Effectiveness and tolerability of 12-Month Brivaracetam in the real world: EXPERIENCE, an international pooled analysis of individual patient records

Background 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

Project management between will and representation

This article challenges some deep-rooted assumptions of project management. Inspired by the work of the German philosopher, Arthur Schopenhauer, it calls for looking at projects through two complementary lenses: one that accounts for cognitive and representational aspects and one that accounts for material and volitional aspects. Understanding the many ways in which these aspects transpire and interact in projects sheds new light on project organizations, as imperfect and fragile representations that chase a shifting nexus of intractable human, social, technical, and material processes. This, in turn, can bring about a new grasp of notions such as value,\ud knowledge, complexity, and risk

Tolerability and efficacy of adjunctive brivaracetam in adults with focal seizures by concomitant antiseizure medication use: Pooled results from three phase 3 trials.

This study was undertaken to evaluate safety/tolerability and efficacy of adjunctive brivaracetam (BRV) in patients on one or two concomitant antiseizure medications (ASMs) and in patients on one specific concomitant ASM. Post hoc analysis was made of double-blind trials (N01252/NCT00490035, N01253/NCT00464269, and N01358/NCT01261325) in adults with focal seizures randomized to BRV (50-200 mg/day; approved therapeutic dose range for adults) or placebo with concomitant ASM regimen unchanged throughout a 12-week evaluation period. Outcomes were analyzed in patients on one or two concomitant ASMs, and those on concomitant carbamazepine (CBZ), lamotrigine (LTG), oxcarbazepine (OXC), or valproate (VPA) only. Patients randomized to BRV with one or two concomitant ASMs, respectively (n = 181/557), reported similar incidences of treatment-emergent adverse events (TEAEs; 68.0%/66.4%), drug-related TEAEs (41.4%/41.5%), and TEAEs leading to discontinuation (6.6%/5.4%). Respective values for patients randomized to placebo with one or two concomitant ASMs (n = 95/331) were 60.0%/60.7% (TEAEs), 32.6%/30.2% (drug-related TEAEs), and 2.1%/4.5% (TEAEs leading to discontinuation). The incidences of TEAEs, drug-related TEAEs, and TEAEs leading to discontinuation by specific concomitant ASM (CBZ, LTG, OXC, VPA) were similar to the overall incidences in patients taking one concomitant ASM. In patients on one or two concomitant ASMs, respectively, 50% responder rates were numerically higher on BRV (42.3%/36.8% [n = 175/511]) versus placebo (18.3%/19.5% [n = 93/298]). Patients with one or two ASMs on BRV (n = 175/509) versus placebo (n = 92/298) also had numerically higher 100% responder rates (BRV, 9.1%/4.5%; placebo, 1.1%/.3%) and seizure freedom (6.9%/3.7%; 1.1%/0). For patients taking concomitant CBZ, LTG, OXC, or VPA, efficacy was numerically higher with BRV (n = 54/30/27/27) versus placebo (n = 34/13/10/14-15; 50% responder rates: BRV, 31.5%/30.0%/40.7%/70.4%; placebo, 17.6%/7.7%/20.0%/33.3%; 100% responder rates: BRV, 5.6%/10.0%/11.1%/11.1%; placebo, 0 for all; seizure freedom: BRV, 3.7%/6.7%/7.4%/11.1%; placebo, 0 for all). Therapeutic doses of BRV were efficacious and well tolerated regardless of the number of concomitant ASMs (one or two) or specific concomitant ASM (CBZ, LTG, OXC, VPA)

Effectiveness and tolerability of brivaracetam in patients with epilepsy stratified by comorbidities and etiology in the real world: 12-month subgroup data from the international EXPERIENCE pooled analysis

Objective To assess the effectiveness and tolerability of brivaracetam (BRV) in adults with epilepsy by specific comorbidities and epilepsy etiologies. Methods EXPERIENCE/EPD332 was a pooled analysis of individual patient records from several non-interventional studies of patients with epilepsy initiating BRV in clinical practice. Outcomes included ≥ 50% reduction from baseline in seizure frequency, seizure freedom (no seizures within prior 3 months), continuous seizure freedom (no seizures since baseline), BRV discontinuation, and treatment-emergent adverse events (TEAEs) at 3, 6, and 12 months. Analyses were performed for all adult patients (≥ 16 years of age) and stratified by comorbidity and by etiology at baseline (patients with cognitive/learning disability [CLD], psychiatric comorbidity, post-stroke epilepsy, brain tumor−related epilepsy [BTRE], and traumatic brain injury−related epilepsy [TBIE]). Results At 12 months, ≥ 50% seizure reduction was achieved in 35.6% (n = 264), 38.7% (n = 310), 41.7% (n = 24), 34.1% (n = 41), and 50.0% (n = 28) of patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, respectively; and continuous seizure freedom was achieved in 5.7% (n = 318), 13.7% (n = 424), 29.4% (n = 34), 11.4% (n = 44), and 13.8% (n = 29), respectively. During the study follow-up, in patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE, 37.1% (n = 403), 30.7% (n = 605), 33.3% (n = 51), 39.7% (n = 68), and 27.1% (n = 49) of patients discontinued BRV, respectively; and TEAEs since prior visit at 12 months were reported in 11.3% (n = 283), 10.0% (n = 410), 16.7% (n = 36), 12.5% (n = 48), and 3.0% (n = 33), respectively. Conclusions BRV as prescribed in the real world is effective and well tolerated among patients with CLD, psychiatric comorbidity, post-stroke epilepsy, BTRE, and TBIE

