Effectiveness and Tolerability of 12-Month Brivaracetam in the Real World: EXPERIENCE, an International Pooled Analysis of Individual Patient Records

Efectividad; Tolerabilidad; RegistrosEffectiveness; Tolerability; RecordsEficàcia; Tolerabilitat; RegistresBackground and objective: Real-world evidence studies of brivaracetam (BRV) have been restricted in scope, location, and patient numbers. The objective of this pooled analysis was to assess effectiveness and tolerability of brivaracetam (BRV) in routine practice in a large international population. Methods: EXPERIENCE/EPD332 was a pooled analysis of individual patient records from multiple independent non-interventional studies of patients with epilepsy initiating BRV in Australia, Europe, and the United States. Eligible study cohorts were identified via a literature review and engagement with country lead investigators, clinical experts, and local UCB Pharma scientific/medical teams. Included patients initiated BRV no earlier than January 2016 and no later than December 2019, and had ≥ 6 months of follow-up data. The databases for each cohort were reformatted and standardised to ensure information collected was consistent. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within 3 months before timepoint), continuous seizure freedom (no seizures from baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Patients with missing data after BRV discontinuation were considered non-responders/not seizure free. Analyses were performed for all adult patients (≥ 16 years), and for subgroups by seizure type recorded at baseline; by number of prior antiseizure medications (ASMs) at index; by use of BRV as monotherapy versus polytherapy at index; for patients who switched from levetiracetam to BRV versus patients who switched from other ASMs to BRV; and for patients with focal-onset seizures and a BRV dose of ≤ 200 mg/day used as add-on at index. Analysis populations included the full analysis set (FAS; all patients who received at least one BRV dose and had seizure type and age documented at baseline) and the modified FAS (all FAS patients who had at least one seizure recorded during baseline). The FAS was used for all outcomes other than ≥ 50% seizure reduction. All outcomes were summarised using descriptive statistics. Results: Analyses included 1644 adults. At baseline, 72.0% were 16-49 years of age and 92.2% had focal-onset seizures. Patients had a median (Q1, Q3) of 5.0 (2.0, 8.0) prior antiseizure medications at index. At 3, 6, and 12 months, respectively, ≥ 50% seizure reduction was achieved by 32.1% (n = 619), 36.7% (n = 867), and 36.9% (n = 822) of patients; seizure freedom rates were 22.4% (n = 923), 17.9% (n = 1165), and 14.9% (n = 1111); and continuous seizure freedom rates were 22.4% (n = 923), 15.7% (n = 1165), and 11.7% (n = 1111). During the whole study follow-up, 551/1639 (33.6%) patients discontinued BRV. TEAEs since prior visit were reported in 25.6% (n = 1542), 14.2% (n = 1376), and 9.3% (n = 1232) of patients at 3, 6, and 12 months, respectively. Conclusions: This pooled analysis using data from a variety of real-world settings suggests BRV is effective and well tolerated in routine clinical practice in a highly drug-resistant patient population

Understanding, tuning and using the collapse transition of thermoresponsive polymer brushes

This work focuses on the properties of surfaces grafted by responsive polymer brushes. Responsive polymer brushes are an assembly of macromolecules densely grafted from a surface, capable to respond to an external stimulus. They adapt their configuration according to external stimuli including temperature, pH or light. Responsive polymer brushes undergo dramatic variations of properties during the so-called collapse transition. In this work, the thermocollapse transition of polymer brushes from the well-swollen to the collapsed state was investigated in details, in order to describe finely the transition and exploit its specificities in a range of applications. The measurements reveal that the collapse mechanism consists first of the progressive collapse of the bulk of the brush occurring over a wide temperature range, followed by a sharp collapse of the surface occurring at a higher temperature. Reactive and carboxylic acid units were introduced along the backbone of the thermoresponsive polymer chains in order to tune the temperature of the collapse by other stimuli than temperature, such as pH or light. For instance, reactive and thermoresponsive polymer brushes were used as platforms to anchor photochromic trigger molecules in order to induce by light changes in the swelling of the polymer brushes. Furthermore, the coupling of an antibacterial peptide to a reactive and thermoresponsive polymer brush combined to the deeper knowledge of the details of the mechanism of the thermocollapse transition attained in this thesis, finally led to the fabrication of smart surfaces switching from antibacterial at room temperature to antifouling at physiological temperatures, for applications in medicine.(FSA 3) -- UCL, 201

