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1.  Driving with Pets as a Risk Factor for Motor Vehicle Collisions among Older Drivers 
Increasing rates of distraction-related motor vehicle collisions (MVCs) continue to raise concerns regarding driving safety. This study sought to evaluate a novel driving-related distraction, driving with a pet, as a risk factor for MVCs among older, community dwelling adults. Two thousand licensed drivers aged 70 and older were identified, of whom 691 reported pet ownership. Comparing pet owners who did and did not drive with their pets, neither overall MVC rates (rate ratio [RR] 0.97 95% confidence interval [CI] 0.75–1.26) nor at-fault MVC rates (RR 0.84 95% CI 0.57–1.24) were elevated. However, those who reported always driving with a pet in the vehicle had an elevated MVC rate (RR 1.89 95% CI 1.10–3.25), as compared to those who did not drive with a pet. The MVC rate was not increased for those reporting only sometimes or rarely driving with a pet in the vehicle. The current study demonstrates an increased risk of MVC involvement in those older drivers who always take a pet with them when they drive a vehicle. When confronted with an increased cognitive or physical workload while driving, elderly drivers in prior studies have exhibited slower cognitive performance and delayed response times in comparison to younger age groups. Further study of pet-related distracted driving behaviors among older drivers as well as younger populations with respect to driver safety and performance is warranted to appropriately inform the need for policy regulation on this issue.
doi:10.1016/j.aap.2013.04.019
PMCID: PMC4492539  PMID: 23708755
2.  The Driving Visual Field and a History of Motor Vehicle Collision Involvement in Older Drivers: A Population-Based Examination 
Purpose.
We designed a visual field test focused on the field utilized while driving to examine associations between field impairment and motor vehicle collision involvement in 2000 drivers aged 70 years or older.
Methods.
The “driving visual field test” involved measuring light sensitivity for 20 targets in each eye, extending 15° superiorly, 30° inferiorly, 60° temporally, and 30° nasally. The target locations were selected on the basis that they fell within the field region utilized when viewing through the windshield of a vehicle or viewing the dashboard while driving. Monocular fields were combined into a binocular field based on the more sensitive point from each eye. Severe impairment in the overall field or a region was defined as average sensitivity in the lowest quartile of sensitivity. At-fault collision involvement for 5 years prior to enrollment was obtained from state records. Poisson regression was used to calculate crude and adjusted rate ratios (RRs) examining the association between field impairment and at-fault collision involvement.
Results.
Drivers with severe binocular field impairment in the overall driving visual field had a 40% increased rate of at-fault collision involvement (RR, 1.40; 95% confidence interval [CI]: 1.07–1.83). Impairment in the lower and left fields was associated with elevated collision rates (RR, 1.40; 95% CI: 1.07–1.82 and RR, 1.49; 95% CI: 1.15–1.92, respectively), whereas impairment in the upper and right field regions was not.
Conclusions.
Results suggest that older drivers with severe impairment in the lower or left region of the driving visual field are more likely to have a history of at-fault collision involvement.
Older drivers with severe impairment in the lower or left region of the driving visual field are more likely to have a history of at-fault collision involvement.
doi:10.1167/iovs.14-15194
PMCID: PMC4288142  PMID: 25395488
aging; driving; visual field
3.  Eye Care Utilization among a High-Risk Diabetic Population Seen in a Public Hospital’s Clinics 
JAMA ophthalmology  2014;132(2):162-167.
Objective
Little is known regarding eye care utilization among low income persons with diabetes, especially African Americans.
Methods
A retrospective cohort study with two-years of follow-up examined eye care utilization among adult diabetes patients seen in 2007 in the internal medicine clinic of a large, urban, county hospital that serves primarily low income, non-Hispanic African American patients. Patients with a history of retinopathy and macular edema or a current diagnosis indicating ophthalmic complications were excluded. Eye care utilization was defined dichotomously as whether or not patients had a visit to the eye clinic for any eye care examination or procedure. We estimated crude and adjusted rate ratios (aRRs) and 95% confidence intervals (CIs) for the association between eye care utilization and selected clinical and demographic characteristics.
Results
There were 867 patients with diabetes identified: 61.9% women, 76.2% non-Hispanic African American, 61.3% indigent, and average age 51.8 years. Eye care utilization was 33.2% within one-year and 45.0% within two-years. For patients 19–39 years of age compared to those 65+ years, significantly decreased eye care utilization was observed within one-year (aRR=0.48, 95% CI 0.27–0.84) and within two-years (aRR=0.61, 95% CI 0.38–0.99).
Conclusions
Overall eye care utilization was low. Additional education efforts to increase the perception of need among urban minority populations may be enhanced if focused on younger people with diabetes.
doi:10.1001/jamaophthalmol.2013.6046
PMCID: PMC4479276  PMID: 24310149
diabetes; retinopathy; epidemiology; eye exam
4.  Feasibility and efficacy of diabetic retinopathy screening among youth with diabetes in a pediatric endocrinology clinic: a cross-sectional study 
Background
We examined the feasibility and efficacy of using a non-mydriatic camera to screen for diabetic retinopathy (DR) among youth with type 1 or type 2 diabetes seen in a pediatric endocrinology clinic serving Alabama, the state that has the highest diabetes rate in the United States.
Methods
236 youths with type 1 or type 2 diabetes were screened for DR using a non-mydriatic camera. Visual acuity was also assessed. A questionnaire asked parents about diabetes and eye care history.
