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Introduction: Orphan diseases are low-prevalence conditions with chronically debilitating or life-threatening consequences. Their treatments are generally called orphan drugs (OD). Health-technology assessment processes have traditionally considered cost-effectiveness analysis (CEA), when making reimbursement and pricing decisions for health-care plans. Valuing OD with standard CEA raises important issues due to uncertain evidence, inability to meet cost-effectiveness thresholds for reimbursement and high budget impact, among others. Multi-criteria decision analysis (MCDA) allows to overcome these issues and improve the technical and ethical quality of decisions regarding prioritization, coverage, and reimbursement of OD. Areas covered: A scoping review was conducted in order to characterize MCDA frameworks for assessing OD and implementation experiences. We reviewed electronic databases (Medline, Embase, Cochrane Library, EBSCO, CINAHL, EconLit, Web of Science, LILACS, Google Scholar) key journals (Orphanet Journal of Rare Diseases and Value in Health) and organization repositories. Expert opinion: The theoretical framework for MCDA considers areas related to characteristics of orphan diseases and their technologies' clinical and economic impact. Participation processes are critical in incorporating societal values in weighting different dimensions and constructing decision rules. Local implementation pilots considering different stakeholders are necessary in order to pinpoint specific barriers and opportunities.

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Choline is an essential nutrient in poultry diets because it performs various important metabolic functions. The objective of this study was to re-evaluate the choline requirements of male broiler chickens from 1 to 21 days of age at two levels of methionine. Two assays using 2,160 Cobb® chickens (1,080 in each assay) were conducted. The study design was completely randomized and consisted of six treatments and six replicates, with 30 animals per experimental unit. The semipurified basal diet was formulated with corn, soya bean meal, soya protein concentrate, starch and sugar, providing 390 mg/kg choline and 0.593% digestible methionine (requirement level) in Assay 1 and a reduction of about one-quarter in the requirement level of digestible methionine (0.440%) in Assay 2. Choline chloride (62.5%) was added by a supplementation technique to both basal diets to compose crescent levels of choline supplementation (715, 1,040, 1,365, 1,690 and 2,015 mg/kg). The weight gain responses were fitted using quadratic polynomial (QP) and broken-line (BL) models. The ideal intake of choline (mg/bird.day) was estimated from the first intercept of the QP with the BL plateau (BL + QP). The results showed that the diet with the 25% reduction in digestible methionine limited the maximum weight gain by approximately 10%. The choline requirements of broilers from 1 to 7, 1 to 14 and 1 to 21 days of age were 27,013, 44,458 and 62,535 mg/bird.day, respectively, for the requirement level of digestible methionine and 26,796, 41,820 and 56,578 mg/bird.day for the broilers receiving the diet with the 25% reduction in digestible methionine.

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The objective of this study was to evaluate the effect of the dietary addition of different levels of glycerin on the performance, litter moisture, pododermatitis incidence, and carcass and parts yield of broilers. In total, 1,610 broilers were reared in 35 pens with 46 birds each. A completely randomized experimental design, with five treatments with seven replicates was applied. The experimental treatments were: T1: control diet; T2: dietary inclusion of 5% glycerin from 1-42 days of age; T3: dietary inclusion of 10% glycerin from 1-42 days of age; T4: dietary inclusion of 5% glycerin from 7-42 days of age; T5: dietary inclusion of 10% glycerin from 7-42 days of age. The diets containing glycerin fed since the pre-starter period improved broiler weight gain and feed conversion ratio, but did not influence feed intake or livability. At the end of the experiment, the production efficiency index of the broilers fed 10% glycerin during the entire rearing period was significantly reduced compared with the other treatments. Litter moisture in the pens of broilers fed 10% glycerin during the entire rearing period was higher compared to the other treatments since day 21.Diets containing 10% glycerin, both for the entire rearing period (1-42 days) or only after the pre-starter phase (7-42 days), influenced broiler performance and incidence of severe pododermatitis, reducing the production efficiency indexes at 42 days. Glycerin may be added up to 5% in broiler´s diets with no effect on performance, litter moisture and carcass yield, indicating that this co-product of the biodiesel industry can be used as an alternative feedstuff for broilers.

