Prospective monitoring of cefepime in intensive care unit adult patients

Rapport de synthèse :Le céfépime a été associé à un taux de mortalité supérieur à celui des autres bêta-lactamines chez les patients traités pour un sepsis sévère. Une des hypothèses avancées pour expliquer ces échecs thérapeutiques sont de possibles effets secondaires cachés (par ex. neurologiques) ou des paramètres pharmacocinétiques/pharmacodynamiques (PK/PD) inadaptés. Le présent travail a étudié cette problématique en mesurant prospectivement la pharmacocinétique du céfépime chez 21 patients consécutifs hospitalisés aux soins intensifs adultes (SIAD) pour une pneumonie nosocomiale. La population étudiée avec un âge médian 55,1 ans, a reçu par voie intraveineuse du céfépime à raison de 2 g toutes les 12 heures pour une clairance de la créatinine (Clcr)>50 mI/ min, et 2 g toutes les 24 heures ou 36 heures pour une Clcr<50 ml /min. Les taux plasmatiques de céfépime ont été mesurés à plusieurs reprises avant et après administration du médicament après la lèoe dose et à l'état d'équilibre par chromatographie en phase liquide à haute pression. Les taux plasmatiques ont considérablement varié entre les patients. Cent pour cent (21/21) des patients ont eu une durée appropriée d'antibiothérapie avec des taux plasmatiques supérieures à la CMI du céfépime (T>CMI>50%) pour les agents pathogènes retrouvés dans cette étude (CMI<4 mg/I), mais seulement 45-65% d'entre eux ont eu une couverture appropriée pour les agents pathogènes potentiels présentant une CMI> 8 mg/I pour le céfépime. Deux patients avec une insuffisance rénale (Clcr<30 ml/min) ont présenté des symptômes compatibles avec une épilepsie non-convulsive (état confusionnel et myoclonies) attribuée dans un 2ème temps à une toxicité du céfépime après que les taux plasmatiques aient été communiqués aux soignants qui ont suspendu l'antibiothérapie avec disparition des symptômes. Les résultats de cette étude empirique confirment l'existence d'effets secondaires cachés et de paramètres PK/PD inappropriés (pour les agents pathogènes ayant des CMI de limite supérieure) dans notre population de SIAD. En outre, ils mettent en évidence une fenêtre thérapeutique efficace pour une posologie de céfépime de 2 g toutes les 12 heures chez les patients ayant une Clcr>50 ml/min infectés par des pathogènes avec des CMI pour le céfépime <4 mg/I. Les échecs thérapeutiques constatés dans cette étude sont probablement liés à des taux sériques inadaptés, résultant de la difficulté de prescription dans les situations cliniques complexes. Dans ce contexte, un prompt dosage plasmatique du céfépime doit être considéré en cas de diminution de la Clcr ou en présence de CMI élevées.

Increased carotid intima-media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease.

AIM: Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima-media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population. METHODS: The common carotid artery intima-media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high-definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age-matched healthy individuals (83 men, 37 women). RESULTS: The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706+/-211 microm and 749+/-395 microm, respectively) compared with that of the control population (614+/-113 microm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non-homogeneous intima-media thickening greater than 1.2 mm. CONCLUSION: This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.

The future of longevity: background and perspectives

In many developed countries, including Switzerland, the ongoing increase in life expectancy is driven by the mortality decline among older persons. This has important consequences for both the provision of health care and the management of pension funds. In this context, the Swiss Federal Office of Statistics mandated a small group of experts to provide a critical review on the future evolution of mortality in developed countries. The report starts with an analysis of the past trends in life expectancy. Longevity is defined here as the duration (or the length) of life as observed in population or in individuals. The oldest and still most used indicators of longevity are life expectancy at birth (LE0) at a population level, and maximum life span (MLS) at the individual level (page 9) and in healthy life expectancy (page 19). A discussion on the future evolution of mortality and health is then presented (page 27). A set of recommendations is finally proposed (page 39).

