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Haaland B.,Quantitative Medicine | Haaland B.,National University of Singapore | Tan P.S.,National University of Singapore | De Castro Jr. G.,Instituto Do Cancer Do Estado Of Sao Paulo | And 2 more authors.
Journal of Thoracic Oncology | Year: 2014

INTRODUCTION:: Tyrosine kinase inhibitors gefitinib, erlotinib, and afatinib have been compared with chemotherapy as first-line therapies for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor-activating mutations. This meta-analysis compares gefitinib, erlotinib, afatinib, and chemotherapy. METHODS:: Literature search was performed using relevant keywords. Direct and indirect meta-estimates were generated using log-linear mixed-effects models, with random effects for study. Study-to-study heterogeneity was summarized using I statistics and predictive intervals (PIs). RESULTS:: Literature search yielded eight randomized phase 3 clinical trials comparing gefitinib, erlotinib, or afatinib with chemotherapy as first-line therapy in patients with advanced non-small-cell lung cancer during the last 5 years. Hazard ratio meta-estimates for progression-free survival were for gefitinib versus chemotherapy 0.44 (95% confidence interval [CI] 0.31-0.63; 95% PI, 0.22-0.88), erlotinib versus chemotherapy 0.25 (95% CI, 0.15-0.42; 95% PI, 0.11-0.55), afatinib versus chemotherapy 0.44 (95% CI, 0.26-0.75; 95% PI, 0.20-0.98), erlotinib versus gefitinib 0.57 (95% CI, 0.30-1.08; 95% PI, 0.24-1.36), afatinib versus gefitinib 1.01 (95% CI, 0.53-1.92; 95% PI, 0.41-2.42), and erlotinib versus afatinib 0.56 (95% CI, 0.27-1.18; 95% PI, 0.22-1.46). Results for overall response rate and disease control rate were similar. There was no evidence that gefitinib, erlotinib, or afatinib improved overall survival compared with chemotherapy. CONCLUSION:: Gefitinib, erlotinib, and afatinib out-performed chemotherapy in terms of progression-free survival, overall response rate, and disease control rate. Differences among gefitinib, erlotinib, and afatinib were not statistically significant. Copyright © 2014 by the International Association for the Study of Lung Cancer. Source


Ding J.,Singapore Eye Research Institute | Ding J.,Quantitative Medicine | Ding J.,National University of Singapore | Wong T.Y.,Singapore Eye Research Institute | Wong T.Y.,National University of Singapore
Current Diabetes Reports | Year: 2012

With increasing global prevalence of diabetes, diabetic retinopathy (DR) is set to be the principle cause of vision impairment in many countries. DR affects a third of people with diabetes and the prevalence increases with duration of diabetes, hyperglycemia, and hypertension-the major risk factors for the onset and progression of DR. There are now increasing data on the epidemiology of diabetic macular edema (DME), an advanced complication of DR, with studies suggesting DME may affect up to 7 % of people with diabetes. The risk factors for DME are largely similar to DR, but dyslipidemia appears to play a more significant role. Early detection of DR and DME through screening programs and appropriate referral for therapy is important to preserve vision in individuals with diabetes. Future research is necessary to better understand the potential role of other risk factors such as apolipoproteins and genetic predisposition to shape public health programs. © Springer Science+Business Media, LLC 2012. Source


Wong W.L.,Singapore Eye Research Institute | Wong W.L.,National University of Singapore | Su X.,Singapore Eye Research Institute | Su X.,National University of Singapore | And 9 more authors.
The Lancet Global Health | Year: 2014

Background: Numerous population-based studies of age-related macular degeneration have been reported around the world, with the results of some studies suggesting racial or ethnic differences in disease prevalence. Integrating these resources to provide summarised data to establish worldwide prevalence and to project the number of people with age-related macular degeneration from 2020 to 2040 would be a useful guide for global strategies. Methods: We did a systematic literature review to identify all population-based studies of age-related macular degeneration published before May, 2013. Only studies using retinal photographs and standardised grading classifications (the Wisconsin age-related maculopathy grading system, the international classification for age-related macular degeneration, or the Rotterdam staging system) were included. Hierarchical Bayesian approaches were used to estimate the pooled prevalence, the 95% credible intervals (CrI), and to examine the difference in prevalence by ethnicity (European, African, Hispanic, Asian) and region (Africa, Asia, Europe, Latin America and the Caribbean, North America, and Oceania). UN World Population Prospects were used to project the number of people affected in 2014 and 2040. Bayes factor was calculated as a measure of statistical evidence, with a score above three indicating substantial evidence. Findings: Analysis of 129664 individuals (aged 30-97 years), with 12727 cases from 39 studies, showed the pooled prevalence (mapped to an age range of 45-85 years) of early, late, and any age-related macular degeneration to be 8·01% (95% CrI 3·98-15·49), 0·37% (0·18-0·77), and 8·69% (4·26-17·40), respectively. We found a higher prevalence of early and any age-related macular degeneration in Europeans than in Asians (early: 11·2% vs 6·8%, Bayes factor 3·9; any: 12·3% vs 7·4%, Bayes factor 4·3), and early, late, and any age-related macular degeneration to be more prevalent in Europeans than in Africans (early: 11·2% vs 7·1%, Bayes factor 12·2; late: 0·5% vs 0·3%, 3·7; any: 12·3% vs 7·5%, 31·3). There was no difference in prevalence between Asians and Africans (all Bayes factors <1). Europeans had a higher prevalence of geographic atrophy subtype (1·11%, 95% CrI 0·53-2·08) than Africans (0·14%, 0·04-0·45), Asians (0·21%, 0·04-0·87), and Hispanics (0·16%, 0·05-0·46). Between geographical regions, cases of early and any age-related macular degeneration were less prevalent in Asia than in Europe and North America (early: 6·3% vs 14.3% and 12·8% [Bayes factor 2·3 and 7·6]; any: 6·9% vs 18·3% and 14·3% [3·0 and 3·8]). No significant gender effect was noted in prevalence (Bayes factor <1·0). The projected number of people with age-related macular degeneration in 2020 is 196 million (95% CrI 140-261), increasing to 288 million in 2040 (205-399). Interpretation: These estimates indicate the substantial global burden of age-related macular degeneration. Summarised data provide information for understanding the effect of the condition and provide data towards designing eye-care strategies and health services around the world. Funding: National Medical Research Council, Singapore. © 2014 Wong et al. Source


Bush W.S.,Vanderbilt University | Moore J.H.,Quantitative Medicine
PLoS Computational Biology | Year: 2012

Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS. © 2012 Bush, Moore. Source


Moore J.H.,Quantitative Medicine
Methods in Molecular Biology | Year: 2015

Here we introduce the ReliefF machine learning algorithm and some of its extensions for detecting and characterizing epistasis in genetic association studies. We provide a general overview of the method and then highlight some of the modifi cations that have greatly improved its power for genetic analysis. We end with a few examples of published studies of complex human diseases that have used ReliefF. © Springer Science+Business Media New York 2015. Source

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