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Kuhn P.,University of Strasbourg | Dheu C.,University of Strasbourg | Dheu C.,Center Hospitalier Of Colmar | Bolender C.,Center Hospitalier Of Haguenau | And 7 more authors.
Paediatric and Perinatal Epidemiology | Year: 2010

In 2001 France issued a new set of guidelines for the use of antenatal antibiotics (AA). These guidelines recommended intrapartum antimicrobial prophylaxis (IAP) to prevent group B streptococcal (GBS) disease and AA to prolong pregnancy in the event of preterm premature rupture of membranes (AA for PPROM). This study aims to determine the effects of AA, recommended by national guidelines, on the incidence and distribution of pathogens in early-onset neonatal sepsis (EONS). We performed a population-based, prospective, observational study of level II and III perinatal centres throughout the region of Alsace, a northeastern area of France, between March 2004 and February 2005. The study population included all neonates with confirmed or probable EONS, who were treated with antibiotics for at least 5 days. We analysed exposure to AA, as well as clinical and microbiological data obtained from medical records. A total of 20 131 neonates were born during the study period, and 217 were included in the study. Of these, 24 subjects had confirmed sepsis, 140 had probable sepsis and 53 had possible EONS. The overall incidence of confirmed EONS was 1.19 per 1000 births. The infecting bacteria was GBS in 15 of 24 (62.5%) confirmed EONS cases (incidence: 0.75 per 1000 births) and in 81 of 140 (58%) probable sepsis cases. Escherichia coli was identified in 6 of 24 (25%) cases of confirmed EONS (incidence: 0.3 per 1000 births) and in 30 of 140 (21%) cases of clinical sepsis. Among E. coli infections (n = 36), amoxicillin resistance (n = 18) was statistically linked with AA use (P = 0.045). This link was significant in cases of PPROM (P = 0.015), but not when IAP was administered to prevent GBS disease (P = 0.264). IAP was not performed in 18 of 60 (30%) cases and 32 of 93 (34%) cases, despite positive screening or the presence of risk factors for EONS, respectively. Group B streptococcus remains the predominant pathogen in the era of AA. Aminopenicillin-resistant E. coli infections seem to be linked to prolonged AA in cases of PPROM and appear to preferentially affect preterm infants. Therefore, postnatal treatment strategies should consider this possible effect. Our data indicate that the current policy of GBS maternal prophylaxis is not associated with an excessive risk of pathogen resistance. Considering the high incidence of GBS EONS in our region, possible progress could result from better observance of guidelines. These results strengthen the need for continuation of surveillance. © 2010 Blackwell Publishing Ltd.

Schaefer E.,Hopitaux Universitaires Of Strasbourg | Schaefer E.,University of Strasbourg | Collet C.,Service de Biochimie et de Biologie Moleculaire | Genevieve D.,Montpellier University | And 11 more authors.
Genetics in Medicine | Year: 2014

Purpose:Treacher Collins syndrome is a mandibulofacial dysostosis caused by mutations in genes involved in ribosome biogenesis and synthesis. TCOF1 mutations are observed in ∼80% of the patients and are inherited in an autosomal dominant manner. Recently, two other genes have been reported in <2% of patients - POLR1D in patients with autosomal dominant inheritance, and POLR1C in patients with autosomal recessive inheritance.Methods:We performed direct sequencing of TCOF1, POLR1C, and POLR1D in two unrelated consanguineous families.Results:The four affected children shared the same homozygous mutation in POLR1D (c.163C>G, p.Leu55Val). This mutation is localized in a region encoding the dimerization domain of the RNA polymerase. It is supposed that this mutation impairs RNA polymerase, resulting in a lower amount of mature dimeric ribosomes. A functional analysis of the transcripts of TCOF1 by real-time quantitative reverse transcription-polymerase chain reaction was performed in the first family, demonstrating a 50% reduction in the index case, compatible with this hypothesis.Conclusion:This is the first report of POLR1D mutation being responsible for an autosomal recessive inherited Treacher Collins syndrome. These results reinforce the concept of genetic heterogeneity of Treacher Collins syndrome and underline the importance of combining clinical expertise and familial molecular analyses for appropriate genetic counseling.Genet Med 16 9, 720-724. © American College of Medical Genetics and Genomics.

