Publications by authors named "Christopher A Andrews"

36 Publications

Vismodegib for Preservation of Visual Function in Patients with Advanced Periocular Basal Cell Carcinoma: The VISORB Trial.

Oncologist 2021 May 14. Epub 2021 May 14.

Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA.

Background: Basal cell carcinoma (BCC) is a common skin cancer often curable by excision; however, for patients with BCC around the eye, excision places visual organs and function at risk. In this article, we test the hypothesis that use of the hedgehog inhibitor vismodegib will improve vision-related outcomes in patients with orbital and extensive periocular BCC (opBCC).

Materials And Methods: In this open-label, nonrandomized phase IV trial, we enrolled patients with globe- and lacrimal drainage system-threatening opBCC. To assess visual function in the context of invasive periorbital and lacrimal disease, we used a novel Visual Assessment Weighted Score (VAWS) in addition to standard ophthalmic exams. Primary endpoint was VAWS with a score of 21/50 (or greater) considered successful, signifying globe preservation. Tumor response was evaluated using RECIST v1.1. Surgical specimens were examined histologically by dermatopathologists.

Results: In 34 patients with opBCC, mean VAWS was 44/50 at baseline, 46/50 at 3 months, and 47/50 at 12 months or postsurgery. In total, 100% of patients maintained successful VAWS outcome at study endpoint. Compared with baseline, 3% (95% confidence interval [CI], 0.1-15.3) experienced major score decline (5+ points), 14.7% (95% CI, 5 to 31.1) experienced a minor decline (2-4 points), and 79.4% experienced a stable or improved score (95% CI, 62.1-91.3). A total of 56% (19) of patients demonstrated complete tumor regression by physical examination, and 47% (16) had complete regression by MRI/CT. A total of 79.4% (27) of patients underwent surgery, of which 67% (18) had no histologic evidence of disease, 22% (6) had residual disease with clear margins, and 11% (3) had residual disease extending to margins.

Conclusion: Vismodegib treatment, primary or neoadjuvant, preserves globe and visual function in patients with opBCC. Clinical trail identification number.NCT02436408.

Implications For Practice: Use of the antihedgehog inhibitor vismodegib resulted in preservation of end-organ function, specifically with regard to preservation of the eye and lacrimal apparatus when treating extensive periocular basal cell carcinoma. Vismodegib as a neoadjuvant also maximized clinical benefit while minimizing toxic side effects. This is the first prospective clinical trial to demonstrate efficacy of neoadjuvant antihedgehog therapy for locally advanced periocular basal cell carcinoma, and the first such trial to demonstrate end-organ preservation.
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http://dx.doi.org/10.1002/onco.13820DOI Listing
May 2021

Predicting rapid progression phases in glaucoma using a soft voting ensemble classifier exploiting Kalman filtering.

Health Care Manag Sci 2021 May 13. Epub 2021 May 13.

Kellogg Eye Institute, Ann Arbor, MI, 48105, USA.

In managing patients with chronic diseases, such as open angle glaucoma (OAG), the case treated in this paper, medical tests capture the disease phase (e.g. regression, stability, progression, etc.) the patient is currently in. When medical tests have low residual variability (e.g. empirical difference between the patient's true and recorded value is small) they can effectively, without the use of sophisticated methods, identify the patient's current disease phase; however, when medical tests have moderate to high residual variability this may not be the case. This paper presents a framework for handling the latter case. The framework presented integrates the outputs of interacting multiple model Kalman filtering with supervised learning classification. The purpose of this integration is to estimate the true values of patients' disease metrics by allowing for rapid and non-rapid phases; and dynamically adapting to changes in these values over time. We apply our framework to classifying whether a patient with OAG will experience rapid progression over the next two or three years from the time of classification. The performance (AUC) of our model increased by approximately 7% (increased from 0.752 to 0.819) when the Kalman filtering results were incorporated as additional features in the supervised learning model. These results suggest the combination of filters and statistical learning methods in clinical health has significant benefits. Although this paper applies our methodology to OAG, the methodology developed is applicable to other chronic conditions.
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http://dx.doi.org/10.1007/s10729-021-09564-2DOI Listing
May 2021

Plasma 25-Hydroxyvitamin D Concentrations and Serum and Salivary C-Reactive Protein in the Osteoporosis and Periodontal Disease Study.

Nutrients 2021 Mar 31;13(4). Epub 2021 Mar 31.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, State University of New York, Buffalo, NY 14214, USA.

Vitamin D has been hypothesized to play an important role in preventing the development and progression of periodontal disease, but the underlying immune modulatory mechanisms remain understudied. We examined the cross-sectional association between biomarkers of vitamin D status and C-reactive protein (CRP) among postmenopausal women aged 53-81 years. Linear regression was used to examine the association between plasma 25-hydroxyvitamin D (25[OH]D) concentrations, a biomarker of vitamin D status, and both salivary and serum CRP concentrations in 567 women from the Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) Study (1997-2000). CRP concentrations were measured with multiplex arrays and transformed for normality using the natural log. Concentrations above and below the limit of detection were included in analysis as right- and left-censored observations. An inverse association was observed between 25(OH)D and salivary CRP in a model adjusted for age, smoking status, frequency of tooth brushing and flossing, and hormone therapy use (-7.56% difference in salivary CRP concentrations per 10 nmol/L increase in 25(OH)D, 95% CI: -12.78 to -2.03). Further adjustment for percent body fat attenuated this association (-2.48%, 95% CI: -7.88 to 3.24). No significant associations were found between 25(OH)D and serum CRP. Plasma vitamin D concentrations were not associated with salivary or serum CRP concentrations in this cohort of postmenopausal women.
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http://dx.doi.org/10.3390/nu13041148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067277PMC
March 2021

Subgingival microbiome is associated with alveolar bone loss measured 5 years later in postmenopausal women.

J Periodontol 2021 May 3;92(5):648-661. Epub 2020 Nov 3.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo - SUNY, Buffalo, New York, USA.

Background: The aim of this study was to quantify the association between subgingival microbiota and periodontal disease progression in older women, for which limited published data exist.

Methods: A total of 1016 postmenopausal women, aged 53 to 81 years, completed baseline (1997 to 2001) and 5-year (2002 to 2006) dental exams that included probing depth, clinical attachment level, gingival bleeding, and radiographic alveolar crestal height (ACH). Baseline microbiota were measured in subgingival plaque using 16S rRNA sequencing. Associations between 52 microbiota we previously found statistically significantly associated with clinical periodontal disease at baseline, were examined with disease progression. The traditional Socransky microbiota complexes also were evaluated. Side-by-side radiograph comparisons were used to define progression as ≥2 teeth with ≥1 mm ACH loss or ≥1 new tooth loss to periodontitis. The association between baseline centered log(2) ratio transformed microbial relative abundances and 5-year periodontal disease progression was measured with generalized linear models.

Results: Of 36 microbiota we previously showed were elevated in moderate/severe disease at baseline, 24 had statistically significantly higher baseline mean relative abundance in progressing compared with non-progressing women (P < .05, all); which included all Socransky red bacteria (P. gingivalis, T. forsythia, T. denticola). Of 16 microbiota elevated in none/mild disease at baseline, five had statistically significantly lower baseline abundance in non-progressing compared with progressing women (P < 0.05, all), including one Socransky yellow bacteria (S. oralis). When adjusted for baseline age, socioeconomic status, and self-rated general health status, odds ratios for 5-year progression ranged from 1.18 to 1.51 (per 1-standard deviation increment in relative abundance) for microbiota statistically significantly (P < 0.05) positively associated with progression, and from 0.77 to 0.82 for those statistically significantly (P < 0.05) inversely associated with progression. These associations were similar when stratified on baseline levels of pocket depth, gingival bleeding, ACH, and smoking status.

