Debulking surgery in the setting of very high-risk prostate cancer scenarios

What's known on the subject? and What does the study add? Nowadays radical prostatectomy (RP) is considered an effective treatment in high-risk prostate cancer (PCa) and the indications for a surgical approach are expanding, even in cases of very high PSA or node-positive disease. We explored the outcomes of debulking surgery in the setting of these very high-risk PCa patients, in order to assess its feasibility. This review confirms the important role achieved by surgery in the complex setting of patients with very high-risk PCA. Excellent survival rates have been reported, even when PSA exceeds 100 ng/mL. The completion of RP with lymphadenectomy might give a survival benefit in patients who were found intraoperatively to be node-positive. Furthermore, salvage RP confirmed to be the most effective treatment option after RT failure. On the contrary, up-to-date surgery of isolated nodal recurrences has shown only little benefit. Finally, there is no evidence supporting the efficacy of debulking surgery in metastatic or in hormone-refractory tumours. An accurate selection of the patient is essential.

Time Constraints in the School Environment: What Does a Sleepy Student Tell Us?

In this article, we discuss school schedules and their implications in the context of chronobiological contemporary knowledge, arguing for the need to reconsider time planning in the school setting. We present anecdotal observations regarding chronobiological challenges imposed by the school system throughout different ages and discuss the effects of these schedules in terms of sleepiness and its deleterious consequences on learning, memory, and attention. Different settings (including urban vs. rural habitats) influence timing, which also depends on self-selected sleep schedules. Finally, we criticize the traditional view of a necessary strict stability of sleep-wake habits.

The effects of clinical support surfaces on pressure as a risk factor in the development of pressure ulcers, from a radiographical perspective: a narrative literature review

Purpose: Pressure ulcers are a high cost, high volume issue for health and medical care providers, having a detrimental effect on patients and relatives. Pressure ulcer prevention is widely covered in the literature, but little has been published regarding the risk to patients in the radiographical setting. This review of the current literature is to identify findings relevant to radiographical context. Methods: Literature searching was performed using Science Direct and Medline databases. The search was limited to articles published in the last ten years to remain current and excluded studies containing participants less than 17 years of age. In total 14 studies were acquired; three were excluded as they were not relevant. The remaining 11 studies were compared and reviewed. Discussion: Eight of the studies used ‘healthy’ participants and three used symptomatic participants. Nine studies explored interface pressure with a range of pressure mat technologies, two studies measured shear (MRI finite element modelling, and a non-invasive instrument), and one looked at blood flow and haemoglobin oxygenation. A range of surfaces were considered from trauma, nursing and surgical backgrounds for their ability to reduce pressure including standard mattresses, high specification mattresses, rigid and soft layer spine boards, various overlays (gel, air filled, foam). Conclusion: The current literature is not appropriate for the radiographic patient and cannot be extrapolated to a radiologic context. Sufficient evidence is presented in this review to support the need for further work specific to radiography in order to minimise the development of PU in at risk patients.

On the analytical solutions of the Hindmarsh-Rose neuronal model

In this article we analytically solve the Hindmarsh-Rose model (Proc R Soc Lond B221:87-102, 1984) by means of a technique developed for strongly nonlinear problems-the step homotopy analysis method. This analytical algorithm, based on a modification of the standard homotopy analysis method, allows us to obtain a one-parameter family of explicit series solutions for the studied neuronal model. The Hindmarsh-Rose system represents a paradigmatic example of models developed to qualitatively reproduce the electrical activity of cell membranes. By using the homotopy solutions, we investigate the dynamical effect of two chosen biologically meaningful bifurcation parameters: the injected current I and the parameter r, representing the ratio of time scales between spiking (fast dynamics) and resting (slow dynamics). The auxiliary parameter involved in the analytical method provides us with an elegant way to ensure convergent series solutions of the neuronal model. Our analytical results are found to be in excellent agreement with the numerical simulations.

