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.

[Profile of active investigators involved in a clinical trial in general medical practice]. / Profil des investigateurs actifs au cours d'un essai clinique en médecine générale.

INTRODUCTION: Depiscan was the pilot phase of a large trial to evaluate low dose computed tomography as a screening method for lung cancer (GranDepiscan). The goal of the study presented in this manuscript was to predict the activity of general practitioners (GPs) involved as investigators in a clinical trial. METHODS: A questionnaire about GP's socio-demographic characteristics, initial involvement and perception of difficulties was sent to 189 GPs volunteers after enrollment into the Depiscan trial was complete. RESULTS: Among the 97 respondents, 61 were active investigators. Age lower than 50 years and presence during the initiation visit were significantly associated with the participation of investigators. Two other factors at the limit of significance were: the status and the type of initiation visit. The following factors: gender, type of practice, membership of a medical society, parallel activity in the public sector and knowledge of the referring pulmonary oncologist were not associated with the level of recruitment, as well as the difficulties mentioned by the investigators. CONCLUSIONS: These results will help for selection of investigators for future clinical trials in general medical practice, particularly for the GranDépiscan trial.

Novel lipoprotein density profiling in laminitic, obese, and healthy horses.

Lipoproteins are water-miscible macromolecules enabling the transport of lipids in blood. In humans, altered proportions of lipoproteins are used to detect and classify metabolic diseases. Obesity and obesity-related comorbidities are common in horses. The pathophysiology of obesity is poorly understood and likely multifactorial. Development of new diagnostic tests to identify horses at risk of developing obesity to implement preventative measures is critical; however, a necessary first step to accomplish this goal is to improve our understanding of the pathophysiology of disease. Thus, the objective of this study was to characterize and compare lipoprotein profiles of horses with normal and excess body conditions, with and without laminitis using a novel method of continuous lipoprotein density profiling (CLPDP). Comparisons were made between 4 groups of horses: (1) laminitic, obese horses (n = 66); (2) laminitic, nonobese horses (n = 35); (3) nonlaminitic, obese horses (n = 41); and (4) nonlaminitic, nonobese horses (n = 95). Lipoprotein profiling, including evaluation of triglyceride-rich lipoprotein (TRL), low-density lipoproteins (LDLs), and high-density lipoproteins (HDLs) was performed using CLPDP, and all 4 groups were compared. A significant difference was observed among groups for the subfractions TRL, LDL1, LDL2, HDL2b, HDL2a, HDL3a, HDL3b, HDL3c, and total HDL. This is the first known description of CLPDP to characterize equine lipid profiles and holds promise as a useful method for lipid characterization of horses.

Innate immunity: involvement of new neuropeptides.

Secretory granules of chromaffin cells from the adrenal medulla store catecholamines and a variety of peptides that are secreted in the extracellular medium during exocytosis. Among these fragments, several natural peptides displaying antimicrobial activities at the micromolar range have been isolated and characterized. We have shown that these peptides, derived from the natural processing of chromogranins (CGs), proenkephalin-A (PEA) and free ubiquitin (Ub), are released into the circulation and display antibacterial and antifungal activities. In this review we focus on three naturally secreted antimicrobial peptides corresponding to CGA1-76 (vasostatin-I), the bisphosphorylated form of PEA209-237 (enkelytin) and Ub. In addition, the antimicrobial properties of the synthetic active domains of vasostatin-I (CGA47-66 or chromofungin) and Ub (Ub65-76 or ubifungin) are reported.

Structural and biological characterization of chromofungin, the antifungal chromogranin A (47-66)-derived peptide.

The antifungal peptide named chromofungin is the most active vasostatin-I-derived peptide, corresponding to the sequence 47-66 of chromogranin A. (1)H-NMR analysis revealed that it adopts a helical structure. The mechanism implicated in the interaction of chromofungin with fungi and yeast cells was studied by penetration of monolayers and confocal laser microscopy. Chromofungin is able to interact with the cell wall, to cross the plasma membrane, to accumulate in the microorganism, and to inhibit calcineurin activity.

[Familial myopathy with exclusively cardiac clinical expression]. / Myopathie familiale d'expression clinique exclusivement cardiaque.

A case is presented of a familial form of apparently primary cardio-myopathy with findings on investigation and histology which were in favour of a generalised subclinical muscular disorder: a raised serum creatinine phosphokinase, persistent carnosinuria on a vegetarian diet, and under the light microscope several features indicative of a myogenic dystrophic condition on deltoid biopsy. From their clinical features, these original cases may be classified somewhere between primary familial heart disease and the cardiac complications of myopathies. The value of the creatinine phosphokinase isoenzymes and of muscle biopsy in situations such as these is discussed.

[Loops and folds of the carotid and vertebral arteries: indications for surgery]. / Boucles et plicatures des artères carotides et vertébrales: indications de la chirurgie.

Tortuous variants of the carotid or vertebral morphology are apparent on 10 to 43% of angiograms. It is probable that the incidence of these anomalies is lower in the normal population. Rarely, their etiology is congenital explaining the existence of some pediatric cases. The etiology of most cases is acquired and linked with hypertension, atheroma and aging. Basically consisting of an excess of length of the common or the internal carotid artery, the tortuosity may take the form of simple or multiple kinking, coiling or looping. Isolated, these anomalies are asymptomatic in a large majority of the cases. However, hemispheric, vertebrobasilar or ocular ischemic symptoms may be caused by them through a thromboembolic or hemodynamic mechanism. Moreover, given their frequent association with atherosclerotic occlusive lesions, their participation in the production of ischemic symptoms is not easy to determine. Although not yet investigated by prospective randomized studies, symptomatic isolated of kinking or coiling of cerebral arteries are amenable to surgical revascularization in order to prevent stroke or blindness. Besides, the endarterectomy of atherosclerotic occlusive lesions of tortuous carotids requires a technical adaptation.

