Economic and disease burden of RSV-associated hospitalizations in young children in France, from 2010 through 2018.

BACKGROUND: Respiratory syncytial virus (RSV) is the main cause of infant and child hospitalizations. The study objective is to estimate the RSV-associated hospitalizations and economic burden in young children in France to inform future preventive strategies. METHODS: We conducted a retrospective analysis of RSV-associated hospitalizations data from the French Hospital database (PMSI-MCO) which covers the entire French population. All children aged < 5 years hospitalized with RSV ICD-10 codes (J210, J219, J45, J121, J205, R062) from 2010 to 2018, were included. Descriptive analyses were conducted by RSV seasons (Oct to March), by respiratory years (July to June) and per age groups. RESULTS: On average 45,225 RSV-associated hospitalizations (range: 43,715 - 54,616) per season was reported in France, 69% among children < 1 year old. This represents 28% of all-cause hospitalizations that occurred among children < 1 year old, and less than 10% of all-cause hospitalizations in older children. Number of RSV-associated hospitalizations were similar for infants born during (Oct-March) or outside (April-September) their first RSV season. The highest risk being reported for infants born from September through November. The associated hospitalization cost increased between 2010 - 11 and 2017-18, from €93.2 million to €124.1 million, respectively, and infants < 1 year old represented 80% of the economic burden. CONCLUSION: RSV is an important cause of child hospitalization in France. The burden on healthcare system is mainly driven by < 1 year olds, and preventive strategies should be implemented before the first RSV season.

Immunity against influenza A(H1N1) infections is determined by age at the time of initial strain circulation.

We explored age-dependent patterns in haemagglutination inhibition (HI) titre to seasonal [1956 A(H1N1), 1977 A(H1N1), 2007 A(H1N1)] and pandemic [A(H1N1)pdm09] influenza strains using serological data collected from an adult French influenza cohort. Subjects were recruited by their general practitioners from 2008 to 2009 and followed until 2010. We explored age-related differences between strain-specific HI titres using 1053 serological samples collected over the study period from 398 unvaccinated subjects. HI titres against the tested seasonal and pandemic strains were determined using the HI technique. Geometric mean titres (GMTs) were estimated using regression models for interval-censored data. Generalized additive mixed models were fit to log-transformed HI estimates to study the relationship between HI titre and age (age at inclusion and/or age at initial strain circulation). GMT against one strain was consistently highest in the birth cohort exposed to that strain during childhood, with peak titres observed in subjects aged 7-8 years at the time of initial strain circulation. Our results complete previous findings on influenza A(H3N2) strains and identify a strain-dependent relationship between HI titre and age at initial strain circulation.

[The REDSIAM network]. / Le réseau REDSIAM (Réseau données Sniiram) ­ Spécial REDSIAM.

The French national health database (SNIIRAM) proved to be very useful for epidemiology, health economics, evaluation, surveillance or public health. However, it is a complex database requiring important resources and expertise for being used. The REDSIAM network has been set up for promoting the collaboration of teams working on the Sniiram. The main aim of REDSIAM is to develop and validate methods for analyzing the Sniiram database for research, surveillance, evaluation and public health purposes by sharing the knowledge and experience of specialized teams in the fields of diseases identification from the Sniiram data. The work conducted within the network is devoted to the development and the validation of algorithms using Sniiram data for identifying specific diseases. The REDSIAM governance includes the Steering Committee composed of the main organizations in charge of producing and using the Sniiram data, the Bureau and the Technical Committee. The network is organized in thematic working groups focused on specific pathological domains, and a charter defines the rules for participation in the network, the functioning of the thematic working groups, the rules for publishing and making available algorithms. The articles in this special issue of the journal present the first results of some of the thematic working groups.

[The use of administrative health databases in infectious disease epidemiology and public health]. / Apport des bases médico-administratives en épidémiologie et santé publique des maladies infectieuses.

