Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

First finding of Chagas disease vectors associated with wild bushes in the Metropolitan Region of Chile Primer hallazgo de vectores de la enfermedad de Chagas asociados a matorrales silvestres en la Región Metropolitana, Chile

Background: Insects of the subfamily triatominae are the biological vectors of Trypanosoma cruzi, the causal agent of Chagas disease. Aim: To search for wild colonies of triatomines in the Metropolitan Region of Chile. Material and Methods: Ad hoc traps were placed in two endemic zones of the Metropolitan Region of Chile, during 30 nights. The dejections of 16 T infestans and 43 M spinolai specimens were examined under the microscope, searching for live metacyclic trypomastigotes. A polymerase chain reaction (PCR) was performed in macerates of all insects looking for T cruzi DNA. Results: A total of 269 bugs were captured. Forty four were Triatoma infestans and 225 were Mepraia spinolai. They were not syntopic, since T infestans was restricted to a Southern zone (Calera de Tango) while M spinolai was only found in the Northern zone (Til-Til). Both species were found associated to terrestrial bromeliads (Puya sp) but M spinolai was also detected in stony grounds. Microscopic examinatio

Visual Merchandising Y Escaparatismo-DI173-201801

Descripción: Visual Merchandising y Escaparatismo es un curso que busca que el estudiante a través de la observación y el análisis se familiarice con el diseño de espacios complejos elaborando propuestas experimentales basadas en el análisis de tipologías tradicionales. El alumno se acerca al diseño desde la función y el programa creando una estrategia de diseño distinta y particular que le permita plantear sus ideas sustentadas en estudios casos y análisis de precedentes.Propósito: El propósito del curso es desarrollar en el alumno habilidades para observar analizar plantear y diseñar espacios complejos que formen parte de una tipología específica entendiendo los sistemas de relaciones y sus particularidades apoyándose en la investigación académica y en los casos de estudio. Este curso desarrolla en un nivel avanzado (nivel 3) las competencias generales de Pensamiento Innovador comunicación oral y comunicación escrita y las competencias específicas de Diseño Comercial y planificación. Patrimonio histórico es el curso previo como pre requisito

Data from: Why has transparency evolved in aposematic butterflies? insights from the largest radiation of aposematic butterflies, the Ithomiini

Defended species are often conspicuous and this is thought to be an honest signal of defences, i.e. more toxic prey are more conspicuous. Neotropical butterflies of the large Ithomiini tribe numerically dominate communities of chemically-defended butterflies and may thus drive the evolution of mimetic warning patterns. Although many species are brightly coloured, most are transparent to some degree. The evolution of transparency from a warningly coloured ancestor is puzzling as it is generally assumed to be involved in concealment. Here we show that transparent Ithomiini species are indeed less detectable by avian predators (i.e. concealment). Surprisingly, transparent species are not any less unpalatable, and may in fact be more unpalatable than opaque species, the latter spanning a larger range of unpalatability. We put forth various hypotheses to explain the evolution of weak aposematic signals in these butterflies and other cryptic defended prey. Our study is an important step in determining the selective pressures and constraints that regulate the interaction between conspicuousness and unpalatability

Phylogeny of 33 Ithomiini species

Phylogeny of the 33 Ithomiini species used in the study and extracted from the 340 species Ithomiini phylogeny by Chazot et al. (accepted in Global Ecology and Biogeography

Data of transparency & detectability of 33 Ithomiini species, and PA concentration and measures of unpalatability for 10 of these species

1-Average transparency and detectability by avian predators (chromatic & achromatic contrast in just noticeable difference units [JNDs] for UVS- & VS-vision in large gap & forest shade light conditions) for the 33 Ithomiini species of the study. 2-Data for behavioural experiments with chicks to test unpalatability of 10 Ithomiini taxa (indicated in bold red in the first list) are also provided, including the number (& assigned colour ) of experimental pellets attacked at each trial (for a total of 12 trials per chick) for all 6 chicks tested for each butterfly species. 3-PA concentrations (μg/mg) measured for individual butterflies of the 10 selected taxa are also given

High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease

Because of its potent immunosuppressive yet stem cell–sparing activity, high-dose cyclophosphamide was tested as sole prophylaxis of graft-versus-host disease (GVHD) after myeloablative allogeneic bone marrow transplantation (alloBMT). We treated 117 patients (median age, 50 years; range, 21-66 years) with advanced hematologic malignancies; 78 had human leukocyte antigen (HLA)–matched related donors and 39 had HLA-matched unrelated donors. All patients received conventional myeloablation with busulfan/cyclophosphamide (BuCy) and T cell–replete bone marrow followed by 50 mg/kg/d of cyclophosphamide on days 3 and 4 after transplantation. The incidences of acute grades II through IV and grades III through IV GVHD for all patients were 43% and 10%, respectively. The nonrelapse mortality at day 100 and 2 years after transplantation were 9% and 17%, respectively. The actuarial overall survival and event-free survivals at 2 years after transplantation were 55% and 39%, respectively, for all patients and 63% and 54%, respectively, for patients who underwent transplantation while in remission. With a median follow-up of 26.3 months among surviving patients, the cumulative incidence of chronic GVHD is 10%. These results suggest that high-dose posttransplantation cyclophosphamide is an effective single-agent prophylaxis of acute and chronic GVHD after BuCy conditioning and HLA-matched BMT (clinicaltrials.gov no. NCT00134017)