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1.
Clin. transl. oncol. (Print) ; 26(1): 239-244, jan. 2024.
Artigo em Inglês | IBECS | ID: ibc-229162

RESUMO

Purpose To estimate the cost-effectiveness of adding a CDK4/6 inhibitor to standard endocrine therapy in the first-line setting for advanced HR+/HER2− breast cancer in postmenopausal and premenopausal women, from the perspective of the Mexican public healthcare system. Methods We used a partitioned survival model to simulate relevant health outcomes in a synthetic cohort of patients with breast cancer derived from the PALOMA-2, MONALEESA-2, MONARCH-3 trials for postmenopausal patients, and from the MONALEESA-7 study for premenopausal patients. Effectiveness was measured in life years gained. Cost-effectiveness is reported through incremental cost-effectiveness ratios (ICER). Results In postmenopausal patients, palbociclib led to an increase of 1.51 life years, ribociclib of 1.58 years, and abemaciclib of 1.75 years, compared to letrozole alone. The ICER was 36,648 USD, 32,422 USD, and 26,888 USD, respectively. In premenopausal patients, ribociclib led to an increase of 1.82 life years when added to goserelin and endocrine therapy, with an ICER of 44,579 USD. In the cost minimization analysis, for postmenopausal patients, ribociclib was the treatment with the highest costs due to follow-up requirements. Conclusion Palbociclib, ribociclib, and abemaciclib demonstrated a significant increase in effectiveness in postmenopausal patients, and ribociclib in premenopausal patients, when added to standard endocrine therapy for patients with advanced HR+/HER2− breast cancer. At the national stablished willingness to pay, only the addition of abemaciclib to standard endocrine therapy in postmenopausal women would be considered cost-effective. However, differences on results between therapies for postmenopausal patients were not statistically significant (AU)


Assuntos
Humanos , Feminino , 4-Aminopiridina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Neoplasias da Mama/tratamento farmacológico , Proteínas Inibidoras de Quinase Dependente de Ciclina/administração & dosagem , México
2.
Acta otorrinolaringol. esp ; 71(1): 40-44, ene.-feb. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-192434

RESUMO

OBJETIVO: Presentar los resultados del tratamiento con fampridina de liberación prolongada (4-AP-SR) en pacientes con nistagmo vertical inferior. MATERIAL Y MÉTODO: Serie de casos de nistagmo vertical inferior tratados con 10 mg de 4-AP-SR cada 12h. Se valoraron la mejoría clínica y la variación del nistagmo antes y después del tratamiento, registrando la puntuación en el Dizziness Handicap Inventory, la velocidad de la fase lenta del nistagmo y su frecuencia. RESULTADOS: Se trataron 3 pacientes, ninguno de los cuales notó cambios durante el tratamiento en relación con los síntomas visuales, aunque 2 pacientes notaron mejoría subjetiva de la marcha. No se detectaron diferencias significativas en la puntuación del Dizziness Handicap Inventory ni en las variables videonistagmográficas estudiadas. CONCLUSIÓN: No se han detectado cambios en los síntomas visuales con el tratamiento con 4-AP-SR. La contradicción con estudios previos puede estar producida por un bajo tamaño muestral, la etiología de los casos o la forma de medir los resultado


OBJECTIVE: To present the results of treatment with sustained-release fampridine (4-AP-SR) in patients with downbeat nystagmus. MATERIAL AND METHOD: Series of cases with downbeat nystagmus treated with 10 milligrams of 4-AP-SR every 12 hours. The clinical improvement and the variation of the nystagmus before and after the treatment were evaluated, recording the score in the Dizziness Handicap Inventory, the velocity of the slow phase of the nystagmus and its frequency. RESULTS: Three patients were treated, none of whom reported significant subjective changes during the treatment. No significant differences were detected in the Dizziness Handicap Inventory score or in the studied videonystagmographic variables. CONCLUSION: This communication does not present positive results on the use of 4-AP-SR. The contradiction with previous studies may be caused by a small sample size, by the etiology of the cases or by the way in which the results were measured


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Nistagmo Patológico/tratamento farmacológico , 4-Aminopiridina/administração & dosagem , Espectroscopia de Ressonância Magnética , Nistagmo Patológico/diagnóstico por imagem , Tontura , Índice de Gravidade de Doença
3.
Neurología (Barc., Ed. impr.) ; 33(5): 327-337, jun. 2018. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-175910