Biotyping, serotyping and ribotyping as epidemiological tools in the evaluation of Acinetobacter baumannii dissemination in hospital units, Sorocaba, São Paulo, Brazil

Dissemination of Acinetobacter baumannii strains in different units of a hospital in Sorocaba, São Paulo, Brazil was evaluated over a period of two years. By using biotyping, serotyping and ribotyping, 27 distinct clones were differentiated among 76 strains isolated between 1993-94, from clinical specimens of hospitalized patients. Two clones, 2:O4:A (biotype:serotype:ribotype) and 2:O29:A accounted for the majority of strains widely disseminated in the units during 1993. The introduction in the hospital setting, of a new clone, 6:O13:B, at the end of 1993 and its predominance through 1994 is discussed. Among 15 strains isolated from neonates, 6 (40%) belonged to the same clone, 2:O4:A. Interestingly, this clone was almost all recovered in neonatal intensive care unit, nursery and in pediatric unit. All strains were susceptible to imipenem and polymyxcin B. Multiresistant strains (up to 12 antimicrobial agents) accounted for 66.7% and 84.8% of the strains isolated in 1993 and in 1994, respectively.

Influence of the wood mechanical properties in the dovetail joint behavior

The force distribution inside a dovetail joint is complex. Wood is simultaneously loaded in different directions in the several connected surfaces. The analytical solutions available for the analysis of the behavior of those carpentry joints rely on the mechanical properties of wood. In particular, the stiffness properties of wood under compression are crucial for the forces equilibrium. Simulations showed that the stiffness values considered in each of the springs normally assumed in the analytical models, have great influence in the bearing capacity and stiffness of the dovetail joints, with important consequence on the stress distribution over the overall structure. In a wide experimental campaign, the properties under compression of the most common wood species of existing timber structures have been determined. Then, a solved example of a dovetail joint is presented assuming different wood species and the corresponding strength and stiffness properties values obtained in the tests.

La prévention du suicide en milieu scolaire est-elle possible [Is it possible to run suicide prevention interventions within the school setting?]

Suicide represent the second cause of death in Switzerland and, between 15 and 20 years of age, 8% of girls and 4% of boys have attempted suicide at least once in their life. "Universal" primary prevention in schools is usually run through courses dealing with the issue of suicide and which are systematically provided to all pupils. There is no evidence that they have any positive effect and even they may be in some instances harmful. The training of professionals working in the school setting to better identify and refer adolescents facing risky situation is probably effective. Another promising approach is the one which aims at improving the school climate in increasing social connectedness and the pupils' life skills. Finally, the school which faces a suicide should set up debriefing activities, thus deterring vulnerable pupils to engage in violent acting as a result of a contamination process.

Services standardization in the United-States and in Europe: an institutional analysis of private authority

This contribution explores the role of international standards in the rules governing the internationalisation of the service economy. It analyses on a cross-institutional basis patterns of authority in the institutional setting of service standards in the European and Amercian context. The entry into force of the World Trade Organisation (WTO) in 1995 gave international standards a major role in harmonising the technical specifications of goods and services traded on the global market Despite the careful wording of the WTO, a whole range of international bodies still have the capacity to define generic as well as detailed technical specifications affecting how swelling offshore services are expected to be traded on worldwide basis. The analysis relies on global political economy approaches to identify constitutive patterns of authority mediating between the political and the economic spheres on a transnational space. It extends to the area of service standards the assumption that the process of globalisation is not opposing states and markets, but a joint expression of both of them including new patterns and agents of structural change through formal and informal power and regulatory practices. The paper argues that service standards reflect the significant development of a form of transnational hybrid authority, that blurs the distinction between private and public actors, whose scope spread all along from physical measures to societal values, and which reinforces the deterritorialisation of regulatory practices in contemporary capitalism. It provides evidence of this argument by analysing the current European strategy regarding service standardization in response to several programming mandate of the European Commission and the American views on the future development of service standards.

Behaviour evaluation for risk-taking adolescents (BERTA): an easy to use and assess instrument to detect adolescent risky behaviours in a clinical setting.

