First Australian estimates of incidence and prevalence of uterine fibroids: a data linkage cohort study 2000-2022.

STUDY QUESTION: What is the estimated prevalence and incidence of uterine fibroids diagnosed in Australian women of reproductive age? SUMMARY ANSWER: An estimated 7.3% of Australian women had a diagnosis of uterine fibroids by the age of 45-49 years, with age-specific incidence highest in women aged 40-44 years (5.0 cases per 1000 person-years). WHAT IS KNOWN ALREADY: Uterine fibroids are associated with a high symptom burden and may affect overall health and quality of life. Studies in different countries show a wide variation in both the prevalence (4.5-68%) and incidence (2.2-37.5 per 1000 person-years) of uterine fibroids, which may be partly explained by the type of investigation, method of case ascertainment, or the age range of the study population, necessitating the reporting of country-specific estimates. STUDY DESIGN, SIZE, DURATION: This observational prospective cohort study using self-report survey and linked administrative data (2000-2022) included 8066 women, born between 1973 and 1978, in the Australian Longitudinal Study on Women's Health. PARTICIPANTS/MATERIALS, SETTING, METHODS: A combination of self-report survey and linked administrative health data (hospital, emergency department, the Medicare Benefits Schedule, and the Pharmaceutical Benefits Scheme) were used to identify women with a report of a diagnosis of uterine fibroids between 2000 and 2022. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 8066 Australian women followed for 22 years, an estimated 7.3% of women (95% CI 6.9, 7.6) had a diagnosis of uterine fibroids by the age of 45-49 years. The incidence increased with age and was highest in women aged 40-44 years (5.0 cases per 1000 person-years, 95% CI 4.3, 5.7 cases per 1000 person-years). Women with uterine fibroids were more likely to experience heavy or painful periods. They were also more likely to report low iron levels, endometriosis, and poor self-rated health and to have two or more annual visits to their general practitioner. LIMITATIONS, REASONS FOR CAUTION: Our estimates are based on self-report of doctor diagnosis or treatment for fibroids and/or data linked to treatment and procedure administrative records. This predominantly captures women with symptomatic fibroids, but has the potential for misclassification of asymptomatic women and an underestimate of overall prevalence and incidence. In addition, questions on fibroids were only asked in surveys when women were 37-42 years of age to 43-48 years of age, so cases at younger ages may have been underestimated (particularly in women with less severe symptoms) as these were only ascertained through data linkage. WIDER IMPLICATIONS OF THE FINDINGS: These are the first population-based estimates of the prevalence and incidence of uterine fibroids in women of reproductive age in Australia. Establishing these first estimates will help inform health policy and health care provision in the Australian context. STUDY FUNDING/COMPETING INTEREST(S): The ALSWH is funded by the Australian Government Department of Health and Aged Care. L.FW. was supported by an Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence grant (APP1153420) and G.D.M. was supported by an NHMRC Leadership Fellowship (APP2009577). The funding bodies played no role in the design, the collection, analysis or interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Delayed diagnosis of endometriosis disadvantages women in ART: a retrospective population linked data study.

STUDY QUESTION: Do the outcomes and use of ART differ between women with and without endometriosis? SUMMARY ANSWER: ART use and outcome do not appear to differ for women with and without endometriosis, as long as endometriosis is diagnosed prior to commencing ART. WHAT IS KNOWN ALREADY: Approximately 40% of women with endometriosis have infertility and ART is the recommended treatment option for these women. However, diagnosis of endometriosis can be complex and lengthy, and a delay in diagnosis can reduce the likelihood of achieving a live birth. STUDY DESIGN, SIZE, DURATION: This retrospective national cohort study used longitudinal self-report data (collected 1996-2018) from women born in 1973-1978 who are participants in the Australian Longitudinal Study on Women's Health (ALSWH). The study also used linked administrative data on Endometriosis (1970-2018), ART (1996-2020) and births (1996-2018). PARTICIPANTS/MATERIALS, SETTING, METHODS: The outcome measures were: age at first ART cycle; use of ART treatments (IVF only; IUI only/and IVF); number of ART cycles (1-3; 4-10; 11-36); and births after first ART (no; yes) (note that births could not be tied to ART). MAIN RESULTS AND THE ROLE OF CHANCE: One in three (34.7%, n = 459/1322) women using ART had endometriosis, with 65.6% of these diagnosed before first ART and 34.4% after. Adjusted regression analyses showed women with endometriosis diagnosed before first ART were not significantly different to women without endometriosis on any outcome. However, women with endometriosis diagnosed after first ART were more likely to use IUI (adjusted odds ratio (aOR) 2.14, 95% CI 1.48, 3.09) and do more cycles (11-36 cycles: aOR 4.09, 95% CI 2.41, 6.95), and less likely to report a birth (aOR 0.67, 95% CI 0.45, 0.99), compared to women without endometriosis, despite no significant difference in starting age (coefficient = -0.62, 95% CI -1.36, 0.13). LIMITATIONS, REASONS FOR CAUTION: We did not have information on the severity of endometriosis, or the reasons for using ART, which can influence treatment and outcomes. We were not able to reliably link births with ART treatment. Finally, it is possible that some of the women in our 'no endometriosis' group did have endometriosis and were unaware of it, although prevalence rates match population estimates. WIDER IMPLICATIONS OF THE FINDINGS: These findings support previous studies that have found no difference in outcome of ART for women with endometriosis, but add the new insight that this is only true if endometriosis is diagnosed prior to commencing ART. A delayed diagnosis can create disadvantage during ART treatment. Early recourse to IVF may be advantageous for pregnancy prospects for women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The ALSWH is funded by the Australian Government Department of Health. G.D.M. is supported by an NHMRC Principal Research Fellowship (APP11218449). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Self-reported pain or injury from equipment used on military deployment.

