CFTR pharmacological modulators: A great advance in cystic fibrosis management.

Cystic fibrosis is a severe monogenic disease that affects around 7400 patients in France. More than 2100 mutations in the cystic fibrosis conductance transmembrane regulator (CFTR), the gene encoding for an epithelial ion channel that normally transports chloride and bicarbonate, lead to mucus dehydration and impaired bronchial clearance. Systematic neonatal screening in France since 2002 has enabled early diagnosis of cystic fibrosis. Although highly demanding, supportive treatments including daily chest physiotherapy, inhaled aerosol therapy, frequent antibiotic courses, nutritional and pancreatic extracts have improved the prognosis. Median age at death is now beyond 30 years. Ivacaftor was the first CFTR modulator found to both reduce sweat chloride concentration and improve pulmonary function in the rare CFTR gating mutations. Combinations of modulators such as lumacaftor + ivacaftor or tezacaftor + ivacaftor were found to improve pulmonary function both in patients homozygous for the F508del mutation characterized by the lack of CFTR protein and those heterozygous for F508del with minimal CFTR activity. The triple combination of ivacaftor + tezacaftor + elexacaftor was recently shown to significantly improve pulmonary function and quality of life, to normalize sweat chloride concentration, and to reduce the need for antibiotic therapy in patients with at least one F508del mutation (83% in France). These impressive data, however, need to be confirmed in the long term. Nevertheless, it is encouraging to hear treated patients testify about their markedly improved quality of life and to observe that the number of lung transplants for cystic fibrosis decreased dramatically in France after 2020, despite the COVID pandemic, with no increase in deaths without lung transplant.

Children and screens: Groupe de Pédiatrie Générale (Société française de pédiatrie) guidelines for pediatricians and families.

The Groupe de Pédiatrie Générale (General Pediatrics Group), a member of the Société française de pédiatrie (French Pediatrics Society), has proposed guidelines for families and doctors regarding children's use of digital screens. A number of guidelines have already been published, in particular by the French Academy of Sciences in 2013 and the American Academy of Pediatrics in 2016. These new guidelines were preceded by an investigation into the location of digital screen use by young children in France, a survey of medical concerns on the misuse of digital devices, and a review of their documented benefits. The Conseil Supérieur de l'Audiovisuel (Higher Council on Audiovisual Technology) and the Union Nationale de Associations Familiales (National Union of Family Associations) have taken part in the preparation of this document. Five simple messages are proposed: understanding without demonizing; screen use in common living areas, but not in bedrooms; preserve time with no digital devices (morning, meals, sleep, etc.); provide parental guidance for screen use; and prevent social isolation.

[Contribution of teledermatology in a hospital pediatrics department]. / Apport de la télédermatologie dans un service de pédiatrie hospitalière.

The hospital of Versailles no longer has a dermatologist; consequently the pediatrics department suggested assess to the system put in place in 2015 based on the telemedicine software platform WebDCR developed throughout the hospital. The acceptability of this was based on its implementation as well as speed and ease of use. METHODS: In 2015, 47 reviews were submitted. RESULTS: No patient refusal was noted. The answer was obtained in 100 % of cases on the day the requests were made, during the week. A diagnosis was made in 36 % of cases and one or more hypotheses were formulated in the 64 % of the remaining cases. The review resulted in a further consultation in 28 % of cases, and in one case to transfer to the dermatology department. The quality of the data collected was considered good or excellent in 96 % of cases. DISCUSSION: This first teledermatology experiment seems to show its utility in terms of the services provided. Given the successful deployment of the system, it was extended to the pediatric emergency department. The response time was reduced to 1h. CONCLUSION: This first teledermatology experiment seems to show its real value in terms of services rendered. However, it is necessary to have more experience to confirm the contribution of this tool, and to reassess the sustainability and economic relevance of the device.

Children and screens: A survey by French pediatricians.

