Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study.

OBJECTIVE: Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain. DESIGN: Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up. RESULTS: Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5-9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (Ptrend<0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73-0.87). CONCLUSION: Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient.

Subgingival microbial changes in Down Syndrome adults with periodontitis after chlorhexidine adjunct non-surgical therapy and monthly recalls-A 12-month case series study.

OBJECTIVES: Down Syndrome (DS) adults are at risk for periodontitis. Previous reports indicated difficulties in periodontopathogen reduction or eradication in DS individuals after periodontal treatment. This case series follows the subgingival microbial changes in adult DS individuals with periodontitis who received chlorhexidine adjunct non-surgical therapy plus 12-month recalls. METHODS: Twenty periodontitis DS participants (7 females; 25.5 ± 5.6 years of age; 3 with generalized periodontitis) partook in a study involving non-surgical mechanical periodontal therapy, twice daily chlorhexidine gel toothbrushing, chlorhexidine mouthwash, and monthly recalls. The subgingival microbiota profile was followed at baseline, 6-, and 12-months post-operation. RESULTS: Desulfobulbus, Saccharibacteria (TM7), Tannerella, and Porphyromonas were the major subgingival genera in this DS cohort. Favorable chlorhexidine adjunct non-surgical treatment outcomes were observed, with the relative abundance of Desulfobulbus sp. HMT 041, Saccharibacteria (TM7) [G-1] bacterium HMT 346 or 349, and Tannerella forsythia significantly reduced at the end of the study, but no significant reduction of Porphyromonas gingivalis or Aggregatibacter actinomycetemcomitans could be observed. Relative abundance of Desulfobulbus sp. HMT 041 and T. forsythia were also found to be significantly associated with plaque, bleeding on probing, and probing pocket depth (PPD, in mm) at a site level, while the relative abundance of Halomonas pacifica was negatively associated with PPD. CONCLUSIONS: Successful chlorhexidine adjunct non-surgical treatment with hygiene care was accompanied by a subgingival microbial shift involving certain periodontopathogenic species, except P. gingivalis and A. actinomycetemcomitans. Further investigations are required to clarify the mechanism underpinning the unchanged relative abundance of the above two pathogens despite favorable clinical responses. CLINICAL SIGNIFICANCE: DS adults face challenges achieving optimal home care or hygiene for periodontal healing and disease prevention. Chemical adjunct mechanical periodontal therapy plus regular recalls appeared promising clinically and microbiologically, with subgingival periodontopathogenic species reduction. The persistence of A. actinomycetemcomitans and P. gingivalis in subgingival niches post-treatment warrants further investigation.

Oral health through primary healthcare in a developed economy dominated by private dental practitioners: A leap forward in Hong Kong?

After two and a half decades of preparation, and prompted by advocacy from the World Health Organization in 2014, the Health Bureau of Hong Kong recently implemented the city's primary healthcare blueprint. Integrated within it is an approach to primary oral healthcare. This review provides a brief background and discusses the development of primary oral healthcare in Hong Kong - a developed economy in Asia dominated by private dental services.

Validating an Assessment Tool for Oral Health and Oral Care Procedures Performed by Healthcare Workers for Older Residents in Long-Term Care Institutions.

Poor oral health is a growing concern among older populations. It is often caused by a failure to maintain proper oral hygiene and inaccessible dental care. Poor oral health in older individuals in long-term care institutions (LTCIs) can be attributed to the fact that healthcare workers might be poorly trained in oral care assessment and practice. To address this issue, an assessment tool has been developed and validated to guide and evaluate healthcare workers' oral care practices, ensuring the delivery of adequate care and early detection of dental diseases in LTCIs. The tool includes an oral health assessment and an assessment of oral care procedures. It was developed following a robust literature review, two stages of expert reviews, content validity checks, and a pilot study. A total of twenty-three items were developed and validated, with seven items related to oral health assessment and sixteen related to oral care procedures. The items were assessed for content validity and relevance, with high values of 1 obtained for all Item-level Content Validity Index (I-CVI), Scale-level Content Validity Index (S-CVI), and S-CVI/Universal Agreement (UA) scores. This indicates a high level of agreement among the experts (n = 12) regarding the relevance and importance of the items. A pilot study involving 20 nursing students confirmed the tool's reliability, applicability, and feasibility, demonstrating its high appropriateness and applicability. The newly developed and validated assessment tool can effectively guide and evaluate healthcare workers' oral care practices, enhancing their competence and improving the oral health of older residents.

RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

Metabolic memory: mechanisms and diseases.

Metabolic diseases and their complications impose health and economic burdens worldwide. Evidence from past experimental studies and clinical trials suggests our body may have the ability to remember the past metabolic environment, such as hyperglycemia or hyperlipidemia, thus leading to chronic inflammatory disorders and other diseases even after the elimination of these metabolic environments. The long-term effects of that aberrant metabolism on the body have been summarized as metabolic memory and are found to assume a crucial role in states of health and disease. Multiple molecular mechanisms collectively participate in metabolic memory management, resulting in different cellular alterations as well as tissue and organ dysfunctions, culminating in disease progression and even affecting offspring. The elucidation and expansion of the concept of metabolic memory provides more comprehensive insight into pathogenic mechanisms underlying metabolic diseases and complications and promises to be a new target in disease detection and management. Here, we retrace the history of relevant research on metabolic memory and summarize its salient characteristics. We provide a detailed discussion of the mechanisms by which metabolic memory may be involved in disease development at molecular, cellular, and organ levels, with emphasis on the impact of epigenetic modulations. Finally, we present some of the pivotal findings arguing in favor of targeting metabolic memory to develop therapeutic strategies for metabolic diseases and provide the latest reflections on the consequences of metabolic memory as well as their implications for human health and diseases.

Educational Programme on Knowledge, Attitudes, and Practice of Oral Care/Hygiene Provision by Healthcare Providers to Older Residents in Long-Term Care Institutions: A Case-Control Study.

BACKGROUND: Much attention has been paid to advocate proper oral care/hygiene provision by healthcare providers in long-term care institutions (LTCIs). This study aimed to evaluate the effects of an oral health education (OHE) programme (intervention) on knowledge, attitudes, and practice (KAP) of healthcare providers in providing oral care/hygiene to older residents in LTCIs. METHODS: A case control study was conducted at two LTCIs, with one assigned as the intervention group and the other as the control group. A KAP survey was administered before and after the intervention, and oral status was assessed by standardized clinical photographs taken before and after oral hygiene provision on three older residents. RESULTS: A total of 40 healthcare providers (20 in intervention and 20 in control groups) participated, with the attitudes and overall KAP significantly improved in the intervention group after the OHE programme. Interestingly, the knowledge of those in the control LTCI was significantly declined at re-evaluation (mean scores were from 17.25 to 14.30), indicating inadequate oral health and care training despite having more experience in taking care of older people. Significant differences in practice were observed between the two groups after the OHE programme (p = 0.006). The three older residents exhibited poor oral health and multiple oral problems. CONCLUSIONS: This study revealed that the OHE programme effectively improved attitudes of the healthcare providers and provided a sustaining effect on attitude towards oral health and oral care. However, there were still inadequacies in oral hygiene provision by some healthcare providers, possibly due to unattended oral diseases and hygiene needs, as well as personal and environmental barriers that merit further investigation. Regular evaluation and enforcement of oral care/hygiene provision in LTCIs are necessary to maintain oral health and prevent dental and gum diseases in older residents. Immediate referral for dental treatment is recommended for older people with signs of dental/oral disease(s).

Mass Spectrometry-Based Proteomics for Discovering Salivary Biomarkers in Periodontitis: A Systematic Review.

