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H Hernandez - One of the best experts on this subject based on the ideXlab platform.
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intraocular pressure elevation after uncomplicated pars plana vitrectomy results of the pan american collaborative retina study group
Retina-the Journal of Retinal and Vitreous Diseases, 2014Co-Authors: Maria H Berrocal, Fernando J Arevalo, Francisco Rodriguez, Mauricio Maia, Virgilio Moralescanton, Marta S Figueroa, Martin Serrano, Jose A Roca, Rodrigo M Navarro, H HernandezAbstract:PURPOSE To compare the incident rates of sustained elevation of intraocular pressure (IOP) after uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane and the unoperated fellow eye. METHODS Retrospective multicenter study of 198 patients who underwent pars plana vitrectomy for an idiopathic epiretinal membrane that was followed for at least 12 months. The diagnosis of sustained IOP elevation was defined as an elevation of IOP ≥ 24 mmHg or an increase of ≥ 5 mmHg in the IOP from baseline on 2 separate visits that warranted the initiation of ocular hypotensive therapy. The main outcome measured was the development of sustained IOP elevation as defined above. RESULTS Patients were followed for an average of 47.3 ± 24 months (range, 12-106 months). In the vitrectomized eyes, 38 of the 198 (19.2%) patients developed elevated IOP compared with 9 of the 198 (4.5%) unoperated fellow eyes (P < 0.0001, Fisher Exact Test; odds ratio, 4.988). Possible risk factors include a family history of open-angle glaucoma (P = 0.0004 Fisher Exact Test; odds ratio, 7.206) and cataract surgery (P = 0.0270 Fisher Exact Test; odds ratio, 2.506). CONCLUSION Uncomplicated PPV seems to increase the IOP, particularly in those who are pseudophakic and have a family history of open-angle glaucoma. This increase in IOP may lead to glaucomatous damage if not managed appropriately. Patients with a previous PPV need to be followed by an ophthalmologist to monitor the IOP in the vitrectomized eye.
Yohei Kawasaki - One of the best experts on this subject based on the ideXlab platform.
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bayesian noninferiority Test for 2 binomial probabilities as the extension of Fisher Exact Test
Statistics in Medicine, 2017Co-Authors: Masaaki Doi, Fumihiro Takahashi, Yohei KawasakiAbstract:Noninferiority trials have recently gained importance for the clinical trials of drugs and medical devices. In these trials, most statistical methods have been used from a frequentist perspective, and historical data have been used only for the specification of the noninferiority margin Δ>0. In contrast, Bayesian methods, which have been studied recently are advantageous in that they can use historical data to specify prior distributions and are expected to enable more efficient decision making than frequentist methods by borrowing information from historical trials. In the case of noninferiority trials for response probabilities π1 ,π2 , Bayesian methods evaluate the posterior probability of H1 :π1 >π2 -Δ being true. To numerically calculate such posterior probability, complicated Appell hypergeometric function or approximation methods are used. Further, the theoretical relationship between Bayesian and frequentist methods is unclear. In this work, we give the Exact expression of the posterior probability of the noninferiority under some mild conditions and propose the Bayesian noninferiority Test framework which can flexibly incorporate historical data by using the conditional power prior. Further, we show the relationship between Bayesian posterior probability and the P value of the Fisher Exact Test. From this relationship, our method can be interpreted as the Bayesian noninferior extension of the Fisher Exact Test, and we can treat superiority and noninferiority in the same framework. Our method is illustrated through Monte Carlo simulations to evaluate the operating characteristics, the application to the real HIV clinical trial data, and the sample size calculation using historical data.
Maria H Berrocal - One of the best experts on this subject based on the ideXlab platform.