INTRODUCTION: Screens are increasingly prevalent within families. The excessive use of screens by children has negative consequences. To measure the use of screens, we undertook an investigation among children being followed by pediatricians. METHODS: An invitation to participate was sent electronically to 1460 private practice pediatricians. They were asked to complete the questionnaire on screen use by children under 12 years of age during a consultation, according to statements made by parents. RESULTS: One hundred and forty-four pediatricians submitted completed questionnaires involving 428 children. Among the 197 children under 3 years of age, 92 had played with an interactive screen for a median duration of 30min during the preceding week; 29% of the children were alone at the time. One hundred and thirty-nine children had watched television for a median weekly duration of 75min. Of the 231 children 3-11 years of age, 108 had played with an interactive screen for a median time of 30min the day before the consultation, and 50% of them were alone at the time. One hundred and seventy-two children watched television for a median daily duration of 45min. There was a correlation between these children's screen time and their mother's (r=0.36). The television was on during meals and continuously in 35% and 21% of the families, respectively. CONCLUSIONS: Children start looking at screens early, too often watching unsuitable programs, and too often without a parent's present. Regardless of the child's age, pediatricians must ask parents how much time their children are viewing screens, advise them accordingly, and warn them of the consequences of excessive use.

[Acute hemorrhagic edema of infancy associated with Coxsackie virus infection]. / Œdème aigu hémorragique du nourrisson associé à une infection à Coxsackie virus.

Acute hemorrhagic edema of infancy is a rare but benign vasculitis occurring in infants aged from 4 to 24 months. Skin lesions can take various forms, including extensive hemorrhagic purpura, and can therefore be mistaken for purpura fulminans if associated with fever, which leads to initiating broad-spectrum antibiotic treatment. In the present case, we describe a 7-month-old boy with acute hemorrhagic edema of infancy and rapidly extensive purpura lesions that led to intravenous cefotaxime and amikacin treatment. Diagnosis was made on the next day by a dermatologist, based on the typical aspect of skin lesions, hemodynamic stability, and negative bacteriological samples. Coxsackie virus B5, a pathogenic enterovirus, was found by specific PCR in cerebrospinal fluid. The outcome was spontaneously favorable after discontinuation of antibiotics on day 2. We discuss the imputability of the enterovirus in triggering this case of acute hemorrhagic edema of infancy.

[Teledermatology between two French hospitals: Two years of experience]. / Télédermatologie unissant deux hôpitaux : deux ans d'expérience.

BACKGROUND: Teledermatology is currently booming. Due to the shortage of dermatologists in hospitals access to dermatological consultations is very limited in some hospitals. We present our experience of collaboration between an expert center, the dermatology department of the Victor-Dupouy Hospital Centre in Argenteuil, and all medical structures under the André-Mignot Hospital in Versailles (CHV), including 2 prison medical centers (UCSA), traditional departments and emergency department. PATIENTS AND METHODS: Teledermatology, developed in the form of tele-expertise, began at the UCSA in November 2013. This expertise was then extended in June 2014 to the Internal Medicine department of CHV, and in December 2014 to all departments, including the emergency department. The rules and ethics of teledermatology were strictly adhered to. While UCSA could file all expertise dossiers, only urgent or difficult cases could be filed by other CHV departments. RESULTS: In 26 months, 347 expertise requests were filed: 231 by prisons and 116 by the other departments of the CHV. No patients refused teledermatology. The quality of information and photographs was considered good or excellent in over 95% of cases. A response was given within 3hours in more than 50% of cases and in all cases within 24hours (on working days). Analysis of diseases diagnosed illustrates the wide variety of conditions encountered in dermatology, with different structures having their own specific features. CONCLUSION: Our example illustrates the possibility of developing such an inter-hospital platform. However, it does not yet cater for requests made by patients to dermatologists, by dermatologists to dermatologists, or by dermatologists to the hospital teledermatology department. Acceptability was considered excellent by patients (with no refusals), physicians at the CHV, and the expert center.