BACKGROUND: The public health burden resulting from infectious diseases requires efforts in surveillance and evaluation of health care. The use of administrative health databases (AHD) and in particular the French national health insurance database (SNIIRAM) is an opportunity to improve knowledge in this field. The SNIIRAM data network (REDSIAM) workshop dedicated to infectious diseases conducted a narrative literature review of studies using French AHD. From the results, benefits and limits of these new tools in the field of infectious diseases are presented. METHODS: Publications identified by the members of the workgroup were collected using an analytical framework that documented the pathology of interest, the aim of the study, the goal of the developed algorithm, the kind of data, the study period, and the presence of an evaluation or a discussion of the performance of the performed algorithm. RESULTS: Fifty-five articles were identified. A majority focused on the field of vaccination coverage and joint infections. Excluding vaccine coverage field, the aim of 28 studies was epidemiological surveillance. Twenty-six studies used hospital databases exclusively, 18 used ambulatory databases exclusively and 4 used both. Validation or discussion of the performed algorithm was present in 18 studies. CONCLUSIONS: The literature review confirmed the interest of the French AHD in the infectious diseases field. The AHD are additional tools of the existing surveillance systems and their use will probably be more frequent in the coming years given their advantage and reliability. However, incoming users need to be assisted. Thus, the workgroup will contribute to a reasonable use of AHD and support future developments.

A new highly penetrant form of obesity due to deletions on chromosome 16p11.2.

Obesity has become a major worldwide challenge to public health, owing to an interaction between the Western 'obesogenic' environment and a strong genetic contribution. Recent extensive genome-wide association studies (GWASs) have identified numerous single nucleotide polymorphisms associated with obesity, but these loci together account for only a small fraction of the known heritable component. Thus, the 'common disease, common variant' hypothesis is increasingly coming under challenge. Here we report a highly penetrant form of obesity, initially observed in 31 subjects who were heterozygous for deletions of at least 593 kilobases at 16p11.2 and whose ascertainment included cognitive deficits. Nineteen similar deletions were identified from GWAS data in 16,053 individuals from eight European cohorts. These deletions were absent from healthy non-obese controls and accounted for 0.7% of our morbid obesity cases (body mass index (BMI) >or= 40 kg m(-2) or BMI standard deviation score >or= 4; P = 6.4 x 10(-8), odds ratio 43.0), demonstrating the potential importance in common disease of rare variants with strong effects. This highlights a promising strategy for identifying missing heritability in obesity and other complex traits: cohorts with extreme phenotypes are likely to be enriched for rare variants, thereby improving power for their discovery. Subsequent analysis of the loci so identified may well reveal additional rare variants that further contribute to the missing heritability, as recently reported for SIM1 (ref. 3). The most productive approach may therefore be to combine the 'power of the extreme' in small, well-phenotyped cohorts, with targeted follow-up in case-control and population cohorts.

[The legal limits and ambiguities of the role of the family caregivers]. / Limites et ambiguïtés juridiques du rôle des aidants familiaux.

INTRODUCTION: While living in a period easily characterized by the self-actualization of the patient as the support of a non-professional valuation, it seems useful to evaluate the situation concerning the limits of the involvement of the non-professional caregivers who take care of dependent or disabled persons. They become involved in the course of care in order to protect their relative the best way they can. This involvement has an influence on the evolution of the care, particularly from a psychic point of view, as well as in the way any medical act will be conducted. OBJECTIVES: This work analyses the French legal context, reflecting the practical experience of the gerontopsychiatric teams. A legal point is established on the outlines of the voluntary help provided by the relatives and/or close friends. The approach, aiming at recognizing the family caregivers as such and bearing in mind that they can almost become the persons' guardians if need be, cannot but provoke several ethical issues as well as difficulties concerning the way of taking care of the patient. The difficulties the caregivers may have are in a way related to the lack of clear legal definitions of the medical act, as well as to the lack of definitions of the tasks one may expect from the family caregiver. CONCLUSIONS: This lack also shows the difficulties the law-maker is confronted with when defining what concerns the natural family care and what concerns the collective solidarity. The evolution of the role of caregivers in our society, which must face the pandemic of chronic diseases, thus means an evolution in the substantive law in the field of family care.

