Análisis de coste-efectividad del interferón beta-1b en el tratamiento de pacientes con síndrome desmielinizante aislado indicativo de esclerosis múltiple en España / Cost-effectiveness analysis of interferon beta-1b as treatment for patients with clinically isolated syndrome suggestive of multiple sclerosis in Spain

INTRODUCCIÓN: El estudio BENEFIT ha mostrado los beneficios del uso precoz del interferón beta 1 b (IFNβ-1b). El objetivo del trabajo fue estimar la eficiencia del tratamiento precoz vs. diferido del IFNβ-1b en pacientes con un síndrome desmielinizante aislado (SDA) indicativo de esclerosis múltiple (EM) en España. MÉTODOS: Se desarrolló un modelo de Markov desde la perspectiva social, con un horizonte temporal de 2 años hasta toda la vida. Una cohorte de 1.000 pacientes con SDA y estados de salud definidos por la Expanded Disability Syndrome Scale (EDSS) fue tratada o no con IFNβ-1b al inicio. Los datos del BENEFIT se usaron para la progresión en la EDSS y las transiciones a EM. Los costes se estimaron de la literatura. Las utilidades derivaron del EQ-5D y publicaciones y la mortalidad de tablas de mortalidad y de la EDSS. Costes (€ de 2013) y resultados se descontaron al 3% anual. Se realizó un análisis de sensibilidad probabilístico. RESULTADOS: En el caso base, tanto la razón de coste utilidad incremental (RCUI) como la razón de coste efectividad incremental (RCEI) del IFNβ-1b vs. no tratamiento fueron dominantes (más eficaz y menos costoso) bajo la perspectiva social. Bajo la perspectiva del SNS, la RCUI fue de 40.702 €/AVAC y la RCEI de 13 €/recaída evitada. CONCLUSIÓN: El tratamiento precoz con IFNβ-1b después de un SDA frente al tratamiento diferido es eficiente desde la perspectiva social, pero puede no ser eficiente desde la perspectiva del SNS al no tener en cuenta los costes no sanitarios

INTRODUCTION: The BENEFIT study has demonstrated the benefits of early treatment with interferon beta 1 b (IFNβ-1b). The objective of this study was to estimate the efficiency of early vs delayed IFNβ-1b treatment in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) in Spain. METHODS: A Markov model reflecting the social perspective was developed with time horizons ranging from 2 years to lifetime. A cohort of 1000 patients with CIS, whose health status had been measured on the Expanded Disability Symptom Scale (EDSS), included patients who received early IFNβ-1b treatment and those who did not. Data from the BENEFIT study were used to model EDSS progression and transitions to MS. Costs were estimated from published literature. Patient utilities were derived from EQ-5D data and published data. Mortality was estimated using life tables and EDSS data. Costs (€ at 2013 rates) and outcomes were discounted at 3% per annum. A probabilistic sensitivity analysis was performed. RESULTS: In the base case, both the incremental cost utility ratio (ICUR) and the incremental cost effectiveness ratio (ICER) of IFNβ-1b versus no treatment were dominant (more effective and less costly) from a social perspective. From the perspective of the Spanish Health System, the ICUR was € 40,702/QALY and the ICER was € 13/relapse avoided. CONCLUSION: Early treatment with IFNβ-1b after a CIS versus delayed treatment is efficient from a social perspective, but it may not be efficient from the perspective of the NHS which does not take non health-related costs into account

[Cost-effectiveness analysis of interferon beta-1b as treatment for patients with clinically isolated syndrome suggestive of multiple sclerosis in Spain]. / Análisis de coste-efectividad del interferón beta-1b en el tratamiento de pacientes con síndrome desmielinizante aislado indicativo de esclerosis múltiple en España.

