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1.
Cogn Emot ; 36(8): 1491-1508, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36196884

RESUMO

Recent work has shown that memory for various types of information associated with social targets (impressions based on behaviours and political ideology) influences decisions to approach or avoid those same targets. The current study was intended to better understand the extent that memory for other types of details associated with targets (beliefs and behaviours) affects subsequent approach/avoidance decisions. In this investigation, participants formed impressions of social targets represented by a picture and a sentence (a belief in Experiment 1; either a belief or behaviour in Experiment 2). Later, memory for the impressions and sentences associated with each target was tested. Finally, participants decided whether they would want to approach or avoid each target. Results demonstrated that accurate memory strongly influenced approach/avoidance decisions for targets associated with different types of information (beliefs; behaviours), although there was no difference in the effect of memory between beliefs and behaviours. Overall, results suggest an important role of memory in decisions to approach or avoid others.


Assuntos
Tomada de Decisões , Memória , Comportamento Social , Humanos
2.
Philos Trans A Math Phys Eng Sci ; 379(2210): 20200448, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34565229

RESUMO

Data-poor tropical wetlands constitute an important source of atmospheric CH4 in the world. We studied CH4 fluxes using closed chambers along a soil moisture gradient in a tropical seasonal swamp in the Okavango Delta, Botswana, the sixth largest tropical wetland in the world. The objective of the study was to assess net CH4 fluxes and controlling environmental factors in the Delta's seasonal floodplains. Net CH4 emissions from seasonal floodplains in the wetland were estimated at 0.072 ± 0.016 Tg a-1. Microbial CH4 oxidation of approximately 2.817 × 10-3 ± 0.307 × 10-3 Tg a-1 in adjacent dry soils of the occasional floodplains accounted for the sink of 4% of the total soil CH4 emissions from seasonal floodplains. The observed microbial CH4 sink in the Delta's dry soils is, therefore, comparable to the global average sink of 4-6%. Soil water content (SWC) and soil organic matter were the main environmental factors controlling CH4 fluxes in both the seasonal and occasional floodplains. The optimum SWC for soil CH4 emissions and oxidation in the Delta were estimated at 50% and 15%, respectively. Electrical conductivity and pH were poorly correlated (r2 ≤ 0.11, p < 0.05) with CH4 fluxes in the seasonal floodplain at Nxaraga. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part1)'.

3.
Nature ; 593(7860): 548-552, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33882562

RESUMO

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

4.
Lett Appl Microbiol ; 72(1): 98-103, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33245575

RESUMO

We retrospectively investigated cases of false-positive diagnoses using the BIOFIRE® FilmArray® meningitis/encephalitis (ME) panel to measure the impact of using a dedicated biosafety cabinet combined with preventive measures to reduce the prevalence of false-positive diagnoses due to pre-analytical in-laboratory contamination. False-positive results were identified by reviewing clinical data, biological parameters and cytology results of cerebrospinal fluid (CSF) samples showing discrepant results between the FilmArray ME panel and routine PCR assays. A total of 327 CSF were analysed over 16 weeks in point-of-care (POC) A and B, over two 8-week periods, periods 1 and 2. The analysis yielded 30 (9·17%) detection of at least one pathogen including 21/30 (70%) viruses and 9/30 (30%) bacteria. During period 1, POC-A and POC-B manipulated CSF under a non-dedicated hood featuring laminar flow, whereas during period 2, CSFs were manipulated under a dedicated biosafety cabinet without any airflow in POC-A. During period 1, false positives were detected in 3/114 CSF (2·63%) in POC-A and 1/36 (2·77%) in POC-B (P = 0·97); during period 2, false positives were detected in 0/139 CSF (0%) in POC-A and 1/38 (2·63%) in POC-B (P = 0·23). All false positives were bacterial. The use of a dedicated cabinet without ventilation along with preventive measures during period 2 in POC-A significantly reduced the number of false-positive results (P = 0·05). Preventive measures described in this study can mitigate false positives when using PCR-based multiplex assays such as the BIOFIRE FilmArray ME Panel for the diagnosis of meningitis and other infectious diseases.


