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1.
Phys Rev Lett ; 125(18): 187401, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33196216

RESUMO

We investigate the frontier between classical and quantum plasmonics in highly doped semiconductor layers. The choice of a semiconductor platform instead of metals for our study permits an accurate description of the quantum nature of the electrons constituting the plasmonic response, which is a crucial requirement for quantum plasmonics. Our quantum model allows us to calculate the collective plasmonic resonances from the electronic states determined by an arbitrary one-dimensional potential. Our approach is corroborated with experimental spectra, realized on a single quantum well, in which higher order longitudinal plasmonic modes are present. We demonstrate that their energy depends on the plasma energy, as is also the case for metals, but also on the size confinement of the constituent electrons. This work opens the way toward the applicability of quantum engineering techniques for semiconductor plasmonics.

2.
J Med Econ ; 21(1): 27-37, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28830258

RESUMO

OBJECTIVE: To conduct cost-effectiveness analyses comparing the addition of golimumab to the standard of care (SoC) for treatment of patients with moderate-to-severe ulcerative colitis (UC) who are refractory to conventional therapies in Quebec (Canada). METHODS: An individual patient state transition microsimulation model was developed to project health outcomes and costs over 10 years, using a payer perspective. The incremental benefit estimates for golimumab were driven by induction response and risk of a flare. Flare risks post-induction were derived for golimumab from the PURSUIT maintenance trial and extension study, while those for SoC were derived from the placebo arms of the Active Ulcerative Colitis Trials (ACT) 1 and 2. Other inputs were derived from multiple sources, including retrospective claims analyses and literature. Costs are reported in 2014 Canadian dollars. A 5% annual discount rate was applied to costs and quality-adjusted life-years (QALYs). RESULTS: Compared with SoC, golimumab was projected to increase the time spent in mild disease or remission states, decrease flare rates, and increase QALYs. These gains were achieved with higher direct medical costs. The incremental cost-effectiveness ratio for golimumab vs SoC was $63,487 per QALY. LIMITATIONS: The long-term flare projections for SoC were based on the data available from the ACT 1 and 2 placebo arms, as data were not available from the PURSUIT maintenance or extension trial. Additionally, the study was limited to only SoC and golimumab, due to the availability of individual patient data to analyze. CONCLUSION: This economic analysis concluded that treatment with golimumab is likely more cost-effective vs SoC when considering cost-effectiveness acceptability thresholds from $50,000-$100,000 per QALY.


Assuntos
Anticorpos Monoclonais/economia , Colite Ulcerativa/tratamento farmacológico , Análise Custo-Benefício , Custos de Cuidados de Saúde , Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/economia , Feminino , Humanos , Masculino , Cadeias de Markov , Modelos Econômicos , Quebeque , Índice de Gravidade de Doença
3.
J Med Econ ; 20(7): 692-702, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28294645

RESUMO

BACKGROUND: A phase III trial evaluated the efficacy and safety of Daklinza (daclatasvir or DCV) in combination with sofosbuvir (SOF) for treatment of genotype (GT) 3 hepatitis C virus (HCV) patients. AIM: This study evaluated the cost-effectiveness of DCV + SOF vs SOF in combination with ribavirin (RBV) over a 20-year time horizon from the perspective of a United States (US) payer. METHODS: A published Markov model was adapted to reflect US demographic characteristics, treatment patterns, costs of drug acquisition, monitoring, disease and adverse event management, and mortality risks. Clinical inputs came from the ALLY-3 and VALENCE trials. The primary outcome was the incremental cost-utility ratio. Life-years, incidence of complications, number of patients achieving sustained virological response (SVR), and the total cost per SVR were secondary outcomes. Costs (2014 USD) and quality-adjusted life years (QALYs) were discounted at 3% per year. Deterministic, probabilistic, and scenario sensitivity analyses were conducted. RESULTS: DCV + SOF was associated with lower costs and better effectiveness than SOF + RBV in the base case and in almost all scenarios (i.e. treatment-experienced, non-cirrhotic, time horizons of 5, 10, and 80 years). DCV + SOF was less costly, but also slightly less effective than SOF + RBV in the cirrhotic and treatment-naïve population scenarios. Results were sensitive to variations in the probability of achieving SVR for both treatment arms. DCV + SOF costs less than $50,000 per QALY gained in 79% of all probabilistic iterations compared with SOF + RBV. CONCLUSION: DCV + SOF is a dominant option compared with SOF + RBV in the US for the overall GT 3 HCV patient population.


