RESUMEN
An experiment was conducted to test the hypothesis that a coarse limestone diet improves productivity, reproductive performance and the calcium utilization of molted broiler breeders. In total, 640 broiler breeder females, 73-week-old and sixty-four 27-week-old cockerels, Cobb 500, were evaluated during 10 weeks, according to a randomized block design composed of 4 treatments with 8 replicates each. Treatments consisted of diets with the inclusion of 100% fine limestone-fine PS (0.2 mm GMD-geometric mean diameter); PS1: 30% fine limestone+70% limestone with 1.0 mm GMD; PS2: 30% fine limestone+70% limestone with 2.0 mm GMD; and PS3: 30% fine limestone+70% limestone with 3.0 mm GMD. Calcium retention in the gizzard of the breeders, bone characteristics, and breeder performance, egg characteristics, eggshell quality, incubation performance, chick quality and yield, chick pre-starter live performance, and chick bone characteristics were determined. There was no significant difference (P>0.05) in the rate of lay, percentage of non-settable eggs, egg weight, egg shape index, egg specific gravity, eggshell weight, thickness, and percentage hatchability and egg weight loss of broiler breeders fed with diets with different limestone particle sizes. The chick quality and yield, chick pre-starter live performance, and chick bone characteristics were not affected (P>0.05) by any of the limestone particle sizes. It was concluded that live and reproductive performance parameters of broiler breeders post molting is not affected by limestone particle size in the feed.
Asunto(s)
Carbonato de Calcio/metabolismo , Calcio de la Dieta/metabolismo , Pollos/fisiología , Tamaño de la Partícula , Alimentación Animal/análisis , Animales , Huesos/efectos de los fármacos , Huesos/fisiología , Dieta/veterinaria , Cáscara de Huevo/efectos de los fármacos , Cáscara de Huevo/fisiología , Femenino , Distribución Aleatoria , Reproducción/efectos de los fármacosRESUMEN
This study evaluated the effect of different dietary vitamin E levels and different selenium sources on the productive and reproductive performance of broiler breeders. In total 640 females and 64 males between 22 and 52 weeks old were studied. A completely randomized experimental design in factorial arrangement, with 4 treatments of 8 replicates with 20 females and 2 males each, was applied. Treatments consisted of 2 vitamin E levels (30 and 120 mg/kg) and two selenium sources (sodium selenite and zinc-L-selenomethionine). Egg production (rate of lay and eggs per breeder), egg characteristics (egg, yolk, eggshell, and albumen weights), fertility, incubation responses (egg weight loss during incubation, hatchability, and hatching window), and hatchling characteristics (weight and yield) were evaluated. There was no influence of dietary vitamin E levels or selenium sources on egg production (P > 0.05). Mature breeders (47 weeks old) fed zinc-L-selenomethionine and 120 mg vitamin E/kg feed produced heavier eggs and albumen. Hatchability of the eggs of breeders fed 120 mg vitamin E/kg feed was higher than breeders fed 30 mg vitamin at 29 wks. The dietary inclusion of organic selenium also promoted heavier hatchling weight until egg production peak (33 wk), but did not influence hatchling quality or hatching window. It was concluded that the dietary supplementation of zinc-L-selenomethione and vitamin E (120 mg/kg feed) could be used to improve egg characteristics and incubation response.
Asunto(s)
Pollos/fisiología , Suplementos Dietéticos , Selenometionina/farmacología , Selenito de Sodio/farmacología , Vitamina E/farmacología , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Peso Corporal , Dieta/veterinaria , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal , Reproducción/efectos de los fármacos , Selenometionina/administración & dosificación , Selenito de Sodio/administración & dosificación , Vitamina E/administración & dosificaciónRESUMEN
In post hoc analyses of an open-label, phase 3b study (FIRST), relapse rates during 4 months of fingolimod therapy were compared in patients with and without previous natalizumab exposure. Reductions in the proportion of patients experiencing relapses and annualized relapse rates (ARRs) from years 1 and 1-2 pre-study were evident between months 1 and 2 of fingolimod treatment, and were most pronounced in natalizumab-naïve patients and those who discontinued natalizumab >6 months pre-study. Patients who discontinued natalizumab 3-6 months pre-study had a peak ARR during month 1 of fingolimod treatment, followed by a decrease during months 2-4. These data indicate that fingolimod has the potential to reduce disease reactivation but that timing of treatment initiation may be critical for achieving an optimal effect.