Assuntos
Bactérias/isolamento & purificação , Contenção de Riscos Biológicos/veterinária , Encefalite/diagnóstico , Meningite/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Vírus/isolamento & purificação , Encefalite/parasitologia , Feminino , Humanos , Laboratórios , Masculino , Meningite/microbiologia , Reação em Cadeia da Polimerase Multiplex , Prevalência , Estudos Retrospectivos , Vírus/genética
6.
J Fr Ophtalmol ; 43(8): 691-696, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32896450

RESUMO

PURPOSE: The goal of this study is to determine a link between benign essential blepharospasm and Sjogren's syndrome by analyzing the presence of extractable nuclear antigens in this population. METHODS: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We eliminated patients with hemifacial spasm or blepharospasm secondary to corneal pathology. We collected the values of the Schirmer I test and the results of the anti-SSA and anti-SSB antibodies. RESULTS: Our study included 72 patients (144 eyes) whose 62 women (86.1%). Mean age was 74.3 years±10.73. Average Schirmer I test was 3.14mm±4.00mm. Five women (8% of this female population) had positive anti-SSA and SSB antibodies. Their mean age was 65.66 years±13.24 whereas the negative antibody patients had an average age of 75.42±9.27. There was no significant difference between their Schimer I test and the Schirmer I of negative antibody population. CONCLUSION: This study illustrates the possible association between the presence of Sjögren's syndrome and the occurrence of a BEB justifying the search for anti-SSA and anti SSB in blepharospasm patients.


Assuntos
Anticorpos Antinucleares/sangue , Antígenos Nucleares/imunologia , Blefarospasmo/sangue , Blefarospasmo/epidemiologia , Síndromes do Olho Seco/sangue , Síndromes do Olho Seco/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Blefarospasmo/complicações , Síndromes do Olho Seco/complicações , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Síndrome de Sjogren/sangue , Síndrome de Sjogren/complicações , Síndrome de Sjogren/epidemiologia
7.
Epidemiol Infect ; 148: e184, 2020 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-32811577

RESUMO

Purpose: The novel coronavirus (severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)) first appeared in Wuhan, China, in December 2019, and rapidly spread across the globe. Since most respiratory viruses are known to show a seasonal pattern of infection, it has been hypothesised that SARS-CoV-2 may be seasonally dependent as well. The present study looks at a possible effect of atmospheric temperature, which is one of the suspected factors influencing seasonality, on the evolution of the pandemic. Basic procedures: Since confirming a seasonal pattern would take several more months of observation, we conducted an innovative day-to-day micro-correlation analysis of nine outbreak locations, across four continents and both hemispheres, in order to examine a possible relationship between atmospheric temperature (used as a proxy for seasonality) and outbreak progression. Main findings: There was a negative correlation between atmospheric temperature variations and daily new cases growth rates, in all nine outbreaks, with a median lag of 10 days. Principal conclusions: The results presented here suggest that high temperatures might dampen SARS-CoV-2 propagation, while lower temperatures might increase its transmission. Our hypothesis is that this could support a potential effect of atmospheric temperature on coronavirus disease progression, and potentially a seasonal pattern for this virus, with a peak in the cold season and rarer occurrences in the summer. This could guide government policy in both the Northern and Southern hemispheres for the months to come.


Assuntos
Infecções por Coronavirus , Modelos Estatísticos , Pandemias , Pneumonia Viral , Temperatura , Betacoronavirus , COVID-19 , China , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Humanos , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Estudos Retrospectivos , SARS-CoV-2 , Estações do Ano , Tempo (Meteorologia)
8.
J Fr Ophtalmol ; 43(7): e211-e215, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32532571