Assuntos
Antivirais/economia , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Adulto , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Carbamatos , Análise Custo-Benefício , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Imidazóis/economia , Imidazóis/uso terapêutico , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Modelos Econômicos , Pirrolidinas , Anos de Vida Ajustados por Qualidade de Vida , Sofosbuvir/economia , Sofosbuvir/uso terapêutico , Análise de Sobrevida , Estados Unidos , Valina/análogos & derivados
4.
J Med Econ ; 18(11): 930-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26086535

RESUMO

OBJECTIVE: This study evaluates the cost-effectiveness of memantine extended release (ER) as an add-on therapy to acetylcholinesterase inhibitor (AChEI) [combination therapy] for treatment of patients with moderate-to-severe Alzheimer's disease (AD) from both a healthcare payer and a societal perspective over 3 years when compared to AChEI monotherapy in the US. METHODS: A phase III trial evaluated the efficacy and safety of memantine ER for treatment of AD patients taking an AChEI. The analysis assessed the long-term costs and health outcomes using an individual patient simulation in which AD progression is modeled in terms of cognition, behavior, and functioning changes. Input parameters are based on patient-level trial data, published literature, and publicly available data sources. Changes in anti-psychotic medication use are incorporated based on a published retrospective cohort study. Costs include drug acquisition and monitoring, total AD-related medical care, and informal care associated with caregiver time. Incremental cost-utility ratio (ICUR), life years, care time for caregiver, time in community and institution, time on anti-psychotics, time by disease severity, and time without severe symptoms are reported. Costs and health outcomes are discounted at 3% per annum. RESULTS: Considering a societal perspective over 3 years, this analysis shows that memantine ER combined with an AChEI provides better clinical outcomes and lower costs than AChEI monotherapy. Discounted average savings were estimated at $18,355 and $20,947 per patient and quality-adjusted life-years (QALYs) increased by an average of 0.12 and 0.13 from a societal and healthcare payer perspective, respectively. Patients on combination therapy spent an average of 4 months longer living at home and spend less time in moderate-severe and severe stages of the disease. CONCLUSION: Combination therapy for patients with moderate-to-severe AD is a cost-effective treatment compared to AChEI monotherapy in the US.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/economia , Inibidores da Colinesterase/uso terapêutico , Memantina/economia , Memantina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/administração & dosagem , Cuidadores/economia , Cuidadores/estatística & dados numéricos , Inibidores da Colinesterase/administração & dosagem , Análise Custo-Benefício , Preparações de Ação Retardada , Progressão da Doença , Quimioterapia Combinada , Feminino , Humanos , Masculino , Cadeias de Markov , Memantina/administração & dosagem , Anos de Vida Ajustados por Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença
5.
Pharmacoeconomics ; 32(6): 559-72, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24643323

RESUMO

The growing number of disease-modifying treatments (DMTs) for patients with multiple sclerosis (MS) and the high acquisition costs of these DMTs are likely to increase the demand for information on their cost effectiveness. To improve the comparability and applicability of the findings from future cost-effectiveness analyses, it would be useful to have a clear understanding of the methodological challenges of modelling the cost effectiveness of DMTs in MS and the different approaches taken by such studies to date. In contrast to previous review studies, this review focuses on long-term time horizon (≥10 years) simulation-based cost-effectiveness analyses with homogeneous contexts of analysis (i.e. those with similar study objectives, comparators, and target populations) published over the past decade. By doing so, it provides a clearer picture of how modelling approaches taken in the existing studies truly differ across studies, and reveals major areas for improvement in conducting future cost-effectiveness analyses of DMTs for patients with MS.