BACKGROUND: Information about pain and injury from equipment on a particular deployment is not disaggregated in the literature; thus, the nature of the issue is unclear. AIMS: To determine the prevalence of pain or injury during a particular deployment that military personnel attributed to equipment they used on this deployment; and to document the types of equipment they identified, the type of pain or injury and how they thought the pain or injury occurred. METHODS: This paper analyses data from a deployment and health survey of Australian Defence Force personnel. The participants are 8932 personnel who deployed to Iraq and 6534 who deployed to Afghanistan. Participants indicated whether they experienced pain or injury from equipment they used on deployment and detailed their experiences in response to an open-ended question (n = 563). RESULTS: Sixteen per cent of Iraq-deployed and 21% of Afghanistan-deployed participants reported pain or injury from equipment they used on deployment. Body armour was the most common equipment identified; however, a wide range of equipment was related to pain or injury. A new finding is that pain or injury related to armour was attributed to its wear in vehicles and during vehicle ingress or egress. CONCLUSIONS: Knowledge of the nature of pain or injury related to equipment used on deployment may help inform improved designs and practices to reduce or prevent avoidable harm to serving personnel.

Individuals with high bone mass have increased progression of radiographic and clinical features of knee osteoarthritis.

OBJECTIVE: High bone mass (HBM) is associated with an increased prevalence of radiographic knee OA (kOA), characterized by osteophytosis. We aimed to determine if progression of radiographic kOA, and its sub-phenotypes, is increased in HBM and whether observed changes are clinically relevant. DESIGN: A cohort with and without HBM (L1 and/or total hip bone mineral density Z-score≥+3.2) had knee radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Medial/lateral tibial/femoral osteophyte and medial/lateral joint space narrowing (JSN) grades were summed and Δosteophytes, ΔJSN derived. Pain, function and stiffness were quantified using the WOMAC questionnaire. Associations between HBM status and sub-phenotype progression were determined using multivariable linear/poisson regression, adjusting for age, sex, height, baseline sub-phenotype grade, menopause, education and total body fat mass (TBFM). Generalized estimating equations accounted for individual-level clustering. RESULTS: 169 individuals had repeated radiographs, providing 330 knee images; 63% had HBM, 73% were female, mean (SD) age was 58 (12) years. Whilst HBM was not clearly associated with overall Kellgren-Lawrence measured progression (RR = 1.55 [0.56.4.32]), HBM was positively associated with both Δosteophytes and ΔJSN individually (adjusted mean differences between individuals with and without HBM 0.45 [0.01.0.89] and 0.15 [0.01.0.29], respectively). HBM individuals had higher WOMAC knee pain scores (ß = 7.42 [1.17.13.66]), largely explained by adjustment for osteophyte score (58% attenuated) rather than JSN (30% attenuated) or TBFM (16% attenuated). The same pattern was observed for symptomatic stiffness and functional limitation. CONCLUSIONS: HBM is associated with osteophyte progression, which appears to contribute to increased reported pain, stiffness and functional loss.

The use of unfixed bone marrow trephines for multicolour flow cytometry.

An adequate bone marrow aspirate is essential for a rapid diagnosis of acute leukaemia by multicolour flow cytometry enabling the simultaneous assessment of multiple antigens on the cell surface as well as intracellular or nuclear ones. In the context of acute leukaemia, it is important to have a diagnosis of the blasts lineage as soon as possible to decide the appropriate treatment. This is sometimes delayed due to difficulties in obtaining a bone marrow aspirate due to a "dry tap". In this study we evaluated retrospectively cell markers results by flow cytometry of unfixed bone marrow trephines of 65 patients with leukaemia at diagnosis and including a few after treatment. Our aims were: 1) To compare cell markers results between bone marrow trephine (BMT) and bone marrow aspirate (BMA) 24 cases and BMT with peripheral blood (PB) 14 cases in paired samples to establish if they were reproducible with results of the unfixed bone marrow trephine biopsies. 2) To ascertain a precise diagnosis in 27 (42%) of the cases in which only a bone marrow trephine was available. We demonstrated that unfixed bone marrow trephine provides an adequate and representative cell suspension for flow cytometry and it is a powerful tool when no other material (bone marrow aspirate or peripheral blood) is available to make a rapid diagnosis. Furthermore when marrow aspirate or peripheral blood paired samples were available, flow cytometry results obtained were identical across all the sample types. Applicability to the clinical laboratory: We described a method to obtain a cell suspension from core biopsies that can easily be implemented routinely in a laboratory that performs diagnostic flow cytometry immunophenotyping. This method is simple, inexpensive and it doesn't require extra equipment.

