Fabiana Marques

Efficacy and Tolerability of Antiepileptic Drugs in Patients with Focal Epilepsy: Systematic Review and Network Meta-analyses

Several newer antiepileptic drugs (AEDs) have been introduced into clinical practice, offering choices for individualizing the treatment of epilepsy since AEDs have different efficacy and tolerability profiles. In particular, questions exist regarding which AEDs are the best options for the monotherapy of focal epilepsy. Is carbamazepine (CBZ), which is considered the standard treatment for focal epilepsy, still the best option for monotherapy of focal epilepsy, despite the emergence of new AEDs? In this systematic review, we compared the relative tolerability of all available AEDs for monotherapy of all types of epilepsy as well as their efficacy in the monotherapy of focal epilepsy. In addition, we compared CBZ with other AEDs for the monotherapy of focal epilepsy. We performed a search of the MEDLINE/PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for randomized controlled clinical trials. To compare the relative efficacy and tolerability of the AEDs, we performed network meta‐analyses using a Bayesian random‐effects model. Sensitivity analyses were conducted to determine the robustness of the results. A total of 65 studies were included in this review, composing 16,025 patients. Clobazam, levetiracetam, lamotrigine, oxcarbazepine, sulthiame, topiramate, and valproate had the best efficacy profiles and demonstrated no evidence of superiority or inferiority compared with CBZ. However, CBZ showed the greatest risk of patient discontinuation due to intolerable adverse reactions, whereas lamotrigine had the best safety profile and an 81% probability of being the best for the tolerability outcome of patient withdrawals from the study due to intolerable adverse reactions, followed by sulthiame (60%) and clobazam (51%). The newer AEDs—levetiracetam, lamotrigine, oxcarbazepine, sulthiame, and topiramate—should be considered for monotherapy of focal epilepsy because they were demonstrated to be as effective as the older ones (CBZ, clobazam, and valproate) for the treatment of focal epilepsy and were more tolerable. Lamotrigine was the AED with the best tolerability profile, suggesting that it may be the best option for the treatment of focal epilepsy in children and adults.

Aerobic Training after Myocardial Infarction: Remodeling Evaluated by Cardiac Magnetic Resonance

Background Numerous studies show the benefits of exercise training after myocardial infarction (MI). Nevertheless, the effects on function and remodeling are still controversial. Objectives To evaluate, in patients after (MI), the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR). Methods 26 male patients, 52.9 ± 7.9 years, after a first MI, were assigned to groups: trained group (TG), 18; and control group (CG), 8. The TG performed supervised aerobic exercise on treadmill twice a week, and unsupervised sessions on 2 additional days per week, for at least 3 months. Laboratory tests, anthropometric measurements, resting heart rate (HR), exercise test, and CMR were conducted at baseline and follow-up. Results The TG showed a 10.8% reduction in fasting blood glucose (p = 0.01), and a 7.3-bpm reduction in resting HR in both sitting and supine positions (p < 0.0001). There was an increase in oxygen uptake only in the TG (35.4 ± 8.1 to 49.1 ± 9.6 mL/kg/min, p < 0.0001). There was a statistically significant decrease in the TG left ventricular mass (LVmass) (128.7 ± 38.9 to 117.2 ± 27.2 g, p = 0.0032). There were no statistically significant changes in the values of left ventricular end-diastolic volume (LVEDV) and ejection fraction in the groups. The LVmass/EDV ratio demonstrated a statistically significant positive remodeling in the TG (p = 0.015). Conclusions Aerobic exercise of moderate intensity improved physical capacity and other cardiovascular variables. A positive remodeling was identified in the TG, where a left ventricular diastolic dimension increase was associated with LVmass reduction.

Use of the Wasserman equation in optimization of the duration of the power ramp in a cardiopulmonary exercise test: a study of Brazilian men

This study aimed to analyze the agreement between measurements of unloaded oxygen uptake and peak oxygen uptake based on equations proposed by Wasserman and on real measurements directly obtained with the ergospirometry system. We performed an incremental cardiopulmonary exercise test (CPET), which was applied to two groups of sedentary male subjects: one apparently healthy group (HG, n=12) and the other had stable coronary artery disease (n=16). The mean age in the HG was 47±4 years and that in the coronary artery disease group (CG) was 57±8 years. Both groups performed CPET on a cycle ergometer with a ramp-type protocol at an intensity that was calculated according to the Wasserman equation. In the HG, there was no significant difference between measurements predicted by the formula and real measurements obtained in CPET in the unloaded condition. However, at peak effort, a significant difference was observed between oxygen uptake (V˙O2)peak(predicted)and V˙O2peak(real)(nonparametric Wilcoxon test). In the CG, there was a significant difference of 116.26 mL/min between the predicted values by the formula and the real values obtained in the unloaded condition. A significant difference in peak effort was found, where V˙O2peak(real)was 40% lower than V˙O2peak(predicted)(nonparametric Wilcoxon test). There was no agreement between the real and predicted measurements as analyzed by Lin’s coefficient or the Bland and Altman model. The Wasserman formula does not appear to be appropriate for prediction of functional capacity of volunteers. Therefore, this formula cannot precisely predict the increase in power in incremental CPET on a cycle ergometer.