Asunto(s)
Clorhidrato de Fingolimod/farmacología , Factores Inmunológicos/farmacología , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Natalizumab/uso terapéutico , Adulto , Ensayos Clínicos Fase III como Asunto , Femenino , Clorhidrato de Fingolimod/administración & dosificación , Clorhidrato de Fingolimod/efectos adversos , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Temperatures continuously higher and lower than the standard incubation temperature by 3°C from embryonic d 16 until embryonic d 18.5 result in differential effects on embryonic development, the hatching process, and embryonic metabolism. Embryos in the high-temperature group were forced into a state of malnutrition by the temperature treatment, as reflected by reduced embryo growth and yolk consumption, resulting in a significantly lower chick weight at hatch. In addition, altered air cell and blood gases as well as a retarded hatching process further indicated reduced growth of embryos exposed to higher incubation temperatures during the latter part of incubation. In addition, hatchability was significantly reduced by the high-temperature treatment due to higher embryonic mortality during the treatment period and the hatching process. Levels of blood glucose, lactate, liver glycogen, plasma triglycerides, and nonesterified fatty acids indicated an altered carbohydrate and lipid metabolism for the high-temperature group. Although the hatching process of embryos exposed to lower incubation temperatures was also significantly retarded, their embryonic development and growth were strikingly similar to those of the control group.
Asunto(s)
Embrión de Pollo/fisiología , Desarrollo Embrionario/fisiología , Animales , Temperatura Corporal , Dióxido de Carbono/análisis , Frío , Cáscara de Huevo/fisiología , Huevos , Femenino , Muerte Fetal/veterinaria , Calor , Oxígeno/análisis , Temperatura , Tiroxina/sangre , Triyodotironina/sangre , Pérdida de PesoRESUMEN
BACKGROUND: Subcutaneous IFNbeta-1b (Betaferon) is an established immunomodulatory treatment for relapsing remitting MS and active secondary progressive multiple sclerosis (SPMS). It modulates cytokine and adhesion molecule expression but long term in vivo effects of IFNbeta-1b on the immune system are not known in multiple sclerosis. OBJECTIVE: To address the effects of IFNbeta-1b on serum levels for soluble adhesion molecules and cytokine receptors from MS patients. METHODS: Serial blood samples were obtained from 40 patients of the frequent MRI subgroup (20 patients each from the placebo and the IFNbeta-1b treatment group), participating in the European multi-center clinical trial with IFNbeta-1b for secondary progressive MS, at regular intervals for up to 36 months. Soluble adhesion molecules (sVCAM, sICAM-1, sL-Selectin) as well as TNF-receptor I and II were analysed in the serum of patients by enzyme linked immunosorbent assays (ELISAs). Monthly brain MRI was performed in 34 of these patients (16 patients from the placebo and 18 from the IFNbeta-1b group) during months 1-6 and 19-24 to monitor disease activity as assessed by newly occurring gadolinium (Gd) enhancing lesions. RESULTS: An early and significant increase in sVCAM and sTNF-RII serum levels was detected in 16 out of 20 patients (80 %) treated with subcutaneous IFNbeta-1b already at month 1 but was absent in all but one patient during placebo treatment (p < 0.01). Raised sVCAM and TNF RII serum levels during months 1-6 inversely correlated with less MRI activity in the 19-24 months treatment interval in the IFNa-1b treatment group ( p = 0.0093 for TNF-RII; p = 0.047 for VCAM). CONCLUSIONS: sVCAM and sTNF RII levels in the serum of SPMS patients are increased during IFNbeta-1b therapy and may at least in part explain some of the treatment effects, like reduced immune cell transmigration.