Conclusions: These prospective results affirm clearly that subgingival microbiota are measurably elevated several years prior to progression of alveolar bone loss, and include antecedent elevations in previously undocumented taxa additional to known Socransky pathogenic complexes.
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http://dx.doi.org/10.1002/JPER.20-0445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089116PMC
May 2021

The association between serum inflammatory biomarkers and incident hypertension among postmenopausal women in the Buffalo OsteoPerio Study.

J Hum Hypertens 2020 Oct 7. Epub 2020 Oct 7.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, State University of New York, Buffalo, NY, USA.

Several serum inflammatory biomarkers have been associated with blood pressure and hypertension prevalence in cross-sectional studies. Few of these associations have been evaluated prospectively. We examined associations for 10 serum inflammatory biomarkers with incident hypertension among 471 postmenopausal women (mean age = 65) in the Buffalo OsteoPerio Study. Concentrations of C-reactive protein, interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein (MCP)-1, adiponectin, and leptin were measured using multiplexed sandwich immunoassays on fasting serum samples collected at baseline (1997-2001). Incident hypertension (195 cases) was defined as physician-diagnosed hypertension and treatment with medication identified on annual mailed health surveys during follow-up (mean 10 years). Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) between log-transformed biomarkers (per 1-SD) and hypertension. When adjusted for age, leptin was significantly associated with hypertension risk (HR = 1.55, 95% CI: 1.04, 2.29), however, the association was attenuated and not significant after adjustment for demographic and lifestyle factors, including BMI. Significant (P < 0.10) interactions were observed for smoking (never, ever) with CRP (HR: never, 1.31; ever, 0.91; P = 0.06) and MCP-1 (HR: never, 0.59; ever, 5.11; P = 0.004); for BMI (<25, ≥25) with MCP-1(HR: <25, 3.45; ≥25, 0.95; P = 0.07); for systolic BP with IL-10 (HR: <120, 0.85; 120-139, 1.11; P = 0.07); and for diastolic BP with MCP-1 (HR: <80, 1.29; 80-89, 0.84; P = 0.03) and with adiponectin (HR: <80, 0.86; 80-89, 1.50; P = 0.03). This study adds needed understanding on prospective associations between several serum inflammatory biomarkers and hypertension risk in older postmenopausal women, among whom hypertension burden is substantial.
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http://dx.doi.org/10.1038/s41371-020-00422-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024412PMC
October 2020

Walking Volume and Speed Are Inversely Associated With Incidence of Treated Hypertension in Postmenopausal Women.

Hypertension 2020 11 28;76(5):1435-1443. Epub 2020 Sep 28.

From the Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo-SUNY, NY (C.R.M., J.W.-W., K.M.H., M.J.L.).

Few studies have evaluated hypertension incidence in relation to walking, which is a common physical activity among adults. We examined the association between walking and hypertension incidence in 83 435 postmenopausal women who at baseline were aged 50 to 79 years, without known hypertension, heart failure, coronary heart disease, or stroke, and reported the ability to walk at least one block without assistance. Walking volume (metabolic equivalent hours per week) and speed (miles per hour) were assessed by questionnaire. Incident physician-diagnosed hypertension treated with medication was ascertained through annual questionnaires. During a mean 11-year follow-up, 38 230 hypertension cases were identified. After adjustment for covariates including nonwalking activities, a significant inverse association with hypertension was observed across categories of baseline walking volume (0 [referent], >0-3.5, 3.6-7.5, and >7.5 metabolic equivalent hours per week), hazard ratio: 1.00 (referent), 0.98, 0.95, 0.89; trend <0.001. Faster walking speeds (<2, 2-3, 3-4, and >4 miles per hour) also were associated with lower hypertension risk, hazard ratio: 1.00 (referent), 1.07, 0.95, 0.86, 0.79; trend <0.001. Further adjustment for walking duration (h/wk) had little impact on the association for walking speed (hazard ratio: 1.00 [referent], 1.08, 0.96, 0.86, 0.77; trend <0.001). Significant inverse associations for walking volume and speed persisted after additional control for baseline blood pressure. Results for time-varying walking were comparable to those for baseline exposures. This study showed that walking at guideline-recommended volumes (>7.5 metabolic equivalent hours per week) and at faster speeds (≥2 miles per hour) is associated with lower hypertension risk in postmenopausal women. Walking should be encouraged as part of hypertension prevention in older adults.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544673PMC
November 2020

Association of Dietary Magnesium Intake with Fatal Coronary Heart Disease and Sudden Cardiac Death.

J Womens Health (Larchmt) 2020 01 12;29(1):7-12. Epub 2019 Dec 12.

Department of Family Medicine, Alpert Medical School of Brown University, Pawtucket, Rhode Island.

Postmenopausal women represent the highest population-based burden of cardiovascular disease, including sudden cardiac death (SCD). Our understanding of the etiology and risk factors contributing to fatal coronary heart disease (CHD) and SCD, particularly among women, is limited. This study examines the association between dietary magnesium intake and fatal CHD and SCD. We examined 153,569 postmenopausal women who participated in the Women's Health Initiative recruited between 1993 and 1998. Magnesium intake at baseline was assessed using a validated food frequency questionnaire, adjusting for energy via the residual method. Fatal CHD and SCD were identified over an average follow-up of 10.5 years. For every standard deviation increase in magnesium intake, there was statistically significant risk reduction, after adjustment for confounders, of 7% for fatal CHD (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.89-0.97), and 18% risk reduction for SCD (HR 0.82, 95% CI 0.58-1.15) the latter of which did not reach statistical significance. In age-adjusted quartile analysis, women with the lowest magnesium intake (189 mg/day) had the greatest risk for fatal CHD (HR 1.54, 95% CI 1.40-1.69) and SCD (HR 1.70, 95% CI 0.94-3.07). This association was attenuated in the fully adjusted model, with HRs of 1.19 (95% CI 1.06-1.34) for CHD and 1.24 (95% CI 0.58-2.65) for SCD for the lowest quartile of magnesium intake. This study provides evidence of a potential inverse association between dietary magnesium and fatal CHD and a trend of magnesium with SCD in postmenopausal women. Future studies should confirm this association and consider clinical trials to test whether magnesium supplementation could reduce fatal CHD in high-risk individuals.
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http://dx.doi.org/10.1089/jwh.2019.7775DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6983733PMC
January 2020

Composition and diversity of the subgingival microbiome and its relationship with age in postmenopausal women: an epidemiologic investigation.

BMC Oral Health 2019 11 13;19(1):246. Epub 2019 Nov 13.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, 270 Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA.

Background: The extent to which the composition and diversity of the oral microbiome varies with age is not clearly understood.

Methods: The 16S rRNA gene of subgingival plaque in 1219 women, aged 53-81 years, was sequenced and its taxonomy annotated against the Human Oral Microbiome Database (v.14.5). Composition of the subgingival microbiome was described in terms of centered log(2)-ratio (CLR) transformed OTU values, relative abundance, and prevalence. Correlations between microbiota abundance and age were evelauted using Pearson Product Moment correlations. P-values were corrected for multiple testing using the Bonferroni method.