Periodontitis is one of the primary causes of tooth loss, and is also related to various systemic diseases. Early detection of this condition is crucial when it comes to preventing further oral damage and the associated health complications. This study offers a systematic review of the literature published up to April 2023, and aims to clearly explain the role of proteomics in identifying salivary biomarkers for periodontitis. Comprehensive searches were conducted on PubMed and Web of Science to shortlist pertinent studies. The inclusion criterion was those that reported on mass spectrometry-driven proteomic analyses of saliva samples from periodontitis cohorts, while those on gingivitis or other oral diseases were excluded. An assessment for risk of bias was carried out using the Newcastle-Ottawa Scale and Quality Assessment of Diagnostic Accuracy Studies or the NIH quality assessment tool, and a meta-analysis was performed for replicable candidate biomarkers, i.e., consistently reported candidate biomarkers (in specific saliva samples, and periodontitis subgroups, reported in ≥2 independent cohorts/reports) were identified. A Gene Ontology enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery bioinformatics resources, which consistently expressed candidate biomarkers, to explore the predominant pathway wherein salivary biomarkers consistently manifested. Of the 15 studies included, 13 were case-control studies targeting diagnostic biomarkers for periodontitis participants (periodontally healthy/diseased, n = 342/432), while two focused on biomarkers responsive to periodontal treatment (n = 26 participants). The case-control studies were considered to have a low risk of bias, while the periodontitis treatment studies were deemed fair. Summary estimate and confidence/credible interval, etc. determination for the identified putative salivary biomarkers could not be ascertained due to the low number of studies in each case. The results from the included case-control studies identified nine consistently expressed candidate biomarkers (from nine studies with 230/297 periodontally healthy/diseased participants): (i) those that were upregulated: alpha-amylase, serum albumin, complement C3, neutrophil defensin, profilin-1, and S100-P; and (ii) those that were downregulated: carbonic anhydrase 6, immunoglobulin J chain, and lactoferrin. All putative biomarkers exhibited consistent regulation patterns. The implications of the current putative marker proteins identified were reviewed, with a focus on their potential roles in periodontitis diagnosis and pathogenesis, and as putative therapeutic targets. Although in its early stages, mass spectrometry-based salivary periodontal disease biomarker proteomics detection appeared promising. More mass spectrometry-based proteomics studies, with or without the aid of already available clinical biochemical approaches, are warranted to aid the discovery, identification, and validation of periodontal health/disease indicator molecule(s). Protocol registration number: CRD42023447722; supported by RD-02-202410 and GRF17119917.

Risk of autoimmune diseases following COVID-19 and the potential protective effect from vaccination: a population-based cohort study.

Background: Case reports suggest that SARS-CoV-2 infection could lead to immune dysregulation and trigger autoimmunity while COVID-19 vaccination is effective against severe COVID-19 outcomes. We aim to examine the association between COVID-19 and development of autoimmune diseases (ADs), and the potential protective effect of COVID-19 vaccination on such an association. Methods: A retrospective cohort study was conducted in Hong Kong between 1 April 2020 and 15 November 2022. COVID-19 was confirmed by positive polymerase chain reaction or rapid antigen test. Cox proportional hazard regression with inverse probability of treatment weighting was applied to estimate the risk of incident ADs following COVID-19. COVID-19 vaccinated population was compared against COVID-19 unvaccinated population to examine the protective effect of COVID-19 vaccination on new ADs. Findings: The study included 1,028,721 COVID-19 and 3,168,467 non-COVID individuals. Compared with non-COVID controls, patients with COVID-19 presented an increased risk of developing pernicious anaemia [adjusted Hazard Ratio (aHR): 1.72; 95% Confidence Interval (CI): 1.12-2.64]; spondyloarthritis [aHR: 1.32 (95% CI: 1.03-1.69)]; rheumatoid arthritis [aHR: 1.29 (95% CI: 1.09-1.54)]; other autoimmune arthritis [aHR: 1.43 (95% CI: 1.33-1.54)]; psoriasis [aHR: 1.42 (95% CI: 1.13-1.78)]; pemphigoid [aHR: 2.39 (95% CI: 1.83-3.11)]; Graves' disease [aHR: 1.30 (95% CI: 1.10-1.54)]; anti-phospholipid antibody syndrome [aHR: 2.12 (95% CI: 1.47-3.05)]; immune mediated thrombocytopenia [aHR: 2.1 (95% CI: 1.82-2.43)]; multiple sclerosis [aHR: 2.66 (95% CI: 1.17-6.05)]; vasculitis [aHR: 1.46 (95% CI: 1.04-2.04)]. Among COVID-19 patients, completion of two doses of COVID-19 vaccine shows a decreased risk of pemphigoid, Graves' disease, anti-phospholipid antibody syndrome, immune-mediated thrombocytopenia, systemic lupus erythematosus and other autoimmune arthritis. Interpretation: Our findings suggested that COVID-19 is associated with an increased risk of developing various ADs and the risk could be attenuated by COVID-19 vaccination. Future studies investigating pathology and mechanisms would be valuable to interpreting our findings. Funding: Supported by RGC Collaborative Research Fund (C7154-20GF).

