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We used cluster analysis to determine the profiles of individuals who sustained wrist fractures. We found two groups: (1) young and active and (2) older and less active. This information may be used to identify individuals who require further bone health interventions to optimize healthy aging., Introduction: Distal radial fractures (DRF) are the most common of all fractures, with 6% of males and 33% of females having one at some point in their lifetime. We hypothesize that DRF consists of two subpopulations: one with compromised bone health that is early in the osteoporosis (OP) trajectory and another which are active and healthy and suffer a misfortune fracture due to their high activity levels or risk-taking behaviors. The latter is likely to recover with a minimal disability, while the former may signal a negative health trajectory of disability and early mortality., Objective: To determine the profiles of individuals who sustained wrist fractures using cluster analysis within the Comprehensive Cohort of the Canadian Longitudinal Study on Aging (CLSA) database considering factors that reflect bone health and activity levels., Methods: We included all the individuals who had a wrist fracture within the CLSA comprehensive cohort of the database (n = 968). The baseline data was used for this analysis. A 2-step cluster analysis was used to identify profiles that were both statistically and clinically meaningful. Variables that were used in the cluster analysis include demographic variables, physical activity status indicators, general health indicators, mobility indicators, bone health indicators, comorbid conditions, and lifestyle factors., Results: We were able to identify two distinct profiles that were statistically and clinically meaningful confirming our hypothesis. One cluster included a predominantly younger cohort, who are physically active, with less comorbid conditions, better bone health, and better general health, while the opposite was true of the first cohort., Conclusion: We were able to identify two clusters-a healthy profile and a bone health compromised profile. This information may be used to identify the subgroup of people who should be targeted in the future for more intensive preventive health services to optimize healthy aging., (© 2023. The Author(s).)

Background: Oral health plays a role in overall health, indicating the need to identify barriers to accessing oral care. The objective of this study was to identify barriers to accessing oral health care and examine the association between socioeconomic, psychosocial, and physical measures with access to oral health care among older Canadians., Methods: A cross-sectional study was conducted using data from the Canadian Longitudinal Study on Aging (CLSA) follow-up 1 survey to analyze dental insurance and last oral health care visit. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between socioeconomic, psychosocial, and physical measures with access to oral care, measured by dental insurance and last oral health visit., Results: Among the 44,011 adults included in the study, 40% reported not having dental insurance while 15% had not visited an oral health professional in the previous 12 months. Several factors were identified as barriers to accessing oral health care including, no dental insurance, low household income, rural residence, and having no natural teeth. People with an annual income of <$50,000 were four times more likely to not have dental insurance (adjusted OR: 4.09; 95% CI: 3.80-4.39) and three times more likely to report not visiting an oral health professional in the previous 12 months (adjusted OR: 3.07; 95% CI: 2.74-3.44) compared to those with annual income greater than $100,000., Conclusions: Identifying barriers to oral health care is important when developing public health strategies to improve access, however, further research is needed to identify the mechanisms as to why these barriers exist., (© 2023. The Author(s).)

Chronic graft-versus-host disease (cGVHD) targets include the oral mucosa and salivary glands after allogeneic hematopoietic stem cell transplant (HSCT). Without incisional biopsy, no diagnostic test exists to confirm oral cGVHD. Consequently, therapy is often withheld until severe manifestations develop. This proteomic study examined saliva and human salivary gland for a biomarker profile at first onset of oral cGVHD prior to initiation of topical steroid therapy. Whole saliva collected at onset of biopsy-proven oral GVHD was assessed using liquid chromatography-coupled tandem mass spectrometry with identification of 569 proteins, of which 77 significantly changed in abundance. ZG16B, a secretory lectin protein, was reduced 2-fold in oral cGVHD saliva (p <0.05), and significantly decreased in salivary gland secretory cells affected by cGVHD. Single-cell RNA-seq analysis of healthy MSG localized ZG16B expression to two discrete acinar cell populations. Reduced ZG16B expression may indicate specific cGVHD activity and possibly general salivary gland dysfunction., Competing Interests: No competing interests from the authors., (© 2021.)

