Colágeno e pele: da estrutura às evidências de sua suplementação oral / Collagen and skin: from the structure to scientific evidence of oral supplementation

Durante o processo de envelhecimento, as rotas intracelulares que regulam a homeostase do colágeno são influenciadas pelo expossoma, resultando na sua degradação e diminuição de síntese, levando à flacidez da pele. As evidências atuais disponíveis apontam que a suplementação oral de colágeno poderia promover redução de rugas na região dos olhos, cicatrização de feridas, melhora da elasticidade e hidratação da pele, melhora da celulite, de algumas dermatites e da fragilidade das unhas. Ainda são necessários mais estudos em larga escala e metodologicamente mais robustos para afirmar que o uso do colágeno oral para tratamento adjuvante de diferentes condições dermatológicas seja realmente eficaz.

In the aging process, the intracellular routes that regulate collagen homeostasis are influenced by the exposome, resulting in its degradation and decreased synthesis, leading to sagging skin. Current evidence indicates that oral collagen supplementation may promote wrinkles reduction in the eye area, wound healing, skin elasticity and hydration improvement, enhancement of cellulite, some dermatitis, and nails fragility. Large-scale and methodologically more robust studies are still needed to consider the use of oral collagen as an effective adjuvant treatment to different dermatological conditions

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy.

BACKGROUND: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. OBJECTIVE: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. METHODS: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. RESULTS: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. CONCLUSION: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

Efficacy and safety of levetiracetam as adjunctive therapy for refractory focal epilepsy / Eficácia e segurança do levetiracetam como terapia adjunta na epilepsia focal refratária

ABSTRACT Background: Epilepsy affects about 50 million people worldwide and around 30% of these patients have refractory epilepsy, with potential consequences regarding quality of life, morbidity and premature mortality. Objective: The aim of treatment with antiseizure medications (ASMs) is to allow patients to remain without seizures, with good tolerability. Levetiracetam is a broad-spectrum ASM with a unique mechanism of action that differs it from other ASMs. It has been shown to be effective and safe for treating adults and children with epilepsy. Methods: This was a phase III, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of levetiracetam in children and adults (4-65 years) as an adjuvant treatment for focal-onset seizures. It was conducted among 114 patients undergoing treatment with up to three ASMs. The primary efficacy analysis was based on the proportion of patients who achieved a reduction of ≥ 50% in the mean number of focal seizures per week, over a 16-week treatment period. The patients were randomized to receive placebo or levetiracetam, titrated every two weeks from 20 mg/kg/day or 1,000 mg/day up to 60 mg/kg/day or 3,000 mg/day. Results: Levetiracetam was significantly superior to placebo (p = 0.0031); 38.7% of the participants in the levetiracetam group and 14.3% in the control group shows reductions in focal seizures. Levetiracetam was seen to have a favorable safety profile and an adverse event rate similar to that of placebo. Conclusion: Corroborating the results in the literature, levetiracetam was shown to be effective and safe for children and adults with refractory focal-onset epilepsy.

RESUMO Introdução: A epilepsia afeta cerca de 50 milhões de pessoas em todo o mundo e aproximadamente 30% desses pacientes apresentam epilepsia refratária, com possíveis consequências na qualidade de vida, morbidade e mortalidade prematura. Objetivo: O objetivo do tratamento com fármacos antiepilépticos (FAEs) é permitir que os pacientes permaneçam sem crises epilépticas com boa tolerabilidade. O levetiracetam (LEV) é um FAE de amplo espectro, com mecanismo de ação único, diferente dos demais e que demonstra ser eficaz e seguro no tratamento de adultos e crianças. Métodos: Estudo de fase III, multicêntrico, randomizado, duplo-cego e controlado por placebo avalia a eficácia e a segurança do LEV em crianças e adultos (4-65 anos) como tratamento adjuvante para crises de início focal em 114 pacientes já tratados com até três FAEs. A análise de eficácia primária foi baseada na proporção de pacientes que apresentaram redução ≥50% no número médio de crises epilépticas focais semanais, durante 16 semanas. Os pacientes foram randomizados para receber placebo ou LEV, titulado a cada duas semanas de 20 mg/kg/dia ou 1.000 mg/dia até 60 mg/kg/dia ou 3.000 mg/dia. Resultados: LEV foi significativamente superior ao placebo (p=0,0031), com 38,7% dos participantes no grupo LEV e 14,3% no grupo controle que apresentaram redução das crises focais. LEV apresenta bom perfil de segurança com eventos adversos semelhantes ao placebo. Conclusão: Corroborando com os resultados da literatura, o levetiracetam mostra-se eficaz e seguro para crianças e adultos com epilepsia focal refratária.

Efficacy and Tolerability of a Fixed-Dose Combination of Rosuvastatin and Ezetimibe Compared with a Fixed-Dose Combination of Simvastatin and Ezetimibe in Brazilian Patients with Primary Hypercholesterolemia or Mixed Dyslipidemia: A Multicenter, Randomized Trial.