Do different measures of early life socioeconomic circumstances predict adult mortality? Evidence from the British Whitehall II and French GAZEL studies

BACKGROUND: Father's occupational position, education and height have all been used to examine the effects of adverse early life socioeconomic circumstances on health, but it remains unknown whether they predict mortality equally well. METHODS: We used pooled data on 18,393 men and 7060 women from the Whitehall II and GAZEL cohorts to examine associations between early life socioeconomic circumstances and all-cause and cause-specific mortality. RESULTS: During the 20-y follow-up period, 1487 participants died. Education had a monotonic association with all mortality outcomes; the age, sex and cohort-adjusted HR for the lowest versus the highest educational group was 1.45 (95% CI 1.24 to 1.69) for all-cause mortality. There was evidence of a U-shaped association between height and all-cause, cancer and cardiovascular mortality robust to adjustment for the other indicators (HR 1.41, 95% CI 1.03 to 1.93 for those shorter than average and HR 1.36, 95% CI 0.98 to 1.88 for those taller than average for cardiovascular mortality). Greater all-cause and cancer mortality was observed in participants whose father's occupational position was manual rather than non-manual (HR 1.11, 95% CI 1.00 to 1.23 for all-cause mortality), but the risks were attenuated after adjusting for education and height. CONCLUSIONS: The association between early life socioeconomic circumstances and mortality depends on the socioeconomic indicator used and the cause of death examined. Height is not a straightforward measure of early life socioeconomic circumstances as taller people do not have a health advantage for all mortality outcomes.

Reelin controls progenitor cell migration in the healty and pathological adult brain

Understanding the signals that control migration of neural progenitor cells in the adult brain may provide new therapeutic opportunities. Reelin is best known for its role in regulating cell migration during brain development, but we now demonstrate a novel function for reelin in the injured adult brain. First, we show that Reelin is upregulated around lesions. Second, experimentally increasing Reelin expression levels in healthy mouse brain leads to a change in the migratory behavior of subventricular zone-derived progenitors, triggering them to leave the rostral migratory stream (RMS) to which they are normally restricted during their migration to the olfactory bulb. Third, we reveal that Reelin increases endogenous progenitor cell dispersal in periventricular structures independently of any chemoattraction but via cell detachment and chemokinetic action, and thereby potentiates spontaneous cell recruitment to demyelination lesions in the corpus callosum. Conversely, animals lacking Reelin signaling exhibit reduced endogenous progenitor recruitment at the lesion site. Altogether, these results demonstrate that beyond its known role during brain development, Reelin is a key player in post-lesional cell migration in the adult brain. Finally our findings provide proof of concept that allowing progenitors to escape from the RMS is a potential therapeutic approach to promote myelin repair.

Counselor motivational interviewing skills and young adult change talk articulation during brief motivational interventions.

The process of eliciting client language toward change (change talk [CT]) is implicated as a causal mechanism in motivational interviewing (MI) and brief motivational interventions (BMI). We investigated the articulation of counselor behaviors and CT during BMI with young men. We coded 149 sessions using the Motivational Interviewing Skill Code and summarized these codes into three counselor categories (MI-consistent [MICO], MI-inconsistent [MIIN], other) and three client categories (CT, counter CT [CCT], follow/neutral [F/N]). We then computed immediate transition frequencies and odds ratios using sequential analysis software. CT was significantly more likely following MICO behaviors, whereas MIIN behaviors only led to CCT and F/N. This strongly supports the use of MI skills to elicit CT during BMI with young men, whose speech also predicted counselor behaviors (particularly CT to MICO and CCT to MIIN). Additional analyses showed that among MICO behaviors, reflective listening may be a particularly powerful technique to elicit CT.

D-3 2009 Dependent Adult Abuse Report, July - December 2009.

D-3 Dependent Adult Abuse Report

D-3 2010 Dependent Adult Abuse Report, January - June 2010.

D-3 Dependent Adult Abuse Report

D-3 2010 Dependent Adult Abuse Report, July - December 2010

D-3 Dependent Adult Abuse Report

D-3 2010 Dependent Adult Abuse Report, January 1,2009 - June, 30 2010

D-3 Dependent Adult Abuse Report

Adult native septic arthritis: 10 years in review in order to establish local guidelines on empiric antibiotic therapy.