Is telemedicine helping or hindering the delivery of stroke thrombolysis in rural areas? A qualitative analysis.

BACKGROUND: Fast diagnosis and delivery of treatment to patients experiencing acute stroke can reduce subsequent disability. While telemedicine can improve rural community access to specialists and facilitate timely diagnosis and treatment decisions, it is not widely used for stroke in Australia. AIM: Identifying the barriers and facilitators to clinician engagement with, and utilisation of, telemedicine consultations could expedite implementation in rural and remote locations. METHODS: Purposive sampling was used to identify and recruit medical and nursing staff varying in telemedicine experience across one hospital department. Twenty-four in-depth, face-to-face interviews were conducted examining aspects surrounding stroke telemedicine uptake. Inductive qualitative thematic analysis was undertaken, and two further researchers verified coding. RESULTS: The main barriers identified were contrasting opinions about the utility of thrombolysis for treating acute stroke, lack of confidence in the telemedicine system, perceived limited need for specialist advice and concerns about receiving advice from an unfamiliar doctor. Facilitators included assistance with diagnosis and treatment, the need for a user-friendly system and access to specialists for complex cases. CONCLUSIONS: Acceptability of telemedicine for acute stroke was multifaceted and closely aligned with regional clinician beliefs about the value of thrombolysis for stroke, highlighting an important area for education. Addressing beliefs about treatment efficacy and other perceived barriers is important for establishing a stroke telemedicine programme.

Loneliness and low life satisfaction associated with older adults' poor oral health.

Objective: To examine the association of older adults' loneliness, life satisfaction, and other psychological stressors and resources with oral health status. Methods: This study merged 2018 data from the Health and Retirement Study (HRS) CORE survey with the HRS-Dental Module, and Psychosocial and Lifestyle Questionnaire-Panel A "Leave Behind" surveys (HRS-LB)(N = 418). Dental Module outcomes of interest were self-rated oral health status (SROH), and oral health-related quality of life (OHQOL). Older adults reported on loneliness, life satisfaction, perceived age, social status, control, mastery, and chronic stressors. Three distinct profiles based on the distribution of loneliness and life satisfaction were previously identified in the combined HRS and HRS-LB study population (N = 4,703) using latent class analysis (LCA). Class A:"Not Lonely/Satisfied" adults had the fewest psychosocial risk factors and most resources; Class C:"Lonely/Unsatisfied" adults exhibited the opposite profile (most risk factors, fewest resources); Class B:"Lonely/Satisfied" adults exhibited loneliness with favorable life satisfaction. Regression models examined associations between LCA classes and fair/poor SROH and the OHQOL scale score and individual items, after adjusting for socio-demographics. Results: About 13% of older adults experienced loneliness, and about 16% reported low life satisfaction. About one-quarter (28%) of older adults reported fair/poor SROH, and they experienced more psychosocial risk factors than their counterparts with better oral health status. Nearly half the older adults were categorized in Class A:"Not Lonely/Satisfied" (n = 201), and about one-quarter each in Class B:"Lonely/Satisfied" (n = 103) and Class C:"Lonely/Unsatisfied" (n = 112). In fully adjusted models, Class B older adults had 1.81 (1.11-2.96) times greater odds of fair/poor SROH, and Class C had 4.64 (2.78-7.73) times greater odds of fair/poor SROH than Class A. Fully adjusted linear regression model results indicated a gradient by LCA class. OHQOL varied; Class A older adults had the best (lowest) OHQOL score (mean = 8.22, 4.37-12.10), Class B scored in the middle (mean = 12.00, 7.61-16.50), while Class C had the worst (highest) OHQOL score (mean = 16.20, 11.80-20.60). Conclusion: Loneliness, as a defining characteristic distinguishing three latent classes of older adults, was associated with more risk factors and poorer oral health outcomes. Loneliness, life satisfaction, perceived age, social status, control, mastery, and chronic stressors vary widely for older adults and matter for oral health and OHQOL.

Edentulism Predicts Cognitive Decline in the US Health and Retirement Cohort Study.

