[Pediatric exposure to endocrine disruptors and carcinogenic, mutagenic or reprotoxic substances by pharmaceutical forms intended for the cutaneous route: Regulatory provisions in France, in Europe, and state of the art of scientific knowledge]. / Exposition pédiatrique aux perturbateurs endocriniens et substances cancérogènes, mutagènes ou reprotoxiques par des formes pharmaceutiques destinées à la voie cutanée : dispositions réglementaires en France, en Europe, et état de l'art des connaissances scientifiques.

OBJECTIVES: The objective is to conduct a review of pediatric exposure to substances whose endocrine disrupting (ED), carcinogenic, mutagenic, or reprotoxic (CMR) character has been confirmed or remains controversial, through their use in pharmaceutical forms intended for the cutaneous route, as well as regulatory measures diligent at the national and European levels. METHODS: A bibliographical search was carried out on the databases PubMed, Web of Science, Cochrane Library, supplemented by a search for recommendations from French and European authorities. References were selected following an assessment of their relevance to our topic. RESULTS: Seventy-one references were selected. Pediatric exposure to endocrine disruptors and CMR substances remains through products formulated for their use, but also through indirect exposure to products commonly used by adults. Exposure arises both from the choice of excipients (parabens, phenoxyethanol), packaging materials (bisphenols, phthalates) and the qualitative or quantitative nature of the active ingredients (iodine, boron, pyrethroids, organic sunscreens). CONCLUSION: The health professional must be able to develop a critical mind on such substances in order to inform and promote therapeutic adherence, guaranteeing the safety of the child's care.

[Dermocorticoides and sun exposure: A misunderstanding?] / Dermocorticoïdes et exposition solaire : un malentendu ?

INTRODUCTION: Fear of dermocorticoids (DCs) or corticophobia is based on an overestimation of the risks of actual side effects and on unfounded beliefs such as DCs-induced photosensitivity among community pharmacists. The objective of this study was to assess the community pharmacy teams' fear of dermocorticoids in atopic dermatitis (DA) in sunny weather and its impact on drug use advice. MATERIAL ET METHODS: A questionnaire as a real case (a summer prescription for atopic dermatitis for an 18-month-old child) was posted on Facebook via groups of pharmacists, technicians and students. Data collected concerned the health professional, his or her reluctance to DCs, advice associated with dispensation, detailed concerns about the DC and sun association, and sources of information. RESULTS: In total, 126 participants responded (48.4% pharmacists, 40.5% technicians, 10.3% students): 12% were reluctant to DCs, 36% were reluctant to DCs and considered them photosensitizing, and 51% were not reluctant but considered them photosensitizing. The impact on the patient advice was: a suggestion to stop DC during sun exposure (28%), to stop or limit DC (dose, duration) (43%). Concerns about the association DC/sun were mainly due to UV rays (46%). Sources cited were: monographs (54%), Internet (6%), training courses (13%). CONCLUSION: The false belief of DC/sun incompatibility in DA is strong among pharmacists and impacts on patients' advice. The role of the official team in dispensing dermocorticoids is essential: training and information for professionals helps to fight false information.

[Enoxaparin and tinzaparin in pediatrics: Impact of recommendation on prescription quality and anti-Xa levels]. / Énoxaparine et tinzaparine en pédiatrie : impact de recommandations sur la qualité des prescriptions et l'activité anti-Xa.

