31 research outputs found
Predicting glaucoma progression using random forests for correlated binary response based on longitudinally collected standard automated perimetry data
No full textIncludes bibliographical references (pages 114-119).Clustered outcomes with longitudinally collected covariates arise frequently in applied research and present difficulties in statistical analysis because of the complex dependence structure. Due to their nonparametric approach and interpretable results, tree-based methods have become some of the most flexible and popular analytic tools for modeling complex data structures. This dissertation is intended to propose new statistical methods used in determining true visual field progression in high-risk ocular hypertension or early glaucoma patients. Traditional tree models such as classification and regression trees (CART) cannot be readily applied to data arising from ophthalmologic studies. This is because data from the two eyes of the same patient are usually correlated. To overcome the analytical difficulty with correlated outcome data, a simplifying approach is to randomly select one eye per patient. Analyses based on a single observation per cluster are convenient in that a standard tree method can be employed. However, the major disadvantage of this approach is a loss of information because half of all the information collected is unused in the analysis. Tree based methods that can incorporate correlated data are much needed because using data from both eyes can provide more power in any statistical hypothesis testing and improve prediction accuracy in a classification problem. In Chapter 1, we give an introduction to tree-based methods and discuss the motivation behind this thesis. It introduces the challenges in managing glaucoma and detecting glaucomatous visual field progression based on standard automated perimetry. In Chapter 2, we propose a classification tree method for correlated binary data by modifying the splitting function of CART. By applying a robust Wald test from the generalized estimating equations (GEE), data from both eyes can be used while adjusting correlation between two eyes of the same patient. Simulations were conducted under a variety of model configurations to investigate the performance of the split criteria. The proposed approach was also applied to data from the perimetry and psychophysics in glaucoma (PPIG) study to look for baseline prognostic indicators for visual field glaucomatous progression. Both traditional CART and the proposed method based on the robust Wald statistic were applied to the PPIG study data. Results based on test sample (a portion of data not used in the model building process) also show improved accuracy when using data from both eyes. In terms of finding important predictors of glaucoma progression, results based on the proposed method were consistent with many locations that have been discussed in the ophthalmology literature to indicate progression risk. In addition, some new test point locations were uncovered that appear to be associated with increased risk of glaucomatous progression. In Chapter 3, we propose an extension of the existing random forests (RF) classification method based on the new tree method from Chapter 2. We then apply the new RF method to the PPIG study data incorporating both baseline and longitudinal covariates. In order to account for the correlated nature of sequential data (i.e., data collected over time), we rectify the pointwise linear regression (PLR) method that is popular in the ophthalmology literature by performing generalized least square (GLS) regression for longitudinal visual field data from each test point location of each eye of each patient. The slopes and the associated p-values for slopes indicate the magnitude and statistical significance of the change in the visual sequence and are used in the RF construction. As can be seen from the results, the application of RF to the PPIG data by incorporating data from both eyes as well as features from the longitudinal data provides improved accuracy for predicting glaucoma progression. In Chapter 4, we further extend the RF method to deal with visual field data that are known to be noisy. We propose a two-step splitting strategy. First, a measurement error, or random effects, model is fit to the longitudinal visual field data from all test points of all eyes of all patients. This model is designed to remove the measurement errors in the visual field data. Second, the true slopes from the random effects model, together with all the clinical and social-economical baseline covariates, are then considered as potential splitting variables to split the node. In addition, we apply the same longitudinal data set from the PPIG study to showcase the improved fit and prediction accuracy. In order to apply the proposed two-step splitting approach to RF, computational efficiency becomes particularly challenging. RF methods have been recognized to be highly effective and ideally suited for parallelization. The final chapter presents a parallel formulation of the proposed method with RF incorporating joint models for correlated binary outcome and longitudinal covariates. We also provide the analysis of the longitudinal PPIG data to demonstrate excellent speedups and scalability. The last chapter provides a summary of this work, noting the novel contributions to the field of work; and gives suggestions for future wor
One-year outcomes of aflibercept in recurrent or persistent neovascular age-related macular degeneration
No full textPURPOSE:
To evaluate 6-month and 1-year outcomes of every-8-weeks (Q8W) aflibercept in patients with resistant neovascular age-related macular degeneration (AMD).
DESIGN:
Retrospective, interventional, consecutive case series.
METHODS:
Retrospective review of patients with resistance (multiple recurrences or persistent exudation) to every-4-weeks (Q4W) ranibizumab or bevacizumab that were switched to Q8W aflibercept.