Hydrogel-Forming Microneedles with Applications in Oral Diseases Management.

Controlled drug delivery in the oral cavity poses challenges such as bacterial contamination, saliva dilution, and inactivation by salivary enzymes upon ingestion. Microneedles offer a location-specific, minimally invasive, and retentive approach. Hydrogel-forming microneedles (HFMs) have emerged for dental diagnostics and therapeutics. HFMs penetrate the stratum corneum, undergo swelling upon contact, secure attachment, and enable sustained transdermal or transmucosal drug delivery. Commonly employed polymers such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone are crosslinked with tartaric acid or its derivatives while incorporating therapeutic agents. Microneedle patches provide suture-free and painless drug delivery to keratinized or non-keratinized mucosa, facilitating site-specific treatment and patient compliance. This review comprehensively discusses HFMs' applications in dentistry such as local anesthesia, oral ulcer management, periodontal treatment, etc., encompassing animal experiments, clinical trials, and their fundamental impact and limitations, for example, restricted drug carrying capacity and, until now, a low number of dental clinical trial reports. The review explores the advantages and future perspectives of HFMs for oral drug delivery.

Diagnostic application of intraoral ultrasonography to assess furcation involvement in mandibular first molars.

OBJECTIVES: The objectives were to clarify if intraoral ultrasonography (USG) is: (1) more accurate than conventional periodontal examinations in detection of furcation involvement, and (2) comparable to conventional periodontal examinations in accurate horizontal classification of furcation involvement in comparison to cone beam computed tomography (CBCT). METHODS: The buccal furcation in 61 lower first molars were evaluated with conventional periodontal examinations, intraoral USG and CBCT. The presence and classification of the horizontal depth of furcation involvement were defined clinically by assessment with a Nabers periodontal probe and a periapical radiograph with reference to the bone loss under the fornix. The horizontal depth of furcation involvement was measured in intraoral USG and CBCT images. Based on the measurements, presence diagnosis and horizontal classification were performed. Results from conventional periodontal examinationsand intraoral USG were compared with those from CBCT. RESULTS: κ value (κ) for agreement of presence diagnosis of furcation involvement between intraoral USG and CBCT was 0.792, while agreement with conventional periodontal examinations was 0.225. Diagnostic accuracy of intraoral USG exhibited higher values (sensitivity: 98.3%, accuracy: 98.4 %) than conventional periodontal examinations (81.4% and 81.9 %). Weighted κ statistics showed substantial agreement in the classification between intraoral USG and CBCT (κ = 0.674). High agreement (ICC: 0.914) for the measurement of horizontal depth of furcation involvement was found between intraoral USG and CBCT. CONCLUSIONS: Intraoral USG may be a reliable diagnostic tool for assessment of furcation involvement of mandibular molars with a similar performance to CBCT, but without ionizing radiation.