RESUMO

PURPOSE: To study whether there is an association between benign essential blepharospasm and Sjögren's syndrome by analyzing the presence of antibodies to extractable nuclear antigens in this population. METHODS: Seventy-two patients with benign essential blepharospasm (BEB) were included in this study. We excluded patients with hemifacial spasm or blepharospasm secondary to known corneal pathology. We recorded results of Schirmer I testing as well as levels of anti-SSA/Ro and anti-SSB/La antibodies. RESULTS: Our study included 72 patients (144 eyes), of which 62 (86.1%) were women. The mean age was 74.3±10.73 years. The mean Schirmer I test result was 3.14±4.00mm. Five women (8% of this female population) were found to have positive anti-SSA/Ro and anti-SSB/La antibodies. Their mean age was 65.66±13.24 years, while the mean age of the antibody-negative patients was 75.42±9.27 years. There was no statistically significant difference between the Schirmer I tests of the antibody positive and negative patients. CONCLUSION: This study demonstrates a possible association between Sjögren's syndrome and benign essential blepharospasm, justifying anti-SSA/Ro and anti-SSB/La testing in these patients.


Assuntos
Anticorpos Antinucleares/sangue , Blefarospasmo/sangue , Blefarospasmo/epidemiologia , Síndromes do Olho Seco/sangue , Síndromes do Olho Seco/epidemiologia , Síndrome de Sjogren/sangue , Síndrome de Sjogren/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/análise , Antígenos Nucleares/imunologia , Blefarospasmo/complicações , Blefarospasmo/diagnóstico , Comorbidade , Síndromes do Olho Seco/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Sjogren/complicações , Síndrome de Sjogren/diagnóstico
9.
J Fr Ophtalmol ; 42(10): 1062-1067, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31733914

RESUMO

PURPOSE: To determine the significance of dry eye syndrome in benign essential blepharospasm. DESIGN: Retrospective consecutive case series. PARTICIPANTS: One hundred and forty-four patients (288 eyes) with benign essential blepharospasm. METHODS: All subjects had Schirmer I tear tests. Those scores were analysed as a function of patient age, sex, and blepharospasm severity. MAIN OUTCOME MEASURES: Individual Schirmer-test scores in both eyes of all patients. RESULTS: A total of 144 eligible subjects (mean age±SD: 68.3±11.5 years; 76% females) were evaluated. Benign essential blepharospasm was significantly associated with female sex (P=0.0044). The mean Schirmer-test value was 5.9±7.5 (median: 2.5) mm; it was <15mm for 86.8% of the patients and <10mm for 75%, with no difference observed between men and women (P=0.27). Dry-eye syndrome severity was not correlated with age at diagnosis, for men (r=-0.22, P=0.22) or women (r=-0.067, P=0.49), or benign essential blepharospasm severity (P=0.15), but was strongly associated with benign essential blepharospasm independently of age, sex or blepharospasm intensity. CONCLUSION: Dry-eye syndrome and benign essential blepharospasm are strongly linked, independently of age, sex or BEB severity, and should be considered for the diagnosis of benign essential blepharospasm. The useful symptomatic treatment of dry eye will not cure the blepharospasm or the ocular pain, and specific treatment for blepharospasm is required, i.e., quarterly injections of botulinum toxin A into the orbicularis oculi muscle.


Assuntos
Blefarospasmo/epidemiologia , Síndromes do Olho Seco/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Blefarospasmo/complicações , Blefarospasmo/patologia , Síndromes do Olho Seco/complicações , Síndromes do Olho Seco/patologia , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Lágrimas
10.
Environ Int ; 128: 362-370, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31078005

