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1.
Phys Rev Lett ; 131(20): 201802, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38039466

RESUMO

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

2.
J Appl Microbiol ; 131(3): 1113-1122, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33544957

RESUMO

AIMS: For the effective production of 146S particles, which determines foot-and-mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy-to-use, productive and economically affordable for the large-scale production of FMD vaccine. METHODS AND RESULTS: Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK-200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy. CONCLUSIONS: Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale-up process easy and helps in saving the time and labour involved in spent media removal. SIGNIFICANCE AND IMPACT OF THE STUDY: Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial-scale production of FMD vaccines.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Antígenos Virais , Meios de Cultura , Febre Aftosa/prevenção & controle
3.
Phys Rev Lett ; 123(3): 031302, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31386435

RESUMO

We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.

4.
Phys Rev Lett ; 122(13): 131802, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-31012610

RESUMO

A search for inelastic boosted dark matter (IBDM) using the COSINE-100 detector with 59.5 days of data is presented. This relativistic dark matter is theorized to interact with the target material through inelastic scattering with electrons, creating a heavier state that subsequently produces standard model particles, such as an electron-positron pair. In this study, we search for this electron-positron pair in coincidence with the initially scattered electron as a signature for an IBDM interaction. No excess over the predicted background event rate is observed. Therefore, we present limits on IBDM interactions under various hypotheses, one of which allows us to explore an area of the dark photon parameter space that has not yet been covered by other experiments. This is the first experimental search for IBDM using a terrestrial detector.

5.
Phys Rev Lett ; 118(12): 121802, 2017 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-28388195

RESUMO

An experiment to search for light sterile neutrinos is conducted at a reactor with a thermal power of 2.8 GW located at the Hanbit nuclear power complex. The search is done with a detector consisting of a ton of Gd-loaded liquid scintillator in a tendon gallery approximately 24 m from the reactor core. The measured antineutrino event rate is 1976 per day with a signal to background ratio of about 22. The shape of the antineutrino energy spectrum obtained from the eight-month data-taking period is compared with a hypothesis of oscillations due to active-sterile antineutrino mixing. No strong evidence of 3+1 neutrino oscillation is found. An excess around the 5 MeV prompt energy range is observed as seen in existing longer-baseline experiments. The mixing parameter sin^{2}2θ_{14} is limited up to less than 0.1 for Δm_{41}^{2} ranging from 0.2 to 2.3 eV^{2} with a 90% confidence level.

6.
Curr Oncol ; 24(6): e531-e539, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29270063

RESUMO

BACKGROUND: The standard first-line systemic therapy for advanced gastrointestinal stromal tumour (gist) is imatinib. However, most gists develop imatinib resistance, highlighting the need for new agents in the imatinib-refractory setting. Currently, no randomized studies have directly compared the available post-first-line treatments. METHODS: In a systematic review, the medline, embase, and central databases, and American Society of Clinical Oncology abstracts to July 2014 were searched to identify randomized controlled trials that included gist patients treated with post-first-line therapies. Hazard ratios (hrs) for progression-free (pfs) and overall survival (os) were extracted. Direct pairwise meta-analyses and indirect comparisons using the Butcher method were performed. RESULTS: Four studies were identified for the systematic review. One study showed that sunitinib in the second-line setting (vs. placebo) was associated with improved pfs, but not improved os. Three studies examined the third-line setting (imatinib resumption vs. placebo, regorafenib vs. placebo, nilotinib vs. best supportive care). In the third-line settings, the two placebo-controlled and the non-placebo-controlled trials showed significant heterogeneity (I2 = 98%). Indirect comparisons of imatinib resumption and regorafenib suggested that the hr for pfs was 0.59 (95% confidence interval: 0.31 to 1.12; p = 0.10), trending in favour of regorafenib. Indirect comparisons found that toxicities were higher in the regorafenib group, with a risk difference of 27.8% for any-grade toxicities and 19.5% for grades 3 and 4 toxicities. CONCLUSIONS: Because a head-to-head study of imatinib resumption compared with regorafenib is unlikely ever to be conducted, our study suggests that, in terms of pfs, regorafenib might be the preferred treatment. However, given the increased toxicity observed with regorafenib, clinicians should interpret that evidence with caution at an individual patient level.