INTRODUCTION: The BENEFIT study has demonstrated the benefits of early treatment with interferon beta 1b (IFNß-1b). The objective of this study was to estimate the efficiency of early vs delayed IFNß-1b treatment in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS) in Spain. METHODS: A Markov model reflecting the social perspective was developed with time horizons ranging from 2 years to lifetime. A cohort of 1000 patients with CIS, whose health status had been measured on the Expanded Disability Symptom Scale (EDSS), included patients who received early IFNß-1b treatment and those who did not. Data from the BENEFIT study were used to model EDSS progression and transitions to MS. Costs were estimated from published literature. Patient utilities were derived from EQ-5D data and published data. Mortality was estimated using life tables and EDSS data. Costs (€ at 2013 rates) and outcomes were discounted at 3% per annum. A probabilistic sensitivity analysis was performed. RESULTS: In the base case, both the incremental cost utility ratio (ICUR) and the incremental cost effectiveness ratio (ICER) of IFNß-1b versus no treatment were dominant (more effective and less costly) from a social perspective. From the perspective of the Spanish Health System, the ICUR was € 40,702/QALY and the ICER was € 13/relapse avoided. CONCLUSION: Early treatment with IFNß-1b after a CIS versus delayed treatment is efficient from a social perspective, but it may not be efficient from the perspective of the NHS which does not take non health-related costs into account.

Carga epidemiológica y económica de la hipertensión arterial en pacientes con síndrome metabólico en España: un modelo basado en la prevalencia / Epidemiological and economic burden of arterial hypertension in patients with metabolic syndrome in spain: a prevalence-based model

Introducción: La presencia del síndrome metabólico en pacientes hipertensos aumenta significativamente el riesgo de enfermedades cardiovasculares, diabetes tipo 2 y mortalidad. El objetivo fue calcular la carga epidemiológica y económica del síndrome metabólico en pacientes hipertensos para el Sistema Nacional de Salud español en 2008 y 2020. Material y métodos: Modelo de coste de la enfermedad basado en la prevalencia según grupo de edad, sexo y riesgo. Se utilizaron datos publicados sobre prevalencia, patrones de tratamiento, incidencia de mortalidad y episodios cardiovasculares, prevalencia de diabetes tipo 2 y costes del manejo, estimaciones de población y grupos de riesgo y del crecimientofuturo. Resultados: La prevalencia de la hipertensión arterial con síndrome metabólico en la población general fue del 11% en 2008 y del 22% según la estimación para 2020. La proporción de hipertensos con síndrome metabólico fue del 23% en 2008 y del 45% en 2020. La incidencia de episodios cardiovasculares y mortalidad fue dos veces superior en pacientes hipertensos con síndrome metabólico frente a hipertensos sin SM y la prevalencia de diabetes tipo 2 fue casi seis veces superior. La carga económica en 2008 ascendió a 1.909 millones de euros en 2008para los pacientes con síndrome metabólico. Conclusión: Los pacientes con síndrome metabólico representan casi la cuarta parte de la población hipertensa, pero generan casi la mitad de los costes. La carga económica probablemente se incrementará en el futuro por el envejecimiento de la población y el aumento de la prevalencia de los componentes del síndrome metabólico (AU)

Introduction: The presence of metabolic syndrome in patients with hypertension significantly increases the risk of cardiovascular disease, type 2 diabetes and mortality. This study has aimed to estimate the epidemiological and economic burden of the metabolic syndrome in patients with hypertension in Spain in 2008 and 2020 for the Spanish National Health System. Material and methods: A model on the cost of the diseased based on prevalence according to age, sex and risk group was used. The data published on prevalence, treatment patterns, mortality incidence and cardiovascular events, prevalence of type 2 diabetes and cost of management as well as population and risk groups and future growth estimates were used. Results: The prevalence of arterial hypertension with metabolic syndrome in the general population was 11% in 2008 and a value of 22% has been estimated for 2020. The proportion of hypertensive population with metabolic syndrome was 23% in 2008 and 45% has been estimated for 2020. Incidence of cardiovascular events and mortality was two fold higher among hypertensive patients with metabolic syndrome compared to those without it and prevalence of type2 diabetes was nearly six times higher. The economic burden in 2008 was estimated at D1, 909 million in 2008 for patiens with metabolic syndrome. Conclusion: Patients with metabolic syndrome currently make up about one-fourth of the population with hypertension but account for nearly half the costs. The economic burden is likely to increase in the future due to an aging population and an increase in the prevalence of components of metabolic syndrome (AU)

Telomere length is a prognostic factor for overall survival in colorectal cancer.

