Lipid profile with eslicarbazepine acetate and carbamazepine monotherapy in adult patients with newly diagnosed focal seizures: post hoc analysis of a phase III trial and open-label extension study.

Background: Antiseizure medications can have negative effects on plasma lipid levels. Objectives: To evaluate plasma lipid changes in patients with newly diagnosed focal epilepsy treated with eslicarbazepine acetate (ESL) or controlled-release carbamazepine (CBZ-CR) monotherapy during a phase III, randomized, double-blind (DB) trial and 2 years of ESL treatment in an open-label extension (OLE). Design: Post hoc analysis of a phase III trial and OLE study. Methods: Proportions of patients with elevated levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were assessed at DB baseline, OLE baseline (last visit of DB trial), and end of OLE. Results: A total of 184 patients received ESL monotherapy during the OLE: 96 received ESL monotherapy in the DB trial and 88 patients received CBZ-CR monotherapy. The proportions of patients with elevated total cholesterol and LDL cholesterol increased significantly during the DB trial in those treated with CBZ-CR monotherapy [total cholesterol, +14.9% (p < 0.001); LDL cholesterol, +11.5% (p = 0.012)] but decreased significantly after switching to ESL monotherapy in the OLE [total cholesterol, -15.3% (p = 0.008); LDL cholesterol, -11.1% (p = 0.021)]. No significant changes were observed in those treated with ESL monotherapy during the DB trial and OLE. At the end of the DB trial, between-group differences (ESL-CBZ-CR) in the proportions of patients with elevated total and LDL cholesterol were -13.6% (p = 0.037) and -12.3% (p = 0.061), respectively; at the end of the OLE, these between-group differences were -6.0% (p = 0.360) and -0.6% (p = 1.000), respectively. Conclusion: A lower proportion of patients with newly diagnosed focal epilepsy had increased levels of total and LDL cholesterol, compared to baseline, following monotherapy with ESL versus CBZ-CR; after switching from CBZ-CR to ESL, the proportions of patients with increased levels decreased significantly. Registration: ClinicalTrials.gov NCT01162460/NCT02484001; EudraCT 2009-011135-13/2015-001243-36.

The impact of treatment with either eslicarbazepine acetate or controlled-release carbamazepine on cholesterol levels in patients with newly diagnosed focal epilepsy Patients with epilepsy have an increased risk of having cardiovascular and cerebrovascular diseases (e.g., myocardial infarction and stroke). Treatment with antiseizure medications can have a negative effect on blood cholesterol levels [such as total cholesterol and low-density lipoprotein (LDL) cholesterol], which can further increase the risk of cardiovascular and cerebrovascular diseases. We examined the impact of monotherapy treatment (i.e., treatment with only one antiseizure medication) using either eslicarbazepine acetate (ESL) or a controlled-release formulation of carbamazepine (CBZ-CR) in 184 patients with newly diagnosed focal epilepsy (ESL, 96 patients; CBZ-CR, 88 patients). Patients received monotherapy with ESL or CBZ-CR for approximately 1 year in a phase III clinical trial. After this, the patients could continue into a 2-year extension study during which they all received monotherapy with ESL. We assessed the proportions of patients with elevated levels of total cholesterol and LDL cholesterol at the beginning and end of the phase III trial, and at the end of the extension study. At the beginning of the phase III trial, the proportions of patients with elevated total cholesterol and elevated LDL cholesterol were similar between treatment groups. During the phase III trial, the proportions of patients with elevated total cholesterol and elevated LDL cholesterol increased in those treated with CBZ-CR monotherapy (total cholesterol, +14.9%; LDL cholesterol, +11.5%) but decreased after switching to ESL monotherapy in the extension study (total cholesterol, −15.3%; LDL cholesterol, −11.1%). By contrast, the proportions of patients with elevated levels of total cholesterol and LDL cholesterol remained relatively stable in those treated with ESL monotherapy during the phase III trial and extension study. These findings indicate that ESL monotherapy may be an appropriate treatment option for patients with newly diagnosed focal epilepsy who either already have, or who are at risk of developing, high levels of cholesterol, since this may reduce their likelihood of having cardiovascular and cerebrovascular diseases.