To create an instrument to be used in an outpatient clinic to detect adolescents prone to risk-taking behaviours. Based on previous research, five identified variables (relationship with parents and teachers, liking going to school, average grades, and level of religiosity) were used to create a screening tool to detect at least one of ten risky behaviours (tobacco, alcohol, cannabis and other illegal drugs use; sexual intercourse and sexual risky behaviour; driving while intoxicated, riding with an intoxicated driver, not always using a seat belt, and not always using a helmet). The instrument was tested using the Barcelona Adolescent Health Survey 1993. A Receiver Operating Characteristics curve was used to find the best cut-off point between high and low risk score. Odds ratios and 95% confidence intervals were calculated to detect at least one risky behaviour and for each individual behaviour. In order to assess its predictive value, the analysis was repeated using the Barcelona Adolescent Health Survey 1999. In both cases, analyses were conducted for the whole sample and for younger and older adolescents. Adolescents with a high-risk score were more likely to take at least one risky behaviour both when the whole sample was analysed and by age groups. With very few exceptions, the Behaviour Evaluation for Risk-Taking Adolescents showed significant odds ratios for each individual variable. CONCLUSION: The Behaviour Evaluation for Risk-Taking Adolescents has shown its potential as an easy to use instrument to screen for risk-taking behaviours. Future research must aim towards assessing this instrument's predictive value in the clinical setting and it's application to other populations.

Beyond the Transatlantic Divide: The Multiple Authorities of Standards in the Global Political Economy of Services

This paper explores the plurality of institutional environments in which standards for the service sector are expected to support the rise of a global knowledge-based economy. Despite the careful wording of the World Trade Organization (WTO), a whole range of international bodies still have the capacity to define technical specifications affecting how services are expected to be traded on worldwide basis. The analysis relies on global political economy approaches to extend to the area of service standards the assumption that the process of globalization is not opposing states and markets, but a joint expression of both of them including new patterns and agents of structural change through formal and informal power and regulatory practices. It analyses on a cross-institutional basis patterns of authority in the institutional setting of service standards in the context of the International Organisation for Standardisation (ISO), the European Union, and the United States. In contrast to conventional views opposing the American system to the ISO/European framework, the paper questions the robustness of this opposition by showing that institutional developments of service standards are likely to face trade-offs and compromises across those systems and between two opposing models of standardisation.

Interrogation of related clinical pan-azole-resistant Aspergillus fumigatus strains: G138C, Y431C, and G434C single nucleotide polymorphisms in cyp51A, upregulation of cyp51A, and integration and activation of transposon Atf1 in the cyp51A promoter.

Multiple Aspergillus fumigatus isolates from a patient with two aspergillomas complicating chronic pulmonary aspergillosis were pan-azole resistant. Microsatellite typing was identical for all isolates despite major phenotypic and some growth rate differences. Three different cyp51A mutations were found (G138C, Y431C, and G434C), of which the first two were demonstrated by heterologous expression in a hypersusceptible Saccharomyces cerevisiae strain to be at least partly responsible for elevated MICs. cyp51A and cyp51B gene duplication was excluded, but increased expression of cyp51A was demonstrated in three isolates selected for additional study (7-to 13-fold increases). In the isolate with the greatest cyp51A expression, an Aft1 transposon was found inserted 370 bp upstream of the start codon of the cyp51A gene, an integration location never previously demonstrated in Aspergillus. Two transcription start sites were identified at 49 and 136 bp upstream of the start codon. The role of the Aft1 transposon, if any, in modulating cyp51A expression remains to be established. Increased mRNA expression of the transporters AfuMDR1 and AfuMDR4 also was demonstrated in some isolates, which could contribute to azole resistance or simply represent a stress response. The diversity of confirmed and possible azole resistance mechanisms demonstrated in a single series of isogenic isolates is remarkable, indicating the ability of A. fumigatus to adapt in the clinical setting.