Objective: Antibiotic stewardship includes development of practice guidelines incorporating local microbiology and resistance patterns. In case of septic arthritis (SA), addition of vancomycin to the empiric therapy and broad-spectrum antibiotherapy in some clinical settings are subjects of discussion. Our objective was to review the local epidemiology of native septic arthritis in adults, in order to establish local guidelines for empiric therapy. Methods: Retrospective study based on positive synovial fluid cultures and hospital discharge diagnoses of SA obtained from 1999 to 2008 in patients _16 years. Medical records were reviewed to assess the diagnosis and complete relevant clinical information. Results: During this ten-year period, we identified 233 SA on native joints in 231 patients. 107 episodes (46%) were obtained through positive synovial fluid cultures, and 126 episodes (54%) through the discharge diagnosis. 147 SA (63%) were large joint infections (LJI). 35 SA (15%) occurred in intravenous drug users. Preexisting arthropathy was present in 51% of cases. 42% of patients with small joint infection (SJI) were diabetic, vs. 23% with LJI (p = 0.003). When available, synovial fluid direct examination was positive in 35% of cases. Etiologic agents are reported in the table. Five of the 11 MRSA SA (45%) occurred in known carriers. SJI were more frequently polymicrobial (24% vs. 1%, p<0.001). For LJI, an empiric treatment with amoxicillin/clavulanate (A/C) would have been appropriate in 85% of cases. MRSA (8 cases) and tuberculous (7 cases) arthritis would have been the most frequently untreated pathogens. Addition of vancomycin to A/C in MRSA carriers would rise the adequacy to 87%. In contrast, A/C would cover only 75% of SJI (82% if restricted to non-diabetic patients). MRSA (3 cases) and P. aeruginosa (9 cases, 7 monomicrobial) would be the main untreated pathogens. An anti-pseudomonal penicillin would have been appropriate in 94% of cases of SJI (P = 0.002 vs. A/C, p = 0.19 if diabetic patients not included). Conclusions: Treatment with A/C seems adequate for empiric coverage of LJI in our setting. Broad-spectrum antibiotherapy was significantly superior for SJI in diabetic patients, due to different causative bacteria. In an area of low MRSA incidence, our results do not justify a systematic empiric therapy for MRSA, which should be considered in a known carrier.

Aportación de la resonancia magnética en un caso de criptorquidia bilateral en un paciente adulto [Contribution of magnetic resonance in a case of bilateral cryptorchism in an adult patient].

Report of one case of bilateral cryptorchism with non-palpable testes in a 26-year old patient with progressive muscle dystrophy. Physical examination and ultrasound study to detect the testicular location were inconclusive. An analysis is made of data obtained with the NMR study as well as a review of the advantages and contributions from this new technique in the location and characterization of undescended testes.

Differential distribution of MAP1A isoforms in the adult mouse barrel cortex and comparison with the serotonin 5-HT2A receptor.

Microtubule-associated protein 1A (MAP1A) is essential during the late differentiation phase of neuronal development. Here, we demonstrated the presence of two MAP1A isoforms with a differential spatial distribution in the adult mouse barrel cortex. Antibody A stained MAP1A in pyramidal and stellate cells, including dendrites that crossed layer IV in the septa between barrels. The other antibody, BW6 recognized a MAP1A isoform that was mainly confined to the barrel hollow and identified smaller caliber dendrites. Previously, an interaction of MAP1A and the serotonin 5-hydroxytryptamine 2A (5-HT(2A)) receptor was shown in the rat cortex. Here, we identified, by double-immunofluorescent labeling, MAP1A isoform and serotonin 5-HT(2A) receptor distribution. MAP1A co-localized mainly with 5-HT(2A) receptor in larger apical dendrites situated in septa. This differential staining of MAP1A and a serotonin receptor in defined barrel compartments may be due to changes in the expression or processing of MAP1A during dendritic transport as a consequence of functional differences in processing of whisker-related sensory input.

T cell receptor alpha gene rearrangement and transcription in adult thymic gamma delta cells.

T cells belong to two separate lineages based on surface expression of alpha beta or gamma delta T cell receptors (TCR). Since during thymus development TCR beta, gamma, and delta genes rearrange before alpha genes, and gamma delta cells appear earlier than alpha beta cells, it has been assumed that gamma delta cells are devoid of TCR alpha rearrangements. We show here that this is not the case, since mature adult, but not fetal, thymic gamma delta cells undergo VJ alpha rearrangements more frequently than immature alpha beta lineage thymic precursors. Sequence analysis shows VJ alpha rearrangements in gamma delta cells to be mostly (70%) nonproductive. Furthermore, VJ alpha rearrangements in gamma delta cells are transcribed normally and, as shown by analysis of TCR beta-/- mice, occur independently of productive VDJ beta rearrangements. These data are interpreted in the context of a model in which precursors of alpha beta and gamma delta cells differ in their ability to express a functional pre-TCR complex.