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Hôpital-Camfrout, France

Josseran L.,French Institute for Public Health Surveillance | Fouillet A.,French Institute for Public Health Surveillance | Caillere N.,French Institute for Public Health Surveillance | Brun-Ney D.,Assistance Publique des Hopitaux de Paris | And 4 more authors.

Background: Syndromic surveillance systems have been developed in recent years and are now increasingly used by stakeholders to quickly answer questions and make important decisions. It is therefore essential to evaluate the quality and utility of such systems. This study was designed to assess a syndromic surveillance system based on emergency departments' (ED) morbidity rates related to the health effects of heat waves. This study uses data collected during the 2006 heat wave in France. Methods: Data recorded from 15 EDs in the Ile-de-France (Paris and surrounding area) from June to August, 2006, were transmitted daily via the Internet to the French Institute for Public Health Surveillance. Items collected included diagnosis (ICD10), outcome, and age. Several aspects of the system have been evaluated (data quality, cost, flexibility, stability, and performance). Periods of heat wave are considered the most suitable time to evaluate the system. Results: Data quality did not vary significantly during the period. Age, gender and outcome were completed in a comprehensive manner. Diagnoses were missing or uninformative for 37.5% of patients. Stability was recorded as being 99.49% for the period overall. The average cost per day over the study period was estimated to be J287. Diagnoses of hyperthermia, malaise, dehydration, hyponatremia were correlated with increased temperatures. Malaise was most sensitive in younger and elderly adults but also the less specific. However, overall syndrome groups were more sensitive with comparable specificity than individual diagnoses. Conclusion: This system satisfactorily detected the health impact of hot days (observed values were higher than expected on more than 90% of days on which a heat alert was issued). Our findings should reassure stakeholders about the reliability of health impact assessments during or following such an event. These evaluations are essential to establish the validity of the results of syndromic surveillance systems. © 2010 Josseran et al. Source

Kemp S.,University of Amsterdam | Berger J.,Medical University of Vienna | Aubourg P.,Assistance Publique des Hopitaux de Paris | Aubourg P.,University of Paris Descartes
Biochimica et Biophysica Acta - Molecular Basis of Disease

X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. The two main clinical phenotypes of X-ALD are adrenomyeloneuropathy (AMN) and inflammatory cerebral ALD that manifests either in children or more rarely in adults. About 65% of heterozygote females develop symptoms by the age of 60. years. Mutations in the ABCD1 gene affect the function of the encoded protein ALDP, an ATP-binding-cassette (ABC) transporter located in the peroxisomal membrane protein. ALDP deficiency impairs the peroxisomal beta-oxidation of very long-chain fatty acids (VLCFA) and facilitates their further chain elongation by ELOVL1 resulting in accumulation of VLCFA in plasma and tissues. While all patients have mutations in the ABCD1 gene, there is no general genotype-phenotype correlation. Environmental factors and a multitude of modifying genes appear to determine the clinical manifestation in this monogenetic but multifactorial disease. This review focuses on the clinical, biochemical, genetic and pathophysiological aspects of X-ALD. This article is part of a Special Issue entitled: Metabolic Functions and Biogenesis of Peroxisomes in Health and Disease. © 2012 Elsevier B.V.. Source

Mitchell P.,University of Sydney | Bandello F.,San Raffaele Scientific Institute | Schmidt-Erfurth U.,University of Vienna | Lang G.E.,University of Ulm | And 7 more authors.

Objective: To demonstrate superiority of ranibizumab 0.5 mg monotherapy or combined with laser over laser alone based on mean average change in best-corrected visual acuity (BCVA) over 12 months in diabetic macular edema (DME). Design: A 12-month, randomized, double-masked, multicenter, laser-controlled phase III study. Participants: We included 345 patients aged <18 years, with type 1 or 2 diabetes mellitus and visual impairment due to DME. Methods: Patients were randomized to ranibizumab + sham laser (n = 116), ranibizumab + laser (n = 118), or sham injections + laser (n = 111). Ranibizumab/sham was given for 3 months then pro re nata (PRN); laser/sham laser was given at baseline then PRN (patients had scheduled monthly visits). Main Outcome Measures: Mean average change in BCVA from baseline to month 1 through 12 and safety. Results: Ranibizumab alone and combined with laser were superior to laser monotherapy in improving mean average change in BCVA letter score from baseline to month 1 through 12 (+6.1 and +5.9 vs +0.8; both P<0.0001). At month 12, a significantly greater proportion of patients had a BCVA letter score <15 and BCVA letter score level >73 (20/40 Snellen equivalent) with ranibizumab (22.6% and 53%, respectively) and ranibizumab + laser (22.9% and 44.9%) versus laser (8.2% and 23.6%). The mean central retinal thickness was significantly reduced from baseline with ranibizumab (-118.7 μm) and ranibizumab + laser (-128.3 μm) versus laser (-61.3 μm; both P<0.001). Health-related quality of life, assessed through National Eye Institute Visual Function Questionnaire (NEI VFQ-25), improved significantly from baseline with ranibizumab alone and combined with laser (P<0.05 for composite score and vision-related subscales) versus laser. Patients received ∼7 (mean) ranibizumab/sham injections over 12 months. No endophthalmitis cases occurred. Increased intraocular pressure was reported for 1 patient each in the ranibizumab arms. Ranibizumab monotherapy or combined with laser was not associated with an increased risk of cardiovascular or cerebrovascular events in this study. Conclusions: Ranibizumab monotherapy and combined with laser provided superior visual acuity gain over standard laser in patients with visual impairment due to DME. Visual acuity gains were associated with significant gains in VFQ-25 scores. At 1 year, no differences were detected between the ranibizumab and ranibizumab + laser arms. Ranibizumab monotherapy and combined with laser had a safety profile in DME similar to that in age-related macular degeneration. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. © 2011 American Academy of Ophthalmology. Source

