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Browning D.J.,NC Associates | Kaiser P.K.,Cleveland Clinic | Rosenfeld P.J.,Bascom Palmer Eye Institute
American Journal of Ophthalmology | Year: 2012

• PURPOSE: To describe the pharmacokinetics, preclinical studies, and clinical trials of the newly approved anti-vascular endothelial growth factor (VEGF) drug aflibercept (Eylea (VEGF Trap-Eye); Regeneron; and Bayer). • DESIGN: Review with editorial commentary. • METHODS: A review of the medical literature and pertinent Internet postings combined with analysis of key studies with expert opinion regarding the use of aflibercept for the treatment of exudative age-related macular degeneration. • RESULTS: Aflibercept, a fusion protein with binding domains from native VEGF receptors, binds VEGF-A, VEGF-B, and placental growth factors 1 and 2 with high affinity. Preclinical ophthalmologic studies demonstrated that aflibercept suppresses choroidal neovascularization in several animal models. The results of phase 1 and 2 trials showed excellent short-term suppression of choroidal neovascularization in patients with exudative agerelated macular degeneration and suggested a longer durability of aflibercept compared with other anti-VEGF drugs. The pivotal phase 3 Vascular Endothelial Growth Factor (VEGF) Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration 1 and 2 trials showed that monthly and bimonthly aflibercept were noninferior to monthly ranibizumab at preventing vision loss (< 15-letter loss) with comparable vision gains and safety. Year 2 treatment involved monthly pro re nata injections with required injections every 3 months and maintained vision gains from the first year, with an average of 4.2 injections of aflibercept and 4.7 injections of ranibizumab. • CONCLUSIONS: Aflibercept promises to deliver excellent visual outcomes for exudative age-related macular degeneration patients while undergoing fewer injections compared with ranibizumab. With a wholesale cost of $1850 per dose, the cost per patient with aflibercept treatment promises to be lower than with ranibizumab. © 2012 by Elsevier Inc. All rights reserved.


Castro D.C.,University of North Carolina at Chapel Hill | Samuels M.,Orange County Partnership for Young Children | Harman A.E.,NC Associates
American Journal of Preventive Medicine | Year: 2013

Background: Childhood obesity has increased dramatically in the past 3 decades, particularly among children aged 2-5 years. In this group, Latino children are among those with the highest prevalence of obesity. Purpose: This paper describes a pilot study to evaluate a community intervention, known as the Growing Healthy Kids Program (GHK), to prevent childhood obesity among low-income families in a Southern state. Methods: The intervention included a weekly gardening session, a 7-week cooking and nutrition workshop, and social events for parents and children. Matched pre- and post-program height and weight data were collected for 95 children aged 2-15 years. Children's BMI was determined. Also, families reported on the availability and consumption of fruits and vegetables at the beginning and the end of the family's participation in the GHK program. Data were collected in2008-2010 and analyzed in 2011. Results: About 60% of participants who enrolled in the program were Latino families (n=60 families/120 children). By the end of their participation in the program, 17% (n=6, p< 0.004) of obese or overweight children had improved their BMI classification and 100% of the children with a BMI classification of normal had maintained that BMI classification. According to parental reports, there was an increase of 146% (p<0.001) in the availability of fruits and vegetables and an increase in the consumption of fruits (28%; p<0.001) and vegetables (33%; p<0.001) among children of families participating in the GHK program. Conclusions: Findings from this pilot study are consistent with previous studies reporting an increase in availability and consumption of fruits and vegetables among families participating in community gardens. Although there are limitations because this is a pilot study, this strategy seems to be promising for addressing childhood obesity, particularly among low-income Latino immigrant families. © 2013 American Journal of Preventive Medicine.


Ionic transport resistance is a key performance property of polymer electrolyte membranes (PEMs) and can be determined for transport within the plane of material (in-plane, longitudinal or transverse directions) and through the thickness of the membrane (throughplane). The conductivity of extruded Nafion® 112, dispersion-cast Nafion® NR-212 and two Gore-Select® membranes that contain a non-conductive support were characterized as a function of orientation, temperature and relative humidity. The conductivity of extruded Nafion 112 was highest in the extrusion direction and lowest in the through-plane orientation. In contrast, the conductivity of dispersion-cast NR-212 was isotropic. The effective conductivity of Gore-Select material was higher in-plane vs. through-plane, consistent with the analytical treatment of a membrane composed of layers of unequal intrinsic ion transport resistivity. The results highlight the need to make measurements in the relevant orientation. © 2011 ECS - The Electrochemical Society.