OBJECTIVES: A protocol has been written and distributed in May 2017 to all prescribers in a pediatric hospital to standardize and to secure the prescriptions of enoxaparin and tinzaparin considered as two high risk medications. The aim of this study is to evaluate the impact of the protocol on those prescriptions in a pediatric population. METHODS: This is a monocentric retrospective study comparing prescriptions of this two low-molecular-weight heparins for patients under 18 years old in 2016 and 2018, thus before and after the protocol redaction. RESULTS: In 2016, 2246 prescriptions of enoxaparin and tinzaparin were analyzed for 627 patients. Among them, 142 (22.6%) patients have had at least one anti-Xa level dosed. On the other hand, in 2018, 2061 prescriptions were written for 628 patients including 96 (15.3%) who have had at least one anti-Xa level dosed. The conformity rate of the first dose in IU/kg/administration of the first enoxaparin prescription goes from 36.3% before protocol to 52.1% after (P=0.03*). Concerning tinzaparin, the conformity rate goes from 69.2% to 83.3%. (P=0.19). The rate of first anti-Xa level in the range 0.4 to 1.2 IU/ml increase between 2016 and 2018 from 27.7% to 43.8% (P<0.001*). CONCLUSION: This protocol enabled to improve the quality of prescriptions in terms of: dosage written in IU/kg/administration, frequency of administration, dilution conformity, and result of the first anti-Xa level. Some efforts must be made in writing the dose in IU not in mg or ml.

[Attitudes and experiences of off-label prescribing among paediatricians in a French university teaching hospital]. / Attitudes et expériences des médecins face à la prescription hors autorisation de mise sur le marché dans un hôpital pédiatrique français.

PURPOSE: The lack of drugs specifically assessed for paediatric use results in a widespread off-label drug use. The aim of this work is to identify experiences and attitudes towards paediatrics off-label prescribing in a university teaching paediatric hospital. METHODS: A questionnaire of 24 items was sent by email to 409 paediatricians in February 2013. DATA COLLECTED: frequency of off-label prescribing, sources of information, concern about safety and adverse events with off-label drug use, proportion of parents informed and order with "off-label" mention. RESULTS: Eighty questionnaires were returned. Over 81% of responders were familiar with the concept of off-label drugs prescribing. The most common reason given for off-label prescribing was for a younger age (74%) and for another indication (28%). They (79%) used a colleague's opinion and the most important sources of information used were the literature (72%), international guidelines (62%), the French National Formulary Vidal (56%) and national guidelines (46%). Although 54% of responders expressed concerns about safety about off-label prescription, only 29% had observed adverse event with off-label drug use. Two third of respondents informed the parents but off-label prescribing cannot be always explained to family. Many respondents (81%) did not write "off-label" mention on prescription. However, 52% stated that they would be willing to undertake off-label prescription monitoring with a local observatory. CONCLUSION: Our study describes the perceptions and attitudes of paediatrician's regarding off-label prescribing for children. Patient information and documentation in the patient file remain incomplete. The prospective collection of off-label prescription will locally be performed.

[Determinants of the evolution of hospital pharmacy in France and Quebec: Perception of hospital pharmacists]. / Déterminants de l'évolution de la pharmacie hospitalière en France et au Québec : perception de pharmaciens hospitaliers.

BACKGROUND: Hospital pharmacy practice has evolved differently between France and Quebec. While this development is part of broader systems, French and Quebec hospitals have undergone significant changes over the years to cope with challenges, among others, the economic and demographic realities. PURPOSE: The main objective is to evaluate and compare the perception of French and Quebec hospital pharmacists about the factors that have contributed to the evolution of pharmacy practice in their respective context. METHODS: This is a descriptive cross-sectional study. The study focuses on a sample of experienced hospital pharmacists in France and Quebec. We targeted a convenience sample of 50 respondents per country. An online questionnaire with 15 pharmaceutical activities to which are connected nine factors that may have influenced the implementation of each of these activities in each country was used. The mean score was calculated for each of the nine factors for each activity. The perception of French and Quebec hospital pharmacists was then compared. A P value less than 0.05 was considered statistically significant. RESULTS: Two hundred and sixty hospital pharmacists were directly contacted in France and 79 in Quebec. Seventy-eight French pharmacists and 77 Quebec pharmacists responded to the survey, that is a respective response rate of 30% and 97%, respectively. The hierarchy of factors that contributed to the evolution of pharmacy practice was similar between the two countries, legislative and regulatory factors as well as the concern for risk management and quality dominate; scientific human, economic factors and training have a relatively similar position. For cons, the news factor (6th in France against the 10th position in Quebec) and the academic factor (10th position in France against the 6th position in Quebec) obtained inverse scores between France and Quebec. CONCLUSION: There are few data on the determinants of the evolution of hospital pharmacy in France and Quebec. The hierarchy of factors that contributed to the evolution of pharmacy practice is similar between the two countries, although differences of rank were found for the news and academic factors. Further studies are needed to better understand the factors that influence the evolution of pharmacy practice in health care institutions.