AIM: The aim of this study was to determine whether telomere length is an independent prognostic factor for the prevention and survival of colorectal cancer. METHOD: Terminal restriction fragment (TRF) length was determined by Southern blot in tumours and paired normal tissue samples from 147 patients with sporadic colorectal cancer who had undergone surgery. The TRF length ratio (TRFLR) was determined as the ratio between the length of the patient's tumour and normal tissue.The classification and regression tree technique was used to determine optimal cut-off values (≤ 1 or > 1). RESULTS: Mean TRF length was 6.79 Kbp (1.19-13.99) in tumour tissue and 7.81 Kbp (3.63-15.70) in normal mucosa (P < 0.001). Mean TRFLR was 0.88. Telomere length and telomere length ratio were not correlated with any clinicopathological factors. In univariate analysis, overall survival was related to N stage (lymph node +/-; P = 0.002), TNM classification (P = 0.019) and TRFLR (≤ 1 or > 1; P = 0.014). In multivariate analysis, overall survival was significantly associated with TRFLR and N stage. Colorectal cancer patients with TRFLR ≤ 1 and negative lymph node involvement had a higher overall survival rate. CONCLUSION: Telomere length ratio is an independent prognostic factor for survival in colorectal cancer patients, and the telomere lengths in the normal and tumour mucosa of the same patient present with parallel behaviour.

Estimation of pharmacokinetic parameters of sodium tungstate after multiple-dose during preclinical studies in beagle dogs.

In this paper, an empirical Bayes methodology was used to determine the pharmacokinetic profile of sodium tungstate in beagle dogs after multiple oral dosing using the P-PHARM computer program. The population estimation algorithm used in P-PHARM is an EM-type procedure. Sodium tungstate was administered orally, three times a day, (i) for 11 days (21 and 42 mg/kg per day) to 18 dogs (nine males and nine females) and (ii) for 13 weeks (15, 30 and 60 mg/kg per day) to 28 dogs (14 males, 14 females). Six other dogs received the compound intravenously (25 and 50 mg/kg). Plasma concentration profiles versus time were compatible with a two-compartment model and first-order kinetics. After oral administration, F (0.61+/-0.086 vs. 0.48+/-0.093), and normalized (to a 7-mg/kg dose of sodium tungstate) AUC (54+/-8.4 vs. 41.2+/-8.5 mg/l x h), C(max) (10.6+/-0.49 vs. 8.5+/-0.57 microg/ml) and C(min) (3.04+/-0.23 vs. 2.04+/-0.22 microg/ml), were higher in male than in female dogs. However, the introduction of the gender in the final model did not contribute statistically to an improvement of the fit of the population pharmacokinetic model. In males, t(1/2) elimination averaged 3.1+/-0.56 vs. 2.6+/-0.18 h in females. The duration of treatment did not modify statistically the pharmacokinetic parameters. After repeated multiple oral administration of 15-60 mg/kg per day of sodium tungstate, tungsten plasma concentrations increased in proportion to dose. No dose-dependent changes in pharmacokinetic parameters occurred.

Complicaciones de la enfermedad diverticular del colon. Estudio comparativo de dos poblaciones / Complications of colonic diverticular disease. Comparative study of two series