RESUMO

Trapezoidal integration by linear interpolation of data points is by far the most commonly used method of cumulative flux calculations of nitrous oxide (N2O) in studies that use flux chambers; however, this method is incapable of providing accurate uncertainty estimates. A Bayesian approach was used to calculate N2O emission factors (EFs) and their associated uncertainties from flux chamber measurements made after the application of nitrogen fertilisers, in the form of ammonium nitrate (AN), urea (Ur) and urea treated with Agrotain® urease inhibitor (UI) at four grassland sites in the UK. The comparison between the cumulative fluxes estimated using the Bayesian and linear interpolation methods were broadly similar (R2 = 0.79); however, the Bayesian method was capable of providing realistic uncertainties when a limited number of data points is available. The study reports mean EF values (and 95% confidence intervals) of 0.60 ±â€¯0.63, 0.29 ±â€¯0.22 and 0.26 ±â€¯0.17% of applied N emitted as N2O for the AN, Ur and UI treatments, respectively. There was no significant difference between N2O emissions from the Ur and UI treatments. In the case of the automatic chamber data collected at one site in this study, the data did not fit the log-normal model, implying that more complex models may be needed, particularly for measurement data with high temporal resolution.


Assuntos
Poluentes Atmosféricos/análise , Monitoramento Ambiental , Fertilizantes/análise , Nitrogênio/análise , Óxido Nitroso/análise , Teorema de Bayes , Inglaterra , Pradaria , Escócia , País de Gales
11.
Pancreas ; 47(6): 653-666, jul. 2018.
Artigo em Inglês | BIGG - guias GRADE | ID: biblio-968285

RESUMO

Recurrent acute pancreatitis (RAP) is a clinically significant problem globally. The etiology remains unclear in approximately 10% to 15% of patients despite a thorough workup. Data on natural history and efficacy of treatments are limited. We aimed to establish criteria for diagnosis, evaluate the causative factors, and arrive at a consensus on the appropriate workup and management of patients with RAP. The organizing committee was formed, and a set of questions was developed based on the current evidence, controversies, and topics that needed further research. After a vetting process, these topics were assigned to a group of experts from around the world with special interest in RAP. Data were presented as part of a workshop on RAP organized as a part of the annual meeting of the America Pancreatic Association. Pretest and Posttest questions were administered, and the responses were tabulated by the current Grades of Recommendation Assessment, Development and Evaluation system. The consensus guidelines were established in the format of a diagnostic algorithm. Several deficiencies were identified with respect to data on etiology, treatment efficacies, and areas that need immediate research


Assuntos
Humanos , Pancreatite , Pancreatite/diagnóstico , Pancreatite/terapia
12.
J Eur Acad Dermatol Venereol ; 32(10): 1702-1709, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29633363

RESUMO

BACKGROUND: The physical, social and mental burden of psoriasis is well known, but its occupational impact has been less investigated. OBJECTIVE: To assess the impact of psoriasis on the working life of patients compared with the general population. METHODS: A national survey compared people with and without psoriasis using online questionnaires. In addition to the demographic, medical and professional characteristics, data on recent absenteeism and presenteeism were captured using the validated WPAI-PSO questionnaire. RESULTS: The patient sample comprised 714 with psoriasis (PsO), including 81 treated with systemic therapies (PsoST), and 84 with associated psoriatic arthritis (PsO + PsA). The control sample comprised 604 active subjects representative of the French population. Compared to controls, the impact of the disease on working life was no greater in PsO patients. Conversely, unemployment within the past 5 years and mean number of sick leaves within the previous year were more frequent in PsO + PsA. In patients with active psoriasis skin lesions, all aspects of the WPAI questionnaire were negatively impacted in PsoST and PsO + PsA patients, but not in PsO patients: Levels of absenteeism were 3.3% in controls, 5.6% in PsO (NS), 8.3% in PsoST (P < 0.05) and 13.0% in Ps0 + PsA (P < 0.05); impairment in presenteeism reached 27.0%, 21.2% (NS), 43.5% (P < 0.05) and 53.2% (P < 0.05), respectively, while overall work impairment was 27.9%, 22.2% (NS), 46.3% (P < 0.05) and 57.6% (P < 0.05), respectively. Nevertheless, a higher proportion of PsoST and PsO + PsA patients reported that work was more important than any other activity in their life. CONCLUSION: The occupational impact of psoriasis is important and significant in patients who receive systemic therapy or have concurrent PsA but minimal or absent in other psoriasis patients. The findings show that psoriasis patients have a high level of motivation to work.


