Drug exposure for PDA closure in France: a prospective, cohort-based, analysis.

PURPOSE: To describe the exposure to drugs used for the treatment of patent ductus arteriosus (PDA) in a large cohort of preterm infants born before 32 weeks of gestation. METHODS: A prospective observational cohort analysis was conducted during 2 years in 28 French level 3 NICU using the same computerized order-entry system. The main outcome was "a medically treated PDA," defined as exposure to ibuprofen, indomethacin, or paracetamol prescribed with the indication of PDA closure. Secondary outcomes were as follows: time of the first treatment administration; total exposure to furosemide during hospitalization; and rate of PDA refractory to pharmacological closure. RESULTS: The study cohort consisted of 2614 infants. Among them, 474 (18.1%) received a medical treatment for PDA, with a mean postnatal age at treatment of 4.3 ± 6.6 days. The drug used as a first-line treatment was ibuprofen in 89.5% and paracetamol in 10.5%. One hundred and ninety-five infants (7.4%) had a PDA refractory to pharmacological closure. At the multivariate analysis, factors associated with PDA refractory to pharmacological closure (OR; 95% CI) were as follows: gestational age (GA) (0.81; 0.72-0.90), paracetamol as the first-line treatment (0.32; 0.15-0.68), and pharmacological treatment before 48 h of life (0.63; 0.43-0.94). 24.6% of the study cohort was exposed to furosemide (cumulative dose 6.5 ± 12.6 mg/kg). Variables significantly associated with higher cumulative doses of furosemide were lower GA and ibuprofen treatment (both p < 0.0001). CONCLUSION: Drug utilization patterns in infants with PDA vary among centers. Pharmacoepidemiology studies can provide new information on factors associated with PDA refractory to medical treatment.

Diuretic drug utilization in neonates: a French prescription database analysis.

Background: The use of diuretics is extremely common in infants cared for in neonatal wards, despite the lack of proven efficacy for many conditions. The main objective of this study was to assess the rate of diuretics exposure in a multicenter French cohort. The secondary objectives were to describe the evolution of this exposure over time, the indications, the prescription practices, and the exposure rates among centers. Methods: An observational study was conducted in 40 Level 3 French neonatal intensive care units using the same computerized order-entry system. Neonates hospitalized between January 2017 to December 2021 with a corrected age between 24 and 44 weeks of gestation at admission were eligible. Results: A total of 86,032 patients were included. The exposure rate was 8.5%, more specifically 29.4% for children born at < 32 weeks of gestation and 3.7% for neonates born at term. There was no significant variation over the study period, but the exposure ranged from 2.4% to 26.5% depending on the center. The main drugs prescribed were furosemide, spironolactone and dopamine with a diuretic purpose. The main indications were "fluid retention," and to a lesser extent "bronchopulmonary dysplasia" and "post-transfusion." For furosemide, the first exposure occurred in mean at 16.5 (±17.8) days of life, mean duration of exposure was 6.2 (±9.5) days, and the cumulative dose was in mean 10.7 (23.9) mg/kg. Conclusion: Diuretic prescription practices vary between centers. The administration of these drugs is often non-evidence based, doses and duration of treatment easily exceed toxic thresholds.

Postnatal corticosteroid exposure in very preterm infants: A French cohort study.

