Determining the value contribution of emicizumab (Hemlibra®) for the prophylaxis of haemophilia A with inhibitors in Spain by multi-criteria decision analysis

Haemophilia A; Inhibitors; Drug valueHemofilia A; Inhibidores; Valores del medicamentoHemofília A; Inhibidors; Valors del medicamentPatients with moderate to severe haemophilia A are at a higher risk of developing FVIII inhibitors that require the use of more costly and less effective treatments. The objective of this study was to determine the value of emicizumab for the prophylaxis of haemophilia A with inhibitors compared to the current therapeutic alternatives, activated prothrombin complex concentrate and recombinant factor VIIa through reflective Multi-Criteria Decision Analysis. The EVIDEM framework adapted to orphan drugs and weighted by a sample of 98 national and regional Spanish evaluators was used. Two structured evidence matrices were developed: emicizumab against activated prothrombin complex concentrate and emicizumab against recombinant factor VIIa. A multidisciplinary team of haemophilia experts rated each of the criteria. Mean and standard deviation were calculated by each criterion and discussed among all participants. Haemophilia A with inhibitors was perceived as a severe disease with high unmet needs. Emicizumab was rated with higher efficacy, therapeutic benefit and quality of life than comparators. When administered alone for the prevention of bleeding events, emicizumab had slightly better safety and tolerability profile than activated prothrombin complex concentrate and similar with recombinant factor VIIa. The inclusion of emicizumab in clinical practice guidelines was valued positively by the members of the panel. Overall, value of emicizumab was higher than activated prothrombin complex concentrate and recombinant factor VIIa, mostly because of efficacy and therapeutic benefit in reducing treated haemorrhages. Reflective Multi-Criteria Decision Analysis has proven to be a feasible method to determine the value contribution of comparative therapies in haemophilia.This work was supported by Hoffmann-La Roche

High mammographic density in long-term night shift workers: DDM-Spain /Var-DDM

[EN] Background: Night-shift work (NSW) has been suggested as a possible cause of breast cancer, and its association with mammographic density (MD), one of the strongest risk factors for breast cancer, has been scarcely addressed. This study examined NSW and MD in Spanish women. Methods: The study covered 2,752 women aged 45-68 years recruited in 2007-2008 in 7 population-based public breast cancer screening centers, which included 243 women who had performed NSW for at least one year. Occupational data and information on potential confounders were collected by personal interview. Two trained radiologist estimated the percentage of MD assisted by a validated semiautomatic computer tool (DM-scan). Multivariable mixed linear regression models with random screening center-specific intercepts were fitted using log-transformed percentage of MD as the dependent variable and adjusting by known confounding variables. Results: Having ever worked in NSW was not associated with MD [e(beta):0.96; 95% confidence interval (CI), 0.86-1.06]. However, the adjusted geometric mean of the percentage of MD in women with NSW for more than 15 years was 25% higher than that of those without NSW history (MD>15 (years):20.7% vs. MDnever:16.5%; e(beta):1.25; 95% CI, 1.01-1.54). This association was mainly observed in postmenopausal participants (e(beta):1.28; 95% CI, 1.00-1.64). Among NSW-exposed women, those with <= 2 night-shifts per week had higher MD than those with 5 to 7 nightshifts per week (e(beta):1.42; 95% CI, 1.10-1.84). Conclusions: Performing NSW was associated with higherMD only in women with more than 15 years of cumulated exposure. These findings warrant replication in futures studies. (C)2017 AACR.We would like to thank the participants in the DDM-Spain/Var-DDM-Spain study for their contribution to breast cancer research. Other members of DDM-Spain/Var-DDM: Gonzalo. López-Abente, Roberto Pastor-Barriuso, Pablo Fernández-Navarro, Anna Cabanes, Soledad Laso, Manuela Alcaraz, María Casals, Inmaculada Martínez, Juan Carlos Pérez Cortés, Joaquín Antón, Nieves Ascunce, Isabel González-Román, Ana Belén Fernández, Montserrat Corujo, Soledad Abad, and Jesús Vioque. A.M. Pedraza-Flechas FI14CIII/00013 PFIS; B. Perez-Gomez FIS PS09/0790; M. Pollán FIS PI060386, EPY1306/06 collaboration agreement between Astra-Zeneca and ISCIII, and FECMA 485 EPY 1170 10; R. LLobet Gent per Gent Fund (EDEMAC Project); All authors: European Regional Development Fund (FEDER). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.Pedraza-Flechas, AM.; Lope, V.; Sanchez-Contador, C.; Santamarina, C.; Pedraz-Pingarron, C.; Moreo, P.; Ederra, M.... (2017). High mammographic density in long-term night shift workers: DDM-Spain /Var-DDM. Cancer Epidemiology Biomarkers & Prevention. 26(6):905-913. https://doi.org/10.1158/1055-9965.EPI-16-0507S90591326