RESULTS:
Sixty-three eyes of 58 patients had a median of 13 (interquartile range [IQR], 7-22) previous anti-vascular endothelial growth factor (anti-VEGF) injections. At 6 months after changing to aflibercept, 60.3% of eyes were completely dry, which was maintained up to 1 year. The median maximum retinal thickness improved from 355 μm to 269 μm at 6 months (P < .0001) and 248 μm at 1 year (P < .0001). There was no significant improvement in ETDRS visual acuity at 6 months (P = .2559) and 1 year follow-up (P = .1081) compared with baseline. The mean difference in ETDRS visual acuity compared to baseline at 6 months was -0.05 logMAR (+2.5 letters) and 0.04 logMAR at 1 year (-2 letters).
CONCLUSION:
Sixty percent of eyes with resistant AMD while on Q4W ranibizumab or bevacizumab were completely dry after changing to Q8W aflibercept at the 6-month and 1-year follow-ups, but visual acuity did not significantly improve. Only a third of eyes needed to be switched from Q8W to Q4W aflibercept owing to persistence of fluid; Q8W dosing of aflibercept without the initial 3 monthly loading doses may be a good alternative in a select group of patients who may have developed ranibizumab or bevacizumab resistance
One-Year Outcomes of Aflibercept in Recurrent or Persistent Neovascular Age-Related Macular Degeneration
No full textUse of Statistical Analyses in the Ophthalmic Literature
No full textPurpose: To identify the most commonly used statistical analyses in the ophthalmic literature and to determine the likely gain in comprehension of the literature that readers could expect if they were to add knowledge of more advanced techniques sequentially to their statistical repertoire.Design: Cross-sectional study.Methods: All articles published from January 2012 through December 2012 in Ophthalmology, the American Journal of Ophthalmology, and Archives of Ophthalmology were reviewed. A total of 780 peer-reviewed articles were included. Two reviewers examined each article and assigned categories to each one depending on the type of statistical analyses used. Discrepancies between reviewers were resolved by consensus.Main Outcome Measures: Total number and percentage of articles containing each category of statistical analysis were obtained. Additionally, we estimated the accumulated number and percentage of articles that a reader would be expected to be able to interpret depending on their statistical repertoire.Results: Readers with little or no statistical knowledge would be expected to be able to interpret the statistical methods presented in only 20.8% of articles. To understand more than half (51.4%) of the articles published, readers would be expected to be familiar with at least 15 different statistical methods. Knowledge of 21 categories of statistical methods was necessary to comprehend 70.9% of articles, whereas knowledge of more than 29 categories was necessary to comprehend more than 90% of articles. Articles related to retina and glaucoma subspecialties showed a tendency for using more complex analysis when compared with articles from the cornea subspecialty.Conclusions: Readers of clinical journals in ophthalmology need to have substantial knowledge of statistical methodology to understand the results of studies published in the literature. the frequency of the use of complex statistical analyses also indicates that those involved in the editorial peer-review process must have sound statistical knowledge to appraise critically the articles submitted for publication. the results of this study could provide guidance to direct the statistical learning of clinical ophthalmologists, researchers, and educators involved in the design of courses for residents and medical students. (C) 2014 by the American Academy of Ophthalmology.Univ Calif San Diego, Hamilton Glaucoma Ctr, La Jolla, CA 92093 USAUniv Calif San Diego, Dept Ophthalmol, La Jolla, CA 92093 USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilBoston Univ, Sch Med, Boston, MA 02118 USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilWeb of ScienceNational Eye Institute, National Institutes of Health, Bethesda, MarylandBrazilian National Research CouncilCarl-Zeiss Meditec, Inc (Jena, Germany)Heidelberg Engineering, GmBH (Dosseinheim, Germany)Alcon (Hunenberg, Switzerland)Allergan (Irvine, California)Topcon (Itabashi, Tokyo, Japan)Reichert, Inc (Depew, New York)National Eye Institute, National Institutes of Health, Bethesda, Maryland: EY021818National Eye Institute, National Institutes of Health, Bethesda, Maryland: P30EY022589Brazilian National Research Council: 200178/2012-
The effect of delaying initiation with umeclidinium/vilanterol in patients with COPD: an observational administrative claims database analysis using marginal structural models
