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Objectives: To describe the PHAGEinLYON Clinic programme, set up in 2022 to improve access to phage therapy in France using pharmaceutical-grade phages., Methods: All phage therapy requests received during 2022 were collected prospectively, and reviewed retrospectively to analyse the decision and the patient care pathway (NCT05883995)., Results: Of 143 requests for phage therapy, the indication was confirmed at a multidisciplinary team meeting for 57 (40%) patients. Forty-four patients were infected with bacteria that could be targeted easily by phages in France. Finally, 33 patients were treated, including 26 at the study institution, through a compassionate access programme or in a clinical trial. The main indication were complex bone and joint infections, endovascular infection and lung infection. In order to manage these patients, 172 pharmaceutical phage cocktails targeting Staphylococcus aureus and/or Pseudomonas aeruginosa were prepared: 57 for local injection and 99 for intravenous injection. During follow-up, 18 (69%) patients showed a favourable clinical evolution, and six (23%) patients required subsequent phage therapy, either with the same phage with greater exposure, or with a different phage from elsewhere., Conclusions: Implementation of the PHAGEinLYON Clinic programme in 2022 was associated with groundbreaking access to phage therapy in France., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Endocrine disruptors (ED) are ubiquitous pollutants, possibly implicated in chronic disease. Exposure of vulnerable populations; including neonates, infants and children; must therefore be limited. Informing parents is now a public health challenge. We conducted a quantitative cross-sectional study at the Lyon Mother and child Hospital. We used questionnaires to assess the beliefs and knowledge about ED of parents and pediatric healthcare professionals in the pediatric ward in Lyon, France. A total of 746 questionnaires were completed: 444 for professionals and 302 for parents. The majority of both populations had already heard of ED but only 10% of parents and 5% of professionals felt sufficiently informed. Professionals answered better than parents (73% vs. 60%). The main source of information was similar: media. Only 20% of professionals had read a scientific article about ED and 4% have followed a training. Environmental exposure and EDs is an increasing concern for parents but specific knowledge remains scare for parents and professionals. Specific training is needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Portefaix, Loppinet, Tourvieilhe, Balice, de Veron de La Combe, Kassai and Bacchetta.)

Background and Objectives: Identifying virilisation of the genitalia in female newborns early during the neonatal period is important to diagnose pathologies. However, there is no clear threshold for clitoromegaly or for the anogenital ratio. The objective of this study was to define reference values for the external genitalia of full-term and pre-term female neonates., Design: This was a prospective study of all females born in the study centre between May 2014 and July 2016. Clitoral length and anogenital ratio were measured in 619 newborns with a gestational age of 24+2 to 41+3 weeks during their first 3 days of life. Associations between the values at day 3 and gestational age, birth weight and other newborn characteristics were examined by linear regression., Results: The mean clitoral length at day 3 of life was 3.69±1.53 mm (n=551; 95th percentile, 6.5 mm; maximum, 8 mm), and the mean anogenital ratio was 0.42±0.09 (95th percentile, 0.58). There was no significant variation with gestational age or birth weight, and no significant difference between the results at day 0 and day 3., Conclusion: These results suggest that clitoromegaly can be defined as a clitoral length >6.5 mm. Values ≥8 mm should prompt further investigations. An anogenital ratio >0.6 should be considered a sign of virilisation. Since clitoral size does not vary with gestational age or birth weight, clitoromegaly should not be attributed to prematurity., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Rare diseases usually concern small and disseminated population. Implementing clinical research with the right design, outcomes measures and the recruitment of patients are challenges. Collaborations, training and multidisciplinary approach are often required. In this article, we provide an overview of a successful collaboration in nephropathic cystinosis (NC), focusing on what was the key of success, the interactions between academics, the pharmaceutical company and patients organizations. NC is considered as a very rare disease. In 2010, a new formulation of cysteamine, the only available treatment to improve renal outcome of the disease, was proposed by a small American company. Studies were implemented in France under the coordination of an expert of the disease and the clinical investigation center of Lyon. The collaboration resulted in a good recruitment and retention of the patients in the study and most of all in the availability of the new formulation in France. Patients could have facilitated the research by being involved in the early stages of the studies. Involving patients and public early in the process is particularly important in rare diseases as the patient is a great source of knowledge and has his own expectations. Priorities of research, design, conduct and reporting of clinical trials can be defined in collaboration with adults but also with young patients or public, the first concerned in rare diseases. This concept is still to be developed and improved especially with paediatric patients., (Copyright © 2020. Published by Elsevier Masson SAS.)