Objetivo: comparar el modo de presentación y manejo de la enfermedad en dos Servicios de cirugía de poblaciones geográficas distintas. Diseño: estudio observacional, retrospectivo. Pacientes y método: 203 casos de la 2ª Cátedra de Cirugía del Hospital Universitario de Clínicas de Asunción, Paraguay y 150 casos del Hospital Universitario de Lleida, España. Se analizaron: motivo de ingreso, antecedentes, tratamiento y morbi-mortalidad postoperatoria. Resultados: serie paraguaya: edad media hombres 53 (3484) años y 62 (36-92) mujeres. 55 por ciento ingresaron por complicaciones hemorrágicas y 45 por ciento por diverticulitis aguda. El tratamiento médico se inició en 109 casos y quirúrgico en 110, 72 de urgencia y 38 electivas. La morbilidad fue del 31,8 por ciento (40,2 por ciento en urgencia y 16 por ciento programada, (p<0,05) y la mortalidad del 15,5 por ciento, 22,2 por ciento urgentes y 2,6 por ciento programados p<(0,003).Serie de Lleida: edad media hombres 65,5 (38-85) p<0,005 y mujeres 71,4(30-93) p<0,01) años. 86 por ciento ingresaron por diverticulitis aguda, 10,7 por ciento por hemorragia (p<0,001). Presentaron crisis previa el 16 por ciento (p<0,001). El tratamiento fue médico en 111 casos y quirúrgico en 39 (p<0,001); 33 de urgencia y 6 electivas (p<0,04). La morbilidad fue de 41 por ciento y la mortalidad de 5 (12,8 por ciento), todos de urgencia. La técnica operatoria utilizada fue similar: resección con anastomosis primaria en las electivas y mayoría de Hartmann, en las urgencias, con una proporción de anastomosis inmediata del 33 y 21 por ciento. Conclusiones : posiblemente factores dietéticos y de calidad de vida influyen en la aparición de la enfermedad diverticular. Hay que prevenir la cirugía de urgencia. Cada cirujano debe adaptar su estrategia quirúrgica al medio socio-económico-cultural de la población (AU)

Complications of colonic diverticular disease. Comparative study of two series.

OBJECTIVE: To compare the form of presentation and management of the disease in two surgical units covering geographically different populations. DESIGN: Observational retrospective study. PATIENTS AND METHOD: 203 cases from the 2nd Chair of Surgery of the Hospital Universitario de Clínicas de Asunción, Paraguay and 150 cases from the Hospital Universitario de Lleida, Spain. We analyzed the cause of admission, medical history, treatment and post-operative morbidity and mortality. RESULTS: Paraguay series: average age: 53 years (range 34-84) for men and 62 years (range 36-92) for women. Fifty-five per cent were hospitalized because of hemorrhagic complications and 45% because of acute diverticulitis. Medical treatment was provided in 109 cases and surgery in 110, 72 of which were emergencies and 38 elective procedures (p < 0.05). Morbidity was 31.8% (40.2% in emergencies and 16% in elective procedures, p < 0.05) and mortality was 15.5% (20.2% in emergencies and 2.6% in elective procedures, p < 0.003). LLEIDA SERIES: Average age: 65.5 years (range 38-85, p < 0.01) for men and 71.4 years (range 30-93, p < 0.01) for women. Eighty-six per cent were hospitalized because of acute diverticulitis and 10.7% because of acute hemorrhage (p < 0.001). Sixteen per cent have had previous attacks (p < 0.001). Medical treatment was provided to 111 patients and surgery to 39 (p < 0.001), 33 of which were emergencies and 6 elective procedures (p < 0.04). Morbidity was 41% and mortality 12.8% (5 cases), all of which were emergencies. The surgical technique was similar in both groups: resection with primary anastomosis in elective procedures and Hartmann's procedure in most emergencies, with a rate of immediate anastomosis of 33 and 21%, respectively. CONCLUSIONS: Factors related to nutrition and quality of life may influence the development of diverticular disease. Emergency surgery should be prevented. Surgeons must adapt their surgical approach to the socioeconomic and cultural medium of the population.

La utilización de la acarbosa en atención primaria: Evaluación de la tolerancia y seguridad a largo plazo en 2.799 pacientes diabéticos tipo 2

