Iodine status and thyroid function among Spanish schoolchildren aged 6-7 years: the Tirokid study.

I deficiency is still a worldwide public health problem, with children being especially vulnerable. No nationwide study had been conducted to assess the I status of Spanish children, and thus an observational, multicentre and cross-sectional study was conducted in Spain to assess the I status and thyroid function in schoolchildren aged 6-7 years. The median urinary I (UI) and thyroid-stimulating hormone (TSH) levels in whole blood were used to assess the I status and thyroid function, respectively. A FFQ was used to determine the consumption of I-rich foods. A total of 1981 schoolchildren (52 % male) were included. The median UI was 173 µg/l, and 17·9 % of children showed UI<100 µg/l. The median UI was higher in males (180·8 v. 153·6 µg/l; P<0·001). Iodised salt (IS) intake at home was 69·8 %. IS consumption and intakes of ≥2 glasses of milk or 1 cup of yogurt/d were associated with significantly higher median UI. Median TSH was 0·90 mU/l and was higher in females (0·98 v. 0·83; P<0·001). In total, 0·5 % of children had known hypothyroidism (derived from the questionnaire) and 7·6 % had TSH levels above reference values. Median TSH was higher in schoolchildren with family history of hypothyroidism. I intake was adequate in Spanish schoolchildren. However, no correlation was found between TSH and median UI in any geographical area. The prevalence of TSH above reference values was high and its association with thyroid autoimmunity should be determined. Further assessment of thyroid autoimmunity in Spanish schoolchildren is desirable.

Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in combined therapy in the initial phases of breast cancer.

INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil, doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node-positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001 were combined with Spanish costs and longterm efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model. Results are shown as cost per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY). Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was 17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and euro11,586, respectively. The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631, respectively. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective option, but also presents a favourable cost-effectiveness ratio, clearly below the Spanish efficiency threshold in all the scenarios considered.

Neuroblastoma: validation of the INRG classification system in a small series.

PURPOSE: In 2009, the International Neuroblastoma Risk Group (INRG) published a new classification system of the childhood neuroblastic tumors. In this work, we present the results of the application of this new classification system in our patients. METHODS/PATIENTS: We conducted a retrospective analysis of the patients diagnosed with a neuroblastic tumor in our center in the last 20 years. We classified them according to the new classification and performed a survival analysis based on the Kaplan-Meier method and Mantel-Cox test. RESULTS: The five-year event-free survival (5-year EFS) was 95.8, 80.8, 50 and 45.9% for the very low, low, intermediate and high-risk groups. Mantel-Cox test showed statistically significant differences between these risk groups (p = 0.002). CONCLUSION: The 5-year EFS for the different risk groups was similar to the expected by the INRG. Therefore, this classification allows us to predict the evolution of this tumor and apply the correct intensity of treatment.

[Cost effectiveness analysis of varenicline (Champix) for the treatment of smoking in Spain]. / Análisis coste-efectividad de vareniclina (Champix) en el tratamiento del tabaquismo en España.

OBJECTIVE: To analyse the efficiency of varenicline compared with bupropion, NRT (nicotine replacement therapy) and no pharmacological treatment in Spain. METHODS: A Markov model was developed to analyse the health and economic consequences of smoking cessation therapies. The transition probabilities were taken from published studies. The model allows cost effectiveness analyses for different time frames (10 years, 20 years and life time). Outcomes are measured in terms of incremental life years gained (LYG) and QALYs. Pharmacological costs and costs of medical visits with varenicline and bupropion were considered. Treatment costs of smoking associated morbidity were taken from Spanish studies. RESULTS: The analyses were done under the perspective of the National Health System, discounting costs and health benefits at 3%. The life time cost-effectiveness analysis shows that varenicline dominates all other smoking cessation interventions (more effective at a lower cost). This is due to the higher efficacy of varenicline associated with a reduction in smoking related morbimortality, which, in the long term, accounts for health care cost savings that overcome the extra cost of varenicline. Even when shorter timeframes are considered (20 years), vareniclin is cost-effective in comparison with any other alternative. CONCLUSIONS: Varenicline is a dominant option (more effective at a lower cost) compared with all other smoking cessation treatments when the timeframe is the life span of the patient. Varenicline is cost-effective even when shorter timeframes are considered (20 years or more), with an estimated incremental cost per QALY far bellow any threshold commonly accepted in our environment.

Testicular biopsy in patients with obstructive azoospermia.

