Antibiotic use in ambulatory care in Europe (ESAC data 1997-2002): trends, regional differences and seasonal fluctuations

PURPOSE: The ESAC project (European Study on Antibiotic Consumption) aims to collect antibiotic-use data through a European network of national surveillance systems. This paper reports on the retrospective data collection in ambulatory care for the period 1997-2002. METHODS: Valid data of antibiotic consumption of 24 European countries for 2002 and of 18 countries for the entire 6-year period was classified according to the Anatomical Therapeutic Chemical Classification (ATC) and expressed in defined daily dose (DDD) per 1000 inhabitants per day (DID). Overall and subgroup comparison of antibiotic consumption over time as well as between geographical clusters was performed. RESULTS: Total use of antibiotics in Europe remained at a median level of 20 DID in the period 1997-2002 with a wide variation between countries ranging from 9.8 DID in The Netherlands to 32.2 DID in France. A substantial increase in subclass consumption of co-amoxiclav and fluoroquinolones was noted while the use of narrow-spectrum penicillins, erythromycin, quinolones and sulfonamides decreased. Total consumption as well as seasonal fluctuations showed remarkable geographical clustering with low consumption and low variation between summer and winter in the North, high consumption patterns in the South and a mixed model in the East. CONCLUSIONS: Within the ESAC project, valid time series of antibiotic-use data are publicly available now, enabling to improve the study of determinants of use, the evaluation of governmental antibiotic consumption policies and the investigation of the associated emergence of antibiotic resistance.     

Adolescent substance-use assessment: methodological issues in the use of the Adolescent Drug Abuse Diagnosis (ADAD)

During the past twenty years, various instruments have been developed for the assessment of substance use in adolescents, mainly in the United States. However, few of them have been adapted to, and validated in, French-speaking populations. Consequently, although increasing alcohol and drug use among teenagers has become a major concern, the various health and social programs developed in response to this specific problem have received little attention with regard to follow-up and outcome assessment. A standardized multidimensional assessment instrument adapted for adolescents is needed to assess the individual needs of adolescents and assign them to the most appropriate treatment setting, to provide a single measurement within and across health and social systems, and to conduct treatment outcome evaluations. Moreover, having an available instrument makes it possible to develop longitudinal and transcultural research studies. For this reason, a French version of the Adolescent Drug Abuse Diagnosis (ADAD) was developed and validated at the University Child and Adolescent Psychiatric Clinic in Lausanne, Switzerland. This article aims to discuss the methodological issues that we faced when using the ADAD instrument in a 4-year longitudinal study including adolescent substance users. Methodological aspects relating to the content and format of the instrument, the assessment administration and the statistical analyses are discussed.     

Nucleosome positioning by genomic excluding-energy barriers

Recent genome-wide nucleosome mappings along with bioinformatics studies have confirmed that the DNA sequence plays a more important role in the collective organization of nucleosomes in vivo than previously thought. Yet in living cells, this organization also results from the action of various external factors like DNA-binding proteins and chromatin remodelers. To decipher the code for intrinsic chromatin organization, there is thus a need for in vitro experiments to bridge the gap between computational models of nucleosome sequence preferences and in vivo nucleosome occupancy data. Here we combine atomic force microscopy in liquid and theoretical modeling to demonstrate that a major sequence signaling in vivo are high-energy barriers that locally inhibit nucleosome formation rather than favorable positioning motifs. We show that these genomic excluding-energy barriers condition the collective assembly of neighboring nucleosomes consistently with equilibrium statistical ordering principles. The analysis of two gene promoter regions in Saccharomyces cerevisiae and the human genome indicates that these genomic barriers direct the intrinsic nucleosome occupancy of regulatory sites, thereby contributing to gene expression regulation.     

Chromogranin B P413L variant as risk factor and modifier of disease onset for amyotrophic lateral sclerosis

Recently, chromogranins were reported to interact specifically with mutant forms of superoxide dismutase that are linked to amyotrophic lateral sclerosis (ALS). This interaction led us to analyze the frequencies of sequence variants of the CHGB gene in ALS patients and matched controls from three different countries. Of particular interest was the finding of the P413L CHGB variant present in 10% of ALS patients (n = 705) as compared to 4.5% in controls (n = 751), conferring a 2.2-fold greater relative risk to develop the disease (P < 0.0001). This effect was mainly contributed by the samples of French origin that yielded a frequency of the P413L variation at 17% in ALS (n = 289) and 5% in controls (n = 448), conferring a 3.3-fold greater risk to develop ALS. Furthermore, the P413L CHGB variant is associated with an earlier age of onset by almost a decade in both sporadic ALS and familial ALS cases. Genetic variation influencing age of onset in ALS had not previously been reported. Expression of fusion CHGB-EGFP constructs in SHSY-5Y cells revealed that the P413L variation can cause defective sorting of CHGB into secretory granules. The finding that CHGB may act as a susceptibility gene and modifier of onset in ALS is consistent with the emerging view that dysfunction of the secretory pathway may contribute to increased vulnerability of motor neurons.     