Results: Of the 267 species identified overall, Veillonella dispar was the most abundant bacteria when described by CLR OTU (mean 8.3) or relative abundance (mean 8.9%); whereas Streptococcus oralis, Veillonella dispar and Veillonella parvula were most prevalent (100%, all) when described as being present at any amount. Linear correlations between age and several CLR OTUs (Pearson r = - 0.18 to 0.18), of which 82 (31%) achieved statistical significance (P < 0.05). The correlations lost significance following Bonferroni correction. Twelve species that differed across age groups (each corrected P < 0.05); 5 (42%) were higher in women ages 50-59 compared to ≥70 (corrected P < 0.05), and 7 (48%) were higher in women 70 years and older.

Conclusions: We identified associations between several bacterial species and age across the age range of postmenopausal women studied. Understanding the functions of these bacteria could identify intervention targets to enhance oral health in later life.
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http://dx.doi.org/10.1186/s12903-019-0906-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854792PMC
November 2019

Serum Vitamin D Deficiency Is an Independent Risk Factor for Thyroid Eye Disease.

Ophthalmic Plast Reconstr Surg 2020 Jan/Feb;36(1):17-20

Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan.

Purpose: Thyroid eye disease (TED) is an inflammatory orbitopathy with significant impact on visual function and quality of life. Although studies have shown that patients who are deficient in vitamin D are more likely to develop autoimmune conditions, there are no studies demonstrating a definitive correlation between serum 25-hydroxyvitamin D (25(OH)D) deficiency and an increased risk of TED.

Methods: This retrospective case-control study compared serum 25(OH)D levels among 4 groups: 1) Graves disease (GD) patients with TED (n = 89); 2) GD patients without TED (n = 89); and healthy control patients matched to 3) the TED group (n = 356); and 4) the GD group (n = 356). The authors compared 25(OH)D level in the TED group measured within 1 year of TED diagnosis to the most recently measured 25(OH)D level in the GD group using Student t test of the log transformation of serum levels. Linear regression was used to control for other risk factors. Thyroid eye disease patients and GD patients were compared separately to their matched healthy control patients with linear mixed models.

Results: Thyroid eye disease patients displayed significantly lower serum 25(OH)D levels than GD patients (24.8 ± 13.2 ng/ml vs. 29.4 ± 13.3 ng/ml; p = 0.006). Controlling for smoking status and previous radioactive iodine treatment did not affect this statistically significant difference.

Conclusions: Low serum vitamin D is associated with TED diagnosis. Assessing and supplementing vitamin D levels may be an important addition to the early management of GD patients. Future research should include longitudinal studies and prospective clinical trials to further explore the mechanism responsible for the observed association.Thyroid eye disease is an inflammatory orbitopathy associated with Graves disease. Vitamin D is a known immune system regulator. The authors show that vitamin D deficiency is associated with the development of thyroid eye disease.
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http://dx.doi.org/10.1097/IOP.0000000000001437DOI Listing
March 2021

Is the Oral Microbiome Associated with Blood Pressure in Older Women?

High Blood Press Cardiovasc Prev 2019 Jun 24;26(3):217-225. Epub 2019 Jun 24.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, 273 Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA.

Introduction: A possible role of the oral microbiome, specifically oral nitrate reducing flora, in blood pressure (BP) homeostasis, if proven etiologic in nature, could lead to novel mechanism-based therapy to improve hypertension prevention and control.

Aim: This cross-sectional study characterized and compared the oral microbiome between four study groups based on BP status among 446 postmenopausal women aged 53-82 years.

Methods: Three study groups were not taking hypertension medication and were separated based on BP, as follows: normal BP (systolic < 120 and diastolic < 80; N = 179), elevated BP/Stage I hypertension (systolic 120-139 or diastolic 80-90; N = 106), Stage II hypertension (systolic > 140 or diastolic > 90; N = 42). The forth group consisted of anyone taking hypertension medications, regardless of BP (N = 119). Subgingival microbiome composition was determined using 16S rRNA sequencing with the Illumina MiSeq platform. Kruskal-Wallis tests were used to compare species-level relative abundance of bacterial operational taxonomic units across the four groups.

Results: Sixty-five bacterial species demonstrated significant differences in relative abundance in women with elevated BP or using hypertension medication as compared to those with normal BP. After correction for multiple testing, two species, Prevotella oral (species 317) and Streptococcus oralis, remained significant and were lower in abundance among women taking antihypertension medications compared to those with normal BP (corrected P < 0.05).

Conclusions: These data provide novel description of oral subgingival bacteria grouped according to BP status. Additional larger studies including functional analysis and prospective designs will help further assess the potential role of the oral microbiome in BP regulation and hypertension.
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http://dx.doi.org/10.1007/s40292-019-00322-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610722PMC
June 2019

Serum 25-Hydroxyvitamin D Concentrations and Incidence of Age-Related Macular Degeneration: The Atherosclerosis Risk in Communities Study.

Invest Ophthalmol Vis Sci 2019 04;60(5):1362-1371

Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, The University of Wisconsin-Madison, Madison, Wisconsin, United States.

Purpose: To investigate the association between serum 25-hydroxyvitamin D (25[OH]D) concentrations at visit 2 (1990-1992) and the 18-year incidence of age-related macular degeneration (AMD) between visit 3 (1993-1995) and visit 5 (2011-2013).

Methods: This prospective analysis was conducted in a subset of participants (n = 1225) from the Atherosclerosis Risk in Communities Study. We evaluated the incidence of any, early, and late AMD from visit 3 to 5. The 25(OH)D concentrations were assessed in 2012-2013 by using stored serum from visit 2. Retinal fundus photographs taken at both visits were graded side by side to determine the incidence of AMD. Logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for incident AMD outcomes during 18 years of follow-up (1993-1995 to 2011-2013) by tertile of 25(OH)D adjusted for age, race, and smoking status. P for linear trend was estimated by using continuous 25(OH)D concentrations. Sensitivity analyses applied inverse probability weights to account for selection to have eye photographs, death, and loss to follow-up.

Results: There was a decreased odds of any incident AMD (n = 139) and large, soft drusen (n = 80) in 25(OH)D tertile 3 versus 1, with OR (95% CI) = 0.57 (0.36-0.90), P trend = 0.11 and with 0.52 (0.28-0.93), P trend = 0.18, respectively. Applying sampling weights attenuated these results to 0.66 (0.38-1.16), P trend = 0.32 (any incident AMD) and 0.54 (0.27-1.09), P trend = 0.36 (large, soft drusen), respectively, suggesting these associations may be biased by loss to follow-up and sampling for retinal photographs at visit 5. No statistically significant results were observed with pigmentary abnormalities (n = 46) or incident late AMD (n = 26).

Conclusions: High 25(OH)D concentrations, approximately >70 nM, may be associated with decreased odds of incident early AMD.
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http://dx.doi.org/10.1167/iovs.18-25945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892376PMC
April 2019

Orbital Septum Fibrosis in Congenital Ptosis Correlates With Eyelid Function: A Clinicopathologic Study.

Ophthalmic Plast Reconstr Surg 2019 Sep/Oct;35(5):469-473

Department of Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, U.S.A.