Hanssen M.,Center Hospitalier Of Haguenau | Cottin Y.,University of Burgundy | Khalife K.,Center Hospitalier Re Gional Of Metz | Hammer L.,Intensive Care Cardiology | And 10 more authors.
Heart | Year: 2012

Aim of FAST-MI 2010: To gather data on characteristics, management and outcomes of patients hospitalised for acute myocardial infarction (AMI) at the end of 2010 in France. Interventions: To provide cardiologists and health authorities national and regional data on AMI management every 5 years. Setting: Metropolitan France. 213 academic (n=38), community (n=110), army hospitals (n=2), private clinics (n=63), representing 76% of centres treating AMI patients. Inclusion from 1 October 2010. Population: Consecutive patients included during 1 month, with a possible extension of recruitment up to one additional month (132 centres); 4169 patients included over the entire recruitment period, 3079 during the first 31 days; 249 additional patients declining participation (5.6%). Startpoints: Consecutive adults with ST-elevation and non-ST-elevation AMI with symptom onset ≤48 h. Patients with AMI following cardiovascular procedures excluded. Data capture: Web-based collection of 385 items (demographic, medical, biologic, management data) recorded online from source files by external research technicians; case-record forms with automatic quality checks. Centralised biology in voluntary centres to collect DNA samples and serum. Long-term follow-up organised centrally with interrogation of municipal registry offices, patients' physicians, and direct contact with the patients. Data quality: Data management in Toulouse University. Statistical analyses: Université Paris Descartes, Université de Toulouse, Université Pierre et Marie Curie- Paris 06, Paris. Endpoints and linkages to other data: In-hospital events; cardiovascular events, hospital admissions and mortality during follow-up. Linkage with Institute for National Statistics. Access to data: Available for research to any participating clinician upon request to executive committee (fastmi2010@yahoo.fr).

Steinbach M.,Center Hospitalier Of Haguenau | Douchet M.-P.,University of Strasbourg | Bakouboula B.,University of Strasbourg | Bronner F.,University of Strasbourg | Chauvin M.,University of Strasbourg
Archives of Cardiovascular Diseases | Year: 2011

Background: The prognosis for patients aged over 75 years who receive a pacemaker in the context of sinus node dysfunction is unclear. Aims: We sought to evaluate the incidences of atrial fibrillation, heart failure and death in such patients, and the role of the pacing mode in their prognosis. Methods: This was a retrospective study of 102 patients aged over 75 years (mean 82.2 ± 4.4 years) who received a pacemaker in the context of sinus node dysfunction. Results: During the follow-up period (mean 806 days), 36 patients (35.3%) experienced heart failure, 47 patients (46.1%) had an episode of paroxysmal atrial fibrillation, 19 patients (18.6%) progressed to chronic atrial fibrillation and 29 (28.4%) died, the fatal event being sudden death or of cardiac origin in almost half of these patients (44.8%). Patients assigned to dual-chamber minimal ventricular pacing showed significantly lower rates of heart failure episodes (P = 0.023) and all-cause mortality (P < 0.001) than those assigned to conventional dual-chamber pacing. In contrast, the two groups did not differ with regard to either paroxysmal or chronic atrial fibrillation. Conclusion: In patients aged over 75 years, the use of dual-chamber pacemakers incorporating an algorithm minimizing ventricular pacing for sinus node dysfunction seems to decrease the number of heart failure episodes and mortality. On the basis of this finding, the implantation of such devices seems justifiable, even in this age group. © 2010 Elsevier Masson SAS. All rights reserved.

Didier C.,University of Strasbourg | Streicher M.-P.,Center Hospitalier Of Haguenau | Chognot D.,Center Hospitalier Of Colmar | Campagni R.,Center Hospitalier Of Mulhouse | And 7 more authors.
European Journal of Pediatrics | Year: 2012

Widespread use of intrapartum antimicrobial prophylaxis has significantly reduced the incidence of earlyonset neonatal infection (EONI); however, little is known about the effects of increased maternal exposure to antibiotics on late-onset neonatal infection (LONI). This study aims to evaluate LONI epidemiology in our region after the application of French recommendations and to determine whether LONI-causing organisms and their antibiotic susceptibility are influenced by peripartum antibiotic exposure. We performed a prospective epidemiologic study of 139 confirmed and possible cases of bacterial LONI in patients treated with antibiotics for at least 5 days of the 22,458 infants born in our region in the year 2007. The overall incidence of LONI caused by all pathogens, Group B streptococcus (GBS) and Escherichia coli (E. coli) were 6.19, 0.36 and 2.72, respectively, per 1,000 live births. Our findings revealed three major types of LONI: E. coli-induced urinary tract infection (UTI) among term infants, coagulase negative Staphylococcus septicemia affecting preterm infants, and GBS infections with severe clinical presentation. Univariable analysis revealed that maternal antibiotic exposure was significantly associated with the risk of amoxicillin-resistant E. coli infection (p00.01). Postnatal antibiotic exposure was associated with an increased risk of E. coli LONI (p00.048). This link persisted upon multivariable analysis; however, no additional risk factors were identified for LONI caused by antibiotic-resistant E. coli. Conclusion Our findings confirm that despite the benefits of antenatal antibiotics, this treatment can increase the risk of antibiotic-resistant cases of LONI. National and international surveillance of LONI epidemiology is essential to assess benefits and potential negative consequences of perinatal antibiotic exposure. © Springer-Verlag 2011.

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