Background: Postnatal corticosteroids (PC) are widely used in very preterm infants. International reports and national multicenter trials describe a marked variability across countries and inter-sites, in the use of PC. Few information is available on therapeutic indications and prescription characteristics of PC. Aim: The main objective of this study was to describe the exposure to PC in a large cohort of preterm infants born at less than 32 weeks of gestation, according to the prescription data of 41 tertiary-care NICUs in France. Secondary objectives were to describe therapeutic indications, day of life (DOL) of the first exposure, route of administration, duration, cumulative dose for each drug, and differences in exposure rates across centers. Methods: We conducted a prospective observational cohort analysis from January 2017 to December 2021, in 41 French tertiary-care NICUs using the same computerized order-entry system. Results: In total, 13,913 infants [birth weight 1144.8 (±365.6) g] were included. Among them, 3633 (26.1%) were exposed to PC, 21.8% by systemic and 10.1% by inhaled route. Within the study population, 1,992 infants (14.3%) received the first corticosteroid treatment in the first week of life and 1641 (11.8%) after DOL 7. The more frequent indications were prevention and/or treatment of bronchopulmonary dysplasia, and arterial hypotension. Hydrocortisone was the more often prescribed molecule. For systemic PC the first exposure occurred in mean at DOL 9.4 (±13.5), mean duration of treatment was 10.3 (±14.3) days, and the cumulative dose (expressed as the equivalent dose of hydrocortisone) was in median [IQR] 9.0 [5.5-28.8] mg/kg. For inhaled PC, the first exposure occurred in mean at DOL 34.1 (±19.7), and mean duration of treatment 28.5 (±24.4) days. The exposure rate ranged from a minimum of 5% to a maximum of 56% among centers, and significantly increased over the study period (p < 0.0001). Conclusion: In this French cohort of very preterm infants, around one patient out to five was exposed to PC during hospital stay in the NICU. The exposure occurred early, starting from the first week of life. Exposure rate widely varied among centers. Pharmacoepidemiology studies are useful to increase knowledge on corticosteroid utilization patterns in preterm infants.

Paraben exposure through drugs in the neonatal intensive care unit: a regional cohort study.

Background and objectives: Environmental factors influence the development of very preterm infants (VPIs, born at less than 32 weeks of gestation). It is important to identify all potential sources of paraben exposure in these vulnerable infants. We aimed to quantify paraben exposure via drug administration in a cohort of VPI cared for in neonatal intensive care units (NICUs). Methods: A prospective, observational study was carried out over a five-year period in a regional setting (two NICUs using the same computerized order-entry system). The main outcome was exposure to paraben-containing drugs. The secondary outcomes were: time of the first exposure, daily intake, number of infants exceeding paraben acceptable daily intake (ADI: 0-10 mg/kg/d), duration of exposure, and cumulative dose. Results: The cohort consisted of 1,315 VPIs [BW 1129.9 (±360.4) g]. Among them, 85.5% were exposed to paraben-containing drugs. In 40.4% of infants, the first exposure occurred during the second week of life. Mean paraben intake and duration of exposure were, respectively, 2.2 (±1.4) mg/kg/d and 33.1 (±22.3) days. The cumulative paraben intake was 80.3 (±84.6) mg/kg. The ADI was exceeded in 3.5% of exposed infants. Lower GA was associated with higher intake and longer exposure (p < 0.0001). The main molecules involved in paraben exposure were: sodium iron feredetate, paracetamol, furosemide, and sodium bicarbonate + sodium alginate. Conclusion: Commonly used drugs are potential source of parabens, and ADI can be easily exceeded in VPIs cared for in NICUs. Efforts are needed to identify paraben-free alternative formulations for these vulnerable infants.

Frequencies, Modalities, Doses and Duration of Computerized Prescriptions for Sedative, Analgesic, Anesthetic and Paralytic Drugs in Neonates Requiring Intensive Care: A Prospective Pharmacoepidemiologic Cohort Study in 30 French NICUs From 2014 to 2020.