Purpose: Congenital ptosis can threaten visual function and is usually treated with surgical correction. This study tests the hypothesis that congenital ptosis involves not only the levator muscle but also the orbital septum, which may tether the eyelid in the primary position.

Methods: A retrospective chart review was performed on 30 patients (41 eyelids) with congenital ptosis who underwent surgical correction that included partial septum excision. Histologic analysis was performed by a masked pediatric pathologist, with grading of septal tissue disorganization and fibrosis based on standard histologic criteria. An independent comparison of histologic grading with clinical ptosis measures was then performed.

Results: Fifteen eyelids demonstrated significant septal fibrosis, 19 were mild, and 7 were not fibrotic. Thirty-six eyelids demonstrated histologic disorganization. Mildly fibrotic eyelids were found to have reduced preoperative levator function than those that were not fibrotic (2.84 ± 1.92 vs. 9.57 ± 4.76 mm; p < 0.0001). Samples that demonstrated significant fibrosis were also found to have reduced preoperative levator function (4.67 ± 2.12 vs. 9.57 ± 4.76 mm; p = 0.0007). Histologically disorganized samples were also found to have a lower preoperative levator function (9.50 ± 6.04 vs. 3.99 ± 2.49; p = 0.0052).

Conclusions: Orbital septae in patients with congenital ptosis demonstrate histologic disorganization and fibrosis. When decreased levator function is observed clinically, septal fibrosis and/or disorganization is likely present. These observations suggest that debulking the fibrotic septum during congenital ptosis surgery may improve outcomes by releasing the eyelid from its congenitally tethered position, improving eyelid elasticity.
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http://dx.doi.org/10.1097/IOP.0000000000001330DOI Listing
January 2020

Cohort profile: the Buffalo OsteoPerio microbiome prospective cohort study.

BMJ Open 2018 12 4;8(12):e024263. Epub 2018 Dec 4.

Department of Epidemiology and Environmental Health, University at Buffalo, The State University of New York, Buffalo, New York, USA.

Purpose: The Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) study is a prospective cohort study focused on the relationship between the microbiome and oral and systemic health outcomes in postmenopausal women. The cohort was established to examine how the oral microbiome is affected by (and how it affects) periodontal disease presence, severity and progression and to characterise the relationship between the microbiome, lifestyle habits and systemic disease outcomes.

Participants: Participants (n=1342) were postmenopausal women who were participating in the Women's Health Initiative observational study at the Buffalo, New York clinical centre. There were 1026 participants at the 5-year follow-up visit and 518 at the 15-year visit.

Findings To Date: Data collected include questionnaires, anthropometric measures, serum blood and saliva samples. At each clinic visit, participants completed a comprehensive oral examination to measure oral health and the oral microbiome. Preliminary findings have contributed to our understanding of risk factors for periodontal disease and the relationship between the oral microbiome and periodontal disease.

Future Plans: The novel microbiome data collected on a large sample of participants at three time points will be used to answer a variety of research questions focused on temporal changes in the microbiome and the relationship between the oral microbiome and oral and systemic disease outcomes. Little is currently known about the relationship between the oral microbiome and health outcomes in older adults; data from the OsteoPerio cohort will fill this gap. Microbiome samples are currently being analysed using next-generation sequencing technology with an anticipated completion date of late 2018.
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http://dx.doi.org/10.1136/bmjopen-2018-024263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286477PMC
December 2018

Substantial Differences in the Subgingival Microbiome Measured by 16S Metagenomics According to Periodontitis Status in Older Women.

Dent J (Basel) 2018 Oct 19;6(4). Epub 2018 Oct 19.

Department of Epidemiology and Environmental Health, University at Buffalo, 270 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA.

Aging invokes physiological changes, such as immunosenescence and inflammation, that could increase host susceptibility to oral microbiome shifts that enable periodontitis progression in later life. At present, there is a dearth of studies specifically evaluating the oral microbiome and periodontitis in older adults. We used high-throughput untargeted sequencing methods and functional metagenomic analyses to assess and compare the subgingival biofilm of postmenopausal women (mean age 71 years) according to periodontitis status. Subgingival plaque samples were obtained from 15 postmenopausal women with no periodontitis, and from 15 women with severe periodontitis, determined by probing measures. The 16S rRNA gene (V1⁻V3 region) was sequenced on the 454 FLX platform. The PICRUSt technique was used to provide information on what the potential functional characteristics of microbiota might be in healthy, compared with diseased, periodontium. The subgingival microbiome associated with periodontitis showed clear differences to that associated with health. Of the 464 species identified, 22.8% had elevated abundance in disease, while only 6.3% had elevated abundance in health. Among the 12 most prevalent organisms in periodontitis, one-half have previously been recognized as periodontal pathogens by other investigators. The subgingival microbiome in periodontitis contained genes that could code for specific activities, including microbial mobility, synthesis of endotoxin, and proteolytic degradation. The healthy microbiome included genes that could code for sustaining microbial life, including encoding for transporters, glycolysis, gluconeogenesis, the Krebs cycle, and protein kinases. In the present study on postmenopausal women, aged 60 and older, the subgingival microbiome differed in composition and potential function between those with and without periodontitis. Studies of functional gene expression, such as transcriptomics, are needed to definitively identify the molecules carrying out functions associated with pathogenic subgingival complexes. This, in turn, could lead to identification of targets for enhanced management of periodontitis and, possibly, other diseases, in later life.
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http://dx.doi.org/10.3390/dj6040058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313419PMC
October 2018

Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the Women's Health Initiative Observational Study.

Menopause 2018 Jan;25(1):11-20

Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Objective: To determine the association between use of vaginal estrogen and risk of a global index event (GIE), defined as time to first occurrence of coronary heart disease (CHD), invasive breast cancer, stroke, pulmonary embolism, hip fracture, colorectal cancer, endometrial cancer, or death from any cause.

Methods: For this prospective observational cohort study, we used data from participants of the Women's Health Initiative Observational Study, who were recruited at 40 US clinical centers, aged 50 to 79 years at baseline and did not use systemic estrogen therapy during follow-up (n = 45,663, median follow-up 7.2 years). We collected data regarding incident CHD, invasive breast cancer, stroke, pulmonary embolism, hip fracture, colorectal cancer, endometrial cancer, death, and self-reported use of vaginal estrogen (cream, tablet). We used Cox proportional-hazards regression models to adjust for covariates.

Results: Among women with an intact uterus, the risks of stroke, invasive breast cancer, colorectal cancer, endometrial cancer, and pulmonary embolism/deep vein thrombosis were not significantly different between vaginal estrogen users and nonusers, whereas the risks of CHD, fracture, all-cause mortality, and GIE were lower in users than in nonusers (GIE adjusted hazard ratio 0.68, 95% confidence interval 0.55-0.86). Among hysterectomized women, the risks of each of the individual GIE components and of the overall GIE were not significantly different in users versus nonusers of vaginal estrogen (GIE adjusted hazard ratio 0.94, 95% confidence interval 0.70-1.26).

Conclusions: The risks of cardiovascular disease and cancer were not elevated among postmenopausal women using vaginal estrogens, providing reassurance about the safety of treatment.
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http://dx.doi.org/10.1097/GME.0000000000000956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5734988PMC
January 2018

History of Periodontitis Diagnosis and Edentulism as Predictors of Cardiovascular Disease, Stroke, and Mortality in Postmenopausal Women.

