Efficacy and Safety of Canakinumab Vs Triamcinolone Acetonide in Patients with Gouty Arthritis Unable to Use Nonsteroidal Anti-Inflammatory Drugs and Colchicine, and On Stable Urate Lowering Therapy (ULT) or Unable to Use ULT

Background/Purpose: The primary treatment goals for gouty arthritis (GA) are rapid relief of pain and inflammation during acute attacks, and long-term hyperuricemia management. A post-hoc analysis of 2 pivotal trials was performed to assess efficacy and safety of canakinumab (CAN), a fully human monoclonal anti-IL-1_ antibody, vs triamcinolone acetonide (TA) in GA patients unable to use NSAIDs and colchicine, and who were on stable urate lowering therapy (ULT) or unable to use ULT. Methods: In these 12-week, randomized, multicenter, double-blind, double-dummy, active-controlled studies (_-RELIEVED and _-RELIEVED II), patients had to have frequent attacks (_3 attacks in previous year) meeting preliminary GA ACR 1977 criteria, and were unresponsive, intolerant, or contraindicated to NSAIDs and/or colchicine, and if on ULT, ULT was stable. Patients were randomized during an acute attack to single dose CAN 150 mg s.c. or TA 40 mg i.m. and were redosed "on demand" for each new attack. Patients completing the core studies were enrolled into blinded 12-week extension studies to further investigate on-demand use of CAN vs TA for new attacks. The subpopulation selected for this post-hoc analysis was (a) unable to use NSAIDs and colchicine due to contraindication, intolerance or lack of efficacy for these drugs, and (b) currently on ULT, or contraindication or previous failure of ULT, as determined by investigators. Subpopulation comprised 101 patients (51 CAN; 50 TA) out of 454 total. Results: Several co-morbidities, including hypertension (56%), obesity (56%), diabetes (18%), and ischemic heart disease (13%) were reported in 90% of this subpopulation. Pain intensity (VAS 100 mm scale) was comparable between CAN and TA treatment groups at baseline (least-square [LS] mean 74.6 and 74.4 mm, respectively). A significantly lower pain score was reported with CAN vs TA at 72 hours post dose (1st co-primary endpoint on baseline flare; LS mean, 23.5 vs 33.6 mm; difference _10.2 mm; 95% CI, _19.9, _0.4; P_0.0208 [1-sided]). CAN significantly reduced risk for their first new attacks by 61% vs TA (HR 0.39; 95% CI, 0.17-0.91, P_0.0151 [1-sided]) for the first 12 weeks (2nd co-primary endpoint), and by 61% vs TA (HR 0.39; 95% CI, 0.19-0.79, P_0.0047 [1-sided]) over 24 weeks. Serum urate levels increased for CAN vs TA with mean change from baseline reaching a maximum of _0.7 _ 2.0 vs _0.1 _ 1.8 mg/dL at 8 weeks, and _0.3 _ 2.0 vs _0.2 _ 1.4 mg/dL at end of study (all had GA attack at baseline). Adverse Events (AEs) were reported in 33 (66%) CAN and 24 (47.1%) TA patients. Infections and infestations were the most common AEs, reported in 10 (20%) and 5 (10%) patients treated with CAN and TA respectively. Incidence of SAEs was comparable between CAN (gastritis, gastroenteritis, chronic renal failure) and TA (aortic valve incompetence, cardiomyopathy, aortic stenosis, diarrohea, nausea, vomiting, bicuspid aortic valve) groups (2 [4.0%] vs 2 [3.9%]). Conclusion: CAN provided superior pain relief and reduced risk of new attack in highly-comorbid GA patients unable to use NSAIDs and colchicine, and who were currently on stable ULT or unable to use ULT. The safety profile in this post-hoc subpopulation was consistent with the overall _-RELIEVED and _-RELIEVED II population.

Factors influencing Intensive Care Units nurses in end-of-life decisions

OBJECTIVETo identify the factors that influence the Intensive Care Unit nurse in the decision-making process in end-of-life situations.METHODEthnographic case study, which used the theoretical framework of medical anthropology. Data were collected through semi-structured interviews with 10 nurses.RESULTSThe inductive thematic analysis enabled us to identify four themes:The cultural context of the Intensive Care Unit: decision-making in situations of end-of-life; Beliefs and subjectivity of care in end-of-life situations; Professional experience and context characteristics of end-of-life care situations; and Humanization practices in end-of-life situations: the patient and family centered care.CONCLUSIONProfessional maturity, the ability to transmit information and the ability to negotiate are directly related to the inclusion of nurses in the decision-making process.

Post-axial polydactyly type A2, overgrowth and autistic traits associated with a chromosome 13q31.3 microduplication encompassing miR-17-92 and GPC5.