Predicting osteoporosis in patients with a low-energy fracture

The multicenter cross-sectional study was designed to develop a simple rule to predict the risk of osteoporosis in the patients with a low-energy fracture (LEF). Furthermore, we aimed to investigate the incidence of fall-related risk factors. We included 206 patients with age over 50 and an LEF at the emergency room. All patients underwent osteoporosis and fall risk assessment and dual-energy X-ray absorptiometry (DEXA) of both hips and the lumbar spine. The incidence of osteoporosis in our study population was 41% (84 cases of 206). Fifty-four percent of the patients reported at least one fall-related risk factor. Mobility problems occurred in 31% and osteoarthritis in 19%. The final osteoporosis prediction rule included age, positive family history, immobility, and low-body weight. The discrimination of the rule after correction for over-optimism was good (receiver operating curve (ROC)=ROC area=0.79). This simple rule may be helpful to select patients who need further osteoporosis assessment.     

Electrocardiographic Body Surface Mapping: Potential Tool for the Detection of Transient Myocardial Ischemia in the 21st Century?

Coronary artery disease (CAD) is one of the leading causes of cardiovascular mortality and morbidity worldwide. CAD presents as a wide spectrum of clinical disease from stable angina to ST segment elevation myocardial infarction. The 12‐lead electrocardiogram (ECG) has been the main tool for the diagnosis of these events for almost a century but is limited in its diagnostic ability. For patients with suspected angina, the exercise tolerance test is often used to provoke and detect stress‐induced ischemia but does not provide a definitive answer in a substantial proportion of patients. Body surface mapping (BSM) is a technique that samples multiple points around the thorax to provide a more comprehensive electrocardiographic data set than the conventional 12‐lead ECG. Moreover, recent preliminary data demonstrate that BSM can detect and display transient regional myocardial ischemia in an intuitive fashion, employing subtraction color mapping, making it potentially valuable for diagnosing CAD causing transient regional ischemia. Research is ongoing to determine the full extent of its utility.     

Effect of transfusion therapy on cerebral vasculopathy in children with sickle-cell anemia

This retrospective study assessed the long-term effect of transfusional exchange therapy on MRA/MRI abnormalities in 24 homozygous sickle-cell anemia (HbSS) children presenting with abnormal brain MRA. The median time elapsed from baseline to last available MRA was 29 months. Follow-up MRAs showed improvement, stabilization or worsening of cerebrovascular lesions in 11, 6 and 7 patients respectively. Complete normalization of MRA was observed in 6 patients within a mean time of 1.4 years, but stenosis recurred at the same location in the 4 patients in whom transfusion therapy was discontinued. Baseline severe stenosis/occlusion of large cerebral arteries and occurrence of moyamoya syndrome were significantly associated with an absence of improvement of the cerebral vasculopathy. These data emphasize the heterogeneity of the course of cerebrovasculopathy in SS children receiving chronic transfusion. Further studies are needed to determine whether different therapeutic approaches have to be considered according to these different evolutive patterns in SS children.     

Effect of Influenza Vaccination of Nursing Home Staff on Mortality of Residents: A Cluster-Randomized Trial

OBJECTIVES: To evaluate the effect of staff influenza vaccination on all-cause mortality in nursing home residents.
DESIGN: Pair-matched cluster-randomized trial.
SETTING: Forty nursing homes matched for size, staff vaccination coverage during the previous season, and resident disability index.
PARTICIPANTS: All persons aged 60 and older residing in the nursing homes.
INTERVENTION: Influenza vaccine was administered to volunteer staff after a face-to-face interview. No intervention took place in control nursing homes.
MEASUREMENTS: The primary endpoint was total mortality rate in residents from 2 weeks before to 2 weeks after the influenza epidemic in the community. Secondary endpoints were rates of hospitalization and influenza-like illness (ILI) in residents and sick leave from work in staff.
RESULTS: Staff influenza vaccination rates were 69.9% in the vaccination arm versus 31.8% in the control arm. Primary unadjusted analysis did not show significantly lower mortality in residents in the vaccination arm (odds ratio=0.86, P =.08), although multivariate-adjusted analysis showed 20% lower mortality ( P =.02), and a strong correlation was observed between staff vaccination coverage and all-cause mortality in residents (correlation coefficient=−0.42, P =.007). In the vaccination arm, significantly lower resident hospitalization rates were not observed, but ILI in residents was 31% lower ( P =.007), and sick leave from work in staff was 42% lower ( P =.03).
CONCLUSION: These results support influenza vaccination of staff caring for institutionalized elderly people.