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Martin-Loeches I.,St James's Hospital | Povoa P.,Hospital Of Sao Francisco Xavier | Rodriguez A.,Hospital Joan XXIII | Rodriguez A.,Institute Salud Carlos III | And 22 more authors.
The Lancet Respiratory Medicine | Year: 2015

Background: Ventilator-associated tracheobronchitis has been suggested as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia in patients receiving mechanical ventilation. We aimed to establish the incidence and effect of ventilator-associated tracheobronchitis in a large, international patient cohort. Methods: We did a multicentre, prospective, observational study in 114 intensive care units (ICU) in Spain, France, Portugal, Brazil, Argentina, Ecuador, Bolivia, and Colombia over a preplanned time of 10 months. All patients older than 18 years admitted to an ICU who received invasive mechanical ventilation for more than 48 h were eligible. We prospectively obtained data for incidence of ventilator-associated lower respiratory tract infections, defined as ventilator-associated tracheobronchitis or ventilator-associated pneumonia. We grouped patients according to the presence or absence of such infections, and obtained data for the effect of appropriate antibiotics on progression of tracheobronchitis to pneumonia. Patients were followed up until death or discharge from hospital. To account for centre effects with a binary outcome, we fitted a generalised estimating equation model with a logit link, exchangeable correlation structure, and non-robust standard errors. This trial is registered with ClinicalTrials.gov, number NCT01791530. Findings: Between Sept 1, 2013, and July 31, 2014, we obtained data for 2960 eligible patients, of whom 689 (23%) developed ventilator-associated lower respiratory tract infections. The incidence of ventilator-associated tracheobronchitis and that of ventilator-associated pneumonia at baseline were similar (320 [11%; 10·2 of 1000 mechanically ventilated days] vs 369 [12%; 8·8 of 1000 mechanically ventilated days], p=0·48). Of the 320 patients with tracheobronchitis, 250 received appropriate antibiotic treatment and 70 received inappropriate antibiotics. 39 patients with tracheobronchitis progressed to pneumonia; however, the use of appropriate antibiotic therapy for tracheobronchitis was associated with significantly lower progression to pneumonia than was inappropriate treatment (19 [8%] of 250 vs 20 [29%] of 70, p<0·0001; crude odds ratio 0·21 [95% CI 0·11-0·41]). Significantly more patients with ventilator-associated pneumonia died (146 [40%] of 369) than those with tracheobronchitis (93 [29%] of 320) or absence of ventilator-associated lower respiratory tract infections (673 [30%] of 2271, p<0·0001). Median time to discharge from the ICU for survivors was significantly longer in the tracheobronchitis (21 days [IQR 15-34]) and pneumonia (22 [13-36]) groups than in the group with no ventilator-associated lower respiratory tract infections (12 [8-20]; hazard ratio 1·65 [95% CI 1·38-1·97], p<0·0001). Interpretation: This large database study emphasises that ventilator-associated tracheobronchitis is a major health problem worldwide, associated with high resources consumption in all countries. Our findings also show improved outcomes with use of appropriate antibiotic treatment for both ventilator-associated tracheobronchitis and ventilator-associated pneumonia, underlining the importance of treating both infections, since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia. Funding: None. © 2015 Elsevier Ltd.


Burgard M.,Hospital Necker | Jasseron C.,French Institute of Health and Medical Research | Jasseron C.,Hospital Bicetre | Matheron S.,Hospital Bichat | And 105 more authors.
Clinical Infectious Diseases | Year: 2010