This longitudinal cohort study examines if 1) cognitive decline varies by birth cohort, adjusting for covariates, and 2) edentulism and nonuse of dental care predict 10-y cognitive decline (2008-2018). The Health and Retirement Study (HRS) features a representative sample of US adults over age 50. Eligibility criteria included having cognitive interview data available and responding to the question, "Have you lost all of your upper and lower natural permanent teeth?" at 2+ time points between 2006 and 2018. Use of dental care in the past 2 y was assessed. Linear mixed models for repeated measures estimated the trajectories of mean cognition over time for the birth cohorts, adjusted for baseline cognition, dentition status, dental care use, and covariates (demographic characteristics, health behaviors, and medical conditions). Cohort-by-time interaction terms were included to assess if cognitive decline varied by birth cohort. Ten-year change in cognition status (measured by HRS Cogtot27)-categorized as dementia (<7); cognitive impairment, not demented (7-11) 7≤Cogtot27<12; and normal (≥12)-was also investigated according to birth cohort, dentition status, and dental care use. Mean (SD) baseline age was 63.4 (10.1) y (n = 22,728). Older birth cohorts had greater cognitive decline than younger cohorts. Linear mixed-model estimates and 95% confidence intervals for protective factors for cognitive decline included higher baseline cognition (HRS Cogtot27) (0.49; 0.48-0.50), use of dental care in the past 2 y (0.17; 0.10-0.23), and covariates such as greater household wealth and being married. Risk increased with being edentulous (-0.42; -0.56 to -0.28), history of stroke or diabetes, less education, Medicaid recipient, current smoker, loneliness, and poor/fair self-rated health. Edentulism and irregular dental care are among important predictors of cognitive decline. Tooth retention and regular dental care throughout life appear to be important for maintaining oral and cognitive health.

Prediction Model Development and Validation of 12-Year Incident Edentulism of Older Adults in the United States.

INTRODUCTION: Edentulism affects health and quality of life. OBJECTIVES: Identify factors that predict older adults becoming edentulous over 12 y in the US Health and Retirement Study (HRS) by developing and validating a prediction model. METHODS: The HRS includes data on a representative sample of US adults aged >50 y. Selection criteria included participants in 2006 and 2018 who answered, "Have you lost all of your upper and lower natural permanent teeth?" Persons who answered "no" in 2006 and "yes" in 2018 experienced incident edentulism. Excluding 2006 edentulous, the data set (n = 4,288) was split into selection (70%, n = 3,002) and test data (30%, n = 1,286), and Monte Carlo cross-validation was applied to 500 random partitions of the selection data into training (n = 1,716) and validation (n = 1,286) data sets. Fitted logistic models from the training data sets were applied to the validation data sets to obtain area under the curve (AUC) for 32 candidate models. Six variables were included in all models (age, race/ethnicity, gender, education, smoking, last dental visit) while all combinations of 5 variables (income, alcohol use, self-rated health, loneliness, cognitive status) were considered for inclusion. The best parsimonious model based on highest mean AUC was fitted to the selection data set to obtain a final prediction equation. It was applied to the test data to estimate AUC and 95% confidence interval using 1,000 bootstrap samples. RESULTS: From 2006 to 2018, 9.7% of older adults became edentulous. The 2006 mean (SD) age was 66.7 (8.7) for newly edentulous and 66.3 (8.4) for dentate (P = 0.31). The baseline 6-variable model mean AUC was 0.740. The 7-variable model with cognition had AUC = 0.749 and test data AUC = 0.748 (95% confidence interval, 0.715-0.781), modestly improving prediction. Negligible improvement was gained from adding more variables. CONCLUSION: Cognition information improved the 12-y prediction of becoming edentulous beyond the modifiable risk factors of smoking and dental care use, as well as nonmodifiable demographic factors. KNOWLEDGE TRANSFER STATEMENT: This prediction modeling and validation study identifies cognition as well as modifiable (dental care use, smoking) and nonmodifiable factors (race, ethnicity, gender, age, education) associated with incident complete tooth loss in the United States. This information is useful for the public, dental care providers, and health policy makers in improving approaches to preventive care, oral and general health, and quality of life for older adults.

Exploring dimensions of quality-of-life in survivors of stroke with communication disabilities - a brief report.

BACKGROUND: People with communication disabilities post-stroke have poor quality-of-life. OBJECTIVES: We aimed to explore the association of self-reported communication disabilities with different dimensions of quality-of-life between 90 and 180 days post-stroke. METHODS: Cross-sectional survey data were obtained between 90 and 180 days post-stroke from registrants in the Australian Stroke Clinical Registry recruited from three hospitals in Queensland. The usual follow-up survey included the EQ5D-3L. Responses to the Hospital Anxiety and Depression Scale, and extra questions (e.g. communication disabilities) were also collected. We used χ2 statistics to determine differences. RESULTS: Overall, 244/647 survivors completed the survey. Respondents with communication disabilities (n = 72) more often reported moderate to extreme problems in all EQ5D-3L dimensions, than those without communication disabilities (n = 172): anxiety or depression (74% vs 40%, p < .001), pain or discomfort (58% vs 39%, p = .006), self-care (46% vs 18%, p < .001), usual activities (77% vs 49%, p < .001), and mobility (68% vs 35%, p < .001). Respondents with communication disabilities reported less fatigue (66% vs 89%, p < .001), poorer cognitive skills (thinking) (16% vs 1%, p < .001) and lower social participation (31% vs 6%, p < .001) than those without communication disabilities. CONCLUSIONS: Survivors of stroke with communication disabilities are more negatively impacted across different dimensions of quality-of-life (as reported between 90 and 180 days post-stroke) compared to those without communication disabilities. This highlights the need for timely and on-going comprehensive multidisciplinary person-centered support.

