Laurence Watier

Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007

Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children.

Rhythm Reproduction in Kindergarten, Reading Performance at Second Grade, and Developmental Dyslexia Theories

Temporal processing deficit could be associated with a specific difficulty in learning to read. In 1951, Stambak provided preliminary evidence that children with dyslexia performed less well than good readers in reproduction of 21 rhythmic patterns. Stambaks task was administered to 1,028 French children aged 5-6 years. The score distribution (from 0 to 21) was quasi-normal, with some children failing completely and other performing perfectly. In second grade, reading was assessed in 695 of these children. Kindergarten variables explained 26% of the variance of the reading score at second grade. The Stambak score was strongly and linearly related to reading performance in second grade, after partialling out performance on other tasks (oral repetition, attention, and visuo-spatial tasks) and socio-cultural level. Findings are discussed in relation to perceptual, cerebellar, intermodal, and attention-related theories of developmental dyslexia. It is concluded that simple rhythm reproduction tasks in kindergarten are predictive of later reading performance.

Coinfection with Plasmodium falciparum and Schistosoma haematobium: Additional Evidence of the Protective Effect of Schistosomiasis on Malaria in Senegalese Children

Parasitic infections are associated with high morbidity and mortality in developing countries. Several studies focused on the influence of helminth infections on malaria but the nature of the biological interaction is under debate. Our objective was to undertake a study to explore the influence of the measure of excreted egg load caused by Schistosoma haematobium on Plasmodium falciparum parasite densities. Ten measures of malaria parasite density and two measures of schistosomiasis egg urinary excretion over a 2-year follow-up period on 178 Senegalese children were considered. A linear mixed-effect model was developed to take data dependence into account. This work showed that children with a light S. haematobium infection (1-9 eggs/mL of urine) presented lower P. falciparum parasite densities than children not infected by S. haematobium (P < 0.04). Possible changes caused by parasite coinfections should be considered in the anti-helminth treatment of children and in malaria vaccination development.

Genome Wide Linkage Study, Using a 250K SNP Map, of Plasmodium falciparum Infection and Mild Malaria Attack in a Senegalese Population

Multiple factors are involved in the variability of hosts response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genome-wide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP) genome scan (Affimetrix GeneChip Human Mapping 250K-nsp) was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT) method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value = 5×10−5 and 9×10−5 respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value = 1.5×10−4). Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31–q33 region (p-value = 3.7×10−5). This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection. Furthermore, we detected one gene associated with malaria infection in the 5q31–q33 region.

Accounting for pregnancy dependence in epidemiologic studies of reproductive outcomes.

The aim of this paper is to evaluate the contribution of hierarchical mixed models to the analysis of epidemiologic studies of environmental exposure and reproductive outcomes. We have re‐analyzed, with a logistic‐normal mixed model, four studies investigating the relation between the frequency of spontaneous abortions and paternal or maternal environmental exposures. The data include multiple pregnancies for some women. The fitted models allow for between‐woman variation of the propensity for spontaneous abortion, by including a random intercept in the logistic model to adjust for within‐woman correlations on pregnancy outcomes. We have discussed and implemented two estimation methods, maximum likelihood and Bayesian inference. We found similar values in the various epidemiologic studies of the between‐woman variance of the intrinsic risk of spontaneous abortion. The size of this variance corresponds to a substantial variability in risk between women. Indeed, the risk of spontaneous abortion calculated for “nonexposed” pregnancies, that is, with mothers age, birth order, tobacco consumption, and maternal environmental exposure equal to the referent class, can vary, according to this model, from 2% to 17%.

Assessing pneumococcal meningitis association with viral respiratory infections and antibiotics: insights from statistical and mathematical models

Pneumococcus is an important human pathogen, highly antibiotic resistant and a major cause of bacterial meningitis worldwide. Better prevention requires understanding the drivers of pneumococcal infection incidence and antibiotic susceptibility. Although respiratory viruses (including influenza) have been suggested to influence pneumococcal infections, the underlying mechanisms are still unknown, and viruses are rarely considered when studying pneumococcus epidemiology. Here, we propose a novel mathematical model to examine hypothetical relationships between Streptococcus pneumoniae meningitis incidence (SPMI), acute viral respiratory infections (AVRIs) and antibiotic exposure. French time series of SPMI, AVRI and penicillin consumption over 2001–2004 are analysed and used to assess four distinct virus–bacteria interaction submodels, ascribing the interaction on pneumococcus transmissibility and/or pathogenicity. The statistical analysis reveals strong associations between time series: SPMI increases shortly after AVRI incidence and decreases overall as the antibiotic-prescription rate rises. Model simulations require a combined impact of AVRI on both pneumococcal transmissibility (up to 1.3-fold increase at the population level) and pathogenicity (up to threefold increase) to reproduce the data accurately, along with diminished epidemic fitness of resistant pneumococcal strains causing meningitis (0.97 (0.96–0.97)). Overall, our findings suggest that AVRI and antibiotics strongly influence SPMI trends. Consequently, vaccination protecting against respiratory virus could have unexpected benefits to limit invasive pneumococcal infections.