Application of low temperature thermochronology to understanding cooling and exhumation in the Central Swiss Alps

THESIS ABSTRACT : Low-temperature thermochronology relies on application of radioisotopic systems whose closure temperatures are below temperatures at which the dated phases are formed. In that sense, the results are interpreted as "cooling ages" in contrast to "formation ages". Owing to the low closure-temperatures, it is possible to reconstruct exhumation and cooling paths of rocks during their residence at shallow levels of the crust, i.e. within first ~10 km of depth. Processes occurring at these shallow depths such as final exhumation, faulting and relief formation are fundamental for evolution of the mountain belts. This thesis aims at reconstructing the tectono-thermal history of the Aar massif in the Central Swiss Alps by means of zircon (U-Th)/He, apatite (U-Th)/He and apatite fission track thermochronology. The strategy involved acquisition of a large number of samples from a wide range of elevations in the deeply incised Lötschen valley and a nearby NEAT tunnel. This unique location allowed to precisely constrain timing, amount and mechanisms of exhumation of the main orographic feature of the Central Alps, evaluate the role of topography on the thermochronological record and test the impact of hydrothermal activity. Samples were collected from altitudes ranging between 650 and 3930 m and were grouped into five vertical profiles on the surface and one horizontal in the tunnel. Where possible, all three radiometric systems were applied to each sample. Zircon (U-Th)/He ages range from 5.1 to 9.4 Ma and are generally positively correlated with altitude. Age-elevation plots reveal a distinct break in slope, which translates into exhumation rate increasing from ~0.4 to ~3 km/Ma at 6 Ma. This acceleration is independently confirmed by increased cooling rates on the order of 100°C/Ma constrained on the basis of age differences between the zircon (U-Th)/He and the remaining systems. Apatite fission track data also plot on a steep age-elevation curve indicating rapid exhumation until the end of the Miocene. The 6 Ma event is interpreted as reflecting tectonically driven uplift of the Aar massif. The late Miocene timing implies that the increase of precipitation in the Pliocene did not trigger rapid exhumation in the Aar massif. The Messinian salinity crisis in the Mediterranean could not directly intensify erosion of the Aar but associated erosional output from the entire Alps may have tapered the orogenic wedge and caused reactivation of thrusting in the Aar massif. The high exhumation rates in the Messinian were followed by a decrease to ~1.3 km/Ma as evidenced by ~8 km of exhumation during last 6 Ma. The slowing of exhumation is also apparent from apatite (U-Th)1He age-elevation data in the northern part of the Lötschen valley where they plot on a ~0.5km/Ma line and range from 2.4 to 6.4 Ma However, from the apatite (U-Th)/He and fission track data from the NEAT tunnel, there is an indication of a perturbation of the record. The apatite ages are youngest under the axis of the valley, in contrast to an expected pattern where they would be youngest in the deepest sections of the tunnel due to heat advection into ridges. The valley however, developed in relatively soft schists while the ridges are built of solid granitoids. In line with hydrological observations from the tunnel, we suggest that the relatively permeable rocks under the valley floor, served as conduits of geothermal fluids that caused reheating leading to partial Helium loss and fission track annealing in apatites. In consequence, apatite ages from the lowermost samples are too young and the calculated exhumation rates may underestimate true values. This study demonstrated that high-density sampling is indispensable to provide meaningful thermochronological data in the Alpine setting. The multi-system approach allows verifying plausibility of the data and highlighting sources of perturbation. RÉSUMÉ DE THÈSE : La thermochronologie de basse température dépend de l'utilisation de systèmes radiométriques dont la température de fermeture est nettement inférieure à la température de cristallisation du minéral. Les résultats obtenus sont par conséquent interprétés comme des âges de refroidissement qui diffèrent des âges de formation obtenus par le biais d'autres systèmes de datation. Grâce aux