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The objective of this study was to evaluate the effect of the dietary addition of different levels of glycerin on the performance, litter moisture, pododermatitis incidence, and carcass and parts yield of broilers. In total, 1,610 broilers were reared in 35 pens with 46 birds each. A completely randomized experimental design, with five treatments with seven replicates was applied. The experimental treatments were: T1: control diet; T2: dietary inclusion of 5% glycerin from 1-42 days of age; T3: dietary inclusion of 10% glycerin from 1-42 days of age; T4: dietary inclusion of 5% glycerin from 7-42 days of age; T5: dietary inclusion of 10% glycerin from 7-42 days of age. The diets containing glycerin fed since the pre-starter period improved broiler weight gain and feed conversion ratio, but did not influence feed intake or livability. At the end of the experiment, the production efficiency index of the broilers fed 10% glycerin during the entire rearing period was significantly reduced compared with the other treatments. Litter moisture in the pens of broilers fed 10% glycerin during the entire rearing period was higher compared to the other treatments since day 21.Diets containing 10% glycerin, both for the entire rearing period (1-42 days) or only after the pre-starter phase (7-42 days), influenced broiler performance and incidence of severe pododermatitis, reducing the production efficiency indexes at 42 days. Glycerin may be added up to 5% in broiler´s diets with no effect on performance, litter moisture and carcass yield, indicating that this co-product of the biodiesel industry can be used as an alternative feedstuff for broilers.(AU)

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The objective of the present study was to evaluate the quality of different glycerine sources produced in Brazil and to analyze their metabolizable energy levels and digestibility for broilers. Firstly, the composition of 10 samples of glycerine from different sources was analyzed. Secondly, glycerine from four different sources presenting contrasting compositions were selected to determine their metabolizable energy levels and digestibility in metabolism assays using 200 broilers between 21 and 29 days of age, applying the method of total excreta collection. The values of apparent metabolizable energy corrected for nitrogen balance of the four glycerine sources were 3145, 5026, 2828, and 2892 kcal/kg.

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The objective of the present study was to evaluate the quality of different glycerine sources produced in Brazil and to analyze their metabolizable energy levels and digestibility for broilers. Firstly, the composition of 10 samples of glycerine from different sources was analyzed. Secondly, glycerine from four different sources presenting contrasting compositions were selected to determine their metabolizable energy levels and digestibility in metabolism assays using 200 broilers between 21 and 29 days of age, applying the method of total excreta collection. The values of apparent metabolizable energy corrected for nitrogen balance of the four glycerine sources were 3145, 5026, 2828, and 2892 kcal/kg.(AU)

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This study evaluated the metabolic response of broilers fed diets containing increasing crude glycerine levels in two bioassays. Birds were house in metabolic cages, and were distributed according to a completely randomized experimental design with five treatments of 4 replicates each (1st assay: 5 birds/ cage; 2nd assay: 1-20 days = 8 birds/ cage, and 21-42 days = 4 birds/cage). Treatments consisted of a control diet based on corn and soybean meal, and four other diets containing 2.5%, 5.0%, 7.5% and 10.0% glycerine derived from biodiesel. In experiment I, there was no effect (p>0.05) of glycerol level on liver weight or blood parameters. Serum blood glycerol levels of the birds fed 10% crude glycerine increased during the first nine days of diet intake (p 0.05). In experiment II, water intake increased (p 0.05) in the birds fed 7.5 and 10.0% crude glycerine at 4 and 8 days of age. Feed intake increased (p 0.05) on days 8 and 12 in birds fed 2.5 and 7.5% glycerine. Fecal moisture increased (p 0.05) in birds fed diets with 5.0, 7.5, and 10.0% crude glycerine on days 16 and 20. Ileal content moisture was not different (p>0.05) among treatments when birds were 42 days old. High dietary glycerine levels may induce metabolic change in broilers, such as increased blood glycerol level, water intake and fecal moisture.(AU)

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Foi avaliada a eficiência de uma fitase (FT) bacteriana na liberação de fósforo fítico utilizando-se curvas de calibração para características ósseas e de desempenho em frangos de corte. O delineamento experimental foi inteiramente ao acaso, com seis tratamentos e seis repetições até 28 dias de idade. O tratamento-controle foi uma dieta à base de milho e farelo de soja deficiente em fósforo (P). Dois tratamentos corresponderam às dietas basais acrescidas de P suplementar, 0,05 por cento e 0,10 por cento, e os outros à dieta basal com 66, 99 e 131 FTU/kg de ração. A curva padrão é definida pelo efeito da adição de P suplementar consumido sobre características ósseas e de desempenho, e os resultados dos tratamentos com fitase são confrontados com a curva para cálculo de P liberado. A adição de P suplementar influenciou o ganho de peso, o peso vivo e o consumo de ração de forma quadrática, bem como miligramas de cinzas ósseas de forma linear. A curva padrão adotada foi da variável miligramas de cinzas ósseas, pois a resposta linear melhor descreve a curva. As inclusões de 66, 99 e 131 FTU/kg liberaram, respectivamente, 0,048 por cento, 0,049 por cento e 0,062 por cento de P. A fitase bacteriana é eficiente na liberação de fósforo fítico e possui viabilidade econômica.