Assuntos
Absenteísmo , Artrite Psoriásica , Efeitos Psicossociais da Doença , Emprego/estatística & dados numéricos , Presenteísmo/estatística & dados numéricos , Adulto , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/economia , Estudos de Casos e Controles , Eficiência , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Licença Médica/estatística & dados numéricos , Inquéritos e Questionários
13.
Expert Rev Pharmacoecon Outcomes Res ; 18(3): 297-304, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29303374

RESUMO

BACKGROUND: To enhance usage of health technology assessment (HTA) in decision-making, it is important to prioritise important barriers and facilitators to the uptake of HTA. This study aims to quantify and compare the relative importance of barriers and facilitators regarding the use of HTA in several European countries. METHODS: A survey containing two best-worst scaling (BWS) object case studies (i.e. barriers and facilitators) were conducted among 136 policy makers and HTA researchers from the Netherlands, Germany, France, and United Kingdom. Hierarchical Bayes analysis generated the mean relative importance score (RIS) for each factor and subgroup analyses assessed differences between countries. RESULTS: Six barriers (RIS≥5) and five facilitators (RIS≥6) were deemed highly important. Eleven barriers and ten facilitators differed in their importance between countries. Policy characteristics, research & researcher characteristics, and organisation & resources were particularly important to facilitate uptake of HTA, such as an explicit framework for decision-making and research of sufficient quality. CONCLUSION: The most paramount barriers and facilitators to HTA usage were quantified. For all countries it is crucial to create an explicit framework for the decision-making context to include HTA evidence. Country differences in the quality of research emphasize the need for enhanced international collaboration in HTA.


Assuntos
Tomada de Decisões , Política de Saúde , Avaliação da Tecnologia Biomédica/métodos , Pessoal Administrativo , Europa (Continente) , Humanos , Cooperação Internacional , Pesquisa/normas
14.
Atmos Environ (1994) ; 194: 170-178, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30740027

RESUMO

Fluxes of carbon monoxide (CO) were measured using a fast-response quantum cascade laser absorption spectrometer and the eddy covariance method at a long-term intensively grazed grassland in southern Scotland. Measurements lasted 20 months from April 2016 to November 2017, during which normal agricultural activities continued. Observed fluxes followed a regular diurnal cycle, peaking at midday and returning to values near zero during the night, with occasional uptake observed. CO fluxes correlated well with the meteorological variables of solar radiation, soil temperature and soil moisture content. Using a general additive model (GAM) we were able to gap fill CO fluxes and estimate annual fluxes of 0.38 ±â€¯0.046 and 0.35 ±â€¯0.045 g C m-2 y-1g C m-2 y-1 for 2016 and 2017, respectively. If the CO fluxes reported in this study are representative of UK grasslands, then national annual emissions could be expected to be in the order of 61.91 (54.3-69.5) Gg, which equates to 3.8% (3.4-4.3%) of the current national inventory total.

16.
Br J Dermatol ; 177(1): 206-211, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27992062

RESUMO

BACKGROUND: Leg ulcers (LUs) are a chronic and severe complication of sickle cell disease (SCD). A prospective study in patients with SCD to identify factors associated with complete healing and recurrence of LUs is lacking. OBJECTIVES: To determine clinical and biological factors associated with SCD-LU complete healing and recurrence. METHODS: This prospective, observational cohort study was conducted at two adult SCD referral-centre sites (2009-2015) and included 98 consecutive patients with at least one LU lasting ≥ 2 weeks. The primary end points compared patients with healed vs. nonhealed LUs at week 24, and patients with vs. without recurrence during follow-up. RESULTS: The median (interquartile range) LU area, duration and follow-up were, respectively, 6·2 cm2 (3-12·8), 9 weeks (4-26) and 65·8 weeks (23·8-122·1). At week 24, LUs were healed in 47% of patients, while 49% of LUs recurred. Univariate analyses identified inclusion LU area < 8 cm2 (82% vs. 35%; P < 0·001), inclusion LU duration < 9 weeks (65% vs. 35%; P = 0·0013) and high median fetal haemoglobin level (P = 0·008) as being significantly associated with complete healing at week 24, and low lactate dehydrogenase level (P = 0·038) as being associated with recurrence. Multivariate analyses retained LU area < 8 cm2 (odds ratio 6·73, 95% confidence interval 2·35-19. 31; P < 0·001) and < 9 weeks' duration (OR 3·19, 95% confidence interval 1·16-8·76; P = 0·024) as being independently associated with healing at week 24. Factors independently associated with recurrence could not be identified. CONCLUSIONS: SCD-LU complete healing is independently associated with the clinical characteristics of LUs rather than the clinical or biological characteristics of SCD.