Results
Mean duration since diabetes diagnosis was 5.5 years. 66 % reported receiving an eye examination within the previous year. 97.5 % had images that were gradable. DR was detected in 3.8 % of participants. 9.1 % were visually impaired.
Conclusions
Use of a non-mydriatic fundus camera is feasible and efficacious for DR screening in youth with diabetes. DR screening at routine endocrinology visits may be beneficial in managing youth with diabetes and preventing irreversible vision loss, particularly for those in regions where diabetes rates are high.
doi:10.1186/s13098-015-0054-z
PMCID: PMC4487844  PMID: 26136849
Diabetes mellitus; Diabetes complications; Diabetic retinopathy; Pediatrics; Visual acuity
5.  Ocular neovascularization in eyes with a central retinal artery occlusion or a branch retinal artery occlusion 
Purpose
To investigate the ocular neovascularization (ONV) rate in eyes with a branch retinal artery occlusion (BRAO) or a central retinal artery occlusion (CRAO), and to study factors that may influence the ONV rate secondary to CRAO.
Methods
This was a retrospective case series of consecutive patients (286 total eyes: 83 CRAOs and 203 BRAOs) who were diagnosed with a retinal artery occlusion from 1998 to 2013 at the Retina Consultants of Alabama and University of Alabama at Birmingham, Birmingham, AL, USA. Generalized estimating equations were used to evaluate the association between hypothesized risk factors and ONV development.
Results
Twelve (14.5%) of the 83 eyes with a CRAO developed ONV. Eleven of 12 eyes (91.7%) had iris neovascularization, ten of 12 eyes (83.3%) had neovascular glaucoma, and two of 12 eyes (16.7%) had neovascularization of the optic disc. The average time for ONV development secondary to CRAO was 30.7 days, ranging from the date of presentation to 137 days. Only two (<1.0%) of the 203 eyes with a BRAO developed iris neovascularization. Diabetes mellitus type 2 was a risk factor for ONV development following a CRAO with an adjusted odds ratio of 5.2 (95% confidence interval: 1.4–19.8) (P=0.02).
Conclusion
ONV is an important complication of CRAO and is a less-frequent complication of BRAO. Patients with a CRAO, especially those with diabetes mellitus type 2, should be closely monitored for the first 6 months for ONV.
doi:10.2147/OPTH.S82796
PMCID: PMC4467756  PMID: 26089631
neovascularization; neovascular glaucoma; retinal artery occlusion; central retinal artery occlusion; branch retinal artery occlusion; diabetes mellitus
6.  Association Between Vision Impairment and Driving Exposure in Older Adults Aged 70 Years and Over: A Population-Based Examination 
Acta ophthalmologica  2013;92(3):e207-e212.
Purpose
To examine the relationship between vision impairment and driving exposure (amount of driving one does) in a population-based sample of older drivers, and to examine to what extent cognitive status impacts this relationship.
Methods
Enrollees consisted of a population-based sample of older adults from Alabama who were ≥ 70 years old, held a current driver’s license, and had driven within the last 3 months. Three aspects of visual function were measured under binocular conditions – habitual distance visual acuity, contrast sensitivity, and visual processing speed. General cognitive status was assessed with the Mini-mental status examination. Driving exposure was estimated by the Driving Habits Questionnaire that asked about the number of miles, places, trips and days driven per week.
Results
Drivers with impaired contrast sensitivity exhibited reduced annual mileage, and a decreased number of places and trips driven per week compared to those with normal contrast sensitivity, even after adjustment for other factors. Slowed visual processing speed was associated with reduced number of days driven per week after adjustment. Visual acuity deficit was not associated with changes in driving exposure. Cognitive status did not impact any of the associations between vision impairment and driving exposure.
Conclusion
Older drivers with contrast sensitivity impairment exhibit reduced driving exposure in terms of number of trips and places they drive per week, as well as decreased annual mileage. These apparent self-regulatory practices should be viewed as adaptive since contrast sensitivity impairment elevates motor vehicle collision (MVC) risk and reduction in driving exposure can reduce MVC risk.
doi:10.1111/aos.12050
PMCID: PMC3720764  PMID: 23601553
driving; aging; vision impairment; visual acuity; contrast sensitivity; visual processing speed
7.  FcγRIIIa SNPs and haplotypes affect human IgG binding and association with lupus nephritis in African Americans 
Objective
To investigate whether the FcγRIIIa-66R/H/L polymorphism influences net effective receptor function and to assess if the FCGR3A combined genotypes formed by FcγRIIIa-66R/H/L and FcγRIIIa-176F/V as well as copy number variation (CNV) confer risk for development of SLE and lupus nephritis.
Methods
FcγRIIIa variants, expressed on A20 IIA1.6 cells, were used in flow cytometry-based human IgG binding assays. FCGR3A SNP and CNV genotypes were determined by Pyrosequencing methodology in a cohort of 1728 SLE patients and 2404 healthy controls.
Results
The FcγRIIIa-66L/H/R (rs10127939) polymorphism influences ligand binding capacity in the context of the FcγRIIIa-176V (rs396991) allele. The low binding FcγRIIIa-176F allele was associated with SLE nephritis (p = 0.0609) in African Americans but not in European Americans (p > 0.10). Nephritis among African American SLE subjects was associated with FcγRIIIa low binding haplotypes containing the 66R/H/L and 176F variants (p = 0.03) and with low binding genotype combinations (p = 0.002). No association was observed in European American SLE patients. The distribution of FCGR3A CNV was not significantly different between controls and SLE patients with or without nephritis.
