning of oral from systemic humoral immunity.

Treatment of stage IV periodontitis: The EFP S3 level clinical practice guideline.

BACKGROUND: The recently published clinical practice guideline (CPG) for the treatment of periodontitis in stages I-III provided evidence-based recommendations for the treatment of periodontitis patients, defined according to the 2018 classification. Stage IV periodontitis shares the severity and complexity characteristics of stage III periodontitis, but includes the anatomical and functional sequelae of tooth and periodontal attachment loss (tooth flaring and drifting, bite collapse, etc.), which require additional interventions following completion of active periodontal therapy. AIM: To develop an S3 Level CPG for the treatment of stage IV periodontitis, focusing on the implementation of inter-disciplinary treatment approaches required to treat/rehabilitate patients following associated sequelae and tooth loss. MATERIALS AND METHODS: This S3 Level CPG was developed by the European Federation of Periodontology (EFP), following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, the formulation of specific recommendations and a structured consensus process with leading experts and a broad base of stakeholders. RESULTS: The S3 Level CPG for the treatment of stage IV periodontitis culminated in recommendations for different interventions, including orthodontic tooth movement, tooth splinting, occlusal adjustment, tooth- or implant-supported fixed or removable dental prostheses and supportive periodontal care. Prior to treatment planning, it is critically important to undertake a definitive and comprehensive diagnosis and case evaluation, obtain relevant patient information, and engage in frequent re-evaluations during and after treatment. The periodontal component of therapy should follow the CPG for the treatment of periodontitis in stages I-III. CONCLUSIONS: The present S3 Level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat patients with stage IV periodontitis and to maintain a healthy dentition over lifetime, according to the available evidence at the time of publication.

Discovery, validation, and diagnostic ability of multiple protein-based biomarkers in saliva and gingival crevicular fluid to distinguish between health and periodontal diseases.

AIM: To discover and validate differential protein biomarker expression in saliva and gingival crevicular fluid (GCF) to discriminate objectively between periodontal health and plaque-induced periodontal disease states. MATERIALS AND METHODS: One-hundred and ninety participants were recruited from two centres (Birmingham and Newcastle upon Tyne, UK) comprising healthy, gingivitis, periodontitis, and edentulous donors. Samples from the Birmingham cohort were analysed by quantitative mass spectrometry proteomics for biomarker discovery. Shortlisted candidate proteins were then verified by enzyme-linked immunosorbent assay in both cohorts. Leave-one-out cross validation logistic regression analysis was used to identify the best performing biomarker panels. RESULTS: Ninety-five proteins were identified in both GCF and saliva samples, and 15 candidate proteins were selected based upon differences discovered between the donor groups. The best performing panels to distinguish between: health or gingivitis and periodontitis contained matrix metalloproteinase-9 (MMP9), S100A8, alpha-1-acid glycoprotein (A1AGP), pyruvate kinase, and age (area under the curve [AUC] 0.970); health and gingivitis contained MMP9, S100A8, A1AGP, and pyruvate kinase, but not age (AUC 0.768); and mild to moderate and advanced periodontitis contained MMP9, S100A8, A1AGP, pyruvate kinase, and age (AUC 0.789). CONCLUSIONS: Biomarker panels containing four proteins with and without age as a further parameter can distinguish between periodontal health and disease states.

Oxidative stress links periodontal inflammation and renal function.

AIMS: Patients with chronic kidney disease (CKD) are also susceptible to periodontitis. The causal link between periodontitis and CKD may be mediated via systemic inflammation/oxidative stress. Using structural equation modelling (SEM), this cross-sectional study aimed to explore the causal relationship between periodontal inflammation (PI) and renal function. MATERIALS AND METHODS: Baseline data on 770 patients with stage 3-5 (pre-dialysis) CKD from an ongoing cohort study were used. Detailed, bioclinical data on PI and renal function, as well as potential confounders and mediators of the relationship between the two, were collected. SEMs of increasing complexity were created to test the causal assumption that PI affects renal function and vice versa. RESULTS: Structural equation modelling confirmed the assumption that PI and renal function are causally linked, mediated by systemic oxidative stress. The magnitude of this effect was such that a 10% increase in PI resulted in a 3.0% decrease in renal function and a 10% decrease in renal function resulted in a 25% increase in PI. CONCLUSIONS: Periodontal inflammation represents an occult source of oxidative stress in patients with CKD. Further clinical studies are needed to confirm whether periodontal therapy, as a non-pharmacological approach to reducing systemic inflammatory/oxidative stress burden, can improve outcomes in CKD.

Consumer Safety Considerations of Skin and Oral Microbiome Perturbation.

Microbiomes associated with human skin and the oral cavity are uniquely exposed to personal care regimes. Changes in the composition and activities of the microbial communities in these environments can be utilized to promote consumer health benefits, for example, by reducing the numbers, composition, or activities of microbes implicated in conditions such as acne, axillary odor, dandruff, and oral diseases. It is, however, important to ensure that innovative approaches for microbiome manipulation do not unsafely disrupt the microbiome or compromise health, and where major changes in the composition or activities of the microbiome may occur, these require evaluation to ensure that critical biological functions are unaffected. This article is based on a 2-day workshop held at SEAC Unilever, Sharnbrook, United Kingdom, involving 31 specialists in microbial risk assessment, skin and oral microbiome research, microbial ecology, bioinformatics, mathematical modeling, and immunology. The first day focused on understanding the potential implications of skin and oral microbiome perturbation, while approaches to characterize those perturbations were discussed during the second day. This article discusses the factors that the panel recommends be considered for personal care products that target the microbiomes of the skin and the oral cavity.

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.

Treatment of stage I-III periodontitis-The EFP S3 level clinical practice guideline.

BACKGROUND: The recently introduced 2017 World Workshop on the classification of periodontitis, incorporating stages and grades of disease, aims to link disease classification with approaches to prevention and treatment, as it describes not only disease severity and extent but also the degree of complexity and an individual's risk. There is, therefore, a need for evidence-based clinical guidelines providing recommendations to treat periodontitis. AIM: The objective of the current project was to develop a S3 Level Clinical Practice Guideline (CPG) for the treatment of Stage I-III periodontitis. MATERIAL AND METHODS: This S3 CPG was developed under the auspices of the European Federation of Periodontology (EFP), following the methodological guidance of the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). The rigorous and transparent process included synthesis of relevant research in 15 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, the formulation of specific recommendations and consensus, on those recommendations, by leading experts and a broad base of stakeholders. RESULTS: The S3 CPG approaches the treatment of periodontitis (stages I, II and III) using a pre-established stepwise approach to therapy that, depending on the disease stage, should be incremental, each including different interventions. Consensus was achieved on recommendations covering different interventions, aimed at (a) behavioural changes, supragingival biofilm, gingival inflammation and risk factor control; (b) supra- and sub-gingival instrumentation, with and without adjunctive therapies; (c) different types of periodontal surgical interventions; and (d) the necessary supportive periodontal care to extend benefits over time. CONCLUSION: This S3 guideline informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat periodontitis and to maintain a healthy dentition for a lifetime, according to the available evidence at the time of publication.

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.

Periodontitis and cardiovascular diseases: Consensus report.

BACKGROUND: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. MATERIAL AND METHODS: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations RESULTS AND CONCLUSIONS: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.