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INTRODUCTION: Venoactive drugs (VADs) are considered an important component of the medical (conservative) treatment of chronic venous disorders (CVDs). However, the efficacy of certain VADs on one or more individual leg symptoms may have not been extensively studied to justify a high level or grade of recommendation in guidelines on CVD. The aim of the present systematic review and meta-analysis was to study the effectiveness of VADs containing Ruscus across the spectrum of defined venous symptoms. EVIDENCE ACQUISITION: On November 14 2016, a literature search of the databases MEDLINE and Scopus was performed, supplemented by hand searching, to identify randomized double-blind placebo-controlled trials on Ruscus extracts in patients with CVD. EVIDENCE SYNTHESIS: The main outcome measures were the effects of Ruscus on individual symptoms and leg edema, which were expressed as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). Trial quality of evidence was graded using the GRADE system. We identified 10 trials, mostly with low risk of bias, on 719 patients. On qualitative analysis, Ruscus significantly improved seven defined leg symptoms, including pain, heaviness, fatigue, feeling of swelling, cramps, itching and paresthesia compared to placebo. On quantitative analysis, Ruscus compared with placebo, assessed as a categorical variable, reduced leg pain (RR=0.35, P=0.01, number needed to treat [NNT] 5, with no heterogeneity), heaviness (RR=0.26, P<0.00001, NNT=2.4, with a small amount of heterogeneity), feeling of swelling (RR=0.53, P<0.0001, NNT=4, with considerable heterogeneity, minimized after sensitivity analysis), paresthesia (RR=0.27, P<0.0001, NNT=1.8), global symptoms (RR=0.54, P<0.00001, NNT=4.3) and the total number of venous symptoms (RR 0.41, P=0.002). Similarly, Ruscus compared to placebo, assessed as a continuous variable reduced pain (SMD=-0.80, 95% CI:-1.21 to-0.39), heaviness (SMD=-1.23, 95% CI:-1.60 to-0.86), fatigue (SMD-1.16, 95% CI:-1.71 to-0.61), feeling of swelling (SMD=-2.27, 95% CI:-3.83 to-0.70), and paresthesia (SMD=-0.86, 95% CI:-1.51 to-0.21). Regarding objective assessments of leg edema, the use of Ruscus compared with placebo reduced ankle circumference (SMD=-0.74, 95% CI:-1.01 to-0.47) and leg or foot volume (SMD=-0.61, 95% CI:-0.91 to-0.31). The existing evidence, where sufficient, was mostly of high quality. CONCLUSIONS: Based on high quality evidence, Ruscus extracts are highly effective in reducing symptoms and edema of patients with CVD.


Ambert-Balay K.,University Hospital of Dijon | Pothier P.,University Hospital of Dijon
Journal of Clinical Virology | Year: 2013

Background: The rapid detection of noroviruses is essential to implement measures to reduce the rapid spread of gastroenteritis infections they cause, notably in institutions. Objectives: To evaluate 4 rapid immunochromatographic tests: RIDA®QUICK Norovirus, ImmunoCardSTAT!® Norovirus, NOROTOP® and SD BIOLINE NOROVIRUS by determining their sensitivity and specificity on a large panel of samples representing 11 genotypes of norovirus genogroup I and 14 of genogroup II, and their cross-reactivity with other enteric viruses. Study design: Thawed stool samples containing norovirus genogroup I or II or other enteric viruses, and negative samples, were tested by the 4 assays and compared to the reference standard RT-PCR. Fresh stool samples were also tested by RIDA®QUICK. Results: The sensitivity of RIDA®QUICK, ImmunoCardSTAT!®, NOROTOP® and SD BIOLINE for the detection of norovirus genogroup I on thawed samples was 17%, 26%, 52% and 23%, respectively. For genogroup II, the sensitivity was 64%, 39%, 50% and 54%, respectively. For GII.4, the main circulating genotype, the sensitivity was 78%, 59%, 61% and 67%, respectively. For all tests, the specificity was 100% and no cross-reactivity with other enteric viruses was observed. The sensitivity of RIDA®QUICK on fresh stool samples positive for GII.4 was 71%. Conclusions: Knowing that most gastroenteritis cases are due to GII.4, the immunochromatographic tests may be useful for preliminary screening, notably in outbreaks. However, negative samples need to be tested using RT-PCR methods. © 2012 Elsevier B.V.