températures de refroidissement basses, il est aisé de reconstruire les chemins de refroidissement et d'exhumation des roches lors de leur résidence dans la croute superficielle (jusqu'à 10 km). Les processus qui entrent en jeu à ces faibles profondeurs tels que l'exhumation finale, la fracturation et le faillage ainsi que la formation du relief sont fondamentaux dans l'évolution des chaînes de montagne. Ces dernières années, il est devenu clair que l'enregistrement thermochronologique dans les orogènes peut être influencé par le relief et réinitialisé par l'advection de la chaleur liée à la circulation de fluides géothermaux après le refroidissement initial. L'objectif de cette thèse est de reconstruire l'histoire tectono-thermique du massif de l'Aar dans les Alpes suisses Centrales à l'aide de trois thermochronomètres; (U-Th)/He sur zircon, (U-Th)/He sur apatite et les traces de fission sur apatite. Afin d'atteindre cet objectif, nous avons récolté un grand nombre d'échantillons provenant de différentes altitudes dans la vallée fortement incisée de Lötschental ainsi que du tunnel de NEAT. Cette stratégie d'échantillonnage nous a permis de contraindre de manière précise la chronologie, les quantités et les mécanismes d'exhumation de cette zone des Alpes Centrales, d'évaluer le rôle de la topographie sur l'enregistrement thermochronologique et de tester l'impact de l'hydrothermalisme sur les géochronomètres. Les échantillons ont été prélevés à des altitudes comprises entre 650 et 3930m selon 5 profils verticaux en surface et un dans le tunnel. Quand cela à été possible, les trois systèmes radiométriques ont été appliqués aux échantillons. Les âges (U-Th)\He obtenus sur zircons sont compris entre 5.l et 9.4 Ma et sont corrélés de manière positive avec l'altitude. Les graphiques représentant l'âge et l'élévation montrent une nette rupture de la pente qui traduisent un accroissement de la vitesse d'exhumation de 0.4 à 3 km\Ma il y a 6 Ma. Cette accélération de l'exhumation est confirmée par les vitesses de refroidissement de l'ordre de 100°C\Ma obtenus à partir des différents âges sur zircons et à partir des autres systèmes géochronologiques. Les données obtenues par traces de fission sur apatite nous indiquent également une exhumation rapide jusqu'à la fin du Miocène. Nous interprétons cet évènement à 6 Ma comme étant lié à l'uplift tectonique du massif de l'Aar. Le fait que cet évènement soit tardi-miocène implique qu'une augmentation des précipitations au Pliocène n'a pas engendré cette exhumation rapide du massif de l'Aar. La crise Messinienne de la mer méditerranée n'a pas pu avoir une incidence directe sur l'érosion du massif de l'Aar mais l'érosion associée à ce phénomène à pu réduire le coin orogénique alpin et causer la réactivation des chevauchements du massif de l'Aar. L'exhumation rapide Miocène a été suivie pas une diminution des taux d'exhumation lors des derniers 6 Ma (jusqu'à 1.3 km\Ma). Cependant, les âges (U-Th)\He sur apatite ainsi que les traces de fission sur apatite des échantillons du tunnel enregistrent une perturbation de l'enregistrement décrit ci-dessus. Les âges obtenus sur les apatites sont sensiblement plus jeunes sous l'axe de la vallée en comparaison du profil d'âges attendus. En effet, on attendrait des âges plus jeunes sous les parties les plus profondes du tunnel à cause de l'advection de la chaleur dans les flancs de la vallée. La vallée est creusée dans des schistes alors que les flancs de celle-ci sont constitués de granitoïdes plus durs. En accord avec les observations hydrologiques du tunnel, nous suggérons que la perméabilité élevée des roches sous l'axe de la vallée à permi l'infiltration de fluides géothermaux qui a généré un réchauffement des roches. Ce réchauffement aurait donc induit une perte d'Hélium et un recuit des traces de fission dans les apatites. Ceci résulterait en un rajeunissement des âges apatite et en une sous-estimation des vitesses d'exhumation sous l'axe de la vallée. Cette étude à servi à démontrer la nécessité d'un échantillonnage fin et précis afin d'apporter des données thermochronologiques de qualité dans le contexte alpin. Cette approche multi-système nous a permi de contrôler la pertinence des données acquises ainsi que d'identifier les sources possibles d'erreurs lors d'études thermochronologiques. RÉSUMÉ LARGE PUBLIC Lors d'une orogenèse, les roches subissent un cycle comprenant une subduction, de