Multiple health care visits related to a pediatric emergency visit for young children with common illnesses.

UNLABELLED: We aim to describe the number of health care visits before and after pediatric emergency department (PED) visits for common illnesses in a French tertiary pediatric hospital. This was a prospective cohort study with 501 children under 6 years of age who were evaluated and discharged from a tertiary care PED. Enrollment occurred on eight randomly selected study days between November 2010 and June 2011. The caregivers were then contacted via telephone 8 days later to obtain follow-up data, including information about return visits to health care facilities. Multiple visits were made by 206 (41 %) children, previous visits had occurred for 139 (28 %) children, and return visits had occurred for 94 (19 %) children. Previous and return visits were made at the PED as well as in general practitioners' offices and private pediatric offices. The median age of the subjects was 18 months. Fever was the most common complaint and was associated with more frequent multiple heath care visits. CONCLUSION: Multiple heath care visits for the same illness are frequent, especially for febrile children. Interestingly, this phenomenon concerns every type of health care facility, including the PED, general practitioners' offices, and private pediatric offices. Further studies should be performed to achieve a better understanding of this phenomenon and to test specific interventions, such as parental education and improvement of the information system.

Understanding and preventing vaccination errors.

INTRODUCTION: Vaccine-related medication errors can occur at each step of the vaccination process: prescribing, dispensing, preparation, administration, monitoring, transport, and storage. We aimed to describe current knowledge of vaccination-related errors to identify areas for improvement. MATERIAL AND METHODS: We performed a literature review on PubMed, using MeSH terms, from 1998 to 2020 to identify articles that would illustrate vaccine-related medication errors. We developed a questionnaire for health professionals concerning prescribing, dispensing, or administering vaccines via Facebook, and then identified priority areas for information to reduce vaccine-related medication errors. RESULTS: A total of 227 answers were collected from midwives (N = 90), pharmacists or technicians (N = 75), and physicians or interns (N = 62). Practitioners gave wrong answers on live vaccines administered during pregnancy (>10 % of physicians), incorrect acronyms for the DTCaP (diphtheria, tetanus, pertussis, poliomyelitis) vaccine corresponding to branded products (72 % of midwives), lack of marketing authorization knowledge for the influenza vaccine (46 %), duration of vaccine conservation outside of the refrigerator (52 %), or intravenous administration of the rotavirus vaccine (23 %). Most health professionals mentioned the possibility of writing procedures for the various steps of the vaccine process, but only few of them have actually done it (15 % for dispensing/administration versus 61 % for storage). Ten key points for initial or ongoing training of health professionals have been summarized. CONCLUSION: There is partial mastery of vaccine knowledge among health professionals. Our final table presents the most important elements of these results for educating health professionals on potential vaccine-related medication errors.

Use of continuous infusion of clonidine for sedation in critically ill infants and children.

BACKGROUND: Adequate sedation and analgesia are required for critically ill children in order to minimize discomfort, reduce anxiety, and facilitate care. This is commonly achieved through a combination of opioids and benzodiazepines. Prolonged use of these agents is associated with tolerance and withdrawal. Clonidine as an adjunctive sedative agent may reduce sedation-related adverse events. OBJECTIVE: Our first aim was to describe the indication for clonidine administration and its secondary effects in a mixed cohort of critically ill children. Our secondary aim was to measure the consumption of sedatives during two study periods: before and after the use of clonidine in our pediatric intensive care unit (PICU). METHODS: This was a single-center study conducted in a tertiary PICU and encompassed retrospective chart review of patients who received clonidine between November 2013 and April 2015. We collected data on clonidine dosage, duration of administration, indication for the prescription, and potential side effects. We analyzed the total consumption of sedatives over 18 months, before and after the introduction of clonidine in our sedation protocol. RESULTS: A total of patients received clonidine, with a mean age of 2.2 ± 2.8 years. The primary reason for intensive care admission was respiratory failure (48%). The main indication for clonidine administration was increasing requirement for morphine and midazolam (60%). The mean duration of clonidine infusion was 9 ± 7.3 days. Bradycardia and hypotension occurred in five patients (11.6%) and nine patients (21%), respectively. These side effects did not result in any major intervention. Younger age was a risk factor for clonidine-associated bradycardia. We observed a significant decrease in morphine and midazolam consumption with clonidine as a comedication. Compared with the pre-study period, consumption decreased by 19.7% for morphine and by 59% for midazolam (calculated as milligram/admission). CONCLUSION: Continuous infusion of clonidine in critically ill children is safe and effective. Clonidine is a sedative-sparing agent and this can help reduce complications associated with prolonged use of opioids and benzodiazepines.