Maintenance of lung function is an often underappreciated, yet critical component of healthy aging. Given the unprecedented shift in the average age of Canadians over the next half century, it will be important to investigate the determinants of lung function in the elderly. In the following study, we estimated the association between lung function and a broad array of factors related to sociodemographics, lifestyle, chronic medical conditions and psychosocial factors in older adults aged 45-86 years old using cross-sectional data from the Canadian Longitudinal Study of Aging (n = 21,338). In addition to examining the entire cohort, we also performed stratified analyses within men/women, adults aged 45-64/65+, and healthy/comorbid. In multivariable regression, our explanatory factors (excluding age, sex, height and ethnicity) were able to explain 17% and 11% of the total variance in FEV 1 and FEV 1 /FVC, respectively. Notable and significant contributions were observed for respiratory disease, smoking, obesity, income, and physical activity, while psychosocial factors mainly exhibited non-significant associations. Generally, these associations were stronger for males than females, and adults 65 and older as compared to those aged 45-64. Our findings indicate that there are pervasive and generally under-recognized sociodemographic and lifestyle factors that exhibit significant associations with FEV 1 and FEV 1 /FVC in older adults. While implication of causality in these relationships is not possible due to the cross-sectional nature of the study, future work aiming to investigate determinants of lung health in older adults may choose to target these factors, given that many are modifiable., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To compare the prevalence of poor self-reported oral health (SROH) and dental service-use in a representative sample of Canadian residents, and to identify associations between SROH and psychosocial determinants of health at baseline of the Canadian Longitudinal Study on Aging., Methods: Data from baseline interviews from 2010 to 2015 involving 93% of 51 388 adults (n = 47 761) were weighted to compare the prevalence of oral health characteristics adjusted for age, sex, socioeconomics, general health and residence. SROH was assessed as 'excellent', 'very good', 'good', 'fair' or 'poor', and dichotomized as 'fair/poor' and 'good/very good/excellent'. Multivariable logistic regression was used to assess the association of fair/poor oral health with psychosocial determinants of health., Results: Most participants reported 'good/very good/excellent' oral health (92.5%), natural teeth (92.0%) and dental service-use in the previous year (79.6%), yet over 10% had discomfort when eating. Reports of 'fair/poor' oral health were significantly more frequent among participants who had dental concerns, had low socioeconomic status, smoked tobacco or reported poor general health. Dental service-use and tooth loss differed by province. The odds of poor/fair SROH were high (odds ratio ≥1.5) among participants who avoided foods, did not use dental services frequently, had low incomes, smoked tobacco, were depressed, felt unhealthy or had multiple chronic conditions, but by neither sex or age. There were no interprovincial differences., Conclusions: Most Canadian residents feel in good oral health and use dental services. Oral health inequality is evident between different socioeconomic groups and between healthy and unhealthy people. SROH is strongly associated with socioeconomic and general health status but not with place of residence. However, there were substantial differences in reports of tooth loss and dental service-use across provinces., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pathogenic germline variation in the microRNA processing gene DICER1 gives rise to an autosomal dominant, tumor-predisposition disorder. Conditional deletion of Dicer1 in murine dental epithelium shows that it controls tooth patterning, size, number, and shape. The human dental phenotype of people with germline pathogenic variation in DICER1 is unknown. DICER1-carriers (n = 57) and family controls (n = 55) were evaluated at the NIH Clinical Center dental clinic as part of a comprehensive medical evaluation. Digital panoramic radiographs, bite-wing radiographs, and oral photographs were collected. A single observer, blind to DICER1 status, reviewed the dental records and determined the presence or absence of 11 dental characteristics as described in the clinic notes, radiographs, or oral photographs. Subjective phenotypes were reviewed on radiographs by two examiners (blind to DICER1 status) for the presence or absence of the dental characteristics to reduce inconsistencies. By simple association, bulbous crown, periodontitis, and taurodontism were all significant (p < .05). Logistic regression with chi-square maximum likelihood estimates showed that bulbous crown and periodontitis remained significant. Recognition of these phenotypes may aid identification of individuals and families at risk for DICER1-associated neoplasms. These findings may also guide dental care for individuals with germline DICER1 pathogenic variation., (© 2019 Wiley Periodicals, Inc.)

