Associations Among Tooth Loss, Periodontitis, and Carotid Intima-Media Thickness: the Nagahama Study.

AIMS: This study aimed to clarify the relationships among tooth loss, periodontal condition, and subclinical atherosclerosis from the aspect of intensity, extent, and duration of inflammation. METHODS: This cross-sectional study included 9,778 people from the Nagahama Study, a large-scale, general population-based study conducted in Japan. The number of teeth and periodontal status, including the attachment level (AL) and pocket depth (PD) of representative teeth from six regions, were evaluated by dentists. The maximum intima-media thickness (IMT) of the common carotid artery was used as an index of atherosclerosis. RESULTS: In the multivariate analysis adjusted for conventional risk factors, a large number of missing teeth (＜9 remaining teeth), which related to long-lasting inflammation indicative of the highest stage of periodontitis, was identified as an independent determinant of IMT in a general population (coefficient: 0.042; 95% confidence interval [CI]: 0.016 to 0.068). The presence of two or more regions with an AL ≥4 mm, which is indicative of the progressing, long-lasting stages of periodontal inflammation, was also independently associated with IMT (coefficient: 0.016; 95% CI: 0.004 to 0.028). On the contrary, PD, a measure of the early and reversible phases of periodontal inflammation, and loss of AL in the group without tooth loss were not significantly associated with IMT, because of the limited degree of accumulated periodontitis. CONCLUSION: The present results suggest that the association between periodontitis and atherosclerosis depends on the inflammation intensity, extent, and duration.

Nonexposed antiresorptive agent-related osteomyelitis of the jaw: a single-center cohort study.

INTRODUCTION: The nonexposed variant of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) presents with nonspecific clinical findings. The diagnosis of nonexposed ARONJ poses a critical challenge, and there is little evidence regarding its treatment and outcomes. This study aimed to examine the clinical outcomes in patients with nonexposed antiresorptive agent-related osteomyelitis of the jaw (AROMJ). The terms ARONJ and AROMJ were used separately in this study. MATERIALS AND METHODS: We enrolled patients with nonexposed AROMJ (osteomyelitis of the jaw without bone exposure associated with antiresorptive agents) with partial reference to an existing position paper on ARONJ. The initiating event of osteomyelitis was limited to periodontitis. Based on the findings of bone scintigraphy, panoramic radiography, computed tomography, and histopathological examination, we also used the hierarchical diagnostic criteria (HDC) for osteomyelitis of the jaw. RESULTS: There were 58 confirmed cases of nonexposed AROMJ based on the HDC. All patients had sufficient clinical findings to be diagnosed with nonexposed AROMJ as osteomyelitis underwent extraction with bone debridement. The healing rate was 93.1% (54/58). Univariable analysis showed a strong association between the healing status and malignant disease, while multivariable analysis showed no strong association between them. CONCLUSIONS: The present study had a relatively large sample size of patients with nonexposed AROMJ. The primary disease in patients with nonexposed AROMJ may not have a strong association with the healed status of the lesion. Based on its high healing rate, extraction with bone debridement in confirmed nonexposed AROMJ may prevent progression.

Association Between Tooth Loss and Longitudinal Changes in B-Type Natriuretic Peptide Over 5 Years in Postmenopausal Women: The Nagahama Study.