Assuntos
Anemia Falciforme/fisiopatologia , Úlcera da Perna/fisiopatologia , Cicatrização/fisiologia , Adulto , Anemia Falciforme/complicações , Bandagens Compressivas , Feminino , Humanos , Úlcera da Perna/complicações , Úlcera da Perna/terapia , Masculino , Prognóstico , Estudos Prospectivos , Recidiva
17.
Encephale ; 43(4): 311-320, 2017 Aug.
Artigo em Francês | MEDLINE | ID: mdl-27623123

RESUMO

INTRODUCTION: The course of schizophrenia can vary widely, and patients experience remission phases alternating with relapse episodes, which generally lead to hospitalisation and have a significant impact on the burden of disease. The prevalence of schizophrenia in France is estimated to be approximately 600,000 people, with an incidence of 10,000 new patients per year. Patients with schizophrenia represent the largest group of hospitalised patients in French public institutions and specialised centres, and the French authorities recognise that the management of schizophrenia is a major public health concern. The Haute Autorité de Santé (HAS) and most of the evidence-based guidelines for the maintenance treatment of schizophrenia recommend long-acting injectable (LAI) antipsychotics to be used predominantly in the prevention of relapse for non-compliant patients; however, in clinical practice, the use of LAIs remains low. OBJECTIVE: This analysis aimed to estimate and to compare the cost-effectiveness of the most common antipsychotic strategies in France in the management of schizophrenia. METHODS: A Markov model was developed to simulate the progression of a cohort of patients with schizophrenia through four health states (stable treated, stable non-treated, relapse and death) and considered up to three lines of treatment to account for changes in treatment management. Antipsychotics including aripiprazole LAI (ALAI), olanzapine LAI (OLAI), paliperidone LAI (PLAI), risperidone LAI (RLAI), haloperidol decanoate (HD) and oral olanzapine (OO) were compared in terms of costs and clinical outcomes. Thus, costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over five years based on three-month cycles from a French health insurance perspective with a discount rate of 4 %. Patients were considered to be stabilised after clinical decompensation and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or discontinuation rates) for the initiation phase came from randomised clinical trials, whereas relapse rates in the prevention phase were derived from hospitalisation risks based on French real-life data in order to capture adherence effects. Safety and utility data were derived from international publications. Additionally costs were retrieved from French health insurance databases and publications. Robustness of results was assessed through deterministic and probabilistic sensitivity analyses. RESULTS: First and second generations of LAIs were found to have similar costs over five years; i.e. approximately € 55,000, except for PLAI which was associated with a discounted cost of € 50,880. Oral antipsychotics were found to be less costly (i.e. OO cost € 50,379 after five years) but associated with a lower number of QALYs gained and relapse avoided. PLAI and RLAI were associated with the greatest number of QALYs gained; i.e. PLAI dominated ALAI, OLAI and HD and was associated with an incremental costs-effectiveness ratio (ICER) of € 2411 per QALY gained versus OO. Finally, PLAI and OLAI were associated with the lowest number of relapses; i.e. PLAI dominated RLAI, ALAI and HLAI and was associated with an ICER of € 1782 per avoided relapse compared to OO. OO and HD were found to have led to the highest number of relapses. CONCLUSION: This analysis, to the best of our knowledge, is the first of its kind to assess the cost-effectiveness of antipsychotics based on French observational data. PLAI was associated with the highest probability of being the optimal treatment from the French health insurance perspective.


