Physical Activity in Functionally Monocular Persons in the United States, 2003-2006.

Purpose: Real-world physical activity patterns in monocular persons have not been previously characterized. This study uses a nationally representative sample to compare the physical activity levels of functionally monocular to binocularly sighted persons in the United States. Methods: This cross-sectional study uses data from the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey (NHANES) to compare differences in physical activity between functionally monocular and binocular participants. The main outcome measures were accelerometer-measured mean steps per day and mean daily minutes of moderate or vigorous physical activity (MVPA). Statistical analysis was conducted using multivariable negative binomial regression models adjusted for age. Results: In total, 7967 NHANES participants had complete visual acuity and accelerometer data. The mean age at baseline was 44.5 years, and a majority were Caucasian (73%) and female (51%). In models adjusted for age only, functionally monocular participants (n = 172) took fewer steps (9277 with 95% confidence interval [CI], 8800-9753 vs. 10,057 with 95% CI, 9832-10,281) and engaged in similar minutes of MVPA (26.75 with 95% CI, 22.0-31.5 vs. 26.70 with 95% CI, 25.6-27.7) per day compared to binocularly sighted participants (n = 7758). In our final model, functionally monocular participants took 16% fewer steps per day (P < 0.01) and engaged in 26% fewer minutes per day of MVPA (P = 0.01). Poorer visual acuity, older age, female gender, obesity, congestive heart failure, and arthritis were also associated with a statistically significant decrease in physical activity in both models. Conclusions: Functionally monocular persons have lower physical activity levels compared to those with binocular eyesight in the United States, even after adjusting for better-eye visual acuity. Translational Relevance: Our translational study provides insight into the epidemiology of physical activity and its impact on population health. We quantify real-world physical activity in two at-risk populations, monocular and blind individuals.

Incidence of Drug Use-Related Endogenous Endophthalmitis Hospitalizations in the United States, 2003 to 2016.

Importance: Complications arising from the nationwide opioid epidemic led to an increase in health care use. Few studies have investigated whether this is reflected in hospital admissions for endogenous endophthalmitis. Objective: To report changing trends in epidemiology, risk factors, hospital course, and costs associated with drug use-related endogenous endophthalmitis hospitalizations in the United States from 2003 to 2016. Design, Setting, and Participants: Nationwide, retrospective cross-sectional study using the National Inpatient Sample. A total of 56 839 patients admitted with a diagnosis of endogenous endophthalmitis were included. Data were analyzed between 2003 and 2016. Exposures: Inpatient admission for endogenous endophthalmitis during the years 2003 to 2016. Main Outcomes and Measures: The Nationwide Inpatient Sample was queried to identify all inpatient admissions with a diagnosis of endogenous endophthalmitis in the United States between the years 2003 and 2016. Analyses were performed to identify national and regional trends in incidence and prevalence of associated infectious and noninfectious comorbidities in patients with or without a history of drug dependence or use. Median and cumulative inflation-adjusted costs for admissions were calculated. Results: Of all patients, 55.6% were White, 13.6% were Black, and 10.6% were Hispanic. There were an estimated 56 839 endogenous endophthalmitis-related hospitalizations; 13.7% of these patients (n = 7783) had a history of drug dependence or use. The drug-using population was significantly younger (49.6 vs 57.5 years; difference, 7.9; 95% CI, 6.93-8.88; P < .001) and more likely to be male (61.8% [n = 35 127] vs 49.0% [n = 21 712]; difference, 12.8%; 95% CI, 11.6%-14.0%; P < .001). The incidence of endogenous endophthalmitis associated with drug dependence or use increased from 0.08 per 100 000 in 2003 to 0.32 per 100 000 population in 2016 across all 4 US geographic regions. Conclusions and Relevance: A 4-fold increase in drug use-related endogenous endophthalmitis hospitalizations was observed in the United States from 2003 to 2016, resulting in substantial health care use burden. These findings support the hypothesis that clinicians should maintain a high index of suspicion for endophthalmitis when evaluating patients with intraocular inflammation in the setting of drug dependence or use.

Trends in Infantile Endogenous Endophthalmitis Hospitalizations in the United States: An Analysis from 2007 through 2014 Using the National Inpatient Sample.