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intraocular pressure elevation after uncomplicated pars plana vitrectomy results of the pan american collaborative retina study group
Retina-the Journal of Retinal and Vitreous Diseases, 2014Co-Authors: Maria H Berrocal, Fernando J Arevalo, Francisco Rodriguez, Mauricio Maia, Virgilio Moralescanton, Marta S Figueroa, Martin Serrano, Jose A Roca, Rodrigo M Navarro, H HernandezAbstract:PURPOSE To compare the incident rates of sustained elevation of intraocular pressure (IOP) after uncomplicated pars plana vitrectomy for idiopathic epiretinal membrane and the unoperated fellow eye. METHODS Retrospective multicenter study of 198 patients who underwent pars plana vitrectomy for an idiopathic epiretinal membrane that was followed for at least 12 months. The diagnosis of sustained IOP elevation was defined as an elevation of IOP ≥ 24 mmHg or an increase of ≥ 5 mmHg in the IOP from baseline on 2 separate visits that warranted the initiation of ocular hypotensive therapy. The main outcome measured was the development of sustained IOP elevation as defined above. RESULTS Patients were followed for an average of 47.3 ± 24 months (range, 12-106 months). In the vitrectomized eyes, 38 of the 198 (19.2%) patients developed elevated IOP compared with 9 of the 198 (4.5%) unoperated fellow eyes (P < 0.0001, Fisher Exact Test; odds ratio, 4.988). Possible risk factors include a family history of open-angle glaucoma (P = 0.0004 Fisher Exact Test; odds ratio, 7.206) and cataract surgery (P = 0.0270 Fisher Exact Test; odds ratio, 2.506). CONCLUSION Uncomplicated PPV seems to increase the IOP, particularly in those who are pseudophakic and have a family history of open-angle glaucoma. This increase in IOP may lead to glaucomatous damage if not managed appropriately. Patients with a previous PPV need to be followed by an ophthalmologist to monitor the IOP in the vitrectomized eye.
Eyoung Shin - One of the best experts on this subject based on the ideXlab platform.
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fatty acid synthase a metabolic enzyme and candidate oncogene in prostate cancer
Journal of the National Cancer Institute, 2009Co-Authors: Toshiro Migita, Stacey Ruiz, Alessandro Fornari, Michelangelo Fiorentino, Carmen Priolo, Giorgia Zadra, Fumika Inazuka, Chiara Grisanzio, Emanuele Palescandolo, Eyoung ShinAbstract:BACKGROUND: Overexpression of the fatty acid synthase (FASN) gene has been implicated in prostate carcinogenesis. We sought to directly assess the oncogenic potential of FASN. METHODS: We used immortalized human prostate epithelial cells (iPrECs), androgen receptor-overexpressing iPrECs (AR-iPrEC), and human prostate adenocarcinoma LNCaP cells that stably overexpressed FASN for cell proliferation assays, soft agar assays, and Tests of tumor formation in immunodeficient mice. Transgenic mice expressing FASN in the prostate were generated to assess the effects of FASN on prostate histology. Apoptosis was evaluated by Hoechst 33342 staining and by fluorescence-activated cell sorting in iPrEC-FASN cells treated with stimulators of the intrinsic and extrinsic pathways of apoptosis (ie, camptothecin and anti-Fas antibody, respectively) or with a small interfering RNA (siRNA) targeting FASN. FASN expression was compared with the apoptotic index assessed by the terminal deoxynucleotidyltransferase-mediated UTP end-labeling method in 745 human prostate cancer samples by using the least squares means procedure. All statistical Tests were two-sided. RESULTS: Forced expression of FASN in iPrECs, AR-iPrECs, and LNCaP cells increased cell proliferation and soft agar growth. iPrECs that expressed both FASN and androgen receptor (AR) formed invasive adenocarcinomas in immunodeficient mice (12 of 14 mice injected formed tumors vs 0 of 14 mice injected with AR-iPrEC expressing empty vector (P < .001, Fisher Exact Test); however, iPrECs that expressed only FASN did not. Transgenic expression of FASN in mice resulted in prostate intraepithelial neoplasia, the incidence of which increased from 10% in 8- to 16-week-old mice to 44% in mice aged 7 months or more (P = .0028, Fisher Exact Test), but not in invasive tumors. In LNCaP cells, siRNA-mediated silencing of FASN resulted in apoptosis. FASN overexpression protected iPrECs from apoptosis induced by camptothecin but did not protect iPrECs from Fas receptor-induced apoptosis. In human prostate cancer specimens, FASN expression was inversely associated with the apoptotic rate (mean percentage of apoptotic cells, lowest vs highest quartile of FASN expression: 2.76 vs 1.34, difference = 1.41, 95% confidence interval = 0.45 to 2.39, Ptrend = .0046). CONCLUSIONS: These observations suggest that FASN can act as a prostate cancer oncogene in the presence of AR and that FASN exerts its oncogenic effect by inhibiting the intrinsic pathway of apoptosis.