Vaccine coverage in CF children: A French multicenter study.

BACKGROUNDS: Recent reports have pointed the low vaccine coverage in patients with chronic diseases. Data are lacking in patients with cystic fibrosis (CF). Gaining more information on coverage both for mandatory vaccines and those more specifically recommended would help to optimize care of these patients. METHODS: Data were extracted from the "MucoFlu" study, which was a prospective study performed in 2009 in the 5 cystic fibrosis centers of the Paris metropolitan area. Data on mandatory and recommended vaccines in CF were collected in the health booklet and compared to the coverage of the general population. RESULTS: A total of 134 CF children were included. Vaccination coverage for mandatory vaccines was insufficient (DTPCaHi, conjugate pneumococcal, BCG, MMR and hepatitis B) at 1year of age with no catching-up with age in contrast to the general population. Approximately 66% of the children had immunization for seasonal influenza and 91% for 2009 pandemic flu. Coverage for vaccines specifically recommended in CF was low for hepatitis A, non conjugate pneumococcal and varicella. CONCLUSION: This study shows a defect in vaccine coverage for both routine immunization and vaccines more specifically recommended in CF.

[Prognostic value of VZV PCR in cerebrospinal fluid in neurological manifestations of varicella]. / Manifestations neurologiques associées à la varicelle : apport de l'amplification génique dans le liquide céphalo-rachidien.

Varicella-zoster virus (VZV) is, like other alphaherpes viruses, neurotropic. Of the admissions to hospital for varicella, 7.6-25% are due to neurologic manifestations. Most of the time, the concomitant skin lesions facilitate the diagnosis. The justification of qualitative PCR (polymerase chain reaction) for VZV DNA in cerebrospinal fluid in the management of these patients is not clear. The aim of this study was to evaluate the prognostic value of qualitative PCR for VZV DNA in cerebrospinal fluid and to assess its impact on patient management. We conducted a retrospective monocentric study in Versailles Hospital (France). It included every child admitted for neurologic manifestations associated with varicella and compared the patients with positive PCR for VZV DNA to those with a negative PCR in the cerebrospinal fluid. Seven patients with positive PCR and 16 patients with negative PCR were included. The median age of the children included was 3 years (range, 1.6-12 years) and 2 years (range, 0.6-5 years), respectively. In the positive PCR group, 86% of the children had fever on first examination and the average time between the onset of skin lesions and neurological signs was +1.28 days (range, -2 to +5 days). In comparison, in the negative PCR group, 81% of the children had fever and the average time delay was +1.75 days (-2 to +7 days). There was no significant difference in terms of length of hospitalization; 3 days (range, 0-6 days) and 3 days (range, 2-7 days), respectively. All patients discharged from our department went home. In addition, there was no significant difference between the two groups in terms of treatment with acyclovir; two children (28.5%) were treated in the positive PCR group versus four (25%) in the negative PCR group. Our study showed no prognostic value for qualitative PCR for VZV DNA in the cerebrospinal fluid of patients with neurologic manifestations of varicella. Therefore, its relevance can be questioned in clinical practice. However, in case of encephalitis and meningitis during primary infection with VZV, quantitative PCR for VZV DNA might have a prognostic value and therefore requires further study.

[Severe human parechovirus-3 sepsis in a 6-week-old infant]. / Infection sévère à paréchovirus de type 3 chez un nourrisson de 6semaines.

Febrile infants under 3 months of age are often treated with broad-spectrum intravenous antibiotics while awaiting culture results, to prevent mother-to-child bacterial infections. Human parechoviruses (HPeV) have recently been described as etiologic agents of meningitis and severe sepsis in neonates and young infants. They are rarely investigated and are therefore probably underestimated. They cause acute clinical symptoms that can incorrectly suggest a bacterial infection. In the present case, a 6-week-old infant infected with HPeV developed severe sepsis, complicated by hepatic cytolysis, meningitis, acute renal failure, and mild hemophagocytic lymphohistiocytosis. HPeV type 3 was found by routine specific RT-PCR in cerebrospinal fluid, stools, and plasma. The outcome was spontaneously favorable after 4 days. Early diagnosis of the HPeV infection by routine specific RT-PCR reduces unnecessary antibiotic use and extended hospitalization in febrile young infants.

