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1.  The Relationship between Fuchs' Endothelial Corneal Dystrophy Severity and Glaucoma and/or Ocular Hypertension 
Archives of ophthalmology  2012;130(11):1384-1388.
Objective
To investigate if Fuchs' Endothelial Corneal Dystrophy (FECD) severity is associated with glaucoma and/or ocular hypertension (G/OHTN).
Methods
A subset of eyes (n=1610) from the FECD Genetics Multi-Center Study were examined to estimate the association between FECD severity (grades 0–6 based on guttae confluence) and G/OHTN. Logistic regression models were fit that accounted for the correlation between eyes and adjusted for age, sex, central corneal thickness, intraocular pressure, presence of diabetes, and time of day of initial evaluation.
Results
107 eyes (6.6%) had G/OHTN based on the study definition. The prevalence of G/OHTN in the control group was 6%. Prevalence was lower in index cases with an FECD grade of 1 through 3 and family members with a grade of 0 or 1 through 3 (0% and 2%, respectively) but higher in index cases and family members with a grade of 4 through 6 (11% and 9%, respectively). Adjusting for covariates, eyes with a grade of 4 through 6 were more likely to have concurrent G/OHTN than eyes with no FECD (index cases vs. controls: OR=2.10, p=0.04; affected vs. unaffected family: OR=7.06, p=0.07). Age (OR=1.06 per 1 year increase, p<0.001) and intraocular pressure (OR=1.15 per 1 mmHg increase, p<0.001) were also associated with an increased prevalence of G/OHTN. Sex, diabetes, time of day of evaluation, and central corneal thickness were not associated with the prevalence of G/OHTN (p>0.15).
Conclusions
Glaucoma and/or ocular hypertension occurs more often in eyes affected with severe FECD compared to unaffected eyes. Therefore, it may be beneficial to monitor for the development of glaucoma in these patients.
doi:10.1001/archophthalmol.2012.1969
PMCID: PMC3954552  PMID: 22777534
2.  Relationship of Fuchs’ Endothelial Corneal Dystrophy Severity to Central Corneal Thickness 
Archives of ophthalmology  2012;130(4):10.1001/archophthalmol.2011.1626.
Objective
To define the relationship between Fuchs’ endothelial corneal dystrophy (FECD) severity and central corneal thickness (CCT).
Methods
Eyes from a subset of index cases, family members, and unrelated controls with normal corneas from the FECD Genetics Multi-Center Study (n=1610) were examined. To estimate the association between FECD severity grade (7-point severity scale based on guttae confluence) and CCT measured by ultrasonic pachymetry, a multivariable model was used that adjusted for eye, age, race, gender, glaucoma or ocular hypertension history, diabetes, contact lens wear, intraocular pressure and familial relationship to index case. An interaction between FECD severity grade and edema (stromal or epithelial) on slit lamp examination was used to investigate if the effect of FECD severity grade on CCT differed between those with and without edema.
Results
Average CCT was thicker in index cases for all FECD grades compared to unaffected controls (p ≤ 0.003) and in affected family members with an FECD grade of 4 or greater compared to unaffected family members (p ≤ 0.04). Similar results were observed for subjects without edema. Average CCT of index cases was greater than that of affected family members for grades 4, 5 and 6 (p ≤ 0.02). Intraocular pressure was also associated with CCT (p<0.01).
Conclusions
An increase in CCT occurs with increasing severity of FECD, including at lower FECD grades where clinically observable edema is not present. Monitoring corneal thickness changes serially could be a more sensitive measure of disease progression with surgical therapeutic implications.
doi:10.1001/archophthalmol.2011.1626
PMCID: PMC3859299  PMID: 22491913
3.  Effect of Nadir CD4+ T Cell Count on Clinical Measures of Periodontal Disease in HIV+ Adults before and during Immune Reconstitution on HAART  
PLoS ONE  2013;8(10):e76986.
Background
The contribution of HIV-infection to periodontal disease (PD) is poorly understood.  We proposed that immunological markers would be associated with improved clinical measures of PD.
Methods
We performed a longitudinal cohort study of HIV-infected adults who had started highly active antiretroviral therapy (HAART) <2 years. PD was characterized clinically as the percent of teeth with ≥1 site with periodontal probing depth (PPD) ≥5.0mm, recession (REC) >0mm, clinical attachment level (CAL) ≥4.0mm, and bleeding on probing (BOP) at ≥4 sites/tooth and microbiologically as specific periodontopathogen concentration. Linear mixed-effects models were used to assess the associations between immune function and PD.