Purpose: We described the medication use during pregnancy in the French population using the French Pregnancy Cohort (FPC)., Methods: The FPC was built with the sampling of all pregnant women included in the French Echantillon généraliste des bénéficiaires (EGB), which is a 1/97th representative sample of the population covered by the French health insurance. The EGB includes anonymized information on the socio-demographic and medical characteristics of beneficiaries, and the health care services they have received such as diagnoses and procedure codes as well as data on filled reimbursed medication; EGB also includes data on hospital stays in all public and private French health facilities. Each filled prescription record contains information on drug brand and generic names, date of prescription and date of dispensing, quantity dispensed, mode of administration, duration of prescription, dosage, and prescribing physician specialty. FPC includes data on all pregnancies of women in the EGB (2010-2013). Date of entry in the FPC is the first day of pregnancy regardless of pregnancy outcome (spontaneous abortions or planned abortions (with or without medical reasons), deliveries), and data on women are collected retrospectively for a period of one year before pregnancy, and prospectively during pregnancy, and up to one year after delivery. The prevalence of prescribed medications before, during and after pregnancy was compared; comparison was also done between trimesters. Pregnancy outcomes are described and include spontaneous and planned abortions, livebirths, and stillbirths., Results: FPC includes data on 36,065 pregnancies. Among them, 27,253 (75.6%) resulted in a delivery including 201 stillbirths (0.7%). The total number of spontaneous abortions was 6,718 (18.6%), and planned abortions 2,094 (5.8%). The prevalence of filled medication use was 91.1%, 89.9%, and 95.6% before, during and after pregnancy, respectively. Although there was a statistically significant decrease in the proportion of use once the pregnancy was diagnosed (first trimester exposure, 76.4% vs. exposure in the year prior to pregnancy, 91.1% (p < .01)), post-pregnancy medication use was above the pre-pregnancy level (95.6%). Maternal depression was the most prevalent comorbidity during pregnancy (20%), and post-partum depression was higher in those who delivered a stillborn infant (38.8%) as well as in those with a spontaneous (19.5%) or planned abortion (22.4%) compared to those with a liveborn (12.0%)., Conclusion: FPC is an excellent tool for the study of the risk and benefit of drug use during the perinatal period. FPC has the advantage of including a representative sample of French pregnant women, and study medications only available in France in addition to others available worldwide., Competing Interests: The authors have declared that no competing interests exist.

Objective: The objectives of this study are to carefully describe the context of methotrexate medication errors, to details medical consequences and management approaches, and to determine the rate of fatal outcome., Methods: Data on methotrexate medication errors were obtained from the French network of poison control and pharmacovigilance centres, which collected and documented reported drug-induced adverse effects. Cases were included if the intake was more than 2-fold the intended weekly dose or a weekly cumulative dose ≥ 30 mg and a follow-up of at least 4 days after the last dose. Data were analysed for demographics, treatment indication, prescribed dose, drug interactions, clinical complications and medical outcomes., Results: Seventy four patients were included. The causes of methotrexate errors resulted from an erroneous prescription renewal (23.3%), incomprehensiveness of the weekly schedule by patients or at-home caregivers (56.2%) and administration of a wrong dose by a health care professional (20.5%). Of the 70 patients who took methotrexate daily, the mean daily dose received over the whole duration of the error was 9.6 ± 4.1 mg (range 2.5-22.5) with a mean duration of the error of 11.7 ± 12.2 days (range 2 to 90). Thirteen (18%) patients remained asymptomatic and 61 (82%) developed complications of which 46 (62.2%) were severe. Nine (14.8%) patients died within 11 to 45 days after the first dosing error. Compared to patients with no or mild symptoms, those with severe symptoms were more likely to be older (75.6 ± 10.8 vs. 69.5 ± 12.9 years) and to be exposed to a higher cumulative dose (94.8 ± 46.2 vs. 68.0 ± 45.7 mg)., Conclusions: This study confirms that dosing errors with methotrexate can be lethal and persisted despite several warnings from drug agencies. Further measures are awaited from the European Medicine Agency., (Copyright © 2018 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To describe clinical consequences of risperidone medication errors in children of less than 13 years and to estimate a clinically relevant toxic dose., Methods: All cases of risperidone medication errors managed by French Poison Centres from 2001 to 2012 were analyzed. Inclusion criteria were a delay of at least 2 hours between ingestion and request to the FPC in asymptomatic children, an ingested dose above two-fold the maximal daily dose for children above 5 years or any symptomatic patient at the time of first contact., Results: One hundred and sixty cases met our criteria. Median age was 8 years (range 0.9-12) and 28.1% were aged 5 years or less. Causes of the error were an incorrect dose in treated children (84.2%) or a dose given to a wrong child (15.8%). The median ingested dose was 0.1 mg/kg or 3.3-fold the maximum recommended dose. Overall, 59 children had no symptoms, 95 experienced minor symptoms and six moderate symptoms. Somnolence/sedation was the most common (73.3%). Of the 17 children who developed extrapyramidal disorders, all had minor or moderate symptoms and only five required a symptomatic treatment., Conclusions: Risperidone medication errors in children cause minimal effects. Somnolence and mild to moderate extrapyramidal reactions were the main features of toxicity, and significant cardiac or other neurological features were not observed. No case with severe toxicity was noted. At home surveillance can be proposed for children exposed to a dose ≤0.15 mg/kg.

