Evolution des transferts interhospitaliers au départ d'un centre hospitalier universitaire suisse [Trends in interhospital transfers from a Swiss university hospital center].

OBJECTIVE: Research on interhospital transfers provides a basis for describing and quantifying patient flow and its evolution over time, offering an insight into hospital organization and management and hospital overcrowding. The purpose of this study was to conduct a qualitative and quantitative analysis of patient flow and to examine trends over an eight-year period. METHODS: A retrospective descriptive study of interhospital transfers was conducted between 2003 and 2011 based on an analysis of demographic, medical and operational characteristics. Ambulance transfers and transfers requiring physician assistance were analyzed separately. RESULTS: The number of interhospital transfers increased significantly over the study period,from 4,026 in 2003 to 6,481 in 2011 (+60.9%). The number of ambulance transfers increased by almost 300% (616 in 2003 compared to 2,460 in 2011). Most of the transfers (98%) were to hospitals located less than 75 km from the university hospital (median: 24 km, 5-44). In 2011, 24% of all transfers were to psychiatric institutions. 26% of all transfer cases were direct transfers from the emergency department. An increasing number of transfers required physician assistance. 18% of these patients required ventilatory support, whole 9.8% required vasoactive drugs. 11.6% of these transfers were due to hospital overcrowding. Conclusion: The study shows that there has been a significant increase in interhospital transfers. This increase is related to hospital overcrowding and to the network-based systems governing patient care strategies.

Antiretroviral resistance and genetic diversity of human immunodeficiency virus type 1 isolates from the Federal District, Central Brazil

In the context of universal access to antiretroviral therapy, the surveillance of human immunodeficiency virus type 1 (HIV-1) genetic diversity and resistance becomes pivotal. In this work our purpose was to describe the genetic variability; prevalence of drug-resistance mutations; and genotypic resistance profiles in HIV-1 infected individuals under antiretroviral treatment, from the Federal District, Brasília, Central Brazil. The entire viral protease and codons 19 to 234 of the reverse transcriptase gene from 45 HIV-1 isolates were amplified and sequenced for subtyping and genotyping. By phylogenetic analysis, 96% of the samples clustered with subtype B and the remaining 4% with HIV-1 subtype F sequences. One major protease inhibitor resistance-associated mutation, I50V, was detected in 38% of the samples. Minor mutations were also found at the protease gene: L10I/V (7%), K20M (2%), M36I (11%), L63P (20%), A71T (2%), and V77I (7%). Many mutations associated with reduced susceptibility to nucleoside or non-nucleoside reverse transcriptase inhibitors were detected: M41L (11%), E44D (4%), D67N (11%), T69D (2%), K70R (11%), L74V (2%), L100I (4%), K103N (18%), V118I (9%), Y181C (11%), M184V (18%), G190A (4%), T215Y (4%), and K219E (4%). This study has shown that 84% of the studied population from the Federal District, showing evidences of therapy failure, presented viral genomic mutations associated with drug resistance. The main antiretrovirals to which this population showed resistance were the PI amprenavir (38%), the NNRTIs delavirdine, nevirapine (31%), and efavirenz (24%), and the NRTIs lamivudine (18%), abacavir, and zidovudine (13%).

The Genus Cyclospora (Apicomplexa: Eimeriidae), with a description of Cyclospora schneideri n.sp. in the snake Anilius scytale scytale (Aniliidae) from Amazonian Brazil: a review

A review is made of the recorded species of the coccidian genus Cyclospora and major events leading up to the discovery of C. cayetanensis, which is responsible for serious outbreaks of diarrhoea in man and is one of the aetiological agents of "traveller's diarrhoea". Humans appear to be the specific hosts, with the entire life-cycle in the intestine: to date there is no convincing evidence that the disease is a zoonosis. A description is given of oocysts and endogenous stages of C. schneideri n.sp., in the snake Anilius scytale scytale. Sporulation is exogenous and completed after about one week at 24-26º. Mature oocysts 19.8 × 16.6 (15.1 × 13.8-25.7 × 20.1), shape-index 1.2 (1.0-1.3): no oocyst residuum or polar bodies. Oocyst wall a single colourless, smooth layer with no micropyle: it is rapidly deformed or broken. Sporocysts 13.6 × 9.4 (11.3 × 8.3-15.1 × 9.9), shape-index 1.4 (1.2-1.5) with an inconspicuous Stieda body. Sporozoites 11-13 × 2.5-3. Endogenous stages are intracytoplasmic in the epithelial cells of the small intestine and with the characters of the Eimeriorina.