7.
Public Health ; 129(9): 1204-10, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26198685

RESUMO

OBJECTIVES: The impact of characteristics of neighbourhood environment on physical activity and obesity-related diseases is still the subject of debate. This study aimed to explore the impact of urban neighbourhood environment on physical activity and obesity-related diseases. STUDY DESIGN: Cross-sectional study. METHODS: Individuals who participated in the 2009 national health-screening programme, submitted all necessary information, and had lived in Community 1 (Haengdang) or Community 2 (Ilsan) for at least 2 years (n = 16,178) were selected for inclusion in this study. Anthropometric measures were taken and physical activity was assessed using a short questionnaire. RESULTS: No significant difference in the trigger factors for walking, including the amount of neighbourhood park space, number of shopping malls, and distance between the community and shopping malls, was found between the two communities. However, Community 2 had a better street environment than Community 1. Participants who lived in Community 2 were more physically active [adjusted odds ratio (OR) 1.31, 95% confidence interval (CI) 1.16-1.48] and walked more regularly (adjusted OR 1.09, 95% CI 1.02-1.17) than participants who lived in Community 1, and were less likely to have abdominal obesity (adjusted OR 0.83, 95% CI 0.77-0.91), hypertension (adjusted OR 0.88, 95% CI 0.80-0.97) and diabetes (adjusted OR 0.86, 95% CI 0.75-0.99). However, the risk of dyslipidaemia, especially in terms of low-density lipoprotein cholesterol, was higher in Community 2. CONCLUSIONS: These results suggest that a walkable environment has a positive influence on hypertension and diabetes, and physical activity is the possible mechanism for this association. A walkable environment may function as an important tool for health promotion in urban areas.


Assuntos
Planejamento Ambiental/estatística & dados numéricos , Atividade Motora , Obesidade/epidemiologia , Características de Residência/estatística & dados numéricos , Saúde da População Urbana/estatística & dados numéricos , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Caminhada/estatística & dados numéricos , Adulto Jovem
8.
Curr Oncol ; 22(6): e443-52, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26715881

RESUMO

BACKGROUND: Previous Canadian cost-effectiveness analyses in cancer based on the EQ-5D-3L (EuroQoL, Rotterdam, Netherlands) have commonly used U.K. or U.S. tariffs because the Canadian equivalent only just recently became available. The implications of using non-Canadian tariffs to inform decision-making are unclear. We aimed to reevaluate an earlier cost-effectiveness analysis of therapies for metastatic pancreatic cancer (originally performed using U.S. tariffs) with tariffs from Canada and various other countries to determine the impact of using non-country-specific tariffs. METHODS: We used tariffs from Canada, the United States, the United Kingdom, Denmark, France, Germany, Japan, the Netherlands, and Spain to derive EQ-5D-3L utilities for the 10 health states in the pancreatic cancer model. Quality-adjusted life years (qalys) and incremental cost-effectiveness ratios (icers) were generated, and probabilistic sensitivity analyses (psas) were performed. RESULTS: Canadian utilities are generally lower than the corresponding U.S. utilities and higher than those for the United Kingdom. Compared with the Canadian-valued scenarios, U.S. and U.K. estimates were statistically different for 3 and 9 scenarios respectively. Overall, 35% of the non-Canadian utilities (28 of 80) were significantly different, clinically, from the Canadian values. Canadian qalys were 6% lower than those for the United States and 6% higher than those for the United Kingdom. When comparing the qalys of each treatment with those of gemcitabine alone, the average percent change was +6.8% for a U.S. scenario and -7.5% for a U.K. scenario compared with a Canadian scenario. Consequently, Canadian icers were approximately 5.4% greater than those for the United States and 8.6% lower than those for the United Kingdom. Based on the psas and compared with the Canadian threshold value, the minimum willingness-to-pay threshold at which the combination chemotherapy regimen of gemcitabine-capecitabine is the most cost-effective is $5,239 less than in the United States and $11,986 more than in the United Kingdom. CONCLUSIONS: The use of non-country-specific tariffs leads to significant differences in the derived utilities, icers, and psa results. Past Canadian EQ-5D-3L-based cost-effectiveness analyses and related funding decisions might need to be re-visited using Canadian tariffs.