Serum microRNA Levels as a Biomarker for Diagnosing Non-Alcoholic Fatty Liver Disease in Chinese Colorectal Polyp Patients.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and its prevalence is increasing worldwide. It is reported that NAFLD is associated with colorectal polyps. Since identifying NAFLD in its early stages could prevent possible disease progression to cirrhosis and decrease the risk of HCC by early intervention, patients with colorectal polyp may thus be considered a target group for screening NAFLD. This study aimed to investigate the potential of serum microRNAs (miRNAs) in identifying NAFLD for colorectal polyp patients. Serum samples were collected from 141 colorectal polyp patients, of which 38 had NAFLD. The serum level of eight miRNAs was determined by quantitative PCR and delta Ct values of different miRNA pairs which were compared between NAFLD and control groups. A miRNA panel was formulated from candidate miRNA pairs by multiple linear regression model and ROC analysis was performed to evaluate its diagnostic potential for NAFLD. Compared to the control group, the NAFLD group showed significantly lower delta Ct values of miR-18a/miR-16 (6.141 vs. 7.374, p = 0.009), miR-25-3p/miR-16 (2.311 vs. 2.978, p = 0.003), miR-18a/miR-21-5p (4.367 vs. 5.081, p = 0.021) and miR-18a/miR-92a-3p (8.807 vs. 9.582, p = 0.020). A serum miRNA panel composed of these four miRNA pairs significantly identified NAFLD in colorectal polyp patients with an AUC value of 0.6584 (p = 0.004). The performance of the miRNA panel was further improved to an AUC value of 0.8337 (p < 0.0001) when polyp patients with other concurrent metabolic disorders were removed from the analysis. The serum miRNA panel is a potential diagnostic biomarker for screening NAFLD in colorectal polyp patients. This serum miRNA test could be performed for colorectal polyp patients for early diagnosis and for prevention of the disease from progressing into more advanced stages.

Functional Neuroplasticity of Adults with Partial or Complete Denture Rehabilitation with or without Implants: Evidence from fMRI Studies.

Tooth loss may affect food ingestion and, consequently, nutrition intake. The neuroimaging literature using functional magnetic resonance imaging (fMRI) was reviewed to summarize the changes in brain functions in response to denture rehabilitation in patients with partial or complete edentulous dentition. Overall, this review covered nine fMRI studies on denture rehabilitation. Eight recruited complete edentulous patients, whereas one recruited partially edentulous patients. The risk-of-bias assessment revealed concerns regarding all nine studies. Due to the heterogeneity of the studies and the lack of brain coordinates reported, a meta-analysis could not be conducted, and this review could only summarize the findings without statistical validation. The evidence from jaw-clenching studies suggested that implant-supported fixed dentures could be the best option, as compared to implant-supported overdentures and complete dentures, as it was associated with higher brain activity levels in various brain regions, including those corresponding to the primary sensory (postcentral gyrus) and motor cortices (precentral gyrus). Gum-chewing studies indicated that perhaps the medial and middle frontal gyri were associated with food comminuting and food mixing, which could be improved by the full replacement of the dental arch, instead of only partial replacement. All the fMRI studies described the functional neuroplasticity of the patients undergoing denture rehabilitation and suggested that certain rehabilitation options were more beneficial in restoring masticatory functions, as well as their associated brain activity levels.

IL-1ß and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer's disease.

