Correction: Good practices for clinical data warehouse implementation: A case study in France.

[This corrects the article DOI: 10.1371/journal.pdig.0000298.].

Good practices for clinical data warehouse implementation: A case study in France.

Real-world data (RWD) bears great promises to improve the quality of care. However, specific infrastructures and methodologies are required to derive robust knowledge and brings innovations to the patient. Drawing upon the national case study of the 32 French regional and university hospitals governance, we highlight key aspects of modern clinical data warehouses (CDWs): governance, transparency, types of data, data reuse, technical tools, documentation, and data quality control processes. Semi-structured interviews as well as a review of reported studies on French CDWs were conducted in a semi-structured manner from March to November 2022. Out of 32 regional and university hospitals in France, 14 have a CDW in production, 5 are experimenting, 5 have a prospective CDW project, 8 did not have any CDW project at the time of writing. The implementation of CDW in France dates from 2011 and accelerated in the late 2020. From this case study, we draw some general guidelines for CDWs. The actual orientation of CDWs towards research requires efforts in governance stabilization, standardization of data schema, and development in data quality and data documentation. Particular attention must be paid to the sustainability of the warehouse teams and to the multilevel governance. The transparency of the studies and the tools of transformation of the data must improve to allow successful multicentric data reuses as well as innovations in routine care.

Assessing the Risk of Relapse Requiring Corticosteroids After In Vitro Fertilization in Women With Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Several studies have shown an increased risk of relapse after In Vitro Fertilization (IVF) in women with Multiple Sclerosis (MS), especially when a GnRH agonists stimulation protocol was used. Our objective was to investigate the risk of relapse after IVF in women with multiple sclerosis, overall and according to stimulation protocol (GnRH agonists vs antagonists), using data from the French national health insurance database. METHODS: This retrospective cohort study included all women with MS who have benefited from IVF between January 1, 2010 and December 31, 2015 in France. Three-month exposed periods after IVF were compared to unexposed periods before IVF, each woman being her own control. Four outcomes were considered: annualized relapse rate (ARR), proportion of IVF with relapse, difference in the number of relapse "after - before" and the delay from IVF to the first relapse. Relapses were identified by an algorithm based on MS-related hospital admissions and use of corticosteroid therapy. Stimulation protocols and disease-modifying therapies (DMT) were identified using drugs claims. Zero-inflated Poisson regression models adjusted for age at IVF and presence of DMT were used. A random effect on the woman was included because women may have multiple IVF procedures. Subgroup analyses by stimulation protocol and IVF outcome (pregnancy or failure) were conducted. RESULTS: A total of 225 women accounting for 338 IVF were included (mean age at first IVF 34.6 ± 4.5 years; 36% of women had at least two IVF during the period). No increase in the risk of relapse after IVF was found overall (before vs. after IVF: respectively 0.20 vs. 0.18 relapse per patient-year; resp. 7.7% vs. 7.1% of IVF with women having at least one relapse) and in subgroups. A lower ARR before and after IVF was observed among women who remained treated until IVF. DISCUSSION: The maintenance of DMT until IVF appeared to be a determining factor in reducing the risk of relapse. Women with MS should be reassured as we did not show an increased risk of relapse requiring use of corticosteroids therapy after IVF neither with GnRH agonists nor with GnRH antagonists.

Prescribing Trends for Valproate Among Pregnant Women: A Cross-sectional Study in 2013 and 2016 Using the French Health Insurance Database.

BACKGROUND AND OBJECTIVE: To describe the prescribing trends for sodium valproate (VPA) and alternative drugs during and around pregnancy, comparing 2016 (after the recommendations on valproate for women were reinforced by the European Medicines Agency [EMA]) with 2013 (before the recommendations). METHODS: Using the French National Health Insurance Database, a cross-sectional study was carried out in 2013 and in 2016, including women who became pregnant and had at least 1 reimbursement claim for VPA in the 2 years prior to pregnancy or during pregnancy. Exposure to VPA and its alternatives was then measured for each quarter, in the 2 years before pregnancy (preconception), during pregnancy, and in the year after pregnancy (postpartum). RESULTS: Among pregnant women with epilepsy (n = 2,607 pregnancies), the proportion exposed to VPA during pregnancy decreased from 26.4% to 9.3% between 2013 and 2016, alongside an increase in lamotrigine and levetiracetam use. Among pregnant women with bipolar disorder (n = 4,278 pregnancies), the proportion of women exposed during pregnancy decreased from 3.7% in 2013 to 1.9% in 2016, without any switch to alternative drugs. In both populations, fewer than one third had consulted a specialist before pregnancy. DISCUSSION: As recommended by the EMA, a change in practice over the 2013-2016 period was observed, with fewer women exposed to VPA during pregnancy and before pregnancy. However, in 2016, a large number of women were exposed to VPA in the first trimester of pregnancy (n = 471), which could suggest that the timing of pregnancy should be better planned when possible.

