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1.
Eur J Cancer Care (Engl) ; 29(1): e13196, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31825141

RESUMO

BACKGROUND: Using data from the 4-year follow-up results of an open, randomised, phase II study, this patient-based cost-effectiveness analysis compares mFOLFIRI (irinotecan, 5-fluorouracil and leucovorin, the IRI arm) with mFOLFOX7 (oxaliplatin, 5-fluorouracil and leucovorin, the OXA arm) as first-line treatments in patients with locally advanced gastric adenocarcinoma (GC). METHODS: A Markov model was created based on previous results reported at the 2016 Gastrointestinal Cancers Symposium to evaluate mFOLFIRI and mFOLFOX7 for advanced GC quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were examined as the primary outcomes. RESULTS: For the evaluable 128 patients, treatment efficacy was 0.59 QALYs for the IRI arm and 0.70 QALYs for the OXA arm, with a total cost of $13,861.34 for the IRI arm and $14,127.30 for the OXA arm. Hence, the ICER was $2,417.82 per QALY the OXA arm, which was below the threshold of 3 × per capita GDP of China. For subgroup analysis of those receiving mFOLFIRI followed by mFOLFOX7 (the IRI arm) and the reverse (the OXA arm), the OXA arm gained 0.44 more QALYs than the IRI arm with a total cost of $28,890.09 for the IRI arm and $31,147.30 for the OXA arm. However, the cost per QALY was also lower for the OXA arm than for the IRI arm, and the cost per QALY gained was $5,129.55 (below the Chinese WTP). CONCLUSION: mFOLFOX7 is a very high cost-effective alternative as the first-line treatment for those patients with advanced GC compared with mFOLFIRI.

2.
Can Respir J ; 2019: 3859230, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31182983

RESUMO

Objective: To evaluate the difference of clinical efficacy of peramivir alone and peramivir combined with immunomodulators (either ribonucleic acid or thymopetidum) in the treatment of severe influenza A with primary viral pneumonia. Methods: A retrospective analysis was applied to 45 patients who were diagnosed with severe influenza A with primary viral pneumonia in our hospital from December 2017 to March 2018. The cases were divided into three groups: the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group. Results: The duration of viral nucleic acid positivity in the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group was 6.13 ± 2.06, 6.53 ± 2.72, and 6.10 ± 1.37 days, respectively. The remission time of the clinical symptoms of the peramivir group, the peramivir combined with ribonucleic acid group, and the peramivir combined with thymopetidum group was 8.06 ± 2.73, 7.94 ± 2.89, and 7.67 ± 1.58 days, respectively. Comparisons between the peramivir group and the peramivir combined with ribonucleic acid group or the peramivir combined with thymopetidum group revealed no significant differences in the duration of virus nucleic acid positivity, remission time of clinical symptoms, time to fever alleviation, and time to cough alleviation. Conclusions: There is no observed benefit in the addition of ribonucleic acid or thymopetidum when peramivir sodium chloride injection is used in the treatment of severe influenza A with primary viral pneumonia. This trial is registered with ChiCTR1800019417.

4.
Biomed Res Int ; 2018: 7862306, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29984248

RESUMO

Objective: To explore the safety of the essential medicines recorded in China's list through the comparison of the list of essential medicines of China and the World Health Organization (WHO), as well as the analysis of the basic situation and characteristics of adverse drug reactions (ADRs) on the two essential medicines recorded in China's and WHO lists in order to provide a reference for the improvement of China's list. Methods: A retrospective descriptive study was conducted, based on the database in Jiangsu Province ADR Monitoring Center from 2013 to 2015. A total of 266869 cases reports were collected within this period, comparing the differences between the two essential medicines recorded in China's and WHO lists, considering number of ADRs, type of report, and modes of administration. Compare the differences between the two groups of drugs in the presence of new, severe, and new severe adverse events using chi square test. Results: Comparing the two essential medicines list, they have the same 117 species. When comparing ADRs in the two groups, most are antimicrobial, electrolytes, and acid-base balance drugs, regulate water, and are higher in China. In addition, with respect to the number of ADR types in the two groups, there is statistical significance (p<0.001) (total number is 68603 and 47515, new types are 12601 and 7262, the severe are 2714 and 7566, and the new severe are 820 and 716). Conclusion: Compared to the WHO list of essential drugs, China's list is still to be improved.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos Essenciais/efeitos adversos , China , Medicamentos Essenciais/normas , Humanos , Estudos Retrospectivos , Organização Mundial da Saúde
5.
Oncotarget ; 8(40): 67369-67379, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28978039