Genomic rearrangements at chromosome 13q31.3q32.1 have been associated with digital anomalies, dysmorphic features, and variable degree of mental disability. Microdeletions leading to haploinsufficiency of miR17∼92, a cluster of micro RNA genes closely linked to GPC5 in both mouse and human genomes, has recently been associated with digital anomalies in the Feingold like syndrome. Here, we report on a boy with familial dominant post-axial polydactyly (PAP) type A, overgrowth, significant facial dysmorphisms and autistic traits who carries the smallest germline microduplication known so far in that region. The microduplication encompasses the whole miR17∼92 cluster and the first 5 exons of GPC5. This report supports the newly recognized role of miR17∼92 gene dosage in digital developmental anomalies, and suggests a possible role of GPC5 in growth regulation and in cognitive development.

Implementing the intermed in a post-acute care rehabilitation clinic for traumatic injuries: Obstacles and benefits

In 2003, the INTERMED, an instrument to assess biopsycho- social case complexity and to direct care, was introduced in daily clinical practice in the .Clinique romande de réadaptation suvaCare., a national rehabilitation hospital for traumatic injuries, located in the French speaking part of Switzerland. The introduction of the INTERMED was easy to realize and no major obstacles hampered its systematic implementation. Up to now, about 2,000 patients have been evaluated with the INTERMED and are followed for different outcomes. The INTERMED improved not only patients. assessment by including relevant psychosocial aspects of the clinical situation, it also favoured interdisciplinary communication, enhanced work satisfaction of the nursing staff and allowed early identification and adaptation of treatment for the injured patient showing a high degree of case complexity. Upon follow up, patients with a high degree of case-complexity showed a less favourable outcome, i.e. more health care utilization and lower rates of return to work. In conclusion, the systematic implementation of the INTERMED enabled the reorganization of medical rehabilitation, anchored it in a bio-psycho-social framework, improving interdisciplinary communication and collaboration and ameliorated treatment outcome.

Completing contracts ex post: How car manufacturers manage car dealers

This article illustrates how contracts are completed ex post in practice and, in so doing, indirectly suggests what the real function of contracts may be. Our evidence comes from the contracts between automobile manufacturers and their dealers in 23 dealership networks in Spain. Franchising dominates automobile distribution because of the need to decentralize pricing and control of service decisions. It motivates local managers to undertake these activities at minimum cost for the manufacturer. However, it creates incentive conflicts, both between manufacturers and dealers and among dealers themselves, concerning the level of sales and service provided. It also holds potential for expropriation of specific investments. Contracts deal with these conflicts by restricting dealers decision rights and granting manufacturers extensive completion, monitoring and enforcement powers. The main mechanism that may prevent abuse of these powers is the manufacturers reputational capital.

Le syndrome post-thrombotique, préparation d'une étude clinique

Intro. Le syndrome post-thrombotique (SPT) est la complication chronique la plus fréquente après une thrombose veineuse profonde (TVP). Syndrome peu connu, malgré une prévalence de 20-50%, il se caractérise par des symptômes d'insuffisance veineuse chronique apparaissant après une TVP. L'utilisation de bas de compression graduée (BCG) diminue de moitié le risque de développer un SPT. Mais un problème de faible compliance est souvent un obstacle dans la prise en charge. Le but principal de cette étude sera de déterminer le lien entre l'adhérence au BCG et le développement de SPT Méthode. Il s'agit d'une étude cas-témoin, mono-centrique, avec inclusion prospective et consécutive des patients avec une TVP. Les patients recrutés recevront un traitement standard pour une TVP (anticoagulation thérapeutique pendant 3 mois et BCG pour une durée d'un an) et seront suivis sur une année avec 4 visites médicales (V0-V3) et 10 entretiens téléphoniques (I1-I10). A la fin de l'étude, sur la base de l'adhérence au port du BCG, les patients seront divisés en deux groupes: bonne adhérence au traitement (cas) et faible adhérence (témoin). Conclusion. Il est certain que ce sujet a besoin de recherches pour mieux comprendre le développement, trouver une prévention et des traitements efficaces et acceptables afin d'améliorer leur qualité de vie des patients.

Study of the combined radial post-feeding dispersion of the blowflies Chrysomya megacephala (Fabricius) and C. albiceps (Wiedemann) (Diptera, Calliphoridae)

Blowflies use discrete and ephemeral substrates to feed their larvae. After they run out of food, the larvae begin to disperse in order to find adequate places for pupation or additional food sources, a process named post-feeding larval dispersion. Some important aspects of this process were studied in a circular arena allowing the combined radial post-feeding dispersion from the center of the arena of C. albiceps and C. megacephala larvae. To determine the location of each pupa, the arena was divided in 72 identical sections starting from the center. The distance from the center, the depth and weight of each pupa were evaluated. Statistical tests were done to verify the relation between weight, depth and distance for pupation. From the total an average of 976 larvae released (488 for each species) were collected considering both experiments 456 C. megacephala pupae and 488 of C. albiceps. This demonstrates that C. albiceps probably preyed on 32 C. megacephala larvae during post-feeding dispersion. The study of this dispersion process can be used to estimate the postmortem interval (PMI) of human cadavers in legal medicine.

