Disease in the dark: molecular characterization of Polychromophilus murinus in temperate zone bats revealed a worldwide distribution of this malaria-like disease.

For a better understanding of the complex coevolutionary processes between hosts and parasites, accurate identification of the actors involved in the interaction is of fundamental importance. Blood parasites of the Order Haemosporidia, responsible for malaria, have become the focus of a broad range of studies in evolutionary biology. Interestingly, molecular-based studies on avian malaria have revealed much higher species diversity than previously inferred with morphology. Meanwhile, studies on bat haemosporidian have been largely neglected. In Europe, only one genus (Polychromophilus) and two species have been morphologically described. To evaluate the presence of potential cryptic species and parasite prevalence, we undertook a molecular characterization of Polychromophilus in temperate zone bats. We used a nested-PCR approach on the cytochrome b mitochondrial gene to detect the presence of parasites in 237 bats belonging to four different species and in the dipteran bat fly Nycteribia kolenatii, previously described as being the vector of Polychromophilus. Polychromophilus murinus was found in the four bat species and in the insect vector with prevalence ranging from 4% for Myotis myotis to 51% for M. daubentoni. By sequencing 682 bp, we then investigated the phylogenetic relationships of Polychromophilus to other published malarial lineages. Seven haplotypes were found, all very closely related, suggesting the presence of a single species in our samples. These haplotypes formed a well-defined clade together with Haemosporidia of tropical bats, revealing a worldwide distribution of this parasite mostly neglected by malarial studies since the 1980s.

Global and local connectivity changes in schizophrenia investigated by diffusion connectome

Background: New ways of representing diffusion data emerged recently and achieved to create structural connectivitymaps in healthy brains (Hagmann P et al. (2008)). These maps have the capacity to study alterations over the entire brain at the connection and network level. This is of high interest in complex disconnection diseases like schizophrenia. In this Pathology where multiple lines of evidence suggest the association of the pathology with abnormalities in neural circuitry and impaired structural connectivity, the diffusion imaging has been widely applied. Despite the large findings, most of the research using the diffusion just uses some scalar map derived from diffusion to show that some markers of white matter integrity are diminished in several areas of the brain (Kyriakopoulos M et al (2008)). Thanks to the structural connectionmatrix constructed by the whole brain tractography, we report in this work the network connectivity alterations in the schizophrenic patients. Methods: We investigated 13 schizophrenic patients as assessed by the DIGS (Diagnostic Interview for genetic studies, DSM IV criteria) and 13 healthy controls. We have got from each volunteer a DT-MRI as well as Qball imaging dataset and a high resolution anatomic T1 performed during the same session; with a 3 T clinical MRI scanner. The controls were matched on age, gender, handedness, and parental social economic-status. For all the subjects, a low resolution connection matrix is obtained by dividing the cortex into 66 gyral based ROIs. A higher resolution matrix is constructed using 250 ROIs as described in Hagmann P et al. (2008). These ROIs are respectively used jointly with the diffusion tractography to construct the high and low resolution densities connection matrices for each subject. In a first step the matrices of the groups are compared in term of connectivity, and not in term of density to check if the pathological group shows a loss of global connectivity. In this context the density connection matrices were binarized. As some local connectivity changes were also suspected, especially in frontal and temporal areas, we have also looked for the areas where the connectivity showed significant changes. Results: The statistical analysis revealed a significant loss of global connectivity in the schizophrenic's brains at level 5%. Furthermore, by constructing specific statistics which represent local connectivity within the anatomical regions (66 ROIs) using the data obtained by the finest resolution (250 ROIs) to improve the robustness, we found the regions that cause this significant loss of connectivity. The significance is observed after multiple testing corrections by the False Discovery Rate. Discussion: The detected regions are almost the same as those reported in the literature as the involved regions in schizophrenia. Most of the connectivity decreases are noted in both hemispheres in the fronto-frontal and temporo-temporal regions as well as some temporal ROIs with their adjacent ROIs in parietal and occipital lobes.