Assuntos
Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/economia , Adjuvantes Imunológicos/economia , Adjuvantes Imunológicos/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/economia , Antineoplásicos/uso terapêutico , Análise Custo-Benefício , Progressão da Doença , Humanos , Imunossupressores/economia , Imunossupressores/uso terapêutico , Modelos Econômicos
6.
PLoS One ; 8(4): e60045, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23577081

RESUMO

What are the commonalities between genes, whose expression level is partially controlled by eQTL, especially with regard to biological functions? Moreover, how are these genes related to a phenotype of interest? These issues are particularly difficult to address when the genome annotation is incomplete, as is the case for mammalian species. Moreover, the direct link between gene expression and a phenotype of interest may be weak, and thus difficult to handle. In this framework, the use of a co-expression network has proven useful: it is a robust approach for modeling a complex system of genetic regulations, and to infer knowledge for yet unknown genes. In this article, a case study was conducted with a mammalian species. It showed that the use of a co-expression network based on partial correlation, combined with a relevant clustering of nodes, leads to an enrichment of biological functions of around 83%. Moreover, the use of a spatial statistics approach allowed us to superimpose additional information related to a phenotype; this lead to highlighting specific genes or gene clusters that are related to the network structure and the phenotype. Three main results are worth noting: first, key genes were highlighted as a potential focus for forthcoming biological experiments; second, a set of biological functions, which support a list of genes under partial eQTL control, was set up by an overview of the global structure of the gene expression network; third, pH was found correlated with gene clusters, and then with related biological functions, as a result of a spatial analysis of the network topology.


Assuntos
Biologia Computacional , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Locos de Características Quantitativas/genética , Análise por Conglomerados , Humanos , Concentração de Íons de Hidrogênio , Músculos/química , Músculos/metabolismo , Fenótipo
8.
Curr Alzheimer Res ; 8(5): 543-51, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21605049

RESUMO

Alzheimer's disease (AD) is the most common form of dementia. Recently, a number of epidemiological studies have evidence that some dietary factors such as low antioxidants and vitamins intake could increase the risk of AD. In the opposite, diets rich in unsaturated fatty acids, in polyphenols, vitamins and antioxidants were identified as preventive factors. Several studies have reported that adherence to the Mediterranean diet (MeDi) was associated with a reduction in incident of dementia. The beneficial effect of MeDi may be the result of the association of some individual and non-identified food components and high consumption of olive oil. In this study we have investigated the protective effects of two components of olive oil, tyrosol (Tyr) and hydroxytyrosol (OH-Tyr), against Aß-induced toxicity. In cultured neuroblastoma N2a cells, we found that Aß(25-35) (100 µg/ml) treatment induced a decrease of glutathione (GSH) and the activation of the transcription factor NF-κB and cell death. Our results demonstrated that the number of cell death decreased when cells were co-treated with Aß and Tyr or OH-Tyr. However, neither of these phenolic compounds was able to prevent the decrease of GSH induced by H(2)O(2) or Aß. We found that the increase in the nuclear translocation of the NF-κB subunits after Aß exposure was attenuated in the presence of Tyr or OH-Tyr. These results identified two individual food components of the MeDi as neuroprotective agent against Aß and their potential involvement in the beneficial effect of the MeDi for the prevention of AD.


Assuntos
Antioxidantes/farmacologia , NF-kappa B/metabolismo , Álcool Feniletílico/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Peptídeos beta-Amiloides/toxicidade , Animais , Western Blotting , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Glutationa/metabolismo , Imuno-Histoquímica , Camundongos , Azeite de Oliva , Álcool Feniletílico/farmacologia , Óleos de Plantas/química , Transporte Proteico/efeitos dos fármacos
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