Overeating, caloric restriction and mammographic density in Spanish women. DDM-Spain study

Objectives: Mammographic density (MD) is a strong risk factor for breast cancer. The present study evaluates the association between relative caloric intake and MD in Spanish women. Study design: We conducted a cross-sectional study in which 3517 women were recruited from seven breast cancer screening centers. MD was measured by an experienced radiologist using craniocaudal mammography and Boyd's semi-quantitative scale. Information was collected through an epidemiological survey. Predicted calories were calculated using linear regression models, including the basal metabolic rate and physical activity as explanatory variables. Overeating and caloric restriction were defined taking into account the 99% confidence interval of the predicted value. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using center-specific mixed ordinal logistic regression models, adjusted for age, menopausal status, body mass index, parity, tobacco use, family history of breast cancer, previous biopsies, age at menarche and adherence to a Western diet. Main outcome measure: Mammographic density. Results: Those women with an excessive caloric intake ( > 40% above predicted) presented higher MD (OR = 1.41, 95%CI = 0.97-2.03; p = 0.070). For every 20% increase in relative caloric consumption the probability of having higher MD increased by 5% (OR = 1.05, 95%CI = 0.98-1.14; p = 0.178), not observing differences between the categories of explanatory variables. Caloric restriction was not associated with MD in our study. Conclusions: This is the first study exploring the association between MD and the effect of caloric deficit or excessive caloric consumption according to the energy requirements of each woman. Although caloric restriction does not seem to affect breast density, a caloric intake above predicted levels seems to increase this phenotype

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

Study of forward Z + jet production in pp collisions at √s=7 TeV

A measurement of the $Z(\rightarrow\mu^+\mu^-)$+jet production cross-section in $pp$ collisions at a centre-of-mass energy $\sqrt{s} = 7$ TeV is presented. The analysis is based on an integrated luminosity of $1.0\,\text{fb}^{-1}$ recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction ($2.0<\eta<4.5$). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction.A measurement of the $Z(\rightarrow\mu^+\mu^-)$+jet production cross-section in $pp$ collisions at a centre-of-mass energy $\sqrt{s} = 7$ TeV is presented. The analysis is based on an integrated luminosity of $1.0\,\text{fb}^{-1}$ recorded by the LHCb experiment. Results are shown with two jet transverse momentum thresholds, 10 and 20 GeV, for both the overall cross-section within the fiducial volume, and for six differential cross-section measurements. The fiducial volume requires that both the jet and the muons from the Z boson decay are produced in the forward direction ($2.0<\eta<4.5$). The results show good agreement with theoretical predictions at the second-order expansion in the coupling of the strong interaction

Susceptibilidad de las larvas de Aedes aegypti al parasitismo por Romanomermis culicivorax en condiciones de laboratorio y de campo en Oaxaca, México

En junio de 1996, en el Estado de Oaxaca, México, se expusieron larvas de mosquito de la especie Aedes aegypti (Linneo) a los preparásitos infectivos del nemátodo Romanomermis culicivorax, Ross y Smith, en condiciones de laboratorio y de campo. Para los experimentos de laboratorio se utilizaron larvas en estadio I-IV, colectadas en reservorios naturales. Los experimentos se realizaron por triplicado, con 100 larvas de cada estadio larvario por experimento, y se probaron tres dosis de aplicación: 5:1, 10:1 y 15:1 (5, 10 ó 15 preparásitos por larva de mosquito). Para los estudios de campo se tomaron 13 criaderos naturales de A. aegypti con larvas en estadio I-IV y se aplicó una dosis de 15:1 por cada criadero. De acuerdo con los resultados obtenidos en los experimentos de laboratorio, se observó un aumento de la infestación media de las larvas a medida que aumentaba la dosis de aplicación desde 5:1 hasta 15:1. Para la dosis de 10:1, la tasa de parasitismo alcanzó valores de 100, 100, 85 y 74% en las larvas en estadio I, II, III y IV, respectivamente, y, para la dosis de 15:1, valores de 100, 100, 90 y 79%, respectivamente. Los resultados de las pruebas de campo con la aplicación de una dosis de 15:1 en los 13 reservorios naturales proporcionaron elevadas tasas de parasitismo, con valores entre 80-98%, lo que demostró la susceptibilidad de esta especie de mosquito al parasitismo por R. culicivorax en el Estado de Oaxaca, México