Assuntos
Antipsicóticos/economia , Antipsicóticos/uso terapêutico , Esquizofrenia/tratamento farmacológico , Esquizofrenia/economia , Assistência Ambulatorial/economia , Estudos de Coortes , Análise Custo-Benefício , Preparações de Ação Retardada , França , Nível de Saúde , Humanos , Cadeias de Markov , Modelos Econômicos , Programas Nacionais de Saúde/economia , Cooperação do Paciente , Anos de Vida Ajustados por Qualidade de Vida , Recidiva
19.
Endocr Relat Cancer ; 23(8): 625-33, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27353036

RESUMO

Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Dacarbazina/análogos & derivados , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Supressoras de Tumor/metabolismo , Idoso , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos Alquilantes/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/farmacologia , Capecitabina/uso terapêutico , Metilação de DNA , Metilases de Modificação do DNA/genética , Enzimas Reparadoras do DNA/genética , Dacarbazina/farmacologia , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Regiões Promotoras Genéticas , Temozolomida , Resultado do Tratamento , Proteínas Supressoras de Tumor/genética
20.
Thromb Res ; 140 Suppl 1: S170-1, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27161678

RESUMO

INTRODUCTION: Venous thrombo-embolic events (VTE) occur frequently in patients with pancreatic cancer and contribute to elevated morbidity and mortality. Clinical risk factors for thrombosis such as cancer stage and tumor grade have been clearly identified. Recently, several biomarkers have been proposed which may help identifying cancer patients at high risk of thrombosis. Those biomarkers have been studied in heterogeneous cohorts of patients with different cancer types. AIM: To compare pro-thrombotic biomarkers in pancreatic cancer and in chronic pancreatitis to determine whether these biomarkers are related to cancer or inflammation and to validate their association with thrombotic risk in a pancreatic cancer population. MATERIALS AND METHODS: 45 patients with pancreatic cancer, 49 with intraductal papillary mucinous tumor of the pancreas (IPMN), a precancerous lesion, and 50 with chronic pancreatitis were recruited. Plasma levels of factor VIII, D-dimers, thrombin-antithrombin complexes, soluble p-selectin, tissue factor-dependent procoagulant activity of MP (TF-MP), free Tissue Factor Pathway Inhibitor (TFPI) and extracellular DNA were measured. Thrombin generation triggered by 1pM of TF was evaluated with the Calibrated Automated Thrombogram assay. RESULTS: Levels of factor VIII, D-dimers, TF-MP, TFPI and extracellular DNA were significantly higher in cancer patients compared to IPMN or chronic pancreatitis (Table 1). Patients with metastatic cancer (n=27) presented higher levels of D-dimers (mean±sd 1.77±1.28 vs 0.80±0.96 µg/ml, p=0.004) and MP-TF (54.3±53.2 vs 15.8±10.4 fM, p=0.02) compared to patients with localized lesions (n=18). Among cancer patients, 42 were followed for a median duration of 187 days (min 21-max 802 days). VTE occurred in 10 (23%) patients. All had metastatic cancer at the time of thrombosis. Only D-dimers were significantly elevated in cancer patients with VTE compared to patients without VTE (median 1.85 vs 0.7 µg/ml, p=0.02). CONCLUSIONS: Elevation of factor VIII, D-dimers, TF-MP, TFPI and extracellular DNA seems to be related to cancer process, not to local or systemic inflammation as these parameters differentiate cancer from chronic pancreatitis. Interestingly, D-dimers and TF-MP are related to the disseminated cancer stage, suggesting that vascular invasion is a prerequisite to the release of TF-MP from the primary tumor into the bloodstream and to coagulation activation. However, only D-dimers are associated with the occurrence of future VTE. We propose that D-dimers could be a useful tool to predict thrombotic events in pancreatic cancer patients. This should be confirmed in a larger population.

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