Results
Forty (40) subjects with median 2.7 months on HAART and median nadir CD4+ T-cell count of 212 cells/μl completed a median 3 visits. Over 24 months, CD4+ T-cell count increased by a mean 173 cells/µl (p<0.001) and HIV RNA decreased by 0.5 log10 copies/ml (p<0.001); concurrently, PPD, CAL and BOP decreased by a mean 11.7%, 12.1%, and 14.7% respectively (all p<0.001). Lower nadir CD4+ T-cell count was associated with worse baseline REC (-6.72%; p=0.04) and CAL (9.06%; p<0.001). Further, lower nadir CD4+ T-cell count was associated with a greater relative longitudinal improvement in PPD in subjects with higher baseline levels of Porphyromonas gingivalis (p=0.027), and BOP in subjects with higher baseline levels of Porphyromonas gingivalis or Treponema denticola (p=0.001 and p=0.006 respectively). Longitudinal changes from baseline in CD4+ T-cell count and level of HIV RNA were not independently associated with longitudinal changes in any clinical markers of PD.
Conclusion
Degree of immunosuppression was associated with baseline gingival recession. After HAART initiation, measures of active PD improved most in those with lower nadir CD4+ T-cell counts and higher baseline levels of specific periodontopathogens. Nadir CD4+ T-cell count differentially influences periodontal disease both before and after HAART in HIV-infected adults.
doi:10.1371/journal.pone.0076986
PMCID: PMC3795634  PMID: 24146949
4.  Relation Between Sleep Duration and BMI Varies by Age and Sex in Youth Age 8–19 
Pediatric Obesity  2011;7(1):53-64.
Objectives
The objectives of this study were to 1) compare the strength of associations between sleep duration and BMI in middle childhood, early and late adolescence; 2) determine whether sleep duration in middle childhood predicts BMI in early or late adolescence; 3) examine the consistency of these associations by sex.
Methods
Subjects included 313 children/adolescents aged 8–19 participating in a longitudinal cohort study on sleep and health. Participants were assessed at three time points approximately 4 years apart: ages 8–11, 12–15 and 16–19. BMI z-score (BMIz) was calculated using age and sex normative data from the Centers for Disease Control. Sleep duration was reported by the parent (ages 8–15) or the adolescent (ages 16–19).
Results
Half of the participants were male and 79% were Caucasian. Sleep duration had a negative linear association with BMIz for boys but not girls, and the magnitude of this association decreased with age. Sleep duration at age 8–11 predicted BMIz in early and late adolescence for boys but not girls, and associations were largely attenuated after adjusting for BMIz at age 8–11. The strongest predictor of adolescent BMIz was BMIz at age 8–11 for both boys and girls.
Conclusions
We conclude that the association between sleep duration and BMIz varies by sex and age, with stronger associations in boys and in middle childhood compared to adolescence.
doi:10.1111/j.2047-6310.2011.00008.x
PMCID: PMC3313079  PMID: 22434739
Adolescents; BMI; Children; Obesity; Sleep
5.  Metabolic Complications are Common in Elderly Patients with Chronic Kidney Disease 
BACKGROUND/OBJECTIVES
Significant controversy exists as to the meaning of a low glomerular filtration rate (GFR) in the elderly. The goal of the study was to evaluate whether elderly patients with low GFR are at risk for anemia, hyperkalemia, acidosis, and hyperphosphatemia.
DESIGN
Retrospective study
SETTING
Veterans Affairs Medical Center
PARTICIPANTS
All patients over 65 years of age with chronic kidney disease (CKD) and a GFR between 15 and 60 mL/min/1.73m2.
MEASUREMENTS
Anemia was defined as a hemoglobin <10g/dL, hyperkalemia as a potassium >5.5mEq/L, acidosis as a bicarbonate <21mEq/L, and hyperphosphatemia as a phosphorus >4.6mg/dL. Multivariable logistic regression was used to evaluate whether age modifies the effect of low GFR on metabolic complications by including an interaction term between age and GFR in each model.
RESULTS
13874 veterans were included in the study. The average age was 79, the average GFR was 46.5; 3.1% had anemia, 2.5% hyperkalemia, 2.3% acidosis, and 4.4% had hyperphosphatemia. Lower GFR was associated with increased rates of metabolic complications across all age groups (odds ratio per 5mL/min/1.73m2 decrease in GFR in multivariable models was 1.21 for anemia, 1.26 for hyperkalemia, 1.45 for acidosis, and 1.72 for hyperphosphatemia). There was no significant interaction between age and GFR in models including only age and GFR or in multivariable models (p values for the age X GFR interaction term: 0.66 for anemia, 0.19 for hyperkalemia, 0.54 for acidosis, and 0.22 for hyperphosphatemia).
