L’Italia degli anni Sessanta e Settanta attraverso Il Mio Fratello è Figlio Unico di Danielle Luchetti

For this project, I have chosen to study the 1970s and 80s through the movie My Brother Is An Only Child by Danielle Luchetti. The movie covers twenty years of turbulent Italian history, focusing also on the human and emotional relationships between the two brothers. This movie acts as a “laboratory” to analyze the people’s behavior in a specific context of crisis and opposition

Napoleon in Deutschland

My paper is a detailed look at the effects of the Napoleonic Invasion of Germany and how the ideas of democracy and liberty from the French Revolution were ‘exported’ to Germany through Napoleon. In ‘Napoleon in Deutschland’ I pursued to connect the historic events during the Napoleonic Occupation in Germany and the present of German Unity. Additionally, I explored how the ideals of the French Revolution such as Democracy and Liberty were ironically brought to Germany by Napoleon and his Army. Lastly, since most of the time when Napoleon is mentioned he is associated with dictatorship and oppression, I tried to portray Napoleon in this paper as the main contributor for German Unity, which as is discovered through history, was never easy. Thanks to Napoleon, Germans united to fight against his oppression and driven by a growing nationalism finally formed the ground basis for the modern Germany

Tolerability, safety, and efficacy of adjunctive brivaracetam for focal seizures in older patients: A pooled analysis from three phase III studies

Introduction: This analysis was conducted to assess the tolerability, safety, and efficacy of brivaracetam (BRV) for adjunctive treatment of focal (partial-onset) seizures in patients aged ≥65 years. Methods: Safety/tolerability and efficacy data for patients aged ≥65 years were pooled from three randomized, double-blind, placebo-controlled, fixed-dose Phase III studies (NCT00490035, NCT00464269, and NCT01261325). Data were pooled by treatment group: placebo or the proposed therapeutic dose range of 50–200 mg/day: BRV 50, 100, 200 mg/day. Results: Thirty-two patients aged ≥65 years were randomized to placebo or BRV 50–200 mg/day. Of these, 30 patients (93.8%) completed their respective study. In the safety population (n = 32), 87.5% placebo- vs 73.3% BRV-treated patients reported treatment-emergent adverse events (TEAEs) during the treatment period; most commonly, headache (25.0% vs 12.5%), paresthesia (0% vs 12.5%), and somnolence (50.0% vs 12.5%) for placebo- vs BRV-treated patients, respectively. During the treatment period, drug-related TEAEs were reported by 62.5% of placebo- vs 53.3% of BRV-treated patients, and serious TEAEs (SAEs) were reported by 0% of placebo- and 4.2% of BRV-treated patients; there were no drug-related SAEs and no deaths. Three SAEs (placebo 1/8; BRV 2/24) and two deaths (placebo 1/8; BRV 1/24) occurred in the post-treatment period. In the efficacy population (n = 31), median percent reduction from baseline in focal seizure frequency/28 days was 14.0% for placebo vs 25.5%, 49.6%, and 74.9% for BRV 50, 100, and 200 mg/day, respectively. The ≥50% responder rate was 14.3% for placebo vs 25.0%, 50.0%, and 66.7% for BRV 50, 100, and 200 mg/day, respectively. Conclusions: Safety/tolerability and efficacy findings in this small subgroup of older patients treated with adjunctive BRV are consistent with those observed in the much larger overall pooled population. BRV may be a suitable adjunctive treatment for older patients with uncontrolled focal seizures. Further larger studies in this population are warranted

Efficacy and tolerability of adjunctive brivaracetam in patients with prior antiepileptic drug exposure: A post-hoc study.

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV at enrollment were excluded from this analysis. Patients were categorized by their status of prior exposure to LEV, carbamazepine (CBZ), topiramate (TPM), or lamotrigine (LTG), to investigate any consistent trend towards reduced response in AED-exposed subgroups compared to AED-naïve subgroups, regardless of the mechanism of action. Study completion rates, percent reduction from baseline in focal seizure frequency over placebo, ≥50% responder rates, and tolerability were evaluated for each subgroup. A total of 1160 patients were investigated. Study completion rates were similar in the AED-exposed subgroups and AED-naïve subgroups. In subgroups with (531 patients) or without (629 patients) prior LEV exposure, ≥50% responder rates for each dose of BRV compared with placebo were generally higher among the LEV-naïve subgroups than the previously LEV-exposed subgroups. LEV-exposed subgroups receiving BRV doses ≥50mg/day showed greater ≥50% responder rates than those receiving placebo. Similar results were observed for CBZ, TPM, and LTG. Previous treatment failure with commonly prescribed AEDs (LEV, CBZ, TPM, or LTG) is associated with a reduced response to BRV irrespective of the mechanism of action. Hence, this post-hoc analysis indicates that previous treatment failure with LEV does not preclude the use of BRV in patients with epilepsy

Efficacy, safety, and tolerability of adjunctive brivaracetam for secondarily generalized tonic-clonic seizures: Pooled results from three Phase III studies