Conclusion
FcγRIIIa-66R/H/L influences ligand binding. The low binding haplotypes formed by 66R/H/L and 176F confer enhanced risk for lupus nephritis in African Americans. FCGR3A CNVs are not associated with SLE or SLE nephritis in either African Americans or European Americans.
doi:10.1002/art.38337
PMCID: PMC4069204  PMID: 24782186
8.  Methyl-CpG-binding protein 2 (MEPC2) mutation type is associated with disease severity in Rett Syndrome 
Journal of medical genetics  2014;51(3):152-158.
Rett Syndrome (RTT), a neurodevelopmental disorder that primarily affects girls, is characterized by a period of apparently normal development until 6–18 months of age, when motor and communication abilities regress. More than 95% of people with RTT have mutations in Methyl-CpG-binding protein 2 (MECP2), whose protein product modulates gene transcription. Surprisingly, although the disorder is caused by mutations in a single gene, disease severity in affected individuals can be quite variable. To explore the source of this phenotypic variability, we propose that specific MECP2 mutations lead to different degrees of disease severity. Using a database of 1052 participants assessed over 4940 unique visits, the largest cohort of both typical and atypical RTT patients studied to date, we examined the relationship between MECP2 mutation status and measures of growth, motor coordination, communicative abilities, respiratory function, autonomic symptoms, scoliosis, and seizures over time. In general agreement with previous studies, we found that particular mutations, such as p.Arg133Cys, p.Arg294X, p.Arg306Cys, 3′ Truncations, and Other Point Mutations, were relatively less severe in both typical and atypical RTT. In contrast, p.Arg106Trp, p.Arg168X, p.Arg255X, p.Arg270X, Splice Sites, Large Deletions, Insertions, and Deletions were significantly more severe. We also demonstrated that, for most mutation types, clinical severity increases with age. Furthermore, of the clinical features of RTT, ambulation, hand use, and age at onset of stereotypies are strongly linked to overall disease severity. Thus, we have confirmed that MECP2 mutation type is a strong predictor of disease severity. However, clinical severity continues to become progressively worse with advancing age regardless of initial severity. These findings will allow clinicians and families to anticipate and prepare better for the needs of individuals with RTT.
doi:10.1136/jmedgenet-2013-102113
PMCID: PMC4403764  PMID: 24399845
genotype-phenotype; MeCP2; Rett syndrome; RTT
9.  Prevalence of and factors associated with distraction among public transit bus drivers 
Traffic injury prevention  2014;15(7):720-725.
Objective
Recent research has suggested that driver distraction is a major cause of driving performance impairment and motor vehicle collisions. Research on the topic has focused on passenger vehicles, with studies suggesting that drivers may be distracted nearly 33% of the time spent driving. To date, no study has examined the prevalence of distraction specifically among public transit bus drivers.
Methods
Over a three-month period, trained investigators observed and recorded distraction behaviors of bus drivers. Distraction prevalence was compared by route characteristics (e.g., geographic area, travel speed) using chi-square test. A general estimating equation logistic regression was used to estimate p-values for distraction prevalence by driver demographics.
Results
Overall, there was a 39% prevalence of distraction. The most prevalent distractions were due to interactions with another passenger. Distractions were more prevalent among drivers <30 years of age or ≥50 years of age, on city streets or highways (relative to residential streets), and when there were more than 20 passengers. Distractions were the least prevalent in suburban areas, with the highest prevalence observed in city centers and rural areas.
Conclusions
Driver distraction is a common problem for public transit bus drivers, mainly due to other passengers. Drivers should be educated on the hazards of distracted driving and on ways to avoid distraction.
doi:10.1080/15389588.2013.867482
PMCID: PMC4391701  PMID: 24433192
Bus; driver; distraction; prevalence; public transit
10.  Frequent Falling and Motor Vehicle Collision Involvement of Older Drivers 
OBJECTIVES
To examine the relationship between frequent falls in older drivers and motor vehicle collision (MVC) involvement.
DESIGN
Cross-sectional.
SETTING
North central Alabama.
PARTICIPANTS
Population-based sample of 2,000 licensed drivers aged 70 and older.
MEASUREMENTS
Self-reported history of falling two or more times in the prior year was the main predictor. Outcomes were any MVC or at-fault MVC in the prior year.
RESULTS
Approximately 9% of older drivers reported having fallen two or more times in the prior year. Logistic regression models indicated that frequent falling was associated with having any MVC (crude odds ratio (OR) = 1.53, 95% confidence interval (CI) = 0.77–3.02) and an at-fault MVC (OR = 2.21, 95% CI = 0.97–5.06). Adjustment for the potentially confounding effects of demographic, health, visual, and driving characteristics did not meaningfully affect the association with any MVC, whereas the association with at-fault MVC was weakened (adjusted OR = 2.03, 95% CI = 0.84–4.90).
CONCLUSION
Frequent falling was associated with at-fault MVC involvement of older drivers, especially whites. History of falling can be used to identify individuals at risk of MVC involvement and to begin a dialogue about driver safety. J Am Geriatr Soc 2013.
doi:10.1111/jgs.12594
PMCID: PMC4364607  PMID: 24279730
falls; aging; driver safety
11.  Associations Between Abnormal Rod-Mediated Dark Adaptation and Health and Functioning in Older Adults With Normal Macular Health 
Purpose.
Delayed rod-mediated dark adaptation (DA) is characteristic of early age-related macular degeneration (AMD) and also can be observed in some older adults in normal macular health. We examine cross-sectional associations between rod-mediated DA and risk factors for AMD in older adults in normal macular health.