In-plane nanoelectromechanical resonators based on silicon nanowire piezoresistive detection.

We report an actuation/detection scheme with a top-down nanoelectromechanical system (NEMS) for frequency shift based sensing applications with outstanding performance. It relies on electrostatic actuation and piezoresistive nanowire gauges for in-plane motion transduction. The process fabrication is fully CMOS (complementary metal-oxide-semiconductor) compatible. The results show a very large dynamic range of more than 100 dB and an unprecedented signal to background ratio of 69 dB providing an improvement of two orders of magnitude in the detection efficiency presented in the state of the art in NEMS fields. Such a dynamic range results from both negligible 1/f noise and very low Johnson noise compared to the thermomechanical noise. This simple low power detection scheme paves the way for new class of robust mass resonant sensors.

[Use of injectable lorazepam in status epilepticus: a comparative study in French-speaking hospitals]. / Utilisation du lorazépam injectable dans le traitement de l'état de mal épileptique : étude comparative au sein d'hôpitaux pédiatriques francophones.

BACKGROUND: Injectable lorazepam (IL) is marketed in many countries but in France is only available within the framework of a compassionate use program for refractory status epilepticus. This study aims to evaluate the differences of pediatric use and status of IL in the hospitals of the Mother-Child French-speaking Network (Réseau mère-enfant de la francophonie, i.e., RMEF). METHODS: Inclusion criteria are: firstly, RMEF member; secondly, one site per town; thirdly, all the Assistance publique-Hôpitaux de Paris hospitals. After a phone-recruitment in each selected hospital, a survey was sent by e-mail. The data collected concerned the number of beds in the hospital, the official status of IL, its place in the therapeutic strategy, in hospital consumption in 2008 (in milligram) and the therapeutic alternatives. RESULTS: Among the 18 hospitals selected, 17 were contacted and 12 (70%) replied. IL is not marketed in Tunisia and Lebanon. In Switzerland, Canada and Belgium, IL is marketed and used in all the polled hospitals (6.2 to 48.0mg per bed). In France, only the Robert Debré Hospital uses it (3.2mg per bed). In the countries where it is marketed, IL was firstly prescribed for the studied indication. In the other countries, injectable diazepam was the first line treatment (six out of eight hospitals). DISCUSSION/CONCLUSION: France is the only country where IL is available though not marketed. The pharmacokinetic data favor use of IL instead of its principal therapeutic alternative (injectable diazepam) but no currently available evidence concludes that IL is superior to diazepam in the management of pediatric status epilepticus. The official indication of IL in France (last intention) is in contradiction with its use in the countries where it is marketed and with the data of the literature in favor of the first intention. This works presents the first evaluation on the use of IL in pediatric status epilepticus in the RMEF hospitals. It highlights the discrepancies in the management of status epilepticus in comparable pediatric hospitals.

Vaccine-preventable meningitis in French children with incorrect vaccination status from 2011 to 2013.