Tools in pharmacovigilance in psychiatry: therapeutic drug monitoring, pharmacogenetic tests and drug-drug interactions databases

SUMMARYIn order to increase drug safety we must better understand how medication interacts with the body of our patients and this knowledge should be made easily available for the clinicians prescribing the medication. This thesis contributes to how the knowledge of some drug properties can increase and how to make information readily accessible for the medical professionals. Furthermore it investigates the use of Therapeutic drug monitoring, drug interaction databases and pharmacogenetic tests in pharmacovigilance.Two pharmacogenetic studies in the naturalistic setting of psychiatric in-patients clinics have been performed; one with the antidepressant mirtazapine, the other with the antipsychotic clozapine. Forty-five depressed patients have been treated with mirtazapine and were followed for 8 weeks. The therapeutic effect was as seen in other previous studies. Enantioselective analyses could confirm an influence of age, gender and smoking in the pharmacokinetics of mirtazapine; it showed a significant influence of the CYP2D6 genotype on the antidepressant effective S-enantiomer, and for the first time an influence of the CYP2B6 genotype on the plasma concentrations of the 8-OH metabolite was found. The CYP2B6*/*6 genotype was associated to better treatment response. A detailed hypothesis of the metabolic pathways of mirtazapine is proposed. In the second pharmacogenetic study, analyses of 75 schizophrenic patients treated with clozapine showed the influence of CYP450 and ABCB1 genotypes on its pharmacokinetics. For the first time we could demonstrate an in vivo effect of the CYP2C19 genotype and an influence of P-glycoprotein on the plasma concentrations of clozapine. Further we confirmed in vivo the prominent role of CYP1A2 in the metabolism of clozapine.Identifying risk factors for the occurrence of serious adverse drug reactions (SADR) would allow a more individualized and safer drug therapy. SADR are rare events and therefore difficult to study. We tested the feasibility of a nested matched case-control study to examine the influence of high drug plasma levels and CYP2D6 genotypes on the risk to experience an SADR. In our sample we compared 62 SADR cases with 82 controls; both groups were psychiatric patients from the in-patient clinic Königsfelden. Drug plasma levels of >120% of the upper recommended references could be identified as a risk factor with a statistically significant odds ratio of 3.5, a similar trend could be seen for CYP2D6 poor metaboliser. Although a matched case-control design seems a valid method, 100% matching is not easy to perform in a relative small cohort of one in-patient clinic. However, a nested case-control study is feasible.On the base of the experience gained in the AMSP+ study and the fact that we have today only sparse data indicating that routine drug plasma concentration monitoring and/or pharmacogenetic testing in psychiatry are justified to minimize the risk for ADR, we developed a test algorithm named "TDM plus" (TDM plus interaction checks plus pharmacogenetic testing).Pharmacovigilance programs such as the AMSP project (AMSP = Arzneimittelsicherheit in der Psychiatrie) survey psychiatric in-patients in order to collect SADR and to detect new safety signals. Case reports of such SADR are, although anecdotal, valuable to illustrate rare clinical events and sometimes confirm theoretical assumptions of e.g. drug interactions. Seven pharmacovigilance case reports are summarized in this thesis.To provide clinicians with meaningful information on the risk of drug combinations, during the course of this thesis the internet based drug interaction program mediQ.ch (in German) has been developed. Risk estimation is based on published clinical and pharmacological information of single drugs and alimentary products, including adverse drug reaction profiles. Information on risk factors such as renal and hepatic insufficiency and specific genotypes are given. More than 20'000 drug pairs have been described in detail. Over 2000 substances with their metabolic and transport pathways are included and all information is referenced with links to the published scientific literature or other information sources. Medical professionals of more than 100 hospitals and 300 individual practitioners do consult mediQ.ch regularly. Validations with comparisons to other drug interaction programs show good results.Finally, therapeutic drug monitoring, drug interaction programs and pharmacogenetic tests are helpful tools in pharmacovigilance and should, in absence of sufficient routine tests supporting data, be used as proposed in our TDM plus algorithm.RESUMEPour améliorer la sécurité d'emploi des médicaments il est important de mieux comprendre leurs interactions dans le corps des patients. Ensuite le clinicien qui prescrit une pharmacothérapie doit avoir un accès simple à ces informations. Entre autres, cette