The present report studies the testicular biopsy lesions (histologic and semiquantitative) in a series of 48 patients with obstructive azoospermia of known etiology (vasectomy, congenital absence of vas deferens, herniorrhaphy, hydrocelectomy, Young's syndrome, and ejaculatory duct obstruction) in order to establish objective testicular data that permit the pathologist to diagnose an obstructive process, which should not be mistaken with a primary testicular lesion. The semiquantitative study included determinations of the average numbers of spermatogonia, primary spermatocytes, young spermatids (Sa + Sb), and differentiated spermatids (Sc + Sd). According to this study, the testes were classified into the following groups: (1) normal testes whose germ cell numbers were within normal limits (27 testes); (2) testes with lesions in the adluminal compartment; these lesions comprise two subgroups: (2a) late sloughing of primary spermatocytes (both spermatid types were greatly reduced in number while the other germ cell types were in normal numbers) (45 testes); and (2b) early sloughing of primary spermatocytes (normal spermatogonial number, reduced number of spermatocytes, and scanty spermatids) (9 testes); and (3) lesions in the basal compartment; these lesions comprise two subgroups: (3a) pure hypospermatogenesis (a proportionate decrease in the numbers of all germ cell types) (8 testes); and (3b) hypospermatogenesis associated with sloughing of primary spermatocytes (decreased numbers of all germ cell types with a very scanty number spermatids) (4 testes). Two testes appeared hyalinized and one testis was removed owing to cryptorchidism. The most frequent testicular lesion observed (alteration in the adluminal compartment of seminiferous tubules) seems to be related to the increase in hydrostatic pressure in the tight compartment formed by seminiferous tubules, rete testis, efferent ducts, the epididymal duct, and the initial portion of the vas deferens. The severity of the lesions is probably related to the cause and span of the obstruction. In addition, two azoospermic men without obstructive azoospermia and whose testicular biopsy study revealed meiotic anomalies (with the subsequent bad prognosis) were also studied for comparison. The semiquantitative study of these patients permitted the differential diagnosis between two lesion types. Testes with meiotic anomalies had a disproportionately elevated number of primary spermatocytes, and an extremely low number of young spermatids.

Correlation between testicular biopsies (prepubertal and postpubertal) and spermiogram in cryptorchid men.

Twenty-one young men who underwent testicular biopsy and orchidopexy in infancy consulted owing to infertility and had biopsies again. The first and second biopsy specimens from these patients were compared by means of a semiquantitative study of the seminiferous tubules to evaluate the evolution of germ cells and to correlate these data with spermatozoon numbers. The infant testes showing lesions were classified into 3 types according to the mean tubular diameter and tubular fertility index: (1) slight lesions, (2) marked germinal hypoplasia, and (3) severe germinal hypoplasia. In the adult testes, spermatogenesis was evaluated by calculating the average numbers of spermatogonia, primary spermatocytes, young spermatids, and mature spermatids. These testes were classified as (1) normal; (2) having lesions in the adluminal compartment; (3) having lesions in the basal compartment; and (4) mixed atrophy. The number of differentiated spermatids was correlated with the expected number of spermatozoa in the ejaculate by a power regression curve. The observation of certain histologic lesions in the seminiferous tubules was assumed to indicate excretory duct obstruction: ectasia, indented outline of the seminiferous epithelium, intratesticular spermatocele, apical cytoplasmic vacuolation of Sertoli cells, and mosaic distribution of testicular lesions. There was a correlation between the prepubertal lesions and the degree of spermatogenesis in postpubertal biopsy specimens. The evolution of the 40 testes without regard to their location in infancy (cryptorchid or scrotal) was as follows. The 14 infant testes with a normal histologic pattern (5 testes) or minor lesions (9 testes) evolved to testes with lesions of the adluminal compartment (8 testes), mixed atrophy (4 testes), or lesions of the basal and adluminal compartments (2 testes). The 6 testes with marked germinal hypoplasia evolved to testes with mixed atrophy. The 20 testes with severe germinal hypoplasia evolved to testes with mixed atrophy (17 testes), Sertoli-cell-only tubules (2 testes), or lesions in the basal compartment (1 testis). In the 9 patients with a histologic pattern of obstruction bilaterally (6 men) or unilaterally (3 men), the expected number of spermatozoa according to the correlation curve was much higher than the actual number in the spermiogram. This means that the testes of many azoospermic men produce spermatozoa, and this finding corroborates the importance of testicular biopsy in infertility studies.

