Agreement between a regional pharmacovigilance centre and an adjudication committee regarding adverse drug reactions on a cohort of hospitalised children.

BACKGROUND AND PURPOSE: The EREMI project was set up to collect data on adverse drug reactions (ADRs) occurring due to off-label and/or unlicensed drugs prescribed to hospitalised children in France. These events were evaluated by a regional pharmacovigilance centre (RPC) and an adjudication committee (AC). The aim of this study was to assess the agreement between these two different entities on their evaluation of ADRs. EXPERIMENTAL APPROACH: The RPC first validated the ADRs and assessed their causality using the Naranjo scale. The AC assessed then ADRs using all available information, including the RPC evaluation. The agreement on severity and nature of ADRs, role of treatment (suspect or concomitant) and drug causality was calculated using Cohen's nonparametric kappa coefficient (k). KEY RESULTS: Three hundred and eighty-six events were reported in 219 children. The RPC excluded 65 events and validated 321 ADRs. Agreement was very good on nature of ADRs (k=0.85) and role of treatment (k=0.81), moderate on severity of ADRs (k=0.60) and very poor on drug causality (k=0.05). CONCLUSION AND IMPLICATIONS: Agreement between the RPC and the AC was not constant throughout this evaluation. They troubled to agree on severe ADRs and on drug causality.

Implementing efficient and sustainable collaboration between National Immunization Technical Advisory Groups: Report on the 3rd International Technical Meeting, Paris, France, 8-9 December 2014.

Many experts on vaccination are convinced that efforts should be made to encourage increased collaboration between National Immunization Technical Advisory Groups on immunization (NITAGs) worldwide. International meetings were held in Berlin, Germany, in 2010 and 2011, to discuss improvement of the methodologies for the development of evidence-based vaccination recommendations, recognizing the need for collaboration and/or sharing of resources in this effort. A third meeting was held in Paris, France, in December 2014, to consider the design of specific practical activities and an organizational structure to enable effective and sustained collaboration. The following conclusions were reached: (i) The proposed collaboration needs a core functional structure and the establishment or strengthening of an international network of NITAGs. (ii) Priority subjects for collaborative work are background information for recommendations, systematic reviews, mathematical models, health economic evaluations and establishment of common frameworks and methodologies for reviewing and grading the evidence. (iii) The programme of collaborative work should begin with participation of a limited number of NITAGs which already have a high level of expertise. The amount of joint work could be increased progressively through practical activities and pragmatic examples. Due to similar priorities and already existing structures, this should be organized at regional or subregional level. For example, in the European Union a project is funded by the European Centre for Disease Prevention and Control (ECDC) with the aim to set up a network for improving data, methodology and resource sharing and thereby supporting NITAGs. Such regional networking activities should be carried out in collaboration with the World Health Organization (WHO). (iv) A global steering committee should be set up to promote international exchange between regional networks and to increase the involvement of less experienced NITAGs. NITAGs already collaborate at the global level via the NITAG Resource Centre, a web-based platform developed by the Health Policy and Institutional Development Unit (WHO Collaborating Centre) of the Agence de Médecine Préventive (AMP-HPID). It would be appropriate to continue facilitating the coordination of this global network through the AMP-HPID NITAG Resource Centre. (v) While sharing work products and experiences, each NITAG would retain responsibility for its own decision-making and country-specific recommendations.

[Vaccination in childhood in France: Current issues and challenges]. / La vaccination des enfants en France : enjeux et défis actuels.

Vaccination in childhood in France : current issues and challenges. Children are a priority target for immunization programs, in large part because the most contagious vaccine- preventable diseases affect children early in life. If vaccination coverage of infants is very high and consistent with public health objectives, the situation regarding older children and especially adolescents is unsatisfactory. Vaccination coverage against measles and meningococcal C diseases are insufficient, resulting in the occurrence of severe cases, which could have been avoided through better immunization coverage. In adolescents, coverage against hepatitis B and especially papillomavirus are far below the expectation, exposing young adults to contamination by these oncogenic viruses. General practitioners and pediatricians are the cornerstone to increase vaccination coverage. The renewed commitment for the vaccination program of the Ministry of Health and its agencies should give them the support they need, in particular by providing them with tools tailored to their practice.