[Value of polymerase chain reaction in serum for the diagnosis of enteroviral meningitis]. / Intérêt de l'amplification génique dans le sérum pour le diagnostic des méningites à entérovirus.

Enteroviruses (EV) are a common cause of aseptic meningitis in children. Virological diagnosis of EV meningitis is currently based on the detection of the viral genome in the cerebrospinal fluid (CSF). This study attempted to determine the correlation and the temporality of the polymerase chain reaction (PCR) assay in serum and CSF and to evaluate the possibility of diagnosing EV infection only on the serum PCR. The EV genome was sought by RT real-time PCR (Smart Cycler EV Primer and Probe Set(®), Cepheid) in CSF and serum, collected at the same time, for all children who underwent a lumbar puncture for suspected meningitis, between 1 June and 31 July 2010 at the Versailles Hospital. Forty-four patients were included in the study. EV infection was documented for 22 of them. In 10 patients, the EV genome was detected in CSF only; in 3 patients in serum only, and in 9 patients in both. Among patients with acute EV neurological infection, viremic children were significantly younger (1.6 months versus 5.8 years; P<0.001). Viremia was detected when the serum was sampled within 30 h after the beginning of symptoms. These results confirm previous reports of early and transient viremia in young children. This preliminary study shows the limits and added value of EV PCR in serum. It suggests that in some children and under certain conditions (age >3 months, clinical and biological compatibility with a viral infection, no previous antibiotic therapy, time from symptom onset to blood sampling <30 h, PCR in serum analyzed within 3h), PCR in serum, when positive, is a possible alternative. Therefore, it may be possible to diagnose EV infection without performing a lumbar puncture in a limited number of young children (11.4% of our suspected cases). This study needs to be reinforced by a multicenter study with a broader panel of patients.

[Epidemiology of parechovirus infections of the central nervous system in a French pediatric unit]. / Épidémiologie des infections neuroméningées à parechovirus dans un service de pédiatrie générale.

UNLABELLED: Human parechoviruses (HPeV), like their counterpart enteroviruses (EV), are associated with clinical manifestations ranging from asymptomatic disease to infections of the central nervous system. Newborn and young infants are particularly at risk for severe infection. In the last 5 years, the molecular diagnosis of HPeV infection in cerebrospinal fluid (CSF) and the identification of the associated HPeV type revealed the specific association between HPeV3 and meningitis or sepsis-like illness in neonates and infants. HPeV infection is not yet routinely diagnosed in clinical virology laboratories. OBJECTIVES: To determine the clinical, biological, and epidemiological characteristics of HPeV infections of patients hospitalized at the Centre Hospitalier de Versailles, France. METHODS: A total of 380 CSF samples originally referred to our laboratory for enterovirus testing between January 1st, 2007 and August 31st, 2011, were selected and retrospectively screened for the genome detection of HPeV. All HPeV detected were identified by amplification and sequencing of the complete 1D sequence encoding the VP1 protein. RESULTS: The HPeV genome was detected in CSF samples from nine (2.8%) patients. All were young infants under 18 months of age (median, 30 days; age range, 8 days to 18 months). Fever was observed for all children and eight out of nine (89%) presented with irritability. No pleiocytosis and normal glucose and protein levels were observed. The mean duration of the hospital stay was 4 days (range, 2-7 days) and antibiotics were administered to five patients (55.6%). Yearly frequency of genome detection varied remarkably: 1.1% in 2007, 0% in 2008 and 2011, 2.9% in 2009 and 7.1% in 2010. All genotyped viruses were HPeV3. CONCLUSION: This study confirmed the importance of the HPeV genome detection in CSF samples from patients presenting with sepsis-like illness or suspected infection of the central nervous system, particularly in children under 2 years of age. The introduction of the molecular diagnosis of HPeV infection broadens the panel of diagnosis of neonatal sepsis and central nervous system symptoms in young children. Rapid identification of HPeV by PCR could also contribute to shorter duration of both antibiotic use and hospital stay.