Background: Neurofibromatosis type 1 (NF1) is a common, autosomal dominant tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Cephalometry is an inexpensive, readily available and non-invasive technique that is under-utilized in studying the NF1 craniofacial phenotype. An analysis of NF1 cephalometry was first published by Heervä et al. in 2011. We expand here on that first investigation with a larger cohort of adult and pediatric patients affected with NF1 and sought objective insight into the NF1 facies, said to feature hypertelorism and a broad nasal base, from cephalometric analysis., Methods: We obtained cephalograms from 101 patients with NF1 (78 adults and 23 children) from two NF1 protocols at the National Institutes of Health. Each subject had an age-, gender- and ethnicity-matched control. We used Dolphin software to make the cephalometric measurements. We assessed the normality of differences between paired samples using the Shapiro-Wilk test and evaluated the significance of mean differences using paired t-tests and adjusted for multiple testing. We explored the relationship between the cephalometric measurements and height, head circumference and interpupillary distance., Results: In this dataset of American whites with NF1, we confirmed in a modestly larger sample many of the findings found by Heerva et al. in an NF1 Finnish cohort. We found a shorter maxilla, mandible, cranial base, (especially anteriorly, p = 0.0001) and diminished facial height in adults, but not children, with NF1. Only one adult exhibited hypertelorism., Conclusions: The cephalometric differences in adults arise in part from cranial base shortening and thus result in a shorter face, mid-face hypoplasia, reduced facial projection, smaller jaw, and increased braincase globularity. In addition, we suggest that NF1 sphenoid bone shortening, a common event, is consistent with an intrinsic NF1 bone cell defect, which renders the bone more vulnerable to a random "second hit" in NF1, leading to sphenoid wing dysplasia, a rare event., (Published by Elsevier Masson SAS.)

At least half of patients with chronic graft-versus-host-disease (cGVHD), the leading cause of morbidity and non-relapse mortality after allogeneic stem cell transplantation, have oral manifestations: mucosal lesions, salivary dysfunction, and limited mouth-opening. cGVHD may manifest in a single organ or affect multiple organ systems, including the mouth, eyes, and the skin. The interrelationship of the 3 oral manifestations of cGVHD with each other and with the specific manifestations of extraoral cGVHD has not been studied. In this analysis, we explored, in a large group of patients with cGVHD, the potential associations between: (1) oral mucosal disease and erythematous skin disease, (2) salivary gland dysfunction and lacrimal gland dysfunction, and (3) limited mouth-opening and sclerotic skin cGVHD. Study participants, enrolled in a cGVHD Natural History Protocol (NCT00331968, n = 212), underwent an oral examination evaluating: (1) mucosal cGVHD [NIH Oral Mucosal Score (OMS)], (2) salivary dysfunction (saliva flow and xerostomia), and (3) maximum mouth-opening measurement. Parameters for dysfunction (OMS > 2, saliva flow ≤ 1 mL/5 min, mouth-opening ≤ 35 mm) were analyzed for association with skin cGVHD involvement (erythema and sclerosis, skin symptoms), lacrimal dysfunction (Schirmer's tear test, xerophthalmia), Lee cGVHD Symptom Scores, and NIH organ scores. Oral mucosal disease (31% prevalence) was associated with skin erythema (P < 0.001); salivary dysfunction (11% prevalence) was associated with lacrimal dysfunction (P = 0.010) and xerostomia with xerophthalmia (r = 0.32, P = 0.001); and limited mouth-opening (17% prevalence) was associated with skin sclerosis (P = 0.008) and skin symptoms (P = 0.001). There was no association found among these 3 oral cGVHD manifestations. This analysis supports the understanding of oral cGVHD as 3 distinct diseases: mucosal lesions, salivary gland dysfunction, and mouth sclerosis. Clear classification of oral cGVHD as 3 separate manifestations will improve clinical diagnosis, observational research data collection, and the definitions of outcome measures in clinical trials., (© International & American Associations for Dental Research 2015.)