Asunto(s)
Interferón beta/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/sangre , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Molécula 1 de Adhesión Celular Vascular/sangre , Adulto , Método Doble Ciego , Femenino , Humanos , Interferon beta-1b , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/patología , Estadísticas no ParamétricasRESUMEN
BACKGROUND: There is little information regarding the potential of interferon beta (IFNbeta) to induce or exacerbate autoimmune disease. Existing data from uncontrolled studies are contradictory and do not differentiate between autoimmune dysfunction, which is frequent in patients with multiple sclerosis (MS), and untoward drug effects. OBJECTIVE: To evaluate the impact of IFNbeta on hepatic, thyroid, and other markers of autoimmunity using data from the European placebo-controlled double-blind, multicenter study of IFNbeta-1b in patients with secondary progressive MS (SPMS). METHODS: Serum samples obtained at baseline and at 6-month intervals for 24 months were analyzed for the following autoantibodies (AAbs): antinuclear (ANA), antimitochondrial (AMA), smooth muscle (SMA), liver kidney microsome (LKM), thyroid microsome (TPO), and human thyroglobulin (TG). AAb status at baseline and during treatment was related to respective laboratory and clinical deviations. RESULTS: The analysis of AAb data included 355 patients receiving IFNbeta-1b and 353 receiving placebo. There was no difference between treatment groups in de novo AAb positivity. A greater proportion of women were AAb positive at baseline and during treatment. No association was found between liver enzyme elevations and ANA, AMA, or SMA antibody formation in either treatment group. Laboratory-based thyroid alterations during the study were significantly related to TG/TPO status at baseline but were not associated with IFNbeta-1b treatment. Adverse events possibly indicative of other diseases with autoimmune links were not associated with respective AAb status. CONCLUSION: Interferon beta-1b treatment did not induce autoantibody formation in this population of patients with secondary progressive multiple sclerosis.
Asunto(s)
Autoanticuerpos/efectos de los fármacos , Interferón beta/efectos adversos , Esclerosis Múltiple/inducido químicamente , Esclerosis Múltiple/tratamiento farmacológico , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Biomarcadores , Enfermedad Hepática Inducida por Sustancias y Drogas , Estudios de Cohortes , Método Doble Ciego , Femenino , Humanos , Interferon beta-1b , Interferón beta/inmunología , Hígado/efectos de los fármacos , Hígado/inmunología , Hígado/fisiopatología , Hepatopatías/sangre , Hepatopatías/inmunología , Masculino , Mitocondrias/inmunología , Esclerosis Múltiple/inmunología , Efecto Placebo , Distribución por Sexo , Tiroglobulina/inmunología , Enfermedades de la Tiroides/sangre , Enfermedades de la Tiroides/inducido químicamente , Enfermedades de la Tiroides/inmunología , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/inmunología , Glándula Tiroides/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: A European (EU) and a North American (NA) placebo-controlled study with interferon beta-1b (IFNB-1b) in secondary progressive multiple sclerosis (SPMS) showed divergent results with regard to their primary outcome of sustained Expanded Disability Status Scale (EDSS) progression, while effects were similar on relapse and MRI-related endpoints. Reasons for this discrepancy were explored in the combined dataset. METHODS: Baseline characteristics and variability in EDSS assessments were compared. Retrospective combined analyses for time to confirmed progression were performed to assess treatment effects overall and in subgroups defined by pre-study disease activity criteria and other key baseline variables. RESULTS: The variance of EDSS measurements was 6.5% higher in the NA-SPMS study. The EU study included patients in an earlier phase of SPMS and with more active disease both pre-study (relapses, MRI) as well as on study (EDSS, relapses, and MRI variables as assessed in the placebo groups). The pooled analysis showed an overall risk reduction by about 20% in patients treated with 8 MIU (250 mcg) IFNB-1b for EDSS progression confirmed at 6 months (p = 0.008). Risk reduction by 30% to 40% was found for patients with at least one relapse or change in EDSS by >1 in the 2 years prior to study entry. No other consistent across-studies relation of clinical and MRI variables at baseline to potential treatment response was found. CONCLUSIONS: Although post hoc, this combined analysis of the two large studies with IFNB-1b in secondary progressive multiple sclerosis suggests that both pronounced disability progression and continuing relapse activity might help in identifying those patients in the secondary progressive phase of the disease who are more likely to benefit from treatment.