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fatty acid synthase a metabolic enzyme and candidate oncogene in prostate cancer
Journal of the National Cancer Institute, 2009Co-Authors: Toshiro Migita, Stacey Ruiz, Alessandro Fornari, Michelangelo Fiorentino, Carmen Priolo, Giorgia Zadra, Fumika Inazuka, Chiara Grisanzio, Emanuele Palescandolo, Eyoung ShinAbstract:BACKGROUND Overexpression of the fatty acid synthase (FASN) gene has been implicated in prostate carcinogenesis. We sought to directly assess the oncogenic potential of FASN. METHODS We used immortalized human prostate epithelial cells (iPrECs), androgen receptor-overexpressing iPrECs (AR-iPrEC), and human prostate adenocarcinoma LNCaP cells that stably overexpressed FASN for cell proliferation assays, soft agar assays, and Tests of tumor formation in immunodeficient mice. Transgenic mice expressing FASN in the prostate were generated to assess the effects of FASN on prostate histology. Apoptosis was evaluated by Hoechst 33342 staining and by fluorescence-activated cell sorting in iPrEC-FASN cells treated with stimulators of the intrinsic and extrinsic pathways of apoptosis (ie, camptothecin and anti-Fas antibody, respectively) or with a small interfering RNA (siRNA) targeting FASN. FASN expression was compared with the apoptotic index assessed by the terminal deoxynucleotidyltransferase-mediated UTP end-labeling method in 745 human prostate cancer samples by using the least squares means procedure. All statistical Tests were two-sided. RESULTS Forced expression of FASN in iPrECs, AR-iPrECs, and LNCaP cells increased cell proliferation and soft agar growth. iPrECs that expressed both FASN and androgen receptor (AR) formed invasive adenocarcinomas in immunodeficient mice (12 of 14 mice injected formed tumors vs 0 of 14 mice injected with AR-iPrEC expressing empty vector (P < .001, Fisher Exact Test); however, iPrECs that expressed only FASN did not. Transgenic expression of FASN in mice resulted in prostate intraepithelial neoplasia, the incidence of which increased from 10% in 8- to 16-week-old mice to 44% in mice aged 7 months or more (P = .0028, Fisher Exact Test), but not in invasive tumors. In LNCaP cells, siRNA-mediated silencing of FASN resulted in apoptosis. FASN overexpression protected iPrECs from apoptosis induced by camptothecin but did not protect iPrECs from Fas receptor-induced apoptosis. In human prostate cancer specimens, FASN expression was inversely associated with the apoptotic rate (mean percentage of apoptotic cells, lowest vs highest quartile of FASN expression: 2.76 vs 1.34, difference = 1.41, 95% confidence interval = 0.45 to 2.39, Ptrend = .0046). CONCLUSIONS These observations suggest that FASN can act as a prostate cancer oncogene in the presence of AR and that FASN exerts its oncogenic effect by inhibiting the intrinsic pathway of apoptosis.
Masaaki Doi - One of the best experts on this subject based on the ideXlab platform.
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bayesian noninferiority Test for 2 binomial probabilities as the extension of Fisher Exact Test
Statistics in Medicine, 2017Co-Authors: Masaaki Doi, Fumihiro Takahashi, Yohei KawasakiAbstract:Noninferiority trials have recently gained importance for the clinical trials of drugs and medical devices. In these trials, most statistical methods have been used from a frequentist perspective, and historical data have been used only for the specification of the noninferiority margin Δ>0. In contrast, Bayesian methods, which have been studied recently are advantageous in that they can use historical data to specify prior distributions and are expected to enable more efficient decision making than frequentist methods by borrowing information from historical trials. In the case of noninferiority trials for response probabilities π1 ,π2 , Bayesian methods evaluate the posterior probability of H1 :π1 >π2 -Δ being true. To numerically calculate such posterior probability, complicated Appell hypergeometric function or approximation methods are used. Further, the theoretical relationship between Bayesian and frequentist methods is unclear. In this work, we give the Exact expression of the posterior probability of the noninferiority under some mild conditions and propose the Bayesian noninferiority Test framework which can flexibly incorporate historical data by using the conditional power prior. Further, we show the relationship between Bayesian posterior probability and the P value of the Fisher Exact Test. From this relationship, our method can be interpreted as the Bayesian noninferior extension of the Fisher Exact Test, and we can treat superiority and noninferiority in the same framework. Our method is illustrated through Monte Carlo simulations to evaluate the operating characteristics, the application to the real HIV clinical trial data, and the sample size calculation using historical data.