Malnutrition is a known complication of chronic GVHD (cGVHD), but has not been well described in the context of organ-specific manifestations and the recent National Institutes of Health (NIH) criteria. Here, 210 cGVHD patients were analyzed, in a cross-sectional study design, for demographics, transplant-related history, clinical assessments, symptoms, function, quality-of-life, laboratory values and survival in order to determine their associations with nutritional status. Most patients had long-standing, moderate or severe cGVHD and had failed many lines of therapy. Twenty-nine percent (60/210) of subjects were malnourished, using the subjective Patient-Generated Subjective Global Assessment (PG-SGA) questionnaire and evaluation. No demographic or transplant characteristics were associated with malnutrition; cGVHD of the lungs, gastrointestinal (GI) tract and mouth, NIH global score, cGVHD symptoms, worse functioning, low albumin, poorer survival and low BMI were associated with malnutrition. A predictive model was developed from all variables of significance: cGVHD of the lungs, GI tract, mouth and BMI accurately predicted 84.2% of malnourished patients as well as 87.2% of well-nourished patients. The PG-SGA questionnaire may be a useful tool in diagnosing nutritional deficits in cGVHD patients undergoing one-time evaluations. Longitudinal prospective studies should assess the utility of nutritional support interventions in cGVHD.

Oral chronic GVHD (cGVHD) is a common, late complication of alloSCT that is associated with significant patient morbidity. The NIH Oral Mucosal Score (NIH OMS) was developed to assess oral cGVHD therapeutic response, but has not been fully validated. This study's purpose was to conduct a rigorous construct validity and internal consistency analysis of this score and its components (erythema, lichenoid, ulcers, mucoceles) using established measures of oral pain, oral function, oral-related quality-of-life, nutrition and laboratory parameters in 198 patients with cGVHD. The construct validity of the NIH OMS was supported: a moderate correlation was observed between NIH OMS and mouth pain (rho=0.43), while a weaker correlation was observed with low albumin (rho=-0.26). Total NIH OMS, erythema and lichenoid components were associated with malnutrition, oral pain and impaired oral QOL, while ulcers were only associated with oral pain. No associations were found between mucoceles and any indicator evaluated, including salivary function or xerostomia. Kappa determined between scale components was low overall (all 0.35), supporting a conclusion that each component measures a distinct manifestation of oral cGVHD. This study supports the use of the NIH OMS and its components (erythema, lichenoid and ulcerations) to measure clinician-reported severity of oral cGVHD.

Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD. Out of 189 patients enrolled, 125 met the criteria for severe cGVHD on the NIH global score, 62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned average NIH organ score and the corresponding organ scores assigned by subspecialists were highly correlated (r = 0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale, 2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung involvement affected function and quality of life most significantly and showed the greatest correlation with outcome measures. The final Cox model with factors jointly predictive for survival included the time from cGVHD diagnosis (>49 versus ≤49 months, hazard ratio [HR] = 0.23; P = .0011), absolute eosinophil count at the time of NIH evaluation (0-0.5 versus >0.5 cells/μL, HR = 3.95; P = .0006), and NIH lung score (3 versus 0-2, HR = 11.02; P < .0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH organ and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex subspecialist examinations. In this population of severely affected patients, NIH lung score is the strongest predictor of poor overall survival, both alone and after adjustment for other important factors., (Published by Elsevier Inc.)

Purpose: Chronic graft-versus-host disease (cGVHD) is a severe immunological complication that occurs after allogeneic hematopoietic stem cell transplantation (HSCT). Although oral cGVHD occurs in >25% of cGVHD patients and leads to decreased quality of life, its etiology is poorly understood. The present retrospective cross-sectional analysis of oral cGVHD patients sought to (1) test the feasibility of liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify protein biomarkers of oral cGVHD and (2) to gain a clearer understanding of salivary proteins impacted by oral cGVHD., Methods: Using unstimulated whole saliva, we compared pooled saliva from five patients with a diagnosis of moderate or severe oral cGVHD, with a gender-and age- matched pool of five cGVHD patients with no oral mucosal findings. LC-MS/MS was used to identify salivary proteins, followed by Ingenuity Pathway Analysis (IPA). Selected mass spectrometric findings, including lactotransferrin, lactoperoxidase, and albumin, were confirmed by targeted label-free quantification., Results: LC-MS/MS led to confident identification of 180 proteins. Of these proteins, 102 changed in abundance at least 2 fold, including 12 proteins identified only in the No oral cGVHD group. Downregulation of ~0.4 fold was confirmed for both lactotransferrin and lactoperoxidase in Oral cGVHD saliva using targeted label-free quantification. IPA analysis implicated pathways involved in cellular metabolism and immunoregulation., Conclusions: Reduction of salivary lactoperoxidase, lactotransferrin, and several cysteine proteinase inhibitor family proteins suggests impaired oral antimicrobial host immunity in cGVHD patients. This shotgun proteomic analysis of oral cGVHD saliva using targeted label-free quantification of select proteins supports the use of mass spectrometry for future validation in a large patient population as noninvasive tests for screening, early detection, and monitoring of cGVHD.