Psychiatric adverse events in three phase III trials of eslicarbazepine acetate for focal seizures.

OBJECTIVE: Eslicarbazepine acetate (ESL) is a once-daily (QD), oral anti-seizure medication for the treatment of focal (partial-onset) seizures. Here, we evaluate risk factors for the development of psychiatric treatment-emergent adverse events (TEAEs) in clinical trials of adjunctive ESL in adults with focal seizures. METHODS: This post-hoc analysis evaluated data pooled from three Phase III, randomized, double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients were randomized equally to receive placebo, ESL 400 mg (not reported here), 800 mg, or 1200 mg QD (up to 2-week titration; 12-week maintenance; optional open-label extension [OLE]). Incidences of psychiatric TEAEs were evaluated according to three separate criteria: medical history of psychiatric disorders (yes/no); baseline use of psychotropic drugs (yes/no); Montgomery-Åsberg Depression Rating Scale (MADRS) score at baseline (0-6: normal; 7-19: mild depression; 20-34: moderate depression). RESULTS: The analysis populations comprised 1251 patients for the controlled study period and 1137 patients for the 1-year OLE. Psychiatric TEAE incidence was similar between patients taking ESL and placebo in the controlled and OLE study periods and was not related to ESL dose. Psychiatric TEAEs generally occurred more frequently in patients with a medical history of psychiatric disorders, using psychotropic drugs, or with depressive symptoms than in those without a history, not using psychotropic drugs, or with no depressive symptoms. Depression and anxiety were the most frequently reported psychiatric TEAEs. SIGNIFICANCE: Overall, in clinical trials of ESL in adults with focal seizures, incidences of psychiatric events were not statistically different between patients taking ESL and placebo, were not related to ESL dose, and generally occurred more frequently in patients with baseline psychiatric symptoms or a history of psychiatric disorders. Long-term exposure to ESL was not associated with a marked increase in the incidence of psychiatric TEAEs.

Long-term therapeutic effect of eslicarbazepine acetate in children: An open-label extension of a cognition study in children aged 6-16 years.

OBJECTIVE: In Europe, eslicarbazepine acetate (ESL) is approved as adjunctive therapy for the treatment of focal seizures (FS) in children aged >6 years. In the US, ESL is approved as both monotherapy and adjunctive therapy for the treatment of FS in patients aged ≥4 years. In a phase II study of children aged 6-16 years with FS, ESL had no significant effects on attention or behavioral functioning and decreased seizure frequency during double-blind therapy and a 1-year open-label extension (OLE). This report presents data from an additional 2-year OLE of the phase II study. METHODS: Previous recipients of ESL or placebo were treated with open-label ESL (10-30 mg/kg/day, adjusted for clinical response and/or adverse events [AEs]). Safety was assessed by incidence of treatment-emergent AEs (TEAEs). Efficacy endpoints were treatment retention time and change from baseline in Clinical Global Impression-Severity (CGI-S) scale scores. RESULTS: Forty-two patients entered and 31 (73.8%) completed the 2-year OLE. Median treatment retention time was 735 (95% confidence interval 728-741) days. Seven patients (17% of total, 23% of completed) experienced ≥1 TEAE during the 2-year OLE, mostly of mild or moderate intensity. The incidence of serious TEAEs was low (n = 2; 5% of total, 6% of completed) and none were related to ESL. One child was withdrawn because of splenomegaly that was considered possibly related to ESL. The only change from baseline in CGI-S was a 0.5-point reduction in the severity of illness score. All findings were consistent across patient subgroups based on previous double-blind treatment (placebo or ESL) and patient age (6-11 or 12-16 years). CONCLUSIONS: The majority of patients remained on ESL during the 2-year OLE, and treatment efficacy was maintained. Adverse events were consistent with the known safety profile of ESL, and no new safety signals were identified.

Long-term efficacy and safety of eslicarbazepine acetate monotherapy for adults with newly diagnosed focal epilepsy: An open-label extension study.