Objectives: No consensus exists about the doses of analgesics, sedatives, anesthetics, and paralytics used in critically ill neonates. Large-scale, detailed pharmacoepidemiologic studies of prescription practices are a prerequisite to future research. This study aimed to describe the detailed prescriptions of these drug classes in neonates hospitalized in neonatal intensive care units (NICU) from computerized prescription records and to compare prescriptions by gestational age. Materials and Methods: We included all neonates requiring intensive care in 30 French level III units from 2014 through 2020 with a computerized prescription for an analgesic, sedative, anesthetic, or paralytic agent. We described frequencies of prescription, methods of administration, concomitant drug prescriptions, and dosing regimen, and compared them across gestational ages. Results: Among 65,555 neonates, 29,340 (44.8%) were prescribed at least one analgesic (acetaminophen in 37.2% and opioids in 17.8%), sedative (9.8%), anesthetic (8.5%), and/or paralytic agent (1%). Among preterm infants born before 28 weeks, 3,771/4,283 (88.0%) were prescribed at least one of these agents: 69.7% opioids, 41.2% sedatives, 32.5% anesthetics, and 5.8% paralytics. The most frequently prescribed agents were sufentanil (in 10.3% of neonates) and morphine (in 8.0% of neonates) for opioids, midazolam (9.3%) for sedatives, ketamine (5.7%) and propofol (3.3%) for anesthetics. In most neonates, opioids and sedatives were prescribed as continuous infusion, whereas anesthetics were prescribed as single doses. Opioids, sedatives and paralytics were mostly prescribed in association with another agent. Doses varied significantly by gestational age but within a limited range. Gestational age was inversely related to the frequency, cumulative dose and duration of prescriptions. For example, morphine prescriptions showed median (IQR) cumulative doses of 2601 (848-6750) vs. 934 (434-2679) µg/kg and median (IQR) durations of 7 (3-15) vs. 3 (2-5) days in infants born <28 vs. ≥ 37 weeks of gestation, respectively (p-value<0.001). Conclusion: The prescriptions of analgesic, sedative, anesthetic, or paralytic agent were frequent and often combined in the NICU. Lower gestational age was associated with higher frequencies, longer durations and higher cumulative doses of these prescriptions. Dose-finding studies to determine individualized dosing regimens and studies on long-term neurodevelopmental outcome according to received cumulative doses are required.

Prescription of Aminoglycosides in 23 French Neonatal Intensive Care Units.

Background: Aminoglycosides are the most prescribed antibiotics in neonatal intensive care units (NICU). Reducing exposure to antibiotics in the NICU is highly desirable, particularly through benchmarking methods. Methods: Description of aminoglycosides prescriptions in 23 French NICU using the same computerized system over a 4-year period (2017-2020). A benchmarking program of antibiotics prescription was associated. Results: The population included 53,818 patients. Exposition rates to gentamicin and amikacin were 31.7% (n = 17,049) and 9.1% (n = 4894), respectively. Among neonates exposed to gentamicin, 90.4% of gentamicin and 77.6% of amikacin treatments were started within the 1st week of life. Among neonates exposed to amikacin, 77.6% started amikacin within the 1st week. The average daily dose of gentamicin at first prescription increased over the study period from 3.9 in 2017 to 4.4 mg/kg/d in 2020 (p < 0.0001). Conversely, the corresponding amikacin daily doses decreased from 13.0 in 2017 to 12.3 mg/kg/d in 2020 (p = 0.001). The time interval between the first 2 doses of gentamicin was mainly distributed in 3 values during the first week of life: 49.4% at 24 h, 26.4% at 36 h, and 22.9% at 48 h. At first amikacin prescription, the time interval was distributed in 4 categories: 48% at 24 h, 4.1% at 30 h, 8.5% at 36 h, and 37.1% at 48 h. As compared to literature guidelines, the rates of overdose and underdose in gentamicin (1.5% and 2.7%) and amikacin (0.3% and 1.0%). They significantly decreased for gentamicin over the study period. In multivariate analysis, the factors significantly associated with GENT overdose were the year of admission, prematurity, length of stay, and duration of the treatment. Conclusion: This prescription strategy ensured a low rate of overdose and underdose, and some benefits of the benchmarking program is suggested.

Very preterm birth: who has access to antenatal corticosteroid therapy?