Siebor E.,University Hospital of Dijon | Neuwirth C.,University Hospital of Dijon
The Journal of antimicrobial chemotherapy | Year: 2014

OBJECTIVES: To analyse the genetic environment of the antibiotic resistance genes in two clinical Proteus mirabilis isolates resistant to multiple antibiotics.METHODS: PCR, gene walking and whole-genome sequencing were used to determine the sequence of the resistance regions, the surrounding genetic structure and the flanking chromosomal regions.RESULTS: A genomic island of 81.1 kb named Proteus genomic island 1 (PGI1) located at the 3'-end of trmE (formerly known as thdF) was characterized. The large MDR region of PGI1 (55.4 kb) included a class 1 integron (aadB and aadA2) and regions deriving from several transposons: Tn2 (blaTEM-135), Tn21, Tn6020-like transposon (aphA1b), a hybrid Tn502/Tn5053 transposon, Tn501, a hybrid Tn1696/Tn1721 transposon [tetA(A)] carrying a class 1 integron (aadA1) and Tn5393 (strA and strB). Several ISs were also present (IS4321, IS1R and IS26). The PGI1 backbone (25.7 kb) was identical to that identified in Salmonella Heidelberg SL476 and shared some identity with the Salmonella genomic island 1 (SGI1) backbone. An IS26-mediated recombination event caused the division of the MDR region into two parts separated by a large chromosomal DNA fragment of 197 kb, the right end of PGI1 and this chromosomal sequence being in inverse orientation.CONCLUSIONS: PGI1 is a new resistance genomic island from P. mirabilis belonging to the same island family as SGI1. The role of PGI1 in the spread of antimicrobial resistance genes among Enterobacteriaceae of medical importance needs to be evaluated. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


BACKGROUND: The incidence of acute kidney injury (AKI) is estimated at 10 to 20% in patients admitted to intensive care units (ICU) and often requires renal replacement therapy (RRT). ICU mortality in AKI patients can exceed 50%. Venous catheters are the preferred vascular access method for AKI patients requiring RRT, but carry a risk of catheter thrombosis or infection. Catheter lock solutions are commonly used to prevent such complications. Heparin and citrate locks are both widely used for tunneled, long-term catheters, but few studies have compared citrate versus heparin for patients with short-term, non-tunneled catheters. We aim to compare citrate 4% catheter lock solution versus heparin in terms of event-free survival of the first non-tunneled hemodialysis catheter inserted in ICU patients with AKI requiring RRT. Secondary objectives are the rate of fibrinolysis, incidence of catheter thrombosis and catheter-related infection per 1,000 catheter days, length of stay in ICU and in-hospital and 28-day mortality.METHODS/DESIGN: The VERROU-REA study is a randomized, prospective, multicenter, double-blind, parallel-group, controlled superiority study carried out in the medical, surgical and nephrological ICUs of two large university hospitals in eastern France. A catheter lock solution composed of trisodium citrate at 4% will be compared to unfractionated heparin at a concentration of 5,000 IU/mL. All consecutive adult patients with AKI requiring extracorporeal RRT, and in whom a first non-tunneled catheter is to be inserted by the jugular or femoral approach, will be eligible. Catheters inserted by the subclavian approach, patients with acute liver failure, thrombopenia or contraindication to systemic anticoagulation will be excluded. Patients will be followed up daily in accordance with standard practices for RRT until death or discharge.DISCUSSION: Data is scarce regarding the use of non-tunneled catheters in the ICU setting in patients with AKI. This study will provide an evidence base for recommendations regarding the use of anticoagulant catheter locks for the prevention of dysfunction in non-tunneled hemodialysis catheters in patients with AKI in critical or intensive care.TRIAL REGISTRATION: Registered with Clinicaltrials.gov (registration number: NCT01962116) on 27 August 2013.


Bador J.,University Hospital of Dijon | Amoureux L.,University Hospital of Dijon | Blanc E.,University Hospital of Dijon | Neuwirth C.,University Hospital of Dijon
Antimicrobial Agents and Chemotherapy | Year: 2013

Achromobacter xylosoxidans is an innately multidrug-resistant pathogen which is emerging in cystic fibrosis (CF) patients. We characterized a new resistance-nodulation-cell division (RND)-type multidrug efflux pump, AxyXY-OprZ. This system is responsible for the intrinsic high-level resistance of A. xylosoxidans to aminoglycosides (tobramycin, amikacin, and gentamicin). Furthermore, it can extrude cefepime, carbapenems, some fluoroquinolones, tetracyclines, and erythromycin. Some of the AxyXY-OprZ substrates are major components widely used to treat pulmonary infections in CF patients. Copyright © 2013, American Society for Microbiology. All Rights Reserved.


