Testing rimegepant for migraine—time to revise the trial design?

n/

Positivity to p-ANCA in patients with status epilepticus

BACKGROUND: Status epilepticus (SE) may occur in the setting of several internal or neurologic diseases. Anti-neutrophilic cytoplasmic antibodies (ANCA) are a group of Ig that may be observed in patients with different autoimmune disorders but are particularly associated with systemic vasculitis named ANCA-associated-vasculities (AAV). We herein report 3 patients with SE and positivity to p-ANCA. CASE PRESENTATION: One patient had a catastrophic evolution and died 5 months after disease onset. The other two patients had a good outcome and remained seizure-free at 30 months and 5 years of follow-up respectively. CONCLUSION: This report highlights the importance of considering ANCA dosage in patients with SE of unclear origin

Involvement of fractalkine and macrophage inflammatory protein-1 alpha in moderate-severe depression.

Moderate-severe depression (MSD) is linked to overexpression of proinflammatory cytokines and chemokines. Fractalkine (FKN) and macrophage inflammatory protein-1 alpha (MIP-1alpha) are, respectively, members of CX3C and C-C chemokines, and both are involved in recruiting and activating mononuclear phagocytes in the central nervous system. We analysed the presence of FKN and MIP-1alpha in sera of untreated MSD patients and healthy donors. High FKN levels were observed in all MSD patients as compared with values only detectable in 26% of healthy donors. MIP-1alpha was measurable in 20% of patients, while no healthy donors showed detectable chemokine levels. In conclusion, we describe a previously unknown involvement of FKN in the pathogenesis of MSD, suggesting that FKN may represent a target for a specific immune therapy of this disease

Brivaracetam as Early Add-On Treatment in Patients with Focal Seizures: A Retrospective, Multicenter, Real-World Study

Introduction In randomized controlled trials, add-on brivaracetam (BRV) reduced seizure frequency in patients with drug-resistant focal epilepsy. Most real-world research on BRV has focused on refractory epilepsy. The aim of this analysis was to assess the 12-month effectiveness and tolerability of adjunctive BRV when used as early or late adjunctive treatment in patients included in the BRIVAracetam add-on First Italian netwoRk Study (BRIVAFIRST). Methods BRIVAFIRST was a 12-month retrospective, multicenter study including adult patients prescribed adjunctive BRV. Effectiveness outcomes included the rates of sustained seizure response, sustained seizure freedom, and treatment discontinuation. Safety and tolerability outcomes included the rate of treatment discontinuation due to adverse events (AEs) and the incidence of AEs. Data were compared for patients treated with add-on BRV after 1-2 (early add-on) and >= 3 (late add-on) prior antiseizure medications. Results A total of 1029 patients with focal epilepsy were included in the study, of whom 176 (17.1%) received BRV as early add-on treatment. The median daily dose of BRV at 12 months was 125 (100-200) mg in the early add-on group and 200 (100-200) in the late add-on group (p < 0.001). Sustained seizure response was reached by 97/161 (60.3%) of patients in the early add-on group and 286/833 (34.3%) of patients in the late add-on group (p < 0.001). Sustained seizure freedom was achieved by 51/161 (31.7%) of patients in the early add-on group and 91/833 (10.9%) of patients in the late add-on group (p < 0.001). During the 1-year study period, 29 (16.5%) patients in the early add-on group and 241 (28.3%) in the late add-on group discontinued BRV (p = 0.001). Adverse events were reported by 38.7% and 28.5% (p = 0.017) of patients who received BRV as early and late add-on treatment, respectively. Conclusion Brivaracetam was effective and well tolerated both as first add-on and late adjunctive treatment in patients with focal epilepsy

Alterations in the α2 δ ligand, thrombospondin-1, in a rat model of spontaneous absence epilepsy and in patients with idiopathic/genetic generalized epilepsies