[Treatment of encephalopathy by hypothermia in the term newborn]. / Place de l'anoxie et du traitement par hypothermie dans l'encéphalopathie néonatale précoce du nouveau-né à terme.

Criteria defining the involvement of severe perinatal anoxia in neonatal encephalopathy in at-term newborns at birth are stringent and are rarely all present. The simultaneous action of pre- and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy are often observed. Cooling is recommended as there is evidence that it reduces mortality without increasing major disability in survivors. It must be conducted following strict clinical and electroencephalographic criteria. Other strategies for brain protection remain difficult to establish. Follow-up must be long enough to detect cognitive deficiencies, which are frequent, even if cerebral palsy is not observed.

A seroepidemiological study of pandemic A/H1N1(2009) influenza in a rural population of Mali.

The swine-origin H1N1 influenza A virus (pH1N1(2009)) started to circulate worldwide in 2009, and cases were notified in a number of sub-Saharan African countries. However, no epidemiological data allowing estimation of the epidemic burden were available in this region, preventing comprehensive comparisons with other parts of the world. The CoPanFlu-Mali programme studied a cohort of 202 individuals living in the rural commune of Dioro (southern central Mali). Pre-pandemic and post-pandemic paired sera (sampled in 2006 and April 2010, respectively) were tested by the haemagglutination inhibition (HI) method. Different estimates of pH1N1(2009) infection during the 2009 first epidemic wave were used (increased prevalence of HI titre of ≥1/40 or ≥1/80, seroconversions) and provided convergent attack rate values (12.4-14.9%), the highest values being observed in the 0-19-year age group (16.0-18.4%). In all age groups, pre-pandemic HI titres of ≥1/40 were associated with complete absence of seroconversion; and geometric mean titres were <15 in individuals who seroconverted and >20 in others. Important variations in seroconversion rate existed among the different villages investigated. Despite limitations resulting from the size and composition of the sample analysed, this study provides strong evidence that the impact of the pH1N1(2009) first wave was more important than previously believed, and that the determinants of the epidemic spread in sub-Saharan populations were quite different from those observed in developed countries.

Serological study of the 2009 pandemic due to influenza A H1N1 in the metropolitan French population.

We looked for evidence of antibodies to the 2009 influenza A/H1N1 pandemic virus in panels of sera from individuals living in metropolitan France, obtained either before, during or after the epidemic, using standard haemagglutination inhibition and microneutralization tests. The difference between seroprevalence values measured in post- and pre-epidemic panels was used as an estimate of seroconversion rate in different age groups (23.4% (0-24 years, age-group 0); 16.5% (25-34); 7.9% (35-44); 7.2% (45-54); 1.6% (55-64); and 3.1% (>65)), confirming that the distribution of cases in different age groups was similar to that of the seasonal H1N1 virus. During the pre-pandemic period low-titre cross-reactive antibodies were present in a large proportion of the population (presumably acquired against seasonal H1N1) whereas cross-reactive antibodies were detected in individuals over the age of 65 years with significantly higher prevalence and serological titres (presumably acquired previously against Spanish flu-related H1N1 strains). Clinical data and analysis of post-pandemic seroprevalence showed that few of these latter patients were infected by the influenza virus during the epidemic. In contrast, the majority of both clinical cases and seroconversions were recorded in the 0-24 age group and a global inverse relationship between prevalence of antibodies to pH1N1 in the pre-pandemic period and rate of seroconversion was observed amongst age groups. Our results emphasize the complex relationships involved in antigenic reactivity to pandemic and seasonal H1N1 viral antigens; hence the difficulty in distinguishing between low-titre specific and cross-reactive antibodies, establishing precise seroprevalence numbers and fully understanding the relationship between previous immunity to seasonal viruses and protection against the novel variant.

Structural and biological characterization of chromofungin, the antifungal chromogranin A-(47-66)-derived peptide.

Vasostatin-I, the natural fragment of chromogranin A-(1-76), is a neuropeptide able to kill a large variety of fungi and yeast cells in the micromolar range. We have examined the antifungal properties of synthetic vasostatin-I-related peptides. The most active shortest peptide, named chromofungin, corresponds to the sequence Arg(47)-Leu(66). Extensive (1)H NMR analysis revealed that it adopts a helical structure. The biophysical mechanism implicated in the interaction of chromofungin with fungi and yeast cells was studied, showing the penetration of this peptide with different lipid monolayers. In order to examine thoroughly the antifungal activity of chromofungin, confocal laser microscopy was used to demonstrate the ability of the rhodamine-labeled peptide to interact with the fungal cell wall, to cross the plasma membrane, and to accumulate in Aspergillus fumigatus, Alternaria brassicola, and Candida albicans. Our present data reveal that chromofungin inhibits calcineurin activity, extending a previous observation that the N-terminal region of chromogranin A interacts with calmodulin in the presence of calcium. Therefore, the destabilization of fungal wall and plasma membrane, together with the possible intracellular inhibition of calmodulin-dependent enzymes, is likely to represent the mechanism by which vasostatin-I and chromofungin exert antifungal activity.