We describe the administration of antenatal corticosteroid therapy (ACT) for liveborn very preterm neonates in a population-based study. A total of 790 very preterm neonates (between 24 and 31 full weeks of gestation) were included in this regionally defined population of very preterm neonates in France. The main outcome measure was non-access to ACT. Data were analysed using logistic and polytomous models to control for neonatal and sociodemographic characteristics, mechanisms of very preterm birth and neonatal network organisation. As compared with level III, births in levels I-II maternity units were closely related to non-access to ACT (60.1% vs. 8.8%), but not to pregnancy follow-up (19.7% vs. 17.8%). Only 6.3% of very preterm neonates that benefited from antepartum referral did nor receive ACT. Births associated with rupture of membranes and gestational hypertension were significantly more often transferred to level-III units (73.8% and 68.3% respectively) than those due to maternal bleeding and spontaneous labour (57.0% and 50.7% respectively), and the neonates had a lower probability of not receiving ACT (8.5%, 11.5%, 23.0%, 31.2% respectively). Very preterm neonates referred in utero to a level-III unit came from a more favourable socio-economic environment. Non-access to ACT was more often observed in neonates born to 14- to 24-year-old mothers, smokers, of low socio-economic status, and preterm birth resulting from maternal bleeding or spontaneous labour. These data from a French regional study show that access to ACT is not only explained by practitioners' support of recommendations. In our population-based study, ACT access was related to socio-economic factors and to the mechanisms of very preterm birth. Improving the rate of access to ACT should take these organisational, medical and socio-economic dimensions into account.

Antibiotics Prescription Over Three Years in a French Benchmarking Network of 23 Level 3 Neonatal Wards.

Introduction: Prescribing antibiotics to newborns is challenging, as excess antibiotics are a risk factor for increased morbidity and mortality. The objective of this study was to describe the evolution of antibiotic exposure over three years in a large network of level 3 neonatal wards where each center is informed yearly of its own results and the results of other centers and has full autonomy to improve its performance. Patients and Methods: This is a prospective, observational study of antibiotics prescriptions over the 2017-2019 period in a network of 23 French level 3 neonatal wards. The network relied on an internal benchmarking program based on a computerized prescription ordering system. Among others, antibiotics exposure, treatment duration, and antibiotics spectrum index were analyzed. Results: The population consisted of 39,971 neonates (51.5% preterm), 44.3% of which were treated with antibiotics. Of the treated patients, 78.5% started their first antibiotic treatment in the first three days of life. Antibiotic exposure rate significantly declined from 2017 to 2019 (from 46.8% to 42.8%, p < 0.0001); this decline was significant in groups with gestational age >26 weeks, but not in the group with extremely low gestational age <27 weeks. Gentamicin, cefotaxime, amoxicillin (ampicillin), vancomycin, and amikacin were the antibiotics most prescribed. The lower the gestational age, the higher the exposure for cefotaxime, vancomycin, and amikacin. Compared to 2017, cefotaxime exposure in 2019 declined by 12.6%, but the change was only significant in the gestational age group of 32-36 weeks (17.4%) and at term (20.3%). The triple combination of antibiotics in the first three days decreased by 28.8% from 2017 to 2019, and this was significant in each gestational age group. During the study, the delayed ending of antibiotics in unconfirmed early-onset neonatal infection increased from 9.6% to 11.9%. Conclusion: This study showed that a strategy characterized by the collection of information via a computerized order-entry system, analysis of the results by a steering committee representative of all neonatal wards, and complete autonomy of neonatal wards in the choice of prescription modalities, is associated with a significant reduction in the use of antibiotics in newborns with gestational age greater than 26 weeks.

Characteristics of prescription in 29 Level 3 Neonatal Wards over a 2-year period (2017-2018). An inventory for future research.