Objectives Thrombospondins, which are known to interact with the α2δ subunit of voltage-sensitive calcium channels to stimulate the formation of excitatory synapses, have recently been implicated in the process of epileptogenesis. No studies have been so far performed on thrombospondins in models of absence epilepsy. We examined whether expression of the gene encoding for thrombospondin-1 was altered in the brain of WAG/Rij rats, which model absence epilepsy in humans. In addition, we examined the frequency of genetic variants of THBS1 in a large cohort of children affected by idiopathic/genetic generalized epilepsies (IGE/GGEs). Methods We measured the transcripts of thrombospondin-1 and α2δ subunit, and protein levels of α2δ, Rab3A, and the vesicular glutamate transporter, VGLUT1, in the somatosensory cortex and ventrobasal thalamus of presymptomatic and symptomatic WAG/Rij rats and in two control strains by real-time polymerase chain reaction (PCR) and immunoblotting. We examined the genetic variants of THBS1 and CACNA2D1 in two independent cohorts of patients affected by IGE/GGE recruited through the Genetic Commission of the Italian League Against Epilepsy (LICE) and the EuroEPINOMICS-CoGIE Consortium. Results Thrombospondin-1 messenger RNA (mRNA) levels were largely reduced in the ventrobasal thalamus of both presymptomatic and symptomatic WAG/Rij rats, whereas levels in the somatosensory cortex were unchanged. VGLUT1 protein levels were also reduced in the ventrobasal thalamus of WAG/Rij rats. Genetic variants of THBS1 were significantly more frequent in patients affected by IGE/GGE than in nonepileptic controls, whereas the frequency of CACNA2D1 was unchanged. Significance These findings suggest that thrombospondin-1 may have a role in the pathogenesis of IGE/GGEs

La forme financiarisée de la relation de crédit des collectivités locales. De la crise à l’institutionnalisation

La thèse porte sur les évolutions de la relation de crédit des collectivités locales et étudie les différentes formes que celle-ci a pu prendre au cours du temps. Elle développe une approche institutionnaliste où la relation de crédit et ses transformations historiques sont saisies à partir des régulations qui encadrent, au niveau institutionnel et de manière plus ou moins lâche, la demande de crédit émanant des collectivités locales, d’une part, et l’offre de crédit des acteurs financiers, d’autre part. Tout particulièrement, sur la période récente, elle met en évidence l’émergence et l’institutionnalisation d’une « forme financiarisée », caractérisée par l’utilisation de produits financiers distribués sur les marchés financiers dans la gestion de dette des collectivités locales.The thesis focuses on the evolutions of local authorities’ credit relationship and studies the various forms it has taken over time. It develops an institutionnalist approach in which credit relationship, and its historical transformations, are captured from the regulations that frame, more or less loosely, the credit demand from local authorities on the one hand, and the credit supply of financial actors on the other. More particularly, and over the recent period, the thesis highlights the emergence and the institutionnalization of what I identify as a “financialized form”, characterized by the use of financial products, made available by financial markets, in local authorities’ debt management

Benjamin Lemoine, L’ordre de la dette. Enquête sur les infortunes de l’État et la prospérité du marché

Benjamin Lemoine propose dans cet ouvrage de mettre en cause l’évidence de la dette de l’État telle qu’elle est désormais connue, à savoir comme des titres financiers dont les taux d’intérêt s’imposent aux États. Les débats publics ne questionnent plus cette forme de financement mais véhiculent une vision pathologique de la dette qu’il faudrait réduire au plus vite. Le premier constat réalisé consiste ainsi à souligner cet écart entre une technique de financement de l’État, exclue des débats,..

Dexia, ou la faillite d’une régulation du crédit local par le marché

Caught in the torment of the 2008 and the 2011 financial crises, Dexia, the historical lender to local government, was saved from bankruptcy by the Belgian and French states late in 2011. The paper looks back on the genesis of this rescue by developing an historical and institutionalist perspective of changes in local government borrowing and its regulation by the state. It sheds light on the changeover from administered regulation – where central government as from the 1950s strictly shaped supply and demand for credit in its own interest – to market-based regulation – when the state withdrew from local government lending in the 1980s. Once state-controlled, Dexia was privatized in 1993 and embarked on a strategy directed at the financial markets. That strategy collapsed in 2008, requiring state intervention of last resort to avoid contagion spreading to the financial system and a credit crunch for local government. Having created market-based regulation of local government borrowing in the 1980s, it was left to the state to “foot the bill” for the excesses of market regulation

The financialized form of the French local authorities' credit relationship. From the crisis to institutionnalization.