Jambet S.,University Hospital of Dijon
The American journal of emergency medicine | Year: 2012

Several drugs used in psychiatry may induce constipation, paralytic ileus, or acute megacolon (Ogilvie's syndrome). We report here 2 cases of patients presenting with fatal abdominal compartment syndrome related to the absorption of antidepressants and benzodiazepines. Two patients (a 27-year-old man and a 57-year-old woman) with a previous psychiatric history and treatment with psychiatric drugs were admitted to the emergency department for coma. Both presented hypothermia; a hard, distended abdomen; and ischemia of the lower limbs. In both cases, the abdominal scan showed massive colonic dilatation without mechanical obstruction; there was even aortic compression and ischemia of the abdominal viscera. Emergency laparotomy with bowel decompression was performed in both cases, but multiple organ failure led to death in both patients. Psychiatric drugs may induce acute severe megacolon with life-threatening abdominal compartment syndrome.


Siebor E.,University Hospital of Dijon | Neuwirth C.,University Hospital of Dijon
Journal of Antimicrobial Chemotherapy | Year: 2011

Objectives: The clinical strain of Proteus mirabilis VB1248 isolated from a blood culture in August 2009 was multiresistant (i.e. resistant to β-lactams, fluoroquinolones, aminoglycosides and sulphonamides). We searched for the presence of a Salmonella genomic island 1 (SGI1). Methods: The whole genetic structure surrounding the genes involved in antibiotic resistance was characterized by PCR or gene walking followed by DNA sequencing. Results: The new variant SGI1-V (42.9 kb) was located downstream of the thdF chromosomal gene. Genes sharing homology with phage-related genes were detected on a structure of 8.3 kb located between the right junction of the SGI1-V and the hipB/hipA genes. Some genetic rearrangements occurred in the SGI1-V backbone: an insertion of 2349 bp within the open reading frame (ORF) S014, and a deletion of 3766 bp in the region spanning from ORFs S021 to S025 leading to the lack of ORFs S023 and S024. The multidrug resistance (MDR) region of 17.1 kb was located on a complex class 1 integron extremely different from those described so far. The cassette array included aacA4, aadB and dhfrA1. Adjacent to this classical structure, bla VEB-6 was found flanked by 135 bp elements and bracketed by two 3'-conserved segments (3'-CS). Downstream of the second copy of 3'-CS, the qnrA1 gene was associated with common region 1. Conclusions: We have identified in P. mirabilis the new variant SGI1-V containing the bla VEB-6 and qnrA1 genes in the MDR region. This is the first report of an extended-spectrum β-lactamase-encoding gene and a qnr determinant conferring resistance to quinolones on an SGI1-like structure. It might constitute a source of spread of resistance to other bacterial species. © The Author 2011. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Siebor E.,University Hospital of Dijon | Neuwirth C.,University Hospital of Dijon
Journal of Antimicrobial Chemotherapy | Year: 2013

Objectives: Salmonella genomic island 1 (SGI1) is often encountered in antibiotic-resistant Salmonella enterica and exceptionally in Proteus mirabilis. We investigated the prevalence of SGI1-producing clinical isolates of P. mirabilis in our hospital (Dijon, France). Methods: A total of 57 strains of P. mirabilis resistant to amoxicillin and/or gentamicin and/or trimethoprim/ sulfamethoxazole isolated from August 2011 to February 2012 as well as 9 extended-spectrum b-lactamase (ESBL)-producing P. mirabilis from our collection were tested for the presence of SGI1 by PCR. The complete SGI1 structure from positive isolates [backbone and multidrug resistance (MDR) region] was sequenced. Results: SGI1 was detected in 7 isolates; 5 out of the 57 isolates collected during the study period (9%) and 2 out of the 9 ESBL-producing strains of our collection. The structures of the seven SGI1s were distinct. Three different backbones were identified: one identical to the SGI1 backbone from the epidemic Salmonella Typhimurium DT104, one with variations already described in SGI1-K from Salmonella Kentucky (deletion and insertion of IS1359 in the region spanning from S005 to S009) and one with a variation never detected before (deletion from S005 to S009). Six different MDR regions were identified: four simple variants containing resistance genes already described and two variants harbouring a very complex structure including regions derived from several transposons and IS26 elements with aphA1a never reported to date in SGI1. Conclusions: SGI1 variants are widely distributed among P. mirabilis clinical strains and might spread to other commensal Enterobacteriaceae. This would become a serious public health problem. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Vinit J.,University Hospital of Dijon | Bielefeld P.,University Hospital of Dijon | Muller G.,University Hospital of Dijon | Besancenot J.-F.,University Hospital of Dijon
Joint Bone Spine | Year: 2012