AbstractPurposeSecondarily generalized tonic-clonic seizures (SGTCS) are among the most devastating types of seizures, contributing to increased morbidity and mortality. Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle 2A (SV2A), has been shown to be useful for the adjunctive treatment of focal seizures. We sought to determine its specific efficacy in treating SGTCS.MethodsData were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1⿿2 antiepileptic drugs (AEDs) who received placebo or BRV 50⿿200mg/day without titration over a 12-week treatment period. We report efficacy and safety/tolerability data for the BRV therapeutic dose range (50⿿200 mg/day) in patients with focal seizures including baseline SGTCS.ResultsPatients (efficacy population, N=409) had been diagnosed with epilepsy for a mean±standard deviation duration of 22.2±13.1years. Baseline median SGTCS frequency was 3.0 per 28days. The majority (293, 71.6%) had failed ⿥2 AEDs prior to study enrollment. The median percent reduction from baseline in SGTCS frequency/28days was: placebo, 33.3%; BRV 50mg/day, 66.6% (p<0.001); BRV 100mg/day, 61.2% (p=0.002); and BRV 200mg/day, 82.1% (p<0.001). The ⿥50% responder rate for SGTCS was: placebo, 33.0%; BRV 50mg/day, 61.3% (p=0.003); BRV 100mg/day, 55.0% (p<0.001); and BRV 200mg/day, 64.0% (p<0.001). Freedom from SGTCS was achieved by: placebo, 14.8%; BRV 50mg/day, 22.6%; BRV 100mg/day, 31.0%; and BRV 200mg/day, 36.0% of patients. Time to first SGTCS during the treatment period was longer in patients receiving BRV than placebo (26days vs 8days, hazard ratio 0.55, p<0.001). In the SGTCS safety population (N=487), treatment-emergent adverse events (TEAEs) were reported by 60.6% of patients receiving placebo vs 65.0% of patients receiving BRV ⿥50mg/day. Serious TEAEs were reported by 3.1% placebo vs 3.9% BRV ⿥50mg/day. Discontinuations due to TEAEs were 3.9% placebo vs 6.3% BRV ⿥50mg/day.ConclusionsIn patients with drug-resistant focal seizures, adjunctive BRV is effective in reducing the frequency of SGTCS. Almost one-third (30.4%) of patients were rendered completely free of SGTCS during the 12-week treatment period when taking BRV ⿥50mg/day. BRV was well tolerated, with a TEAE profile consistent with that of the overall study population

2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19

We demonstrate a designed scaffold-hop approach to the discovery of 2,8-disubstituted-1,6-naphthyridine- and 4,6-disubstituted-isoquinoline-based dual CDK8/19 ligands. Optimized compounds in both series exhibited rapid aldehyde oxidase-mediated metabolism, which could be abrogated by introduction of an amino substituent at C5 of the 1,6-naphthyridine scaffold or at C1 of the isoquinoline scaffold. Compounds 51 and 59 were progressed to in vivo pharmacokinetic studies, and 51 also demonstrated sustained inhibition of STAT1SER727 phosphorylation, a biomarker of CDK8 inhibition, in an SW620 colorectal carcinoma human tumor xenograft model following oral dosing

Visión de la neurología colombiana desde el exterior

Siempre tenemos que recordar la dimensión y repercusión social de la enfermedad neurológica. Es fundamental poder hacer cada vez más medicina preventiva. Nuestra sociedad no está preparada para la enfermedad, y mucho menos para las importantes repercusiones socioeconómicas. Las enfermedades neurológicas, por su presentación clínica, en ocasiones catastróficas, representan muchas veces la pérdida de la autonomía personal y por ende ocasionan dependencia, afectando la calidad de vida del paciente y de su familia, siendo el neurólogo uno de los especialistas que vive con mayor cercanía las incapacidades físicas y psíquicas y sus consecuencias sociales

Efficacy and safety of brivaracetam for partial-onset seizures in 3 pooled clinical studies

Objective: To assess the efficacy, safety, and tolerability of adjunctive brivaracetam (BRV), a selective, high-affinity ligand for SV2A, for treatment of partial-onset (focal) seizures (POS) in adults. Methods: Data were pooled from patients (aged 16–80 years) with POS uncontrolled by 1 to 2 antiepileptic drugs receiving BRV 50, 100, or 200 mg/d or placebo, without titration, in 3 phase III studies of BRV (NCT00490035, NCT00464269, and NCT01261325, ClinicalTrials.gov, funded by UCB Pharma). The studies had an 8-week baseline and a 12-week treatment period. Patients receiving concomitant levetiracetam were excluded from the efficacy pool. Results: In the efficacy population (n 5 1,160), reduction over placebo (95% confidence interval) in baseline-adjusted POS frequency/28 days was 19.5% (8.0%–29.6%) for 50 mg/d (p 5 0.0015), 24.4% (16.8%–31.2%) for 100 mg/d (p , 0.00001), and 24.0% (15.3%–31.8%) for 200 mg/d (p , 0.00001). The $50$5% patients taking BRV (vs placebo) were somnolence (15.2% vs 8.5%), dizziness (11.2% vs 7.2%), headache (9.6% vs 10.2%), and fatigue (8.7% vs 3.7%). Conclusions: Adjunctive BRV was effective and generally well tolerated in adults with POS. Classification of evidence: This analysis provides Class I evidence that adjunctive BRV is effective in reducing POS frequency in adults with epilepsy and uncontrolled seizures