There is disparity between the sexes in cardiovascular diseases including heart failure (HF). This study aimed to investigate the effect of periodontal disease (PD) on plasma B-type natriuretic peptide (BNP) concentration across sex, age, and menopausal status, as well as the interaction effect of PD and diabetes mellitus (DM) on BNP. This large-scale prospective cohort study enrolled 7539 individuals with no myocardial infarctions or angina pectoris at baseline from the general Japanese population. The association between baseline number of missing teeth (MT) and the longitudinal changes in BNP over 5 years (ΔBNP) was evaluated according to sex and menopausal status. Among 7539 participants, 3190 were postmenopausal women with a mean age ± standard deviation of 61.1 ± 7.6 at baseline. Multivariate analysis revealed a positive association between MT and ΔBNP among postmenopausal women even after adjusting for covariates, including traditional HF risk factors (coefficient, 0.210; 95% confidence interval [CI], 0.107 to 0.312; P < 0.001), but not in men aged > 50. Including an interaction term (MT × DM) in the multivariate model revealed a positive interaction between MT and DM in ΔBNP among postmenopausal women (coefficient for interaction, 1.365; 95% CI, 0.902 to 1.827; P for interaction < 0.001). In conclusion, our study showed a positive association between MT and ΔBNP, as well as a positive effect of the interactive association between MT and DM, among postmenopausal women. Our results suggest a sex difference of an adverse effect of PD on initial myocardial wall stress in the ventricles.

Effectiveness of surgery and hyperbaric oxygen for antiresorptive agent-related osteonecrosis of the jaw: A subgroup analysis by disease stage.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is an adverse event induced by antiresorptive agents (ARAs). The purpose of this study was to evaluate variables, mainly surgery and hyperbaric oxygen (HBO) therapy, associated with treatment outcomes in patients with a diagnosis of ARONJ at a single center. We enrolled consecutive patients who presented to our hospital for the management of stage 2 or 3 ARONJ between January 2003 and December 2019. The relationship between potentially predictive factors and outcome variables was examined using statistical analyses, along with a subgroup analysis based on disease stage. Of 252 patients included in this study, 206 had stage 2 ARONJ and 46 had stage 3 ARONJ. There were 119 patients with osteoporosis and 133 with malignant disease. In total, 139 patients were healed, and the healing rate of patients with stage 3 ARONJ was lower than that of patients with stage 2 ARONJ. With regard to the combination of surgery and HBO therapy, most patients underwent HBO before and after surgery. In the univariable analysis, surgery showed a therapeutic effect in both stage 2 and 3 ARONJ, whereas HBO showed a therapeutic effect in stage 2 ARONJ. In the multivariable analysis for stage 2 ARONJ, extensive surgery showed a stronger association with healing than conservative surgery, whereas ≥46 sessions of HBO therapy was less associated with healing than was non-HBO therapy. Our findings suggest that extensive surgery is highly effective against ARONJ regardless of disease stage if there is a sequestrum separation and systemic tolerance, whereas HBO therapy before and after surgical approach can be effective. Further studies are needed to identify treatment strategies for patients with treatment-refractory ARONJ who may be forced to undergo long-term HBO therapy with the expectation of sequestrum separation.

Diagnostic accuracy of patient-reported dry mouth as a predictor for oral dryness in terminally ill cancer patients.

PURPOSE: The aim of the study was to determine the diagnostic accuracy of patient-reported dry mouth using an oral moisture-checking device in terminally ill cancer patients. METHODS: The study was conducted following the STARD guidelines, and the participants were recruited prospectively from the Palliative Care Unit, Kyoto Medical Center, Japan, between 1 January 2017 and 30 November 2018. Patients reporting dry mouth were asked to rate oral dryness on a 5-point rating scale. The outcome was oral dryness at the lingual mucosa, measured using an oral moisture-checking device. Receiver operating characteristic (ROC) curves were plotted, and the sensitivity, specificity, positive and negative predictive values (PPV and NPV), positive and negative likelihood ratios (LR), and overall diagnostic accuracy were calculated. RESULTS: Of 103 participants, the prevalence of oral dryness was 65.0%. ROC analysis indicated that patient-reported dry mouth was a poor predictor of oral dryness, with an area under the curve of 0.616 (95% confidence interval: 0.508-0.723), a sensitivity of 46.3%, a specificity of 75.8%, a PPV of 55.9%, an NPV of 68.1, a positive LR of 1.9, a negative LR of 0.7, and an overall diagnostic accuracy of 64.1%, with a cut-off value of 3 points. CONCLUSION: In conclusion, patient-reported dry mouth is not a useful parameter for the assessment of oral dryness in terminally ill cancer patients.