BACKGROUND: Systemic activation of the immune system can exert detrimental effects on the central nervous system. Periodontitis, a chronic disease of the oral cavity, is a common source of systemic inflammation. Neuroinflammation might be a result of this to accelerate progressive deterioration of neuronal functions during aging or exacerbate pre-existing neurodegenerative diseases, such as Alzheimer's disease. With advancing age, the progressive increase in the body's pro-inflammatory status favors the state of vulnerability to both periodontitis and Alzheimer's disease. In the present study, we sought to delineate the roles of cytokines in the pathogenesis of both diseases. METHODS: To examine the impacts of periodontitis on the onset and progression of Alzheimer's disease, 6-month-old female 3 × Tg-AD mice and their age-matched non-transgenic mice were employed. Periodontitis was induced using two different experimental models: heat-killed bacterial-induced periodontitis and ligature-induced periodontitis. To delineate the roles of pro-inflammatory cytokines in the pathogenesis of periodontitis and Alzheimer's disease, interleukin 1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were also injected into the buccal mandibular vestibule of mice. RESULTS: Here, we show that IL-1ß and TNF-α were two of the most important and earliest cytokines upregulated upon periodontal infection. The systemic upregulation of these two cytokines promoted a pro-inflammatory environment in the brain contributing to the development of Alzheimer's disease-like pathology and cognitive dysfunctions. Periodontitis-induced systemic inflammation also enhanced brain inflammatory responses and subsequently exacerbated Alzheimer's disease pathology and cognitive impairment in 3 × Tg-AD mice. The role of inflammation in connecting periodontitis to Alzheimer's disease was further affirmed in the conventional magnetization transfer experiment in which increased glial responses resulting from periodontitis led to decreased magnetization transfer ratios in the brain of 3 × Tg-AD mice. CONCLUSIONS: Systemic inflammation resulting from periodontitis contributed to the development of Alzheimer's disease tau pathology and subsequently led to cognitive decline in non-transgenic mice. It also potentiated Alzheimer's disease pathological features and exacerbated impairment of cognitive function in 3 × Tg-AD mice. Taken together, this study provides convincing evidence that systemic inflammation serves as a connecting link between periodontitis and Alzheimer's disease.

Impact of Introducing Infliximab Biosimilars on Total Infliximab Consumption and Originator Infliximab Prices in Eight Regions: An Interrupted Time-Series Analysis.

OBJECTIVE: We aimed to assess whether the introduction of the first infliximab biosimilar was associated with changes in overall infliximab consumption (originator and biosimilars) and price changes to the originator infliximab. METHODS: An interrupted time series analysis using infliximab sales data from 2010 to 2020 from the IQVIA Multinational Integrated Data Analysis System for eight selected regions: Australia, Canada, Hong Kong, Korea, India, Japan, the UK, and the USA. Quarterly measures of infliximab consumption and list prices were respectively defined as the number of standard units (SU)/1000 inhabitants and as 2020 USA dollars (USD)/SU. RESULTS: Following the introduction of infliximab biosimilars, overall infliximab consumption increased in Australia [immediate change: 0.145 SU/1000 inhabitants (P = 0.014); long-term change: 0.022 SU/1000 inhabitants per quarter (P < 0.001)], Canada [immediate change 0.415 (P = 0.008)], the UK [long-term change 0.024 (P < 0.001)], and Hong Kong [immediate change: 0.042 (P < 0.001)]. The list price of originator infliximab also decreased following biosimilar introduction in Australia [immediate change: - 187.84 USD/SU (P < 0.001); long-term change - 6.46 USD/SU per quarter (P = 0.043)], Canada [immediate change: - 145.58 (P < 0.001)], the UK [immediate change: - 34.95 (P = 0.010); long-term change: - 4.77 (P < 0.001)], and Hong Kong [long-term change: - 4.065 (P = 0.046)]. Consumption and price changes were inconsistent in India, Japan, Korea, and the USA. CONCLUSIONS: Introduction of the first infliximab biosimilar was not consistently associated with increased consumption across regions. Additional policy and healthcare system interventions to support biosimilar infliximab adoption are needed.

The Impacts of Computer-Aided Detection of Colorectal Polyps on Subsequent Colonoscopy Surveillance Intervals: Simulation Study.

BACKGROUND: Computer-aided detection (CADe) of colorectal polyps has been shown to increase adenoma detection rates, which would potentially shorten subsequent surveillance intervals. OBJECTIVE: The purpose of this study is to simulate the potential changes in subsequent colonoscopy surveillance intervals after the application of CADe in a large cohort of patients. METHODS: We simulated the projected increase in polyp and adenoma detection by universal CADe application in our patients who had undergone colonoscopy with complete endoscopic and histological findings between 2016 and 2020. The simulation was based on bootstrapping the published performance of CADe. The corresponding changes in surveillance intervals for each patient, as recommended by the US Multi-Society Task Force on Colorectal Cancer (USMSTF) or the European Society of Gastrointestinal Endoscopy (ESGE), were determined after the CADe was determined. RESULTS: A total of 3735 patients who had undergone colonoscopy were included. Based on the simulated CADe effect, the application of CADe would result in 19.1% (n=714) and 1.9% (n=71) of patients having shorter surveillance intervals, according to the USMSTF and ESGE guidelines, respectively. In particular, all (or 2.7% (n=101) of the total) patients who were originally scheduled to have 3-5 years of surveillance would have their surveillance intervals shortened to 3 years, following the USMSTF guidelines. The changes in this group of patients were largely attributed to an increase in the number of adenomas (n=75, 74%) rather than serrated lesions being detected. CONCLUSIONS: Widespread adoption of CADe would inevitably increase the demand for surveillance colonoscopies with the shortening of original surveillance intervals, particularly following the current USMSTF guideline.