Asunto(s)
Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Adulto , Encéfalo/patología , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Interferon beta-1b , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Esclerosis Múltiple Crónica Progresiva/patología , Evaluación de Resultado en la Atención de Salud/métodos , Selección de Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Recurrencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
A retrospective, cross-sectional study was performed to evaluate direct and indirect costs related to multiple sclerosis (MS) in Austria in a representative cohort of patients ( n=895) with typical symptoms. Demographic, socioeconomic, and disease-related data including degree of disability and health-related quality of life as well as consumption of medical and nonmedical resources were recorded and mean total costs per patient and year were calculated (based on 1999 figures). Total direct costs borne by public sources were 15,684 euro per MS patient per year. Overall societal costs increased disproportionately with the progression of the disease, from 12,990 euro per year in patients with mild disability to 69,554 euro per year in patients with severe disability. Increasing disability was reflected by substantial deterioration of health status-related quality of life. Direct costs of MS in Austria are similar to those in other countries.
Asunto(s)
Costos y Análisis de Costo/métodos , Costos de la Atención en Salud/estadística & datos numéricos , Recursos en Salud/economía , Recursos en Salud/estadística & datos numéricos , Esclerosis Múltiple/economía , Esclerosis Múltiple/terapia , Calidad de Vida , Adulto , Austria/epidemiología , Estudios de Cohortes , Evaluación de la Discapacidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/epidemiología , Estudios Retrospectivos , Medición de Riesgo/métodos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Interferon beta (IFNB) is available in parenteral formulations for treatment of multiple sclerosis (MS). The purpose of this study was to evaluate safety, tolerability and effects on MRI lesions of three different doses of oral IFNB-1a compared with placebo over six months in relapsing-remitting (RR) MS patients. METHODS: In this multicenter; double-blind randomized trial, RR-MS patients received 0.06, 0.6 or 6 million international units (MIU) IFNB-1a or placebo every other day for up to six months. Gadolinium DTPA-enhanced brain MRI scans were performed at screening and monthly during treatment. The primary variable was the cumulative number of newly active lesions. Secondary variables included volume of enhancing lesions on T1-weighted images each month and lesion volume on T2-weighted images at months three and six. Safety measures included adverse events, laboratory variables, vital signs, ECG, physical examination, EDSS and number of relapses. Neopterin was measured in 21 patients and neutralizing antibodies in 24 patients. RESULTS: Of 194 screened patients, 173 were randomized (42-44 patients per group) in 15 centers. Median cumulative numbers of newly active lesions over six months were 4.0 in the placebo and 0.6 MIU groups, compared with 7.5 and 9.0 in the 0.06 and 6 MIU groups (no significant differences). Secondary efficacy endpoints showed small and inconsistent differences between groups. Adverse events showed no notable group differences. Approximately two-thirds of patients in each group remained relapse free. No patients showed neutralizing antibodies. Neopterin levels were comparable between groups. CONCLUSION: Oral IFNB-1a showed neither beneficial effects in RRMS nor any systemic biological effects. Treatment was safe and well tolerated.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Interferón beta/administración & dosificación , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Adyuvantes Inmunológicos/efectos adversos , Administración Oral , Adolescente , Adulto , Método Doble Ciego , Femenino , Humanos , Interferón beta-1a , Interferón beta/efectos adversos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Information from patients who are unable to continue their visits to a study centre may be of major importance for the interpretation of results in multiple sclerosis (MS) clinical trials. To validate a questionnaire based on the Expanded Disability Status Scale (EDSS), patients in five different European centres were assessed independently by pairs of trained EDSS raters, first by telephone interview and a few days later by standardized neurological examination. Seventy women and 40 men with an average age of 43.7 years (range 19-74 years) were included in the study. Mean EDSS score at the last visit was 4.5 (0-9). EDSS assessment by telephone was highly correlated with the EDSS determined by physical examination (Pearson's correlation coefficient = 0.95). An intraclass correlation coefficient (ICC) of 94.8% was found for the total sample; 77.6% and 86%, respectively, for patients with EDSS < 4.5 (n = 46) and > 4.5 (n = 64). Kappa values for full agreement were 0.48; for variation by +0.5 steps and +1.0 steps, 0.79 and 0.90, respectively. Best agreement could be found in higher EDSS scores, where assessment by telephone interview might be needed most. The telephone questionnaire is a valid tool to assess EDSS score in cases where the patient is unable to continue visiting a study centre or in long-term follow-up of trial participants.