[Cost-effectiveness analysis of enoxaparin for the prophylaxis of venous thromboembolism in major orthopedic surgery patients]. / Análisis coste-efectividad de enoxaparina en la proxilaxis de la enfermedad tromboembólica venosa en pacientes sometidos a cirugía mayor ortopédica.

OBJECTIVES AND METHODS: A retrospective, modeled, cost-effectiveness analysis was conducted with enoxaparin versus non-prophylaxis, tinzaparin, and unfractionated heparin for venous thromboembolic disease in Spanish patients undergoing major orthopedic surgery from the standpoint of the Spanish national health system. Episodes avoided and life-years gained with each treatment were estimated by a meta-analysis of clinical trials. RESULTS: With enoxaparin fewer thromboembolic episodes and deaths occurred, when compared to the available alternative options. Enoxaparin was the dominant option (lower total cost and equal or greater effectiveness than any alternative option) in comparison with non-prophylaxis, tinzaparin, and unfractionated heparin. A sensitivity analysis confirmed the stability of these results. CONCLUSION: The administration of enoxaparin as a prophylactic treatment for venous thromboembolic disease in patients undergoing hip or knee surgery is a cost-effective intervention in every case, and less expensive than the alternative options used in Spain.

[Autograft of the adrenal medulla to caudate nucleus as Parkinson disease treatment: long-term clinical evaluation]. / Autoinjerto de médula suprarrenal al núcleo caudado como tratamiento de la enfermedad de Parkinson: evaluación clínica a largo plazo.

This work presents the long-term evolution (12-27 months) of the patients with adrenomedullary autotransplants to the caudate nucleus for the treatment of Parkinson's disease. Sixteen men and 6 women, mean age of 49.9 years, received brain implants of their own adrenal medulla using the procedure of Madrazo et al. (1). Nineteen of the transplanted patients suffered idiopathic Parkinson's disease and 3 of them parkinsonism. Before surgery 20 patients were on L-dopa and suffered collateral signs due to the drug. The degree of severity of their disease was evaluated pre and postoperatively, with and without medication, in their "on" and "off" periods, using the international scales of Schwab and England, Hoehn and Yahr, Madrazo, and the UPRS, and was documented by videotape. Biochemical analyses were made of lumbar and ventricular cerebrospinal fluid, and neuropsychological and neurophysiological evaluations were performed before and after surgery. In some patients, the location and viability of the adrenal medullary implants were demonstrated by brain scintigraphy using 131-I-metaiodobenzylguanidine, a chromaffin specific radiopharmaceutical. The clinical evaluations of 18 autotransplanted patients (4 died) showed their significant functional recovery both in their "on" and "off" periods, that for the first patients operated has remained stable for 27 months. Also, their response to L-dopa improved allowing the reduction of their postoperative doses of medication to 30% of their preoperative requirements, with the disappearance of the collateral effects of the drug.

[GATA1 analysis in myeloproliferative disorders associated to trisomy 21]. / Análisis de GATA1 en los trastornos mieloproliferativos asociados a la trisomía 21.

INTRODUCTION: Neonatal transient myeloproliferative disorder and acute megakaryoblastic leukaemia of Down syndrome are considered different manifestations of the same disease. In most cases, transient myeloproliferative disorders require no treatment, while acute megakaryoblastic leukaemia of Down's syndrome is characterised by an increased sensitivity to chemotherapy and its treatment should be adapted with a reduction in dose intensity. Both entities share specific mutations at exón 2 of the transcription factor GATA1. PATIENTS AND METHODS: We analysed biological features and GATA1 mutations in 4 patients with transient abnormal myelopoiesis (2) and acute megakaryoblastic leukaemia (2) including one phenotypically normal trisomy 21 mosaicism. We found abnormal GATA1 mutated clones in each case, and a specific point mutation at exón 2 was detected in three cases. Given the heterogeneous phenotype of megakaryoblastic blasts and the low percentage of blasts at presentation, the recognition of GATA1 mutations was helpful for diagnosis. In addition, molecular remission was established in 2 patients after subsequent normal mutational GATA1 analysis. CONCLUSIONS: We conclude that GATA1 mutational study is a useful tool for the diagnosis and management of trisomy 21 associated myeloproliferative disorders.