[Enterovirus nosocomial infections in a neonatal care unit: from diagnosis to evidence, from a clinical observation of a central nervous system infection]. / Infections nosocomiales à entérovirus en néonatologie : du diagnostic à la preuve, à propos d'une observation d'infection neuroméningée.

Although enteroviruses generally cause asymptomatic or mild disease, neonates are at higher risk for severe illnesses, among which systemic disease characterized by multiorgan involvement is a potentially fatal condition. Enterovirus neonatal infections may be the source of nosocomial infections in neonatology or in pediatric intensive care units. We report central nervous system infections due to Echovirus 11 in two neonates and the molecular evidence of nosocomial transmission of this strain in a neonatal unit by enterovirus genotyping and phylogenetic analysis. This report illustrates the importance of including enterovirus genome detection in the sepsis screening concomitantly with bacteriological investigations performed at admission of a neonate. Rapid diagnosis and subsequent genotyping could have a beneficial impact on clinical practices at the individual level (reducing the length of antibiotic therapy) and public health policy at the collective level by reinforcing hygiene measures to prevent nosocomial infections, with nurseries and neonatal units being at greater risks.

[Transition of adolescents and young adults from pediatric to adult care]. / Passage des adolescents et des jeunes adultes atteints de mucoviscidose en centre adulte.

Nowdays adults with cystic fibrosis are no more attended in pediatric centers. Transition from pediatric to adult care centers must be anticipated. It requires the preparation of patients and families and a cooperation between both teams. Now, there are more patients and they are healthier. Adults centers caregivers have to pay particular attention to new young patients, to manage cystic fibrosis adult issues and to deal with more frequent comorbidities and severe complications. Adults centers will need better resources to maintain good quality of cares and improved life expectancy.

[Vaccination of newborns with high risk of tuberculosis in a French maternity hospital]. / Vaccination des nouveau-nés à risque élevé de tuberculose dans une maternité française.

BACKGROUND: The early vaccination with BCG of children with a high risk of tuberculosis straight from the maternity hospital has been recommended since October 2005. However, this recommendation has not often been followed. Practitioners feared that the suspension of the mandatory character of the BCG vaccine dating from July 2007 would result in a decrease in vaccine coverage. The goal of this study was to assess a program for early vaccination with BCG in the maternity hospital for high-risk children. METHODS: Intradermal vaccination with BCG-SSI of high-risk newborns, as defined by the Conseil Supérieur d'Hygiène Publique de France, at the maternity hospital of Versailles from May 2007 to May 2008. RESULTS: Six hundred and sixty children (35% of births with a sex ratio of 1.13) fulfilled criteria for vaccination in the maternity hospital. Among the high-risk newborns, 596 (89%), were vaccinated. The geographic origin of one or both parents was the main indication (98.6%) for the vaccination. Three main practitioners (two pediatricians and one nurse) performed 72.6% of the BCG intradermal injections. The other BCG vaccinations were given by occasional practitioners: pediatricians, a midwife, or medical students. A papule was subsequently observed more often when the practitioner was experienced: 96.8% for the main practitioners, 83.5% for the occasional practitioners. Fifty-six (8.3%) parents refused vaccination for their eligible newborn. CONCLUSION: From our experience, the early vaccination of the at-risk of tuberculosis newborn is well accepted in the maternity hospital and presents very few technical problems for an experienced team.

[Seasonal outbreak of enteroviral meningitis during summer 2005: experience of a French pediatric unit]. / Epidémie estivale de méningites à entérovirus en 2005: expérience d'un service de pédiatrie générale.