thèse contribue à mieux connaître les caractéristiques pharmacocinétiques de deux médicaments. Elle examine aussi l'utilisation de trois outils en pharmacovigilance : le monitorage thérapeutique des taux plasmatiques des médicaments (« therapeutic drug monitoring »), un programme informatisé d'estimation du risque de combinaisons médicamenteuses, et enfin des tests pharmacogénétiques.Deux études cliniques pharmacogénétiques ont été conduites dans le cadre habituel de clinique psychiatrique : l'une avec la mirtazapine (antidépresseur), l'autre avec la clozapine (antipsychotique). On a traité 45 patients dépressifs avec de la mirtazapine pendant 8 semaines. L'effet thérapeutique était semblable à celui des études précédentes. Nous avons confirmé l'influence de l'âge et du sexe sur la pharmacocinétique de la mirtazapine et la différence dans les concentrations plasmatiques entre fumeurs et non-fumeurs. Au moyen d'analyses énantiomères sélectives, nous avons pu montrer une influence significative du génotype CYP2D6 sur l'énantiomère S+, principalement responsable de l'effet antidépresseur. Pour la première fois, nous avons trouvé une influence du génotype CYP2B6 sur les taux plasmatiques de la 8-OH-mirtazapine. Par ailleurs, le génotype CYP2B6*6/*6 était associé à une meilleure réponse thérapeutique. Une hypothèse sur les voies métaboliques détaillées de la mirtazapine est proposée. Dans la deuxième étude, 75 patients schizophrènes traités avec de la clozapine ont été examinés pour étudier l'influence des génotypes des iso-enzymes CYP450 et de la protéine de transport ABCB1 sur la pharmacocinétique de cet antipsychotique. Pour la première fois, on a montré in vivo un effet des génotypes CYP2C19 et ABCB1 sur les taux plasmatiques de la clozapine. L'importance du CYP1A2 dans le métabolisme de la clozapine a été confirmée.L'identification de facteurs de risques dans la survenue d'effets secondaire graves permettrait une thérapie plus individualisée et plus sûre. Les effets secondaires graves sont rares. Dans une étude de faisabilité (« nested matched case-control design » = étude avec appariement) nous avons comparé des patients avec effets secondaires graves à des patients-contrôles prenant le même type de médicaments mais sans effets secondaires graves. Des taux plasmatiques supérieurs à 120% de la valeur de référence haute sont associés à un risque avec « odds ratio » significatif de 3.5. Une tendance similaire est apparue pour le génotype du CYP2D6. Le « nested matched case-control design » semble une méthode valide qui présente cependant une difficulté : trouver des patients-contrôles dans le cadre d'une seule clinique psychiatrique. Par contre la conduite d'une « nested case-control study » sans appariement est recommandable.Sur la base de notre expérience de l'étude AMSP+ et le fait que nous disposons que de peux de données justifiant des monitorings de taux plasmatiques et/ou de tests pharmacogénétiques de routine, nous avons développé un test algorithme nommé « TDMplus » (TDM + vérification d'interactions médicamenteuses + tests pharmacogénétique).Des programmes de pharmacovigilances comme celui de l'AMSP (Arzneimittelsicherheit in der Psychiatrie = pharmacovigilance en psychiatrie) collectent les effets secondaires graves chez les patients psychiatriques hospitalisés pour identifier des signaux d'alertes. La publication de certains de ces cas même anecdotiques est précieuse. Elle décrit des événements rares et quelques fois une hypothèse sur le potentiel d'une interaction médicamenteuse peut ainsi être confirmée. Sept publications de cas sont résumées ici.Dans le cadre de cette thèse, on a développé un programme informatisé sur internet (en allemand) - mediQ.ch - pour estimer le potentiel de risques d'une interaction médicamenteuse afin d'offrir en ligne ces informations utiles aux cliniciens. Les estimations de risques sont fondées sur des informations cliniques (y compris les profils d'effets secondaires) et pharmacologiques pour chaque médicament ou substance combinés. Le programme donne aussi des informations sur les facteurs de risques comme l'insuffisance rénale et hépatique et certains génotypes. Actuellement il décrit en détail les interactions potentielles de plus de 20'000 paires de médicaments, et celles de 2000 substances actives avec leurs voies de métabolisation et de transport. Chaque information mentionne sa source d'origine; un lien hypertexte permet d'y accéder. Le programme mediQ.ch est régulièrement consulté par les cliniciens de 100 hôpitaux et par 300 praticiens indépendants. Les premières validations et comparaisons avec d'autres programmes sur les interactions médicamenteuses montrent de bons résultats.En conclusion : le monitorage thérapeutique des médicaments, les programmes informatisés contenant l'information sur le potentiel d'interaction médicamenteuse et les tests pharmacogénétiques sont de précieux outils en pharmacovigilance. Nous proposons de les utiliser en respectant l'algorithme « TDM plus » que nous avons développé.