Replacement of carvedilol for propranolol in patients with heart failure

BACKGROUND Large clinical trials using the betablockers carvedilol, metoprolol, bisoprolol and nebivolol have demonstrated improvement of survival and symptoms in patients with heart failure. Despite the lack of scientific evidence, it is plausible that their beneficial effects are extensible to other betablockers. OBJECTIVE To evaluate the impact of the replacement of carvedilol for propranolol on left ventricular function, functional capacity, quality of life, pressure levels, and cardiac autonomic control in patients with heart failure. METHODS Twenty nine patients receiving optimized drug therapy including maximum tolerated doses of carvedilol were divided into two groups: replacement of carvedilol for propranolol (n = 15) and continued carvedilol (n = 14). At baseline and 6 months later, clinical and laboratorial assessments were carried out with radionuclide ventriculography, echocardiography, Minnesota questionnaire, walk test, APBM and Holter monitoring. RESULTS The clinical and demographic characteristics were similar in the two groups at baseline. Individualized propranolol dose adjustment ensured a similar degree of beta-blockade, as assessed by resting heart rate and chronotropic reserve. The mean propranolol dose used was 109 +/- 43 mg/day. Only one patient presented with intolerance to propranolol, thus carvedilol was reintroduced. One death was recorded in group propranolol. Ejection fraction significantly increased in the propranolol group. No significant change was observed in the other cardiovascular variables after betablocker replacement. CONCLUSION Our results indicate that replacement of carvedilol for propranolol in patients with heart failure is not associated with deterioration of the ejection fraction, functional capacity, quality of life, and other cardiovascular variables related to autonomic and blood pressure control., PP.0-0).FUNDAMENTO: Grandes estudos clinicos empregando os betabloqueadores carvedilol, metoprolol, bisoprolol e nebivolol, demonstraram melhora da sobrevida e dos sintomas em pacientes com insuficiencia cardiaca. Apesar da falta de evidencias cientificas, e plausivel que o efeito benefico seja extensivel a outros betabloqueadores. OBJETIVO: Avaliar em pacientes com insuficiencia cardiaca o impacto da substituicao do carvedilol por propranolol sobre a funcao ventricular esquerda, capacidade funcional, qualidade de vida, niveis pressoricos e controle autonomico cardiaco. METODOS: Vinte e nove pacientes com terapeutica medicamentosa otimizada incluindo doses maximas toleradas de carvedilol foram divididos em dois grupos: substituicao de carvedilol por propranolol (n = 15) e manutencao de carvedilol (n = 14). Na condicao basal, e apos 6 meses, foram realizadas avaliacoes clinica e laboratorial com: ventriculografia nuclear, ecocardiografia, questionario de Minnesota, teste de caminhada, MAPA e Holter. RESULTADOS: As caracteristicas laboratoriais e demograficas foram similares nos dois grupos na avaliacao inicial. Ajuste individualizado da dose do propranolol garantiu grau semelhante de betabloqueio avaliado pela frequencia cardiaca em repouso e reserva cronotropica. A dose media de propranolol usada foi 109 ± 43 mg/dia. Apenas um paciente apresentou intolerância ao propranolol com retorno do carvedilol. Foi registrado um obito no grupo propranolol. A fracao de ejecao apresentou aumento significativo no grupo propranolol. As demais variaveis cardiovasculares nao sofreram modificacoes significativas apos troca do betabloqueador. CONCLUSAO: Nossos resultados indicam que a substituicao do carvedilol por propranolol em pacientes com insuficiencia cardiaca nao esta associada a deterioracao da fracao de ejecao, da capacidade funcional, da qualidade de vida e das variaveis cardiovasculares de controle pressorico e autonomico.