Difficultés de langage et de comportement à 3 ans et demi et retard en lecture au cours élémentaire

BACKGROUND Early detection of specific language impairment and dyslexia in children is an important public health problem. Longitudinal studies are needed for the distinction of real impairments from simple transitory delays. METHODS Teachers filled a 29-item questionnaire on language and behavior for 695 children aged 3.5 years. Four years later (at second grade of primary school) the same children were evaluated for reading and writing. Statistical analysis focused on the relationships between teachers early observations and reading delay 4 years later. Associated factors were age, sex, educational level and bilinguism of the parents, and area of the school. RESULTS The delay in written language acquisition (8.5% of the children) was significantly associated with low educational level (but not bilinguism) of the parents and to the area of the school. In univariate analysis, most of the teachers early negative assessments were significantly related to reading/writing delay, with the exception of some behavioral problems. However, when the effect of associated factors was taken into account only a few items, mainly concerning language expression, remained significantly associated with later reading/writing delay. CONCLUSION These data show a major role of associated factors (educational level of the parents, area of the school) in reading delay, and help to select specific teachers observations for an early prediction of this delay.

Outpatient antibiotic use in France between 2000 and 2010: after the nationwide campaign, it is time to focus on the elderly.

ABSTRACT Antibiotic overconsumption is the main force driving the emergence of multidrug-resistant bacterial strains. To promote better antibiotic use in France, a nationwide campaign has been run every year from October to March since 2002. In 2007, it was shown that winter outpatient antibiotic consumption had decreased by 26.5% compared to the 2000-2002 baseline period. Here, we quantified outpatient antibiotic use between 2000 and 2010 as a follow-up analysis of the nationwide campaign. Reimbursed outpatient antibiotic prescriptions were extracted from computerized French National Health Insurance databases. Entire series and age group and antibiotic class analyses were computed. Time series analyses used autoregressive moving-average models with exogenous variables and intervention functions. Two periods were considered: October to March “campaign” periods and April to September “warm” periods. Compared to the precampaign (2000-2002) baseline period, the numbers of weekly antibiotic prescriptions per 1,000 inhabitants during campaign periods decreased until winter 2006 to 2007 (−30% [95% confidence interval {CI}, −36.3 to −23.8%]; P < 0.001) and then stabilized except for individuals >60 years of age, for whom prescriptions reached the precampaign level. During the warm periods from April to September, no significant differences were estimated compared to the baseline level for the entire series, but seniors had an increasing trend that became significant as of 2005, reaching +21% (95% CI, +12.9 to +29.6%) in 2009 (P < 0.0001). These results highlight the need for a better understanding of antibiotic use by the elderly, requiring research with targeted and tailored public health actions for this population.

Is post-mortem ultrasonography a useful tool for forensic purposes?

Purpose To investigate the interest of post-mortem ultrasonography in the diagnosis of pathological background, and manner and cause of death. Methods Post-mortem ultrasonography exams were carried out on 38 fresh human adult cadavers referred to the Department of Forensic Medicine and Pathology (Garches, France). Data obtained from ultrasonography were independently compared with further forensic autopsy findings. Results Two important limitations relative to ultrasound utilization appeared: hyper-echoic abdominal and thoracic walls, with gas distension of the whole digestive tube and subcutaneous tissues (due to precocious putrefactive gas releasing); and difficulty in accessing lateral and posterior structures (i.e. liver, spleen, kidneys, lung bases, aorta) due to rigor mortis and evident non-compliance of the subject. Post-mortem diagnoses (moderate ascites, gallbladder stones, bladder globe, chronic kidney disease, cirrhosis, thyroid gland cysts and hypertrophy, intrauterine device), were strongly limited. False negative diagnoses comprised fatty liver, pleural effusion, thoracic aortic dissection, and focal organ and/or soft tissues lesions (for example, wounds or infarcts). Conclusion According to the results, post-mortem ultrasonography seems to have a very limited role for forensic purposes. Other post-mortem utilizations are cited, proposed, and discussed.

Are suicide rates higher in the cancer population? An investigation using forensic autopsy data

Previous population-based studies have identified increased suicide rates among cancer patients. Available post mortem data on the contribution of cancer to completed suicide are limited, however. This study examines forensic autopsy data in order to assess whether cancer is significantly more frequent in a suicide population compared with a control population. In total, 232 cases were included in both the suicide and the control groups. Based on a complete standard histological examination, cancer was significantly more often found in the suicide group than in the control one (8.6% vs. 3.9%, p=0.03). The multivariate analysis also showed that the presence of cancer increased the risk of suicide. Moreover, cancer was not known to the deceased in 70% of cases, while the most frequent mental disease found in cancer-related suicide cases was depression (75%). In the 20 cancer-related suicide cases analysed herein, it was difficult to ascertain whether malignancy was the only motive for committing suicide, as cancer could be considered to be either a major causative factor for suicide or an incidental finding. Therefore, further research is warranted with the help of the psychological autopsy method to investigate the link between suicide and cancer further.