9.
Curr Oncol ; 22(3): e171-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26089728

RESUMO

BACKGROUND: For cancer patients, information about their disease and its treatment is often delivered within a short time period, potentially leading to patient misunderstanding, which can impede optimal patient care. In this 3-part clinical study, we investigated the utility of an individualized care plan for patients with gastrointestinal (gi) cancer starting a new treatment. METHODS: In part 1, a comprehensive literature search identified items for potential inclusion in the care plan. Those items were formatted into a questionnaire. The questionnaire was then administered to patients as a structured interview. In part 2, health care professionals involved in the care of patients with gi cancer evaluated the resulting care plan for content and relevancy. In part 3, a 20-week prospective cohort study (10 weeks using standard of care, 10 weeks using individualized care plans) was conducted. Outcomes were assessed at baseline and at 2-4 weeks after administration of the care plan. RESULTS: In part 1, a 73-item questionnaire was developed and completed by 20 patients in semi-structured interviews. In part 2, long and short versions of the care plan were created. Most health care professionals preferred the long version. Based on their comments, a final version of the care plan was created. The part 3 study enrolled 104 patients. Overall satisfaction scores were significantly higher in the intervention group at baseline (p = 0.010) and follow-up (p = 0.005). Compared with control patients, the intervention cohort also reported significantly higher overall quality of life (p = 0.044) and fewer symptoms of anxiety (p = 0.048) at follow-up. CONCLUSIONS: Provision of an individualized care plan resulted in improvements in outcome measures at both baseline and follow-up. Future studies are needed to confirm these findings.

10.
Public Health ; 128(3): 254-61, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24612956

RESUMO

OBJECTIVES: The infant mortality rate is a sensitive and commonly used indicator of the socio-economic status of a population. Generally, studies investigating the relationship between infant mortality and socio-economic status have focused on full-term infants in Western populations. This study examined the effects of education level and employment status on full-term and preterm infant mortality in Korea. Data were collected from the National Birth Registration Database and merged with data from the National Death Certification Database. STUDY DESIGN: Prospective cohort study. METHODS: In total, 1,316,184 singleton births registered in Korea's National Birth Registration Database between January 2004 and December 2006 were included in the study. Multivariate logistic regression analysis was performed. RESULTS: Paternal and maternal education levels were inversely related to infant mortality in preterm and full-term infants following multivariate adjusted logistic models. Parental employment status was not associated with infant mortality in full-term infants, but was associated with infant mortality in preterm infants, after adjusting for place of birth, gender, marital status, paternal age, maternal age and parity. CONCLUSIONS: Low paternal and maternal education levels were found to be associated with infant mortality in both full-term and preterm infants. Low parental employment status was found to be associated with infant mortality in preterm infants but not in full-term infants. In order to reduce inequalities in infant mortality, public health interventions should focus on providing equal access to education.


Assuntos
Emprego/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Mortalidade Infantil/tendências , Recém-Nascido Prematuro , Pais , Nascimento a Termo , Adulto , Bases de Dados Factuais , Escolaridade , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Logísticos , Masculino , Gravidez , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco , Adulto Jovem
11.
Curr Oncol ; 21(1): e116-21, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24523608