OBJECTIVE: To assess the efficacy, safety, and tolerability of eslicarbazepine acetate (ESL) monotherapy during long-term treatment. METHODS: An open-label extension (OLE) study was conducted in adults completing a phase 3, randomized, double-blind, noninferiority trial, during which they had received monotherapy with either once-daily ESL or twice-daily controlled-release carbamazepine (CBZ-CR) for newly diagnosed focal epilepsy. In the OLE study, all patients received ESL (800-1600 mg/d) for 2 years. Primary efficacy outcome was retention time (from baseline of the OLE study). Secondary efficacy assessments included seizure freedom rate (no seizures during the OLE study) and responder rate (≥50% seizure frequency reduction from baseline of double-blind trial). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs). RESULTS: Of 206 randomized patients, 96 who received ESL in the double-blind trial (ESL/ESL) and 88 who received CBZ-CR in the double-blind trial (CBZ-CR/ESL) were treated with ESL monotherapy (89.3% overall). Treatment retention time was similar between groups, with low probability of ESL withdrawal overall (<0.07 at any time). After 24 months, the probability of ESL withdrawal was 0.0638 (95% confidence interval [CI] = 0.0292-0.1366) in the ESL/ESL group and 0.0472 (95% CI = 0.0180-0.1210) in the CBZ-CR/ESL group. Seizure freedom rates were 90.6% (ESL/ESL) and 80.7% (CBZ-CR/ESL; P = .0531). Responder rates remained >80% in both groups throughout the study. Incidence of serious TEAEs was similar between groups (7.3% vs 5.7%; 0% vs 1.1% possibly related), as were the incidences of TEAEs considered at least possibly related to treatment (17.7% vs 18.2%) and TEAEs leading to discontinuation (3.1% vs 4.5%). The types of TEAEs were generally consistent with the known safety profile of ESL. SIGNIFICANCE: ESL monotherapy was efficacious and generally well tolerated over the long term, including in patients who transitioned from CBZ-CR monotherapy. No new safety concerns emerged.

Cross-cultural adaptation and validation of the European Portuguese version of the heartland forgiveness scale.

BACKGROUND: Forgiveness is linked with well-being, and social and health research has focused on the role and aspects of forgiveness that has been recently suggested as a phenomenon of public health importance. The Heartland Forgiveness Scale (HFS) was developed gathering three subscales to assess the forgiveness of others, forgiveness of self, and forgiveness of situation. The present study aimed to adapt the HFS into European Portuguese, and investigate its reliability and validity. METHODS: Translation and cross-cultural adaptation were conducted using a multistep forward-back translation process. Internal consistency was assessed by Cronbach's alpha. Confirmatory factor analysis was conducted to verify that the factor structure is the same as in the original HFS. The short version of the Ruminative Response Scale (RRS) and the Satisfaction with Life Scale (SWLS) were used to examine convergent validity. RESULTS: A sample of 222 university students, selected through convenience sampling, was used to access the validity of the European Portuguese version of the HFS (EPHFS). Cronbach's alpha for the European Portuguese HFS subscales were 0.777, 0.814 and 0.816 for Self, Others and Situation, respectively, indicating acceptable reliability. The 3-factor model of the original HFS was replicated in confirmatory factor analysis. As expected by evidence in the literature, positive and statistically significant correlations were found between SWLS and HFS and subscales. RRS showed negative and statistically significant correlations with HFS and subscales. CONCLUSIONS: The European Portuguese version of the HFS presented acceptable internal consistency, construct validity and confirmed the three-factor structure of the original HFS.

Safety, Tolerability and Efficacy of Eslicarbazepine Acetate as Adjunctive Therapy in Patients Aged ≥ 65 Years with Focal Seizures.