RESUMO

INTRODUCCIÓN: La alteración de la marcha es frecuente en la esclerosis múltiple (EM) y tiene un gran impacto negativo en los pacientes pues conlleva a la pérdida progresiva de autonomía personal y social, y de productividad laboral. Esta guía pretende establecer recomendaciones para la evaluación del deterioro de la marcha y el uso de fampridina de liberación prolongada (fampridina-LP) como tratamiento de pacientes con EM y deterioro de la marcha en España. DESARROLLO: Fampridina-LP a dosis de 10 mg cada 12 h es actualmente el único fármaco autorizado para mejorar el trastorno de la marcha en adultos con EM. En la práctica clínica, el fármaco ha demostrado además que mejora de forma significativa la calidad de vida de los pacientes que responden al tratamiento. La respuesta se puede evaluar mediante la prueba cronometrada de la marcha de 25 pies (T25FW) o el cuestionario MSWS-12 que deben realizarse antes y después del inicio del tratamiento. El tiempo mínimo recomendado para evaluar la respuesta inicial es de 2 semanas. Para considerar a un paciente como respondedor y continuar el tratamiento debe presentar, según indica la ficha técnica, una disminución en el tiempo T25FW o mejoría en el MSWS-12. Se recomienda realizar las revaluaciones al menos cada 6 meses. En los casos en que se considere la valoración de la calidad de vida, se recomienda la utilización del cuestionario de salud Short Form-36 (SF-36) o la escala MS Impact Scale-29 (MSIS-29). Es un fármaco en general bien tolerado y con buen perfil de seguridad. Se recomienda su administración en ayunas y control periódico de la función renal. CONCLUSIONES: Estas recomendaciones permiten garantizar una prescripción eficiente y más segura, y ayudan al manejo de fampridina-LP como tratamiento del deterioro de la marcha en pacientes adultos con EM en España


INTRODUCTION: Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain. DEVELOPMENT: PR-fampridine dosed at 10 mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly. CONCLUSIONS: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS


Assuntos
Humanos , Adulto , 4-Aminopiridina/uso terapêutico , Transtornos Neurológicos da Marcha/tratamento farmacológico , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Bloqueadores dos Canais de Potássio/uso terapêutico , Espanha/epidemiologia , Qualidade de Vida , Resultado do Tratamento
4.
J. physiol. biochem ; 74(1): 57-67, feb. 2018. graf
Artigo em Inglês | IBECS | ID: ibc-178918

RESUMO

Rate-dependent repolarization (RDR) of action potential (AP) in cardiomyocyte plays a critical role in the genesis of arrhythmias and RDR in atrium has been linked with atrial fibrillation. However, detailed studies focusing on the role of RDR in rabbit atrium are scant. In this study, atrial cells were isolated from rabbit heart and rate-dependent property was explored in single atrial cell to elucidate the underlying mechanism. Our results indicated that rate-dependent prolongation was evident at the action potential duration at 20% (APD20) and 50% (APD50) repolarization but not at 90% repolarization (APD90) under control condition. Using transient outward potassium current (Ito) inhibitor 4-Aminopyridine (4-AP, 2 mM) effectively eliminated the changes in APD20 and APD50, and unmasked the rate-dependent reduction of APD90 which could be diminished by further adding L-type calcium current (ICaL) inhibitor nifedipine (30 μM). However, using the selective late sodium current (INaL) inhibitor GS-458967 (GS967, 1 μM) caused minimal effect on APD90 of atrial cells both in the absence and presence of 4-AP. In consistence with results from APs, Ito and ICaL displayed significant rate-dependent reduction because of their slow reactivation kinetics. In addition, the magnitude of INaL in rabbit atrium was so small that its rate-dependent changes were negligible. In conclusion, our study demonstrated that Ito and ICaL mediate RDR of AP in rabbit atrium, while minimal effect of INaL was seen


Assuntos
Animais , Coelhos , Canais de Cálcio Tipo L/metabolismo , Átrios do Coração/metabolismo , Miócitos Cardíacos/metabolismo , Canais de Sódio/metabolismo , 4-Aminopiridina/farmacologia , Potenciais de Ação , Antiarrítmicos/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Átrios do Coração/citologia , Átrios do Coração , Miócitos Cardíacos/citologia , Miócitos Cardíacos , Nifedipino/farmacologia , Canais de Sódio/química
5.
Farm. hosp ; 41(2): 283-291, mar.-abr. 2017. tab
Artigo em Inglês | IBECS | ID: ibc-160954

RESUMO

Objective: Assessment of the efficacy and safety of fampridine for walking improvement in adult patients with multiple sclerosis. Method: A descriptive retrospective study of all patients who initiated treatment with fampridine between March, 2014 and February, 2015. Efficacy was assessed through the 25- foot walk test and the 12-item walking scale for multiple sclerosis. It was reviewed whether patients had suffered any of the most frequent adverse effects described in the pivotal clinical trial. Results: Six patients were included, with a 66.7% response rate. At 3-6 months, the mean change in walking speed (compared to baseline) was 39.32% and there was a mean improvement of 15 points in the walking scale. Only one patient presented adverse effects. Conclusions: The results obtained are encouraging, particularly when fampridine is the only drug currently approved to control such a disabling symptom as instability while walking (AU)