RESUMO

Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation. Its damage to the major organs was also evaluated. DC-VEC vaccine resulted in retarded tumor progression and prolonged survival in mice. In DC-VEC group, large amount of immunoglobulin was generated, T cells exhibited greater cytotoxicity against VE-cadherin, and tumor angiogenesis was suppressed. Besides, a decrease of VEGF-A and TGF-ß1, and an increase of IL-4 and IFN-γ were observed. CD4+ and CD8+ T cells were higher, with increased IFN-γ secretion. The percentage of myeloid-derived suppressor cells and regulatory T cells decreased mildly. Also, it had no pathologic changes in major organs. DC-VEC vaccine represents a promising antitumor immunotherapy. The main mechanism is associated with its anti-angiogenesis and immunoregulation response.

6.
Int J Mol Sci ; 18(5)2017 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-28498357

RESUMO

Adiponectin, an adipocyte-derived hormone, exerts pleiotropic biological effects on metabolism, inflammation, vascular homeostasis, apoptosis and immunity. Recently, adiponectin has been suggested to attenuate the progression of human dermal fibrosis. Connective tissue growth factor (CTGF) is induced in keloids and is thought to be participated in the formation of keloid fibrosis. However, the roles played by adiponectin in keloids remain unclear. In this study, we explored the effects of adiponectin on CTGF-induced cell proliferation, migration and the deposition of extracellular matrix (ECM) and their associated intracellular signalling pathways in keloid fibroblasts (KFs). We also explored possible mechanisms of keloid pathogenesis. Primary fibroblast cultures were established from foreskin biopsies and skin biopsies from patients with keloids. The expression of adiponectin and adiponectin receptors (adipoRs) was evaluated by reverse transcription-PCR (RT-PCR), quantitative real-time RT-PCR, immunofluorescence staining, and immunohistochemical analysis. Next, KFs and normal dermal fibroblasts (NFs) were treated with CTGF in the presence or absence of adiponectin. A cell counting kit-8 (CCK-8) and the Transwell assay were used to examine cell proliferation and migration. The level of the collagen I, fibronectin (FN) and α-smooth muscle actin (α-SMA) mRNAs and proteins were determined by quantitative real-time RT-PCR and western blotting. The effects of RNA interference (RNAi) targeting the adipoR genes were detected. Phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase-protein kinase (PI3K-Akt) were examined by western blotting to further investigate the signalling pathways. Furthermore, inhibitors of signal transduction pathways were investigated. The expression levels of adiponectin and adipoRs were significantly decreased in keloids compared with those in normal skin tissue. Adiponectin suppressed the CTGF-induced KFs, but not NFs, proliferation, migration and ECM production. Moreover, adiponectin inhibited the phosphorylation of AMPK, p38 and extracellular-regulated kinase (ERK), but not that of Jun N-terminal kinase (JNK) or Akt, in CTGF-treated KFs. The activity of adiponectin-mediated signalling pathways was attenuated by small interfering RNAs (siRNAs) targeting adipoR1 (but not siRNAs targeting adipoR2, T-cadherin or calreticulin), AMPK (Compound C), p38 (SB203580) inhibitors, and mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059). Based on our results, adiponectin suppresses CTGF-induced KFs proliferation, migration and ECM overproduction. One of the underlying mechanisms is the activation of the adipoR1, AMPK, p38, and ERK signalling pathways. Therefore, adiponectin may play an important role in the progression of keloids, suggesting a potential novel target for keloid treatment.