OBJECTIVES: The primary objective of this study is to determine the current level of patient medication exposure in Level 3 Neonatal Wards (L3NW). The secondary objective is to evaluate in the first month of life the rate of medication prescription not cited in the Summary of Product Characteristics (SmPC). A database containing all the medication prescriptions is collected as part of a prescription benchmarking program in the L3NW. MATERIAL AND METHODS: The research is a two-year observational cohort study (2017-2018) with retrospective analysis of medications prescribed in 29 French L3NW. Seventeen L3NW are present since the beginning of the study and 12 have been progressively included. All neonatal units used the same computerized system of prescription, and all prescription data were completely de-identified within each hospital before being stored in a common data warehouse. RESULTS: The study population includes 27,382 newborns. Two hundred and sixty-one different medications (International Nonproprietary Names, INN) were prescribed. Twelve INN (including paracetamol) were prescribed for at least 10% of patients, 55 for less than 10% but at least 1% and 194 to less than 1%. The lowest gestational ages (GA) were exposed to the greatest number of medications (18.0 below 28 weeks of gestation (WG) to 4.1 above 36 WG) (p<0.0001). In addition, 69.2% of the 351 different combinations of an medication INN and a route of administration have no indication for the first month of life according to the French SmPC. Ninety-five percent of premature infants with GA less than 32 weeks received at least one medication not cited in SmPC. CONCLUSION: Neonates remain therapeutic orphans. The consequences of polypharmacy in L3NW should be quickly assessed, especially in the most immature infants.

A population-based observational study of restrictive guidelines for antibiotic therapy in early-onset neonatal infections.

BACKGROUND: The extensive use of broad-spectrum antibiotics has been associated with major changes in the spectrum of organisms involved in early-onset neonatal infection (EONI), their susceptibility to antibiotics, or both. Therefore, guidelines for a more rational use of antibiotics in neonates have been developed. We conducted a population-based observational study to assess the effectiveness and compliance with restrictive guidelines for the antibiotic therapy in EONI. METHODS: Neonates receiving antibiotics within 72 hours of life were identified prospectively by population-based surveillance in the 18 hospitals of Burgundy, between February 2002 and June 2003. They were treated in accordance with guidelines limiting the use of broad-spectrum antibiotics and shortening the treatment duration. Each neonate included was evaluated for 60 days after birth. An unfavorable outcome was defined as death related to EONI or late-onset infection. RESULTS: Of the 25,480 infants born during the study period, 1012 received antibiotics at birth. Of these 1012 infants, 39 were definitely infected (septicemia), 288 clinically infected and 685 not infected. The EONI cure rate was 96.8% without infectious relapse. Forty-five infants received a second course of antibiotic therapy. Birth weight (OR: 5.6; 95% CI: 2.2-14.1), mechanical ventilation (OR: 4.1; 95% CI: 1.3-13.1), central venous catheterization (OR: 16.1; 95% CI: 1.8-141.9), and antibiotic therapy duration (OR: 2.5; 95% CI: 1.1-5.5) were independently associated with late-onset infection. CONCLUSION: Reducing the antibiotic therapy duration does not increase the risk of infectious relapse and may decrease the incidence of late-onset infection.

Palivizumab efficacy in preterm infants with gestational age < or = 30 weeks without bronchopulmonary dysplasia.

The present study was designed to determine the efficacy of administration of palivizumab to preterm infants with gestational age (GA) < or = 30 weeks without bronchopulmonary dysplasia (BPD). All patients born with GA < or = 30 weeks without BPD on Day 28 and hospitalized for RSV bronchiolitis in Burgundy (12 hospitals) from December 1 to April 30 of the next year were included in this prospective observational study during five successive RSV seasons (1999-2000, 2000-2001, 2001-2002, 2002-2003, and 2003-2004). Palivizumab was given to premature infants with a gestational age < or = 30 weeks without BPD in the 2002-2003 and 2003-2004 periods only. In the cohort of premature infants with GA < or = 30 weeks without BPD, the respiratory syncytial virus (RSV) bronchiolitis hospitalization rate was reduced significantly (P < 0.01) in the two seasons with palivizumab prophylaxis (2002-2003: 0% and 2003-2004: 2%) versus the three previous RSV seasons (1999-2000: 14.3%; 2000-2001: 16.7%; 2001-2002: 10.2%). The number needed to treat to prevent one hospitalization for RSV bronchiolitis was 6 (95%CI: 4-11). Such favorable results have not been always found in the few available postmarketing epidemiological studies on hospitalization rate after palivizumab prophylaxis. Differences in health care organization could explain those discrepancies.