TRAF3IP2-IL-17 Axis Strengthens the Gingival Defense against Pathogens.

Recent genome-wide association studies have suggested novel risk loci associated with periodontitis, which is initiated by dysbiosis in subgingival plaque and leads to destruction of teeth-supporting structures. One such genetic locus was the tumor necrosis factor receptor-associated factor 3 interacting protein 2 (TRAF3IP2), a gene encoding the gate-keeping interleukin (IL)-17 receptor adaptor. In this study, we first determined that carriers of the lead exonic variant rs13190932 within the TRAF3IP2 locus combined with a high plaque microbial burden was associated with more severe periodontitis than noncarriers. We then demonstrated that TRAF3IP2 is essential in the IL-17-mediated CCL2 and IL-8 chemokine production in primary gingival epithelial cells. Further analysis suggested that rs13190932 may serve a surrogate variant for a genuine loss-of-function variant rs33980500 within the same gene. Traf3ip2 null mice (Traf3ip2-/-) were more susceptible than wild-type (WT) mice to the Porphyromonas gingivalis-induced periodontal alveolar bone loss. Such bone loss was associated with a delayed P. gingivalis clearance and an attenuated neutrophil recruitment in the gingiva of Traf3ip2-/- mice. Transcriptomic data showed decreased expression of antimicrobial genes, including Lcn2, S100a8, and Defb1, in the Traf3ip2-/- mouse gingiva in comparison to WT mice prior to or upon P. gingivalis oral challenge. Further 16S ribosomal RNA sequencing analysis identified a distinct microbial community in the Traf3ip2-/- mouse oral plaque, which was featured by a reduced microbial diversity and an overabundance of Streptococcus genus bacteria. More P. gingivalis was observed in the Traf3ip2-/- mouse gingiva than WT control animals in a ligature-promoted P. gingivalis invasion model. In agreement, neutrophil depletion resulted in more local gingival tissue invasion by P. gingivalis. Thus, we identified a homeostatic IL-17-TRAF3IP2-neutrophil axis underpinning host defense against a keystone periodontal pathogen.

'Sink or swim': an evaluation of the clinical characteristics of individuals with high bone mass.

SUMMARY: High bone mineral density on routine dual energy X-ray absorptiometry (DXA) may indicate an underlying skeletal dysplasia. Two hundred fifty-eight individuals with unexplained high bone mass (HBM), 236 relatives (41% with HBM) and 58 spouses were studied. Cases could not float, had mandible enlargement, extra bone, broad frames, larger shoe sizes and increased body mass index (BMI). HBM cases may harbour an underlying genetic disorder. INTRODUCTION: High bone mineral density is a sporadic incidental finding on routine DXA scanning of apparently asymptomatic individuals. Such individuals may have an underlying skeletal dysplasia, as seen in LRP5 mutations. We aimed to characterize unexplained HBM and determine the potential for an underlying skeletal dysplasia. METHODS: Two hundred fifty-eight individuals with unexplained HBM (defined as L1 Z-score ≥ +3.2 plus total hip Z-score ≥ +1.2, or total hip Z-score ≥ +3.2) were recruited from 15 UK centres, by screening 335,115 DXA scans. Unexplained HBM affected 0.181% of DXA scans. Next 236 relatives were recruited of whom 94 (41%) had HBM (defined as L1 Z-score + total hip Z-score ≥ +3.2). Fifty-eight spouses were also recruited together with the unaffected relatives as controls. Phenotypes of cases and controls, obtained from clinical assessment, were compared using random-effects linear and logistic regression models, clustered by family, adjusted for confounders, including age and sex. RESULTS: Individuals with unexplained HBM had an excess of sinking when swimming (7.11 [3.65, 13.84], p < 0.001; adjusted odds ratio with 95% confidence interval shown), mandible enlargement (4.16 [2.34, 7.39], p < 0.001), extra bone at tendon/ligament insertions (2.07 [1.13, 3.78], p = 0.018) and broad frame (3.55 [2.12, 5.95], p < 0.001). HBM cases also had a larger shoe size (mean difference 0.4 [0.1, 0.7] UK sizes, p = 0.009) and increased BMI (mean difference 2.2 [1.3, 3.1] kg/m(2), p < 0.001). CONCLUSION: Individuals with unexplained HBM have an excess of clinical characteristics associated with skeletal dysplasia and their relatives are commonly affected, suggesting many may harbour an underlying genetic disorder affecting bone mass.