RESUMO

Aggressive treatment of colorectal cancer (crc) liver metastases can yield long-term survival and cure. Unfortunately, most patients present with technically unresectable metastases; conventional therapy in such patients consists of systemic therapy. Despite advances in the effectiveness of systemic therapy in the first-line setting, the tumour response rate and median survival remain low in the second-line setting. The preferential blood supply from the hepatic artery to crc liver metastases allows for excellent regional delivery of chemotherapy. Here, we review efficacy and safety data for hepatic artery infusion (hai) pump chemotherapy in patients with metastatic crc from the 5-fluorouracil era and from the era of modern chemotherapy. In selected patients with liver-only or liver-dominant disease who have progressed on first-line chemotherapy, hai combined with systemic agents is a viable therapeutic option when performed at experienced centres. Furthermore, significantly improved survival has been demonstrated with adjuvant hai therapy after liver resection in the phase iii setting. The complication rates and local toxicities associated with hai pump therapy are infrequent at experienced centres and can be managed with careful follow-up and early intervention. The major obstacles to the wide adoption of hai therapy include technical expertise for pump insertion and maintenance, and for floxuridine dose modification. The creation of formal preceptor-focused education and training in hai therapy for interdisciplinary medical professionals might encourage the creation and expansion of this liver-directed approach.

12.
Curr Oncol ; 21(1): e129-36, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24523610

RESUMO

Despite significant improvements in systemic therapy for patients with colorectal liver metastases (crlms), response rates in the first-line setting are not optimal, and response rates in the second-line setting remain disappointing. Hepatic arterial infusion pump (haip) chemotherapy has been extensively studied in patients with crlms, but it remains infrequently used. We convened an expert panel to discuss the role of haip in the contemporary management of patients with crlm. Using a consensus process, we developed these statements: haip chemotherapy should be given in combination with systemic chemotherapy.haip chemotherapy should be offered in the context of a multidisciplinary program that includes expertise in hepatobiliary surgery, medical oncology, interventional radiology, nursing, and nuclear medicine.haip chemotherapy in combination with systemic therapy should be considered in patients with unresectable crlms who have progressed on first-line systemic treatment. In addition, haip chemotherapy is acceptable as first-line treatment in patients with unresectable colorectal liver metastases.haip chemotherapy is not recommended in the setting of extrahepatic disease outside the context of a clinical trial.haip chemotherapy in combination with systemic therapy is an option for select patients with resected colorectal liver metastases. These consensus statements provide a framework that clinicians who treat patients with crlm can use when considering treatment with haip.

13.
Ann Oncol ; 24(7): 1792-1801, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23448807

RESUMO

BACKGROUND: We evaluated AGS-1C4D4, a fully human monoclonal antibody to prostate stem cell antigen (PSCA), with gemcitabine in a randomized, phase II study of metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and previously untreated, metastatic pancreatic adenocarcinoma were randomly assigned 1:2 to gemcitabine (1000 mg/m(2) weekly seven times, 1 week rest, weekly three times q4weeks) or gemcitabine plus AGS-1C4D4 (48 mg/kg loading dose, then 24 mg/kg q3weeks IV). The primary end point was 6-month survival rate (SR). Archived tumor samples were collected for pre-planned analyses by PSCA expression. RESULTS: Between April 2009 and May 2010, 196 patients were randomly assigned to gemcitabine (n = 63) or gemcitabine plus AGS-1C4D4 (n = 133). The 6-month SR was 44.4% (95% CI, 31.9-57.5) in the gemcitabine arm and 60.9% (95% CI, 52.1-69.2) in the gemcitabine plus AGS-1C4D4 arm (P = 0.03), while the median survival was 5.5 versus 7.6 months and the response rate was 13.1% versus 21.6% in the two arms, respectively. The 6-month SR was 57.1% in the gemcitabine arm versus 79.5% in the gemcitabine plus AGS-1C4D4 arm among the PSCA-positive subgroup and 31.6% versus 46.2% among the PSCA-negative subgroup. CONCLUSIONS: This randomized, phase II study achieved its primary end point, demonstrating an improved 6-month SR with addition of AGS-1C4D4 to gemcitabine among patients with previously untreated, metastatic pancreatic adenocarcinoma. ClinicalTrials.gov identifier: NCT00902291.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antígenos de Neoplasias/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Feminino , Proteínas Ligadas por GPI/metabolismo , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Modelos de Riscos Proporcionais , Resultado do Tratamento , Gencitabina
14.
Infection ; 41(1): 9-13, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22723075