Methods.
The sample consisted of adults aged ≥60 years old in normal macular health per grading of fundus photos using an established disease classification system. Rod-mediated DA was measured psychophysically following a photobleach using a computer-automated dark adaptometer with targets centered at 5° on the inferior vertical meridian. The speed of DA was characterized by the rod-intercept value, with abnormal DA defined as rod-intercept ≥ 12.3 minutes. We assessed several health and functional characteristics that the literature has suggested increase AMD risk (e.g., smoking, alcohol use, inflammatory markers, apolipoproteins, low luminance visual acuity, chronic medical conditions, body mass, family history).
Results.
Among 381 participants (mean age, 68.5 years; SD, 5.5), 78% had normal and 22% had abnormal DA, with the prevalence of abnormal DA increasing with age. After age-adjustment, abnormal DA was associated with increased odds of elevated C-reactive protein (CRP), heavy use of or abstention from alcohol, high blood pressure, and drop in visual acuity under mesopic conditions.
Conclusions.
Despite having normal macular health according to accepted definitions of AMD presence, approximately one-quarter of older adults recruited from primary eye care clinics had abnormal DA, which was associated with known risk factors for AMD, including elevated CRP.
Abnormal rod-mediated dark adaptation in older adults in normal macular health is associated with elevated plasma C-reactive protein levels.
doi:10.1167/iovs.14-14502
PMCID: PMC4122017  PMID: 24854857
aging; dark adaptation; rod function; age-related macular degeneration
12.  Quantitative Autofluorescence and Cell Density Maps of the Human Retinal Pigment Epithelium 
Purpose.
Lipofuscin (LF) accumulation within RPE cells is considered pathogenic in AMD. To test whether LF contributes to RPE cell loss in aging and to provide a cellular basis for fundus autofluorescence (AF) we created maps of human RPE cell number and histologic AF.
Methods.
Retinal pigment epithelium–Bruch's membrane flat mounts were prepared from 20 donor eyes (10 ≤ 51 and 10 > 80 years; postmortem: ≤4.2 hours; no retinal pathologies), preserving foveal position. Phalloidin-binding RPE cytoskeleton and LF-AF (488-nm excitation) were imaged at up to 90 predefined positions. Maps were assembled from 83,330 cells in 1470 locations. From Voronoi regions representing each cell, the number of neighbors, cell area, and total AF intensity normalized to an AF standard was determined.
Results.
Highly variable between individuals, RPE-AF increases significantly with age. A perifoveal ring of high AF mirrors rod photoreceptor topography and fundus-AF. Retinal pigment epithelium cell density peaks at the fovea, independent of age, yet no net RPE cell loss is detectable. The RPE monolayer undergoes considerable lifelong re-modeling. The relationship of cell size and AF, a surrogate for LF concentration, is orderly and linear in both groups. Autofluorescence topography differs distinctly from the topography of age-related rod loss.
Conclusions.
Digital maps of quantitative AF, cell density, and packing geometry provide metrics for cellular-resolution clinical imaging and model systems. The uncoupling of RPE LF content, cell number, and photoreceptor topography in aging challenges LF's role in AMD.
Simultaneous RPE cell density and autofluorescence maps of human donor eyes exhibit a significant increase in lipofuscin autofluorescence with age while RPE cell density remains stable, questioning lipofuscin's role in aging and AMD.
doi:10.1167/iovs.14-14802
PMCID: PMC4123894  PMID: 25034602
retinal pigment epithelium; autofluorescence; photoreceptor; lipofuscin; cytoskeleton
13.  Agreement in Assessing Cup-to-Disc Ratio Measurement Among Stereoscopic Optic Nerve Head Photographs, HRT II, and Stratus OCT 
Journal of glaucoma  2006;15(3):183-189.
Purpose
To compare the level of agreement between subjective and objective methods in estimating horizontal and vertical cupto-disc ratios (HCDR and VCDR, respectively) to determine if objective techniques may be used as surrogates for subjective cup-to-disc (CDR) estimation.
Methods
Fifty-one glaucoma patients and 49 control subjects underwent full ophthalmic examination, stereoscopic optic nerve head photographs (ONHPs), confocal scanning laser ophthalmoscopy (Heidelberg Retina Tomography II [HRT II]), and optical coherence tomography (Stratus OCT). The intra-class correlation coefficient (ICC) and Bland Altman plots were used to assess the agreement across the three methods. Repeated measures analysis of variance (ANOVA), Tukey adjustment, and pairwise P values were used to compare the HCDR and VCDR estimates between three clinicians who reviewed photos, Stratus OCT, and HRT II.
Results
For the clinicians, the agreement in subjectively assessed HCDR and VCDR was substantial (ICC = 0.84 and 0.85, respectively), and for all three methods, overall agreement was good (ICC = 0.75 and 0.77 for the HCDR and VCDR, respectively). Stratus OCT provided the largest overall mean ± SD HCDR (0.68 ± 0.14) and VCDR (0.62 ± 0.13). The smallest overall mean ± SD HCDR was provided by ONHP (0.32 ± 0.16), and the smallest overall mean ± SD VCDR was provided by HRT II (0.26 ± 0.20). Repeated measures ANOVA test demonstrated significant differences across the three methods for glaucomatous (P = 0.0017 and 0.0016, HCDR and VCDR, respectively) and normal (P = 0.0001 for both HCDR and VCDR) eyes. Tukey adjustment demonstrated specific statistical differences between pairs of methods.
