EMA Review of Daunorubicin and Cytarabine Encapsulated in Liposomes (Vyxeos, CPX-351) for the Treatment of Adults with Newly Diagnosed, Therapy-Related Acute Myeloid Leukemia or Acute Myeloid Leukemia with Myelodysplasia-Related Changes.

On June 28, 2018, the Committee for Medicinal Products for Human Use adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Vyxeos, intended for the treatment of acute myeloid leukemia (AML). Vyxeos was designated as an orphan medicinal product on January 11, 2012. The applicant for this medicinal product was Jazz Pharmaceuticals Ireland Limited. Vyxeos is a liposomal formulation of a fixed combination of daunorubicin and cytarabine, antineoplastic agents that inhibit topoisomerase II activity and also cause DNA damage. The strength of Vyxeos is 5 units/mL, where 1 unit equals 1.0 mg cytarabine plus 0.44 mg daunorubicin. The marketing authorization holder Jazz Pharmaceuticals had found that this was an optimal ratio for the efficacy of the product. Study CLTR0310-301, a phase III, multicenter, randomized, trial of Vyxeos (daunorubicin-cytarabine) liposome injection versus standard 3+7 daunorubicin and cytarabine in patients aged 60-75 years with untreated high-risk (secondary) AML, showed a statistically significant difference between the two groups in overall survival (OS) with a median OS of 9.56 months in the daunorubicin-cytarabine arm compared with 5.95 months for standard chemotherapy (hazard ratio, 0.69; 95% confidence interval, 0.52-0.90; one-sided p = .003). The most common side effects were hypersensitivity including rash, febrile neutropenia, edema, diarrhea/colitis, mucositis, fatigue, musculoskeletal pain, abdominal pain, decreased appetite, cough, headache, chills, arrhythmia, pyrexia, sleep disorders, and hypotension. IMPLICATIONS FOR PRACTICE: Vyxeos has demonstrated a clinically significant improvement in overall survival compared with the standard of care 7+3 in the proposed population of patients with newly diagnosed acute myeloid leukemia (AML) with myelodysplasia-related changes and therapy-related AML. This is remarkable given the very poor prognosis of these patients and their unmet medical need. Secondary endpoints support the primary outcome, in particular an increased rate of hematopoietic stem cell transplantation, which is potentially the only curative treatment in AML.

Individual Trade-Offs Between Possible Benefits and Risks of Cancer Treatments: Results from a Stated Preference Study with Patients with Multiple Myeloma.

BACKGROUND: The objectives of this study were to elicit the preferences of patients with multiple myeloma regarding the possible benefits and risks of cancer treatments and to illustrate how such data may be used to estimate patients' acceptance of new treatments. PATIENTS AND METHODS: Patients with multiple myeloma from the cancer charity Myeloma UK were invited to participate in an online survey based on multicriteria decision analysis and swing weighting to elicit individual stated preferences for the following attributes: (a) 1-year progression-free survival (PFS, ranging from 50% to 90%), (b) mild or moderate toxicity for 2 months or longer (ranging from 85% to 45%), and (c) severe or life-threatening toxicity (ranging from 80% to 20%). RESULTS: A total of 560 participants completed the survey. The average weight given to PFS was 0.54, followed by 0.32 for severe or life-threatening toxicity and 0.14 for mild or moderate chronic toxicity. Participants who ranked severe or life-threatening toxicity above mild or moderate chronic toxicity (56%) were more frequently younger, working, and looking after dependent family members and had more frequently experienced severe or life-threatening side effects. The amount of weight given to PFS did not depend on any of the collected covariates. The feasibility of using the collected preference data to estimate the patients' acceptance of specific multiple myeloma treatments was demonstrated in a subsequent decision analysis example. CONCLUSION: Stated preference studies provide a systematic approach to gain knowledge about the distribution of preferences in the population and about what this implies for patients' acceptance of specific treatments. IMPLICATIONS FOR PRACTICE: This study demonstrated how quantitative preference statements from a large group of participants can be collected through an online survey and how such information may be used to explore the acceptability of specific treatments based on the attributes studied. Results from such studies have the potential to become an important new tool for gathering patient views and studying heterogeneity in preferences in a systematic way, along with other methods, such as focus groups and expert opinions.