Asunto(s)
Evaluación de la Discapacidad , Entrevistas como Asunto/métodos , Esclerosis Múltiple/diagnóstico , Adulto , Anciano , Europa (Continente) , Femenino , Humanos , Entrevistas como Asunto/normas , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , CaminataRESUMEN
OBJECTIVE: To investigate the relationship between neutralizing antibodies (NAB) and disease progression, relapses, and MR measures of MS. METHODS: Sequential serum samples from all 718 patients of the European Study Group in Interferon beta-1b in Secondary Progressive MS were analyzed to investigate relations between NAB and disease progression, relapses, and MR measures. RESULTS: This study showed no attenuating effect of NAB development on progression in disability. The effects of NAB on relapse rate showed substantial variation, depending on the statistical approach and definition of positivity, though analyses comparing low- and high-NAB+ periods with NAB- periods suggested a titer-related effect. MR T2 lesion volume changes from baseline were significantly higher for NAB+ patients but remained lower than for placebo patients. A substantial proportion of NAB+ patients became NAB-. No untoward effect of NAB development on safety was observed. CONCLUSION: These results support the conclusion that even though high NAB titers appear to have impact on treatment efficacy with respect to relapses, treatment decisions should be based primarily on clinical grounds.
Asunto(s)
Anticuerpos/sangre , Interferón beta/inmunología , Interferón beta/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/inmunología , Esclerosis Múltiple Crónica Progresiva/terapia , Adulto , Estudios de Cohortes , Estudios Transversales , Evaluación de la Discapacidad , Progresión de la Enfermedad , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Inyecciones Subcutáneas , Interferón beta-1a , Interferon beta-1b , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia , Pruebas Serológicas , Resultado del TratamientoRESUMEN
BACKGROUND: Based on a prospectively planned interim analysis, the European study of interferon beta-1b (IFNbeta-1b) provided evidence that the treatment delays neurologic deterioration in patients with secondary progressive MS (SPMS). The authors analyzed all data collected until closure of the double-blind study to further scrutinize the consistency of the findings. METHODS: The multicenter, double-blind, randomized, placebo-controlled trial treated patients for up to 36 months. The primary and all secondary endpoints of this study were evaluated using the data set at study termination, with a mean follow-up under double-blind conditions of 1054 +/- 199 and 1068 +/- 176 days for the placebo and IFNbeta-1b group. Alternative and more demanding definitions of disease progression were explored. Confirmed progression was analyzed in subgroups according to baseline demographics and baseline indicators of disease activity. RESULTS: Forty-eight of 358 placebo and 40 of 360 IFNbeta-1b-allocated patients were lost to follow-up. Time to confirmed 1.0-point Expanded Disability Status Scale (EDSS) progression for patients receiving IFNbeta-1b was delayed (p = 0.007). The proportion of patients with a confirmed 2.0-point EDSS progression was approximately 27% lower for the group treated with IFNbeta-1b, both including and excluding EDSS data collected during relapses. The proportion of patients with either progression or relapses decreased by nearly 30% in patients treated with IFNbeta-1b compared with placebo. Analysis of subgroups suggests that patients with higher prestudy disease activity (more than two relapses or EDSS progression by more than 1.0 point or both) seem to have a more pronounced treatment effect. CONCLUSION: Analysis of the data set at study termination including additional post hoc outcome measures is consistent with the original findings, thus supporting the conclusion that treatment with IFNbeta-1b is effective in patients with SPMS fulfilling the inclusion criteria of this study.