Periodontal Treatment Reduces Circulating Pro-Inflammatory Cytokine and Chemokine Levels in African American HIV+ Individuals with Virological Suppression.

Introduction: Periodontal Disease (PD), a chronic inflammatory disease, is highly prevalent among Persons Living With HIV (PLWH) and is characterized by microbial symbiosis and oxidative stress. Our hypothesis stipulates that periodontal therapy attenuates systemic inflammatory and bacterial burden while improving periodontal status in PLWH. Methods: Sixteen African Americans (AA) with suppressed HIV viremia on long-term Antiretroviral Therapy (ART) were recruited to this study. Participants were placed into two groups, based on their dental care status: group 1 (In-Care, IC) and group 2 (Out of Care, OC). Periodontal health was investigated at baseline, 3 months, 6 months, and 12 months. Cytokine/chemokines, microbial phyla, and Asymmetric Dimethylarginine (ADMA, a marker for endothelial cell dysfunction) levels were assessed in the serum. Statistical comparisons between groups and at different visits were performed using multiple comparison tests. Results: Across longitudinal visits, periodontal treatment significantly reduced the levels of several cytokines and chemokines. At baseline, the out of care group had significantly higher blood levels of ADMA and actinobacteria than the IC group. Periodontal treatment significantly altered the abundance of circulating genomic bacterial DNA for various phyla in out of care group. Conclusions: Periodontal treatment interventions effectively attenuated circulating pro-inflammatory cytokines and altered microbial translocation, both critical drivers of systemic inflammation in PLWH.

Distinct Microbial Signatures between Periodontal Profile Classes.

Precise classification of periodontal disease has been the objective of concerted efforts and has led to the introduction of new consensus-based and data-driven classifications. The purpose of this study was to characterize the microbiological signatures of a latent class analysis (LCA)-derived periodontal stratification system, the Periodontal Profile Class (PPC) taxonomy. We used demographic, microbial (subgingival biofilm composition), and immunological data (serum IgG antibody levels, obtained with checkerboard immunoblotting technique) for 1,450 adult participants of the Dental Atherosclerosis Risk in Communities (ARIC) study, with already generated PPC classifications. Analyses relied on t tests and generalized linear models with Bonferroni correction. Men and African Americans had higher systemic antibody levels against most microorganisms compared to women and Caucasians (P < 0.05). Healthy individuals (PPC-I) had low levels of biofilm bacteria and serum IgG levels against most periodontal pathogens (P < 0.05). Subjects with mild to moderate disease (PPC-II to PPC-III) showed mild/moderate colonization of multiple biofilm pathogens. Individuals with severe disease (PPC-IV) had moderate/high levels of biofilm pathogens and antibody levels for orange/red complexes. High gingival index individuals (PPC-V) showed moderate/high levels of biofilm Campylobacter rectus and Aggregatibacter actinomycetemcomitans. Biofilm composition in individuals with reduced periodontium (PPC-VI) was similar to health but showed moderate to high antibody responses. Those with severe tooth loss (PPC-VII) had significantly high levels of multiple biofilm pathogens, while the systemic antibody response to these microorganisms was comparable to health. The results support a biologic basis for elevated risk for periodontal disease in men and African Americans. Periodontally healthy individuals showed a low biofilm pathogen and low systemic antibody burden. In the presence of PPC disease, a microbial-host imbalance characterized by higher microbial biofilm colonization and/or systemic IgG responses was identified. These results support the notion that subgroups identified by the PPC system present distinct microbial profiles and may be useful in designing future precise biological treatment interventions.

Changes in gingival crevicular fluid inflammatory mediator levels during the induction and resolution of experimental gingivitis in humans.

AIM: The goal of this study is to characterize the changes in 33 biomarkers within the gingival crevicular fluid during the 3-week induction and 4-week resolution of stent-induced, biofilm overgrowth mediated, experimental gingivitis in humans. METHODS: Experimental gingivitis was induced in 25 subjects for 21 days followed by treatment with a sonic powered toothbrush for 28 days. Clinical indices and gingival crevicular fluids were collected weekly during induction and biweekly during resolution. Samples were analysed using a bead-based multiplexing analysis for the simultaneous measurements of 33 biomarkers within each sample including cytokines, matrix-metalloproteinases (MMPs) and adipokines. Prostaglandin-E(2) was measured by enzyme-linked immunoadsorbant assay. Statistical testing using general linear models with structured covariance matrices were performed to compare stent to contralateral (non-stent) changes in clinical signs and in biomarker levels over time. RESULTS: Gingivitis induction was associated with a significant 2.6-fold increase in interleukin 1-beta (IL-beta), a 3.1-fold increase in IL-1alpha and a significant decrease in multiple chemokines as well as MMPs-1, -3 and 13. All changes in clinical signs and mediators rebounded to baseline in response to treatment in the resolution phase. CONCLUSIONS: Stent-induced gingivitis is associated with marked, but reversible increases in IL-alphaa and IL-1beta with suppression of multiple chemokines as well as selected MMPs.