The objective of this study was to determine the number of cases of pediatric meningitis or purpura fulminans associated with an incorrect vaccination status from 2011 to 2013 in France. A total of 48 children with vaccine-preventable meningitis or purpura fulminans, including three deaths, had an incorrect vaccination status: 26 cases were due to Neisseria meningitidis group C (54.2%), 19 to Streptococcus pneumoniae (39.6%), and three to Haemophilus influenzae type b (6.3%). The majority of patients (n=35, 72.9%) had received no injection of the vaccine concerned. Over a 3-year period, 48 cases of bacterial meningitis or purpura fulminans in children could have been avoided if the French immunization schedule had been followed.

[Pilot study about pharmaceutical care implantation in a general paediatric unit in a French hospital. France-Québec collaboration and comparison]. / Etude pilote sur la mise en place des soins pharmaceutiques dans le service de pédiatrie générale d'un hôpital français. Collaboration et comparaison franco-québécoise.

UNLABELLED: STATE OF THE PROBLEM AND OBJECTIVES: French pharmacists are quasi absent from hospital wards. Our objective was to describe the implantation of pharmaceutical care in a patient unit of a French paediatric hospital. MATERIAL AND METHODS: Following an internship in pharmaceutical care at the Sainte-Justine hospital (SJ) in Montreal, a French pharmacist returned to France to implement the pharmaceutical model in a paediatric unit at Robert Debré hospital (RD) in Paris. We first collected pharmaceutical interventions carried out during a 5-month period. In a second phase, we compared pharmaceutical interventions provided by the team composed of the same French pharmacist and a pharmacist from Québec in both settings during 14 days respectively. RESULTS: In the first phase, 556 interventions were done (8.2+/-2,0 per day) with a significant increase observed during the first 2 months. In the second phase, 216 interventions were done at RD and 174 at SJ. The interventions were mainly related to drug information, modification of treatment and seamless care with the pharmacy of the hospital or a community pharmacy. The interventions targeted junior (30.5 to 55.4%), senior physicians (16.2 to 38.5%) and pharmacy (11.5 to 16.2%) in the different phases and sites. A high level of physician acceptance was observed, with respectively 86.0 and 93.1% at RD and SJ. DISCUSSION: French pharmacists can apply the pharmaceutical care model following a specific training. Further studies are required to evaluate the feasibility and the impact of pharmaceutical care in France.

[Mydriatic eye drops for children: Analysis of use]. / Collyres mydriatiques en pédiatrie : analyse des pratiques d'utilisation.

Mydriatic eye drops are indicated for ophthalmologic exams (fundus and cycloplegic effect for refraction diagnosis). Their use must be optimal to avoid adverse reactions. This is even more important in pediatrics, because few clinical studies were conducted in this population during drug development. We reviewed the use of mydriatic eye drops, gathering information from the Summary of Product Characteristics (SPC) from the Theriaque® database (CNHIM) and the manufacturers' information, in terms of dose, concentration and volume administered, age limit indications, recommendations for administration, and our local practice. This tool is useful in our hospital for physicians, pharmacists, and nurses but could be also useful for all healthcare providers using mydriatic eye drops for children.

Guidelines for proton pump inhibitor prescriptions in paediatric intensive care unit.

Background Stress ulcer prophylaxis (SUP) is recommended in some situations to prevent upper gastrointestinal bleeding and is a component of standard care for patients admitted to the intensive care unit (ICU). Proton pump inhibitors (PPIs), already among the most widely prescribed drug classes, are being increasingly used. Objective To describe PPI prescribing patterns and their changes after the dissemination of guidelines. Setting Paediatric ICU (PICU), Robert-Debré Teaching Hospital, Paris, France, which admits about 800 patients annually, from full-term neonates to 18-year-olds. Method Prospective observational study with two 6-week observation periods (July-August and September-October, 2013), before and after dissemination in the PICU of PPI prescribing guidelines. Main outcome measure Changes in PPI prescribing patterns (prevalence, dosage, and indication) after the guidelines. Results The number of patients admitted to the PICU was 77 (mean age 4.6 years [range 1 day-18 years]) before and 70 (mean age 3.8 years [range 1 day-17 years]) after the guidelines. During both periods, SUP was the most common reason for PPI prescribing. The proportion of patients prescribed PPIs dropped significantly, from 51% before the guidelines to 30% after the guidelines (p < 0.001). Mean daily dosage also decreased significantly, from 1.5 mg/kg/(range 0.5-4.4) to 1.1 mg/kg (range 0.7-1.8) (p < 0.002). None of the patients experienced upper gastrointestinal bleeding during either period. Conclusion Off-label PPI prescribing for SUP was common in our PICU. The introduction of guidelines was associated with a significant decrease in PPI use and dosage. This study confirms that guidelines can change PPI prescribings patterns in paediatric practice.