Se diseñó un estudio observacional multicéntrico (343 médicos de Atención Primaria) para evaluar la tolerancia y seguridad del tratamiento a largo plazo (6 meses) con acarbosa (Glucobay®) en 2.799 pacientes diabéticos tipo 2 (glucemia en ayunas superior a 140 mg/dL o glucosa postprandial superior a 200 mg/dL al menos dos veces en la historia del paciente) tratados con dieta o con dieta y cualquier hipoglucemiante oral. Estos pacientes recibieron tratamiento con acarbosa durante 6 meses: 150 mg/día (50 mg x 3) durante las cuatro primeras semanas y 300 mg/día (100 mg x 3) a partir de esa fecha. Resultados. Setecientos noventa pacientes (28,3 por ciento) refirieron algún efecto indeseable (El) (1072 El en total). El porcentaje de pacientes con El disminuyó a lo largo del estudio (del 21,5 por ciento a los dos meses de tratamiento al 10,8 por ciento a los seis meses). Los El más frecuentes fueron de tipo gastrointestinal: meteorismo, flatulencia, diarrea o dolor abdominal. La mayoría fueron considerados leyes o moderados. En el 74 por ciento de los casos estos efectos se resolvieron o mejoraron a lo largo del estudio. Cincuenta y ocho pacientes (2,2 por ciento) refirieron crisis hipoglucémicas a los dos meses de tratamiento, el 2,3 por ciento a los cuatro y el 1,2 por ciento a los seis. Se observó una disminución en la glucemia en ayunas, en la glucemia postprandial y en la cifra de HbAlc. Conclusiones. La acarbosa junto a la dieta, o a la dieta y otros hipoglucemiantes orales, es un fármaco útil en el tratamiento a largo plazo de los pacientes con diabetes tipo 2 en atención primaria ya que es bien tolerada y puede mejorar el control glucémico del paciente (AU)

[Histologic study of experimental spleen transplant in rats]. / Studio istologico del trapianto splenico sperimentale nei ratti.

BACKGROUND: The objective of this paper was to demonstrate that the grafts of cervical splenic transplantation on rats using our experimental model present a normal histological appearance. METHODS: Isogenic consanguineous Lewis rats 12 weeks old and weighing 250 gr. were used. Histological findings of a group of 25 cervical splenic grafts transplanted by means of splinting vascular venous microanastomoses and a group of 25 splenic grafts autotransplanted in the omentum were compared with a control group. The specimens were assigned according to a score of 0 to 4, following Moore's histological criteria. RESULTS: All grafts in transplanted and autotransplanted groups had a score of 3 or 4. Then, all splenic grafts from the transplanted group had histological findings very similar to a normal spleen. In the autotransplantation group, the percentage of grafts with a score 3 (60%) was superior to the transplantation group (46%). However, the transplantation group presented a percentage of score 4 (54%), superior to the autotransplantation group (40%). CONCLUSIONS: In our study all grafts from the cervical spleen transplantation group had histological findings very similar to a normal spleen. The percentage of spleens with histological normality in the transplantation group was superior to the autotransplantation group. However, there was no statistical significance.

Participation in a pharmacological hypolipidaemic trial does not alter participants' dietary habits.

OBJECTIVE: The aim of this study was to observe whether the act of participation in a well-controlled clinical trial can, co-incidentally, modify the dyslipaemic patient's adherence to his/her diet. DESIGN AND SUBJECT: Food diaries of 55 men and 51 women (aged 46.4 +/- 10.6 and 55.8 +/- 12.1 years respectively) were analyzed at the beginning and the end of the double-blind stage of treatment (12 weeks). STATISTICS: Variance analysis and multi-variant analysis with repeated data by SPSS/PC statistical package. RESULTS: In neither sex were there any statistically significant differences between the start and end of the study with respect to the intake of energy, proteins, total lipids, carbohydrates, saturated fatty acids, polyunsaturated fatty acids, cholesterol, fibre and alcohol. CONCLUSIONS: Although in individual cases some changes in dietary awareness can occur, on a larger scale, the hypocholesterolaemic intervention trial induced no significant overall changes in the participants dietary/lifestyle patterns and, as such, augurs well for other such trials in which the effect of the therapy may sometimes be confounded by changes in the patients' life-style patterns coincidental to the act of participation in the trial.

Acarbose in ambulatory treatment of non-insulin-dependent diabetes mellitus associated to imminent sulfonylurea failure: a randomised-multicentric trial in primary health-care. Diabetes and Acarbose Research Group.