The objective was to determine the efficiency of a bacterial phytase to release phytate phosphorus using calibration curves for performance and bone characteristics in broiler chickens. A completely randomized design with 6 treatments and 6 replicates was used in an experiment with chickens from 1 to 28 days of age. The control treatment was a diet based on corn and soybean meal deficient in phosphorus. Two treatments consisted of the basal diet supplemented with additional phosphorus (0.05 percent and 0.10 percent), and the other treatments received 66, 99 and 131 FTU/kg of feed. The standard curves represented the effect of the levels of additional P intake on performance and bone variables. Then, the responses of the phytase treatments were compared to the standard curves to calculate the P released. The increasing levels of supplemental P had a quadratic effect on weight gain, live weight and feed intake, and linear effect on mg of bone ash. The standard curve elected was mg of bone ash because linear response better represents the curve. Inclusion of 66, 99 and 131 FTU/kg released 0.048 percent, 0.049 percent and 0.062 percent. The bacterial phytase is efficient in releasing phytate, which may be of economical significance.

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Foi avaliada a eficiência de uma fitase (FT) bacteriana na liberação de fósforo fítico utilizando-se curvas de calibração para características ósseas e de desempenho em frangos de corte. O delineamento experimental foi inteiramente ao acaso, com seis tratamentos e seis repetições até 28 dias de idade. O tratamento-controle foi uma dieta à base de milho e farelo de soja deficiente em fósforo (P). Dois tratamentos corresponderam às dietas basais acrescidas de P suplementar, 0,05 por cento e 0,10 por cento, e os outros à dieta basal com 66, 99 e 131 FTU/kg de ração. A curva padrão é definida pelo efeito da adição de P suplementar consumido sobre características ósseas e de desempenho, e os resultados dos tratamentos com fitase são confrontados com a curva para cálculo de P liberado. A adição de P suplementar influenciou o ganho de peso, o peso vivo e o consumo de ração de forma quadrática, bem como miligramas de cinzas ósseas de forma linear. A curva padrão adotada foi da variável miligramas de cinzas ósseas, pois a resposta linear melhor descreve a curva. As inclusões de 66, 99 e 131 FTU/kg liberaram, respectivamente, 0,048 por cento, 0,049 por cento e 0,062 por cento de P. A fitase bacteriana é eficiente na liberação de fósforo fítico e possui viabilidade econômica.(AU)

The objective was to determine the efficiency of a bacterial phytase to release phytate phosphorus using calibration curves for performance and bone characteristics in broiler chickens. A completely randomized design with 6 treatments and 6 replicates was used in an experiment with chickens from 1 to 28 days of age. The control treatment was a diet based on corn and soybean meal deficient in phosphorus. Two treatments consisted of the basal diet supplemented with additional phosphorus (0.05 percent and 0.10 percent), and the other treatments received 66, 99 and 131 FTU/kg of feed. The standard curves represented the effect of the levels of additional P intake on performance and bone variables. Then, the responses of the phytase treatments were compared to the standard curves to calculate the P released. The increasing levels of supplemental P had a quadratic effect on weight gain, live weight and feed intake, and linear effect on mg of bone ash. The standard curve elected was mg of bone ash because linear response better represents the curve. Inclusion of 66, 99 and 131 FTU/kg released 0.048 percent, 0.049 percent and 0.062 percent. The bacterial phytase is efficient in releasing phytate, which may be of economical significance.(AU)

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Se realizó un estudio en dos fases: la primera de ellas orientada a hacer ajustes al instrumento -Percepción del Clima Ético Hospitalario- diseñado por la doctora Linda Olson; con base en las recomendaciones formuladas por Gutiérrez; e introducirle nuevas preguntas; acordes al contexto colombiano; para luego evaluar psicométricamente la validez y confiabilidad del instrumento. La segunda fase consistió en aplicar dicho instrumento a 219 enfermeras en tres IPS: una privada; una pública y una de un régimen especial. Los resultados sugieren que el instrumento con las nuevas preguntas registra una validez de contenido que oscila entre 0;66 y 1 y una confiabilidad global de 0.94 con una correlación superior a 0;38 y una validez de constructo donde los 8 primeros factores obtenidos explican el 60;22% de la varianza total; con una carga mínima para cada ítem de 0;3 . Las preguntas elaboradas por el grupo investigador tuvieron un Alpha de Cronbach de 0;87. Los resultados demuestran que este instrumento; a nivel global; tiene una alta validez y confiabilidad para medir Clima Ético Hospitalario como herramienta diagnóstica necesaria para la intervención sobre esta temática y el clima organizacional en general en las instituciones hospitalarias. La aplicación del instrumento arrojó como resultados que en el clima ético organizacional en las IPS objeto de estudio es relevante la ausencia de la confianza en las relaciones del enfermero con la empresa y con los demás profesionales; su actuar se orienta hacia el respeto a la autoridad; hay heteronomía en la relación con el médico y unas conductas mediadas más por los códigos y señales de la profesión que por las señales organizacionales. La responsabilidad de empleados con la empresa y los pacientes es mayor que aquella de la institución con los empleados. Se sugiere investigar en mayor profundidad si las conductas consideradas "responsables" obedecen a una necesidad de cumplir con la obligación legal o si se trata de una genuina responsabilidad moral.