La vaccination des enfants en France : enjeux et défis actuels. Les enfants sont une cible prioritaire des programmes de vaccination, ne serait-ce que parce que les maladies à prévention vaccinale les plus contagieuses touchent les enfants très tôt dans la vie. Si la couverture vaccinale du nourrisson est très élevée et conforme aux objectifs de santé publique, il n'en est pas de même pour l'enfant plus grand et surtout l'adolescent. Les couvertures vaccinales contre la rougeole et les infections à méningocoque C restent insuffisantes, entraînant la survenue de cas graves liés à ces maladies qui auraient pu être évités par une meilleure couverture vaccinale. Chez l'adolescent, la couverture contre l'hépatite B et surtout les papillomavirus sont très en deçà de l'attendu, exposant les jeunes adultes à des contaminations par ces virus oncogènes. Les médecins généralistes et les pédiatres sont la clé de l'amélioration de ces couvertures. Le renouveau de la politique vaccinale insufflé actuellement par le ministère chargé de la Santé et ses agences devrait leur apporter le soutien dont ils ont besoin, en particulier en leur fournissant des outils adaptés à leur pratique.

[VACCINATION AGAINST HEPATITIS B: WHAT'S UP?]. / Vaccination contre l'hépatite B: où en est-on?

The vaccination against hepatitis B has been shown to be effective and safe. 15 years after a scare suggesting a relationship between the HBV vaccine and the development of demyelinating diseases, studies have not confirmed this suspected link. The french HBV vaccination strategy in effect since the 1990's (vaccination of newborns, a catch-up campaign in children and adolescents and vaccination of high risk populations) is well adapted to the existing epidemiological situation. Vaccination coverage in newborns has increased significantly since 2008. Catch-up of children and adolescents is insufficient. The very limited data on vaccination coverage in populations at high risk of HBV suggests that coverage is largely insufficient. The mandatory vaccination of healthcare workers since 1991 has nearly completely eradicated worksite HBV. Nevertheless: persistent circulation of the virus and the risk of healthcare worker-patient transmission, and insufficient coverage justifies continued vaccination and mandatory proof of immunization. Specific vaccination protocols are needed because certain co-morbidities can reduce the probability and strength of the response to the vaccine. The physician should evaluate this risk case-by-case and adapt the vaccination protocol accordingly. Between 2007 and 2012, more than 200 patients have undergone liver transplantation associated with HBV (cirrhosis, hepatocellular carcinoma, fulminant hepatitis). Many of these transplantations could have been avoided thanks to vaccination, and these grafts could have been proposed to other patients.

Vaccination against serogroup B Neisseria meningitidis: Perceptions and attitudes of parents.

BACKGROUND: A vaccine against serogroup B Neisseria meningitidis, major cause of bacterial meningitis in children and adults, has recently been developed. In a context of an increasing parental mistrust against vaccinations, understanding the reason for their choices is crucial in order to improve immunization coverage. Our study aimed at evaluating parental attitudes and perceptions towards serogroup B meningococcal invasive disease vaccination. METHODS: A prospective observational study was conducted in different French independent-practice medical offices (general practitioners and paediatricians) and nurseries between May 1 and December 31, 2013, using a questionnaire distributed in electronic and paper forms to parents having at least one child between the ages of 2 months and 16 years old. RESULTS: 1270 parents were included, of whom 671 (52.8%) spontaneously stated to be in favour of this vaccination. Their choice was mainly justified by the severity of the disease (63.8%) and the desire to protect their child (51.7%). In multivariate analysis, the young age of parents (OR 0.949 per additional year; p<10(-3)), the history of vaccination against serogroup C meningococcal invasive diseases (OR 6.755; p<10(-3)), and the prior knowledge of the vaccine (OR 2.081; p=0.001) were associated with vaccination acceptance. The main reasons for refusal were the lack of hindsight on this new vaccine (50.6%) and the fear of side effects (45.5%). After objective information on the disease and the vaccine, only 6.3% of the entire responding population would refuse to consider vaccination. CONCLUSIONS: The spontaneous acceptance rate of vaccination against serogroup B meningococcal invasive disease is insufficient. However, after objective information by their physician or public health authorities, only a few parents would in the end be completely resistant.

Strategies for decision-making on vaccine use: the French experience.

France enjoys benefits of a good organization of its healthcare system. National Health Insurance is reimbursing vaccines if they are used according to the national recommendation guidelines. Vaccination is the responsibility of the government, advised by its National Immunization Technical Advisory Group (Comité Technique des vaccinations). But France, like many other countries, faces insufficient involvement from the public in immunization programs and, consequently, numerous outbreaks of vaccine-preventable diseases. The French government launched a 5-year national program for improvement in vaccination policy in 2012 to simplify the guidelines, facilitate access to vaccination, invest in research and evaluate its vaccine policy. The role of the public and healthcare professionals to encourage vaccination is crucial for the future.

[Vaccination and pregnancy]. / Vaccinations et grossesse.