N-dimensional dynamical systems exploiting instabilities in full

We report experimental and numerical results showing how certain N-dimensional dynamical systems are able to exhibit complex time evolutions based on the nonlinear combination of N-1 oscillation modes. The experiments have been done with a family of thermo-optical systems of effective dynamical dimension varying from 1 to 6. The corresponding mathematical model is an N-dimensional vector field based on a scalar-valued nonlinear function of a single variable that is a linear combination of all the dynamic variables. We show how the complex evolutions appear associated with the occurrence of successive Hopf bifurcations in a saddle-node pair of fixed points up to exhaust their instability capabilities in N dimensions. For this reason the observed phenomenon is denoted as the full instability behavior of the dynamical system. The process through which the attractor responsible for the observed time evolution is formed may be rather complex and difficult to characterize. Nevertheless, the well-organized structure of the time signals suggests some generic mechanism of nonlinear mode mixing that we associate with the cluster of invariant sets emerging from the pair of fixed points and with the influence of the neighboring saddle sets on the flow nearby the attractor. The generation of invariant tori is likely during the full instability development and the global process may be considered as a generalized Landau scenario for the emergence of irregular and complex behavior through the nonlinear superposition of oscillatory motions

Increased EBV Reactivation in the Cerebrospinal Fluid of Patients with Early Multiple Sclerosis

Epstein-Barr virus (EBV) has been consistently associated with multiple sclerosis (MS), but whether this virus is a trigger of MS remains undetermined. Recently, EBV-infected B cells recognized by activated CD8_ T cells have been detected in the meninges of autopsied MS patients. In addition, a strong EBV-specific CD8_ T cell response in the blood of patients with MS of recent onset was reported. Here, to further explore the putative relationship between MS and EBV, we assessed the EBV-specific cellular and humoral immune responses in the blood and the cerebrospinal fluid (CSF) of patients with early MS or other neurological diseases, separated into inflammatory (IOND) and non-inflammatory (NIOND) groups. The MS non-associated neurotropic herpesvirus cytomegalovirus (CMV) served as a control. Fifty-eight study subjects were enrolled, including 44 patients (13 with early MS (onset of MS less than one year prior to the assay), 15 with IOND and 16 with NIOND) in the immunological arm of the study. The cellular immune response was investigated using a functional CFSE cytotoxic T lymphocyte (CTL) assay performed with short-term cultured EBV- or CMVspecific effector T cells from the CSF and the blood. The humoral immune response specific for these two viruses was also examined in both the blood and the CSF. The recruitment of a given virusspecific antibody in the CSF as compared to the blood was expressed as antibody indexes (AI). We found that, in the CSF of early MS patients, there was an enrichment in EBV-, but not CMV-specific, CD8_ CTL as compared to the CSF of IOND (P_ 0.003) and NIOND patients (P_0.0009), as well as compared to paired blood samples (P_0.005). Additionally, relative viral capsid antigen (VCA)-, but not EBV encoded nuclear antigen 1 (EBNA1)- or CMV-specific, AI were increased in the CSF of early MS as compared to IOND (P_0.002) or NIOND patients (P_0.008) and correlated with the EBVspecific CD8_ CTL responses in the CSF (rs_0.54, P_0.001). Fourteen additional patients were enrolled in the virological arm of the study: using semi-nested PCR, EBV-encoded nuclear RNA1 (EBER1)-a transcript expressed during all stages of EBV infection-was detected in the CSF of 2/4 early MS, but only 1/6 IOND and 0/4 NIOND patients. Altogether, our data suggest that a reactivation of EBV, but not CMV, is taking place in the central nervous system of patients with MS of recent onset. These data significantly strengthen the link between EBV and MS and may indicate a triggering role of EBV in this disease. This work was supported by grants from the Swiss National Foundation and from the Swiss Society for Multiple Sclerosis.