Early optimal parenteral nutrition and metabolic acidosis in very preterm infants.

BACKGROUND: It is currently recognized that an optimized nutritional approach, consisting of an early and substantial supply of protein and energy by parenteral route, may be beneficial for very low birth weight infants and recent guidelines endorse this strategy. However, the impact of the enhanced parenteral nutrition (PN) on acid-basic balance has never been investigated. The aim of the present study is to assess the effect of nutrient intake on acid-base homeostasis in a large population of preterm infants on PN. METHODS: This observational study described the acid-base profile of very preterm infants (≤29 week's gestation) receiving PN during the first week of life. For this purpose three different cohorts of infants who received increasing (group 1 to group 3) nutritional intakes were considered. Nutrition data were recorded daily and correlated to acid-base data (pH, base excess, and lactate). The outcome measure to assess metabolic acidosis was the base excess (BE). RESULTS: 161 infants were included. 1127 daily nutritional records and 795 blood gas data were analyzed. The three groups were different with regard to nutritional intravenous intakes. Group 3 in particular had a higher mean intake of both amino acids (3.3 ± 0.8 g/kg/d) and lipids (2.8 ± 1.4 g/kg/d) during the first week of life. Metabolic acidosis was more severe in the group with the highest parenteral intake of amino acids and lipids: mean BE = -8.7 ± 3.4 (group 3); -6.4 ± 3.4 (group 2); -5.1 ± 3.0 (group 1)]. At the multivariate analysis the significant risk factors for metabolic acidosis were: gestational age, initial base excess, amino acid and lipid intravenous intakes. DISCUSSION: Acid-base homeostasis was influenced by the nutritional intake. Earlier and higher intravenous amino acid and lipid intakes particularly increased the risk of metabolic acidosis. The nutritional tolerance was different depending on gestational age, and the smaller infants (24-26 week's gestation) displayed greater acidotic disequilibrium and a higher need of bicarbonate.

Severe respiratory syncytial virus bronchiolitis: epidemiologic variations associated with the initiation of palivizumab in severely premature infants with bronchopulmonary dysplasia.

BACKGROUND: The efficacy of palivizumab prophylaxis after bronchopulmonary dysplasia (BPD) has been demonstrated in a single placebo-controlled trial. Concern has emerged about the degree of efficacy of palivizumab. This study was designed to determine the efficacy of administration of palivizumab to premature infants with a gestational age

Using discharge abstracts to evaluate a regional perinatal network: assessment of the linkage procedure of anonymous data.

To assess the Burgundy perinatal network (18 obstetrical units; 18 500 births per year), discharge abstracts and additional data were collected for all mothers and newborns. In accordance with French law, data were rendered anonymous before statistical analysis, and were linked to patients using a specific procedure. This procedure allowed data concerning each mother to be linked to those for her newborn(s). This study showed that all mothers and newborns were included in the regional database; the data for all mothers were linked to those for their infant(s) in all cases. Additional data (gestational age) were obtained for 99.9% of newborns.