Assuntos
Adiponectina/metabolismo , Movimento Celular , Proliferação de Células , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Queloide/metabolismo , Adiponectina/genética , Adulto , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/genética , Matriz Extracelular/genética , Feminino , Humanos , Queloide/patologia , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo
7.
J Cancer Res Clin Oncol ; 143(2): 361-368, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27798730

RESUMO

BACKGROUND: Apatinib, a third-line or later treatment for advanced gastric cancer (aGC), was shown to improve overall survival and progression-free survival (PFS) compared with placebo in the phase III trial. Given the modest benefit with high costs, we further evaluated the cost-effectiveness of apatinib for patients with chemotherapy-refractory aGC. METHODS: A Markov model was developed to simulate the disease process of aGC (PFS, progressive disease, and death) and estimate the incremental cost-effectiveness ratio (ICER) of apatinib to placebo. The health outcomes and utility scores were derived from the phase III trial and previously published sources, respectively. Total costs were calculated from the perspective of the Chinese health-care payer. Sensitivity analysis was used to explore model uncertainties. RESULTS: Treatment with apatinib was estimated to provide an incremental 0.09 quality-adjusted life years (QALYs) at an incremental cost of $8113.86 compared with placebo, which resulted in an ICER of $90,154.00 per QALY. Sensitivity analysis showed that across the wide variation of parameters, the ICER exceeded the willingness-to-pay threshold of $23,700.00 per QALY which was three times the Gross Domestic Product per Capita in China. CONCLUSIONS: Apatinib is not a cost-effective option for patients with aGC who experienced failure of at least two lines chemotherapy in China. However, for its positive clinical value and subliminal demand, apatinib can provide a new therapeutic option.


Assuntos
Antineoplásicos/economia , Piridinas/economia , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Análise Custo-Benefício , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Humanos , Cadeias de Markov , Método de Monte Carlo , Piridinas/farmacologia , Piridinas/uso terapêutico , Sensibilidade e Especificidade , Neoplasias Gástricas/mortalidade , Resultado do Tratamento
8.
Medicine (Baltimore) ; 95(27): e3762, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27399059

RESUMO

Cetuximab (Cetux)/Bevacizumab (Bev) treatments have shown considerably survival benefits for patients with metastatic colorectal cancer (mCRC) in the last decade. But they are costly. Currently, no data is available on the health economic implications of testing for extended RAS wild-type (wt) prior to Cetux/Bev treatments of patients with mCRC. This paper aimed to evaluate the cost-effectiveness of predictive testing for extended RAS-wt status in mCRC in the context of targeting the use of Cetux/Bev.Markov model 1 was conducted to provide evidence evaluating the cost-effectiveness of predictive testing for KRAS-wt or extended RAS-wt status based on treatments of chemotherapy plus Cetux/Bev. Markov model 2 assessed the cost-effectiveness of FOLFOX plus Cetux/Bev or FOLFIRI plus Cetux/Bev in extended RAS-wt population. Primary base case data were identified from the CALGB 80405 trial and the literatures. Costs were estimated from West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was calculated.In analysis 1, the cost per QALY was $88,394.09 for KRAS-Cetux, $80,797.82 for KRAS-Bev, $82,590.72 for RAS-Cetux, and $75,358.42 for RAS-Bev. The ICER for RAS-Cetux versus RAS-Bev was $420,700.50 per QALY gained. In analysis 2, the cost per QALY was $81,572.61, $80,856.50, $80,592.22, and $66,794.96 for FOLFOX-Cetux, FOLFOX-Bev, FOLFIRI-Cetux, and FOLFIRI-Bev, respectively. The analyses showed that the extended RAS-wt testing was less costly and more effective versus KRAS-wt testing before chemotherapy plus Cetux/Bev. Furthermore, FOLFIRI plus Bev was the most cost-effective strategy compared with others in extended RAS-wt population.It was economically favorable to identify patients with extended RAS-wt status. Furthermore, FOLFIRI plus Bev was the preferred strategy in extended RAS-wt patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Análise Custo-Benefício , Proteínas ras/análise , Proteínas ras/economia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Metástase Neoplásica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas ras/genética
9.
Tumori ; 2016(3): 294-300, 2016 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-27056335