Análisis del uso de la terminología anatómica entre los estudiantes de la asignatura anatomía de la Licenciatura en Medicina, de la Facultad de Medicina de la Universidad Nacional Autónoma de México / Analysis of the use of the anatomical terminology between students of anatomy courses at the Faculty of Medicine of the Universidad Nacional Autónoma de México

La Anatomía puede ser considerada el primer campo científico específico dentro del área de la medicina, es una ciencia concreta, utilizada para describir las estructuras del cuerpo humano, para lo cual ha desarrollado un lenguaje descriptivo específico, preciso, universal, inequívoco, denominado "Terminologia Anatomica" (TA). El Departamento de Anatomía de la Facultad de Medicina de la Universidad Nacional Autónoma de México (UNAM), privilegia el uso de la TAI considerando que los alumnos deben conocerla y utilizarla desde el primer año de la licenciatura en medicina, sin embargo, existe cierta resistencia por parte de alumnos y profesores, los cuales recurren en más de una ocasión al uso de epónimos. El propósito de esta investigación fue el de conocer las condiciones de uso que la TA presenta entre los estudiantes del primer año de la licenciatura en medicina en la Facultad de Medicina UNAM, participaron 182 estudiantes de la asignatura Anatomía durante el ciclo escolar 2011-2012. El análisis de los resultados pone en evidencia que el 60,2 % de los alumnos utilizan preferentemente los términos propuestos por la TAI durante el desarrollo de las clases de Anatomía, mientras que fuera de clase solamente el 52,1 % la utilizan. Es posible que estas pautas en el uso de la TA afecten el aprendizaje del lenguaje médico científico que los alumnos utilizarán durante toda su vida profesional.

Anatomy can be considered the first specific scientific field within the area of the medicine, is a concrete science, used to describe the structures of the human body, which has developed a specific, unequivocal, precise, universal and descriptive language, called "Anatomical Terminology" (TA). The Department of Anatomy, from the Faculty of Medicine of the Universidad Nacional Autónoma de México (UNAM), favors the use of TA considering students should know and use it from the first year of a degree in medicine. However, there is some resistance on the part of students and teachers, who on more than one occasion, relied on the use of eponyms. The purpose of this research was to determine the knowledge of use of the TA among first year medical students at the Faculty of Medicine UNAM, in which 182 students of the anatomy course, participated during the 2011-2012 school year. The analysis of the results shows that 60.2 % of students prefer to use the terms proposed by the TAI during the anatomy class, while out of class only 52.1 % were using it. It is possible that these guidelines on the use of TA affect learning scientific medical language that students will use throughout their professional life.

The European Medicines Agency Review of Decitabine (Dacogen) for the Treatment of Adult Patients With Acute Myeloid Leukemia: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use.

UNLABELLED: : On September 20, 2012, a marketing authorization valid throughout the European Union (EU) was issued for decitabine for the treatment of adult patients aged 65 years and older with newly diagnosed de novo or secondary acute myeloid leukemia (AML) who are not candidates for standard induction chemotherapy. Decitabine is a pyrimidine analog incorporated into DNA, where it irreversibly inhibits DNA methyltransferases through covalent adduct formation with the enzyme. The use of decitabine was studied in an open-label, randomized, multicenter phase III study (DACO-016) in patients with newly diagnosed de novo or secondary AML. Decitabine (n = 242) was compared with patient's choice with physician's advice (n = 243) of low-dose cytarabine or supportive care alone. The primary endpoint of the study was overall survival. The median overall survival in the intent-to-treat (ITT) population was 7.7 months among patients treated with decitabine compared with 5.0 months for those in the control arm (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.69-1.04; p = .1079). Mature survival data after an additional year of follow-up were consistent with these results, with a median overall survival of 7.7 months in patients treated with decitabine and 5.0 months in the control arm (HR, 0.82; 95% CI, 0.68-0.99; p = .0373). Secondary endpoints, including response rates, progression-free survival, and event-free survival, were increased in favor of decitabine when compared with control treatment. The most common adverse drug reactions reported during treatment with decitabine are pyrexia, anemia, thrombocytopenia, febrile neutropenia, neutropenia, nausea, and diarrhea. This paper summarizes the scientific review of the application leading to approval of decitabine in the EU. The detailed scientific assessment report and product information (including the summary of product characteristics) for this product are available on the EMA website (http://www.ema.europa.eu). IMPLICATIONS FOR PRACTICE: Acute myeloid leukemia (AML) remains an area of significant unmet need, especially in older patients. Older patients and those with comorbidities are often considered ineligible for standard induction therapy, and outcome for these patients is poor. Decitabine has favorable effects in terms of overall survival, which were considered clinically meaningful in the context of a manageable toxicity profile and after consideration of the lack of therapeutic alternatives for these patients. Decitabine is widely used in the treatment of AML in patients aged >60 years, as per current guidelines, including the European LeukemiaNet and the U.S. National Cancer Comprehensive Network.

The European medicines agency review of pomalidomide in combination with low-dose dexamethasone for the treatment of adult patients with multiple myeloma: summary of the scientific assessment of the committee for medicinal products for human use.