No full textAbstract Background Chronic obstructive pulmonary disease (COPD) is associated with high clinical and economic burden. Optimal pharmacological therapy for COPD aims to reduce symptoms and the frequency and severity of exacerbations. Umeclidinium/vilanterol (UMEC/VI) is an approved combination therapy for once-daily maintenance treatment of patients with COPD. This study evaluated the impact of delaying UMEC/VI initiation on medical costs and exacerbation risk. Methods A retrospective analysis of patients with COPD who initiated UMEC/VI between 4/28/2014 and 7/31/2016 was conducted using the Optum Research Database. The index date was the first COPD visit after UMEC/VI available on US formulary (Commercial 4/28/2014; Medicare Advantage 1/1/2015). Patients were followed for 12 months post-index, and categorized into 12 cohorts corresponding to month (30-day period) of UMEC/VI initiation (i.e. Months 1–12) post-index. The outcomes studied during the follow up period included COPD-related and all-cause medical costs, and risk of COPD exacerbations. Marginal structural models (MSM) were used to control for time-varying confounding due to changes in treatment and severity during follow up. Results 2,200 patients initiating UMEC/VI were included in the study sample. Patients’ average age was 69.3 years, 49.9% were female and 69.7% were Medicare insured. Following MSM analysis, 12-month adjusted COPD-related medical costs increased by 2.9% (95% confidence interval [CI]: 0.1–5.9%; p = 0.044) for each monthly delay in UMEC/VI initiation, with a 37.4% higher adjusted cost for patients initiating UMEC/VI in Month 12 versus Month 1 (9524). The 12-month adjusted all-cause medical costs increased by 2.8% (95% CI: 0.6–5.2%; p = 0.013) for each monthly delay, with a 36.1% higher adjusted cost for patients initiating UMEC/VI at Month 12 versus Month 1 (16,727). The monthly risk of severe exacerbation was significantly higher in patients who had not yet initiated UMEC/VI than those who had (hazard ratio: 1.74; 95% CI: 1.35–2.23; p < 0.001). Conclusions Prompt use of UMEC/VI following a physician visit for COPD appears to result in economic and clinical benefits, with reductions in medical costs and exacerbation risk. Additional research is warranted to assess the benefits of initiating UMEC/VI as a first-line therapy compared with escalation to UMEC/VI from monotherapies
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Ganglion cell and retinal nerve fiber layer thickness predict the development of visual field damage in glaucoma suspects
No full textAdditional file 3: of The effect of delaying initiation with umeclidinium/vilanterol in patients with COPD: an observational administrative claims database analysis using marginal structural models
No full textCohort counts by month of UMEC/VI initiation (Nâ=â2200). Additional figure illustrating the number of patients initiating UMEC/VI each month. (DOCX 100 kb
Additional file 4: of The effect of delaying initiation with umeclidinium/vilanterol in patients with COPD: an observational administrative claims database analysis using marginal structural models
No full textMSM sensitivity analyses for COPD-related medical costs. Sensitivity analyses conducted to test the robustness of findings to changes in model structure and assumptions. (DOCX 18 kb
The African Descent and Glaucoma Evaluation Study (ADAGES): Predictors of Visual Field Damage in Glaucoma Suspects
No full textPURPOSE: To evaluate racial differences in the development of visual field (VF) damage in glaucoma suspects.
DESIGN: Prospective, observational cohort study.
METHODS: Six hundred thirty-six eyes from 357 glaucoma suspects with normal VF at baseline were included from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES). Racial differences in the development of VF damage were examined using multivariable Cox proportional hazard models.
RESULTS: Thirty one of 122 African-descent participants (25.4%) and 47 of 235 European-descent participants (20.0%) developed VF damage (P = .078). In multivariable analysis, worse baseline VF mean deviation, higher mean arterial pressure during follow-up, and a race ∗ mean intraocular pressure (IOP) interaction term were significantly associated with the development of VF damage, suggesting that racial differences in the risk of VF damage varied by IOP. At higher mean IOP levels, race was predictive of the development of VF damage even after adjusting for potentially confounding factors. At mean IOPs during follow-up of 22, 24, and 26 mm Hg, multivariable hazard ratios (95% confidence intervals) for the development of VF damage in African-descent compared to European-descent subjects were 2.03 (1.15-3.57), 2.71 (1.39-5.29), and 3.61 (1.61-8.08), respectively. However, at lower mean IOP levels (below 22 mm Hg) during follow-up, African descent was not predictive of the development of VF damage.
CONCLUSION: In this cohort of glaucoma suspects with similar access to treatment, multivariate analysis revealed that at higher mean IOP during follow-up, individuals of African descent were more likely to develop VF damage than individuals of European descent