The author reports on a 59-year-old woman with a history of a chronic, nonhealing skin ulcer who presented with sepsis, neck pain, and rapidly progressive quadriparesis. Precontrast and postcontrast MR imaging studies revealed a multifocal ventral cervical and upper thoracic spinal epidural abscess. Compression of the spinal cord from the abscess was greatest behind the disc space of C2-3 and C7-T1. Because of the patient's tenuous medical status, the author elected to apply a technique that would allow expeditious decompression without necessitating concomitant fusion and instrumentation. Multilevel, contiguous trough corpectomies were performed for evacuation of the compressive lesions. A high-speed matchstick bur was used to create a 5- to 7-mm midline trough in the vertebrae and intervening disc spaces from C-2 to T-3. Rapid and successful decompression of the entire ventral cervical and upper thoracic epidural space was achieved using this technique. Understanding that the surgical treatment of discitis or osteomyelitis can often result in a kyphotic deformity or frank instability, the patient was immobilized in a cervical collar following surgery and underwent vigilant monitoring with serial plain radiographs, CT scans, and MR images. These neuroimaging studies confirmed complete resolution of the abscess and the slow development of a mild, stable kyphotic deformity. At the 1-year follow-up, the patient was ambulating and had returned to work. A trough corpectomy is a viable surgical approach that allows for rapid decompression of ventral cervical and upper thoracic epidural abscesses while obviating the need for same-setting fusion and fixation.


Rhyne D.,NC Associates | Mann T.,NC Associates
Catheterization and Cardiovascular Interventions | Year: 2010

We describe a case of hand ischemia resulting from transradial catheterization. This was successfully treated with angioplasty of the radial artery occlusion, but stresses the importance of a preprocedure evaluation of the dual blood supply to the hand before transradial access. © 2010 Wiley-Liss, Inc.


Purpose: To determine the impact of the revised academy guidelines on screening for hydroxychloroquine retinopathy. Design: Retrospective, observational cohort study. Methods: setting: Private practice of 29 doctors. study population: Total of 183 patients for follow-up and 36 patients for baseline screening. observation procedure: Review of charts, 10-2 visual fields (VFs), multifocal electroretinograms (mfERG), and spectral-domain optical coherence tomography (SD-OCT) images before and after the revised guidelines. main outcome measure: Rates of use of ancillary tests and clinical intervention, costs of screening, follow-up schedules, and comparative sensitivity of tests. Results: New hydroxychloroquine toxicity was found in 2 of 183 returning patients (1.1%). Dosing above 6.5 mg/kg/d was found in 28 of 219 patients (12.8%), an underestimate because patient height, weight, and daily dose were not determined in 77 (35.1%), 84 (38.4%), and 59 (26.9%), respectively. In 10 of the 28 (35.7%), the dose was reduced, in 2 (7.1%) hydroxychloroquine was stopped, but in 16 (57.1%) no action was taken. The cost of screening rose 40%/patient after the revised guidelines. Fundus autofluorescence imaging was not used. No toxicity was detected by adding mfERG or SD-OCT. In no case was a 5-year period free of follow-up recommended after baseline screening in a low-risk patient. Conclusions: Detection of toxic daily dosing is a cost-effective way to reduce hydroxychloroquine toxicity, but height, weight, and daily dose were commonly not checked. The revised guidelines, emphasizing mfERG, SD-OCT, or FAF, raised screening cost without improving case detection. The recommended 5-year screening-free interval for low-risk patients after baseline examination was ignored. © 2013 by Elsevier Inc. All rights reserved.


Chemical hormesis (CH) is currently described as a nonmonotonic, bidirectional dose-response relationship for chemicals, where a stimulatory, (beneficial?) response at low dose or exposure is followed by an inhibitory response at higher doses/exposures (or vice-versa). CH is depicted as U(J)-shaped or inverse U(J)-shaped curves, i.e., curve slopes change sign. Some describe CH as a homeostasis-preserving response; others view CH as adaptive or (pre)conditioning responses to chemical stress. One aspect of CH and stress hormesis in general that has not been researched is its temporal stability, i.e., persistence, particularly in experimental animals and humans having long-term chemical stressing. Once maximized, does the CH response remain operative over the entire time of chemical exposure? One possible reason for the question's neglect is that temporal stability, e.g., ‘steady-state hormesis,’ has been assumed. Another is that CH temporality is not well understood or has been under-appreciated as to its importance. Available data, mainly for simpler biological systems, describe cases of transitory CH. Other examples, in human and experimental animal studies, show transitory existence of CH and, in some specialized cases, persisting CH. Also, certain disease state-induced hormetic responses are transitory over time in humans. The question requires resolution if CH is to be considered (i) a stable and beneficial or adverse response, (ii) a stable dose-response model competitive with stable threshold and linear, nonthreshold (LNT) dose-response models, and (iii) a model having any impact on, or role in, regulatory and public health policies. © 2016