Giant cell arteritis is the most frequent form of vasculitis characterized by a high risk of vascular thrombosis. Major complications are blindness and other vascular ischemia but bowel ischemic involvement is rare. Treatment is based on long-term steroid therapy with numerous side effects. The efficacy of immunosuppressive drugs like azathioprine methotrexate or anti-tumor necrosis factor antibodies appears to be too low to reduce the use of steroids. Th17 lymphocytes and interleukin-6 play an important role in pathogenesis of giant cell arteritis. We report here a case of effective interleukin-6 blocker in the treatment of refractory giant cell arteritis with ileitis and high-dose steroid dependence despite 2. years of treatment with steroids and methotrexate. After infusions of tocilizumab, no relapse at 6. months was found despite the decrease in corticosteroids. © 2011 Société française de rhumatologie.


Benetos A.,University of Lorraine | Benetos A.,Nancy University Hospital Center | Labat C.,University of Lorraine | Rossignol P.,University of Lorraine | And 9 more authors.
JAMA Internal Medicine | Year: 2015

IMPORTANCE: Clinical evidence supports the beneficial effects of lowering blood pressure (BP) levels in community-living, robust, hypertensive individuals older than 80 years. However, observational studies in frail elderly patients have shown no or even an inverse relationship between BP and morbidity and mortality. OBJECTIVE: To assess all-cause mortality in institutionalized individuals older than 80 years according to systolic BP (SBP) levels and number of antihypertensive drugs. DESIGN, SETTING, AND PARTICIPANTS: This longitudinal study included elderly residents of nursing homes. The interaction between low (<130 mm Hg) SBP and the presence of combination antihypertensive treatment on 2-year all-cause mortality was analyzed. A total of 1127 women and men older than 80 years (mean, 87.6 years; 78.1% women) living in nursing homes in France and Italy were recruited, examined, and monitored for 2 years. Blood pressure was measured with assisted self-measurements in the nursing home during 3 consecutive days (mean, 18 measurements). Patients with an SBP less than 130 mm Hg who were receiving combination antihypertensive treatment were compared with all other participants. MAIN OUTCOMES AND MEASURES: All-cause mortality over a 2-year follow-up period. RESULTS: A significant interaction was found between low SBP and treatment with 2 or more BP-lowering agents, resulting in a higher risk of mortality (unadjusted hazard ratio [HR], 1.81; 95% CI, 1.36-2.41); adjusted HR, 1.78; 95% CI, 1.34-2.37; both P < .001) in patients with low SBP who were receiving multiple BP medicines compared with the other participants. Three sensitivity analyses confirmed the significant excess of risk: propensity score-matched subsets (unadjusted HR, 1.97; 95% CI, 1.32-2.93; P < .001; adjusted HR, 2.05; 95% CI, 1.37-3.06; P < .001), adjustment for cardiovascular comorbidities (HR, 1.73; 95% CI, 1.29-2.32; P < .001), and exclusion of patients without a history of hypertension who were receiving BP-lowering agents (unadjusted HR, 1.82; 95% CI, 1.33-2.48; P < .001; adjusted HR, 1.76; 95% CI, 1.28-2.41; P < .001). CONCLUSIONS AND RELEVANCE: The findings of this study raise a cautionary note regarding the safety of using combination antihypertensive therapy in frail elderly patients with low SBP (<130 mm Hg). Dedicated, controlled interventional studies are warranted to assess the corresponding benefit to risk ratio in this growing population. Copyright 2015 American Medical Association. All rights reserved.

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