Amar L.,University of Paris Descartes | Azizi M.,University of Paris Descartes | Azizi M.,French Institute of Health and Medical Research | Menard J.,University of Paris Descartes | And 4 more authors.
Journal of Hypertension

Objective: We compared the effects of aldosterone synthase inhibition with LCI699 with those of mineralocorticoid receptor blockade in patients with primary aldosteronism. Methods: After a 2-week placebo run-in, 14 patients with primary aldosteronism received oral LCI699 (0.5 mg b.i.d.) from day 1 to 14, LCI699 (1 mg b.i.d.) from day 15 to 29, and placebo from day 29 to 36. From day 36 to day 66, patients were treated with eplerenone (50 mg b.i.d., up-titrated to 100 mg b.i.d. in 12/14 patients), in addition to their previous antihypertensive treatment, which was maintained unchanged. Results: Eplerenone significantly decreased more 24-h ambulatory SBP on day 66 than LCI699 on day 29 and the difference between the two treatment was -5.34 [95% confidence interval (CI) -10.30; -0.38)] mmHg (P = 0.027). Plasma potassium concentration achieved on eplerenone (4.30 ± 0.45 mmol/l) was significantly greater than on LCI699 (3.89 ± 0.35 mmol/l; P = 0.009). The increase in plasma renin concentration was significantly greater after eplerenone [+131% (range 61; 231)] than on LCI699 on day 29 [+39% (range 5; 86); P = 0.023]. LCI699 markedly decreased plasma aldosterone concentration by 75% (range -84; -63), whereas eplerenone markedly increased this concentration, from day 36, by 89% (range 40;154; P < 0.0001 vs. day 29). Conclusion: In patients with primary aldosteronism, the effects on blood pressure and plasma potassium and renin concentrations of 4 weeks of eplerenone treatment (50-100mg b.i.d.) were more marked than those of 4 weeks of LCI699 treatment (0.5-1mg b.i.d.). These two drugs had opposite effects on plasma aldosterone concentration. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Kodjikian L.,Hospices Civils de Lyon | Kodjikian L.,University of Lyon | Kodjikian L.,CNRS Laboratory for Materials: Engineering and Science | Souied E.H.,Center Hospitalier Intercommunal Of Creteil | And 12 more authors.

Objective To evaluate the relative efficacy and safety profile of bevacizumab versus ranibizumab intravitreal injections for the treatment of neovascular age-related macular degeneration (AMD). Design Multicenter, prospective, noninferiority, double-masked, randomized clinical trial performed in 38 French ophthalmology centers. The noninferiority limit was 5 letters. Participants Patients aged ≥50 years were eligible if they presented with subfoveal neovascular AMD, with best-corrected visual acuity (BVCA) in the study eye of between 20/32 and 20/320 measured on the Early Treatment of Diabetic Retinopathy Study chart and a lesion area of less than 12 optic disc areas (DA). Methods Patients were randomly assigned to intravitreal administration of bevacizumab (1.25 mg) or ranibizumab (0.50 mg). Hospital pharmacies were responsible for preparing, blinding, and dispensing treatments. Patients were followed for 1 year, with a loading dose of 3 monthly intravitreal injections, followed by an as-needed regimen (1 injection in case of active disease) for the remaining 9 months with monthly follow-up. Main Outcome Measures Mean change in visual acuity at 1 year. Results Between June 2009 and November 2011, 501 patients were randomized. In the per protocol analysis, bevacizumab was noninferior to ranibizumab (bevacizumab minus ranibizumab +1.89 letters; 95% confidence interval [CI], -1.16 to +4.93, P < 0.0001). The intention-to-treat analysis was concordant. The mean number of injections was 6.8 in the bevacizumab group and 6.5 in the ranibizumab group (P = 0.39). Both drugs reduced the central subfield macular thickness, with a mean decrease of 95 μm for bevacizumab and 107 μm for ranibizumab (P = 0.27). There were no significant differences in the presence of subretinal or intraretinal fluid at final evaluation, dye leakage on angiogram, or change in choroidal neovascular area. The proportion of patients with serious adverse events was 12.6% in the bevacizumab group and 12.1% in the ranibizumab group (P = 0.88). The proportion of patients with serious systemic or ocular adverse events was similar in both groups. Conclusions Bevacizumab was noninferior to ranibizumab for visual acuity at 1 year with similar safety profiles. Ranibizumab tended to have a better anatomic outcome. The results are similar to those of previous head-to-head studies. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references. © 2013 by the American Academy of Ophthalmology. Source

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