Cluster analysis to identify the profiles of individuals with compromised bone health versus unfortunate wrist fractures within the Canadian Longitudinal Study of Aging (CLSA) database.

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.

Barriers to oral care: a cross-sectional analysis of the Canadian longitudinal study on aging (CLSA).

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.

Salivary ZG16B expression loss follows exocrine gland dysfunction related to oral chronic graft-versus-host disease.

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.

Organ at Risk Dose Constraints in SABR: A Systematic Review of Active Clinical Trials.

PURPOSE: Organ at risk (OAR) dose constraints are a critical aspect of SABR treatment planning. There is limited evidence supporting preferred dose constraints for many OARs. We sought to evaluate OAR dose constraints used in ongoing clinical trials of SABR for oligometastatic disease. METHODS AND MATERIALS: Clinicaltrials.gov was searched from inception to February 2020 to capture actively accruing clinical trials using SABR in oligometastatic disease. Dose constraints were obtained by contacting principal investigators and abstracted by 2 authors. Variability of constraints was assessed by comparing the width of the interquartile range and difference between the maximum and minimum dose to a volume. RESULTS: Fifty-three of 85 eligible clinical trials contributed OAR constraints used in analysis. Dose constraints for 1 to 8 fractions of SABR were collected for 33 OARs. Variability was found in the absolute allowable OAR doses, use of planning OAR volumes, and whether constraints were optional versus mandatory. For many OARs, modal dose constraints often matched a pre-existing publication, but no single pre-existing publication matched the modes of all OAR dose constraints. Organs displaying the most variability were the rectum, penile bulb, and chest wall and ribs. The esophagus, stomach, duodenum, and small bowel also indicated high variability for at least 1 constraint. OARs previously evaluated by HyTEC appeared to have less variability among study protocols. CONCLUSIONS: We found substantial variability in OAR dose constraints used in current clinical trials evaluating SABR in oligometastatic disease. We are unable to comment on toxicity rates or acceptability of dose constraints used. Future research and recommendations for standardized OAR dose constraints, as well as consistency in implementing planning OAR volume margins, should be priorities for the field of radiation oncology.

A comprehensive analysis of factors related to lung function in older adults: Cross-sectional findings from the Canadian Longitudinal Study on Aging.

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 FEV1 and FEV1/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 FEV1 and FEV1/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.

Self-reported oral health at baseline of the Canadian Longitudinal Study on Aging.

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.

Dental abnormalities in individuals with pathogenic germline variation in DICER1.

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.

Cephalometry in adults and children with neurofibromatosis type 1: Implications for the pathogenesis of sphenoid wing dysplasia and the "NF1 facies".

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.

National Institutes of Health chronic graft-versus-host disease staging in severely affected patients: organ and global scoring correlate with established indicators of disease severity and prognosis.

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.

Quantitative salivary proteomic differences in oral chronic graft-versus-host disease.

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.

Modification of the risk of mortality from pneumonia with oral hygiene care.

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.