Conclusions
Although the overall agreement between various methods was good, the mean estimates were statistically different. Additional studies are needed to evaluate the sources of variability, their level of significance, and longitudinal agreement between various methods of the CDR estimation.
doi:10.1097/01.ijg.0000212216.19804.ee
PMCID: PMC4302161  PMID: 16778638
cup-to-disc ratio; HRT II; Stratus OCT; stereoscopic optic nerve head photographs
14.  Patient versus parental perceptions about pain and disability in children and adolescents with a variety of chronic pain conditions 
BACKGROUND:
Cross-informant variance is often observed in patient self-reports versus parent proxy reports of pediatric chronic pain and disability.
OBJECTIVE:
To assess the relationship and merit of the child versus parent perspective.
METHODS:
A total of 99 patients (eight to 17 years of age [mean 13.2 years]; 71% female, 81% Caucasian) and parents completed the Pediatric Pain Questionnaire and Functional Disability Inventory at their initial clinic visit. Patients’ and parents’ pain intensity and disability scores were analyzed using an intraclass correlation coefficient (ICC), Wilcoxon signed-rank test, Bland-Altman plot and Spearman’s correlation coefficient. The association between clinical/demographic variables and differences in patient/parent pain intensity and disability scores was assessed using multivariable regression.
RESULTS:
There was significant agreement between patients’ self-reports and parents’ proxy reports of their child’s pain intensity (ICC=0.52; P<0.001) and disability (ICC=0.57; P=0.004) at the individual level. There were no significant group differences in patient versus parent-proxy pain intensity scores (P=0.40) and disability scores (P=0.54). The difference between patient and parent-proxy pain intensity was associated with patients’ self-reported pain intensity (P<0.001). The difference between patient and parent-proxy disability was associated with patient’s self-reported pain disability (P<0.001). Bland-Altman plots revealed major inter-rater variation in the Pediatric Pain Questionnaire and Functional Disability Inventory across their score ranges. A significant relationship (r=0.38; P<0.001) was observed between patients’ self-reported pain intensity and disability.
CONCLUSIONS:
While equal merit should ideally be given to pediatric chronic pain patients’ self-reports and their parents’ proxy reports of pain intensity and disability, it would appear that, as needed, pediatric patients or parents can offer a clinically valid, single clinical perspective.
PMCID: PMC3938337  PMID: 24147272
Adolescents; Children; Chronic pain; Disability; Functional capacity; Pain intensity; Parent-child; Pediatrics
15.  A Polymorphism in TLR2 Is Associated With Arterial Thrombosis in a Multiethnic Population of Patients With Systemic Lupus Erythematosus 
Objective
Thrombosis is a serious complication of systemic lupus erythematosus (SLE). Studies that have investigated the genetics of thrombosis in SLE are limited. We undertook this study to assess the association of previously implicated candidate genes, particularly Toll-like receptor (TLR) genes, with pathogenesis of thrombosis.
Methods
We genotyped 3,587 SLE patients from 3 multiethnic populations for 77 single-nucleotide polymorphisms (SNPs) in 10 genes, primarily in TLRs 2, 4, 7, and 9, and we also genotyped 64 ancestry-informative markers (AIMs). We first analyzed association with arterial and venous thrombosis in the combined population via logistic regression, adjusting for top principal components of the AIMs and other covariates. We also subjected an associated SNP, rs893629, to meta-analysis (after stratification by ethnicity and study population) to confirm the association and to test for study population or ethnicity effects.
Results
In the combined analysis, the SNP rs893629 in the KIAA0922/TLR2 region was significantly associated with arterial thrombosis (logistic P = 6.4 × 10−5, false discovery rate P = 0.0044). Two additional SNPs in TLR2 were also suggestive: rs1816702 (logistic P = 0.002) and rs4235232 (logistic P = 0.009). In the meta-analysis by study population, the odds ratio (OR) for arterial thrombosis with rs893629 was 2.44 (95% confidence interval 1.58–3.76), without evidence for heterogeneity (P = 0.78). By ethnicity, the effect was most significant among African Americans (OR 2.42, P = 3.5 × 10−4) and European Americans (OR 3.47, P = 0.024).
Conclusion
TLR2 gene variation is associated with thrombosis in SLE, particularly among African Americans and European Americans. There was no evidence of association among Hispanics, and results in Asian Americans were limited due to insufficient sample size. These results may help elucidate the pathogenesis of this important clinical manifestation.
doi:10.1002/art.38520
PMCID: PMC4269184  PMID: 24578102
16.  Reducing Older Driver Motor Vehicle Collisions via Earlier Cataract Surgery 
Accident; analysis and prevention  2013;61:10.1016/j.aap.2013.01.002.