Flossing Is Associated with Improved Oral Health in Older Adults.

The effect of preventive oral habits is largely unexplored in older individuals. The purpose of this study was to evaluate the associations between home use of flossing and prevalence of periodontal disease and caries in older adults. Five-year incident tooth loss was also evaluated. Data on 686 individuals ≥65 y-old from the Piedmont 65+ Dental Study were examined including: 1) interproximal clinical attachment level (iCAL), 2) interproximal probing depth (iPD), 3) numbers of caries, and 4) missing teeth. Flossing behavior was evaluated according to the Periodontal Profile Class (PPC) system. Five-year follow-up data (n = 375) was evaluated for incident tooth loss. Dichotomous and categorical variables were analyzed using Pearson chi-square tests as well as covariate-adjusted Cochran-Mantel-Haenszel tests. Multiple linear regression compared clinical parameters based on flossing behavior. Elderly flossers had lower (mean, SE) %iCAL≥3 mm (38.2, 2.38 vs. 48.8, 1.56) and %iPD≥4 mm (8.70, 1.41 vs. 14.4, 0.93) compared to nonflossers (P ≤ 0.005). Flossers showed less coronal caries compared to nonflossers (P = 0.02). Baseline number of missing teeth (mean, SE) was 11.5 (0.35) in nonflossers compared to 8.6 (0.53) in flossers (P < 0.0001). Regular dental visitors had lower oral disease levels compared to episodic dental users. The majority of flossers classified into PPC-Stage I (health) whereas nonflossers classified as PPC-Stages V, VI, and VII (disease). At the 5-y follow-up visit, the average tooth loss for flossers was ~1 tooth compared to ~4 teeth lost for nonflossers (P < 0.0001). Among all teeth, molars showed the highest benefit (>40%) for flossing behavior (P = 0.0005). In conclusion, the extent of oral disease for older individuals was significantly less in flossers than in nonflossers. Flossers showed less periodontal disease, fewer dental caries, and loss of fewer teeth over a 5-y period. These findings further support flossing as an important oral hygiene behavior to prevent oral disease progression in older adults.

Increased TLR4 expression in murine placentas after oral infection with periodontal pathogens.

Maternal periodontitis has emerged as a putative risk factor for preterm births in humans. The periodontitis-associated dental biofilm is thought to serve as an important source of oral bacteria and related virulence factors that hematogenously disseminate and affect the fetoplacental unit; however the underlying biological mechanisms are yet to be fully elucidated. This study hypothesized that an oral infection with the human periodontal pathogens Campylobacter rectus and Porphyromonas gingivalis is able to induce fetal growth restriction, placental inflammation and enhance Toll-like receptors type 4 (TLR4) expression in a murine pregnancy model. Female Balb/C mice (n = 40) were orally infected with C. rectus and/or P. gingivalis over a 16-week period and mated once/week. Pregnant mice were sacrificed at embryonic day (E) 16.5 and placentas were collected and analyzed for TLR4 mRNA levels and qualitative protein expression by real-time PCR and immunofluorescence. TLR4 mRNA expression was found to be increased in the C. rectus-infected group (1.98 +/- 0.886-fold difference, P < 0.01, ANOVA) compared to controls. Microscopic analysis of murine placentas showed enhanced immunofluorescence of TLR4 in trophoblasts, mainly in the placental labyrinth layer. Also, combined oral infection with C. rectus and P. gingivalis significantly reduced the overall fecundity compared to controls (16.7% vs. 75%, infected vs. non-infected mice respectively, P = 0.03, Kaplan-Meier). The results supported an enhanced placental TLR4 expression after oral infection with periodontal pathogens. The TLR4 pathway has been implicated in the pathogenesis of preterm births; therefore the abnormal regulation of placental TLR4 may give new insights into how maternal periodontitis and periodontal pathogens might be linked to placental inflammation and preterm birth pathogenesis.

Risk factors for early post-operative psychiatric symptoms in patients undergoing epilepsy surgery for temporal lobe epilepsy.