RESUMO

PURPOSE: Fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GEM-N) have shown a significant survival benefit for the treatment of metastatic pancreatic cancer. The objective of this study was to assess the cost-effectiveness of FOLFIRINOX versus GEM-N for treating metastatic pancreatic cancer based on the PRODIGE and MPACT trials. METHODS: A decision model was performed to compare FOLFIRINOX with GEM-N. Primary base case data were identified from PRODIGE and MPACT trials. Costs were estimated and incremental cost-effectiveness ratio (ICER) was calculated at West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALY). Finally, sensitive analysis was performed by varying potentially modifiable parameters in the model. RESULTS: The base-case analysis showed that FOLFIRINOX cost $37,203.75 and yielded a survival of 0.67 QALY, and GEM-N cost $32,080.59 and yielded a survival of 0.51 QALY in the entire treatment. Thus, the ICER of FOLFIRINOX versus GEM-N was $32,019.75 per QALY gained. CONCLUSIONS: The GEM-N regimen was more cost-effective compared with the FOLFIRINOX regimen for the treatment of metastatic pancreatic cancer from a Chinese perspective.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Análise Custo-Benefício , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/administração & dosagem , Albuminas/economia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/economia , China , Ensaios Clínicos como Assunto , Técnicas de Apoio para a Decisão , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/economia , Custos de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/economia , Humanos , Irinotecano , Leucovorina/administração & dosagem , Leucovorina/economia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/economia , Oxaliplatina , Paclitaxel/administração & dosagem , Paclitaxel/economia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Anos de Vida Ajustados por Qualidade de Vida , Análise de Sobrevida
10.
Cancer Biol Ther ; 16(11): 1577-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26418570

RESUMO

The surprising results published by FIRE-3 revealed that the overall survival (OS) of RAS wild-type metastatic colorectal cancer (mCRC) patients treated with Cetuximab(Cmab) and FOLFIRI combination was prolonged to 33.1 months. The substantial increase in testing and treatment costs, however, impose a considerable health burden on patients and society. Hence the study was aimed to assess the cost-effectiveness of RAS screening before monoclonal antibodies (mAbs) therapy based on FIRE-3 study. Four groups were analyzed: group 1, patients with KRAS testing treated with Cmab and FOLFIRI; group 2, patients with RAS testing treated with Cmab and FOLFIRI; group 3, patients with KRAS testing treated with bevacizumab(Bmab) and FOLFIRI; group 4, patients with RAS testing treated with Bmab and FOLFIRI. A Markov model comprising 3 health states (progression-free survival, progressive disease and death) was built. The costs were calculated from a Chinese payer perspective, and survival was reported in quality-adjusted life-months (QALMs). Average total lifetime costs ranged from $104,682.44 (RAS-Bmab) to $136,867.44 (RAS-Cmab), while the survival gained varied from 16.88 QALMs in RAS-Bmab to 21.85 QALMs in RAS-Cmab. The cost per QALM was $6,263.86 for RAS-Cmab, $6,145.84 for KRAS-Bmab, $6,201.57 for RAS-Bmab and $6,960.70 for KRAS-Cmab respectively. The KRAS-Cmab strategy was dominated by the other 3 groups. The first-treatment cost of RAS-Cmab was the most influential one to the model. In all, the RAS screening prior to Cmab treatment in mCRC seems to be a cost-effective strategy in the time of monoclonal antibodies (mAbs) therapy with the most gained QALMs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Proteínas Proto-Oncogênicas p21(ras)/genética , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/economia , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Análise Custo-Benefício , Análise Mutacional de DNA , Intervalo Livre de Doença , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento , Adulto Jovem
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