The Relationship Between Cephalogram Analysis and Oxygen Desaturation Index During Sleep in Patients Submitted for Mandibular Setback Surgery.

OBJECTIVES: The aim of this study was to examine the relationship between morphologic factors of mandibular protrusion patients and clinical indices of obstructive sleep apnea (OSA). METHODS: Fifty-two Japanese patients divided into 2 groups: 1 jaw surgery group (30 patients) and 2 jaw surgery group (22 patients). Morphologic changes were studied using cephalograms taken before surgery and 1 year after surgery. Functional changes studied using impulse oscillometry and pulse oximetry during sleep, both of which are clinically useful measures in assessing OSA, taken before surgery and 1 year after surgery. RESULT: Lower face cage area significantly decreased in 1 jaw group than in 2 jaw group patients. Positive significant correlation was found between changes in 3% oxygen desaturation index (ODI) and changes of tongue area and vertical position of the hyoid bone in 1 jaw surgery group. Multiple regression analysis indicates that tongue area and airway area were independently significant predictors of 3% ODI in 1 jaw group patients. CONCLUSION: In 2 jaw surgery, maxillary surgery compensated for the effect of mandibular setback surgery. Mandibular setback surgery to mandibular protrusion patients was performed within the range of adequate movement distance, but precautions for risk of postoperative obstructive sleep apnea syndrome should be considered.

Factors That Affect Oral Care Outcomes for Institutionalized Elderly.

The aim of this study was to evaluate the effect of an oral care intervention program on the incidence of pneumonia and fever as a surrogate endpoint. In addition, we tried to determine the oral care risk factors for the incidence of fever. We provided an oral care program for the elderly at one private nursing home in July 2013. The maximum capacity of the nursing home was 60 residents. The body temperatures of all residents were measured twice a day and were summarized as the incidence of fever over a one-month period, which was used as the dependent variable. The residents' life conditions, number of teeth, and prescribed diet were used as independent variables. The factors that affected the incidence of fever were the number of remaining teeth, a prescribed diet of sliced food, the meal care level, and the oral Candida levels. These risk factors affected the incidence of fever independently or interactively with oral care. Some risk factors for the incidence of fever were enhanced by the oral care program. It is important to evaluate and control these factors before the implementation of an oral care program.

The novel association between red complex of oral microbe and body mass index in healthy Japanese: a population based cross-sectional study.

Microbiota has been thought to be one of important environmental factors for obesity or Type 2 diabetes mellitus. Among oral microbe, Porphyromonas gingivalis, Treponema denticola and Tannellera forsythia are known as risk factors, so called red complex, for periodontitis. Red complex could also be a risk factor for obesity. However, recent study indicated that obesity was not improved by periodontal therapy. Thus, we performed a cross sectional study to reveal the association of oral microbe with body mass index in a healthy population. Healthy individuals were randomly recruited. The infections of oral microbe were identified by Taqman polymerase chain reaction. The relationships between number of red complex and body mass index or waist circumference were analyzed. Two hundred and twenty-two apparently healthy Japanese were enrolled. BMI and waist circumference as well as age, periodontitis, number of brushing teeth were significantly associated with the number of red complex after adjusting covariance. The effect size of body mass index or waist circumference was 0.023 (p = 0.028) or 0.024 (p = 0.024), respectively. Body mass index and waist circumference were independently associated with the number of red complex among apparently healthy Japanese. The current observation implies the possibility that oral microbe was associated with obesity in healthy population.

Periodontitis and Porphyromonas gingivalis in preclinical stage of arthritis patients.