[Consensus validation of a tool to identify inappropriate prescribing in pediatrics (POPI)]. / Validation par consensus d'un outil d'identification de prescriptions inappropriées en pédiatrie (POPI).

OBJECTIVE: Medication errors including inappropriate prescriptions and drug omissions are one of the causes of adverse drug events in children. Our aim was to develop a preliminary screening tool to detect omissions and inappropriate prescriptions in pediatrics based on French and international guidelines. MATERIEL AND METHODS: Disease classification was based on the prevalence rate of pathology and hospital statistics. The criteria were obtained by reviewing many French and international references. The Delphi consensus technique was used to establish the content validity of POPI. The level of agreement and the proposals of healthcare professionals was noted on a nine-point Likert scale. RESULTS: The criteria were categorized according to the main physiological systems (gastroenterology, respiratory infections, pain, neurology, dermatology, and miscellaneous). They were distributed to 16 French pediatric panelists (eight pharmacists, eight pediatricians who were hospital-based [50%] or working in the community [50%]). After two rounds of the Delphi process, 101 of 108 criteria were chosen with strong consensus (76 inappropriate prescriptions and 25 omissions). CONCLUSIONS: POPI is the first screening tool to detect inappropriate prescriptions and omissions in pediatrics. It is now necessary to conduct a prospective study to determine inter-rater reliability and the tool's detection capacity.

Evaluation of frequency of paediatric oral liquid medication dosing errors by caregivers: amoxicillin and josamycin.

OBJECTIVE: To study reconstitution and preparation dosing errors of liquid oral medications given by caregivers to children. METHODS: A prospective observational study was carried out in the departments of general paediatrics and emergency paediatrics at the Robert-Debré Children's University Hospital. An interview with caregivers involved (1) practical reconstitution and preparation of an oral liquid medication from a prescription drawn at random (amoxicillin (Clamoxyl, dosing spoon) or josamycin (Josacine, dose-weight pipette)) and (2) a questionnaire about their use. RESULTS: One hundred caregivers were included. Clamoxyl and Josacine were incorrectly reconstituted in 46% (23/50) and 56% (28/50) of cases, respectively, with a risk of underdosing of Clamoxyl (16/23) and overdosing of Josacine (23/28). Dose preparation with the dosing spoon was incorrect in 56% of cases, and in 10% of cases with the dose-weight pipette. Female sex, native French speaker, and age were significantly associated with correct reconstitution. Male sex and medication were significantly associated with correct preparation. CONCLUSIONS: This study highlights the high incidence of errors made by caregivers in reconstituting and preparing doses of these liquid oral medicines, which are associated with considerable risks of over- and underdosing. Factors associated with these errors have been identified which could help health professionals to optimise their strategy for educating families about the use of liquid oral medications and the need to check that they understand these instructions.

NSAIDs in paediatrics: caution with varicella!

Anti-inflammatory drugs have been suspected on several occasions to have promoted development of bacterial infection among varicella patients. Some countries have not implemented childhood varicella vaccination. Three cases in our hospital suggested the predisposing role of NSAIDs in varicella patient deterioration. Open access to these drugs widely increases their use and patient information should be continually provided in the medical offices and at dispensing pharmacy counters. Taking account of the benefit/risk balance and applying the simple precautionary principle, it would be appropriate to be cautious about the use of NSAIDs in the paediatric population.

Development of a consensus-base list of criteria for prescribing medication in a pediatric population.

