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Patient and Physician Preferences for Treating Adjuvant Melanoma: A Discrete Choice Experiment

Journal of Cancer Therapy 2017年第1期8卷 37-50页

作者： Kathleen Beusterien Mark R. Middleton Peter Feng Wang Sumati Rao Srividya Kotapati javier sabater Baiju Aurora John F. P. Bridges ORS Health Washington DC USA Department of Oncology University of Oxford Churchill Hospital Oxford UK Bristol-Myers Squibb Princeton NJ USA Aurora Capital West Orange NJ USA Johns Hopkins Bloomberg School of Public Health Baltimore MD USA

Objective: To evaluate and compare patient and physician preferences for the benefits and risks of currently available adjuvant melanoma treatments. Methods: Patients with stage II/III melanoma and oncologists in the USA were recruited from 6 clinical sites and an online panel to complete a survey. Preferences were assessed using a paired comparison discrete choice experiment that allowed for opt-out (i.e. no treatment). The treatments comprised 7 attributes, each with 3 levels associated with pegylated interferon, high-dose interferon, and ipilimumab. Attributes included efficacy outcomes, dosing regimen, and risks of moderate to severe toxicities. In addition, open-ended maximum acceptable risk (MAR) questions assessed tradeoffs between toxicity risk and efficacy. Results: 142 patients (45 stage II;97 stage III) chose a treatment in 78% of the choice tasks, while physicians (N = 127) chose treatment 79% of the time. The rankings of relative attribute importance were concordant between the patients and physicians for the top 4: 10-year survival in metastatic melanoma, fatigue risk, 3-year recurrence-free survival (RFS), and depression risk. Patients and physicians valued the difference in 21% survival versus no survival benefit about 3 and 4 times as much, respectively, as reducing diarrhea risk from 41% to 1% or reducing depression risk from 40% to 1%. The MAR of severe diarrhea and of a life-threatening event increased as the chance of 3-year RFS increased, with patients reporting higher risks than physicians. Conclusion: Patients and physicians were concordant in their preferences in adjuvant melanoma, preferring treatment versus none and judging potential efficacy to outweigh risks of toxicities.

关键词： Melanoma Adjuvant Therapy Discrete Choice Experiment

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Quantification of corneal neovascularization after ex vivo limbal epithelial stem cell therapy

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International Journal of Ophthalmology(English edition) 2014年第6期7卷 988-995页

作者： Adriano Guarnieri javier Moreno-Monta?és Belén Alfonso-Bartolozzi Alfonso L.sabater María García-Guzmán Enrique J.Andreu Felipe Prosper Department of Ophthalmology Clínica Universidad de Navarra Department of Cell Therapy Clínica Universidad de Navarra

AIM: To assess cultured limbal epithelial stem cell transplantation in patients with limbal stem cell deficiency by analyzing and quantifying corneal ***: This retrospective, interventional case series included eight eyes with total limbal stem cell deficiency. Ex vivo limbal epithelial stem cells were cultured on human amniotic membrane using an animalfree culture method. The clinical parameters of limbal stem cell deficiency, impression cytology, and quantification of corneal neovascularization were evaluated before and after cultured limbal stem cell transplantation. The area of corneal neovascularization,vessel caliber(VC), and invasive area(IA) were analyzed before and after stem cell transplantation by image analysis software. Best-corrected visual acuity(BCVA),epithelial transparency, and impression cytology were also ***: One year after surgery, successful cases showed a reduction(improvement) of all three parameters of corneal neovascularization [neovascular area(NA), VC, IA], while failed cases did not. NA decreased a mean of 32.31%(P =0.035), invasion area29.37%(P =0.018) and VC 14.29%(P =0.072). BCVA improved in all eyes(mean follow-up, 76 ±21mo).Epithelial transparency improved significantly from 2.00 ±0.93 to 0.88±1.25(P =0.014). Impression cytology showed that three cases failed after limbal epithelial stem cell therapy before 1y of ***: This method of analyzing andmonitoring surface vessels is useful for evaluating the epithelial status during follow-up, as successful cases showed a bigger reduction in corneal neovascularization parameters than failed cases. Using this method,successful cases could be differentiated from failed cases.