Plasma leptin levels in men are not related to the development of lipoatrophy during antiretroviral therapy.

OBJECTIVES: To assess the correlations between the hormone leptin and lipoatrophy in HIV-positive, treatment-naive patients on combination antiretroviral therapy (cART). DESIGN: Case-control study nested in a multicentre cohort of HIV-infected adults. Cases were patients that developed lipoatrophy and controls those who did not. PATIENTS AND METHODS: Clinical parameters and plasma leptin determinations were studied in 97 HIV-1-infected, treatment-naive Caucasian men (10 cases and 87 controls) on an unchanged and virologically successful drug regimen with a zidovudine/lamivudine backbone at baseline and after 2 years of cART. The association of plasma leptin levels and the development of lipoatrophy was investigated. RESULTS: Two years of cART was not associated with a change in plasma leptin levels. Plasma leptin levels remained sensible to changes in body mass index. There was no difference in leptin levels between patients who developed lipoatrophy and controls, neither before nor after cART. The only predictor of development of lipoatrophy was a higher age (P = 0.02). CONCLUSIONS: Leptin as measured in plasma is unlikely to play a major role in the genesis of lipoatrophy.

A step-by-step tutorial to use HierFstat to analyse populations hierarchically structured at multiple levels.

The populations of parasites and infectious agents are most of the time structured in complex hierarchy that lies beyond the classical nested design described by Wright's F-statistics (F(IS), F(ST) and F(IT)). In this note we propose a user-friendly step-by-step notice for using recent software (HierFstat) that computes and test fixation indices for any hierarchical structure. We add some tricks and tips for some special data kind (haploid, single locus), some other procedure (bootstrap over loci) and how to handle crossed factors.

Auditory-visual multisensory interactions in humans: timing, topography, directionality, and sources.

Current models of brain organization include multisensory interactions at early processing stages and within low-level, including primary, cortices. Embracing this model with regard to auditory-visual (AV) interactions in humans remains problematic. Controversy surrounds the application of an additive model to the analysis of event-related potentials (ERPs), and conventional ERP analysis methods have yielded discordant latencies of effects and permitted limited neurophysiologic interpretability. While hemodynamic imaging and transcranial magnetic stimulation studies provide general support for the above model, the precise timing, superadditive/subadditive directionality, topographic stability, and sources remain unresolved. We recorded ERPs in humans to attended, but task-irrelevant stimuli that did not require an overt motor response, thereby circumventing paradigmatic caveats. We applied novel ERP signal analysis methods to provide details concerning the likely bases of AV interactions. First, nonlinear interactions occur at 60-95 ms after stimulus and are the consequence of topographic, rather than pure strength, modulations in the ERP. AV stimuli engage distinct configurations of intracranial generators, rather than simply modulating the amplitude of unisensory responses. Second, source estimations (and statistical analyses thereof) identified primary visual, primary auditory, and posterior superior temporal regions as mediating these effects. Finally, scalar values of current densities in all of these regions exhibited functionally coupled, subadditive nonlinear effects, a pattern increasingly consistent with the mounting evidence in nonhuman primates. In these ways, we demonstrate how neurophysiologic bases of multisensory interactions can be noninvasively identified in humans, allowing for a synthesis across imaging methods on the one hand and species on the other.