Older adults who undergo cataract extraction have roughly half the rate of motor vehicle collision (MVC) involvement per mile driven compared to cataract patients who do not elect cataract surgery. Currently in the U.S., most insurers do not allow payment for cataract surgery based upon the findings of a vision exam unless accompanied by an individual’s complaint of visual difficulties that seriously interfere with driving or other daily activities and individuals themselves may be slow or reluctant to complain and seek relief. As a consequence, surgery tends to occur after significant vision problems have emerged. We hypothesize that a proactive policy encouraging cataract surgery earlier for a lesser level of complaint would significantly reduce MVCs among older drivers. We used a Monte Carlo model to simulate the MVC experience of the U.S. population from age 60 to 89 under alternative protocols for the timing of cataract surgery which we call “Current Practice” (CP) and “Earlier Surgery” (ES). Our base model finds, from a societal perspective with undiscounted 2010 dollars, that switching to ES from CP reduces by about 21% the average number of MVCs, fatalities, and MVC cost per person. The net effect on total cost – all MVC costs plus cataract surgery expenditures -- is a reduction of about 16%. Quality Adjusted Life Years would increase by about 5%. From the perspective of payers for healthcare, the switch would increase cataract surgery expenditure for ages 65+ by about 8% and for ages 60 to 64 by about 47% but these expenditures are substantially offset after age 65 by reductions in the medical and emergency services component of MVC cost. Similar results occur with discounting at 3% and with various sensitivity analyses. We conclude that a policy of ES would significantly reduce MVCs and their associated consequences.
doi:10.1016/j.aap.2013.01.002
PMCID: PMC3644302  PMID: 23369786
Motor Vehicle Collision; Cataract Surgery; Monte Carlo Simulation; Elderly; Cost Effectiveness; Medicare; Insurance
17.  Value of Isolated IgA anti-β2GPI Positivity in the Diagnosis of the Antiphospholipid Syndrome 
Arthritis and rheumatism  2013;65(12):3186-3193.
Purpose
To examine the prevalence of isolated IgA anti-β2Glycoprotein I (anti-β2GPI) positivity and the association of these antibodies, and a subgroup that bind specifically to domain IV/V of β2GPI, with clinical manifestations of the Antiphospholipid Syndrome (APS) in three patients groups. The pathogenicity of IgA anti-β2GPI was also evaluated in a mouse model of thrombosis.
Methods
Patients with systemic lupus erythematosus (SLE) from a multiethnic, multicenter cohort (LUpus in MInorities, NAture versus nurture [LUMINA]) (n=558), patients with SLE from the Hopkins Lupus Cohort (n=215), and serum samples referred to the Antiphospholipid Standardization Laboratory (APLS) (n=5,098) were evaluated. IgA anti-β2GPI titers and binding to domain IV/V of β2GPI were examined by enzyme-linked immunosorbent assay (ELISA). CD1 mice were inoculated with purified IgA anti- β2GPI antibodies, and surgical procedures and ELISAs were performed to evaluate thrombus development and tissue factor (TF) activity.
Results
A total of 198 patients were found to be positive for IgA anti-β2GPI isotype, and 57 patients were positive exclusively for IgA anti-β2GPI antibodies. Of these, 13 of 23 patients (56.5%) in the LUMINA cohort, 17 of 17 patients (100%) in the Hopkins cohort, and 10 of 17 patients (58.9%) referred to APLS had at least one APS-related clinical manifestation. Fifty-four percent of all the IgA anti-β2GPI positive serum samples reacted with domain IV/V of anti-β2GPI, and 77% of those had clinical features of APS. Isolated IgA anti-β2GPI positivity was associated with an increased risk for arterial thrombosis (p<0.001), venous thrombosis (p=0.015) and all thrombosis (p<0.001). The association between isolated IgA anti-β2GPI and arterial thrombosis (p=0.0003) and all thrombosis (p=0.0003) remained significant after adjusting for other risk factors for thrombosis. In vivo mouse studies demonstrated that IgA anti-β2GPI antibodies induced significantly larger thrombi and higher TF levels compared to controls.
Conclusion
Isolated IgA anti-β2GPI positive titers may identify additional patients with clinical features of APS. Testing for these antibodies when other antiphospholipid (aPL) tests are negative and APS is suspected is recommended. IgA anti-β2GPI antibodies directed to domain IV/V of β2GPI represent an important subgroup of clinically relevant antiphospholipids.
doi:10.1002/art.38131
PMCID: PMC4048705  PMID: 23983008
19.  Histologic Characteristics of the Fetal Inflammatory Response Associated with Neurodevelopmental Impairment and Death in Extremely Preterm Infants 
The Journal of pediatrics  2013;163(3):652-657.e2.
To test the hypothesis that increasing severity of the fetal inflammatory response would have a dose-dependent relationship with severe neurodevelopmental impairment (NDI) or death in extremely preterm infants.
Study design
We report 347 infants 23 to 28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or NDI at 18–22 month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1: phlebitis; stage 2: arteritis with or without phlebitis; stage 3: subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis).
Results
A fetal inflammatory response was detected in 110 placentas (32%). Severe NDI/death rate was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs. 35%; p<0.05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with higher rates of severe NDI/death (47% vs. 23%; p<0.05). After adjustment for confounding factors, only subacute necrotizing funisitis (RR: 1.87; 95% CI: 1.04 – 3.35; p=0.04) and chorionic plate vasculitis with thrombosis (RR: 2.21; 95% CI: 1.10 – 4.46; p=0.03) were associated with severe NDI/death.
Conclusions
Severe fetal inflammatory response characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis are associated with severe NDI/death in preterm infants.
doi:10.1016/j.jpeds.2013.03.081
PMCID: PMC3744601  PMID: 23664630
chorioamnionitis; infant; premature; prognosis; funisitis; chorionic plate vasculitis
20.  Examining the Association Between Age-Related Macular Degeneration and Motor Vehicle Collision Involvement: A Retrospective Cohort Study 
The British journal of ophthalmology  2013;97(9):10.1136/bjophthalmol-2013-303601.
Background
Little is known about motor vehicle collision (MVC) risk in older drivers with age-related macular degeneration (AMD). The purpose of this study is to examine associations between MVC involvement and AMD presence and severity.