The Romanomermis iyengari parasite for Anopheles pseudopunctipennis suppression in natural habitats in Oaxaca State, Mexico

In September and November 1996 Romanomermis iyengari Welch, a parasite of larval mosquitoes, was released in 44 natural larval habitat sites of Anopheles pseudopunctipennis Theobald in an attempt to reduce the larval populations of this important malaria vector. The selected treatment sites ranged in size from 5 to 500 m². The study was carried out in Pochutla District of Oaxaca State, on the Pacific coast of Mexico. Chemical pesticides to reduce vector populations have been the principal tool in malaria suppression campaigns. However, the excessive use of these chemicals has created pesticide resistance and other serious collateral problems. Therefore, a biological control project using agents that are pathogens of Anopheles larvae was initiated in 1996. The principal objective was to establish mass rearing capacities for R. iyengari. Detailed methodology for rearing and introducing these nematodes into mosquito larval habitats was established at the National Polytechnic Institute of Oaxaca State. Before application of the parasites to larval habitats, site characteristics were determined, including size, depth, aquatic vegetation, salinity, pH, conductivity, temperature, and pretreatment larval density. With a compressed air sprayer, infective mermithid parasites were released at rates of either 2000 or 3000/m², and the parasites produced high levels of infection. Anopheles populations were sampled 72 h posttreatment, and the larvae obtained were taken to the laboratory and examined through microscopic dissection to determine infection levels and mean parasitism. Nematode parasitism ranged from 85 to 100% at all the treatment sites, even though no previous information concerning field parasitism of An. pseudopunctipennis by R. iyengari has been reported. In addition, a significant reduction of mosquito larval density at the treatment sites was found five days after the nematode application. Levels of parasitism were indicative of the number of mosquito larvae killed by the treatment since infected larvae never progressed to the pupal stage. Results from sampling nine of the sites 2 months after the initial application of nematodes indicated that a high number of mosquito larvae were infected by parasites that had emerged from eggs previously deposited in the stratum. This work suggests the potential of this mermithid to reduce An. pseudopunctipennis populations in Oaxaca State

Determining the value contribution of emicizumab (Hemlibra®) for the prophylaxis of haemophilia A with inhibitors in Spain by multi-criteria decision analysis

Haemophilia A; Inhibitors; Drug valueHemofilia A; Inhibidores; Valores del medicamentoHemofília A; Inhibidors; Valors del medicamentPatients with moderate to severe haemophilia A are at a higher risk of developing FVIII inhibitors that require the use of more costly and less effective treatments. The objective of this study was to determine the value of emicizumab for the prophylaxis of haemophilia A with inhibitors compared to the current therapeutic alternatives, activated prothrombin complex concentrate and recombinant factor VIIa through reflective Multi-Criteria Decision Analysis. The EVIDEM framework adapted to orphan drugs and weighted by a sample of 98 national and regional Spanish evaluators was used. Two structured evidence matrices were developed: emicizumab against activated prothrombin complex concentrate and emicizumab against recombinant factor VIIa. A multidisciplinary team of haemophilia experts rated each of the criteria. Mean and standard deviation were calculated by each criterion and discussed among all participants. Haemophilia A with inhibitors was perceived as a severe disease with high unmet needs. Emicizumab was rated with higher efficacy, therapeutic benefit and quality of life than comparators. When administered alone for the prevention of bleeding events, emicizumab had slightly better safety and tolerability profile than activated prothrombin complex concentrate and similar with recombinant factor VIIa. The inclusion of emicizumab in clinical practice guidelines was valued positively by the members of the panel. Overall, value of emicizumab was higher than activated prothrombin complex concentrate and recombinant factor VIIa, mostly because of efficacy and therapeutic benefit in reducing treated haemorrhages. Reflective Multi-Criteria Decision Analysis has proven to be a feasible method to determine the value contribution of comparative therapies in haemophilia.This work was supported by Hoffmann-La Roche