Background: The purpose of this study was to determine the relative sensitivity and specificity of 10-2 visual fields (10-2 VFs), multifocal electroretinography (mfERG), and spectral domain optical coherence tomography (SD-OCT) in detecting hydroxychloroquine retinopathy. Methods: A total of 121 patients taking hydroxychloroquine (n=119) or chloroquine (n=2) with 10-2 VF, mfERG, and SD-OCT tests were retrospectively reviewed. Rates of test abnormality were determined. Results: Retinopathy was present in 14 and absent in 107. Eleven of 14 (78.6%) patients with retinopathy were overdosed. Twelve (85.7%) had cumulative dosing greater than 1,000 g. The sensitivities of 10-2 VF, mfERG, and SD-OCT in detecting retinopathy were 85.7%, 92.9%, and 78.6%, respectively. The specificities of 10-2 VF, mfERG, and SD-OCT in detecting retinopathy were 92.5%, 86.9%, and 98.1%, respectively. Positive predictive values of 10-2 VF, mfERG, and SD-OCT in detecting retinopathy were less than 30% for all estimates of hydroxychloroquine retinopathy prevalence. Negative predictive values were >99% for all tests. Conclusion: Based on published estimates of hydroxychloroquine retinopathy prevalence, all three tests are most reliable when negative, allowing confident exclusion of retinopathy in patients taking ≤6.5 mg/kg/day. Each test is less useful in allowing a confident diagnosis of retinopathy when positive, especially in patients taking ≤6.5 mg/kg/day. © 2014 Browning and Lee.


Background: Acute stroke from tandem extracranial carotid artery and intracranial large vessel occlusion poses challenges for emergency endovascular treatment. Establishing and maintaining patency of the carotid artery and avoiding intracranial hemorrhage are competing concerns. Methods: Twenty-three consecutive cases of emergency carotid stenting followed by mechanical thrombectomy identified by retrospective review of the endovascular ischemic stroke database maintained prospectively at our institution since January 2011 form the basis for this report. No cases were lost to follow-up. Results: Patients were selected with CT angiography or MR angiography and diffusion weighted imaging. Carotid stenting was successful in all cases, and establishment of Thrombolysis in Cerebral Ischemia 2A, 2B or 3 flow was successful in 21/23 (91%). 12/23 (52%) patients achieved a modified Rankin Scale score of 0-2 at 90 days. Symptomatic intracranial hemorrhage (SICH) occurred in 5/23 patients (22%). Of 13 patients receiving an intravenous loading dose of abciximab during the procedure, 4/13 had SICH (31%) compared with 1/10 (10%) of those who did not. Of seven patients who received intravenous tissue plasminogen activator prior to the procedure, none had SICH. 90-day mortality was 9/23 (39%). All patients who had SICH were above the median age. Conclusions: Primary stenting of the extracranial carotid artery combined with intracranial mechanical thrombectomy can be an effective treatment for tandem occlusions, can be performed with a high rate of technical success, and can achieve good clinical outcomes in selected patients. However, the incidence of SICH may be higher than in other patient populations and may be associated with the use of abciximab and advanced patient age.


Irwin J.S.,NC Associates
Journal of the Air and Waste Management Association | Year: 2014

Too often operational atmospheric dispersion models are evaluated in their ability to replicate short-term concentration maxima, when in fact a valid model evaluation procedure would evaluate a model's ability to replicate ensemble-average patterns in hourly concentration values. A valid model evaluation includes two basic tasks: In Step 1 we should analyze the observations to provide average patterns for comparison with modeled patterns, and in Step 2 we should account for the uncertainties inherent in Step 1 so we can tell whether differences seen in a comparison of performance of several models are statistically significant. Using comparisons of model simulation results from AERMOD and ISCST3 with tracer concentration values collected during the EPRI Kincaid experiment, a candidate model evaluation procedure is demonstrated that assesses whether a model has the correct total mass at the receptor level (crosswind integrated concentration values) and whether a model is correctly spreading the mass laterally (lateral dispersion), and assesses the uncertainty in characterizing the transport. The use of the BOOT software (preferably using the ASTM D 6589 resampling procedure) is suggested to provide an objective assessment of whether differences in model performance between models are significant. Regulatory agencies can choose to treat modeling results as "pseudo-monitors," but air quality models actually only predict what they are constructed to predict, which certainly does not include the stochastic variations that result in observed short-term maxima (e.g., arc-maxima). Models predict the average concentration pattern of a collection of hours having very similar dispersive conditions. An easy-to-implement evaluation procedure is presented that challenges a model to properly estimate ensemble average concentration values, reveals where to look in a model to remove bias, and provides statistical tests to assess the significance of skill differences seen between competing models. © 2014 Copyright 2014 A&WMA.

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