Déterminants de l’écart de prix entre médicaments similaires et le premier entrant d’une classe thérapeutique

La prolifération sur le marché de médicaments similaires suscite de nombreux débats autour de leur substituabilité, de leur prix, voire de l’opportunité de leur développement. Cette recherche vise à estimer, au sein de 31 groupes de médicaments homogènes du point de vue de leur structure moléculaire et de leurs indications, l’écart de prix entre la première présentation arrivée sur le marché et les similaires qui l’ont suivie, et à analyser les déterminants de cet écart de prix. Nous nous intéressons au cycle de vie du médicament sur la période entre 2001 et 2009, en prenant en compte non seulement la date de mise sur le marché, mais aussi l’ensemble des modifications ultérieures des prix ou des conditions du marché. Pour cela, nous appliquons un modèle multi-niveaux qui tient compte de l’appartenance des similaires à un groupe et de la structure temporelle des données. Les résultats montrent l’existence d’écarts de prix significatifs avec un écart moyen de 59 % par groupe. Au sein d’un groupe donné, l’innovation accroît les écarts de prix tandis que l’arrivée de génériques dans un groupe ou la mise sous Tarif forfaitaire de responsabilité (TFR) les réduit. Pour les médicaments disponibles dans des dosages différents, la tarification proportionnelle au dosage, assez courante, accroît les écarts de prix au sein d’un groupe et introduit une iniquité horizontale entre les patients consommateurs de différents dosages. Enfin, les écarts de prix augmentent avec la part de marché du médicament, ce qui contraste avec le principe d’une fixation du prix inversement proportionnelle aux volumes de vente prévus ou réalisés.Régulation, régulation du prix du médicament, médicament similaire, me-too, follows-on, écart de prix, modèle multiniveaux.

Preoperative diastolic function predicts the onset of left ventricular dysfunction following aortic valve replacement in high-risk patients with aortic stenosis

INTRODUCTION: Left ventricular (LV) dysfunction frequently occurs after cardiac surgery, requiring inotropic treatment and/or mechanical circulatory support. In this study, we aimed to identify clinical, surgical and echocardiographic factors that are associated with LV dysfunction during weaning from cardiopulmonary bypass (CPB) in high-risk patients undergoing valve replacement for aortic stenosis. METHODS: Perioperative data were prospectively collected in 108 surgical candidates with an expected operative mortality ≥ 9%. All anesthetic and surgical techniques were standardized. Reduced LV systolic function was defined by an ejection fraction <40%. Diastolic function of the LV was assessed using standard Doppler-derived parameters, tissue Doppler Imaging (TDI) and transmitral flow propagation velocity (Vp). RESULTS: Doppler-derived pulmonary flow indices and TDI could not be obtained in 14 patients. In the remaining 94 patients, poor systolic LV was documented in 14% (n = 12) and diastolic dysfunction in 84% of patients (n = 89), all of whom had Vp <50 cm/s. During weaning from CPB, 38 patients (40%) required inotropic and/or mechanical circulatory support. By multivariate regression analysis, we identified three independent predictors of LV systolic dysfunction: age (Odds ratio [OR] = 1.11; 95% confidence interval (CI), 1.01 to 1.22), aortic clamping time (OR = 1.04; 95% CI, 1.00 to 1.08) and Vp (OR = 0.65; 95% CI, 0.52 to 0.81). Among echocardiographic measurements, Vp was found to be superior in terms of prognostic value and reliability. The best cut-off value for Vp to predict LV dysfunction was 40 cm/s (sensitivity of 72% and specificity 94%). Patients who experienced LV dysfunction presented higher in-hospital mortality (18.4% vs. 3.6% in patients without LV dysfunction, P = 0.044) and an increased incidence of serious cardiac events (81.6 vs. 28.6%, P < 0.001). CONCLUSIONS: This study provides the first evidence that, besides advanced age and prolonged myocardial ischemic time, LV diastolic dysfunction characterized by Vp ≤ 40 cm/sec identifies patients who will require cardiovascular support following valve replacement for aortic stenosis

'A bed in the middle of nowhere': parents' meanings of place of death for adults with cystic fibrosis

As populations age and chronic conditions become more prevalent, an individual's ability to choose the location of their end-of-life care and death is increasingly considered important in the provision of good healthcare, with home implied as the 'best' place of death through UK government policy and specialist and voluntary palliative care services. However, considering meanings of place of end-of-life care and death is complex for young adults with life-limiting conditions where the disease course is variable and uncertain, and aggressive and palliative treatments are administered both at home and in hospital often until death. Although 'place' is a pivotal element in healthcare practice, research and policy, there has been little attempt to understand the meaning and importance of place in understanding experiences of care at end of life. Through analysis of in-depth interviews and letters received from parents of 27 young adults in England, Scotland and Wales who died from cystic fibrosis from 1999 to 2002 aged 17-36 years, key factors that influence families' meanings of place at end of life are presented. Both home and hospital deaths are reported, with no deaths in hospices. Preferences for possible locations of death are generally limited early in the disease course by choice of aggressive treatment, particularly lung transplantation. Rate of health decline, organisation and delivery of services, and relationships with specialist and general healthcare staff strongly influence parents' experience of death at home or in hospital, although no physical location was regarded a 'better' place of death. Meanings of, and attachment to place are mediated for families through these factors, questioning the appropriateness of a 'home is best' policy for those dying from life-limiting conditions. © 2009 Elsevier Ltd. All rights reserved

Investigation into the role of the germline epigenome in the transmission of glucocorticoid-programmed effects across generations.