Methods
In a retrospective cohort study pooling the samples from four previous studies, we examined associations between MVC rate and older drivers with early, intermediate, or advanced AMD as compared to those in normal eye health. MVC data were based on accident reports obtained from the state agency that compiles this information.
Results
MVC rate was highest among those in normal eye health and progressively declined among those with early and intermediate disease, and then increased for those with advanced AMD. However, only for drivers with intermediate AMD was the MVC rate significantly different (lower) as compared to those in normal eye health, regardless of whether the rate was defined in terms of person-years (RR 0.34, 95% CI 0.13–0.89) or person-miles (RR 0.35, 95% CI 0.13–0.91) of driving.
Conclusion
These results suggest that older drivers with intermediate AMD have a reduced risk of collision involvement. Further research should investigate whether self-regulatory driving practices by these drivers (avoiding challenging driving situations) underlies this reduced risk.
doi:10.1136/bjophthalmol-2013-303601
PMCID: PMC3837568  PMID: 23832967
driving; age-related macular degeneration; vision impairment
21.  Functional status, life-space mobility, and quality of life: a longitudinal mediation analysis 
Purpose
Using the Wilson–Cleary model of patient outcomes as a conceptual framework, the impact of functional status on health-related quality of life (HRQoL) among older adults was examined, including tests of the mediation provided by life-space mobility.
Methods
Participants were enrollees in a population-based, longitudinal study of mobility among community-dwelling older adults. Data from four waves of the study equally spaced approximately 18 months apart (baseline, 18, 36, and 54 months) were used for participants who survived at least 1 year beyond the 54-month assessment (n = 677). Autoregressive mediation models using longitudinal data and cross-sectional mediation models using baseline data were evaluated and compared using structural equation modeling.
Results
The longitudinal autoregressive models supported the mediating role of life-space mobility and suggested that this effect is larger for the mental component summary score than the physical component summary score of the SF-12. Evidence for a reciprocal relationship over time between functional status, measured by ADL difficulty, and life-space mobility was suggested by modification indices; these model elaborations did not alter the substantive meaning of the mediation effects. Mediated effect estimates from longitudinal autoregressive models were generally larger than those from cross-sectional models, suggesting that mediating relationships would have been missed or were potentially underestimated in cross-sectional models.
Conclusions
These results support a mediating role for life-space mobility in the relationship between functional status and HRQoL. Functional status limitations might cause diminished HRQoL in part by limiting mobility. Mobility limitations may precede functional status limitations in addition to being a consequence thereof.
doi:10.1007/s11136-012-0315-3
PMCID: PMC3618999  PMID: 23161329
Wilson; Cleary model; Activities of daily living; Mobility; SF-12; Longitudinal mediation; Autoregressive mediation modeling
22.  Effectiveness of Booster Seats Compared With No Restraint or Seat Belt Alone for Crash Injury Prevention 
Objectives
The objective was to evaluate the effectiveness of belt-positioning booster seats, compared with no restraint use and with seat belt use only, during motor vehicle crashes among U.S. children.
Methods
This was a retrospective matched cohort study with data from the 1998 through 2009 National Automotive Sampling System (NASS) Crashworthiness Data System (CDS). The study sample consisted of children aged 0 to 10 years who were not seated in the front seat of the vehicle. We used Cox proportional hazards models to estimate the risk of overall, fatal, and regional body injury.
Results
Children using seat belts in belt-positioning booster seats experienced less overall injury (Injury Severity Score [ISS] > 0, adjusted risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.55 to 0.96; Abbreviated Injury Scale [AIS] score of 2 or higher, adjusted RR = 0.30, 95% CI = 0.16 to 0.58; ISS > 8, adjusted RR = 0.19, 95% CI = 0.06 to 0.56), and less injury in most body regions except the neck (adjusted RR = 4.79, 95% CI = 1.43 to 16.00) than did children with no restraint use. Children using seat belts in belt-positioning booster seats had an equal risk of injury but higher risks of neck (adjusted RR = 1.86, 95% CI = 1.02 to 3.40) and thorax (adjusted RR = 2.86, 95% CI = 1.33 to 6.15) injury than did children restrained by seat belts only.
Conclusions
Children using belt-positioning booster seats appear to experience a higher risk of AIS > 0 injury to the neck and thorax than do children using seat belts only. Future research should examine whether the observed increase in neck and thorax injuries can be attributed to improper use of booster seats.
doi:10.1111/acem.12204
PMCID: PMC3798005  PMID: 24050794
23.  Analysis of a grading system to assess the quality of small-bowel preparation for capsule endoscopy: in search of the Holy Grail 
Endoscopy International Open  2014;2(3):E183-E186.
Background: The diagnostic yield of capsule endoscopy is vulnerable to inadequate visualization related to residual bile or chyme remaining in the lumen despite intestinal lavage. It has been challenging to determine the optimal lavage preparation of the bowel and patient diet before capsule endoscopy, as well as the timing of the procedure, because no well-accepted, validated grading system for assessing the quality of intestinal lavage before capsule endoscopy is available. There remains no consensus on the reliability of qualitative, quantitative, or computer-derived assessments of the quality of preparation for capsule endoscopy. This study evaluates intra-observer and interobserver agreement for a previously validated scale.