Three new species of Isospora Schneider, 1881 (Apicomplexa: Eimeriidae) from the double-collared seed eater, Sporophila caerulescens (Passeriformes: Emberizidae), from Eastern Brazil

Three isosporan species are described from the double-collared seedeater, Sporophila caerulescens from Eastern Brazil. Isospora sporophilae n. sp. oocysts spherical to subspherical; oocyst wall bi-layered, smooth, inner layer colorless to pale yellowish, 21.6 × 20.9 (19.20-23.20 × 18.40-22.60) µm, shape-index 1.03 ± 0.02 (1-1.10), with no micropyle or oocyst residuum. Polar bodies splinter-like or comma-like. Sporocysts ovoidal, 15.2 × 10.6 (17.40-12.80 × 12.60-8.40) µm, shape-index 1.43 ± 0.14 (1.17-1.81), with knob-like Stieda body and residuum. Large crystalloid body in the center of the sporocyst. Isospora flausinoi n. sp. oocysts spherical to subspherical, oocyst wall bi-layered, smooth, colorless, 17.30 x 16.53 (14-20 × 13.60-20) µm, shape-index 1.05 ± 0.04 (1-1.21). Micropyle and oocyst residuum absent; presence of a large polar body. Sporocyst piriform, 14.88 x 10.70 (11.80-18 × 8-12.40) µm, shape-index 1.40 ± 0.18 (1.07-1.77), with smooth, thin, single-layered wall. Sporocyst with rounded Stieda body with no substieda body, and residuum composed of granular material. Isospora teixeirafilhoi n. sp. oocysts spherical to subspherical, oocyst wall bi-layered, smooth, colorless, 17.41 x 16.81 (15.60 19.40 × 14.20-18.80) µm. Shape-index 1.04 ± 0.08 (1-1.12). Micropyle and oocyst residuum absent; presence of a small double-lobuled polar body. Sporocyst ovoid, 11.74 × 8.12 (9-14.20 × 6.20-9.40) µm. Shape-index 1.46 ± 0.23 (1.06-1.88). Sporocyst with knob-like Stieda body, no sub-Stieda body and residuum composed of granular material.

Effects of two types of fatigue on the VO(2) slow component.

The aim of the study was to test the hypothesis of the involvement of type II fibres in the V.O (2) slow component phenomenon by using two prior fatiguing protocols on the knee extensor muscles. Nine subjects performed three constant-load cycling exercises at a work rate corresponding to 80 % of their V.O (2) max: (i) preceded by a 20-min fatiguing protocol using electromyostimulation (EMS), (ii) preceded by a 20-min fatiguing protocol using voluntary contractions (VOL), and (iii) without fatiguing protocol (NFP). Voluntary and evoked neuromuscular properties of the knee extensor muscles were tested before (PRE) and after (POST) the two fatiguing protocols. Results show a significant reduction in voluntary force after both fatiguing protocols (-19.9 % and -11.8 %, in EMS and VOL, respectively p<0.01). After EMS, this decrease was greater than after VOL (p<0.05) and was combined with a slackening of muscle contractile properties which was absent after VOL (p<0.05). Regarding the effects on oxygen uptake kinetics, the appearance of the slow component was delayed after EMS and its amplitude was lower than those obtained in VOL and NFP conditions (0.48+/-0.07 vs. 0.75+/-0.09 and 0.69+/-0.08 L . min (-1), respectively; p<0.05). It can thus be concluded that exercises dedicated to preferentially fatiguing type II fibres may alter V.O (2) kinetics.

Early-onset ventilator-associated pneumonia incidence in intensive care units: a surveillance-based study.

ABSTRACT: BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) within the first 48 hours of intensive care unit (ICU) stay has been poorly investigated. The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours after admission. METHODS: We analyzed data from prospective surveillance between 01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion criteria were: first ICU admission, not hospitalized before admission, invasive mechanical ventilation during first ICU day, free of antibiotics at admission, and ICU stay >=48 hours. VAP was defined according to a national protocol. Its incidence was the number of events per 1,000 invasive mechanical ventilation-days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay. RESULTS: Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was 5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48 hours from admission was 11% (9%-17%). CONCLUSIONS: Our study indicates underestimation of early-onset VAP incidence in ICUs, if only VAP occurring [greater than or equal to]48 hours is considered to be hospital-acquired. Clinicians should be encouraged to develop a strategy for early detection after ICU admission.