BACKGROUND: Although many people are involved in the optimal use of a medication within this process, the use of medications carries risks of adverse events, which are greater in the pediatric population because of many factors. OBJECTIVE: In this context, our aim was to develop a consensus-based list of criteria for the safety of the pediatric medication-use process or circuit (referred to from now on as the CIRCUS tool: CIRcuit-of-Child-drug-USe). SETTING: Multicenter with a trio of experts from eight university hospitals. METHODS: A literature search (1998-2013) was conducted in order to identify the different safety practice domains for the pediatric medication use process. Twenty-six safety practice domains were identified and 48 compliance criteria were formulated. In order to reach a consensus on the most relevant compliance criteria for safety practices, an international 24 French-speaking multidisciplinary panelists (8 doctors, 8 pharmacists and 8 nurses) selected to represent a broad range of experience levels and specialties took part in a two round Delphi survey which was conducted between March and July 2013. Each panelist was asked to rate each proposed criterion on a 1-9 Likert scale in order to show their level of agreement (i.e. 1 reflects strong disagreement and 9 reflects strong agreement). MAIN OUTCOME MEASURE: Development of a consensus-base list for safety practices in pediatrics. RESULTS: Twenty-two of the 24 professionals invited to take part in this survey (92% participation rate) completed the two Delphi rounds. At the end of the two Delphi rounds, a total of 38/48 (79%) safety practice compliance criteria achieved consensus by the panelists. The criteria were grouped into 23 domains. CONCLUSION: This study presents the development of a self-assessment tool for safety practices in the pediatric drug-use process using a Delphi method. This tool may be used in order to record and compare the prevalence of best safety practices in the pediatric drug-use process.

[Multiple leiomyomatous pulmonary nodules in women. Apropos of 2 cases of metastasizing benign leiomyoma]. / Nodules léiomyomateux pulmonaires multiples de la femme. A propos de 2 observations de léiomyome bénin métastasiant.

Two cases of multiple pulmonary leiomyomas in women aged 51 and 45 years respectively are reported. The lesions were discovered 21 and 11 years respectively after hysterectomy for uterine fibromyoma without abnormal histological features. The pulmonary nodules were bilateral and either stable or growing slowly. They were revealed by non-specific symptoms. At surgical biopsy the histological picture was one of benign leiomyoma without mitosis. In one of the 2 patients a pulmonary nodule was explored for oestrogen and progesterone receptors with positive results. The various theories on the origin of these multiple leiomyomas are reviewed. Initially regarded as malformative tumours, they were later interpreted as metastases of uterine leiomyomas with a potential for dissemination. The finding of hormone receptors demonstrates a relationship between these pulmonary lesions, uterine leiomyomas and other multifocal leiomyomatous diseases, including lymphangioleiomyomatosis. The slow but benign course of these tumours differentiates them from metastases of low-malignancy leiomyosarcomas.

[Is pediatrics excluded from pharmaceutical innovation?]. / La pédiatrie, toujours exclue de l'innovation pharmaceutique ?

OBJECTIVE: The development of therapeutic strategies for children depends unequivocally on the commercial launching of drugs with pediatric indications. New therapeutic drugs differ from one country to another, particularly considering children. The objective of this study was to compare access to new drugs by children in France (FR) and Canada (CA). MATERIAL AND METHODS: Retrospective study comparing newly marketed drugs in FR and CA from 1 January to 31 December 2009. Data were collected through independent sources: (HAS, Thériaque, ANSM for FR and CEPMB, BDPP for CA). RESULTS: Respectively, 37 and 30 new drugs were put on the market in 2009 in FR and CA. Among them, 38% (n=14) and 27% (n=8) had a pediatric indication. For 91% (FR) and 95% (CA) of the drugs not indicated for children, no clinical study has been planned to define pediatric indications. All the drugs (100%) with pediatric indications presented dosages based on age or weight, but it should be noted that two drugs had no form adapted to children. Fifty-seven percent of these drugs were first available on the French market and later on the Canadian market, with a median delay of 8.5months. CONCLUSION: This study highlights the obvious lack of pediatric drugs contributing to large prescriptions of off-label drugs for children, with no dosage or adapted pharmaceutical form for this population.