PURPOSE: To determine whether the presence of periodontitis (PD) and Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the development of rheumatoid arthritis (RA) in treatment naïve preclinical stage of arthritis patients. METHODS: We conducted a prospective cohort study of 72 consecutive patients with arthralgia who had never been treated with any anti-rheumatic drugs or glucocorticoids. Periodontal status at baseline was assessed by dentists. PD was defined stringently by the maximal probing depth≧4 mm, or by the classification by the 5th European Workshop in Periodontology (EWP) in 2005 using attachment loss. Up to eight plaque samples were obtained from each patient and the presence of Pg was determined by Taqman PCR. The patients were followed up for 2 years and introduction rate of methotrexate (MTX) treatment on the diagnosis of RA was compared in patients with or without PD or Pg. RESULTS: Patients with PD (probing depth≧4mm) had higher arthritis activity (p = 0.02) and higher risk for future introduction of MTX treatment on the diagnosis of RA during the follow up than patients without PD (Hazard ratio 2.68, p = 0.03). Arthritis activity and risk for MTX introduction increased with the severity of PD assessed by EWP, although not statistically significant. On the other hand, presence of Pg was not associated with arthritis activity (p = 0.72) or the risk for MTX introduction (p = 0.45). CONCLUSION: In treatment naïve arthralgia patients, PD, but not the presence of Pg, associates with arthritis activity and future requirement of MTX treatment on the diagnosis of RA.

Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population - The Nagahama study.

Anti-citrullinated peptide antibody (ACPA) is a highly specific autoantibody to rheumatoid arthritis (RA). Recent studies have revealed that periodontal disease (PD) is closely associated with RA and production of ACPA in RA. Analyses of associations between PD and ACPA production in a healthy population may deepen our understandings. Here, we analyzed a total of 9554 adult healthy subjects. ACPA and IgM-rheumatoid factor (RF) was quantified and PD status was evaluated using the number of missing teeth (MT), the Community Periodontal Index (CPI) and Loss of Attachment (LA) for these subjects. PD status was analyzed for its association with the positivity and categorical levels of ACPA and RF conditioned for covariates which were shown to be associated with PD, ACPA or RF. As a result, all of MT, CPI and LA showed suggestive or significant associations with positivity (p = 0.024, 0.0042 and 0.037, respectively) and levels of ACPA (p ≤ 0.00031), but none of the PD parameters were associated with those of RF. These association patterns were also observed when we analyzed 6206 non-smokers of the participants. The significant associations between PD parameters and positivity and levels of ACPA in healthy population support the fundamental involvement of PD with ACPA production.

Risk factors and indices of osteomyelitis of the jaw in osteoporosis patients: results from a hospital-based cohort study in Japan.

BACKGROUND: Several studies have reported osteomyelitis of the jaw (OMJ) as a side effect of bisphosphonates (BPs), and the risk of oral BPs has been recently clarified. However, other systemic risk factors of OMJ remain unclear. Importantly, the possibility of risk classification based on the clinical characteristics of patients has not been explored. Here, we clarified risk factors of OMJ and evaluate the predictive accuracy of risk indices in osteoporosis patients. METHODS: We performed sub-analysis using a database developed for a retrospective cohort study in patients taking medications for osteoporosis at Kyoto University Hospital. Risk indices for OMJ were constructed using logistic regression analysis, and odds ratios (OR) for OMJ cases and 95% confidence intervals (CI) were estimated. Potential risk factors included in the statistical analysis were age; sex; diabetes; use of oral BPs, corticosteroids, cancer chemotherapy, antirheumatic drugs, and biologic agents; and their interactions. Risk indices were calculated by the sum of potential risk factors of an individual patient multiplied by the regression coefficients. The discriminatory power of the risk indices was assessed by receiver operating characteristic (ROC) analysis. RESULTS: In analysis of all patients, oral BPs (OR: 4.98, 95% CIs: 1.94-12.75), age (OR: 1.28, 95% CI: 1.06-1.60) and sex-chemotherapy interaction (OR: 11.70, 95% CI: 1.46-93.64) were significant risk factors of OMJ. Areas under the ROC curves of these risk indices provided moderate sensitivity or specificity regardless of group (0.683 to 0.718). CONCLUSIONS: Our data suggest that oral BP use, age, and sex-chemotherapy are predictors of OMJ in osteoporosis patients. The risk indices are moderately high, and allow the prediction of OMJ incidence.