On August 5, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pomalidomide in combination with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy. Pomalidomide is an immunomodulating agent. The recommended starting dose of pomalidomide is 4 mg once daily taken on days 1-21 of repeated 28-day cycles. The main evidence of efficacy for pomalidomide in MM was based on a phase III multicenter, randomized, open-label study (CC-4047-MM-003) in which pomalidomide plus low-dose dexamethasone therapy (POM+LoDEX) was compared with high-dose dexamethasone alone (HiDEX) in previously treated adult patients with relapsed and refractory multiple myeloma who had received at least two prior treatment regimens, including both lenalidomide and bortezomib, and had demonstrated disease progression on the last therapy. For the intent-to-treat population, median progression-free survival based on International Myeloma Working Group criteria was 15.7 weeks (95% confidence interval [CI]: 13.0-20.1) in the POM+LoDEX group versus 8.0 weeks (95% CI: 7.0-9.0) in the HiDEX group (log-rank p value <.001). Overall survival (secondary endpoint) was also different in the two treatment groups (hazard ratio 0.53 [95% CI: 0.37-0.74]). The most commonly reported adverse reactions to pomalidomide in clinical studies were anemia (45.7%), neutropenia (45.3%) and thrombocytopenia (27%), fatigue (28.3%), pyrexia (21%), peripheral edema (13%), and infections including pneumonia (10.7%). Peripheral neuropathy adverse reactions were reported in 12.3% of patients, and venous embolic or thrombotic (VTE) adverse reactions were reported in 3.3% of patients. Pomalidomide is expected to be teratogenic. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).

The European Medicines Agency review of pixantrone for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin's B-cell lymphomas: summary of the scientific assessment of the committee for medicinal products for human use.

On May 10, 2012, the European Commission issued a conditional marketing authorization valid throughout the European Union for pixantrone for the treatment of adult patients with multiply relapsed or refractory aggressive non-Hodgkin's B-cell lymphoma (NHL). Pixantrone is a cytotoxic aza-anthracenedione that directly alkylates DNA-forming stable DNA adducts and cross-strand breaks. The recommended dose of pixantrone is 50 mg/m(2) administered on days 1, 8, and 15 of each 28-day cycle for up to 6 cycles. In the main study submitted for this application, a significant difference in response rate (proportion of complete responses and unconfirmed complete responses) was observed in favor of pixantrone (20.0% vs. 5.7% for pixantrone and physician's best choice, respectively), supported by the results of secondary endpoints of median progression-free and overall survival times (increase of 2.7 and 2.6 months, respectively). The most common side effects with pixantrone were bone marrow suppression (particularly of the neutrophil lineage) nausea, vomiting, and asthenia. This article summarizes the scientific review of the application leading to approval in the European Union. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu).

[Sensibility and specificity of ultrasonographic study in patients with rotator cuff injuries repaired with surgery]. / Cirugía por síndrome del manguito rotador. Utilidad del ultrasonido.

BACKGROUND: painful shoulder syndrome is a pathology that in some cases requires surgical treatment. The objective was to measure the sensibility and predictability of ultrasonographic study in patients with rotator cuff injuries treated with open surgery. METHODS: thirty-two patients with confirmed rotator cuff injury (either by US and/or arthrography) were surgically intervened through opened surgery technique. Sensibility and specificity of ultrasonographic study were measured and also functional results. RESULTS: functional results after open surgery were as follows; excellent in twenty five, good in five and not satisfactory in two patients. Ultrasound sensitivity was of 90 % and its specificity was 81.81 % with a predictive positive value of 94.73 and a predictive negative value of 90.17 %. CONCLUSIONS: the shoulder function recuperation after open surgery was satisfactory in most patients, allowing them going back to the performance of their activities.

El Significado de la Práctica de Disección para los Estudiantes de Medicina / What the Dissection Meaning for Medical Students

El origen de la práctica de disección se remonta siglos atrás, en el tiempo del Museo de Alejandría (III a.C.). Durante casi 23 siglos esta práctica se ha transformado, desde un ejercicio racional hasta la simulación en la "realidad virtual" pasando por la prohibición y el dictado fiel a los cánones impuestos por los anatomistas galénicos. ¿Qué opinan sobre la disección los alumnos de medicina del siglo XXI quienes durante el primer año de su formación habrán que enfrentarse de manera cotidiana a esta actividad? Eso le preguntamos a los alumnos de primer año de la Facultad de Medicina de la Universidad Nacional Autónoma de México. Los resultados de este trabajo nos hablan de la vigencia de esta antigua y moderna estrategia que permite acercarse a la realidad física y espacial del cuerpo humano.

Many centuries ago during the III century B.C. at the Museum of Alexandria, begun the practice of the anatomy dissection. In almost 23 centuries this practice was transforming from a rational exercise to he virtual reality, pass by the prohibition and the tradition lecture imposed by galenic anatomist. What think about dissection the medical students of the XXI Century, whom during their first year of the medical school to be comforting every day with this practice? We asked that to the students of the Medical School at National Autonomous University of Mexico. The results of that work talk us about the actuality of this ancient at the same time modern learning strategy who allows approach to the physical and spatial reality of the human body.