Asunto(s)
Adyuvantes Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Adyuvantes Inmunológicos/efectos adversos , Adolescente , Adulto , Método Doble Ciego , Europa (Continente) , Femenino , Estudios de Seguimiento , Humanos , Interferón beta-1a , Interferon beta-1b , Interferón beta/efectos adversos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/diagnóstico , Examen Neurológico/efectos de los fármacosRESUMEN
BACKGROUND: The recent randomized, controlled trial of interferon-beta1b (IFN-beta1b) in 718 patients with secondary progressive MS (SP-MS) demonstrated a significant effect on the development of disability as evaluated by the physician. Its effect on patient-reported health-related quality of life (HrQoL) is reported herein. METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial, outpatients with SP-MS scoring between 3.0 and 6.5 on the Expanded Disability Status Scale received either 8 x 10(6) IU of IFN-beta1b or placebo for up to 3 years. A range of outcomes was measured, including HrQoL, which was assessed using the Sickness Impact Profile (SIP), a self-report questionnaire validated for use in MS. Measurements were undertaken at baseline and at 6-monthly intervals thereafter for 36 months. RESULTS: A slight positive effect on the HrQoL of the IFN group in comparison with the placebo group was found, which reached significance in the physical scale of the SIP at 6 and 12 months and at last visit. There was moderate correlation between physician-assessed evaluation of change and patient-reported change. CONCLUSIONS: IFN-beta1b may delay sustained deterioration in patient-reported HrQoL in SP-MS. Methods of interpreting change in HrQoL are currently insufficiently developed to determine how clinically important these changes are for this population.
Asunto(s)
Interferón beta/administración & dosificación , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Calidad de Vida , Actividades Cotidianas/clasificación , Actividades Cotidianas/psicología , Adulto , Atención Ambulatoria , Evaluación de la Discapacidad , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Interferón beta-1a , Interferon beta-1b , Interferón beta/efectos adversos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Crónica Progresiva/psicología , Resultado del TratamientoRESUMEN
BACKGROUND: The recently completed placebo-controlled multicenter randomized trial of interferon beta-1b (Betaferon) in 718 patients with secondary progressive MS shows significant delay of disease progression and reduction of relapse rate. This study provides an opportunity to assess the level of relationship between clinical and MRI outcomes in this cohort of patients with secondary progressive MS. METHODS: Brain T2-weighted lesion volume was measured annually in all available patients, with visual analysis to identify any new or enlarging (active) T2 lesions at each annual time point. A subgroup of 125 patients had monthly gadolinium-enhanced, T1-weighted imaging at months 0 to 6 and 18 to 24. Relapses were documented and expanded disability status scale (EDSS) was measured every 3 months. RESULTS: For the annual MRI outcomes, a significant but modest correlation was identified between the change in T2 lesion volume from baseline to the final scan and the corresponding change from baseline in EDSS (r = 0.17, p < 0.0001). There were significant correlations between the cumulative number of active T2 lesions and 1) change in EDSS (r = 0.18, p < 0.0001) and 2) relapse rate (r = 0.24, p < 0.0001). In the subgroup of 125 patients undergoing monthly imaging, MRI lesion activity was correlated with relapse rate over months 0 to 24 (r = 0.24, p = 0.006) but not with change in EDSS. CONCLUSIONS: These results confirm that the clinical-MRI relationships previously identified in relapsing-remitting MS still are apparent in the secondary progressive phase of the disease and support the use of MRI as a relevant outcome measure. In view of the relatively modest nature of the correlations, it seems unwise to rely on such MRI measures alone as primary efficacy variables in secondary progressive MS trials.
Asunto(s)
Encéfalo/efectos de los fármacos , Encéfalo/patología , Interferón beta/uso terapéutico , Imagen por Resonancia Magnética , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Crónica Progresiva/patología , Europa (Continente) , Femenino , Humanos , Interferon beta-1b , Masculino , Esclerosis Múltiple Crónica Progresiva/fisiopatología , Pronóstico , RecurrenciaRESUMEN
The recently completed European trial of interferon beta-1b (IFNbeta-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T(1)-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNbeta-1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNbeta-1b (placebo 2.6%, IFNbeta-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNbeta. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNbeta-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced disease.