Is the Development of Gestational Diabetes Associated With the ABO Blood Group/Rhesus Phenotype?

Aims: There are few published data on the putative association between the ABO blood group/rhesus (Rh) factor and the risk of developing gestational diabetes mellitus (GDM). Our aim was to explore the link between each one factor and GDM development. Methods: All women having given birth at Lille University Medical Center (Lille, France) between August 1st, 2017, and February 28th, 2018, were tested for GDM, using the method recommended in the French national guidelines. The risk of GDM was assessed for each ABO blood group, each Rh phenotype and combinations thereof, using logistic regression models. Results: 1194 women had at least one GDM risk factor. The percentage of GDM varied with the ABO group (p=0.013). Relative to group O women, group AB women were more likely to develop GDM (OR = 2.50, 95% CI [1.43 to 4.36], p=0.001). Compared with the Rh-positive O group, only the Rh-positive AB group had an elevated risk of developing GDM (OR = 3.02, 95% CI [1.69 to 5.39], p < 0.001). Conclusions: Our results showed that Rh-positive group AB women have a greater risk of GDM. With a view to preventing GDM, at-risk individuals could be identified by considering the ABO blood group phenotype either as a single risk factor or in combination with other risk factors.

The intravenous vancomycin prescription practices of French infectious disease specialists: A cross-sectional observational study.

INTRODUCTION: Vancomycin prescription modalities remain non-consensual. We examined and evaluated the vancomycin prescription habits of infectious disease specialists in France. METHODS: Through an anonymized online questionnaire sent to members of the French Infectious Diseases Society, detailed information on vancomycin prescription modalities was collected. RESULTS: Out of the 712 physicians contacted, 179 (25%) completed the questionnaire; 174 (97%) of them routinely prescribed intravenous vancomycin: 95 (55%) by continuous infusion only, 12 (7%) by intermittent infusion, while 67 (38%) used the two modalities. Among continuous administration users, 157 (97%) applied a loading dose of 15 mg/kg or less (n = 80, 49%), 20-25 mg/kg (n = 33, 20%), or 30 mg/kg or more (n = 45, 28%); 143 (88%) used a maintenance dosage of 30 mg/kg/day and 157 (97%) carried out drug monitoring. CONCLUSION: In France, infectious disease specialists favor continuous administration of vancomycin using a loading dose, with systematic monitoring of vancomycin serum concentrations.

Stable hole doping of graphene for low electrical resistance and high optical transparency.

We report on the p doping of graphene with the polymer TFSA ((CF(3)SO(2))(2)NH). Modification of graphene with TFSA decreases the graphene sheet resistance by 70%. Through such modification, we report sheet resistance values as low as 129 Ω, thus attaining values comparable to those of indium-tin oxide (ITO), while displaying superior environmental stability and preserving electrical properties over extended time scales. Electrical transport measurements reveal that, after doping, the carrier density of holes increases, consistent with the acceptor nature of TFSA, and the mobility decreases due to enhanced short-range scattering. The Drude formula predicts that competition between these two effects yields an overall increase in conductivity. We confirm changes in the carrier density and Fermi level of graphene through changes in the Raman G and 2D peak positions. Doped graphene samples display high transmittance in the visible and near-infrared spectrum, preserving graphene's optical properties without any significant reduction in transparency, and are therefore superior to ITO films in the near infrared. The presented results allow integration of doped graphene sheets into optoelectronics, solar cells, and thermoelectric solar cells as well as engineering of the electrical characteristics of various devices by tuning the Fermi level of graphene.