PURPOSE: To determine the annual change in incidence of neonatal and infantile endogenous endophthalmitis in the United States between 2007 and 2014 and identify associated risk factors for development of endophthalmitis and mortality. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Neonates (<28 days; n = 1650) hospitalized for endogenous endophthalmitis between 2003 and 2014 and infants (age range, 28 days-1 year; n = 1850) hospitalized between 2007 and 2014 across United States community hospitals were analyzed. METHODS: The Nationwide Inpatient Sample database was queried to identify neonates hospitalized for endogenous endophthalmitis between 2003 and 2014 and infants hospitalized between 2007 and 2014 across the United States. National and regional incidence of neonatal and infantile endogenous endophthalmitis and comorbidities as well as risk factors in the development of the disease and predictive factors for mortality from the years 2007 through 2014 were calculated. MAIN OUTCOMES AND MEASURES: National incidence, regional incidence, and risk factors for development of neonatal and infantile endogenous endophthalmitis. RESULTS: The rate of decline in incidence of neonatal endogenous endophthalmitis was 4% from 2003 through 2014. The rate of decline in the infantile population was 7% from 2007 through 2014. In 2007, an estimated 291 total cases of infantile endophthalmitis were identified, in comparison with 140 cases in 2014. Comorbidities prevalent in the endophthalmitis population included prematurity, respiratory disorders, perinatal infections, and retinopathy of prematurity (ROP). Significant positive predictors for the development of endogenous endophthalmitis based on multivariate logistic regression were perinatal infections, candidemia, bacteremia, very low birth weight, prematurity, respiratory disorders, and ROP. Descriptive analyses showed that the in-hospital mortality rate for patients identified with endophthalmitis was 1.55% in comparison with infants without endophthalmitis. CONCLUSIONS: The incidence of endogenous endophthalmitis declined in both the neonatal and infantile population from 2007 through 2014. Odds of endogenous endophthalmitis were higher for premature and low-birthweight infants and those identified with perinatal infections, candidemia, bacteremia, respiratory disorders, or ROP. These findings are consistent with the decline observed in pediatric infectious disease-related hospitalizations in general.

A semi-automated machine-learning based workflow for ellipsoid zone analysis in eyes with macular edema: SCORE2 pilot study.

BACKGROUND AND OBJECTIVE: To develop a semi-automated, machine-learning based workflow to evaluate the ellipsoid zone (EZ) assessed by spectral domain optical coherence tomography (SD-OCT) in eyes with macular edema secondary to central retinal or hemi-retinal vein occlusion in SCORE2 treated with anti-vascular endothelial growth factor agents. METHODS: SD-OCT macular volume scans of a randomly selected subset of 75 SCORE2 study eyes were converted to the Digital Imaging and Communications in Medicine (DICOM) format, and the EZ layer was segmented using nonproprietary software. Segmented layer coordinates were exported and used to generate en face EZ thickness maps. Within the central subfield, the area of EZ defect was measured using manual and semi-automated approaches via a customized workflow in the open-source data analytics platform, Konstanz Information Miner (KNIME). RESULTS: A total of 184 volume scans from 74 study eyes were analyzed. The mean±SD area of EZ defect was similar between manual (0.19±0.22 mm2) and semi-automated measurements (0.19±0.21 mm2, p = 0.93; intra-class correlation coefficient = 0.90; average bias = 0.01, 95% confidence interval of limits of agreement -0.18-0.20). CONCLUSIONS: A customized workflow generated via an open-source data analytics platform that applied machine-learning methods demonstrated reliable measurements of EZ area defect from en face thickness maps. The result of our semi-automated approach were comparable to manual measurements.

Longitudinal Study of Dark Adaptation as a Functional Outcome Measure for Age-Related Macular Degeneration.

PURPOSE: To investigate the natural history of dark adaptation (DA) function as measured by the change in rod intercept time (RIT) over 4 years and to correlate RIT change with age-related macular degeneration (AMD) severity. DESIGN: Longitudinal, single-center, observational study. PARTICIPANTS: A total of 77 participants aged ≥50 years with a range of AMD severities. METHODS: Participants each contributing a single study eye to the analysis were assigned into person-based AMD severity groups based on fundus characteristics (drusen, pigmentary changes, late AMD, and subretinal drusenoid deposits [SDDs]). The DA function was assessed in study eyes at baseline and 3, 6, 12, 18, 24, 36, and 48 months. Mean change in DA function over time was calculated using the slope of linear regression fits of longitudinal RIT data. Patient-reported responses on a Low Luminance Questionnaire (LLQ) were obtained at baseline and yearly. Nonparametric statistical testing was performed on all comparisons. MAIN OUTCOME MEASURE: The RIT, defined as the time taken after a photobleach for visual sensitivity to recover detection of a 5×10-3 cd/m2 stimulus (a decrease of 3 log units), was monitored in study eyes over 4 years, and the mean rate of change was computed. RESULTS: Longitudinal analysis of 65 study eyes followed on the standard testing protocol (mean age, 71±9.3 years; 49% were female) revealed that higher rates of RIT prolongation were correlated with AMD severity group assignment at baseline (P = 0.026) and with severity group assignments at year 4 (P = 0.0011). Study eyes that developed SDD during follow-up demonstrated higher rates of RIT prolongation relative to those that did not (P < 0.0001). Overall, higher rates of RIT prolongation were significantly correlated with greater 4-year decreases in LLQ scores (total mean score, P = 0.0032). CONCLUSIONS: Longitudinal decline in DA function, which correlated with patient-reported functional deficits, was accelerated in eyes with greater AMD severity and especially in eyes with SDD both at baseline and at 4 years. The RIT prolongation as a measure of changing DA function may be a functional outcome measure in AMD clinical studies.