BACKGROUND: The incidence of epilepsy is high within the first few years of life, stabilizes over the second through fifth decades, and then rises again. Treatment of elderly patients with antiepileptic drugs (AEDs) is complicated by increased sensitivity to drug effects, altered pharmacokinetics and an increased risk for drug interactions due to polytherapy. On the other hand, the safety and efficacy data of AEDs attained during clinical development programmes are relatively limited for this age group. OBJECTIVE: The aim of this study was to evaluate the safety, tolerability and efficacy of eslicarbazepine acetate (ESL) as adjunctive therapy in patients aged ≥ 65 years with focal-onset seizures (FOS). METHODS: This was an international, multicentre, open-label, non-controlled, single-arm, post-European approval commitment study with flexible doses of ESL between 400 and 1200 mg/day. Seventy-two elderly patients with at least two FOS in the prior 4 weeks, and treated with one or two AEDs, were enrolled. The study consisted of an 8-week baseline, followed by a 26-week treatment period during which the investigator was allowed to up- or down-titrate the ESL dose, and a 4-week follow-up period. Safety and tolerability were assessed as well as mental sedation, cognitive mental state and suicidal ideation. Efficacy was assessed based on patient diaries regarding the absolute and relative changes in seizure frequency, change in intellectual impairment and quality of life. RESULTS: Overall, 47 (65.3%) patients experienced 152 treatment-emergent adverse events (TEAEs). The most frequent were dizziness (12.5%), somnolence (9.7%), fatigue, convulsion and hyponatraemia (8.3% each). All patients that experienced hyponatraemia (6/72) recovered without sequelae. Three patients died during the study (due to cardiac failure, glioblastoma multiforme and ischaemic stroke, all considered unrelated to ESL). Overall, 16 (22.2%) patients discontinued prematurely due to TEAEs. The incidences of clinically significant findings were low for vital signs, ECG, physical and neurological examinations. No TEAEs of hypothyroidism were reported; however, 24 (33.3%) patients presented post-baseline shifts from normal to decreased free T4 levels (not clinically significant). ESL decreased standardized seizure frequency from a mean of 4.8 seizures at baseline to 3.6 seizures at endpoint (p > 0.05); and mean number of days with seizures significantly decreased from 4.1 (baseline) to 2.8 at endpoint (p = 0.0408). CONCLUSION: ESL taken once daily (400-1200 mg) as adjunctive therapy in patients aged ≥ 65 years was found to be safe, well tolerated and efficacious (EudraCT number: 2009-012587-14).

Rotavirus gastroenteritis in children in 4 regions in Brazil: a hospital-based surveillance study.

BACKGROUND: Rotavirus is a major cause of gastroenteritis in children. Knowledge of rotavirus genotypes is important for vaccination strategies. METHODS: During 2005-2006, rotavirus surveillance studies were conducted in São Paulo, Salvador, Goiânia, and Porto Alegre, Brazil. Stool samples were collected from children <5 years of age who had diarrhea and were screened by the Rotaclone Enzyme Immunoassay for the presence of rotavirus. Confirmed rotavirus-positive samples were characterized for P and G genotypes by reverse-transcriptase polymerase chain reaction. RESULTS: A total of 510 stool samples were collected. Of these, 221 (43.3%) were positive for rotavirus. Overall, G9 was the predominant G type, followed by G2, and G1; P[4] and P[8] were the predominant P types. The most frequent G/P genotype combination detected was G2P[4], followed by G9P[8], G9P[4], and G1P[8]. G2P[4] was the predominant type in Goiânia and Salvador; G9P[8] and G1P[8] were predominant in São Paulo and Porto Alegre, respectively. CONCLUSIONS: The prevalence, seasonality, and genotype distribution of rotavirus infection varied in different regions in Brazil. With immunization programs, continuous monitoring of rotavirus types is important to detect novel and emerging strains.

The effects of prayer, relaxation technique during general anesthesia on recovery outcomes following cardiac surgery.

During general anesthesia the possibility of subconscious perception of intraoperative events is a controversial subject. Some studies found that positive verbal suggestions, or music improved intraoperative relaxation and postoperative recovery. The aim of the current study was to evaluate the effect of prayer and relaxation technique applied while patients are under general anesthesia for open-heart surgery. A randomized, controlled, double-blind trial study included 78 patients who underwent cardiac surgery. During the surgery the patients used a headphone connected to a CD player. They were randomly divided into three groups. One group listened to prayer during the surgery, the other listened to relaxation technique and one, placebo. There was only one significant finding: the prayer group is less likely to believe that prayer would assist conventional medical treatments. Although not statistically significant, we discussed the length of stay (LOS) after surgery and the incidence of sternal wound infection.