Chronic graft-vs.-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Oral cGVHD is manifested by mucosal, salivary, and/or sclerotic changes that have been linked to pain and poor quality of life. Our aim was to describe the demographic, clinical, and laboratory markers of oral cGVHD in alloHSCT patients (N = 187) enrolled in a cGVHD cross-sectional study at the NIH (#NCT00331968). We propose a meaningful and reproducible measure of disease defined by a cut-off point reflecting clinical minimally detectable change (0-2 = no oral cGVHD, 3-15 = oral cGVHD) on the 15-point NIH cGVHD clinician assessment scale. Forty-four patients had oral cGVHD. Oral cGVHD was associated with a quiescent or de novo type of cGVHD onset (p = 0.05), higher cGVHD severity (p = 0.033), lower albumin (p = 0.0008), higher total complement (p = 0.012), greater bother from foods or oral ulcers and greater mouth pain, and sensitivity (p < 0.0001). Multivariable logistic regression modeling with albumin, mouth pain, and total complement was 74.3% predictive of oral cGVHD and 80.2% predictive of non-oral cGVHD. We propose the use of >2 points on the NIH scale as a reproducible definition of clinically significant oral cGVHD, which may be useful in clinical settings or as eligibility criterion or as an endpoint in clinical trials.

Objectives: To investigate the associations between the assignment of an oral hygiene aide staff member and risk factors for mortality from pneumonia in a nursing home and to test the hypothesis that this care would affect the incidence of mortality from pneumonia., Design: Electronic medical records., Setting: Nursing home., Participants: One hundred forty-three residents of a Veterans Affairs Medical Center (VAMC) nursing home., Methods: The electronic medical records of 143 residents of a VAMC nursing home were analyzed for risk factors for pneumonia. A certified nursing assistant had been assigned to provide oral hygiene care for residents on two of four nursing home wards. Researchers performed a longitudinal analysis of resident's medical records to investigate the association between the assignment of an oral hygiene aide with the risk of mortality from pneumonia., Results: Initially, the group that received oral care, an older and less functionally able group, showed approximately the same incidence of mortality from pneumonia as the group that did not receive oral care, but when the data were adjusted for the risk factors found to be significant for mortality from pneumonia, the odds of dying from pneumonia in the group that did not receive oral care was more than three times that of the group that did receive oral care (odds ratio=3.57, P=.03). Modified risk factors included age, functionality, cognitive function, and clinical concern about aspiration pneumonia., Conclusion: Oral hygiene nursing aide intervention may be an efficient risk factor modifier of mortality from nursing home-associated pneumonia.

Periodontitis and type 2 diabetes are co-morbid conditions, both characterized by infectious susceptibility. We investigated procalcitonin (ProCT) levels in the serum and saliva of persons with periodontitis and type 2 diabetes (n = 20), to determine if these levels are altered by periodontitis activity or by hyperglycemia. Persons with severe periodontitis showed higher levels of salivary-ProCT than did those with moderate periodontitis (241 +/- 71 vs. 77 +/- 516 pg/mL, p = 0.02) and higher levels than did healthy control individuals (118 +/- 26 pg/mL, p = 0.05). Salivary-ProCT levels were correlated with bleeding-on-probing (r = 0.45, p = 0.05), as well as with HgbA(1c) (r = 0.49, p = 0.03). Salivary levels of ProCT were higher than serum levels for the periodontitis/diabetes group (152 +/- 37 vs. 78 +/- 17 pg/mL, p = 0.02) and the control group (118 +/- 146 vs. 48 +/- 17 pg/mL, p = 0.01). Persons with periodontitis and type 2 diabetes have salivary-ProCT levels that reflect their degree of periodontitis activity and hyperglycemia. This study demonstrates, for the first time, the presence of procalcitonin (ProCT), an established serum marker of infection, in saliva.