Drug-resistant epilepsy and topiramate: Plasma concentration and frequency of epileptic seizures

Topiramate (TPM) is a second‐generation antiepileptic drug (AED), acting on drug‐resistant epilepsy. The aim of the study was to evaluate the influence of the dose, use of other AEDs on TPM plasma concentration (Cp), and frequency of epileptic seizures. A cross‐sectional analytical study was developed with patients aged 18‐60 years, for diagnosis of drug‐resistant epilepsy, using TPM in monotherapy or associated with other AEDs. The following variables were analyzed: age, frequency of epileptic seizures, pharmacotherapeutic regimen with its respective doses, adherence to medication treatment, and adverse events score. Thirty‐seven patients were included, 83.8% of the patients presented Cp below the therapeutic range. Multiple linear regression estimated that the increase of 1.0 mg/kg/d promoted an increase of 0.68 μg/mL in TPMCp, while the use of inducers predicted a reduction of 2.97 μg/mL (P < .001). Multiple Poisson regression predicts that an increase of 1.0 μg/mL in TPMCp decreased the patients chance of presenting seizures, and patients using AED inducers were about ten times more likely to present seizures than those who do not use (P < .001). In addition, for patients using AED inducers with Cp below the therapeutic range, the mean number of seizures per month was greater than those with Cp within the therapeutic range. The prescribed dose and the use of AED inducers influence Cp of TPM, likewise the low Cp of first‐line AEDs and of the adjuvant in the treatment, TPM, as well as low TPM dose seem to affect the control of epileptic seizures.

Cardiac and Musculoskeletal Responses to the Effects of Passive and Active Tilt Test in Healthy Subjects

Background Maintenance of orthostatism requires the interaction of autonomic and muscle responses for an efficient postural control, to minimize body motion and facilitate venous return in a common type of syncope called neurocardiogenic syncope (NCS). Muscle activity in standing position may be registered by surface electromyography, and body sway confirmed by displacement of the center of pressure (COP) on a force platform. These peripheral variables reflect the role of muscles in the maintenance of orthostatism during the active tilt test, which, compared with muscle activity during the passive test (head-up tilt test), enables the analyses of electromyographic activity of these muscles that may anticipate the clinical effects of CNS during these tests. Objective to evaluate and compare the effects of a standardized protocol of active and passive tests for CNS diagnosis associated with the effects of Valsalva maneuver (VM). Methods twenty-thee clinically stable female volunteers were recruited to undergo both tests. EMG electrodes were placed on muscles involved in postural maintenance. During the active test, subjects stood on a force platform. In addition to electromyography and the platform, heart rate was recorded during all tests. Three VMs were performed during the tests. Results progressive peripheral changes were observed along both tests, more evidently during the active test. Conclusion the active test detected changes in muscle and cardiovascular responses, which were exacerbated by the VM.

Substituição do carvedilol pelo propranolol em pacientes com insuficiência cardíaca

BACKGROUND Large clinical trials using the betablockers carvedilol, metoprolol, bisoprolol and nebivolol have demonstrated improvement of survival and symptoms in patients with heart failure. Despite the lack of scientific evidence, it is plausible that their beneficial effects are extensible to other betablockers. OBJECTIVE To evaluate the impact of the replacement of carvedilol for propranolol on left ventricular function, functional capacity, quality of life, pressure levels, and cardiac autonomic control in patients with heart failure. METHODS Twenty nine patients receiving optimized drug therapy including maximum tolerated doses of carvedilol were divided into two groups: replacement of carvedilol for propranolol (n = 15) and continued carvedilol (n = 14). At baseline and 6 months later, clinical and laboratorial assessments were carried out with radionuclide ventriculography, echocardiography, Minnesota questionnaire, walk test, APBM and Holter monitoring. RESULTS The clinical and demographic characteristics were similar in the two groups at baseline. Individualized propranolol dose adjustment ensured a similar degree of beta-blockade, as assessed by resting heart rate and chronotropic reserve. The mean propranolol dose used was 109 +/- 43 mg/day. Only one patient presented with intolerance to propranolol, thus carvedilol was reintroduced. One death was recorded in group propranolol. Ejection fraction significantly increased in the propranolol group. No significant change was observed in the other cardiovascular variables after betablocker replacement. CONCLUSION Our results indicate that replacement of carvedilol for propranolol in patients with heart failure is not associated with deterioration of the ejection fraction, functional capacity, quality of life, and other cardiovascular variables related to autonomic and blood pressure control., PP.0-0).FUNDAMENTO: Grandes estudos clinicos empregando os betabloqueadores carvedilol, metoprolol, bisoprolol e nebivolol, demonstraram melhora da sobrevida e dos sintomas em pacientes com insuficiencia cardiaca. Apesar da falta de evidencias cientificas, e plausivel que o efeito benefico seja extensivel a outros betabloqueadores. OBJETIVO: Avaliar em pacientes com insuficiencia cardiaca o impacto da substituicao do carvedilol por propranolol sobre a funcao ventricular esquerda, capacidade funcional, qualidade de vida, niveis pressoricos e controle autonomico cardiaco. METODOS: Vinte e nove pacientes com terapeutica medicamentosa otimizada incluindo doses maximas toleradas de carvedilol foram divididos em dois grupos: substituicao de carvedilol por propranolol (n = 15) e manutencao de carvedilol (n = 14). Na condicao basal, e apos 6 meses, foram realizadas avaliacoes clinica e laboratorial com: ventriculografia nuclear, ecocardiografia, questionario de Minnesota, teste de caminhada, MAPA e Holter. RESULTADOS: As caracteristicas laboratoriais e demograficas foram similares nos dois grupos na avaliacao inicial. Ajuste individualizado da dose do propranolol garantiu grau semelhante de betabloqueio avaliado pela frequencia cardiaca em repouso e reserva cronotropica. A dose media de propranolol usada foi 109 ± 43 mg/dia. Apenas um paciente apresentou intolerância ao propranolol com retorno do carvedilol. Foi registrado um obito no grupo propranolol. A fracao de ejecao apresentou aumento significativo no grupo propranolol. As demais variaveis cardiovasculares nao sofreram modificacoes significativas apos troca do betabloqueador. CONCLUSAO: Nossos resultados indicam que a substituicao do carvedilol por propranolol em pacientes com insuficiencia cardiaca nao esta associada a deterioracao da fracao de ejecao, da capacidade funcional, da qualidade de vida e das variaveis cardiovasculares de controle pressorico e autonomico.