Background. Management of pregnant women with human immunodeficiency virus (HIV) type 2 infection remains unclear because of its low prevalence and important differences from HIV-1. Methods. Pregnant women monoinfected with HIV-2 or HIV-1 and their infants enrolled in the prospective, national, multicenter French Perinatal Cohort between 1986 and 2007. Results. Overall, 2.6% (223/8660) of mothers were infected with HIV-2, and they accounted for 3.1% (367/ 11841) of the total births. Most were born in sub-Saharan Africa. A higher proportion of HIV-2-infected mothers than HIV-1-infected mothers had no symptoms, had received no antiretroviral threrapy at conception (85.9% vs 66.7%), and had received no antiretroviral therapy during pregnancy (42.8% vs 19.9%), particularly highly active antiretroviral therapy (HAART) (79.7% vs 46.1%), and they had higher CD4 cell counts near delivery (median, 574 vs 452 cells/mm3; P <.01). If antiretroviral therapy was used, it was started at a later gestational age for HIV-2-infected mothers (median, 28 vs 25 weeks; P <.01). HIV-2-infected mothers were more likely to deliver vaginally (67.9% vs 49.3%) and to breastfeed (3.6% vs 0.6%; P <.01), and their infants less frequently received postexposure prophylaxis. In the period 2000-2007, the proportion with viral load <100 copies/mL at delivery was 90.5% of HIV-2-infected mothers, compared with 76.2% of HIV-1-infected mothers (P =.1). There were 2 cases of transmission: 1 case in 1993 occurred following maternal primary infection, and the other case occurred postnatally in 2002 and involved a mother with severe immune deficiency. The mother-to-child transmission rate for HIV-2 was 0.6% (95% confidence interval, 0.07%-2.2%). Conclusions. Care for HIV-2-infected pregnant women rests on expert opinion. The mother-to-child transmission residual rate (0.07%-2.2%) argues for systematic treatment: protease inhibitor-based HAART for women requiring antiretroviral therapy or for primary infection and simplified prevention of mother-to-child transmission in other instances. © 2010 by the Infectious Diseases Society of America. All rights reserved.


PubMed | Hospital Joan XXIII, Instituto Nacional Of Cancer, Hospital Universitario Marques Of Valdecilla, Autonomous University of Barcelona and 15 more.
Type: Journal Article | Journal: The Lancet. Respiratory medicine | Year: 2015

Ventilator-associated tracheobronchitis has been suggested as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia in patients receiving mechanical ventilation. We aimed to establish the incidence and effect of ventilator-associated tracheobronchitis in a large, international patient cohort.We did a multicentre, prospective, observational study in 114 intensive care units (ICU) in Spain, France, Portugal, Brazil, Argentina, Ecuador, Bolivia, and Colombia over a preplanned time of 10 months. All patients older than 18 years admitted to an ICU who received invasive mechanical ventilation for more than 48 h were eligible. We prospectively obtained data for incidence of ventilator-associated lower respiratory tract infections, defined as ventilator-associated tracheobronchitis or ventilator-associated pneumonia. We grouped patients according to the presence or absence of such infections, and obtained data for the effect of appropriate antibiotics on progression of tracheobronchitis to pneumonia. Patients were followed up until death or discharge from hospital. To account for centre effects with a binary outcome, we fitted a generalised estimating equation model with a logit link, exchangeable correlation structure, and non-robust standard errors. This trial is registered with ClinicalTrials.gov, number NCT01791530.Between Sept 1, 2013, and July 31, 2014, we obtained data for 2960 eligible patients, of whom 689 (23%) developed ventilator-associated lower respiratory tract infections. The incidence of ventilator-associated tracheobronchitis and that of ventilator-associated pneumonia at baseline were similar (320 [11%; 102 of 1000 mechanically ventilated days] vs 369 [12%; 88 of 1000 mechanically ventilated days], p=048). Of the 320 patients with tracheobronchitis, 250 received appropriate antibiotic treatment and 70 received inappropriate antibiotics. 39 patients with tracheobronchitis progressed to pneumonia; however, the use of appropriate antibiotic therapy for tracheobronchitis was associated with significantly lower progression to pneumonia than was inappropriate treatment (19 [8%] of 250 vs 20 [29%] of 70, p<00001; crude odds ratio 021 [95% CI 011-041]). Significantly more patients with ventilator-associated pneumonia died (146 [40%] of 369) than those with tracheobronchitis (93 [29%] of 320) or absence of ventilator-associated lower respiratory tract infections (673 [30%] of 2271, p<00001). Median time to discharge from the ICU for survivors was significantly longer in the tracheobronchitis (21 days [IQR 15-34]) and pneumonia (22 [13-36]) groups than in the group with no ventilator-associated lower respiratory tract infections (12 [8-20]; hazard ratio 165 [95% CI 138-197], p<00001).This large database study emphasises that ventilator-associated tracheobronchitis is a major health problem worldwide, associated with high resources consumption in all countries. Our findings also show improved outcomes with use of appropriate antibiotic treatment for both ventilator-associated tracheobronchitis and ventilator-associated pneumonia, underlining the importance of treating both infections, since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia.None.