In order to measure the nursing-perceived ethics status prevailing in three Health Service Providers HSP in Bogota, a two-stage project was performed. In the first stage, Dr. Linda Olson´s designed perception instrument "Ethics Status Perception in Hospitals" was adjusted according to Gutierrez suggestions to include new items applicable to the Colombian context, and to re-asses its reliability. In the second stage, the adjusted instrument was applied to 219 nurses from three HSP: One public, and one special. The reliability of the new instrument included a Cronback´s alpha of 0.87, a validity index of 0.66, a trustworthiness index of 0.94, and an inter-item correlation of 0.38. Accounting for 60.22% of the total variance, eigth factors were obtained. The corresponding statistics showed that the adjusted instrument is highly reliable to measure the ethics status in hospitals, and that it could be usedas an organizational diagnostic tool. A HSP nursing-perception finding was the lack of confidence among nurses, hospitals, and other professionals. They perceived that organizational ethics are oriented towards respect to the authority, unilateral commanding, and behavior mediated, more by professional codes, than by organizational signal. They also perceived that more responsibility on patients is deposited on nurses than on other institutional employees. It is suggested to further insight if the "responsible" conducts arise from a legal obligation or from a genuine moral attitude.

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The moderate quality of beta obesity and its relatively slow evolution make it potentially useful for defining the sequence of events that lead to the overt syndrome. Estimates of food intake, live body weight, deep body temperature, triglyceridemia and glycemia were obtained at several times during the day in beta genetically obese and alpha (alpha) control male rats at peripuberal age, in order to characterize the dynamic phase of this obesity and to attempt the definition of some previous proceedings that eventually produce the full obesity syndrome. Beta higher food intake in the light cycle preceded its whole day hyperphagia. Both genotypes showed the normal pattern of predominantly nocturnal feeding. A lower light phase's weight loss in beta preceded the overweight. Thus, beta rats were not significantly heavier than alpha until the end of the last period studied, when they were 75 days old. A defect in adaptive thermogenesis in beta genotype is suggested, as values on deep body temperature in relation to alpha were significantly lower at all times of day tested. Correlation coefficient value between daily net weight gain versus deep body temperature was: r = -0.601 (p less than 0.01), suggesting a diminished lipolytic stimulation in beta brown adipose tissue. A sustained hypertriglyceridemia in beta at every time of the day studied suggested its endogenous source. Differences in glycemia values were not statistically significant between genotypes, though apparently wider variations in beta could reflect a certain glycemic regulation lability in the obese genotype.

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The moderate quality of beta obesity and its relatively slow evolution make it potentially useful for defining the sequence of events that lead to the overt syndrome. Estimates of food intake, live body weight, deep body temperature, triglyceridemia and glycemia were obtained at several times during the day in beta genetically obese and alpha (alpha) control male rats at peripuberal age, in order to characterize the dynamic phase of this obesity and to attempt the definition of some previous proceedings that eventually produce the full obesity syndrome. Beta higher food intake in the light cycle preceded its whole day hyperphagia. Both genotypes showed the normal pattern of predominantly nocturnal feeding. A lower light phases weight loss in beta preceded the overweight. Thus, beta rats were not significantly heavier than alpha until the end of the last period studied, when they were 75 days old. A defect in adaptive thermogenesis in beta genotype is suggested, as values on deep body temperature in relation to alpha were significantly lower at all times of day tested. Correlation coefficient value between daily net weight gain versus deep body temperature was: r = -0.601 (p less than 0.01), suggesting a diminished lipolytic stimulation in beta brown adipose tissue. A sustained hypertriglyceridemia in beta at every time of the day studied suggested its endogenous source. Differences in glycemia values were not statistically significant between genotypes, though apparently wider variations in beta could reflect a certain glycemic regulation lability in the obese genotype.

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