Objetivo: Evaluación de la efectividad y seguridad de la fampridina en la mejoría de la marcha de pacientes adultos con esclerosis múltiple. Método: Estudio descriptivo retrospectivo de todos los pacientes que iniciaron tratamiento con fampridina entre marzo de 2014 y febrero de 2015. Se evaluó la efectividad utilizando el test de marcha de los 25 pies y la escala de movilidad de 12 ítems de la esclerosis múltiple. Se revisó si los pacientes habían sufrido alguno de los efectos adversos más frecuentes descritos en el ensayo pivotal. Resultados: Se incluyeron 6 pacientes, con una tasa de respuesta del 66,7%. A los 3-6 meses, el cambio medio en la velocidad de la marcha (comparado con el basal) fue del 39,32% y hubo una mejora media de 15 puntos en la escala de movilidad. Solo uno de los pacientes presentó efectos adversos. Conclusiones: Los resultados obtenidos son esperanzadores, sobre todo cuando la fampridina es el único fármaco autorizado actualmente para controlar un síntoma tan discapacitante como es la inestabilidad de la marcha (AU)


Assuntos
Humanos , Transtornos Neurológicos da Marcha/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , 4-Aminopiridina/farmacocinética , Estudos Retrospectivos , Segurança do Paciente , Resultado do Tratamento
6.
J. physiol. biochem ; 62(4): 227-236, dic. 2006.
Artigo em Inglês | IBECS | ID: ibc-122984

RESUMO

Most excitable cells, including gastrointestinal smooth muscle cells, express several types of K+channels. The aim of this study was to examine the types of K+ channels involved in the contractility of longitudinal smooth muscle of rabbit small intestinein vitro. Spontaneous contractions and KCl-stimulated contractions were reduced by atropine, phentolamine, propranolol, suramin, tetrodotoxin and indomethacin. The amplitude and tone of spontaneous contractions were increased by apamin, charybdotoxin, iberiotoxin, E4031, tetraetylammonium (TEA) and BaCl2. The frequency of contractions was reduced in the presence of apamin and TEA and increased by charybdotoxin. It was found that 4-aminopyridine increased the tone of spontaneous contractions and reduced the amplitude and frequency of contractions. Glibenclamide did not modify the amplitude, frequency or tone of contractions. KCl-stimulated contractions were increased by E4031, were not modified by apamin, glibenclamide, NS1619 or diazoxide, and were reduced by charybdotoxin, TEA, 4-aminopyridine or BaCl2. These results suggest that both Ca2+-activated K+ channels of small and high conductance, and HERG K+ channels and inward rectifier K+ channels participate in spontaneous contractions of small intestine. On the other hand, voltage-dependent K+ channels, HERG K+ channels, inward rectifier K+ channels and high conductance Ca2+-activated K+ channels are involved in KCl-stimulated contractions (AU)


La mayoría de las células excitables, incluyendo las células lisas gastrointestinales, expresan varios tipos de canales de K+. El objetivo de este estudio es examinar los tipos de canales de K+que están involucrados en la contractilidad del músculo liso longitudinal del intestino delgado de conejoin vitro. Las contracciones espontáneas y las producidas por KCl se redujeron por atropina, fentolamina, propranolol, suramina, tetrodotoxina e indometacina. La amplitud y tono de las contracciones espontáneas aumentaron por apamin, charybdotoxina, iberiotoxina, E4031, tetraetilamonio (TEA) y BaCl2, mientras que la frecuencia de las contracciones se redujo en presencia de apamin, charybdotoxina y TEA. La 4-aminopiridina aumentó el tono de las contracciones espontáneas y redujo la amplitud y frecuencia de las contracciones. La glibenclamida no modificó la amplitud, frecuencia y tono de las contracciones. Las contracciones producidas por el KCl aumentaron en presencia de E4031, no fueron modificadas por el apamin, glibenclamida, NS1619 o diazóxida y disminuyeron en presencia de la charybdotoxina, TEA, 4-aminopiridina o BaCl2. Estos resultados sugieren que los canales de K+ activados por Ca2+ de pequeña y gran conductancia, canales de K+ HERG canales de K+ rectificadores de entrada participan en las contracciones espontáneas del intestino delgado. Por otra parte, los canales de K+ voltaje-dependientes, canales de K+ HERG, canales de K+ rectificadores de entrada y canales de K+activados por Ca2+ de gran conductancia están implicados en las contracciones producidas por el KCl (AU)


Assuntos
Animais , Coelhos , Canais de Potássio/farmacocinética , Músculo Liso/fisiopatologia , Acoplamento Excitação-Contração/fisiologia , Intestino Delgado/fisiopatologia , Apamina/farmacocinética , Charibdotoxina/farmacocinética , Tetraetilamônio/farmacocinética , 4-Aminopiridina/farmacocinética , Glibureto/farmacocinética
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