Efficacy of benznidazol treatment for asymptomatic chagasic patients from state of Rio Grande do Sul evaluated during a three years follow-up

The efficacy of benznidazol on the treatment of chagasic patients from the state of Rio Grande do Sul was evaluated during a three-year follow-up. A cohort of 80 asymptomatic chronic chagasic patients or blood bank donors (49 male and 31 female) was studied. Their ages varied from 17-42 years, with a mean and a median of 30 and 35 years, respectively. The 80 patients presented positive serology, hemoculture and polymerase chain reaction (PCR). They were treated with 5 mg/Kg benznidazol twice a day for 60 days. Serological, parasitological and PCR methods were used to evaluate response. Serology was performed using commercial ELISA and indirect immunofluorescence (IFI) tests, parasitemia was monitored by hemoculture in LIT medium and PCR with primers S35/S36 was used to amplify a Trypanosoma cruzi 330 bp kDNA repetitive sequence. PCR positivity of 240 seropositive individuals was compared using DNA preparations from whole blood/guanidine EDTA (GE), buffy-coat/GE and frozen buffy-coat. Fifty non-chagasic individuals were used as negative controls. PCR positivity was 86.7% for the frozen buffy-coat, 71.7% for the GE/buffy-coat and 69.2% for the GE/whole blood. The hemocultures became negative just after treatment and remained negative during the three years of follow-up. In the third year after treatment, 9/80 (11.3%) patients presented negative PCR and, from those, four also presented negative serological tests. Furthermore, a reduction in three serological titers was observed in 27/80 (33.8%) of the patients treated. Taken together, the results show that four of the 80 (5.0%) chronic chagasic patients from the state of Rio Grande do Sul were cured after treatment with benznidazol.

Determinants and burden of chronic kidney disease in the population-based CoLaus study: a cross-sectional analysis.

BACKGROUND: Chronic kidney disease (CKD) represents an increasing health burden. We present the population-based prevalence of CKD and compare the CKD Epidemiology collaboration (CKD-EPI) and modification of diet in renal disease (MDRD) equations to estimate the glomerular filtration rate, using the revised CKD classification with three albuminuria classes. We also explore factors associated with CKD. METHODS: The Swiss population-based, cross-sectional CoLaus study conducted in Lausanne (2003-2006) included 2810 men and 3111 women aged 35-75. CKD prevalence was assessed using CKD-EPI and MDRD equations and albuminuria estimated by the albumin-to-creatinine ratio in spot morning urine. Multivariate logistic regression was used to analyse determinants of CKD. RESULTS: Prevalence [95% confidence interval (CI)] of all stages CKD was 10.0% (9.2-10.8%) with CKD-EPI and 13.8% (12.9-14.6%) with MDRD. Using the revised CKD classification, the prevalence of low-, medium-, high- and very high-risk groups was 90.0, 8.46, 1.18 and 0.35% with CKD-EPI, respectively. With MDRD, the corresponding values were 86.24, 11.86, 1.55 and 0.35%. Using the revised classification, CKD-EPI systematically reclassified people in a lower risk category than MDRD. Age and obesity were more strongly associated with CKD in men [odds ratio (95% CI): 2.23(1.95; 2.56) per 10 years and 3.05(2.08;4.47), respectively] than in women [1.46 (1.29; 1.65) and 1.78 (1.30;2.44), respectively]. Hypertension, type 2 diabetes, serum homocysteine and uric acid were positively independently associated with CKD in men and women. CONCLUSIONS: One in 10 adults suffers from CKD in the population of Lausanne. CKD-EPI systematically reclassifies people in a lower CKD risk category than MDRD. Serum homocysteine and uric acid levels are associated with CKD independently of classical risk factors such as age, hypertension and diabetes.

Reliability and validity of physiological data obtained within a cycle-run transition test in age-group triathletes.