RESUMO

PURPOSE: The assessment and early recognition of risk factors for infections due to extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) are important for infection control and proper treatment. The aim of the present study was to investigate the prevalence of fecal carriage of ESBL-E in healthy individuals and hospitalized high-risk patients in Korea and to compare the characteristics of ESBL-E in these two groups. METHODS: A total of 384 samples from 290 healthy individuals and 94 high-risk patients were collected. The screening of ESBL-E was performed using a commercial chromogenic medium. Bacterial identification and antibiotic susceptibility testing were performed using the Vitek 2 system. RESULTS: The prevalence of ESBL-E carriage was 20.3 % in healthy individuals and 42.5 % in high-risk patients. Escherichia coli comprised a large majority (96.6 %) of the isolates from healthy individuals, but Klebsiella pneumoniae was more commonly detected (45.0 %) in high-risk patients than in healthy individuals. K. pneumoniae isolates exhibited significantly higher resistance to ceftazidime, ampicillin, and carbapenem, and E. coli exhibited higher resistance to cefotaxime. E. coli from high-risk patients exhibited significantly higher resistance to levofloxacin and cefepime than that from healthy individuals. CONCLUSIONS: We demonstrated the high prevalence of ESBL-E carriage in Korea and clarified the characteristics of ESBL-E carriage in healthy individuals and high-risk patients. The distribution and antibiotic susceptibility of colonizing ESBL-E were different between the group of healthy individuals and the high-risk patients. Active surveillance of ESBL-E carriage is suggested for infection control, and the use of chromogenic agar appears to be an efficient method.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Infecções por Enterobacteriaceae/diagnóstico , Enterobacteriaceae/metabolismo , Fezes/microbiologia , beta-Lactamases/biossíntese , Adulto , Idoso , Infecções Comunitárias Adquiridas/epidemiologia , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco
15.
Public Health ; 127(5): 473-81, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23608023

RESUMO

OBJECTIVE: To identify factors associated with smoking and heavy alcohol consumption among women of reproductive age. STUDY DESIGN: Cross-sectional study. METHODS: Data from 5031 women aged 20-49 years who participated in the Fourth Korean National Health and Nutrition Examination Survey 2007-2009 were analysed. Variables were classified as sociodemographic factors, psychological factors, gynaecological factors and chronic conditions. Factors that influence high-risk behaviours associated with adverse pregnancy outcomes were identified using multiple logistic regression analysis. RESULTS: Among women of reproductive age, prevalence rates of smoking, heavy alcohol consumption and both were 7.3%, 21.4% and 4.3%, respectively. Among the sociodemographic factors, young age, a lower level of education and unmarried status were more likely to be associated with high-risk behaviours such as smoking, heavy alcohol consumption and both. Psychological factors such as stress intensity and suicidal ideation were also significantly associated with all the above-mentioned high-risk behaviours. In addition, an association was found between high-risk behaviours and oral contraceptive use. CONCLUSIONS: Identifying the factors associated with high-risk behaviours may help in the design of interventions to decrease the prevalence of smoking and heavy alcohol consumption. Population-level reduction of these high-risk behaviours among women of reproductive age may improve pregnancy outcomes and also decrease the prevalence of chronic diseases, including cancer, in the long term.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Assunção de Riscos , Fumar/epidemiologia , Fumar/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos Nutricionais , Gravidez , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Fatores Socioeconômicos , Adulto Jovem
16.
Curr Oncol ; 20(2): e90-e106, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23559890