MBNL1 and CUGBP1 modify expanded CUG-induced toxicity in a Drosophila model of myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a neuromuscular disorder caused by a CTG expansion in the 3' UTR of the dystrophia myotonica protein kinase (DMPK) gene. It has been hypothesized that the pathogenesis in DM1 is triggered by a toxic gain of function of the expanded DMPK RNA. This expanded RNA is retained in nuclear foci where it sequesters and induces alterations in the levels of RNA-binding proteins (RNA-BP). To model DM1 and study the implication of RNA-BP in CUG-induced toxicity, we have generated a Drosophila DM1 model expressing a non-coding mRNA containing 480 interrupted CUG repeats; i.e. [(CUG)20CUCGA]24. This (iCUG)480 transcript accumulates in nuclear foci and its expression leads to muscle wasting and degeneration in Drosophila. We also report that altering the levels of two RNA-BP known to be involved in DM1 pathogenesis, MBNL1 and CUGBP1, modify the (iCUG)480 degenerative phenotypes. Expanded CUG-induced toxicity in Drosophila is suppressed when MBNL1 expression levels are increased, and enhanced when MBNL1 levels are reduced. In addition, (iCUG)480 also causes a decrease in the levels of soluble MBNL1 that is sequestered in the CUG-containing nuclear foci. In contrast, increasing the levels of CUGBP1 worsens (iCUG)480-induced degeneration even though CUGBP1 distribution is not altered by the expression of the expanded triplet repeat. Our data supports a mechanism for DM1 pathogenesis in which decreased levels of MBNL and increased levels of CUGBP mediate the RNA-induced toxicity observed in DM1. Perhaps more importantly, they also provide proof of the principle that CUG-induced muscle toxicity can be suppressed.

CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation.

CHIP (C terminus of Hsc-70 interacting protein) is an E3 ligase that links the protein folding machinery with the ubiquitin-proteasome system and has been implicated in disorders characterized by protein misfolding and aggregation. Here we investigate the role of CHIP in protecting from ataxin-1-induced neurodegeneration. Ataxin-1 is a polyglutamine protein whose expansion causes spinocerebellar ataxia type-1 (SCA1) and triggers the formation of nuclear inclusions (NIs). We find that CHIP and ataxin-1 proteins directly interact and co-localize in NIs both in cell culture and SCA1 postmortem neurons. CHIP promotes ubiquitination of expanded ataxin-1 both in vitro and in cell culture. The Hsp70 chaperone increases CHIP-mediated ubiquitination of ataxin-1 in vitro, and the tetratricopeptide repeat domain, which mediates CHIP interactions with chaperones, is required for ataxin-1 ubitiquination in cell culture. Interestingly, CHIP also interacts with and ubiquitinates unexpanded ataxin-1. Overexpression of CHIP in a Drosophila model of SCA1 decreases the protein steady-state levels of both expanded and unexpanded ataxin-1 and suppresses their toxicity. Finally we investigate the ability of CHIP to protect against toxicity caused by expanded polyglutamine tracts in different protein contexts. We find that CHIP is not effective in suppressing the toxicity caused by a bare 127Q tract with only a short hemagglutinin tag, but it is very efficient in suppressing toxicity caused by a 128Q tract in the context of an N-terminal huntingtin backbone. These data underscore the importance of the protein framework for modulating the effects of polyglutamine-induced neurodegeneration.

Proposal for the creation of a European healthcare identifier.

In France, the European health card was created in June 2004 to increase the quality of healthcare granted to european citizen anywhere in europe and to facilitate the reimbursement of the healthcare costs. The patient identifier included in this card is essentially based on the healthcare insurance number of the patient and does not allow any linkage with his (her) previous health care data if he (she) is affiliated to another national healthcare insurance system when working for a long duration outside France. The purpose of this paper is to present the concept of a personal identifier based on familial components which has been validated by the French authority for personal data protection in the framework of a genetic study. Results issued from the Burgundy perinatal network demonstrate the interest and the faisability of adding a maternal component to the individual component of the new-born to allow Mother/new-born healthcare data linkage after anonymization. The advantage of adding a familial component to the healthcare insurance number is debated. This proposal will permit to link the data of a patient even when residing outside his country in Europe. It will also contribute to establish european public health statistics by matching healthcare data of the patients' records with other administrative data (mortality, social information ..) after anonymisation of these data in accordance with the European directive on data protection.