Sustitución del carvedilol por el propranolol en pacientes con insuficiencia cardíaca

BACKGROUND Large clinical trials using the betablockers carvedilol, metoprolol, bisoprolol and nebivolol have demonstrated improvement of survival and symptoms in patients with heart failure. Despite the lack of scientific evidence, it is plausible that their beneficial effects are extensible to other betablockers. OBJECTIVE To evaluate the impact of the replacement of carvedilol for propranolol on left ventricular function, functional capacity, quality of life, pressure levels, and cardiac autonomic control in patients with heart failure. METHODS Twenty nine patients receiving optimized drug therapy including maximum tolerated doses of carvedilol were divided into two groups: replacement of carvedilol for propranolol (n = 15) and continued carvedilol (n = 14). At baseline and 6 months later, clinical and laboratorial assessments were carried out with radionuclide ventriculography, echocardiography, Minnesota questionnaire, walk test, APBM and Holter monitoring. RESULTS The clinical and demographic characteristics were similar in the two groups at baseline. Individualized propranolol dose adjustment ensured a similar degree of beta-blockade, as assessed by resting heart rate and chronotropic reserve. The mean propranolol dose used was 109 +/- 43 mg/day. Only one patient presented with intolerance to propranolol, thus carvedilol was reintroduced. One death was recorded in group propranolol. Ejection fraction significantly increased in the propranolol group. No significant change was observed in the other cardiovascular variables after betablocker replacement. CONCLUSION Our results indicate that replacement of carvedilol for propranolol in patients with heart failure is not associated with deterioration of the ejection fraction, functional capacity, quality of life, and other cardiovascular variables related to autonomic and blood pressure control., PP.0-0).FUNDAMENTO: Grandes estudos clinicos empregando os betabloqueadores carvedilol, metoprolol, bisoprolol e nebivolol, demonstraram melhora da sobrevida e dos sintomas em pacientes com insuficiencia cardiaca. Apesar da falta de evidencias cientificas, e plausivel que o efeito benefico seja extensivel a outros betabloqueadores. OBJETIVO: Avaliar em pacientes com insuficiencia cardiaca o impacto da substituicao do carvedilol por propranolol sobre a funcao ventricular esquerda, capacidade funcional, qualidade de vida, niveis pressoricos e controle autonomico cardiaco. METODOS: Vinte e nove pacientes com terapeutica medicamentosa otimizada incluindo doses maximas toleradas de carvedilol foram divididos em dois grupos: substituicao de carvedilol por propranolol (n = 15) e manutencao de carvedilol (n = 14). Na condicao basal, e apos 6 meses, foram realizadas avaliacoes clinica e laboratorial com: ventriculografia nuclear, ecocardiografia, questionario de Minnesota, teste de caminhada, MAPA e Holter. RESULTADOS: As caracteristicas laboratoriais e demograficas foram similares nos dois grupos na avaliacao inicial. Ajuste individualizado da dose do propranolol garantiu grau semelhante de betabloqueio avaliado pela frequencia cardiaca em repouso e reserva cronotropica. A dose media de propranolol usada foi 109 ± 43 mg/dia. Apenas um paciente apresentou intolerância ao propranolol com retorno do carvedilol. Foi registrado um obito no grupo propranolol. A fracao de ejecao apresentou aumento significativo no grupo propranolol. As demais variaveis cardiovasculares nao sofreram modificacoes significativas apos troca do betabloqueador. CONCLUSAO: Nossos resultados indicam que a substituicao do carvedilol por propranolol em pacientes com insuficiencia cardiaca nao esta associada a deterioracao da fracao de ejecao, da capacidade funcional, da qualidade de vida e das variaveis cardiovasculares de controle pressorico e autonomico.