To assess the efficacy and safety of acarbose as an adjunct to high sulfonylurea (SU) doses in patients with imminent SU failure, a randomised, multicentric, 6 month double-blind, parallel and placebo-controlled trial was performed in primary healthcare. Entry criteria were: NIDDM patients in concomitant dietary follow-up, age > 40 year-old, more than 3 years of diagnosed diabetes, baseline HbAlc levels between 8-12% (N: 4-6%), stable body mass index < 35 kg m-2 and glibenclamide daily dose > 10 mg. After 1 month placebo run-in period all patients were randomly allocated into two groups of treatment (acarbose 100 mg t.i.d. vs placebo). HbAlc levels, the main efficacy variable, lipid profile, fasting and postprandial blood glucose levels were performed and adverse events were also recorded. A total number of 65 patients were randomised, 36 in acarbose and 29 in a placebo group. No statistical differences were found on age (60.2/61.7 year-old), BMI (28.7/27.4 kg m-2), glibenclamide dose (14.5/14.0 mg/day) and baseline HbAlc (9.0/8.8%). Acarbose-treated patients significantly reduced HbAlc levels (9.0/7.9 vs 8.8/8.5%; P < 0.01), based upon a marked decrease, but statistically not significant, in mean postprandial plasma glucose levels (11.9/9.6 vs 12.4/11.1 mmol l-1). No significant differences between fasting plasma glucose and lipid profile were detected. A total of 31 patients (47.7%) reported adverse events, 20 (55.5%) and 11 (37.9%) in acarbose and placebo treatment group respectively. Relationship with drug was estimated as possible or probable in 16 (44.4%) of acarbose-treated patients. None of them were excluded from study participation due to insulin requirement. Only seven patients (10.7%), six with acarbose (16.6%) and one with placebo (3.8%), withdrew the study because of the adverse events. Thus, acarbose seems to be a useful option in order to improve HbAlc levels in non-insulin-dependent diabetes mellitus with imminent sulfonylurea failure.

Nitrendipine and enalapril in the treatment of diabetic hypertensive patients with microalbuminuria.

A trial to study the efficacy, safety and tolerability of nitrendipine and enalapril in the treatment of diabetic hypertensive patients with microalbuminuria (MA) was performed to compare the effects of both drugs in the prevention of the renal impairment. Twenty-eight valid patients [13 with nitrendipine (N) and 15 with enalapril (E) with NIDDM, hypertension (diastolic blood pressure between 90 to 114 mm Hg) and MA (urinary albumin between 30 to 300 mg/24 hr) were recruited in a double blind, randomized trial. Following a placebo run-in period of two to four weeks, all eligible patients were randomly allocated to either N or E treatment. Treatment lasted six months, with two different visits at three and six months in which blood pressure (BP), heart rate (HR), renal function and MA were measured. No statistically significant differences on BP and metabolic parameters were found between both treatment groups. The geometric mean of final glomerular filtration rate (GFR) in the N group was 34.5% higher than in the E group, while the reduction on MA was most important in the E group. Eleven patients reported adverse events (AEs) and there were four dropouts, three of them due to AEs. We conclude that both treatments are a good choice for treating diabetic hypertensive patients with early altered renal function, as they reduce BP without altering metabolic parameters, increase GFR and reduce MA with a low frequency of AEs.

Appearance of ear tumors in Sprague-Dawley rats treated with 1,2-dimethylhydrazine when used as a model for colonic carcinogenesis.

One of the models of colon carcinogenesis in rats is produced by s.c. injections of 1,2-dimethylhydrazine (DMH). This specific colon carcinogen provokes other tumors in the rat, notably intestinal tumors. Ear tumors are just marginally mentioned in the literature. We have studied the appearance and histologic characteristics of ear tumors produced by 19 s.c. injections of 21 mg/kg of DMH in 18 Sprague-Dawley rats: 15 tumors appeared in 13 ears of 10 rats (55% of the animals). Simultaneously there were 23 colonic tumors: four (26.6%) of the tumors were carcinomas, 10 (66.6%) papillomas and one (6.6%) pseudoepitheliomatous hyperplasia. We conclude that ear tumors induced by DMH appear in 55% of the rats and that it is not possible to distinguish macroscopically in terms of size and aspect between benign and malignant lesions.