OBJECTIVE: De-novo psychiatric symptoms may develop within 3 months after a temporal lobectomy for epilepsy. The objective of this study was to identify presurgical risk factors for psychiatric symptoms. METHODS: Twenty-seven patients who had a temporal lobectomy for epilepsy were included. Twenty-four had hippocampal sclerosis or gliosis, and three had cavernous haemagiomata. Twelve had operations on the left, and 15 on the right side. Twenty-four patients were rendered free of seizures (SZ) with loss of awareness, three had early post-operative convulsions, one continued to have habitual SZ. RESULTS: Nine patients (33%) developed low mood, anxiety and emotional lability within 3 months after surgery. Patients with early post-operative psychiatric symptoms were younger (27.9/34.8 years, P = 0.01), and more anxious on the presurgical Hospital Anxiety and Depression Scale (12/8.44, P = 0.02) than patients without post-operative psychiatric symptoms. There was also an association between right temporal lobectomies and early post-surgical symptoms (P = 0.02 Fisher's exact test). CONCLUSION: Potential risk factors were age, anxiety and operation on the right side. Larger studies are required to determine if these risk factors are independent.

Levels of serum interleukin (IL)-6 and gingival crevicular fluid of IL-1beta and prostaglandin E(2) among non-smoking subjects with gingivitis and type 2 diabetes.

BACKGROUND: The goal of this study was to assess whether non-smoking patients with type 2 diabetes present with increased levels of local and systemic proinflammatory mediators and, if so, whether such an increase is associated with enhanced clinical gingival inflammation compared to non-smoking patients without diabetes. METHODS: We used a cross-sectional database consisting of 725 self-reported lifelong non-smokers aged 53 to 74 years. Gingival crevicular fluid (GCF) levels of interleukin (IL)-1beta and prostaglandin E(2) (PGE(2)) and serum levels of IL-6 were measured using enzyme-linked immunosorbent assay. No participant had probing depth >3 mm. Participants with bleeding on probing (BOP) in <10% of sites were classified as healthy, whereas those with BOP in >or=10% of sites were defined as having biofilm-gingival interface (BGI) gingivitis. RESULTS: Approximately 53% (n = 385) and 11% (n = 80) of the sample had BGI gingivitis and type 2 diabetes, respectively. The mean age-adjusted level of GCF IL-1beta was significantly elevated in the diabetic group compared to the non-diabetic group (P = 0.048), but serum IL-6 (P = 0.14) and GCF PGE(2) were not (P = 0.98). The mean GCF IL-1beta and PGE(2) levels were significantly elevated in subjects with BGI gingivitis (136.2 +/- 112.9 ng/ml and 277.2 +/- 187.2 ng/ml, respectively) compared to subjects with gingival health (95.9 +/- 82.9 ng/ml and 205.7 +/- 149.6 ng/ml, respectively), regardless of diabetic status (P <0.001 for both). However, serum IL-6 was elevated in subjects with BGI gingivitis compared to subjects with gingival health only among subjects with diabetes (2.9 +/- 3.2 pg/ml versus 1.5 +/- 1.4 pg/ml; P = 0.008). With the exception of serum IL-6 in subjects without diabetes, an increase in the levels of proinflammatory mediators was associated with increased odds of having BGI gingivitis. The associations were stronger in the diabetic group. CONCLUSIONS: Type 2 diabetes may increase the host inflammatory response to oral biofilm, which, in turn, may exacerbate preconditions associated with gingivitis in susceptible individuals. Furthermore, systemic inflammation, as demonstrated by the increased level of serum IL-6, is associated with BGI gingivitis among non-smoking patients with diabetes.

The effect of changes in pain expectations on persistent pain following a road traffic crash.

BACKGROUND: Recovery expectations can influence outcomes after injury, but little is known about the course of expectations over time or factors predicting changes in expectations. This study aimed to describe how expectations of persistent pain change over time following a non-catastrophic injury sustained in a road traffic crash (RTC); identify the early predictors of change in expectations over time; and examine whether change in expectations predicted pain at 24 months post-RTC. METHODS: One hundred and seventy-seven participants (Mage = 49.25; SD = 14.15; 66.1% female) reported their expectations of persistent pain (1 = no risk that pain will become persistent, 10 = highest risk) at approximately 6, 12 and 24 months post-injury via survey. Measures of pain, emotional distress, post-traumatic stress, fear avoidance beliefs, social support and quality of life were also measured via survey at each time point. RESULTS: Cluster analysis revealed four clusters: 42% of participants showed a pattern of stable expectations (stable high-risk, n = 74), whereas 58% of participants showed changes in expectations over time (decreasing risk, n = 31; increasing risk, n = 44; risk peaking at 12 months, n = 28). Hierarchical linear regression models demonstrated that the clusters were a better statistical predictor of pain at 24 months than a single measure of expectation taken at 6 months post-injury. Pain, anxiety, depression and physical health-related quality of life at 6 months were associated with cluster affiliation. CONCLUSIONS: Assessment of patterns of pain expectancy change is a superior means of determining long-term pain levels. Understanding expectancy change patterns will help provide more nuanced targets for pain intervention. SIGNIFICANCE: This study extends previous work by investigating persistent pain expectancies over time in a compensation-seeking cohort with non-catastrophic injuries. It identifies factors that are associated with changing expectations, providing targets for clinical intervention. The study shows that expectations can change over time. Conversations with patients about their expectations should be ongoing.