Adherence to Direct Oral Anticoagulants in Patients With Non-Valvular Atrial Fibrillation: A Cross-National Comparison in Six European Countries (2008-2015).

Aims: To describe and compare the adherence to different direct oral anticoagulants (DOACs) in eight European databases representing six countries. Methods: Longitudinal drug utilization study of new users (≥18 years) of DOACs (dabigatran, rivaroxaban, apixaban) with a diagnosis of non-valvular atrial fibrillation (2008-2015). Adherence was examined by estimating persistence, switching, and discontinuation rates at 12 months. Primary non-adherence was estimated in BIFAP and SIDIAP databases. Results: The highest persistence rate was seen for apixaban in the CPRD database (81%) and the lowest for dabigatran in the Mondriaan database (22%). The switching rate for all DOACs ranged from 2.4 to 13.1% (Mondriaan and EGB databases, respectively). Dabigatran had the highest switching rate from 5.0 to 20.0% (Mondriaan and EGB databases, respectively). The discontinuation rate for all DOACs ranged from 16.0 to 63.9% (CPRD and Bavarian CD databases, respectively). Dabigatran had the highest rate of discontinuers, except in the Bavarian CD and AOK NORDWEST databases, ranging from 23.2 to 64.6% (CPRD and Mondriaan databases, respectively). Combined primary non-adherence for examined DOACs was 11.1% in BIFAP and 14.0% in SIDIAP. There were differences in population coverage and in the type of drug data source among the databases. Conclusion: Despite the differences in the characteristics of the databases and in demographic and baseline characteristics of the included population that could explain some of the observed discrepancies, we can observe a similar pattern throughout the databases. Apixaban was the DOAC with the highest persistence. Dabigatran had the highest proportion of discontinuers and switchers at 12 months in most databases (EMA/2015/27/PH).

Orofacial granulomatosis--a 20-year review.

Orofacial granulomatosis (OFG) is the presence of persistent enlargement of the soft tissues of the oral and maxillofacial region, characterized by non-caseating granulomatous inflammation in the absence of diagnosable systemic Crohn's disease (CD) or sarcoidosis. Over 20 years have passed since OFG was first described and an extensive review of the literature reveals that there is no consensus whether OFG is a distinct clinical disorder or an initial presentation of CD or sarcoidosis. Furthermore, the precise cause of OFG is still unknown although several theories have been suggested including infection, genetic predisposition and allergy. The clinical outcome of OFG patients continues to be unpredictable. Current therapies remain unsatisfactory. Regular clinical review is indicated to identify the development of gastrointestinal or systemic involvement. The aim of this review was to analyse the developments in our understanding of the aetiology, pathogenesis and treatment protocols, with particular emphasis on management and outcomes of OFG since this entity was first described in 1985.

Localization of TGF-Bs and perlecan in mouse skull development.

Post-natal growth of the skull vault occurs by the addition of new bone at the margins of individual calvarial bones. Continued growth depends on the maintenance of a proliferating osteogenic precursor cell population in the sutural membrane between the bones. Mutations in fibroblast growth factor receptors (FGFRs) have recently been detected as the cause of a number of human abnormalities characterized by premature sutural closure, i.e., craniosynostosis. These are activating mutations causing early differentiation of osteogenic precursor cells. Transforming growth factor-betas (TGF-Bs) are another family of developmentally important growth factors. In particular, they play important roles in bone differentiation and are known to be expressed in cranial sutures, and to be upregulated at the time of sutural fusion. It is therefore clear that the FGF and TGF-B signalling pathways interact co-operatively in calvarial bone growth and sutural fusion. The purpose of this study is to investigate this interaction. The long term aim of this work is to gain information that can be used to slow down the process of craniosynostosis after detection of this problem at birth.

Comparison of cervicovertebral dimensions in Australian Aborigines and Caucasians.