Association of Mortality with Ocular Diseases and Visual Impairment in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 13.

PURPOSE: To evaluate the association of mortality with visual acuity (VA) impairment, age-related macular degeneration (AMD), and cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Participants with at least intermediate AMD enrolled in a randomized controlled clinical trial of lutein/zeaxanthin and/or omega-3 fatty acids, the Age-Related Eye Disease Study 2 (AREDS2), for treatment of AMD and cataract. METHODS: Baseline and annual eye examinations included best-corrected visual acuity (BCVA) assessments, slit-lamp examinations, and stereoscopic fundus photographs that were centrally graded for development of late AMD (central geographic atrophy or neovascular AMD) or pseudophakia. Cause-specific mortality was determined on the basis of the International Classification of Diseases 9th or 10th Revision codes. Risk of all-cause and cause-specific mortality was assessed with Cox proportional hazards models adjusted for age, sex, AMD severity, VA, history of cataract surgery, and assigned AREDS2 study treatment. Analyses included baseline covariates: race, education, smoking status, diabetes, and cardiovascular disease. RESULTS: During follow-up (median 5 years), 368 (9%) of the 4203 AREDS2 participants died. Participants with neovascular AMD in 1 eye at baseline had a statistically significant increased risk for mortality compared with participants with no or few drusen (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.21-2.01; P < 0.001). Poorer survival was associated with bilateral cataract surgery before enrollment compared with baseline bilateral phakia (HR, 1.63; 95% CI, 1.29-2.07; P < 0.001) and with BCVA of less than 20/40 compared with participants with 20/40 or better (HR, 1.56; 95% CI, 1.06-2.30; P = 0.024), adjusted for age, sex, and statistically significant covariates. Participants who received antivascular endothelial growth factor therapies for neovascular AMD had decreased mortality compared with those who did not (HR, 0.71; 95% CI, 0.57-0.88; P = 0.002). The association between all-cause mortality and AREDS2 treatment whether assessing the main or individual treatment effect was not significantly different (omega-3 fatty acids main effect HR, 1.18; 95% CI, 0.96-1.45; P = 0.12; lutein/zeaxanthin main effect HR, 1.04; 95% CI, 0.85-1.28; P = 0.71). CONCLUSIONS: In AREDS2, the presence of late AMD, bilateral cataract surgery, and VA less than 20/40 was associated with decreased survival. However, oral supplementation with omega-3 fatty acids, lutein plus zeaxanthin, zinc, or beta-carotene had no statistically significant impact on mortality.

Elbasvir/grazoprevir for treatment of chronic hepatitis C virus infection.

Hepatitis C is the leading cause of progressive liver fibrosis worldwide and results in cirrhosis, liver cancer, liver failure and death. Successful treatment for hepatitis C virus (HCV) has rapidly evolved in recent years to a well-tolerated, highly efficacious all-oral therapy. Elbasvir/grazoprevir (Zepatier) is the newest of the oral combinations of HCV direct-acting agents that was approved by the US Federal Drug Administration. This review focuses on the pharmacology, mechanism of action and clinical trial data that support the use of this new combination treatment for HCV infection. The data suggest that Zepatier offers an excellent treatment efficacy, safety and tolerability in HCV treatment naïve and experienced patients and those with and without cirrhosis across multiple genotypes. Also, it has the selective advantage of safety and efficacy in patients with renal disease, especially in those with end-stage renal disease and/or hemodialysis patients.

Neuronal BDNF signaling is necessary for the effects of treadmill exercise on synaptic stripping of axotomized motoneurons.

The withdrawal of synaptic inputs from the somata and proximal dendrites of spinal motoneurons following peripheral nerve injury could contribute to poor functional recovery. Decreased availability of neurotrophins to afferent terminals on axotomized motoneurons has been implicated as one cause of the withdrawal. No reduction in contacts made by synaptic inputs immunoreactive to the vesicular glutamate transporter 1 and glutamic acid decarboxylase 67 is noted on axotomized motoneurons if modest treadmill exercise, which stimulates the production of neurotrophins by spinal motoneurons, is applied after nerve injury. In conditional, neuron-specific brain-derived neurotrophic factor (BDNF) knockout mice, a reduction in synaptic contacts onto motoneurons was noted in intact animals which was similar in magnitude to that observed after nerve transection in wild-type controls. No further reduction in coverage was found if nerves were cut in knockout mice. Two weeks of moderate daily treadmill exercise following nerve injury in these BDNF knockout mice did not affect synaptic inputs onto motoneurons. Treadmill exercise has a profound effect on synaptic inputs to motoneurons after peripheral nerve injury which requires BDNF production by those postsynaptic cells.