CONCLUSION
Elderly patients with CKD are at risk for anemia, hyperkalemia, acidosis, and hyperphosphatemia; age does not modify the relationship between GFR and development of metabolic complications. Elderly patients with low GFR should be monitored for metabolic complications, regardless of age.
doi:10.1111/j.1532-5415.2011.03818.x
PMCID: PMC3527008  PMID: 22283563
chronic renal insufficiency; aging; anemia; hyperkalemia; acidosis; hyperphosphatemia
6.  A Prospective Cohort Study of Periodontal Disease Measures and Cardiovascular Disease Markers in HIV-Infected Adults 
AIDS Research and Human Retroviruses  2011;27(11):1157-1166.
Abstract
The determinants of HIV-associated cardiovascular disease (CVD) are not well understood. Periodontal disease (PD) has been linked to CVD but this connection has not been examined in HIV infection. We followed a cohort of HIV-infected adults to ascertain whether PD was associated with carotid artery intima media thickness (IMT) and brachial artery flow-mediated dilation (FMD). We performed a longitudinal observational study of HIV-infected adults on HAART for <2 years with no known heart disease. PD was characterized clinically and microbiologically. Cardiovascular disease was assessed by IMT/FMD. Linear mixed models assessed cross-sectional and longitudinal associations between PD and FMD/IMT. Forty three HIV+ adults completed a median of 24 (6–44) months on the study. Defining delta to be the change in a variable between baseline and a follow-up time, longitudinally, on average and after adjusting for change in time, CVD-specific and HIV-specific potential confounding covariates, a 1-log10 increase in delta Porphyromonas gingivalis was associated with a 0.013 mm increase in delta IMT (95% CI: 0.0006–0.0262; p=0.04). After adjusting for the same potential confounding covariates, a 10% increase in delta gingival recession was associated with a 2.3% increase in delta FMD (95% CI: 0.4–4.2; p=0.03). In a cohort of HIV-infected adults, an increase in subgingival Porphyromonas gingivalis, a known periodontal pathogen, was significantly associated with longitudinal increases in IMT, while increased gingival recession, which herein may represent PD resolution, was significantly associated with longitudinal improvement in FMD. In the context of HIV infection, PD may contribute to CVD risk. Intervention studies treating PD may help clarify this association.
doi:10.1089/aid.2010.0320
PMCID: PMC3206743  PMID: 21443451
7.  Sleep-disordered Breathing and Prothrombotic Biomarkers 
Rationale: Individuals with sleep-disordered breathing (SDB) are at increased cardiovascular risk, possibly due to SDB-related stresses contributing to atherosclerosis.
Objectives: We postulate that pathways associated with a prothrombotic potential are up-regulated in SDB.
Methods: Morning and evening plasminogen activator inhibitor-1 (PAI-1), morning fibrinogen, and morning D-dimer were measured in 537 Cleveland Family Study adults. Piecewise multivariable linear mixed models estimated relative mean change or mean change in the biomarker per 5-unit increase in apnea-hypopnea index (AHI) in two groups: AHI less than 15 and AHI greater than or equal to 15, and hypoxia defined as percentage of sleep time with SaO2 less than 90% (< 2%, ≥ 2%).
Measurements and Main Results: Nonlinear associations were demonstrated: morning and evening PAI-1 increased by 12% (95% confidence interval [CI], 5–20%; P < 0.001) and 11% (95% CI, 2–20%; P = 0.01), respectively per 5-unit AHI increase until an AHI of 15, when no further increase in PAI-1 was demonstrated. The association between AHI and morning PAI-1 remained significant after adjusting for evening PAI-1 level (10%; 95% CI, 3–17%; P < 0.01). Morning fibrinogen increased on average by 8.4 mg/dl (95% CI, 3.12–13.65; P = 0.002) per five-unit AHI increase until an AHI of 15. There was no association between AHI and morning D-dimer. Hypoxia severity was not associated with thrombotic marker levels.
Conclusions: PAI-1 and fibrinogen levels increase monotonically with AHI at degrees of SDB considered mildly to moderately abnormal, suggesting that even mild SDB levels may increase prothrombotic processes. There may be a plateau in this effect, occurring at levels considered to reflect only moderate SDB severity. These relationships with mild-to-moderate SDB were not observed with D-dimer.
doi:10.1164/rccm.201001-0020OC
PMCID: PMC2949407  PMID: 20508215
sleep apnea; thrombosis; cardiovascular disease

Results 1-7 (7)