BACKGROUND: The addition of ezetimibe to statin therapy has been reported to result in increased efficacy for reduction of LDL-C levels and achievement of lipid targets, compared with monotherapy. OBJECTIVE: This study was designed to demonstrate the noninferiority of therapy with fixed-dose rosuvastatin plus ezetimibe formulations versus fixed dose simvastatin and ezetimibe formulations for reduction of LDL-C levels in Brazilian patients with hypercholesterolemia or mixed dyslipidemia. METHODS: Phase III, multicenter, randomized, parallel, open-label, noninferiority study that included male and female participants (aged 21-80 years) with hypercholesterolemia or mixed dyslipidemia. After a 1-week screening period with washout of lipid-lowering medications when needed, patients were treated with simvastatin 20 mg/d for 5 weeks. Participants with LDL-C levels ≥100 mg/dL after the initial treatment were submitted to a 1-week washout period, and then randomized 1:1 to receive either combined rosuvastatin 10 mg + ezetimibe 10 mg (R/E) or simvastatin 20 mg + ezetimibe 10 mg (S/E) for 4 weeks and, if they still did not achieve the stipulated target, doses were readjusted to rosuvastatin 20 mg + ezetimibe 10 mg or simvastatin 40 mg + ezetimibe 10 mg, respectively, for 4 weeks. RESULTS: One hundred twenty-nine participants were enrolled, including 66 in R/E and 63 in S/E. At the end of simvastatin 20 mg treatment period, mean LDL-C values were 124.79 mg/dL and 121.27 mg/dL for participants randomized to R/E and S/E arms, respectively. After 4 weeks of R/E 10 mg + 10 mg or S/E 20 mg + 10 mg combined treatments, adjusted mean LDL-C values were 74.21 mg/dL and 85.58 mg/dL, respectively (P = 0.0005), and after 9 weeks, with dose adjustment to R/E 20 mg + 10 mg in 6 patients and to S/E 40 mg +10 mg in 19 patients, LDL-C adjusted mean values were 75.29 mg/dL and 86.62 mg/dL, respectively (P = 0.0006). There was a statistically significant difference between the association R/E and S/E (P = 0.0013) in percentage change of LDL-C after 9 weeks of combined treatments. The adjusted mean difference was estimated at -10.32% (95% CI, -16.94% to -3.70%). The LDL-C <100 mg/dL target was achieved in a significantly greater proportion of participants at week 4 in the R/E compared with the S/E arm (84.8% vs 68.2%; P = .0257), and at week 9, the proportion was 81.2% versus 73.0%, respectively (P = 0.23). LDL-C <70 mg/dL was achieved at a significantly greater proportion in the R/E arm, both at week 4 (45.4% vs 15.9%; P = 0.003) and week 9 (40.9% vs 15.9%; P = 0.0017). A statistically significant difference at week 9 (P = 0.0106) was observed in fasting blood glucose in the R/E arm, but the overall incidence of adverse events was not significantly different between groups. CONCLUSIONS: Rosuvastatin and ezetimibe fixed dose combination in both 10 mg/10 mg and 20 mg/10 mg doses, respectively, provided significantly lower levels of LDL-C compared with simvastatin and ezetimibe in doses of 20 mg/10 mg and 40 mg/10 mg, respectively. The fixed-dose combinations were both effective and well tolerated in this Brazilian study population. ClinicalTrials.gov identifier: NCT01420549. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Ablação por cateter em pacientes com arritmias cardíacas refratárias utilizando técnicas de radiofrequência / Catheter ablation of refractory cardiac arrhythmias by radiofrequency current

Objetivo: Descrever a experiência inicial do Setor Eletrofisiologia Clínica da Escola Paulista de Medicina com as técnicas de ablaçäo por radiofreqüência. Métodos - Vinte pacientes com arritmias refratárias ao tratamento clínico foram submetidos a estudo eletrofisiológico para diagnóstico e ablaçäo por radiofreqüência dos circuitos de suas arritmias. Dez pacientes eram homens e 10 mulheres com idades variando de 13 a 76 anos (média de 42,4 anos). Dezenove pacientes apresentavam taquiarritmias supraventriculares: 1 taquicardia atrial e 1 fibrilaçäo atrial com resposta ventricular rápida, 5 pacientes com taquicardia reentrante nodal e 12 pacientes com taquicardia reentrante atrioventricular. Um pacientes apresentava taquicardia ventricular de via de saída de ventrículo direito. Resultados - O tempo médio do procedimento foi de 4,17 horas e o número de aplicaçöes variou de 1 a 10 (média de 3,4 aplicaçöes), 30 - 40 V cada. Obteve-se sucesso em 18/20 (90%) dos pacientes, sendo que em 15/18 (83%) dos pacientes tratados com sucesso, o procedimento diagnóstico e terapêutico foi feito só exame. Um paciente apresentou oclusäo arterial aguda relacionada ao procedimento, necessitando de trombectomia por cateter de Fogarty. Durante um seguimento médio de 4 meses nenhum paciente apresentou recorrência de taquicardia. Conclusäo - Os resultados da experiência inicial das técnicas de ablaçäo por radiofreqüencia em nosso meio sugerem que esse proceimento possa beneficiar um grande número de pacientes com taquiarritmias

Purpose - evaluate the efficacy of radiofrequency catheter ablation in patients with refractory cardiac arrhythmias. Methods - Twenty patients with refractory cardinc arrhythmias were undertaken to electrophysiologic studies for diagnosis and radiofrequency catheter ablation of their reentrant arrhythmias. Ten patients were men and 10 women with ages varyingfrom 13 to 76 years (mean = 42,4 years).Nineteen patients had supraventricular tachyarrhythmias: One patient had atrial tachycardia and 1 atrial fibrillation with rapid ventricular rate, 5 patients had reentrant nodal tachycardia, 12 patients had reentrant atrioventricular tachycardia and 1 patient had right ventricular outflow tract tachycardia. Results - the mean time of the procedure was 4,1 hours. The radiofrequency current energy applied was 40-50 V for 30-40 seconds. Ablation was successful in 18/20 (90%) patients; in 15/18 (83%) of sucessfully treated patients the same study was done for diagnosis and radiofrequency ablation. One patient had femoral arterial occlusion and was treated with no significant sequelae. During a mean follow-up of 4 months no preexcitacion or reentrant tachycardia occurred. Conclusions - the results of our experience with radiofrequency catheter ablation of cardiac arrhythmias suggest that this technique can benefit an important number of patients with cardiac arrhythmias