Análisis coste-efectividad de vareniclina (Champix®) en el tratamiento del tabaquismo en España / Cost effectiveness analysis of varenicline (Champix®) for the treatment of smoking in Spain

Objetivos: Analizar la eficiencia de la vareniclina (Champix®) versus bupropion y TSN (terapia sustitutiva con nicotina) y tratamiento no farmacológico en España. Métodos: Se utilizó un modelo de Markov para analizar las consecuencias clínicas y económicas del tabaquismo y distintas intervenciones para dejar de fumar. Las probabilidades fueron tomadas de la literatura y ensayos clínicos, siendo utilizadas para estimar la efectividad de las opciones comparadas (vareniclina, bupropión, TSN y no tratamiento farmacológico), para distintos horizontes temporales. Los resultados se expresaron en años de vida (AV) ganado y coste por años de vida ajustados por calidad (AVAC) ganado de vareniclina vs comparadores. El análisis se realizó desde la perspectiva del Sistema Nacional de Salud, descontando los costes al 3,5% anual. Resultados: La mayor eficacia de vareniclina supone una reducción de la morbi-mortalidad asociada al tabaquismo, que a largo plazo, compensa totalmente el coste adicional del tratamiento respecto a los comparadores.Vareniclina se muestra como una opción dominante respecto a todas las alternativas en el análisis a largo plazo (toda la vida de los sujetos). Incluso tomando horizontes temporales más cortos (20 años) resulta coste efectivo, siempre menos de 9.000 €/AVAC ganado en comparación con cualquier alternativa. Conclusiones: Vareniclina es una opción dominante (más efectiva amenor coste) comparada con los demás tratamientos, cuando se considera toda la vida del sujeto. Vareniclina es una terapia coste-efectiva incluso cuando se consideran horizontes temporales más cortos (a partir de 20 años), con un coste efectividad incremental muy por debajo del umbral aceptado en nuestro entorno

Objective: To analyse the efficiency of varenicline compared with bupropion, NRT (nicotine replacement therapy) and no pharmacological treatment in Spain. Methods: A Markov model was developed to analyse the health and economic consequences of smoking cessation therapies. The transition probabilities were taken from published studies. The model allows cost effectiveness analyses for different time frames (10 years, 20 years and life time). Outcomes are measured in terms of incremental life years gained (LYG) and QALYs. Pharmacological costs and costs of medical visits with varenicline and bupropion were considered. Treatment costs of smoking associated morbidity were taken from Spanish studies. Results: The analyses were done under the perspective of the National Health System, discounting costs and health benefits at 3%. Results:The life time cost-effectiveness analysis shows that varenicline dominates all other smoking cessation interventions (more effective at a lower cost).This is due to the higher efficacy of varenicline associated with a reductionin smoking related morbimortality, which, in the long term, accounts for health care cost savings that overcome the extra cost of varenicline. Even when shorter time frames are considered (20 years), vareniclin is cost-effective in comparison with any other alternative. Conclusions: Varenicline is a dominant option (more effective at a lower cost) compared with all other smoking cessation treatments when the timeframe is the life span of the patient. Varenicline is cost-effective even when shorter timeframes are considered (20 years or more), withan estimated incremental cost per QALY far bellow any thresh old commonly accepted in our environment

Análisis de GATA1 en los trastornos mieloproliferativos asociados a la trisomía 21 / GATA1 analysis in myeloproliferative disorders associated to trisomy 21

Introducción: La enfermedad mieloproliferativa transitoria neonatal y la leucemia aguda megacarioblástica del síndrome de Down se consideran manifestaciones distintas de la misma enfermedad. La mayoría de casos de enfermedad mieloproliferativa transitoria no requiere tratamiento mientras que la leucemia aguda megacarioblástica del síndrome de Down se caracteriza por una elevada sensibilidad a la quimioterapia, lo que ha llevado a la reducción en la intensidad de dosis de tratamiento administrada. Ambas entidades comparten mutaciones específicas en los exones 2 y 3,1 del factor de transcripción GATA1. Pacientes y métodos: Hemos analizado los hallazgos biológicos incluyendo la presencia de mutaciones de GATA1 en cuatro pacientes con enfermedad mieloproliferativa transitoria neonatal (2) y leucemia aguda megacarioblástica (2) incluyendo un paciente fenotípicamente normal portador de un mosaicismo para la trisomía 21. Resultados: En los cuatro casos hemos encontrado la presencia de una clona GATA1 mutante y en tres de ellos se describe una mutación puntual en el exón 2 de dicho gen. Dada la heterogeneidad fenotípica de los blastos megacariocíticos y el bajo porcentaje de estos elementos, la detección de mutaciones en GATA1 resultó de gran utilidad para establecer el diagnóstico. Además, sucesivos resultados normales del análisis mutacional de GATA1 permitieron establecer la remisión molecular en 2 pacientes. Conclusiones: Concluimos que el análisis mutacional de GATA1 es una herramienta útil para el diagnóstico y manejo de los trastornos mieloproliferativos asociados a la trisomía 21 (AU)