Effects of COVID-19 pandemic lockdown on gestational diabetes mellitus: A retrospective study.

OBJECTIVE: The objective of our study was to evaluate the impact of the lockdown period on the glycemic balance in patients with GDM. METHODS: A retrospective study in one center (Lille, France) compared two periods: the COVID-19 lockdown of 18 March 2020 to 7 May 2020 versus the same period during 2019. Glucose targets were defined by a capillary fasting glucose target < 5.1mmol/L and/or a 2-hour postprandial capillary glucose < 6.6 mmol/L. GDM control was defined as: good (< 20% of the glycemic values were not within the target range), acceptable (20 to 40% of the glycemic values were not within the target range) or poor (> 40% of the glycemic values were not within the target range). RESULTS: Two hundred twenty-nine patients were included in 2019 and 222 in 2020. The same mean number of capillary blood sugar tests was performed by the two groups. Postprandial blood sugar was significantly less well controlled in 2020, with a lower rate of good control (61.6% vs 69.4%) and higher rates of acceptable (24.7% vs 21.8%) and poor control (13.7% and 8.7%) (p < 0.05). Use of insulin therapy was significantly higher in 2020 compared with 2019 (47.7% and 36.2%, respectively; p < 0.05). CONCLUSION: Diabetes control was lower during the COVID-19 pandemic lockdown, even if follow-up was not impacted. This may be explained by reduced physical activity, modified dietary habits and anxiety during this period.

Atmospheric physics and Earth observations: sample performance of the grille spectrometer.

The grille spectrometer observed the setting and rising sun 18 times during the Spacelab 1 mission. In addition to solar absorption lines, many of which had not been observed before, atmospheric spectral absorptions due to carbon monoxide and carbon dioxide were observed at heights tangent to the thermosphere (greater than 85 kilometers), and absorptions due to ozone, water, methane, and nitrous oxide were observed in the mesosphere (greater than 50 kilometers). The strongly coupled molecules NO-NO(2) and HC1-HF were observed as pairs in the stratosphere. Methane is presented as an example of the instrumental operations because of the characteristic aspect of the Q branch of its v(3) band.

Assessing assistive technology requirements in children with written language disorders. A decision tree to guide counseling.

Children with a written language disorder are sometimes dependent upon help from others for their schoolwork. A computer can be a way to circumvent this difficulty. Various software programs and plug-in peripheral devices are available, some of which specifically target the needs of these young people. There is no consensus, however, with regard to how best to counsel parents and children with regard to these tools. Furthermore, written language disorders and existing technical supports are not always clearly understood. In many cases, healthcare and teaching professionals have only limited knowledge of the potentially specific advantages for patients with written language disorders. A child's full integration into daily activities and school life can be hampered by counseling that was inadequately tailored or by a lack of support in using this equipment. Joint consultations involving both an occupational and a speech therapist have been set up in our department to improve counseling with regard to technical supports. Using our daily practice as a basis, we have developed a decision tree that we see as a necessary tool for helping professionals make the most appropriate practical choices.

Assessment of conversational pragmatics: A screening tool for pragmatic language impairment in a control population of children aged 6-12 years.

Pragmatics can be defined as the way in which language is used to communicate in a given social context. Although there is a lack of a standardized assessment, healthcare professionals find themselves confronted with pragmatic language skill impairments in children with neurodevelopmental disorders or brain injuries. The characterization of language use causes problems in social interactions, which has clinical implications in daily life. However, this is still underestimated because there is currently no quick, easy-to-use screening device to rank these deficits. We have developed a pragmatic deficits screening chart that has been tested on a control population of children aged 6-12 years. The chart comprises 26 items exploring seven areas of pragmatics (intentionality, governance of exchange, organization of information, adaptation strategies, conversational implicit language, nonverbal skills, and paralinguistic aspects). Parents select one of four possible answers to describe how frequently their child demonstrates each type of behavior ("never, rarely, sometimes, often"). We distributed 1666 charts; 760 were returned, of which 552 could be analyzed. Internal consistency as measured with Cronbach's alpha coefficient (0.88) was satisfactory. There was no influence of age on total score, nor of the department/type of schooling. The population distribution was non-Gaussian so the results are presented in percentiles. We propose a first-line screening tool that is quick and easy to complete by family, which facilitates referral to specialists for further investigations into the etiological implications of pragmatic language impairment.