J Am Heart Assoc 2017 Mar 29;6(4). Epub 2017 Mar 29.

Department of Epidemiology and Environmental Health, University at Buffalo, NY.

Background: Few studies have reported associations between periodontitis and cardiovascular disease (CVD) risk in older women, which is the objective of the present investigation.

Methods And Results: Participants were 57 001 postmenopausal women ages 55 to 89 years (mean 68 years; >85% 60 and older) who were enrolled (1993-1998) in the Women's Health Initiative Observational Study, and were without known CVD when history of periodontitis and edentulism was assessed by questionnaire at study Year-5 (1998-2003). There were 3589 incident CVD events and 3816 total deaths during a mean follow-up of 6.7 years. In multivariable analysis, periodontitis was not associated with CVD events, but was associated with higher total mortality (hazard ratio (HR)=1.12, 95% CI: 1.05-1.21). Edentulism was associated with higher age- and smoking-adjusted risks of CVD (HR=1.42, 95% CI: 1.27-1.59) and mortality (HR=1.47, 95% CI: 1.32-1.63). Further adjustment eliminated the association with CVD, but mortality remained significantly increased (HR=1.17, 95% CI: 1.02-1.33). Stratification on age, race-ethnicity, smoking, and diabetes mellitus yielded comparable results; however, edentulism was more strongly associated with CVD in women reporting ≥1 dental visit (HR=1.57) compared with <1 visit (HR 1.03, interaction =0.004) annually.

Conclusions: In community-dwelling older women, edentulism was associated with increased risks of CVD and total mortality, and presence of periodontitis, which is more prevalent than edentulism, was associated with 17% higher mortality rate. These findings suggest that improving periodontal condition of the general population could reduce overall mortality.
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http://dx.doi.org/10.1161/JAHA.116.004518DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532989PMC
March 2017

Adequate vitamin D status is associated with the reduced odds of prevalent diabetic retinopathy in African Americans and Caucasians.

Cardiovasc Diabetol 2016 09 1;15(1):128. Epub 2016 Sep 1.

Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, The University of Wisconsin-Madison, Madison, WI, USA.

Background: Vitamin D status has been hypothesized to protect against development of diabetic retinopathy via its anti-inflammatory and anti-angiogenic properties. Additionally, in vitro and in vivo studies suggest vitamin D favorably influences blood pressure and blood glucose control, strong risk factors for diabetic retinopathy. We examined the association between vitamin D status and prevalent diabetic retinopathy in participants with diabetes from a population-based cohort.

Methods: Among participants in the Atherosclerosis Risk in Communities (ARIC) study with diabetes at visit 3 (1993-1995), 1339 (906 Caucasians, 433 African Americans) had serum 25-hydroxyvitamin (25[OH]D) concentrations assessed at visit 2 (1989-1992) and nonmydriatic retinal photographs taken at visit 3. Dietary intake of vitamin D was assessed at visit 1 (1987-1989). Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for diabetic retinopathy by categories of season-adjusted 25(OH)D (<30 [referent], 30-<50, 50-<75 and ≥75 nmol/L), by quartile of vitamin D intake (IU/day), and use of vitamin D or fish oil supplements (yes/no). P for trend was estimated using continuous 25(OH)D or vitamin D intake. ORs were adjusted for race, and duration of diabetes. We further adjusted for HBA1c and hypertension to examine if 25(OH)D influenced diabetic retinopathy via its effects on either glycemic control or blood pressure.

Results: ORs (95 % CIs) for retinopathy, adjusted for race and duration, were 0.77 (0.45-1.32), 0.64 (0.37-1.10), and 0.39 (0.20-0.75), p for trend = 0.001, for participants with 25(OH)D of 30-<50, 50-<75, and ≥75 nmol/L, respectively. Further adjustment for hypertension minimally influenced results (data not show), but adjustment for HBA1c attenuated the OR among those with 25(OH)D ≥75 (0.47 [0.23-0.96], p for trend = 0.030). No statistically significant association was observed between vitamin D intake from foods or supplements and retinopathy.

Conclusions: 25(OH)D concentrations ≥75 nmol/L were associated with lower odds of any retinopathy assessed 3 years later. We speculate this may be due in part to vitamin D's influence on blood glucose control.
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http://dx.doi.org/10.1186/s12933-016-0434-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5009647PMC
September 2016

Optimism, Cynical Hostility, Falls, and Fractures: The Women's Health Initiative Observational Study (WHI-OS).

J Bone Miner Res 2017 Feb 20;32(2):221-229. Epub 2016 Sep 20.

Vanderbilt University Medical Center, Nashville, TN, USA.

Traits of optimism and cynical hostility are features of personality that could influence the risk of falls and fractures by influencing risk-taking behaviors, health behaviors, or inflammation. To test the hypothesis that personality influences falls and fracture risk, we studied 87,342 women enrolled in WHI-OS. Optimism was assessed by the Life Orientation Test-Revised and cynical hostility, the cynicism subscale of the Cook-Medley questionnaire. Higher scores indicate greater optimism and hostility. Optimism and hostility were correlated at r = -0. 31, p < 0.001. Annual self-report of falling ≥2 times in the past year was modeled using repeated measures logistic regression. Cox proportional hazards models were used for the fracture outcomes. We examined the risk of falls and fractures across the quartiles (Q) of optimism and hostility with tests for trends; Q1 formed the referent group. The average follow-up for fractures was 11.4 years and for falls was 7.6 years. In multivariable (MV)-adjusted models, women with the highest optimism scores (Q4) were 11% less likely to report ≥2 falls in the past year (odds ratio [OR] = 0.89; 95% confidence intervals [CI] 0.85-0.90). Women in Q4 for hostility had a 12% higher risk of ≥2 falls (OR = 1.12; 95% CI 1.07-1.17). Higher optimism scores were also associated with a 10% lower risk of fractures, but this association was attenuated in MV models. Women with the greatest hostility (Q4) had a modest increased risk of any fracture (MV-adjusted hazard ratio = 1. 05; 95% CI 1.01-1.09), but there was no association with specific fracture sites. In conclusion, optimism was independently associated with a decreased risk of ≥2 falls, and hostility with an increased risk of ≥2 falls, independent of traditional risk factors. The magnitude of the association was similar to aging 5 years. Whether interventions aimed at attitudes could reduce fall risks remains to be determined. © 2016 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.2984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7079733PMC
February 2017

EZH2, Proliferation Rate, and Aggressive Tumor Subtypes in Cutaneous Basal Cell Carcinoma.

JAMA Oncol 2016 07;2(7):962-3

Department of Ophthalmology and Visual Sciences, W. K. Kellogg Eye Center, Ann Arbor, Michigan3Comprehensive Cancer Center, University of Michigan, Ann Arbor.

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http://dx.doi.org/10.1001/jamaoncol.2016.0021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945394PMC
July 2016

Periodontal Disease and Breast Cancer: Prospective Cohort Study of Postmenopausal Women.

Cancer Epidemiol Biomarkers Prev 2016 Jan 21;25(1):43-50. Epub 2015 Dec 21.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, State University of New York, Buffalo, New York.

Background: Periodontal disease has been consistently associated with chronic disease; there are no large studies of breast cancer, although oral-associated microbes are present in breast tumors.