Capilaroscopia periungueal: proposiçäo de uma nova metodologia e aplicaçäo em indivíduos hígidos e portadores de enfermidades reumáticas / Periungual capillaroscopy: proposition of a new method and aplication in healthy individuals and bearing of rheumatic diseases

A capilaroscopia periungueal (CPU) é um método que visa a observaçäo direta da rede microvascular periungueal. Essa rede pode ser de alguns processos mórbidos, especialmente no campo da Reumatologia. Apesar de ter sido anteriormente estudada, foi Maricq que reconheceu e firmou definitivamente a utilidade da abordagem panorâmica, bem como sua aplicaçäo nas doenças reumáticas. O objetivo deste trabalho é demonstrar uma metodologia de interpretaçäo dos achados capilaroscópicos que sejam abrangente, reprodutível e objetiva. Foram compilados os vários pârametros que traduzem os fenômenos capilaroscópicos, sendo entäo selecionados os mais interessantes. Foi testada a reprodutibilidade de cada parâmetro e aqueles considerados confiáveis foram estudados frente a uma populaçäo normal. Aplicou-se esta metodologia também em uma série de indivíduos com diversas doenças reumáticas, objetivando definir e dimensionar a intensidade do quadro microangiopático em cada enfermidade. Utilizando-se um estereomicroscópio, foram examinados 800 indivíduos hígidos, sendo que em 50 desses, escolhidos ao acaso, o exame foi repetido em outra ocasiäo para se testar a reprodutibilidade. Além disso, o exame foi realizado em 210 pacientes reumáticos, com diferentes diagnósticos, sendo estes firmados pelos critérios da Associaçäo Americana de Reumatismo (ARA). A metodologia proposta permite uma avaliaçäo analítica e quantitativa de alguns dos fenômenos microangiopáticos, presentes nas colagenoses. É possível que seja útil no estudo das correlaçöes entre intensidade e/ou pecularidade do quadro capilaroscópico e variáveis clínicas, com extensäo do comprometimento visceral, prognóstico e resposta terapêutica

Estudo clínico-radiológico das manifestaçöes osteoarticulares do lúpus eritematoso sistêmico / Clinical and radiological study of osteoarticulars manifestations of systemic lupus erythematosus

O comprometimento osteoarticular no lúpus eritematoso sistêmico (LES) é a manifestaçäo mais frequente desta doença, que evolui com períodos de atividade e remissäo. Apesar da recorrência, apresenta-se sem sequelas clínicas na maioar parte dos casos. Este estudo teve por objetivo avaliar os pacientes que apresentaram quadro articular prolongado, deixando ou näo sequelas. Dentre um total de 115 pacientes lúpicos, foram estudados 21 que apresentavam evidências clínicas de sinovite crônica, atropatia deformante com presença de cistos, erosöes, reduçäo de espaço articular e osteopenia periepifisária e quatro casos de artropatia deformante isolada. Em apenas dois casos de sinovite crônica com alteraçöes radiológicas näo houve associaçäo com artropatia deformante. Necrose asséptica múltipla ocorreu em oito casos e simétrica em sete casos. A associaçäo com ouso prévio de corticosteróides foi encontrada em todos os pacientes, assim como importante atividade sistêmica da doença no período que antecedeu o diagnóstico da necrose asséptica.

Influência da bromohexine sobre os níveis de lisozima da secreçäo lacrimal, o teste de rosa bengala e os sintomas oculares na síndrome de Sjögren / Influence of bromohexine on tear lysozyme level, rose-bengal test and ocular symptoms in Sjogren's syndrome

Foram estados, em 21 pacientes portadoras de Síndrome de Sjögren primária ou secundária, a influência da bromohexine sobre os níveis de lisozima da secreçäo lacrimal, teste de rosa bengala e sintomas oculares. Realizamos estudo cego com administraçäo de placebo (um comprimido por dia) e bromohexine (um comprimido de 48 mg por dia), durante 2 períodos consecutivos de 3 semanas (21 dias), com avaliaçöes do nível de lisozima lacrimal, sintomas oculares e teste de rosa bengala no dia antecedente ao ínicio do tratamento e após o uso de placebo (22§) e de bromohexine (44§ dia). Näo houve influência estatisticamente significante da bromohexine sobre os parâmetros analisados