la déformation, du métamorphisme et, finalement, un retour à la surface (ou exhumation). L'exhumation résulte de la déformation au sein de la zone de collision, menant à un raccourcissement et un apaissessement de l'édifice rocheux, qui se traduit par une remontée des roches, création d'une topographie et érosion. Puisque l'érosion agit comme un racloir sur la partie supérieure de l'édifice, des tentatives de corrélation entre les épisodes d'exhumation rapide et les périodes d'érosion intensive, dues aux changements climatiques, ont été effectuées. La connaissance de la chronologie et du lieu précis est d'une importance capitale pour une quelconque reconstruction de l'évolution d'une chaîne de montagne. Ces critères sont donnés par un retraçage des changements de la température de la roche en fonction du temps, nous donnant le taux de refroidissement. L'instant auquel les roches ont refroidit, passant une certaine température, est contraint par l'application de techniques de datation par radiométrie. Ces méthodes reposent sur la désintégration des isotopes radiogéniques, tels que l'uranium et le potassium, tous deux abondants dans les roches de la croûte terrestre. Les produits de cette désintégration ne sont pas retenus dans les minéraux hôtes jusqu'au moment du refroidissement de la roche sous une température appelée 'de fermeture' , spécifique à chaque système de datation. Par exemple, la désintégration radioactive des atomes d'uranium et de thorium produit des atomes d'hélium qui s'échappent d'un cristal de zircon à des températures supérieures à 200°C. En mesurant la teneur en uranium-parent, l'hélium accumulé et en connaissant le taux de désintégration, il est possible de calculer à quel moment la roche échantillonnée est passée sous la température de 200°C. Si le gradient géothermal est connu, les températures de fermeture peuvent être converties en profondeurs actuelles (p. ex. 200°C ≈ 7km), et le taux de refroidissement en taux d'exhumation. De plus, en datant par système radiométrique des échantillons espacés verticalement, il est possible de contraindre directement le taux d'exhumation de la section échantillonnée en observant les différences d'âges entre des échantillons voisins. Dans les Alpes suisses, le massif de l'Aar forme une structure orographique majeure. Avec des altitudes supérieures à 4000m et un relief spectaculaire de plus de 2000m, le massif domine la partie centrale de la chaîne de montagne. Les roches aujourd'hui exposées à la surface ont été enfouies à plus de 10 km de profond il y a 20 Ma, mais la topographie actuelle du massif de l'Aar semble surtout s'être développée par un soulèvement actif depuis quelques millions d'années, c'est-à-dire depuis le Néogène supérieur. Cette période comprend un changement climatique soudain ayant touché l'Europe il y a environ 5 Ma et qui a occasionné de fortes précipitations, entraînant certainement une augmentation de l'érosion et accélérant l'exhumation des Alpes. Dans cette étude, nous avons employé le système de datation (U-TH)/He sur zircon, dont la température de fermeture de 200°C est suffisamment basse pour caractériser l'exhumation du Néogène sup. /Pliocène. Les échantillons proviennent du Lötschental et du tunnel ferroviaire le plus profond du monde (NEAT) situé dans la partie ouest du massif de l'Aar. Considérés dans l'ensemble, ces échantillons se répartissent sur un dénivelé de 3000m et des âges de 5.1 à 9.4 Ma. Les échantillons d'altitude supérieure (et donc plus vieux) documentent un taux d'exhumation de 0.4 km/Ma jusqu'à il y a 6 Ma, alors que les échantillons situés les plus bas ont des âges similaires allant de 6 à 5.4 Ma, donnant un taux jusqu'à 3km /Ma. Ces données montrent une accélération dramatique de l'exhumation du massif de l'Aar il y a 6 Ma. L'exhumation miocène sup. du massif prédate donc le changement climatique Pliocène. Cependant, lors de la crise de salinité d'il y a 6-5.3 Ma (Messinien), le niveau de la mer Méditerranée est descendu de 3km. Un tel abaissement de la surface d'érosion peut avoir accéléré l'exhumation des Alpes, mais le bassin sud alpin était trop loin du massif de l'Aar pour influencer son érosion. Nous arrivons à la conclusion que la datation (U-Th)/He permet de contraindre précisément la chronologie et l'exhumation du massif de l'Aar. Concernant la dualité tectonique-érosion, nous suggérons que, dans le cas du massif de l'Aar, la tectonique prédomine.