Methods: In the Women's Health Initiative Observational Study, a prospective cohort of postmenopausal women, 73,737 women without previous breast cancer were followed. Incident, primary, invasive breast tumors were verified by physician adjudication. Periodontal disease was by self-report. HRs and 95% confidence intervals (CI) were estimated by Cox proportional hazards, adjusted for breast cancer risk factors. Because the oral microbiome of those with periodontal disease differs with smoking status, we examined associations stratified by smoking.

Results: 2,124 incident, invasive breast cancer cases were identified after mean follow-up of 6.7 years. Periodontal disease, reported by 26.1% of women, was associated with increased breast cancer risk (HR 1.14; 95% CI, 1.03-1.26), particularly among former smokers who quit within 20 years (HR 1.36; 95% CI, 1.05-1.77). Among current smokers, the trend was similar (HR 1.32; 95% CI, 0.83-2.11); there were few cases (n = 74) and the CI included the null. The population attributable fraction was 12.06% (95% CI, 1.12-21.79) and 10.90% (95% CI, 10.31-28.94) for periodontal disease among former smokers quitting within 20 years and current smokers, respectively.

Conclusion: Periodontal disease, a common chronic inflammatory disorder, was associated with increased risk of postmenopausal breast cancer, particularly among former smokers who quit in the past 20 years.

Impact: Understanding a possible role of the oral microbiome in breast carcinogenesis could impact prevention.
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http://dx.doi.org/10.1158/1055-9965.EPI-15-0750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713270PMC
January 2016

Periodontal disease severity and cancer risk in postmenopausal women: the Buffalo OsteoPerio Study.

Cancer Causes Control 2016 Feb 10;27(2):217-28. Epub 2015 Dec 10.

Department of Epidemiology and Environmental Health, University at Buffalo, State University of New York, Buffalo, NY, USA.

Purpose: Few prospective studies have reported on relationships between objective periodontal disease (PD) measures and cancer risk. This association was examined in 1,337 postmenopausal women participating in the Buffalo OsteoPerio Study.

Methods: Oral alveolar crestal height (ACH) was measured using oral radiographs. Incident cancers were adjudicated with medical records. Hazard ratios (HRs) and 95 % confidence intervals (CIs) for associations between ACH and incident cancer outcomes were estimated using Cox proportional hazards models.

Results: There were 203 confirmed total incident cancer cases during follow-up (12.2 ± 4.2 years). After adjusting for age and smoking, there were no statistically significant associations between ACH-defined PD categories and total cancer risk (mild/moderate vs. none: HR 1.33, 95 % CI 0.91-1.94; severe vs. none: HR 1.20, 95 % CI 0.77-1.86). ACH-defined PD categories were not associated with common site-specific cancers. Whole-mouth mean and worst-site ACH (per 1 mm loss) were significantly associated with increased risk of lung (adjusted HR 1.81, 95 % CI 1.30-2.54; adjusted HR 1.34, 95 % CI 1.08-1.66, respectively), but not total or other site-specific cancer. Smoking status modified the associations between continuous ACH variables and total cancer risk; measures of PD were associated with total cancer among smokers but not never smokers (interaction p = 0.02 and p < 0.01 for whole-mouth mean and worst-site ACH, respectively).

Conclusions: ACH-defined PD was associated with total cancer risk in ever but not never smoking postmenopausal women. Whole-mouth mean and worst-site ACH were associated with increased lung cancer risk. However, these results need to be interpreted cautiously given the small number of lung cancer cases (n = 18). Further research utilizing a larger sample is warranted to confirm the relationships among oral bone loss, site-specific cancers, and total cancer.
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http://dx.doi.org/10.1007/s10552-015-0699-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724219PMC
February 2016

Periodontal Pathogens and Risk of Incident Cancer in Postmenopausal Females: The Buffalo OsteoPerio Study.

J Periodontol 2016 Mar 29;87(3):257-67. Epub 2015 Oct 29.

Department of Epidemiology and Environmental Health, University at Buffalo, State University of New York, Buffalo, NY.

Background: Extraoral translocation of oral bacteria may contribute to associations between periodontal disease and cancer. The associations among the presence of three orange-complex periodontal pathogens (Fusobacterium nucleatum, Prevotella intermedia, and Campylobacter rectus), two red-complex periodontal pathogens (Porphyromonas gingivalis and Tannerella forsythia), and cancer risk were investigated.

Methods: A total of 1,252 postmenopausal females enrolled in the Buffalo Osteoporosis and Periodontal Disease Study were followed prospectively. Baseline subgingival plaque samples were assessed for the presence of periodontal pathogens using indirect immunofluorescence. Incident cancer cases were adjudicated by staff physicians via review of medical records. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of periodontal pathogens with total cancer and site-specific cancer risk in unadjusted and multivariable-adjusted models.

Results: Neither the presence of individual pathogens nor the presence of any red-complex pathogens was associated with total cancer or site-specific cancers. Borderline associations were seen among the presence of any orange-complex pathogens (F. nucleatum, P. intermedia, and C. rectus), total cancer risk (HR = 1.35, 95% CI = 1.00 to 1.84), and lung cancer risk (HR = 3.02, 95% CI = 0.98 to 9.29).

Conclusions: No associations were found between the presence of individual subgingival pathogens and cancer risk. However, there were suggestions of borderline positive associations of the presence of any orange-complex pathogens with total cancer and lung cancer risk. The study is limited by the small number of cancer cases and the assessment of only five oral bacteria. Additional research is needed to understand the possible role of periodontal disease in carcinogenesis.
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http://dx.doi.org/10.1902/jop.2015.150433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915107PMC
March 2016

Bone Mineral Density as a Predictor of Subsequent Wrist Fractures: Findings From the Women's Health Initiative Study.

J Clin Endocrinol Metab 2015 Nov 14;100(11):4315-24. Epub 2015 Sep 14.

Department of Medicine (C.J.C.), David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90024; Department of Epidemiology and Environmental Health (K.M.H., J.W.-W.), State University of New York at Buffalo, Buffalo, New York 14260; Department of Ophthalmology and Visual Sciences (C.A.A.), University of Michigan, Ann Arbor, Michigan 48109; Department of Epidemiology (J.A.C.), Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261; Division of Preventive Medicine (J.E.M.) and Department of Medicine, Endocrine, Diabetes and Hypertension Division (M.S.L.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02467; Department of Epidemiology (N.C.W.) and Division of Clinical Immunology and Rheumatology (J.R.C.), University of Alabama at Birmingham, Birmingham, Alabama 35294; Division of Preventive and Behavioral Medicine (W.L.), University of Massachusetts Medical School, Worcester, Massachusetts 01655; and Department of Health and Exercise Science (K.B.), Wake Forest University, Winston-Salem, North Carolina 27106.

Context: Wrist fractures are common among postmenopausal women. Associations of bone mineral density (BMD) and 10-year predicted risk of major osteoporotic fracture (MOF) with wrist fractures are poorly characterized.

Objective: The objective was to examine associations between the Fracture Risk Assessment Tool (FRAX)-predicted risk of MOF, BMD, BMD change, and wrist fracture.

Design: This was a prospective observational study with a mean follow-up of 8.5 years.

Setting: This study included 40 US centers.

Participants: A total of 11 392 participants from the Women's Health Initiative BMD Cohort aged 50-79 years at baseline were included in this study.

Interventions: None.

Main Outcome: The goal was to measure incident wrist fracture.