This study examined the validity and reliability of a sequential "Run-Bike-Run" test (RBR) in age-group triathletes. Eight Olympic distance (OD) specialists (age 30.0 ± 2.0 years, mass 75.6 ± 1.6 kg, run VO2max 63.8 ± 1.9 ml· kg(-1)· min(-1), cycle VO2peak 56.7 ± 5.1 ml· kg(-1)· min(-1)) performed four trials over 10 days. Trial 1 (TRVO2max) was an incremental treadmill running test. Trials 2 and 3 (RBR1 and RBR2) involved: 1) a 7-min run at 15 km· h(-1) (R1) plus a 1-min transition to 2) cycling to fatigue (2 W· kg(-1) body mass then 30 W each 3 min); 3) 10-min cycling at 3 W· kg(-1) (Bsubmax); another 1-min transition and 4) a second 7-min run at 15 km· h(-1) (R2). Trial 4 (TT) was a 30-min cycle - 20-min run time trial. No significant differences in absolute oxygen uptake (VO2), heart rate (HR), or blood lactate concentration ([BLA]) were evidenced between RBR1 and RBR2. For all measured physiological variables, the limits of agreement were similar, and the mean differences were physiologically unimportant, between trials. Low levels of test-retest error (i.e. ICC <0.8, CV<10%) were observed for most (logged) measurements. However [BLA] post R1 (ICC 0.87, CV 25.1%), [BLA] post Bsubmax (ICC 0.99, CV 16.31) and [BLA] post R2 (ICC 0.51, CV 22.9%) were least reliable. These error ranges may help coaches detect real changes in training status over time. Moreover, RBR test variables can be used to predict discipline specific and overall TT performance. Cycle VO2peak, cycle peak power output, and the change between R1 and R2 (deltaR1R2) in [BLA] were most highly related to overall TT distance (r = 0.89, p < 0. 01; r = 0.94, p < 0.02; r = 0.86, p < 0.05, respectively). The percentage of TR VO2max at 15 km· h(-1), and deltaR1R2 HR, were also related to run TT distance (r = -0.83 and 0.86, both p < 0.05).

Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza.

INTRODUCTION Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. METHODS We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. RESULTS Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1beta), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-gamma) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-alpha, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. CONCLUSIONS While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.

Two mechanisms of caspase 9 processing in double-stranded RNA- and virus-triggered apoptosis.

Viral double-stranded RNA (dsRNA) is a ubiquitous intracellular "alert signal" used by cells to detect viral infection and to mount anti-viral responses. DsRNA triggers a rapid (complete within 2-4 h) apoptosis in the highly-susceptible HeLa cell line. Here, we demonstrate that the apical event in this apoptotic cascade is the activation of procaspase 8. Downstream of caspase 8, the apoptotic signaling cascade bifurcates into a mitochondria-independent caspase 8/caspase 3 arm and a mitochondria-dependent, caspase 8/Bid/Bax/Bak/cytochrome c arm. Both arms impinge upon, and activate, procaspase 9 via two different cleavage sites within the procaspase 9 molecule (D330 and D315, respectively). This is the first in vivo demonstration that the "effector" caspase 3 plays an "initiator" role in the regulation of caspase 9. The dsRNA-induced apoptosis is potentiated by the inhibition of protein synthesis, whose role is to accelerate the execution of all apoptosis steps downstream of, and including, the activation of caspase 8. Thus, efficient apoptosis in response to viral dsRNA results from the co-operation of the two major apical caspases (8 and 9) and the dsRNA-activated protein kinase R (PKR)/ribonuclease L (RNase L) system that is essential for the inhibition of protein synthesis in response to viral infection.

Early profiles of clinical evolution after intravenous thrombolysis in an unselected stroke population.