Asunto(s)
Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Interferón beta/uso terapéutico , Imagen por Resonancia Magnética/normas , Esclerosis Múltiple Crónica Progresiva/tratamiento farmacológico , Esclerosis Múltiple Crónica Progresiva/patología , Adulto , Atrofia/patología , Progresión de la Enfermedad , Método Doble Ciego , Femenino , Humanos , Interferón beta-1a , Interferon beta-1b , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Distribuciones EstadísticasRESUMEN
In this article, the authors examine the effect of lisuride on 22 patients with probable Alzheimer's disease (NINCDS/ADRDA criteria) in a randomized double-blind, placebo-controlled, parallel group design. Ten patients received lisuride and 12 patients received placebo. Lisuride was administered in a dose-finding phase of four weeks and an efficacy phase of eight weeks, with a maximum dose of 0.3 mg daily. Outcome measures included global clinical impression, general cognitive function, mood, verbal and visual memory, attention, and psychomotor function. Average decline in Mini-Mental State Examination score after 12 weeks treatment was less often statistically significant in lisuride treated patients than in patients receiving a placebo (p < 0.05). Patients treated with lisuride improved their average total score and short-delay cued recall score on the California Verbal Learning Test, a test of verbal memory, whereas placebo-treated patients showed worse performance compared with baseline. These differences approached statistical significance, with p = 0.06 and p = 0.05, respectively. No other differences between the treatment groups were evident. The authors failed to find a consistent effect of lisuride on symptoms of Alzheimer's disease. However, this study's sample size was relatively small, and larger studies are needed to ascertain the treatment effects of serotonergic antagonists on Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Agonistas de Dopamina/uso terapéutico , Lisurida/uso terapéutico , Agonistas de Receptores de Serotonina/uso terapéutico , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Memoria a Corto Plazo/efectos de los fármacos , Memoria a Corto Plazo/fisiología , Escalas de Valoración Psiquiátrica , Psicometría , Seguridad , Resultado del Tratamiento , Conducta Verbal/efectos de los fármacosRESUMEN
This manuscript describes the outline of a double-blind, placebo-controlled, (European), multicentre phase III study to evaluate the safety and efficacy of 8 MIU of interferon beta-Ib given subcutaneously every other day for 3 years in patients with secondary progressive multiple sclerosis. The primary efficacy variable of this trial is the time to confirmed neurological deterioration as documented by the Expanded Disability Status Scale. The essentials of the study design are presented, including the rationale for the performance of the study and the selection of both clinical and magnetic resonance imaging outcome parameters.
Asunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Interferón beta/administración & dosificación , Esclerosis Múltiple/terapia , Adolescente , Adulto , Ensayos Clínicos como Asunto , Ensayos Clínicos Fase III como Asunto , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/etiología , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
The Clinical Global Impression Scale (CGI) is a recognized rating scale for global clinical judgments comprising scores for disease severity, change of disease conditions, and a so-called "efficacy index." In this report, the authors subject the CGI to a methodological analysis. Thirty-seven physicians working in psychogeriatric wards were interviewed on 12 patients each with a DSM-III diagnosis of a dementia syndrome. After the physicians made global judgments on the patients with the CGI, "personal" assessment criteria were elicited. The CGI data were correlated in the statistical analysis with the physicians' assessments of the patients on their personal criteria and on "recognized" assessment criteria obtained from DSM-III-R diagnostic criteria for dementia syndrome. Interrater reliabilities between physicians and nursing staff as well as retest reliabilities for the CGI criteria were also measured. While the CGI-severity reflects primarily the cognitive aspects of dementia, the CGI global assessment of change of the disease condition was poorly correlated with the assessments based on "personal" or the recognized DSM-III-R criteria. This was also indicated by the result that the reliability scores for CGI-severity were high and did not vary greatly, whereas the reliability scores for CGI change showed wide confidence intervals.
Asunto(s)
Demencia/psicología , Escalas de Valoración Psiquiátrica , Demencia/diagnóstico , HumanosRESUMEN
Eleven patients with chronic spastic hemiparesis were treated with biosignal processing (BSP), a modified biofeedback method in which the patient practices useful tasks, not isolated individual movements. A surface EMG measures sequential movements, and an acoustic signal monitors muscle exertion. The patient first learns how the signal develops by using the unaffected limb. Then the patient tries to reproduce the course of the signal in the paretic limb. Patients received 12 to 30 treatments for upper and/or lower extremities. We measured maximum strength as expressed through the EMG signal; ability to perform the trained action as measured by specific grading systems; and general increase in movement competence during a Bobath movement test. Ten patients showed improved strength; four made marked progress in the performance of specific tasks with the upper extremity, as did four with the lower extremity. Four patients in each group improved in general movement. We recommend the integration of useful tasks into movement exercises in EMG biofeedback therapy.