Objectives: Off-label drug prescribing is a public health and economic issue. The aim of this study was to describe off-label prescription in general practice in France, in terms of frequency and nature, and to identify its main determining factors., Design: Multicentre cross-sectional study SETTING: Twenty-three training general practice offices PARTICIPANTS: All the voluntary patients coming for a medical consultation or visited at home over a cumulative period of 5 days per office between November 2015 and January 2016., Methods: Eleven interns, acting as observers, collected data. Two reviewers analysed the drugs prescribed by the trainers, in order to identify those prescribed off-label in terms of their indication or the age of the patient. We used a univariate, then a multivariate model, based on hierarchical mixed-effects logistic regression., Results: Among the 4932 drug prescriptions registered, 911 (18.5%[95% CI17.4% to 19.6%]) were off-label, of which 865 (17.6%) due to the indication of the drug and 58 (1.2%) due to the age of the patient. The prescription never mentioned the off-label use, neither was the patient informed of it, as required by the French law. With the multivariate analysis, variables contributing to off-label prescription were the number of drugs (OR=1.05 for each additional drug), the initiation of new drug therapy (OR=1.26) and the non-specific goal of the prescription (OR=1.43); the age of the patient ≤14 years (OR=1.42); the rural location of the physician's practice (OR=1.38) and the low frequency of the visits of national health insurance representatives (OR=0.93)., Conclusion: Almost one out of five drugs prescribed in French general practice was off-label. It seems necessary to better train physicians in clinical pharmacology, to provide them with more effective drug prescription software, to reinforce postmarketing surveillance and to clearly define off-label use by consensus., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The objectives of this study were to describe the characteristics and natural history of beta-lactam-induced severe neutropaenia and to evaluate the risk of recurrences after another beta-lactam readministration. Reports of pure agranulocytosis associated with a beta-lactam exposure within the 10 days preceding the neutropaenia were extracted from the French Pharmacovigilance Database over the year 2010. Cases with another evident cause or more likely attributable to another drug were excluded. Data were analyzed for demographics, clinical and biological features, prognosis factors, granulocyte colony stimulating factors administration and outcome. Sixty-two cases were included (median age: 65 years). The median duration of treatment before neutropaenia was 16 days. In 47% of cases, the diagnosis was made on a systematic blood cell count. The median neutrophil count at nadir was 0.125 × 10 9 /L, and bone marrow examination evidenced features of neutrophilic maturation arrest or aplasia in 21 patients, hyperplasia of granulopoietic cells in three and normal findings in five. Three patients developed severe sepsis. All but one recovered a normal blood cell count within 2-56 days after beta-lactam discontinuation. The last patient died from recurrent severe septic shock. No significant effect of granulocyte colony stimulating factor on the mean duration of haematological recovery was found. Among the 21 patients who later received another beta-lactam, two experienced recurrence of the neutropaenia after receiving a beta-lactam from another subfamily. Beta-lactam-induced agranulocytosis was usually observed after prolonged treatment, and severe complications are uncommon. In most patients, a subsequent treatment with another beta-lactam was well tolerated., (© 2018 Société Française de Pharmacologie et de Thérapeutique.)

Objective: To describe pain assessment, the pattern of analgesic and sedative drug use, and adverse drug reactions in a neonatal intensive care unit (NICU) during the postsurgery phase., Method: Demographic characteristics, pain scores, and drug use were extracted and analyzed from electronic patient medical files for infants after surgery, admitted consecutively between January 2012 and June 2013., Result: One hundred and sixty-eight infants were included. Acute (DAN score) and prolonged (EDIN score) pain assessment scores were used in 79% and 64% of infants, respectively, on the 1st day. This percentage decreased over the 7 days following surgery. The weekly average scores postsurgery were 2/15 (±2.2) for the EDIN score and 1.6/10 (±2.0) for the DAN score. The rates of pain control were 88% for the EDIN and 72% for the DAN. The most prescribed opiate drug was fentanyl (98 patients; 58%) with an average dose of 1.8 (±0.6) μg/kg/h. Midazolam was used in 95 patients (56%), with an average dose of 35 (±14) μg/kg/h. A bolus was administered in 7% (±7.4) of the total dose for fentanyl and 8% (±9.3) for midazolam. Similar doses were used in term and preterm neonates. Of 118 patients receiving fentanyl and/or midazolam, 40% presented urinary retention, 28% a weaning syndrome. Paracetamol (155 patients; 92%) and nalbuphine (55 patients; 33%) were the other medications most often prescribed., Conclusion: The off-label use of fentanyl and midazolam was necessary to treat pain after surgery. Pain assessment should be conducted for all neonates in order to optimize their treatment. Research on analgesic and sedative medicine in vulnerable neonates seems necessary to standardize practices and reduce adverse drug reactions., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