BACKGROUND: Intravenous recombinant tissular plasminogen activator (rt-PA) is the only approved pharmacological treatment for acute ischaemic stroke. The authors aimed to analyse potential causes of the variable effect on early course and late outcome. METHODS AND RESULTS: 136 patients (42% women, 58% men) treated with intravenous rt-PA within 3 h of stroke onset in an acute stroke unit over a 3-year period, were included. Early clinical profiles of evolution at 48 h were divided into clinical improvement (CI) (decrease >4 points in the National Institute of Health Stroke Scale (NIHSS)); clinical worsening (CW) (increase >4 points NIHSS); clinical worsening after initial improvement (CWFI) (variations of >4 points in the NIHSS). Patients with clinical stability (no NIHSS modification or <4 points) were excluded. The patients showed in 66.9% CI, 13.2% CW 8.1 % CWFI and 11.8% remained stable. Female sex, no hyperlipaemia and peripheral arterial disease were associated with CW. Male sex and smoking were associated with CI. Absence of arterial occlusion on admission (28.4%) and arterial recanalisation at 24 h were associated with CI. Main causes of clinical deterioration included symptomatic intracranial haemorrhage (sICH), persistent occlusion and cerebral oedema. 23.5% developed ICH, 6.6% of which had sICH. At 3 months, 15.5% had died. Mortality was increased in CW, mainly related to sICH and cerebral oedema. The outcome of CWFI was intermediate between CW and CI. CONCLUSIONS: Early clinical profiles of evolution in thrombolysed patients vary considerably. Even with CI, it is critical to maintain vessel permeability to avoid subsequent CW.

Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism.

BACKGROUND: The Pulmonary Embolism Severity Index (PESI) estimates the risk of 30-day mortality in patients with acute pulmonary embolism (PE). We constructed a simplified version of the PESI. METHODS: The study retrospectively developed a simplified PESI clinical prediction rule for estimating the risk of 30-day mortality in a derivation cohort of Spanish outpatients. Simplified and original PESI performances were compared in the derivation cohort. The simplified PESI underwent retrospective external validation in an independent multinational cohort (Registro Informatizado de la Enfermedad Tromboembólica [RIETE] cohort) of outpatients. RESULTS: In the derivation data set, univariate logistic regression of the original 11 PESI variables led to the removal of variables that did not reach statistical significance and subsequently produced the simplified PESI that contained the variables of age, cancer, chronic cardiopulmonary disease, heart rate, systolic blood pressure, and oxyhemoglobin saturation levels. The prognostic accuracy of the original and simplified PESI scores did not differ (area under the curve, 0.75 [95% confidence interval (CI), 0.69-0.80]). The 305 of 995 patients (30.7%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.0% (95% CI, 0.0%-2.1%) compared with 10.9% (8.5%-13.2%) in the high-risk group. In the RIETE validation cohort, 2569 of 7106 patients (36.2%) who were classified as low risk by the simplified PESI had a 30-day mortality of 1.1% (95% CI, 0.7%-1.5%) compared with 8.9% (8.1%-9.8%) in the high-risk group. CONCLUSION: The simplified PESI has similar prognostic accuracy and clinical utility and greater ease of use compared with the original PESI.

Efficacy of an eradication protocol in case of Pseudomonas aeruginosa primo-infections in children with cystic fibrosis

Introduction: Patients with cystic fibrosis (CF) are more susceptible to pathogens like P. aeruginosa (PA). PA primo-­‐infections require particular attention, as with failure in eradication, there is accelerated lung deterioration. The main aim of this study is to assess the rate of PA eradication according to our particular protocol with inhaled tobramycin and oral ciprofloxacin, as there is no consensus in the literature on what eradication protocol the best is. Methods: Retrospective single centre study with data analysis from June 1st 2007 to June 1st 2011 of patients who had primo-­‐infections exclusively treated by 3 x 28 days of inhaled tobramycin and oral ciprofloxacin for the first and last 21 days. Success in eradication is defined by ≥ 3 negative bacteriologies for 6 months after the beginning of the protocol. If ≥ 1 bacteriology is positive, we consider the eradication as a failure. Results: Out of 41 patients, 18 were included in our analysis. 7 girls (38.9%) and 11 boys (61.1%) followed the eradication protocol. Boys had 12 primo-­‐infections and girls had 8. Among these 20 primo-­‐infections, 16 (80%) had an all-­‐overall success in eradication and 4 (20%) a failure. No significant statistical difference for age between these groups (t-­‐test = 0.07, p = 0.94), neither for FEV1% (t-­‐test = 0.96, p = 0.41) nor BMI (t-­‐test = 1.35, p = 0.27). Rate of success was 100% for girls and 66.6% for boys. Conclusion: Our protocol succeeded in an overall eradication rate of 80%, without statistical significant impact on FEV1 % and BMI values. However, there is a sex difference with eradication rates in girls (100%) and boys (66.6%). A sex difference has not yet been reported in the literature. This should be evaluated in further studies.