Introduction: Neonatal transient myeloproliferative disorder and acute megakaryoblastic leukaemia of Down syndrome are considered different manifestations of the same disease. In most cases, transient myeloproliferative disorders require no treatment, while acute megakaryoblastic leukaemia of Down's syndrome is characterised by an increased sensitivity to chemotherapy and its treatment should be adapted with a reduction in dose intensity. Both entities share specific mutations at exón 2 of the transcription factor GATA1. Patients and methods: We analysed biological features and GATA1 mutations in 4 patients with transient abnormal myelopoiesis (2) and acute megakaryoblastic leukaemia (2) including one phenotypically normal trisomy 21 mosaicism. We found abnormal GATA1 mutated clones in each case, and a specific point mutation at exón 2 was detected in three cases. Given the heterogeneous phenotype of megakaryoblastic blasts and the low percentage of blasts at presentation, the recognition of GATA1 mutations was helpful for diagnosis. In addition, molecular remission was established in 2 patients after subsequent normal mutational GATA1 analysis. Conclusions: We conclude that GATA1 mutational study is a useful tool for the diagnosis and management of trisomy 21 associated myeloproliferative disorders (AU)

Cost-effectiveness analysis of docetaxel (Taxotere) vs. 5-fluorouracil in combined therapy in the initial phases of breast cancer

INTRODUCTION: The randomised controlled trial BCIRG001 has recently demonstrated that docetaxel in combination with doxorubicin and cyclophosphamide (TAC) has better efficacy than the standard treatment (FAC, i.e., 5-fluorouracil, doxorubicin and cyclophosphamide) in the adjuvant treatment of patients with node-positive breast cancer. The cost-effectiveness of TAC vs. FAC in the Spanish setting is analysed. PATIENTS AND METHODS: Clinical outcomes from trial BCIRG001 were combined with Spanish costs and longterm efficacy of FAC and TAC extrapolated up to 5 years by means of a Markov model. Results are shown as cost per life year gained (C/LYG) and cost per quality-adjusted life year (C/QALY). Costs and effects were discounted at a rate of 3%. RESULTS: Mean survival was 17.8 and 16.5 years for TAC and FAC, with total costs of euro14,611 and euro11,586, respectively. The results of the cost-effectiveness analysis showed that TAC achieves a C/LYG and a C/QALY of only euro2345 and euro2631, respectively. Sensitivity analysis confirmed the robustness of the results. CONCLUSIONS: Combined therapy based on docetaxel (TAC) is not only an effective option, but also presents a favourable cost-effectiveness ratio, clearly below the Spanish efficiency threshold in all the scenarios considered (AU)

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Análisis coste-efectividad de enoxaparina en la profilaxis de laenfermedad tromboembólica venosa en pacientes sometidos acirugía mayor ortopédica / Cost-effectiveness analysis of enoxaparin for the prophylaxis of venous thromboembolism in major orthopedic surgery patients

Objetivos y métodos: Se hizo un análisis coste-efectividad, retrospectivo y modelizado, de enoxaparina frente a la no profilaxis, tinzaparina y heparina no fraccionada de la enfermedad tromboembólica venosa, en pacientes españoles sometidos a cirugía mayor ortopédica, desde la perspectiva del Sistema Nacional de Salud. Los episodios evitados y años de vida ganados con cada tratamiento se estimaron mediante un metaanálisis de ensayos clínicos. Resultados: Con enoxaparina hubo un menor número de episodios tromboembólicos y muertes que con las opciones alternativas. Enoxaparina fue la opción dominante (costes totales menores y efectividad igual o mayor que la opción alternativa) en comparación con la no profilaxis, tinzaparina y las heparinas no fraccionadas. El análisis de sensibilidad confirmó la estabilidad de estos resultados. Conclusión: La administración de enoxaparina como profilaxis de la enfermedad tromboembólica venosa, en la cirugía de cadera o rodilla, es una intervención coste-efectiva en todos los casos, suponiendo un ahorro respecto a opciones alternativas utilizadas en nuestro país. (AU)