Mastication and risk for diabetes in a Japanese population: a cross-sectional study.

BACKGROUND: Associations between mastication and insufficient nutrient intake, obesity, and glucose metabolism have been shown in previous studies. However, the association between mastication and diabetes has not been clarified. Our objective was to examine the association between mastication, namely masticatory performance or rate of eating, and diabetes in a population-based cohort. METHODS: We conducted a cross-sectional study of the association between mastication and diabetes in the Nagahama Prospective Cohort Study, an ongoing study which recruits citizens of Nagahama City in Shiga Prefecture, central Japan. 2,283 male and 4,544 female residents aged 40-74 years were enrolled from July 2009 to November 2010. Masticatory performance was evaluated by spectrophotometric measurement of color changes after masticating color-changeable chewing gum. Categorical rate of eating (fast, intermediate or slow) was self-assessed using a questionnaire. RESULTS: 177 males (7.7%) and 112 (2.4%) females were diagnosed with diabetes. We divided participants into four groups by quartile of masticatory performance, namely Q1 (lowest), 2, and 3 and 4 (highest). Compared to the lowest performance group, the multivariable adjusted odds ratio (OR) of diabetes was 0.91 (95% confidence interval (CI), 0.58-1.4) in Q2, 0.77 (95% CI, 0.48-1.2) in Q3, and 0.53 (95% CI, 0.31-0.90) in the highest group in males, and 1.2 (95% CI, 0.73-2.0), 0.95 (95% CI, 0.54-1.6) and 0.56 (95% CI, 0.30-1.0) in females. We also estimated ORs of diabetes by rate of eating. Compared to the fast eating group, ORs in males were 0.87 (95% CI, 0.61-1.2) in the intermediate group and 0.38 (95% CI, 0.16-0.91) in the slow group, and ORs in females were 0.92 (95% CI, 0.59-1.4) and 1.5 (95% CI, 0.73-3.0). CONCLUSIONS: These findings support the hypothesis that higher masticatory performance and slow eating prevent the occurrence of diabetes.

Assessing anteroposterior basal bone discrepancy with the Dental Aesthetic Index.

OBJECTIVE: To investigate dental appearance and cephalometric features, using a sample of orthognathic and/or orthodontic patients. A special interest was to identify the relationship of the Dental Aesthetic Index (DAI) with anteroposterior basal bone discrepancy (APBBD) and cephalometric indicators. MATERIALS AND METHODS: A full sample of 159 patients in two Japanese hospitals was used. Each patient was assessed with a preorthodontic dental cast and cephalometric radiography. RESULTS: Malocclusion with APBBD was more prevalent among high DAI subjects (P  =  .034, OR  =  1.04, 95% CI: 1.00-1.08), Class III malocclusion patients (P  =  .048, OR  =  2.32, 95% CI: 1.01-5.34) and male patients (P  =  .008, OR  =  2.96, 95% CI: 1.33-6.61). Participants scoring 88 points (the highest score in this sample) of the DAI had 16.84 times the risk of APBBD of those who scored 17 points (the lowest score in this sample). Patients with APBBD presented with a greater adjusted ANB angle (t  =  -8.10, P < .001) and a larger adjusted A-B/NF appraisal (t  =  -9.65, P < .001). The SNA angle (P < .001), the SNB angle (P  =  .002), the adjusted ANB angle (P  =  .001), and the adjusted A-B/NF appraisal (P  =  .035) were associated with DAI scores in cubic regression models. CONCLUSION: This study has demonstrated a relationship between the DAI and APBBD. Feasibility of using the adjusted ANB angle and the adjusted A-B/NF appraisal to assess severity of APBBD has been confirmed. The DAI may provide a supportive method to evaluate orthognathic needs. Future investigations are indicated.