We assessed the accuracy of the French version of the Autism Spectrum Quotient (AQ) in adolescents with Asperger syndrome (AS) and high-functioning autism (HFA) compared to healthy controls and adolescents with psychiatric disorders (PDs). Three groups of adolescents, aged 11-18, were assessed: 116 with AS/HFA (93 with IQ ≥ 85 and 20 with 70 ≤ IQ < 85), 39 with other PDs, and 199 healthy controls. The AS/HFA group scored significantly higher than the healthy control and PD groups. A cut-off score of 26 was used to differentiate the autism group from healthy controls with 0.89 sensitivity and 0.98 specificity. Scores did not vary by age or sex.

Background/objective: Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population., Patients/methods: We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort., Results: In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient., Conclusions: The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance.

Aim: No tools are currently available in France, for the detection of autism without mental retardation (high functioning autism and Asperger syndrome here referred as TED SDI). Use of screening tests by first-line clinicians would allow better detection of children who are likely to display such difficulties and to improve patients' care. In England, 3 questionnaires have been evaluated: Autism Spectrum Quotient (AQ), Empathy Quotient (EQ), and Systemizing Quotient (SQ). This is the translation and evaluation of 3 questionnaires in France for TED SDI and control adolescents., Methods: The translation of the questionnaires into French required two simultaneous translations, two back-translations and two consensus meetings. This is a cross-sectional study comparing scores obtained with the three AQ, EQ and SQ questionnaires. These questionnaires were completed by the parents of four groups of adolescents 11-18 years: 100 TED SDI adolescents (50 with IQ ≥ 85 and 50 with 70≤IQ<85), 50 adolescents with another psychiatric disorder (TP) and 200 control adolescents (T)., Results: 580 questionnaires have been sent to 40 recruiting centres. By the 28th of February, 2010, 277 completed questionnaires were received completed (TED SDI: 70 (70%); TP: 25 (50%) et T: 182 (91%)). In the control group, 92 girls (mean 14.4±1.7 years) and 66 boys (14.5±1.7 years) were recruited. In the TED SDI group, 4 girls (14.3±2.4 years) and 42 boys (14.5±1.7 years) were recruited. One girl (81) and 6 boys (72.2±7.7) have an IQ between 70 and 85, and 3 girls (95.3±4.2) and 36 boys (102.9±12) have an IQ higher than 85. In the TP group, 9 girls (15.9±1.7 years) and 4 boys (15.8±1.9 years) were recruited., Conclusion: The aim of this study is to make the AQ, EQ and SQ questionnaires available in French for French speaking clinicians. This study will allow a rigorous evaluation of the usefulness of the AQ questionnaire in the screening of TED SDI in adolescents., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

The network of Paediatric Clinical Investigation Centres (CIC.P) consists of eight research centres integrated into teaching hospitals. They collaborate with all medical and surgical departments, medico-technical departments, INSERM research units, and with university research units. The aims of the network were to conduct paediatric clinical research in the areas of drug evaluation and pathophysiology (primarily growth and neurosciences) and contribute to technical innovations. The CIC.P Network provides support to investigators, from design through the conduct of investigator-initiated or industrially sponsored clinical research protocols. It also provides physicians, pharmacists and nurses with specific training in paediatric clinical research. It has facilities specifically designed for the conduct of research in children. In accordance with Good Clinical Practice (GCP) guidelines, the CIC Network also supports parents and their children during participation in medical research.

Internet is a tool allowing a wide distribution of information. Initially reserved to the field of scientific research, it develops currently in many sectors of the socio-economic life and saved the area of the health. Each day appear new services allowing the access to the information on the diagnostic and treatment of different pathologies. Patients and physicians share their knowledge and their information, through newsgroups and electronic mail. This paper presents the Internet and cancer resources to allow clinicians and researchers a rapid access to the relevant information.