Results: A FRAX-predicted MOF risk ≥9.3% identified 17% of the women aged <65 years who subsequently experienced wrist fracture. Each one standard deviation lower BMD was associated with higher wrist fracture risk, with adjusted hazard ratio (95% confidence interval) of 1.66 (1.42-1.93) for femoral neck (FN) BMD and 1.45 (1.28-1.64) for lumbar spine BMD. Compared with FN BMD T score ≥ -1.0, wrist fracture adjusted hazard ratios (95% confidence interval) were: 1.51 (1.06-2.16) for a T score between -1.01 and -1.49; 1.93 (1.36-2.72) for T score between -1.50 and -1.99; 2.52 (1.77-3.60) for a T score between -2.00 and -2.49; and 2.65 (1.78-3.95) for a T score ≤ -2.5. Decrease in FN BMD between baseline and year 3 was associated with increased risk of subsequent wrist fracture; however, change in lumbar spine BMD was not.

Conclusions: Lumbar spine and femoral neck BMDs were associated with incident wrist fracture, but the FRAX threshold recommended to identify screening candidates did not identify the majority of women who subsequently experienced wrist fracture. Improved understanding of determinants of wrist fractures is warranted.
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http://dx.doi.org/10.1210/jc.2015-2568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702460PMC
November 2015

Wrist Fracture and Risk of Subsequent Fracture: Findings from the Women's Health Initiative Study.

J Bone Miner Res 2015 Nov 12;30(11):2086-95. Epub 2015 Jun 12.

Department of Medicine, Endocrine, Diabetes and Hypertension Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Wrist fractures are common in postmenopausal women and are associated with functional decline. Fracture patterns after wrist fracture are unclear. The goal of this study was to determine the frequency and types of fractures that occur after a wrist fracture among postmenopausal women. We carried out a post hoc analysis of data from the Women's Health Initiative Observational Study and Clinical Trials (1993-2010) carried out at 40 US clinical centers. Participants were postmenopausal women aged 50 to 79 years at baseline. Mean follow-up duration was 11.8 years. Main measures included incident wrist, clinical spine, humerus, upper extremity, lower extremity, hip, and total non-wrist fractures and bone mineral density (BMD) in a subset. Among women who experienced wrist fracture, 15.5% subsequently experienced non-wrist fracture. The hazard for non-wrist fractures was higher among women who had experienced previous wrist fracture than among women who had not experienced wrist fracture: non-wrist fracture overall (hazard ratio [HR] = 1.40, 95% confidence interval [CI] 1.33-1.48), spine (HR = 1.48, 95% CI 1.32-1.66), humerus (HR = 1.78, 95% CI 1.57-2.02), upper extremity (non-wrist) (HR = 1.88, 95% CI 1.70-2.07), lower extremity (non-hip) (HR = 1.36, 95% CI 1.26-1.48), and hip (HR = 1.50, 95% CI 1.32-1.71) fracture. Associations persisted after adjustment for BMD, physical activity, and other risk factors. Risk of non-wrist fracture was higher in women who were younger when they experienced wrist fracture (interaction p value 0.02). Associations between incident wrist fracture and subsequent non-wrist fracture did not vary by baseline BMD category (normal, low bone density, osteoporosis). A wrist fracture is associated with increased risk of subsequent hip, vertebral, upper extremity, and lower extremity fractures. There may be substantial missed opportunity for intervention in the large number of women who present with wrist fractures.
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http://dx.doi.org/10.1002/jbmr.2559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4615529PMC
November 2015

Urinary Tract Stones and Osteoporosis: Findings From the Women's Health Initiative.

J Bone Miner Res 2015 Nov 14;30(11):2096-102. Epub 2015 Jul 14.

Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.

Kidney and bladder stones (urinary tract stones) and osteoporosis are prevalent, serious conditions for postmenopausal women. Men with kidney stones are at increased risk of osteoporosis; however, the relationship of urinary tract stones to osteoporosis in postmenopausal women has not been established. The purpose of this study was to determine whether urinary tract stones are an independent risk factor for changes in bone mineral density (BMD) and incident fractures in women in the Women's Health Initiative (WHI). Data were obtained from 150,689 women in the Observational Study and Clinical Trials of the WHI with information on urinary tract stones status: 9856 of these women reported urinary tract stones at baseline and/or incident urinary tract stones during follow-up. Cox regression models were used to determine the association of urinary tract stones with incident fractures and linear mixed models were used to investigate the relationship of urinary tract stones with changes in BMD that occurred during WHI. Follow-up was over an average of 8 years. Models were adjusted for demographic and clinical factors, medication use, and dietary histories. In unadjusted models there was a significant association of urinary tract stones with incident total fractures (HR 1.10; 95% CI, 1.04 to 1.17). However, in covariate adjusted analyses, urinary tract stones were not significantly related to changes in BMD at any skeletal site or to incident fractures. In conclusion, urinary tract stones in postmenopausal women are not an independent risk factor for osteoporosis.
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http://dx.doi.org/10.1002/jbmr.2553DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618440PMC
November 2015

Statin use and risk of haemorrhagic stroke in a community-based cohort of postmenopausal women: an observational study from the Women's Health Initiative.

BMJ Open 2015 Feb 25;5(2):e007075. Epub 2015 Feb 25.

Division of Preventive Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, Massachusetts, USA.

Objectives: To determine whether statin treatment is associated with increased risk of haemorrhagic stroke (HS) in older women. A secondary objective was to evaluate HS risk in users of combined statin and antiplatelet treatment.

Design: Observational study: secondary data analysis from the Women's Health Initiative (WHI) clinical trials.

Setting: Women were recruited from 40 participating sites.

Participants: Cohort of 68,132 women followed through 2005 (parent study) and for an additional 5 years in the extension study.

Main Outcome Measures: Statin use was assessed at baseline and at follow-up visits (1, 3, 6 and 9 years). Women brought medications in original containers for inventory. Strokes were ascertained semiannually and centrally adjudicated. Risk of HS by statin use (time-varying covariate, with the 'no use' category as the referent) was estimated from Cox proportional hazard regression models adjusted for age (model 1); risk factors for HS (model 2); and possible confounders by indication (model 3). Prespecified subgroup analyses were conducted by use of antiplatelet medications.

Results: Final models included 67,882 women (mean age, 63±7 years). Over a mean follow-up of 12 years, incidence rates of HS were 6.4/10,000 person-years among statin users and 5.0/10,000 person-years among non-users (p=0.11). The unadjusted risk of HS in statin users was 1.21 (CI 0.96 to 1.53); after adjusting for age and HS risk factors the HR was 0.98 (CI 0.76 to 1.26). Risk of HS was higher among women on statins and antiplatelet agents versus women on antiplatelet medications alone (HR=1.59; CI 1.03 to 2.47); p for interaction=0.011.

Conclusions: This retrospective analysis did not show an association between statin use and HS risk among older women. HS risk was higher among women taking statins with antiplatelet agents. These findings warrant further investigation, given potential implications for clinical decision-making.
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http://dx.doi.org/10.1136/bmjopen-2014-007075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342587PMC
February 2015

History of periodontal disease diagnosis and lung cancer incidence in the Women's Health Initiative Observational Study.

Cancer Causes Control 2014 Aug 10;25(8):1045-53. Epub 2014 Jun 10.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, 270 Farber Hall, Buffalo, NY, 14214, USA,

Purpose: While some evidence suggests that periodontal disease (PD) might be positively associated with lung cancer, prospective studies in women are limited. Previous findings may reflect residual confounding by smoking. The study aims to determine whether history of PD diagnosis is associated with incident lung cancer in a large cohort of postmenopausal women.