RESUMO

PURPOSE: Gemcitabine and capecitabine (gem-cap), gemcitabine and erlotinib (gem-e), and folfirinox (5-fluorouracil-leucovorin-irinotecan-oxaliplatin) are new treatment options for metastatic pancreatic cancer, but they are also more expensive and potentially more toxic than gemcitabine alone (gem). We conducted a cost-effectiveness analysis of these treatment options compared with gem. METHODS: A Markov model was constructed to examine costs and outcomes of gem-cap, gem-e, folfirinox, and gem in patients with metastatic pancreatic cancer from the perspective of a government health care plan. Ontario health economic and costing data (2010 Canadian dollars) were used. Efficacy data for the treatments were obtained from the published literature. Resource utilization data were derived from a chart review of consecutive metastatic patients treated for pancreatic cancer at Princess Margaret Hospital, Toronto, Ontario, 2008-2009, and supplemented with data from the literature. Utilities were obtained by surveying medical oncologists across Canada using the EQ-5D. Incremental cost-effectiveness ratios (icers) were calculated. RESULTS: The icers for gem-cap, gem-e, and folfirinox compared with gem were, respectively, CA$84,299, CA$153,631, and CA$133,184 per quality-adjusted life year (qaly). The model was driven mostly by drug acquisition costs. Given a willingness-to-pay (wtp) threshold greater than CA$130,000/qaly, folfirinox was most cost-effective treatment. When the wtp threshold was less than CA$80,000/qaly, gem alone was most cost-effective. The gem-e option was dominated by the other treatments. CONCLUSIONS: The most cost-effective treatment for metastatic pancreatic cancer depends on the societal wtp threshold. If the societal wtp threshold were to be relatively high or if drug costs were to be substantially reduced, folfirinox might be cost-effective.

17.
Ann Oncol ; 23(1): 53-58, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21765178

RESUMO

BACKGROUND: The purpose of this study was to determine the clinical activity of patupilone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel. PATIENTS AND METHODS: Eligible patients had progressive disease within 6 months of receiving docetaxel. Patupilone was administered 10 mg/m2 i.v. every 3 weeks. The primary end point was the proportion of patients with a confirmed≥50% prostate-specific antigen (PSA) decline. RESULTS: Eighty-three patients were enrolled. At baseline, the median time to progression after prior docetaxel was 1.4 months (range 0-5.7). Gastrointestinal serious adverse events occurred in four of the six initial patients leading to a reduction of the starting dose of patupilone to 8 mg/m2 for subsequent patients. Grade 3-4 toxicity at this dose included diarrhea (22%), fatigue (21%), and anorexia (10%). One patient experienced grade 3-4 hematologic toxicity. A PSA decline of ≥50% occurred in 47% of patients. A partial measurable disease response occurred in 24% of assessable patients. A patient-reported pain response was observed in 59% of assessable patients. Median time to PSA progression was 6.1 months [95% confidence interval (CI) 4.7-8.0] and median overall survival was 11.3 months (95% CI 9.8-15.4). CONCLUSIONS: Patupilone at 8 mg/m2 was tolerable, had antitumor activity, and was associated with symptomatic improvement in patients previously treated with docetaxel.


Assuntos
Antineoplásicos/uso terapêutico , Epotilonas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Terapia de Salvação/métodos , Idoso , Idoso de 80 Anos ou mais , Canadá , Castração , Intervalo Livre de Doença , Docetaxel , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Taxoides/uso terapêutico
18.
Cytogenet Genome Res ; 138(1): 11-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22889989