Programa de fertilización sustentable para plantaciones de cítricos en Tabasco, México

Abstract: Tell the Integrated fertilization (SIRDF) to generate a program for sustainable fertilization in citrus groves of the Savanna de Huimanguilo, Tabasco, Mexico System was used. To apply the SIRDF, local climate data were recorded, they determined the physical and chemical properties of soils and nutrient demand plantations Persian lime and orange Valencia 10 nutrients was estimated based on the yield potential. The fertilization rate for N, P and Κ was determined for each soil subunit of local ecological conditions. The results show that temperatures in the region are suitable for growing citrus fruits, but the low rainfall recorded from February to May is a limiting factor for the production of these crops. Acrisols and Cambisols, both with restricted supply of nutrients for growing the acrisols occupy the largest area: two groups of soils were determined. According to the SIRDF the fertilization of N, P2O5 and K2O for Persian limes are: 207-69-240 in Acrisols Distri-Hiperférricos; 207-69-300 on Acrisols plinthic Lynch; 184-69-240 on Acrisols Humi-plinthic, Acrisols Humi-umbric and Acrisols Umbri-plinthic; 230-92-300 on Acrisols Umbri-gleyic. While in Valencia orange growing the following fertilization were generated: 115-46-120 in Acrisols Distri-Hiperférricos; 138-46-180 on Acrisols plinthic Lynch, Acrisol Humi-Plinthic and Acrisol Humi-Umbric; 138-46-150 on Acrisols Lynch umbric and Acrisols Umbri-gleyic; 115-46-180 on Acrisols Gleyi-plinthic; and 115-46-150 in Acrisols Umbri-plinthic.Resumen: Se utilizó el Sistema Integrado para Recomendar Dosis de Fertilización (SIRDF) para generar un programa de fertilización sustentable en plantaciones de cítricos de la Sabana de Huimanguilo, Tabasco, México. Para aplicar el SIRDF, se obtuvieron datos climáticos locales, determinaron las propiedades físicas y químicas de los suelos, y la demanda de nutrientes del limón Persa y naranja Valencia se estimó para 10 nutrientes en función del potencial de rendimiento. La tasa de fertilización para Ν, Ρ y Κ se determinó para cada subunidad de suelo. Los resultados muestran que las temperaturas de la región son adecuadas para los cítricos, pero la escasa precipitación registrada de febrero a mayo limita la producción de estos cultivos. Se determinaron dos grupos de suelos: Acrisoles y Cambisoles, ambos con suministro restringido de nutrientes para el cultivo. De acuerdo con el SIRDF las dosis de fertilización de de N, P2O5 y K2O para limón persa son: 207-69-240 para Acrisoles Distri-Hiperférricos; 207-69-300 para Acrisoles Ferri-Plínticos; 184-69-240 para Acrisoles Humi-Plínticos, Acrisoles Humi-Úmbricos y Acrisoles Umbri-Plínticos; 23092-300 para Acrisoles Umbri-Gléyicos. Mientras que en el cultivo de naranja Valenciana se generaron las siguientes dosis de fertilización: 115-46-120 para Acrisoles Distri-Hiperférricos; 138-46-180 para Acrisoles Ferri-Plínticos, Acrisol Humi-Plíntico y Acrisol Humi-Úmbrico; 138-46-150 para Acrisoles Ferri-Úmbricos y Acrisoles Umbri-Gléyicos; 115-46180 para Acrisoles Gleyi-Plínticos; y 115-46-150 para Acrisoles Umbri-Plínticos

Switching strategic perspective : The reframing of accounts of responsibility

We provide an empirical study of the reframing of accounts of responsibility for strategy. We found that top management ambivalence about strategy provided a middle management team with wide scope for interpretation of responsibility for developing and implementing a strategic initiative. In the early stage, responsibility as well as expectations about the strategy's successful outcome were 'talked up'. In the later stage, when it was considered that the strategic initiative was failing, the middle management implementation team engaged in 'talking down' of expectations. We show that reframing from initial duty to capability to later accountability shaped and reflected actors' changing goals. By focusing on responsibility we increase understanding of the division of labour in the actual practice of strategizing, including where and how strategizing is done. Most important, we show how protagonists' goals drive the framing and reframing of strategic agendas, and how linguistic devices such as disclaimers and self-handicapping influence this process