Cervicovertebral dimensions were compared in a group of 30 male and 30 female young adult Australian Aborigines from the Northern Territory, and a control sample consisting of 60 Caucasian dental students from Adelaide, matched for sex and age. Thirty-six variables, 22 cervical and 14 craniofacial, were derived from standardized lateral roentgenograms with the use of a computerized cephalometric system. Vertebral body height and length were significantly greater in Aboriginal males than females for C3 to C7, while dorsal arch height of C1 and C2 displayed the greatest dimensional variability in both sexes. The antero-posterior length of C1, dens height, and body heights of C3 and C4 were significantly shorter in Aborigines than Caucasians for both males and females. Total length of the column from C2 to C6 was approximately 12 per cent shorter in the Aborigines compared with Caucasians. The height of the posterior arch of C1 was significantly correlated with one or both posterior cranial base lengths in Aborigines and Caucasians. Associations were also noted between mandibular lengths and posterior arch heights of the upper two vertebrae. The results confirm and clarify several previous observations on the relative shortness of the cervical spine in Australian Aboriginals. They also indicate some associations between dimensions of the cervical vertebrae and craniofacial lengths, particularly those representing the posterior cranial base and the mandible.

No increase in blood-brain barrier permeability after intraperitoneal injection of endotoxin in the rat.

Reactions mediated by the brain are part of the response to intraperitoneal administration of endotoxin, a model of gram-negative bacterial infection. To test the hypothesis that a compromised blood-brain barrier (BBB) may contribute to these reactions, the integrity of the BBB was measured following lipopolysaccharide administration. Rats received intraperitoneal injections of 50 microg/kg or 2 mg/kg of endotoxin. Brain uptake of a macromolecular vascular marker, 3H-labelled rat serum albumin, and of a poorly permeable low molecular weight substance, [14C]sucrose, was then measured with the intravenous bolus injection method. Compared to controls, neither dose of endotoxin affected the BBB permeability for these tracers. This was true when brain uptake was measured 5 min or 2 h after lipopolysaccharide injection. It is concluded that intraperitoneal endotoxin even at a high dose does not acutely disrupt the BBB.

Leiurotoxin I (scyllatoxin), a peptide ligand for Ca2(+)-activated K+ channels. Chemical synthesis, radiolabeling, and receptor characterization.

Leiurotoxin I (scyllatoxin) is a 31-amino acid polypeptide from the venom of the scorpion Leiurus quinquestriatus hebraeus which has been previously isolated and sequenced by others. This paper reports (i) the total synthesis of this scorpion neurotoxin as well as some aspects of its structure-function relationships; (ii) the synthesis of the analog [Tyr2]leiurotoxin I (scyllatoxin) that has been monoiodinated at high specific radioactivity (2000 Ci/mmol) and has served for the characterization of the properties of 125I-[Tyr2]leiurotoxin I binding sites (Kd = 80 pM, molecular mass of 27 and 57 kDa for two polypeptides in the leiurotoxin I binding protein); (iii) the similarity of physiological actions between leiurotoxin I and apamin. Both toxins contract Taenia coli previously relaxed with epinephrine, both toxins block the after-hyperpolarization due to Ca2(+)-activated K+ channel activity in muscle cells in culture; (iv) the probable identity of binding sites for apamin and leiurotoxin I. In spite of a different chemical structure apamin competitively inhibits 125I-[Tyr2] leiurotoxin I binding and vice versa. Moreover, the peculiar effects of K+ on 125I-[Tyr2]leiurotoxin I binding are identical to those previously observed for 125I-apamin binding.

[Unilateral hematoma of the adrenal gland. Review of the literature. A case report]. / Hématome unilatéral de la surrénale. Revue de la littérature. A propos d'une observation.

The authors report one case of post-traumatic hematic pseudocyst of the right adrenal demonstrated with magnetic resonance imaging. Total adrenalectomy was performed; the clinicopathological examination confirms the absence of any underlying tumoral process and allows the hypothesis that stress was a fostering factor. After a review of the literature noting that the risk of hemorrhagic recurrence is underestimated, while the number of underlying cancers is small and easily detected since imaging of the adrenals has been refined, the authors discuss the procedure of treatment and the technical aspects of surgery for the hematomas confined to the adrenal space: surgical exeresis is proposed as a rule, but this should be qualified, as a medical alternative can be justified provided the causal affection disappears and a strict observation with computed tomography or magnetic resonance imaging is ensured.

Epidemiology of Cryptococcus neoformans.

The concept of the epidemiology of Cryptococcus neoformans as the causative agent of cryptococcosis and as a basidiomycetous yeast is based on the fact that bird manure has been until now its only known habitat but not plant material which likewise harbours various nonpathogenic Cryptococcus species. It could be shown that the possible influence of nutritional factors on the morphology and morphogenesis earns attention not only in view of the epidemiology of C. neoformans but of its perfect states, too.