Jasseron C.,French Institute of Health and Medical Research | Jasseron C.,Hospital Bicetre | Mandelbrot L.,French Institute of Health and Medical Research | Mandelbrot L.,University Paris Diderot | And 15 more authors.
AIDS and Behavior | Year: 2013

Our objective was to study relations between non-disclosure of HIV to partner, socio demographics and prevention of HIV mother-to-child transmission (PMTCT), among HIV-infected pregnant women enrolled in the French Perinatal Cohort (ANRS-EPF-CO1) from 2005 to 2009 (N = 2,952). Fifteen percent of the women did not disclose their HIV status to their partner. Non-disclosure was more frequent in women diagnosed with HIV infection late in pregnancy, originating from Sub-Saharan Africa or living alone, as well as when the partner was not tested for HIV. Non-disclosure was independently associated with non optimal PMTCT: late initiation of antiretroviral therapy, detectable viral load at delivery and lack of neonatal prophylaxis. Nonetheless, the rate of transmission did not differ according to disclosure status. Factors associated with non-disclosure reflect vulnerability and its association with non optimal PMTCT is a cause for concern although the impact on transmission was limited in this context of universal free access to care. © 2011 Springer Science+Business Media, LLC.


Rachas A.,French Institute of Health and Medical Research | Warszawski J.,French Institute of Health and Medical Research | Warszawski J.,University Paris - Sud | Warszawski J.,Bicetre Hospital | And 13 more authors.
AIDS | Year: 2013

OBJECTIVE: A part of women starting antiretroviral therapy during pregnancy fail to attain undetectable viral load by delivery. Here we studied whether pregnancy affects the early immunovirological response to combined antiretroviral therapy (cART), taking into account treatment duration and baseline characteristics. DESIGN: Antiretroviral-naive women initiating cART since 2004 and followed in three French ANRS multicenter HIV cohorts (French Perinatal Cohort, PRIMO and COPANA). METHODS: The early virological response (at 1, 3 and 6 months) and immunological increase after cART initiation were compared between women starting cART during (n=708) and outside (n=110) pregnancy. Relative risks were estimated in multivariate models adjusted for treatment duration, baseline viral load and CD4, sociodemographic factors and chronic hepatitis B. CD4 increases were compared by using mixed models. RESULTS: Only 63.8% of treated pregnant women attained a viral load less than 50copies/ml by delivery. Similarly to nonpregnant women, nearly 90% of pregnant women reached a viral load less than 400copies/ml at M3 [adjusted RR: 1.0 (95% confidence interval 0.7-1.4)], and nearly 100% at M6 following cART initiation [0.9 (0.4-1.9)]. viral load less than 50copies/ml was attained by 61.5% of pregnant versus 67.9% of nonpregnant women at M3 (P=0.26), and by 82.1 versus 87.0% at M6 (P=0.48). CD4 recovery (both number and percentage) was similar in pregnant and nonpregnant women. Results were similar for the subset of women starting a boosted protease inhibitor-containing cART. CONCLUSION: Pregnancy does not affect the virological response to cART below 400copies/ml, or CD4 increase. The main reason for pregnant women not achieving viral load less than 50copies/ml at delivery appears to be a short duration of treatment. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Adam F.,University Paris - Sud | Khatib A.-M.,French Institute of Health and Medical Research | Lopez J.J.,University Paris - Sud | Vatier C.,French Institute of Health and Medical Research | And 23 more authors.
Blood | Year: 2016

Apelin peptide and its receptor APJ are directly implicated in various physiological processes ranging from cardiovascular homeostasis toimmunesignaling. Here,weshow that apelin is a key player in hemostasis with an ability to inhibit thrombin- And collagenmediated platelet activation. Mice lacking apelin displayed a shorter bleeding time and a prothrombotic profile. Their platelets exhibited increased adhesion and a reduced occlusion time in venules, and displayed a higher aggregation rate after their activation by thrombin compared with wild-type platelets. Consequently, human and mouse platelets express apelin and its receptor APJ. Apelin directly interferes with thrombin-mediated signaling pathways and platelet activation, secretion, and aggregation, but not with ADP and thromboxane A2-mediated pathways. IV apelin administration induced excessive bleeding and prevented thrombosis in mice. Taken together, these findings suggest that apelin and/or APJ agonists could potentially be useful adducts in antiplatelet therapies and may provide a promising perspective for patients who continue to display adverse thrombotic events with current antiplatelet therapies. © 2016 by The American Society of Hematology.

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