A pragmatic method for electronic medical record-based observational studies: developing an electronic medical records retrieval system for clinical research.

OBJECTIVE: The use of electronic medical record (EMR) data is necessary to improve clinical research efficiency. However, it is not easy to identify patients who meet research eligibility criteria and collect the necessary information from EMRs because the data collection process must integrate various techniques, including the development of a data warehouse and translation of eligibility criteria into computable criteria. This research aimed to demonstrate an electronic medical records retrieval system (ERS) and an example of a hospital-based cohort study that identified both patients and exposure with an ERS. We also evaluated the feasibility and usefulness of the method. DESIGN: The system was developed and evaluated. PARTICIPANTS: In total, 800 000 cases of clinical information stored in EMRs at our hospital were used. PRIMARY AND SECONDARY OUTCOME MEASURES: The feasibility and usefulness of the ERS, the method to convert text from eligible criteria to computable criteria, and a confirmation method to increase research data accuracy. RESULTS: To comprehensively and efficiently collect information from patients participating in clinical research, we developed an ERS. To create the ERS database, we designed a multidimensional data model optimised for patient identification. We also devised practical methods to translate narrative eligibility criteria into computable parameters. We applied the system to an actual hospital-based cohort study performed at our hospital and converted the test results into computable criteria. Based on this information, we identified eligible patients and extracted data necessary for confirmation by our investigators and for statistical analyses with our ERS. CONCLUSIONS: We propose a pragmatic methodology to identify patients from EMRs who meet clinical research eligibility criteria. Our ERS allowed for the efficient collection of information on the eligibility of a given patient, reduced the labour required from the investigators and improved the reliability of the results.

Risk of osteomyelitis of the jaw induced by oral bisphosphonates in patients taking medications for osteoporosis: a hospital-based cohort study in Japan.

Oral bisphosphonates (BPs) represent the first line of prevention and treatment for osteoporosis. However, several studies have reported osteonecrosis of the jaw (ONJ), also known as osteomyelitis of the jaw (OMJ), as a side effect of these drugs. Although absolute risk is suggested to be low, information to date on the relative risk or attributable risk has in fact been limited. Here, we estimated risk of oral BPs for OMJ in osteoporosis patients taking oral BPs compared with other osteoporosis drugs. Using an electronic medical records retrieval system and manual confirmation of OMJ, we conducted a retrospective cohort study of patients taking medications for osteoporosis at Kyoto University Hospital between November 2000 and October 2010. To evaluate relative risks of oral BPs for OMJ, logistic regression analysis was performed and odds ratios (ORs) and 95% confidence interval (CIs) were estimated. In addition, sensitivity analyses were performed according to hierarchical diagnosis. A total of 4129 patients (59.6%) were prescribed BPs while 2794 (40.3%) received other osteoporosis drugs. Absolute risk for OMJ was estimated to range from 0.46% to 0.99% (95% CIs: 0.25-0.66 to 0.69-1.2) among patients receiving oral BPs and 0.071% to 0.17% (95% CIs: 0-0.17 to 0.022-0.33) among patients receiving other osteoporosis drugs. The attributable risks of oral BPs for OMJ were estimated to range from 0.38% to 0.81% (95% CIs: 0.38-0.39 to 0.80-0.81). ORs (95% CIs) adjusted for confounding factors were 5.0 (1.9-12.9) to 6.0 (1.3-26.1) for confirmed cases only. In terms of absolute and attributable risks, the risk of oral BPs for OMJ is considered to be less than 1% in patients with osteoporosis. However, oral BPs may increase the risk of OMJ compared with patients treated with other osteoporosis medications and the risk of side effects should be kept in mind.