[Mathematical learning disability: A multiple origin? Examples of Turner and Fragile X syndromes]. / Troubles en mathématiques : une origine multiple ? L'exemple des syndromes de Turner et de l'X Fragile.

Problems in mathematics are a frequent major complaint in neuropediatric departments, for which there are two explanatory theoretical models: the hypothesis of a genetic and modular origin (with a number sense deficit) and a multidetermined origin. The purpose of this paper is to review the mathematical difficulties described in Turner syndrome and Fragile X syndrome, because a specific mathematical disorder is usually reported in these populations, supporting the existence of a number sense. Analysis of the literature reveals highly variable cognitive phenotypes in these populations, especially regarding mathematical abilities. Performance heterogeneity might be related to different factors such as the abilities needed to perform the task, the variability of definitions, the different tests used in the studies and the heterogeneity of the syndromes themselves. A number sense deficit is usually described in these syndromes, but variable cognitive impairments are also observed. The idea of a modular functioning is then debated and we argue for the necessity of a global cognitive evaluation approach.

Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009-2014.

BACKGROUND: Management of inflammatory bowel disease (IBD) has evolved in the last decade. AIM: To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). METHODS: All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed. RESULTS: A total of 210 001 patients were diagnosed with IBD [Crohn's disease (CD), 100 112; ulcerative colitis (UC), 109 889]. Five years after diagnosis, cumulative probabilities of anti-TNF monotherapy and combination therapy exposures were 33.8% and 18.3% in CD patients and 12.9% and 7.4% in UC patients, respectively. Among incident patients who received thiopurines or anti-TNFs, the first treatment was thiopurine in 69.1% of CD and 78.2% of UC patients. Among patients treated with anti-TNFs, 45.2% and 54.5% of CD patients and 38.2% and 39.9% of UC patients started monotherapy and combination therapy within 3 months after diagnosis, respectively; 31.3% of CD and 27.1% of UC incident patients withdrew from thiopurine or anti-TNFs for more than 3 months after their first course of treatment. Five years after diagnosis, the cumulative risks of first intestinal resection in CD patients and colectomy in UC patients were 11.9% and 5.7%, respectively. CONCLUSIONS: Step-up approach remains the predominant strategy, while exposure to anti-TNFs is high. Surgery rates are low. Treatment withdrawal in IBD is more common than expected.

Simultaneous A8344G heteroplasmy and mitochondrial DNA copy number quantification in myoclonus epilepsy and ragged-red fibers (MERRF) syndrome by a multiplex molecular beacon based real-time fluorescence PCR.

The association of a particular mitochondrial DNA (mtDNA) mutation with different clinical phenotypes is a well-known feature of mitochondrial diseases. A simple genotype-phenotype correlation has not been found between mutation load and disease expression. Tissue and intercellular mosaicism as well as mtDNA copy number are thought to be responsible for the different clinical phenotypes. As disease expression of mitochondrial tRNA mutations is mostly in postmitotic tissues, studies to elucidate disease mechanisms need to be performed on patient material. Heteroplasmy quantitation and copy number estimation using small patient biopsy samples has not been reported before, mainly due to technical restrictions. In order to resolve this problem, we have developed a robust assay that utilizes Molecular Beacons to accurately quantify heteroplasmy levels and determine mtDNA copy number in small samples carrying the A8344G tRNA(Lys) mutation. It provides the methodological basis to investigate the role of heteroplasmy and mtDNA copy number in determining the clinical phenotypes.