A variant in the gene FUT9 is associated with susceptibility to placental malaria infection

Malaria in pregnancy forms a substantial part of the worldwide burden of malaria, with an estimated annual death toll of up to 200,000 infants, as well as increased maternal morbidity and mortality. Studies of genetic susceptibility to malaria have so far focused on infant malaria, with only a few studies investigating the genetic basis of placental malaria, focusing only on a limited number of candidate genes. The aim of this study therefore was to identify novel host genetic factors involved in placental malaria infection. To this end we carried out a nested case-control study on 180 Mozambican pregnant women with placental malaria infection, and 180 controls within an intervention trial of malaria prevention. We genotyped 880 SNPs in a set of 64 functionally related genes involved in glycosylation and innate immunity. A SNP located in the gene FUT9, rs3811070, was significantly associated with placental malaria infection (OR = 2.31, permutation p-value = 0.028). Haplotypic analysis revealed a similarly strong association of a common haplotype of four SNPs including rs3811070. FUT9 codes for a fucosyl-transferase that is catalyzing the last step in the biosynthesis of the Lewis-x antigen, which forms part of the Lewis blood group-related antigens. These results therefore suggest an involvement of this antigen in the pathogenesis of placental malaria infection.

Geometry-based demosaicking

Demosaicking is a particular case of interpolation problems where, from a scalar image in which each pixel has either the red, the green or the blue component, we want to interpolate the full-color image. State-of-the-art demosaicking algorithms perform interpolation along edges, but these edges are estimated locally. We propose a level-set-based geometric method to estimate image edges, inspired by the image in-painting literature. This method has a time complexity of O(S) , where S is the number of pixels in the image, and compares favorably with the state-of-the-art algorithms both visually and in most relevant image quality measures.

Interplay of spectral efficiency, power and doppler spectrum for reference-signal-assisted wireless communication

Expressions relating spectral efficiency, power, and Doppler spectrum, are derived for Rayleigh-faded wireless channels with Gaussian signal transmission. No side information on the state of the channel is assumed at the receiver. Rather, periodic reference signals are postulated in accordance with the functioning of most wireless systems. The analysis relies on a well-established lower bound, generally tight and asymptotically exact at low SNR. In contrast with most previous studies, which relied on block-fading channel models, a continuous-fading model is adopted. This embeds the Doppler spectrum directly in the derived expressions, imbuing them with practical significance. Closed-form relationships are obtained for the popular Clarke-Jakes spectrum and informative expansions, valid for arbitrary spectra, are found for the low- and high-power regimes. While the paper focuses on scalar channels, the extension to multiantenna settings is also discussed.

Calibration and Validation of SWAT for the Upper Maquoketa River Watershed, June 2005

A validation study has been performed using the Soil and Water Assessment Tool (SWAT) model with data collected for the Upper Maquoketa River Watershed (UMRW), which drains over 16,000 ha in northeast Iowa. This validation assessment builds on a previous study with nested modeling for the UMRW that required both the Agricultural Policy EXtender (APEX) model and SWAT. In the nested modeling approach, edge-offield flows and pollutant load estimates were generated for manure application fields with APEX and were then subsequently routed to the watershed outlet in SWAT, along with flows and pollutant loadings estimated for the rest of the watershed routed to the watershed outlet. In the current study, the entire UMRW cropland area was simulated in SWAT, which required translating the APEX subareas into SWAT hydrologic response units (HRUs). Calibration and validation of the SWAT output was performed by comparing predicted flow and NO3-N loadings with corresponding in-stream measurements at the watershed outlet from 1999 to 2001. Annual stream flows measured at the watershed outlet were greatly under-predicted when precipitation data collected within the watershed during the 1999-2001 period were used to drive SWAT. Selection of alternative climate data resulted in greatly improved average annual stream predictions, and also relatively strong r2 values of 0.73 and 0.72 for the predicted average monthly flows and NO3-N loads, respectively. The impact of alternative precipitation data shows that as average annual precipitation increases 19%, the relative change in average annual streamflow is about 55%. In summary, the results of this study show that SWAT can replicate measured trends for this watershed and that climate inputs are very important for validating SWAT and other water quality models.