BACKGROUND: Early life exposure to adverse environments affects cardiovascular and metabolic systems in the offspring. These programmed effects are transmissible to a second generation through both male and female lines, suggesting germline transmission. We have previously shown that prenatal overexposure to the synthetic glucocorticoid dexamethasone (Dex) in rats reduces birth weight in the first generation (F1), a phenotype which is transmitted to a second generation (F2), particularly through the male line. We hypothesize that Dex exposure affects developing germ cells, resulting in transmissible alterations in DNA methylation, histone marks and/or small RNA in the male germline. RESULTS: We profile epigenetic marks in sperm from F1 Sprague Dawley rats expressing a germ cell-specific GFP transgene following Dex or vehicle treatment of the mothers, using methylated DNA immunoprecipitation sequencing, small RNA sequencing and chromatin immunoprecipitation sequencing for H3K4me3, H3K4me1, H3K27me3 and H3K9me3. Although effects on birth weight are transmitted to the F2 generation through the male line, no differences in DNA methylation, histone modifications or small RNA were detected between germ cells and sperm from Dex-exposed animals and controls. CONCLUSIONS: Although the phenotype is transmitted to a second generation, we are unable to detect specific changes in DNA methylation, common histone modifications or small RNA profiles in sperm. Dex exposure is associated with more variable 5mC levels, particularly at non-promoter loci. Although this could be one mechanism contributing to the observed phenotype, other germline epigenetic modifications or non-epigenetic mechanisms may be responsible for the transmission of programmed effects across generations in this model

Near-infrared Emission Spectrum of WASP-103b Using Hubble Space Telescope/Wide Field Camera 3

We present here our observations and analysis of the dayside emission spectrum of the hot Jupiter WASP-103b. We observed WASP-103b during secondary eclipse using two visits of the Hubble Space Telescope with the G141 grism on Wide Field Camera 3 in spatial scan mode. We generated secondary eclipse light curves of the planet in both blended white-light and spectrally binned wavechannels from 1.1-1.7 µm and corrected the light curves for flux contamination from a nearby companion star. We modeled the detector systematics and secondary eclipse spectrum using Gaussian process regression and found that the near-IR emission spectrum of WASP-103b is featureless across the observed near-IR region to down to a sensitivity of 175 ppm, and shows a shallow slope toward the red. The atmosphere has a single brightness temperature of T_B = 2890 K across this wavelength range. This region of the spectrum is indistinguishable from isothermal, but may not manifest from a physically isothermal system, i.e., pseudo-isothermal. A solar-metallicity profile with a thermal inversion layer at 10^(−2) bar fits the spectrum of WASP-103b with high confidence, as do an isothermal profile with solar metallicity and a monotonically decreasing atmosphere with C/O > 1. The data rule out a monotonically decreasing atmospheric profile with solar composition, and we rule out a low-metallicity decreasing profile as unphysical for this system. The pseudo-isothermal profile could be explained by a thermal inversion layer just above the layer probed by our observations, or by clouds or haze in the upper atmosphere. Transmission spectra at optical wavelengths would allow us to better distinguish between potential atmospheric models

Editorial

As of 2013, the review Travail et emploi is opening its pages to the English-speaking public with a biennial English translation of articles selected from those published during the two preceding years. Published as a Special Edition, this selection follows the same distribution norms as those for the four issues published annually: available in a “paper edition,” it can also be accessed online on several portals: the web site of the review; Revues.org; Cairn-info; and it will soon appear on ..