Linear 2' O-Methyl RNA probes for the visualization of RNA in living cells.

U1snRNA, U3snRNA, 28 S ribosomal RNA, poly(A) RNA and a specific messenger RNA were visualized in living cells with microinjected fluorochrome-labeled 2' O-Methyl oligoribonucleotides (2' OMe RNA). Antisense 2' OMe RNA probes showed fast hybridization kinetics, whereas conventional oligodeoxyribonucleotide (DNA) probes did not. The nuclear distributions of the signals in living cells were similar to those found in fixed cells, indicating specific hybridization. Cytoplasmic ribosomal RNA, poly(A) RNA and mRNA could hardly be visualized, mainly due to a rapid entrapment of the injected probes in the nucleus. The performance of linear probes was compared with that of molecular beacons, which due to their structure should theoretically fluoresce only upon hybridization. No improvements were achieved however with the molecular beacons used in this study, suggesting opening of the beacons by mechanisms other than hybridization. The results show that linear 2' OMe RNA probes are well suited for RNA detection in living cells, and that these probes can be applied for dynamic studies of highly abundant nuclear RNA. Furthermore, it proved feasible to combine RNA detection with that of green fluorescent protein-labeled proteins in living cells. This was applied to show co-localization of RNA with proteins and should enable RNA-protein interaction studies.

[Classification of children with specific language impairments: What can we think about them in 2016?] / Les classifications des troubles spécifiques du langage oral : qu'en penser en 2016 ?

Specific language impairments are characterized by a strong semiological heterogeneity. Numerous classifications have been used to bring out this heterogeneity and to create subgroups after outlining specific symptoms and deficits. However, semiological fixed profiles would not be adequate for these disorders related to neurodevelopmental trajectories. This heterogeneity is not only semiological: it is also found within underlying mechanisms, as well as in the etiopathogenesis, which is still not well understood today. The aim of this article is to introduce the main semiological classifications to highlight the fact that the symptomatic level alone is not sufficient to characterize specific language impairments.

[Adequacy of antibiotic therapy for urinary tract infection in a Medical Department from the university hospital of Lille: A retrospective cohort study]. / Évaluation de la qualité de l'antibiothérapie des infections urinaires dans le service de médecine polyvalente post-urgence du CHRU de Lille: une étude de cohorte rétrospective.

INTRODUCTION: The main objective of the study was to assess the adequacy of antibiotic therapy for urinary tract infections (UTI) in a French hospital medical department. The secondary objective was to identify factors associated with inadequacy of the antibiotic therapy. METHODS: A retrospective single centre cohort study was performed in the Post-Emergency Medicine Department (PEMD) of the university hospital of Lille. All patients presenting with an UTI from May 2012 to April 2014 were included. Adequacy of antibiotic therapy was assessed with reference to local guidelines. Factors associated with inadequacy of antibiotic prescription were determined using a multivariate logistic regression model. RESULTS: Two hundred and twenty-eight patients were included. The antibiotic prescription was fully adequate in 173 patients (76%) with appropriate use of a single or a combination antibiotic therapy in 96%, appropriate drug in 80%, appropriate dosage in 89% and appropriate route of administration in 95%. The risk for antibiotic inadequacy was significantly higher in patients with cystitis than in those with pyelonephritis (OR 12.01; 95% CI 4.17-34.65), when antibiotics were prescribed in the Emergency Department (OR 6.84; 95% CI 2.29-20.47) or before hospital admission (OR 382.46; 95% CI 19.61≥999.99) compared to when antibiotics were first administered in the PEMD, and in patients with severe UTI (OR 19.55; 95% CI 2.79-137.01). CONCLUSION: Adequacy of antibiotic therapy for UTI is relatively high in our study, reflecting the effective dissemination of antibiotic guidelines. However, antibiotic therapy is still inappropriate in cystitis, severe UTI and in case of prescription before the admission in the PEMD.