Vaccination against influenza is recommended during the vaccination period in pregnant women regardless of trimester. In contrast, administration of live vaccines, such as the vaccine against varicella, MMR (measles-mumps-rubella) is contraindicated in pregnant women. Vaccinations against hepatitis B, diphtheria, tetanus, poliomyelitis, hepatitis A can be made as indicated. Vaccination against yellow fever may be considered in pregnant women travelling to endemic countries. In post-partum period, live vaccines may be administered if necessary, especially vaccination against whooping cough for women not to date with their vaccinations. Vaccination against yellow fever is contraindicated in case of breast feeding. Prevention of pertussis in newborns is based in France on vaccination of the mothers in the post-partum period, and the close contacts of the newborn during the pregnancy ("cocooning").

Knowledge and risk perception of measles and factors associated with vaccination decisions in subjects consulting university affiliated public hospitals in Lyon, France, after measles infection.

In 2011, a large number of European countries faced measles outbreaks, France accounting for more than half of the reported cases. The Rhône-Alpes region, located in south-east France, was one of the most affected provinces, with an incidence rate of 97.9 cases per 100 000 inhabitants. We conducted a retrospective survey of adults and parents of children consulting university affiliated public hospitals because of measles infections between January 1, 2010 and September 2012 in Lyon, France. Our main objectives were to evaluate (1) the level of study population knowledge of measles, (2) vaccination practices, and (3) changes in opinion with regard to measles vaccination after disease onset. Overall, 73.64% of patients were not vaccinated or partially vaccinated. The main reason for non-vaccination in children was inappropriate age while among non-vaccinated adults, 29.3% could not give any reason. In total, 29.1% of the responding parents and 24.2% of adult cases were opposed to vaccination "in principle." A large number of patients did not recognize measles as a serious illness and were unaware of its complications. Among parents of infected children, knowledge of transmission mode (odds ratio [OR] = 5.9; 95% confidence interval [95% CI]: 1.64-21.26), perceived severity of measles (OR = 1.5; 95% CI: 1.06-2.13), and absence of hepatitis B vaccination (OR = 0.17; 95% CI: 0.04-0.65) were independently associated with a more positive opinion about measles vaccination after disease onset. In adult patients, low education level (OR = 3.39; 95% CI: 1.03-11.11) and lack of knowledge of sequelae (OR = 10.19; 95% CI: 1.14-91.31) were linked with a more positive opinion. Individuals affected by vaccine-preventable diseases are interesting populations to study disease impact on vaccine perception.

Clinical presentation of severe viral encephalitis with known causative agents in children: a retrospective study on 16 patients hospitalized in a pediatric intensive care unit (2008-2011).

A retrospective analysis was conducted in a French pediatric hospital in Lyon. Subjects were 16 patients diagnosed with acute viral encephalitis with identified causative agents who were admitted to the pediatric intensive care unit from 2008 to 2011. The median length of stay was 6 days. The outcome was favorable for 77% of the patients. Analysis of biological and clinical findings based on causative agents did not reveal clinical patterns or neurological findings specific to the causal viruses. Nevertheless, uncommon clinical pictures and severe neurological complications were highlighted, in particular for children with influenza-related encephalitis and herpes simplex encephalitis. This case series exemplifies the difficulties, even pitfalls, in establishing a diagnosis of encephalitis, especially in neonates. It points out significant differences in the clinical presentation of encephalitis in children compared with clinical pictures described in previously published large-scale studies on encephalitis mainly conducted in adults.

[The immunization schedule]. / Le calendrier vaccinal.

Vaccination offers individual and collective protection against a number of infectious diseases. The immunisation schedule is updated every year and published by the French Ministry for Health. In 2013, the schedule was simplified in order to improve the vaccination coverage of the French population. Specific recommendations are made for health professionals.

[Age for HPV vaccination: recommandations from the French high council of public health]. / Vaccins contre les papillomavirus humains (HPV) - Dernières recommandations du Haut conseil de la santé publique, et premiers résultats cliniques et virologiques.

The French high council of public health has recently amended age for HPV vaccination. The paper will describe reasons that have contributed to the development of these new guidelines. Parental and adolescent acceptance of HPV vaccination is reported as well as potential barriers among medical practices. First results of immunogenicity of vaccines using alternative dosing schedules are presented. Finally, preliminary data on clinical efficacy of the quadrivalent vaccine on genital warts and cervical precancerous lesions are presented. A decrease in the prevalence of infection with genotypes included in the vaccine has now been reported in several studies. This decrease may be partly attributable to herd immunity.

Stroke by carotid artery complete occlusion in Kawasaki disease: case report and review of literature.