Mutual information of IID complex Gaussian signals on block Rayleigh-faded channels

We present a method to compute, quickly and efficiently, the mutual information achieved by an IID (independent identically distributed) complex Gaussian signal on a block Rayleigh-faded channel without side information at the receiver. The method accommodates both scalar and MIMO (multiple-input multiple-output) settings. Operationally, this mutual information represents the highest spectral efficiency that can be attained using Gaussiancodebooks. Examples are provided that illustrate the loss in spectral efficiency caused by fast fading and how that loss is amplified when multiple transmit antennas are used. These examples are further enriched by comparisons with the channel capacity under perfect channel-state information at the receiver, and with the spectral efficiency attained by pilot-based transmission.

Mutual Information of IID complex Gaussian signals on block Rayleigh-faded channels

We present a method to compute, quickly and efficiently, the mutual information achieved by an IID (independent identically distributed) complex Gaussian signal on a block Rayleigh-faded channel without side information at the receiver. The method accommodates both scalar and MIMO (multiple-input multiple-output) settings. Operationally, this mutual information represents the highest spectral efficiency that can be attained using Gaussiancodebooks. Examples are provided that illustrate the loss in spectral efficiency caused by fast fading and how that loss is amplified when multiple transmit antennas are used. These examples are further enriched by comparisons with the channel capacity under perfect channel-state information at the receiver, and with the spectral efficiency attained by pilot-based transmission.

Bloodstream infections related to totally implantable venous access port: What is the situation in our hospital?

Port-a-Cath© (PAC) are totally implantable devices that offer an easy and long term access to venous circulation. They have been extensively used for intravenous therapy administration and are particularly well suited for chemotherapy in oncologic patients. Previous comparative studies have shown that these devices have the lowest catheter-related bloodstream infection rates among all intravascular access systems. However, bloodstream infection (BSI) still remains a major issue of port use and epidemiology data for PAC-associated BSI (PABSI) rates differ strongly depending on studies. Also, current literature about PABSI risk factors is scarce and sometimes controversial. Such heterogeneity may depend on type of studied population and local factors. Therefore, the aim of this study was to describe local epidemiology and risk factors for PABSI in adult patients in our tertiary- care university hospital. We conducted a retrospective cohort study in order to describe local epidemiology. We also performed a nested case-control study to identify local risk factors of PABSI. We analyzed medical files of adult patients who had a PAC implanted between January 1st, 2008 and December 31st, 2009 and looked for PABSI occurrence before May 1st, 2011 to define cases. Thirty nine PABSI occurred in this population with an attack rate of 5.8%. We estimated an incidence rate of 0.08/1000 PAC-days using the case-control study. PABSI causative agents were mainly Gram positive cocci (62%). We identified three predictive factors of PABSI by multivariate statistical analysis: neutropenia on outcome date (Odds Ratio [OR]: 4.05; 95% confidence interval [CI]:1.05- 15.66; p=0.042), diabetes (OR: 11.53; 95% CI: 1.07-124.70; p=0.044) and having another infection than PABSI on outcome date (OR: 6.35; 95% CI: 1.50-26.86; p=0.012). Patients suffering from acute or renal failure (OR: 4.26; 95% CI: 0.94-19.21; p=0.059) or wearing another invasive device (OR: 2.99; 95%CI:0.96-9.31; p=0.059) did not have a statistically increased risk for developing a PABSI according to classical threshold (p<0.05) but nevertheless remained close to significance. Our study demonstrated that local epidemiology and microbiology of PABSI in our institution was similar to previous reports. A larger prospective study is required to confirm our results or to test preventive measures.