Plastic brain mechanisms for attaining auditory temporal order judgment proficiency.

Accurate perception of the order of occurrence of sensory information is critical for the building up of coherent representations of the external world from ongoing flows of sensory inputs. While some psychophysical evidence reports that performance on temporal perception can improve, the underlying neural mechanisms remain unresolved. Using electrical neuroimaging analyses of auditory evoked potentials (AEPs), we identified the brain dynamics and mechanism supporting improvements in auditory temporal order judgment (TOJ) during the course of the first vs. latter half of the experiment. Training-induced changes in brain activity were first evident 43-76 ms post stimulus onset and followed from topographic, rather than pure strength, AEP modulations. Improvements in auditory TOJ accuracy thus followed from changes in the configuration of the underlying brain networks during the initial stages of sensory processing. Source estimations revealed an increase in the lateralization of initially bilateral posterior sylvian region (PSR) responses at the beginning of the experiment to left-hemisphere dominance at its end. Further supporting the critical role of left and right PSR in auditory TOJ proficiency, as the experiment progressed, responses in the left and right PSR went from being correlated to un-correlated. These collective findings provide insights on the neurophysiologic mechanism and plasticity of temporal processing of sounds and are consistent with models based on spike timing dependent plasticity.

Relationship Between the Development of the Spinal Canal and the Etiopathogenesis of Lumbar Spinal Stenosis

INTRODUCTION: The presence of a pre-existing narrow spinal canal may have an important place in the ethiopathogenesis of lumbar spinal stenosis. By consequence the study of the development of the spinal canal is crucial. The first goal of this work is to do a comprehensive literature search and to give an essential view on the development of spinal canal and its depending factors studied until now. The second goal is to give some considerations and hypothesize new leads for clinically useful researches. MATERIALS AND METHODS: A bibliographical research was executed using different search engines: PubMed, Google Schoolar ©, Ovid ® and Web Of Science ©. Free sources and avaible from the University of Lausanne (UNIL) and Centre Hospitalier Universitaire Vaudois (CHUV) were used. At the end of the bibliographic researches 114 references were found, 85 were free access and just 41 were cited in this work. Most of the found references are in English or in French. RESULTS AND DISCUSSION: The spinal canal is principally limited by the vertebrae which have a mesodermal origin. The nervous (ectodermal) tissue significantly influences the growth of the canal. The most important structure participating in the spinal canal growth is the neurocentral synchondrosis in almost the entire vertebral column. The fusion of the half posterior arches seems to have less importance for the canal size. The growth is not homogeneous but, depends on the vertebral level. Timing, rate and growth potentials differ by regions. Especially in the case of the lumbar segment, there is a craniocaudal tendency which entails a greater post-natal catch-up growth for distal vertebrae. Trefoil-shape of the L5 canal is the consequence of a sagittal growth deficiency. The spinal canal shares some developmental characteristics with different structures and systems, especially with the central nervous system. It may be the consequence of the embryological origin. It is supposed that not all the related structures would be affected by a growth impairment because of the different catch-up potentials. Studies found that narrower spinal canals might be related with cardiovascular and gastrointestinal symptoms, lower thymic function, bone mineral content, dental hypoplasia and Harris' lines. Anthropometric correlations found at birth disappear during the pediatric age. All factors which can affect bone and nervous growth might be relevant. Genetic predispositions are the only factors that can never be changed but the real impact is to ascertain. During the antenatal period, all the elements determining a good supply of blood and oxygen may influence the vertebral canal development, for example smoking during pregnancy. Diet is a crucial factor having an impact on both antenatal and postnatal growth. Proteins intake is the only proved dietetic relationship found in the bibliographic research of this work. The mechanical effects due to locomotion changes are unknown. Socioeconomic situation has an impact on several influencing factors and it is difficult to study it owing to numerous bias. CONCLUSIONS: A correct growth of spinal canal is evidently relevant to prevent not-degenerative stenotic conditions. But a "congenital" narrower canal may aggravate degenerative stenosis. This concerns specific groups of patient. If the size of the canal is highly involved in the pathogenesis of common back pains, a hypothetical measure to prevent developmental impairments could have a not- negligible impact on the society. It would be interesting to study more about dietetic necessities for a good spinal canal development. Understanding the relationship between nervous tissues and vertebra it might be useful in identifying what is needed for the ideal development. Genetic importance and the post-natal influences of upright standing on the canal growth remain unsolved questions. All these tracks may have a double purpose: knowing if it is possible to decrease the incidence of narrower spinal canal and consequently finding possible preventive measures. The development of vertebral canal is a complex subject which ranges over a wide variety of fields. The knowledge of this subject is an indispensable tool to understand and hypothesize the influencing factors that might lead to stenotic conditions. Unfortunately, a lack of information makes difficult to have a complete and satisfactory interdisciplinary vision.