Methods: Prospective analyses were conducted in a cohort of 77,485 postmenopausal women enrolled in the Women's Health Initiative Observational Study. History of PD (prevalence of 26.1 %) was self-reported, and 754 incident lung cancer cases occurred during an average 6.8 (SD ± 2.6) years of follow-up. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs).

Results: Overall, PD was positively associated with lung cancer risk after adjusting for detailed smoking history including smoking status and pack-years of smoking (HR 1.24, 95 % CI 1.07-1.45). There was a positive additive interaction between PD with pack-years of smoking (p = 0.02), suggesting a potential synergistic effect between PD and smoking intensity on lung cancer. The association between PD and lung cancer was stronger in former smokers. When restricted to never-smokers, PD was not associated with lung cancer (HR 1.02, 95 % CI 0.68-1.53).

Conclusions: Periodontal disease was not independently associated with lung cancer in non-smoking postmenopausal women. However, smoking and PD jointly increased lung cancer risk beyond that expected from the sum of the each effect separately. The potential synergism between PD and smoking on lung cancer warrants further examination.
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http://dx.doi.org/10.1007/s10552-014-0405-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117379PMC
August 2014

Association between metabolic syndrome and periodontal disease measures in postmenopausal women: the Buffalo OsteoPerio study.

J Periodontol 2014 Nov 26;85(11):1489-501. Epub 2014 May 26.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, State University of New York, Buffalo, NY.

Background: The objective of this study is to characterize the association between metabolic syndrome (MetS) and periodontitis in women, for which there is limited evidence.

Methods: Cross-sectional associations between MetS and periodontitis were examined in 657 postmenopausal women aged 50 to 79 years enrolled in a periodontal disease study ancillary to the Women's Health Initiative Observational Study. Whole-mouth measures of alveolar crest height (ACH), clinical attachment level (CAL), probing depth (PD), gingival bleeding, and supragingival plaque and measures to define MetS using National Cholesterol Education Program criteria were from a clinical examination. Study outcomes were defined as: 1) mean ACH ≥3 mm, two sites ≥5 mm, or tooth loss to periodontitis; 2) ≥2 sites with CAL ≥6 mm and ≥1 site with PD ≥5 mm; 3) gingival bleeding at ≥50% of sites; and 4) supragingival plaque at ≥50% of sites. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results: In unadjusted analyses, MetS (prevalence: 25.6%) was significantly associated with supragingival plaque (OR = 1.74; 95% CI: 1.22 to 2.50) and non-significantly associated with periodontitis defined by ACH (OR = 1.23; 95% CI: 0.81 to 1.85) and gingival bleeding (OR = 1.20; 95% CI: 0.81 to 1.77). Adjustment for age, smoking, and other confounders attenuated observed associations, though supragingival plaque remained significant (OR = 1.47; 95% CI: 1.00 to 2.16; P = 0.049). MetS was not associated with periodontitis defined by CAL and PD.

Conclusions: A consistent association between MetS and measures of periodontitis was not seen in this cohort of postmenopausal women. An association between MetS and supragingival plaque requires further investigation.
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http://dx.doi.org/10.1902/jop.2014.140185DOI Listing
November 2014

Vitamin D status and 5-year changes in periodontal disease measures among postmenopausal women: the Buffalo OsteoPerio Study.

J Periodontol 2014 Oct 2;85(10):1321-32. Epub 2014 May 2.

Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, University at Buffalo, The State University of New York, Buffalo, NY.

Background: Vitamin D is hypothesized to prevent periodontal disease progression through its immune-modulating properties and its role in maintaining systemic calcium concentrations. The authors investigated associations between plasma 25-hydroxyvitamin D [25(OH)D] (collected 1997 to 2000) and the 5-year change in periodontal disease measures from baseline (1997 to 2000) to follow-up (2002 to 2005) among 655 postmenopausal women in a Women's Health Initiative Observational Study ancillary study. Exploratory analyses were conducted in 628 women who also had 25(OH)D measures at follow-up.

Methods: Four continuous measures of the 5-year change in periodontal disease were assessed using alveolar crest height (ACH), clinical attachment level (CAL), probing depth (PD), and percentage of gingival sites that bled on assessment. Linear regression was used to estimate β-coefficients, standard errors, and P values corresponding to change in periodontal disease (a 1-mm change in ACH, CAL, or PD or a 1-unit change in the percentage of gingival sites that bled) for a 10-nmol/L difference in 25(OH)D. Models were adjusted for age, education, dental visit frequency, smoking, diabetes status, current medications affecting bone health, baseline measures of periodontal disease, body mass index, and recreational physical activity.

Results: No statistically significant associations were observed between baseline 25(OH)D and change in periodontal disease measures, overall or in a subset (n = 442) of women with stable 25(OH)D concentrations [25(OH)D change <20 nmol/L from baseline to follow-up]. RESULTS also did not vary significantly in analyses that were stratified by baseline periodontal disease status.

Conclusions: No association between baseline 25(OH)D and the subsequent 5-year change in periodontal disease measures was observed. Vitamin D status may not influence periodontal disease progression. More studies are needed to confirm these results.
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http://dx.doi.org/10.1902/jop.2014.130686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861231PMC
October 2014

Associations of lifetime active and passive smoking with spontaneous abortion, stillbirth and tubal ectopic pregnancy: a cross-sectional analysis of historical data from the Women's Health Initiative.

Tob Control 2015 Jul 26;24(4):328-35. Epub 2014 Feb 26.

Department of Social & Preventive Medicine, University at Buffalo School of Public Health & Health Professions, Buffalo, New York, USA.

Objective: To examine the associations between tobacco exposure and adverse pregnancy outcomes using quantitative measures of lifetime active smoking and secondhand smoke (SHS) exposure.

Methods: Historical reproductive data on 80 762 women who participated in the Women's Health Initiative Observational Study were examined with a cross-sectional analysis. We assessed self-reported lifetime active and passive tobacco smoke exposure, self-reported spontaneous abortions, stillbirths and ectopic pregnancies.

Results: When compared with never-smoking women, participants who were ever active smokers during their reproductive years had ORs (OR) of 1.16 (95% CI 1.08 to 1.26) for 1 or more spontaneous abortions, 1.44 (95% CI 1.20 to 1.73) for 1 or more stillbirths, and 1.43 (95% CI 1.10 to 1.86) for 1 or more ectopic pregnancies. Never-smoking women participants with the highest levels of lifetime SHS exposure, including childhood >10 years, adult home >20 years and adult work exposure >10 years, when compared with never-smoking women with no SHS exposure had adjusted ORs of 1.17 (95% CI 1.05 to 1.30) for spontaneous abortion, 1.55 (95% CI 1.21 to 1.97) for stillbirth, and 1.61 (95% CI 1.16 to 2.24) for ectopic pregnancy.

Conclusions: Women who were ever-smokers during their reproductive years had significantly greater estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy. Never-smoking women with the highest levels of lifetime exposure to SHS had significantly increased estimates of risk for spontaneous abortion, stillbirth and tubal ectopic pregnancy.
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http://dx.doi.org/10.1136/tobaccocontrol-2013-051458DOI Listing
July 2015