OBJECTIVE: To describe the clinical and biological characteristics of children presenting with enteroviral (EV) meningitis in a French paediatric unit during summer 2005. METHODS: Retrospective study of children with EV meningitis from May to September 2005, diagnosed by PCR and/or viral culture in cerebrospinal fluid (CSF), serum or throat. RESULTS: We reported 99 cases of EV meningitis (96 confirmed and 3 probable). The sex ratio was 2/1, and the median age was 5 years. Peak incidence was reached during the second week of July. The predominant symptom was meningism. ENT (16%), digestive (10%), cutaneous (15%) or respiratory (4%) symptoms were rare. Blood leucocyte count found a predominance of neutrophils (73%), and lymphopenia in half of the children. The mean value of CRP was 25,5 mg/l. The median leukocyte count in CSF was 65 cells/mm(3), with a prevalence of neutrophils in 60% of cases. Pleiocytosis was absent in 20 children. CSF protein level was increased in 20% of cases. The rate of hospitalization was 57,5%. Intravenous antibiotic treatment, initiated among 18 patients, was stopped in 66,6% of the cases on reception of PCR result. The latter result was obtained in 2,3 days on average. CONCLUSION: The epidemic of 2005 EV meningitis was as widespread as that of summer 2000. Characteristics of these meningitis are strong proportion of CSF without pleiocytose and high prevalence of neutrophils in blood and CSF.

[Pseudomonas aeruginosa and cystic fibrosis: non-antibiotic strategy]. / Pseudomonas aeruginosa et mucoviscidose: stratégie non antibiotique.

The Pseudomonas aeruginosa bronchopulmonary infection is, when chronical, a poor prognosis factor for cystic fibrosis children. The higher life expectancy is partly linked to the progresses of the antipseudomonal antibiotherapy: treatment modulated to the stage of infection; possible use of nebulized and oral (ciprofloxacin) antibiotics. But the antipseudomonal strategy does not limit to the antibiotherapy. The preventive approach includes: preservation of a good nutritional status; daily chest physiotherapy with combined use of aerosolized recombinant human DNase for more than 5 years old children with significative bronchorrea; early anti-infammatory treatment with inhaled corticosteroids, despite a poor efficacy proof level; hygiene measures to reduce the environmental and domestic reservoirs and to avoid nosocomial infections. The development of vaccines for the prevention of P. aeruginosa infection is a promising way but stays in the field of clinical research. In case of chronical infection, long-term macrolids reduce the virulence factors expression of the bacteria, leading to antibiofilm properties in spite of subinhibitory concentrations.

[Post lumbar puncture headache in general pediatrics: a prospective multicenter study]. / Les céphalées après ponction lombaire en pédiatrie générale: étude prospective multicentrique.

PURPOSE: To investigate the frequency of post lumbar puncture headaches (PLPH) after diagnostic lumbar puncture (LP) and to search for influence factors. PATIENTS AND METHODS: Conducted over 6 months into 8 paediatric services, the study concerned 2 to 15 years old children. The LP technic (cannula gauge, bevel orientation, child position, reinsertion of the stylet) was standardised. For each child questionnaires were filled with the parents 3 and 8 days after LP for inquiring headaches, postural characteristics, length and clinical consequences. RESULTS: Among 84 charts, 71 were exploitable. PLPH were observed in 25% of children. The mean duration was 5.9 days, mean bed rest was 1.4 day and mean antalgic treatment 1.7 day. The frequency of PLPH was not significantly influenced by age and sex, neither by the qualification of the physician performing the LP. The frequency was significantly lower when LP execution was easy (19.6 vs. 46.7%; P < 0.05), and when the child had viral meningitis (8 vs. 34.8%; P < 0.05). CONCLUSION: We have found a more important frequency of PLPH than in previous paediatric studies. Clinical consequences justify other researches to precise influence factors and reduce the frequency of this complication.