BACKGROUND: Kawasaki disease is an acute and time-limited systemic vasculitis primarily affecting young children. PATIENT: We describe an 18-month-old girl with Kawasaki disease who developed cerebral infarction following complete occlusion of her right internal carotid artery. RESULTS: The occlusion occurred 10 days after the onset of fever, while she was on high-dose aspirin, and the day after she received intravenous immunoglobulin treatment. We present the first literature review on this very rare complication. CONCLUSION: Stroke is a rare neurological complication in Kawasaki disease. Optimal treatment should be begun as soon as possible after diagnosis. Intravenous immunoglobulins seem to reduce the cerebrovascular complications, but evaluation of hydration status is strongly recommended before performing such treatment.

How French physicians manage with a future change in the primary vaccination of infants against diphtheria, tetanus, pertussis and poliomyelitis? A qualitative study with focus groups.

BACKGROUND: As in other European countries, the French vaccination schedule changes according to epidemiological and socio-economic situations. Further changes are planned for 2013, including the withdrawal of one dose for primary vaccination against diphtheria, tetanus, polio, pertussis and Haemophilus influenzae. A partnership between the French Technical Vaccination Committee and the French Institute for Health and Medical Research designed a study to assess primary care physicians' agreement about this modification. METHODS: Qualitative study with focus groups and semi-structured interviews in France. Four focus groups were conducted with physicians, supplemented by four individual interviews. RESULTS: The physicians of the survey had accepted the suggested vaccination schedule well. A few concerns had been underlined: fear of less follow-up care for infants resulting from the removal of one visit driven by the primary vaccination; fear of loss of vaccine efficacy; suspicion of the existence of financial arguments at the origin of this change; and adjustment to current vaccination schedule. Several suggestions were made: providing strong support from health authorities; developing stable and simple recommendations; providing effective tools for monitoring patient's vaccination status. CONCLUSIONS: Physicians' opinions suggested a good acceptance of a possible change about primary vaccination against diphtheria, tetanus, polio, pertussis and Haemophilus influenzae. Physicians' suggestions resulted from this qualitative study on a new vaccination schedule. It showed how that their involvement was feasible for preparing the implementation of a new vaccination schedule.

[Influenza infection and pregnancy]. / Grippe au cours de la grossesse.

Pregnant woman have an increased risk of respiratory complications and hospitalization related to influenza. The flu, like any systemic infection, may also be responsible for uterine contractions constituting a threat of miscarriage or premature labor according to gestational age at which it occurs. There is no specific recommendation regarding the management of influenza-like illness in pregnant women, but a nasopharyngeal sample can be performed in the presence of respiratory or general symptoms occurring during an epidemic to search influenza and establish if a specific treatment with oseltamivir (Tamiflu(®)). Surveillance in hospital or intensive care unit may be necessary. Vaccination against influenza provides a satisfactory immunity in pregnant women and reduces the risk of respiratory complications. Transplacental passage of maternal antibody protects newborns who are more likely to have severe influenza infection and because the vaccine cannot be administered before the age of 6 months. The available data show good tolerance influenza vaccination performed during pregnancy. Since 2012, vaccination against seasonal influenza is recommended for pregnant women, whatever the stage of pregnancy at the time of the vaccination campaign.

Measles elimination efforts and 2008-2011 outbreak, France.

Although few measles cases were reported in France during 2006 and 2007, suggesting the country might have been close to eliminating the disease, a dramatic outbreak of >20,000 cases occurred during 2008-2011. Adolescents and young adults accounted for more than half of cases; median patient age increased from 12 to 16 years during the outbreak. The highest incidence rate was observed in children <1 year of age, reaching 135 cases/100,000 infants during the last epidemic wave. Almost 5,000 patients were hospitalized, including 1,023 for severe pneumonia and 27 for encephalitis/myelitis; 10 patients died. More than 80% of the cases during this period occurred in unvaccinated persons, reflecting heterogeneous vaccination coverage, where pockets of susceptible persons still remain. Although vaccine coverage among children improved, convincing susceptible young adults to get vaccinated remains a critical issue if the target to eliminate the disease by 2015 is to be met.

Correlation between emergency room visits for influenza-like illness during the influenza A (H1/N1) pandemic in children and adults.

Surveillance of incident influenza-like illness (ILI) was implemented in two children and adult medical emergency departments during the influenza A (H1/N1) pandemic to assess correlations in the daily number of ILI-related emergency room visits (ERV) between these departments. A total of 7165 ILIs in children and 610 ILIs in adults were observed. We noticed a high linear correlation between the number of ERV involving ILI on day D in the pediatric department and the number of ERV because of ILI 2 days later in adults (R = 0·82, P < 10(-4)). Therefore, the rate of adult ILI-related ERV might be anticipated based on the rate of pediatric ERV.