Proteomic profile of in situ acquired pellicle on tooth and restorative material surfaces.

OBJECTIVES: To evaluate and compare the proteomic profile of acquired pellicle on smooth bovine tooth and tooth-coloured restorative materials, including resin composite (RC), glass ionomer cement (GIC), and casein phosphopeptide-amorphous calcium phosphate modified GIC (CPP-ACP GIC). METHODS: Two-hour in situ pellicles on tooth/materials specimens mounted in oral appliances worn by ten healthy adults were investigated. Pellicle proteins and corresponding unstimulated whole saliva were quantitatively analysed through liquid chromatography-tandem mass spectrometry. RESULTS: Significantly higher amounts of protein were adsorbed onto tooth surface than restorative materials tested (4.11 ± 0.69 vs. 2.54 ± 0.38/2.98 ± 0.80/3.01 ± 0.37 µg, RC/GIC/CPP-ACP GIC). From the ten participants, 1,444 (487-1,086/person), 1,454 (645-1,051/person), 1,731 (454-1,475/person), or 1,597 (423-1,261/person) pellicle proteins were detected at least once on bovine tooth, RC, GIC, or CPP-ACP GIC, respectively, and with 1,072 (304-793/person) salivary proteins identified. Comparative quantification revealed minor differences between tooth and restorative materials pellicle profiles. High inter-individual variations in pellicle protein composition were demonstrated. Compared to the salivary protein profile, 214/57 proteins showed significantly increased/decreased abundance in pellicle formed on at least one substrate (fold change > 3.325/fold change < 0.301). Gene Ontology enrichment analysis showed some pellicle proteins detected with increased affinity to tooth/material surface were identified as being related to "calcium-dependent protein binding" or "cell-cell adhesion mediator activity". CONCLUSION: Similar protein quantity and composition was observed in 2 h in situ pellicles formed on different smooth restorative material surfaces. The proteomic profile of pellicles appeared distinct from that of the corresponding unstimulated whole saliva. CLINICAL SIGNIFICANCE: Host backgrounds appeared more influential on the proteomic profile of the in situ acquired pellicle than the underlying substrate characteristics among systemically and orally healthy adults. Pellicle proteins preferentially adsorbed on tooth/materials were putatively associated with calcium ion homeostasis or host-microbiota interaction.

Porphyromonas gingivalis infection promotes inflammation via inhibition of the AhR signalling pathway in periodontitis.

Porphyromonas gingivalis (P. gingivalis) is a key pathogen of chronic periodontitis. Aryl hydrocarbon receptor (AhR) is essential in immune homeostasis via modulation of pro-inflammatory cytokines production and indoleamine 2,3-dioxygenase (IDO). In this study, it is demonstrated that P. gingivalis may regulate AhR signalling in periodontitis, which provides a potential target for further immune regulation studies in periodontitis. Experimental periodontitis was induced in C57BL/6 mice by silk ligature and P. gingivalis oral inoculation. The alveolar bone resorption was examined using Micro-CT. Histological structures were observed and related cytokines involved in AhR signalling pathway were analysed. RAW264.7 cells were pretreated with AhR agonist (FICZ) and antagonist (CH223191) and infected with P. gingivalis subsequently. The levels of IDO, AhR and other related cytokines were measured. To demonstrate IDO activity, the concentrations of tryptophan (Trp) and kynurenine (Kyn) were assessed by HPLC. Histological analysis of periodontitis mice showed distinct alveolar bone resorption and inflammatory cell infiltration. The level of AhR and its downstream target factors were significantly decreased in inflamed gingival tissue. Furthermore, RAW 264.7 cells incubated by P. gingivalis exhibited increased pro-inflammatory cytokines production and decreased AhR, CYP1A1, CYP1B1, and IDO expression. Decreased IDO activity was observed as decreased Kyn/Trp ratio in the supernatant. Moreover, FICZ decreased the pro-inflammatory cytokines levels in P. gingivalis infected cells. It is concluded that P. gingivalis may promote inflammatory responses via inhibiting the AhR signalling pathway in periodontitis.