关键词： limbal stem cell corneal neovascularization stem cell therapy impression cytology limbal stem cell deficiency

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Protein phosphatases and chromatin modifying complexes in the inflammatory cascade in acute pancreatitis

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2010年第3期1卷 75-80页

作者： javier Escobar javier Pereda Alessandro Arduini Juan Sastre Juan Sandoval Luis Aparisi Gerardo López-Rodas Luis sabater Department of Physiology University of Valencia 46100 Burjasot (Valencia) Spain Department of Biochemistry & Molecular Biology University of Valencia 46100 Burjasot (Valencia) Spain Laboratory of Pancreatic Function University Clinic Hospital 46010 Valencia Spain Department of Surgery University Clinic Hospital 46010 Valencia Spain

Acute pancreatitis is an inflammation of the pancreas that may lead to systemic inflammatory response syndrome and death due to multiple organ failure. Acinar cells, together with leukocytes, trigger the inflammatory cascade in response to local damage of the pancreas. Amplification of the inflammatory cascade requires up-regulation of proinflammatory cytokines and this process is mediated not only by nuclear factor κB but also by chromatinmodifying complexes and chromatin remodeling. Among the different families of histone acetyltransferases, the p300/CBP family seems to be particularly associated with the inflammatory process. cAMP activates gene expression via the cAMP-responsive element (CRE) and the transcription factor CRE-binding protein (CREB). CREB can be phosphorylated and activated by different kinases, such as protein kinase A and MAPK, and then it recruits the histone acetyltransferase co-activator CREB-binding protein (CBP) and its homologue p300. The recruitment of CBP/p300 and changes in the level of histone acetylation are required for transcription activation. Transcriptional repression is also a dynamic and essential mechanism of down-regulation of genes for resolution of inflammation, which seems to be mediated mainly by protein phosphatases (PP1, PP2A and MKP1) and histone deacetylases(HDACs) .Class HDACs are key transcriptional regulators whose activities are controlled via phosphorylationdependent nucleo/cytoplasmic shuttling. PP2A is responsible for dephosphorylation of class HDACs, triggeringnuclear localization and repression of target genes, whereas phosphorylation triggers cytoplasmic localization leading to activation of target genes. The potential benefit from treatment with phosphodiesterase inhibitors and histone deacetylase inhibitors is discussed.

关键词： Dual specificity protein phosphatases Acute pancreatitis Phosphodiesterase inhibitors Cytokines Histone acetylation Pentoxifylline PP2A Serine/threonine protein phosphatases

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Comparative study measuring the dilatory effect of a mydriatic device(Mydriasert~) versus topical drops

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International Journal of Ophthalmology(English edition) 2013年第6期6卷 801-804页

作者： Manuel Saenz-de-Viteri Patricia Fernandez-Robredo Elisa de Nova Elvira Bonet-Farriol Alfonso L.sabater javier Zarranz-Ventura Josemaria Caire Luis M.Sadaba Angel Salinas-Alaman Alfredo Garcia-Layana Department of Ophthalmology University of Navarra

AIM:To compare the mydriatic efficacy of an ophthalmic insert(Mydriasert,MY)versus phenylephrine and tropicamide(PT)eye ***:Two controlled,prospective,randomized,single-blind studies were *** the first study,a total of 80 eyes from 40 outpatient-clinic patients were *** drops were applied to the right eye,and a MY device was inserted in the left eye for *** until maximal pupil dilation for each eye was then *** the second study,80 eyes from 80 patients undergoing cataract surgery were *** dilation was achieved using either PT drops three-times for one hour prior to surgery(40 patients),or a MY device was inserted one hour prior to surgery(40 patients).RESULTS:In the first study,MY achieved superior mydriasis compared to PT eye drops at 90min(9.04±1.33mm vs 8.78±1.37mm,P=0.012).However MY took longer than PT drops to achieve maximal dilation,and mydriasis was inferior in eyes with MY compared to PT drops at 30min(7.21±1.73mm vs 8.22±1.43mm,P<0.001),the two groups only becoming similar by 60min(8.85±1.44mm vs 8.71±1.27mm,P=0.236).In the second study,both MY and PT achieved similar levels of mydriasis at the beginning of surgery(8.75±0.76mm with MY vs 8.77±0.63mm with PT),and also at the end of surgery(7.96±1.06mm with MY vs 8.32±0.72mm with PT),with no significant difference between groups(P=0.08).MY was well tolerated and cardiovascular effects were not influenced by dilation ***:MY could be a safe and efficacious alternative for *** mydriatic effect of MY is as good as conventional PT eye drops after 60min,and is superior after *** also maintains good pupil dilation during cataract surgery.

关键词： Mydriasert~ mydriasis pupil dilation cataract surgery device

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