La thèse porte sur les évolutions de la relation de crédit des collectivités locales et étudie différentes formes que celle-ci a pu prendre au cours du temps. Tout particulièrement, sur la période récente, nous mettons en évidence l’émergence et l’institutionnalisation de ce que nous identifions comme une « forme financiarisée », caractérisée par l’utilisation de produits financiers distribués sur les marchés financiers dans la gestion de dette des collectivités locales. Nous développons une approche institutionnaliste où la relation de crédit, et ses transformations historiques, sont saisies à partir des régulations qui encadrent, de manière plus ou moins lâche, la demande de crédit émanant des collectivités locales, d’une part, et l’offre de crédit des acteurs financiers, d’autre part. Nous cherchons notamment à rendre compte de la manière dont les interactions entre demande et offre de crédit sont conditionnées et en partie déterminées au niveau institutionnel. Deux types de pratiques d’emprunts que nous qualifions de financiarisés sont au centre de ce travail : l’emprunt structuré et l’emprunt obligataire. Nous suivons le développement à partir des années 1990 des produits structurés qui seront au centre de la crise des emprunts dits « toxiques », ainsi que les formes de gestion puis de sortie de cette crise (2004-2015). Sur la même période, des émissions obligataires groupées de collectivités locales sont développées et vont déboucher sur la création de l’Agence France Locale (AFL), dont nous suivons la structuration (2004-2018). Nous montrons que la période d’incertitude qui s’ouvre à compter de la crise financière de 2008 contribue paradoxalement à la poursuite et l’institutionnalisation du recours, pour les collectivités locales, à des produits faisant appel aux marchés et investisseurs financiers. Ce résultat n’était pas écrit dans la mesure où la crise des emprunts toxiques nourrit une vive critique d’une forme financiarisée qui s’était développée « par le bas » dans un contexte de libéralisation financière pour le prêt aux collectivités locales et de décentralisation. Le moment de réflexion institutionnelle, qui s’ouvre avec la crise, conduit les acteurs à tenter de dissocier la « mauvaise » finance de la « bonne » pour mieux pouvoir continuer à recourir à des formes d’emprunt financiarisées. L’enquête par entretiens (n= 61) et la collecte d’une abondante littérature grise se sont organisées principalement autour du décryptage des outils de gestion, dispositifs de gestion de crise et réglementations qui structurent la relation de crédit. Nous les décodons sous l’angle des conventions qu’ils incorporent et des présupposés qu’ils rendent légitimes, ce qui nous permet d’en souligner les effets de sélection et de disciplinarisation. En ce qui concerne l’emprunt structuré, ce travail est complété par une analyse statistique et économétrique portant sur les communes « intoxiquées » et permettant de discuter des déterminants du développement du recours à ce type d’emprunt.The thesis focuses on the evolutions of local authorities’s credit relationship and studies the various forms it has taken over time. More particularly, and over the recent period, the thesis highlights the emergence and the institutionnalization of what I identify as a “financialized form”, characterized by the use of financial products, made available by financial markets, in local authorities’debt management. The thesis develops an institutionnalist approach in which credit relationship, and its historical transformations, are captured from the regulations that frame, more or less loosely, the credit demand from local authorities on the one hand, and the credit supply of financial actors on the other. The paper aims especially to investigate the ways in which interplays between credit demand and supply are conditioned and partly determined at an institutional level. Two types of debt practices that this paper identifies as “financialized” are at the core of this work : structured debt and bond debt. The thesis follows the development, from the 1990’s onwards, of structured loans which played a key role in the ‘toxix loan crisis’, as well as the subsequent management and resolution of that crisis (2004-2015). Over the same period, local authorities’ joint bonds issues became organized and led to the creation of Agence France Locale, the structuring of which is described in this thesis (2004-2018). The period of incertainty, following the 2008 financial crisis, has seen paradoxically the continuation and the institutionnalization of the use, by local authorities, of financial products that were appealing to markets and financial investors. This result was not given insofar as the toxic loans crisis led to a strong critique of the “financialized form” (which has spread “from the bottom”, within a context of financial liberalization of local authorities’ loans and of decentralization). The post-crisis institutionnal thinking led the actors to attempt to dissociate “bad” finance from “good” finance in order to have better access to financialized forms of debt. The interview-based survey (n=61) and the collection of an abundant grey literature were organised mainly around the decoding of management tools, crisis management devices and regulations which structure local authorities’ credit relationship. The thesis decodes them from the perspective of the conventions they incorporate and the premises which make them look legitimate, and this allows us to emphasize their effects of selection and disciplining. With regard to structured loans, the research is supplemented with a statistical and econometric analysis which focused on the municipalities which have fallen intro the trap of toxic loans, which enables a discussion of the determinants in the development of this type of loan