Bidimensional Response Maps of Adaptive Thermo- and pH-Responsive Polymer Brushes

We depict the collapse transition of adaptive thermo- and pH-responsive copolymer brushes based on poly(di(ethylene glycol) methyl ether methacrylate-co-methacrylic acid) random copolymer chains (P(MEO(2)MA-co-MAA)) by drawing bidimensional (2D) maps of the swelling ratio versus temperature and pH for different brush compositions. The collapse transition is probed by quartz crystal microbalance measurements with dissipation monitoring (QCM-D). While P(MEO(2)MA) brushes exhibit a thermo-collapse transition around 22 degrees C and P(MAA) brushes display a pH-induced collapse transition at pH = 5.5, P(MEO(2)MA-co-MAA) brushes undergo a collapse transition modulated by either temperature or pH from a swollen state at low temperature and high pH to a collapsed state at high temperature and low pH. By varying the composition of the copolymer in MAA units from 4 to 14 mol %, the brushes switch from a pH-modulated thermo-responsive behavior to a temperature-modulated pH-responsive behavior in water. The 2D maps of swelling ratio also illustrate the complex interplay between pH and temperature, and provide a unique view of the response of adaptive brushes

Surface and Bulk Collapse Transitions of Thermoresponsive Polymer Brushes.

We elucidate the sequence of events occurring during the collapse transition of thermoresponsive copolymer brushes based on poly(di(ethyleneglycol) methyl ether methacrylate) chains (PMEO2MA) grown by atom-transfer radical polymerization (ATRP). The collapse of the bulk of the brush is followed by quartz crystal microbalance measurements with dissipation monitoring (QCM-D), and the collapse of its outer surface is assessed by measuring equilibrium water contact angles in the captive bubble configuration. The bulk of the brush collapses over a broad temperature interval (approximately 25 degrees C), and the end of this process is signaled by a sharp first-order transition of the surface of the brush. These observations support theoretical predictions regarding the occurrence of a vertical phase separation during collapse, with surface properties of thermoresponsive brushes exhibiting a sharp variation at a temperature of T(br)(surf). In contrast, the bulk properties of the brush vary smoothly, with a bulk transition T(br)(bulk) occurring on average approximately 8 degrees C below T(br)(surf) and approximately 5 degrees C below the lower critical solution temperature (LCST) of free chains in solution. These observations should also be valid for planar brushes of other neutral, water-soluble thermoresponsive polymers such as poly(N-isopropylacrylamide) (PNIPAM). We also propose a way to analyze more quantitatively the temperature dependence of the QCM-D response of thermoresponsive brushes and deliver a simple thermodynamic interpretation of equilibrium contact angles, which can be of use for other complex temperature-responsive solvophilic systems

Time course of attentional bias for gambling information in problem gambling.

There is a wealth of evidence showing enhanced attention toward drug-related information (i.e., attentional bias) in substance abusers. However, little is known about attentional bias in deregulated behaviors without substance use such as abnormal gambling. This study examined whether problem gamblers (PrG, as assessed through self-reported gambling-related craving and gambling dependence severity) exhibit attentional bias for gambling-related cues. Forty PrG and 35 control participants performed a change detection task using the flicker paradigm, in which two images differing in only one aspect are repeatedly flashed on the screen until the participant is able to report the changing item. In our study, the changing item was either neutral or related to gambling. Eye movements were recorded, which made it possible to measure both initial orienting of attention as well as its maintenance on gambling information. Direct (eye-movements) and indirect (change in detection latency) measures of attention in individuals with problematic gambling behaviors suggested the occurrence of both engagement and of maintenance attentional biases toward gambling-related visual cues. Compared to nonproblematic gamblers, PrG exhibited (a) faster reaction times to gambling-cues as compared to neutral cues, (b) higher percentage of initial saccades directed toward gambling pictures, and (c) an increased fixation duration and fixation count on gambling pictures. In the PrG group, measures of gambling-related attentional bias were not associated with craving for gambling and gambling dependence severity. Theoretical and clinical implications of these results are discussed

Time course of attentional bias for gambling information in problem gambling.

info:eu-repo/semantics/nonPublishe