Materials and methods: The digital images of 34 patients who underwent capsule endoscopy were independently reviewed by two blinded physicians according to a previously validated grading scale. One of the physicians reviewed and graded the patients a second time. The quality of the bowel luminal preparation was assessed with a qualitative parameter (fluid transparency) and a more quantitative parameter (mucosal invisibility) for each of three small-intestinal segments, and an overall small-bowel score for each parameter was assigned as well. A weighted kappa coefficient was used to calculate intra-observer (observer 1A and 1B) and interobserver (observer 1A and observer 2) agreement. A kappa value of 0.60 or more suggests strong agreement, 0.40 to 0.60 moderate agreement, and less than 0.40 poor agreement.
Results: The intra-observer weighted kappa index for both fluid transparency and mucosal visibility was 0.52, which is consistent with moderate agreement. The interobserver weighted kappa indices for fluid transparency and mucosal invisibility were 0.29 and 0.42, respectively, demonstrating suboptimal interobserver agreement. The individual segment interobserver kappa indices were better for mucosal visibility (0.52, 0.39, and 0.47 for small-bowel segments 1, 2, and 3, respectively) than for fluid transparency (0.18, 0.38, and 0.31).
Conclusions: The proposed grading scale for assessing the quality of preparation for capsule endoscopy has inadequate interobserver and intra-observer agreement. Capsule endoscopy preparation grading scales that focus more on quantitative than on qualitative assessment may demonstrate more reliable performance characteristics. Optimizing the quality of preparation and diagnostic yield of capsule endoscopy will first require the development of a well-validated grading scale.
doi:10.1055/s-0034-1377521
PMCID: PMC4423294  PMID: 26134966
24.  Is Familial Lupus Different from Sporadic Lupus?: Data from LUMINA, a Multiethnic US Cohort 
Lupus  2010;19(11):1331-1336.
Purpose
To characterize the clinical features of familial lupus, and determine its influence on damage accrual and survival using data from LUMINA, a longitudinal multiethnic US cohort.
Method
Familial lupus was defined as patients with a first degree relative with SLE. Relative risks were estimated by logistic regression; odds ratios (OR) and their 95% confidence intervals (CI) were the measure of association for familial lupus. Hazard Ratios (HR) were calculated using Cox proportional hazard adjusted for potential confounders for damage and survival.
Results
Thirty-two of 644 patients had familial and 612 had sporadic lupus; both groups were of comparable age (~ 36 years). Familial lupus patients were in decreasing order of frequency siblings, parents and children. In multivariable analyses, mucosal ulcers (OR=1.92, 95% CI 0.65–5.70), mitral valve prolapse (OR=1.74, 95% CI 0.50–6.10), cerebrovascular disease (OR=4.18, 95% CI 0.98–17.76) and oral contraceptive use (ever/never; OR=2.51, 95% CI 0.88–7.19) were more likely in familial lupus but a history of low platelet count (<150,000/mm3; OR=0.31, 95% CI 0.08–1.17) and pulmonary disease activity (OR=0.39, 95% CI 0.14–1.20) were less likely. However, none of these associations reached statistical significance. Familial lupus was not significantly associated with a shorter time to either damage accrual or death (HR=0.77, 95% CI 0.37–1.59, p = 0.4746 and HR=0.20, 95% CI 0.03–1.47, p = 0.2020, respectively).
Conclusions
Although some clinical differences were observed in patients with familial and sporadic lupus, familial lupus was not associated with a significantly greater disease burden (damage, survival) than sporadic lupus.
doi:10.1177/0961203310375264
PMCID: PMC4078734  PMID: 20696771
familial lupus; lupus; sporadic lupus; LUMINA; multiethnic cohort
25.  Visually Impaired Drivers Who Use Bioptic Telescopes: Self-Assessed Driving Skills and Agreement With On-Road Driving Evaluation 
Purpose.
To compare self-assessed driving habits and skills of licensed drivers with central visual loss who use bioptic telescopes to those of age-matched normally sighted drivers, and to examine the association between bioptic drivers' impressions of the quality of their driving and ratings by a “backseat” evaluator.
Methods.
Participants were licensed bioptic drivers (n = 23) and age-matched normally sighted drivers (n = 23). A questionnaire was administered addressing driving difficulty, space, quality, exposure, and, for bioptic drivers, whether the telescope was helpful in on-road situations. Visual acuity and contrast sensitivity were assessed. Information on ocular diagnosis, telescope characteristics, and bioptic driving experience was collected from the medical record or in interview. On-road driving performance in regular traffic conditions was rated independently by two evaluators.
Results.
Like normally sighted drivers, bioptic drivers reported no or little difficulty in many driving situations (e.g., left turns, rush hour), but reported more difficulty under poor visibility conditions and in unfamiliar areas (P < 0.05). Driving exposure was reduced in bioptic drivers (driving 250 miles per week on average vs. 410 miles per week for normally sighted drivers, P = 0.02), but driving space was similar to that of normally sighted drivers (P = 0.29). All but one bioptic driver used the telescope in at least one driving task, and 56% used the telescope in three or more tasks. Bioptic drivers' judgments about the quality of their driving were very similar to backseat evaluators' ratings.
Conclusions.
Bioptic drivers show insight into the overall quality of their driving and areas in which they experience driving difficulty. They report using the bioptic telescope while driving, contrary to previous claims that it is primarily used to pass the vision screening test at licensure.
Drivers with central vision impairment who use bioptic telescopes have insight into the overall quality of their driving and driving skills with which they have difficulty.
doi:10.1167/iovs.13-13520
PMCID: PMC3894796  PMID: 24370830
bioptic telescope; driving; low vision

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