The efficacy of amoxycillin/clavulanate (Augmentin) in the treatment of severe staphylococcal infections.

The experimental and clinical values of amoxycillin/clavulanate in severe Staphylococcus aureus infections are reviewed. Experimentally, amoxycillin/clavulanate was highly effective in the treatment of acute endocarditis due to methicillin-sensitive isolates of S. aureus (MSSA) in rats. In addition, high doses of amoxycillin/clavulanate also cured experimental endocarditis due to methicillin-resistant strains of S. aureus (MRSA) in the animal model. In the clinical setting, a review of 86 patients with either community- or hospital-acquired bacteraemia due to MSSA showed that intravenous treatment with amoxycillin/clavulanate was adequate for empirical (and apparently also long-term) therapy of such severe infections. However, the retrospective nature of the analysis did not allow assessment of the relative efficacy of amoxycillin/clavulanate as compared with standard anti-staphylococcal drugs, such as flucloxacillin or vancomycin. Further prospective studies are warranted to address this issue. Thus, amoxycillin/clavulanate appears to be a good candidate for empirical treatment of severe infections that may be caused by MSSA. Usage of amoxycillin/clavulanate against MRSA is, however, still experimental and is not currently advocated for the treatment of MRSA infections in humans.

Invasive candidiasis as a cause of sepsis in the critically ill patient.

Invasive fungal infections are an increasingly frequent etiology of sepsis in critically ill patients causing substantial morbidity and mortality. Candida species are by far the predominant agent of fungal sepsis accounting for 10% to 15% of health-care associated infections, about 5% of all cases of severe sepsis and septic shock and are the fourth most common bloodstream isolates in the United States. One-third of all episodes of candidemia occur in the intensive care setting. Early diagnosis of invasive candidiasis is critical in order to initiate antifungal agents promptly. Delay in the administration of appropriate therapy increases mortality. Unfortunately, risk factors, clinical and radiological manifestations are quite unspecific and conventional culture methods are suboptimal. Non-culture based methods (such as mannan, anti-mannan, β-d-glucan, and polymerase chain reaction) have emerged but remain investigational or require additional testing in the ICU setting. Few prophylactic or pre-emptive studies have been performed in critically ill patients. They tended to be underpowered and their clinical usefulness remains to be established under most circumstances. The antifungal armamentarium has expanded considerably with the advent of lipid formulations of amphotericin B, the newest triazoles and the echinocandins. Clinical trials have shown that the triazoles and echinocandins are efficacious and well tolerated antifungal therapies. Clinical practice guidelines for the management of invasive candidiasis have been published by the European Society for Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of North America.

Indicators used by clinicians to assess pain in the brain injured

INTRODUCTION. The assessment of pain in critically ill brain-injured patients is challenging for health professionals. In addition to be unable to self-report, the confused and stereotyped behaviors of these patients are likely to alter their ''normal'' pain responses. Therefore, the pain indicators observed in the general critically ill population may not be appropriate. OBJECTIVES. To identify behavioral and physiological indicators used by clinicians to assess pain in critically ill brain-injured patients who are unable to self-report. METHODS.Amixed-method design was used with the first step being the combination of the results of an integrative literature review with the results of nominal groups of 12 nurses and four physicians. The second step involved a web-based survey to establish content validity. Fourteen experts (clinicians and academics) from three French speaking European countries rated the relevance of each indicator. A content validity index (CVI) was computed for each indicator (I-CVI) and for each category (S-CVI). RESULTS. The first step generated 52 indicators. These indicators were classified into six categories: facial expressions, position/movement, muscle tension, vocalization, compliance with ventilator, and physiological indicators. In the second step, the agreement between raters was high with an Intraclass Correlation Coefficient of 0.88 (95% CI 0.83-0.92). The I-CVIs ranged from 0.07 to 1. Indicators with an I-CVI below 0.5 (n = 12) were not retained, resulting in a final list of 30 indicators. The CVI for this final list was 0.75 with categories ranging from 0.67 (compliance with ventilation) to 0.87 (vocalization). CONCLUSIONS. This process identified specific pain indicators for critically ill braininjured patients. Further evaluation is in progress to test the validity and relevance of these indicators in the clinical setting.