Cost-effectiveness of midostaurin in the treatment of acute myeloid leukemia with the FLT3 mutation in Spain

The addition of midostaurin to standard chemotherapy (cytarabine and daunorubicin) has shown significant improvements in the survival of patients with acute myeloid leukemia with the FLT3 mutation (FLT3-AML). The objective of this study was to determine whether this intervention would be cost-effective in Spain. A partitioned survival model with five health states was developed (diagnosis and induction, complete remission, no complete remission, transplantation and death). A lifetime time horizon and the Spanish National Health System perspective were adopted. During the first three years, permanence in the different health states was determined according to the results of the RATIFY study. In successive years, the death rates of the Spanish population adjusted by a factor to reflect long-term disease-related mortality were used. Utilities were obtained from the literature. Pharmacological costs (first and second line) and the costs of other health resources (hospitalizations, visits and tests) were included. The robustness of the model was evaluated by deterministic and probabilistic sensitivity analyses. The addition of midostaurin resulted in 1.46 life years gained (LYG) and 1.23 quality-adjusted life years (QALY) gained and implied an additional cost of € 47,955, resulting in an incremental cost-effectiveness ratio (ICER) of € 32,854/LYG and an incremental cost-utility ratio of € 38,985/QALY. In the univariate sensitivity analysis, the threshold of € 50,000/QALY was not exceeded in any case; taking into consideration potential discounts of 20-40% in the PVL of midostaurin the ICER would be below € 30,000/QALY, a commonly accepted threshold in Spain. In the probabilistic analysis, when the threshold was € 50,000/QALY, midostaurin was cost-effective in 82.3% of simulations. According to our modeling, midostaurin, in combination with standard chemotherapy, could be an efficient alternative for the treatment of FLT3-AML in Spain. © 2019 Arenaza et al

Preparados estándar de nutrición parenteral en situaciones clínicas complejas

Objetivo: Los preparados binarios y ternarios de nu-trición parenteral, en determinados casos pueden ver su utilidad limitada. El objetivo de este estudio es establecer situaciones de difícil manejo nutricional y analizar el tipo de fór-mula utilizada en estas situaciones. Material y métodos: Se incluyen pacientes tratados con nutrición parenteral durante 9 meses. Se definen tres situaciones clínicamente complejas: larga dura-ción, con más de 25 días; insuficiencia renal, uremia > 20 mmol/L o creatinina sérica > 200 µmol/L; e insufi-ciencia hepática, bilirrubina total > 30 mmol/L o ALT > 2 µkat/L y fosfatasa alcalina > 3 µkat/L o GGT > 3 µkat/L. Se estudian la mortalidad e hipoalbuminemia (< 35 g/L) y se comparan mediante un test de Ji cua-drado (p < 0,05) al resto de los pacientes. La utilización de fórmulas individualizadas se estudia con un modelo de regresión logística múltiple, la variable dependiente es la administración o no de fórmulas individualizadas y las variables independientes son los 3 grupos de pa-cientes en situaciones clínicas definidas como comple-jas. Coo medida del riesgo se estudian las ¿Odds Ra-tio¿ (OR). Resultados: Se estudian 511 pacientes con 8.015 NP. 283 resultaron incluidos en una o más de las 3 situacio-nes clínicas complejas. Los tres grupos presentaron ni-veles de mortalidad e hipoalbuminemia superiores con diferencias estadísticamente significativas sobre el grupo de situación clínica no compleja. La utilización de fórmulas individualizadas fue superior en los tres grupos definidos resultando las diferencias estadística-mente significativas: OR = 6,7 (IC 95%; 3,78-11,91) en larga duración, OR = 3,66 (IC 95%: 2,68-5,68) en insuficiencia renal IR y OR = 1,5 (IC 95%: 1,01-2,35) en insuficiencia hepática. Conclusiones: Los pacientes en situación clínica compleja presentan mayor desnutrición visceral, peor evolución clínica y, en nuestro hospital, su tratamiento nutricional por vía parenteral se basa en una mayor utilización de fórmulas individualizadas

The West Indies as a laboratory of biogeography and evolution

Islands have long provided material and inspiration for the study of evolution and ecology. The West Indies are complex historically and geographically, providing a rich backdrop for the analysis of colonization, diversification and extinction of species. They are sufficiently isolated to sustain endemic forms and close enough to sources of colonists to develop a dynamic interaction with surrounding continental regions. The Greater Antilles comprise old fragments of continental crust, some very large; the Lesser Antilles are a more recent volcanic island arc, and the low-lying Bahama Islands are scattered on a shallow oceanic platform. Dating of island lineages using molecular methods indicates over-water dispersal of most inhabitants of the West Indies, although direct connections with what is now southern Mexico in the Early Tertiary, and subsequent land bridges or stepping stone islands linking to Central and South America might also have facilitated colonization. Species–area relationships within the West Indies suggest a strong role for endemic radiations and extinction in shaping patterns of diversity. Diversification is promoted by opportunities for allopatric divergence between islands, or within the large islands of the Greater Antilles, with a classic example provided by the Anolis lizards. The timing of colonization events using molecular clocks permits analysis of colonization–extinction dynamics by means of species accumulation curves. These indicate low rates of colonization and extinction for reptiles and amphibians in the Greater Antilles, with estimated average persistence times of lineages in the West Indies exceeding 30 Myr. Even though individual island populations of birds might persist an average of 2 Myr on larger islands in the Lesser Antilles, recolonization from within the archipelago appears to maintain avian lineages within the island chain indefinitely. Birds of the Lesser Antilles also provide evidence of a mass extinction event within the past million years, emphasizing the time-heterogeneity of historical processes. Geographical dynamics are matched by ecological changes in the distribution of species within islands over time resulting from adaptive radiation and shifts in habitat, often following repeatable patterns. Although extinction is relatively infrequent under natural conditions, changes in island environments as a result of human activities have exterminated many populations and others—especially old, endemic species—remain vulnerable. Conservation efforts are strengthened by recognition of aesthetic, cultural and scientific values of the unique flora and fauna of the West Indies