Severe Periodontitis Is a Major Contributory Factor to Unmet Dental Healthcare Needs among Rheumatoid Arthritis Patients in Hong Kong.

Objective: This study aimed to examine the frequency and predictive factors of adverse oral and dental outcomes in patients with rheumatoid arthritis (RA) with the goal to address their unmet dental healthcare needs in the metropolitan city of Hong Kong. Methods: 238 RA patients followed up at local public hospitals were recruited in this cross-sectional study. A full dental examination was performed. Data were compared with the retrospective data collected from age-matched control groups in the community conducted in a territory-wide oral health survey in 2011. Predictive factors for severe periodontitis including various demographic and disease-specific factors were examined by multiple logistic regression analysis. Results: Loose teeth and gum bleeding were frequent dental complaints. Only 85.0% of RA patients had >20 natural teeth. Total edentulism was observed in 3.8% of patients, which was higher among adult (22-64 years) and elderly (>65 years old) RA patients than their respective age-matched community control groups. RA patients had a higher decayed, missing, and filled tooth score. Adult RA patients had a 5.3-fold increase in risk of severe periodontitis than their community counterparts. The plaque index was the main predisposing factor for severe periodontitis (odds ratio 17.5, p=0.001), which was worse among the 22-34 age group of patients. More RA patients required tooth extraction compared to dental filling for their community controls. Conclusion: Severe periodontitis is a major cause of unmet dental healthcare needs among RA patients in Hong Kong. It is recommended that dental care plans for RA patients be commenced early among newly diagnosed patients.

Validation of the Malay Oral Impacts on Daily Performances and Evaluation of Oral Health-Related Quality of Life in a Multi-Ethnic Urban Malaysian Population: A Cross-Sectional Study.

Oral Impacts on Daily Performances (OIDP) can be used as a generic or condition-specific oral health-related quality of life (OHRQoL) instrument. It offers different contexts on how dental conditions affect OHRQoL. This cross-sectional study aimed to validate a newly translated Malay OIDP (OIDP-M), compare OHRQoL, decayed, missing, or filled teeth (DMFT) in Malaysians, and investigate factors associated with OHRQoL. A total of 368 Malaysians were surveyed and examined for DMFT. Short-form oral health impact profile-Malaysia [S-OHIP(M)] and OIDP-M were used to measure OHRQoL. The OIDP-M was tested for reliability and validity. DMFT, S-OHIP(M), and OIDP-M between ethnicities were compared. Associations between ethnicity, DMFT, S-OHIP(M), and OIDP-M of Malays and Chinese were evaluated through partial correlation. Malays and Chinese had more filled teeth and DMFT compared with Indians. Malays reported worse OHRQoL through S-OHIP(M). Decayed teeth were positively associated with S-OHIP(M), physical, psychological, social disabilities, and handicap. For OIDP-M, decayed teeth were positively associated with OIDP-M, working, and sleeping. Missing teeth and ethnicity were positively associated with eating and speaking. Filled teeth were negatively associated with cleaning teeth. The OIDP-M was reliable and valid for evaluating OHRQoL. There were differences in DMFT and OHRQoL between ethnicities. Ethnicity affects OHRQoL, where Malays experienced worse OHRQoL due to dental problems.