Contribuições do grupo Tutorial Dois para o PET-Saúde/Interprofissionalidade

Introdução: De modo a integrar ensino-serviço-comunidade, o PET-Saúde/Interprofissionalidade em Chapecó/SC reuniu a Secretaria de Saúde de Chapecó (SESAU) e três instituições de ensino superior (IES) do município: a Universidade Federal da Fronteira Sul (UFFS), a Universidade Estadual de Santa Catarina (UDESC) e a Universidade do Oeste de Santa Catarina (UNOESC). Organizaram-se cinco grupos tutoriais compostos por docentes e discentes dos cursos em Educação Física, Enfermagem, Medicina e Psicologia das IES participantes e com os profissionais de saúde das Unidades Básicas de Saúde (UBS). Cada grupo tutorial é designado a uma UBS do município, no qual são responsáveis por desenvolver ações conforme as necessidades locais, estimulando o desenvolvimento de competências colaborativas e do trabalho interprofissional¹. Objetivo: Relatar as ações e experiências com as práticas colaborativas desenvolvidas pelos petianos por meio do programa. Metodologia: Relato de experiência sobre as ações desenvolvidas pelo grupo tutorial dois do PET-Saúde/Interprofissionalidade, que atua no Centro de Saúde da Família (CSF), município de Chapecó/SC. As ações foram e estão sendo desenvolvidas no período que compreende do primeiro semestre de 2019 até os dias atuais. Resultados: Ao iniciar as atividades no CSF Eldorado, identificou-se a necessidade de trabalhar conceitos e fortalecer o conhecimento da equipe de saúde acerca das práticas colaborativas e do trabalho interprofissional. Realizou-se o mapeamento da estrutura do CSF, fluxo de atendimento e percepção dos usuários acerca dos serviços prestados na unidade. Para ampliar o conhecimento dos membros do grupo sobre a Rede de Atenção à Saúde, foram realizadas visitas em locais como&nbsp;o Serviço de Assistência Especializada em HIV/Aids e o Serviço de Atendimento Psicológico da UNOESC. Ainda, desenvolveu-se ações de prevenção do câncer de mama e colo do útero durante a campanha do Outubro Rosa e identificação da gravidez na adolescência como um problema local. Isso impulsionou o planejamento de uma atividade que será desenvolvida após retorno das atividades presenciais, envolvendo o planejamento familiar, possibilidades de inserção no mercado de trabalho, cursos profissionalizantes, ensino técnico e superior, além de atividades de promoção da autoestima de crianças e adolescentes. Em 2020, com as limitações impostas pela pandemia, foram produzidos resumos e artigos científicos, além da utilização das redes sociais como forma de se aproximar da comunidade, com postagens de materiais informativos sobre a COVID-19 e atividades para a promoção da saúde. Considerações Finais: As atividades desenvolvidas possibilitaram interligar os saberes de todas as profissões, promovendo a integração e colaboração, com a criação de oportunidades de aprendizagem conjunta, o que evidencia a possibilidade de se ter autonomia e interdependência simultaneamente. Palavras-chave: Educação interprofissional. Profissionais de saúde. Sistema Único de Saúde. Desenvolvimento de recursos humanos

The fast declining Type Ia supernova 2003gs, and evidence for a significant dispersion in near-infrared absolute magnitudes of fast decliners at maximum light

We obtained optical photometry of SN 2003gs on 49 nights, from 2 to 494 days after T(B_max). We also obtained near-IR photometry on 21 nights. SN 2003gs was the first fast declining Type Ia SN that has been well observed since SN 1999by. While it was subluminous in optical bands compared to more slowly declining Type Ia SNe, it was not subluminous at maximum light in the near-IR bands. There appears to be a bimodal distribution in the near-IR absolute magnitudes of Type Ia SNe at maximum light. Those that peak in the near-IR after T(B_max) are subluminous in the all bands. Those that peak in the near-IR prior to T(B_max), such as SN 2003gs, have effectively the same near-IR absolute magnitudes at maximum light regardless of the decline rate Delta m_15(B). Near-IR spectral evidence suggests that opacities in the outer layers of SN 2003gs are reduced much earlier than for normal Type Ia SNe. That may allow gamma rays that power the luminosity to escape more rapidly and accelerate the decline rate. This conclusion is consistent with the photometric behavior of SN 2003gs in the IR, which indicates a faster than normal decline from approximately normal peak brightness.Comment: 41 pages, 13 figures, to be published in the December, 2009, issue of the Astronomical Journa

Pyrale du buis : une efficacité insuffisante des trichogrammes

editorial reviewedsavebuxus - Afin de poursuivre la mise au point de la lutte contre la pyrale du buis, Cydalima perspectalis, à l’aide de trichogrammes, le programme national SaveBuxus se prolonge jusqu’à décembre 2019. étude - Après un screening d’une cinquantaine de souches de trichogramme en laboratoire, trois espèces ont été retenues pour les essais in situ de 2018 : Trichogramma brassicae, Trichogramma dendrolimi et la souche du produit Trichotop Buxus (commercialisée depuis 2016 en France). Les essais ont eu lieu sur un site expérimental d’Astredhor Sud-Ouest sur des buis infestés grâce aux pyrales de l’élevage de l’Inra UEFM Antibes. Des lâchers hebdomadaires des trois espèces de trichogrammes ont été réalisés pendant toute la période de vol du ravageur, entre juin et octobre, sur buis linéaires et buis isolés. En 2018, la densité du ravageur insignifiante n’a pas permis d’évaluer l’efficacité des trichogrammes pour parasiter et tuer les oeufs de pyrale. Il y a donc eu recours à des oeufs d’élevage produits au laboratoire de l’Inra d’Antibes et envoyés avec des brins de buis sur le terrain. Les brins portant les oeufs étaient disposés le jour de réception sur les buis de la zone d’essai. Au bout de 5 jours, ils étaient récupérés et renvoyés à Antibes pour mise en incubation 6 jours à 25 °C avant analyse des taux d’avortement et de parasitisme des oeufs. La capacité de dispersion des trichogrammes a également été évaluée

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field