RESUMO

Mammalian dosage compensation requires silencing of one of the two X chromosomes in females and is controlled by the X inactivation center (Xic). Xic contains many of the regulatory elements for the mutual interplay of X-inactive specific transcript (Xist) and Tsix, the antisense counterpart of Xist. The regulatory elements control X chromosome inactivation (XCI) via the formation of DNA-DNA and DNA-protein complexes with cis- and trans-acting factors. However, the process-dependent regulation of Xist/Tsix by these elements in each XCI process remains largely unknown. In this study, a 6-thioguanine-resistant female F(1) hybrid mouse cell line (designated HOBMSKI2) was constructed from a cross between a female HPRT-deficient transgenic mouse (designated BM3) and a male wild type Mus spretus mouse (designated MS), which enabled the direct discrimination of both allele-specific expression of X-linked genes and allele-specific binding of proteins associated with XCI due to DNA polymorphisms between BM3 and MS. Using this cell line, we found that Tsix on the active X chromosome (Xa) was not expressed in somatic cells despite the fact that CTCF, which ensures Tsix expression in embryonic stem cells, was still bound to the 5' end of Tsix on Xa, implying that CTCF may function differently during each XCI process and its trans-activating activity for Tsix expression may be lost in the maintenance process. In addition, the monoallelic expression of Tsix on Xa was inhibited by epigenetic modification of the chromatin in the maintenance process, which was mediated by protein complexes recruited by MeCP2. The results indicate the value of HOBMSKI2 in directly detecting the allele-specific binding of CTCF and MeCP2 to the 5' end of Tsix. The HOBMSKI2 mouse line is a versatile and useful resource for studying the molecular mechanism of the XCI process.


Assuntos
Hipoxantina Fosforribosiltransferase/metabolismo , Proteína 2 de Ligação a Metil-CpG/metabolismo , RNA Longo não Codificante/metabolismo , Proteínas Repressoras/metabolismo , Alelos , Animais , Fator de Ligação a CCCTC , Linhagem Celular , Epigênese Genética , Feminino , Hipoxantina Fosforribosiltransferase/deficiência , Masculino , Camundongos , Ligação Proteica
19.
Osteoarthritis Cartilage ; 19(1): 22-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21034839

RESUMO

OBJECTIVE: To assess the effects of joint effusion on proprioceptive status in patients with knee osteoarthritis (OA). DESIGN: A single-blind, randomized, controlled clinical trial in 40 female subjects aged 50 years and over with painful knee OA. All subjects were randomly assigned to either the control or experimental group. A volume of 20 mL of normal saline was injected into the knee joint cavity of subjects in the experimental group under ultrasonographic guidance. Proprioceptive acuity was assessed by active repositioning of the lower limb using an electrogoniometer to measure knee joint position sense (JPS) under both non-weight-bearing (NWB) and weight-bearing (WB) conditions twice, with a 20-min rest interval. The experimental group performed the task twice (Test 1 and Test 2) before and within 5 min after joint infusion. The control group also performed Test 1 and Test 2 without joint infusion. The outcome of interest was the absolute angular error (AAE), ignoring the direction of the error, between the randomized target angle and the patient's reproduced angle of JPS values. RESULTS: Compared with the control group, JPS was significantly compromised in the experimental group in the NWB test after joint infusion (P=0.025). However, no significant differences in the angular error were observed between Test 1 and Test 2 in the control group for the NWB or WB test or in the experimental group for the WB test after infusion (P>0.05). CONCLUSIONS: This study showed that joint effusion impairs proprioceptive function in osteoarthritic knee joints.


Assuntos
Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Propriocepção/fisiologia , Análise de Variância , Feminino , Humanos , Injeções Intra-Articulares , Pessoa de Meia-Idade , Método Simples-Cego , Suporte de Carga
20.
J Chem Phys ; 135(24): 244312, 2011 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-22225161

RESUMO

Using a combination of density functional theory and anion photoelectron spectroscopy experiment, we have studied the structure and electronic properties of CuCl(n)(-) (n = 1-5) and Cu(2)Cl(n)(-) (n = 2-5) clusters. Prominent peaks in the mass spectrum of these clusters occurring at n = 2, 3, and 4 in CuCl(n)(-) and at n = 3, 4, and 5 in Cu(2)Cl(n)(-) are shown to be associated with the large electron affinities of their neutral clusters that far exceed the value of Cl. While CuCl(n) (n ≥ 2) clusters are conventional superhalogens with a metal atom at the core surrounded by halogen atoms, Cu(2)Cl(n) (n ≥ 3) clusters are also superhalogens but with (CuCl)(2) forming the core. The good agreement between our calculated and measured electron affinities and vertical detachment energies confirm not only the calculated geometries of these superhalogens but also our interpretation of their electronic structure and relative stability.

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