Pregnancy in women with multiple sclerosis in France from 2010 to 2015: Incidence, outcomes, and exposure to disease-modifying therapies.

BACKGROUND: Multiple sclerosis (MS) is usually diagnosed between 20-40 years old, when women often plan to have children. OBJECTIVE: Our objectives were to estimate pregnancy incidence rates in women with multiple sclerosis (MS), and to describe the use of disease-modifying therapies (DMTs) before conception and during pregnancy, and pregnancy outcomes. METHODS: This retrospective cohort study included all 15- to 49-year-old women with MS in the French national health insurance database over 2010-2015. A pregnancy was exposed if a DMT reimbursement claim occurred during pregnancy or in the 14 preceding days. We used zero-inflated negative binomial (ZINB) regression models to estimate incidence rates and ordinal and multinomial regression models to estimate DMT exposure and pregnancy outcomes. RESULTS: The pregnancy incidence rate was 4.5 per 100 person-years. The probability of having a DMT-exposed pregnancy increased from 0.22 in 2010 to 0.30 in 2015. The probability of live birth was 0.72 (95% CI = 0.70-0.74) for exposed pregnancies (varied considerably among DMTs), 0.77 (95% CI = 0.76-0.79) without treatment, and 0.81 (95% CI = 0.79-0.83) if treatment was stopped within the previous year. CONCLUSION: In this population-based study, we showed an increase of exposed pregnancies over time, beta-interferon and glatiramer acetate being the most used DMTs and associated with the highest probabilities of live birth. Interrupted exposed pregnancies may reflect undesired pregnancies or fear of an adverse outcome, while recent DMT stop probably reflects pregnancy planning.

Impact of recommendations on sodium valproate prescription among women with epilepsy: An interrupted time-series study.

BACKGROUND: The European Medicines Agency (EMA) has developed risk minimization measures (RMMs) to reduce the use of the teratogenic drug, sodium valproate (VPA). The objective was to assess the impact of these RMMs among females with epilepsy in France. METHODS: We used data from the French National Health Insurance Database (SNDS), including 114,936 females aged under 50, with a reimbursement claim for an antiepileptic drug from January 2011 to December 2017, and identified as people with epilepsy. We used a controlled interrupted time series stratifying on age: girls (0-14 years old) and women of childbearing age (15-49 years), and with 129,917 males as controls. RESULTS: VPA prevalent use among girls and women of childbearing age with epilepsy decreased significantly after the issue of the RMMs (trend changes of, respectively, -5 and -4 users per 1000 females at-risk per quarter in comparison to the control group). We did not detect any significant change in VPA incident use. CONCLUSIONS: VPA use decreased over the study period among females with epilepsy but there were still 317 women and 206 girls started on VPA therapy VPA in 2017 (8 per 1000 at-risk and 18 per 1000, respectively). This suggests that either the measures should be strengthened or that the lowest level of VPA use has been reached. In this context, the introduction of a new RMM (in 2018) needs to be evaluated.

Alcohol and drug consumption among motor vehicle drivers in the Brittany region of France: A 9-year cross-sectional population study.

The primary objective of the present study was to evaluate the frequency of positive tests for alcohol and drugs during roadside testing or after road accidents among drivers in the Brittany region of France. The study's secondary objective was to describe the blood concentrations of the substances found during these tests, in order to provide a scientific basis for the establishment or modification of legislative threshold values for road injuries prevention. We performed a cross-sectional study of a database compiled by Rennes University Hospital's toxicology laboratory in the Brittany region of France between 2010 and 2018. Driver's age, sex, and test status (positive or negative), and blood levels of ethanol, 9-tetrahydrocannabinol (THC), methylene dioxymethamphetamine (MDMA), amphetamine, benzoylecgonine and 6-monoacetylmorphine (6-MAM) were collected. Twelve thousand four hundred and ninety-seven drivers (males: 86.1%; median (range) age: 29 (15-94)) have provided roadside blood samples, giving a total of 25,998 test results. Among the 10,996 drivers with at least one positive test, the median blood concentrations of ethanol, THC, MDMA, amphetamine, benzoylecgonine, and 6-MAM were respectively 1.82 g/L, 2.41 ng/mL, 138.4 ng/mL, 67.7 ng/mL, 173.3 ng/mL, and 0.97 ng/mL. 1159 (10.54%) of the 10,996 drivers tested positive for two or more substances, and 151 (1.4%) tested positive for three or more substances. With the exception of heroin, the currently recommended threshold values appear to be appropriate for road injuries prevention with regard to the concentrations observed in offenders.

Hospital databases for the identification of adverse drug reactions: A 2-year multicentre study in 9 French general hospitals.

AIMS: To estimate the actual number of adverse drug reactions (ADRs), we used the French medical administrative database (PMSI) in addition to ADRs spontaneously reported in the French Pharmacovigilance Database (FPVDB). METHODS: Capture-recapture method was applied to these 2 sources (PMSI and FPVDB), checking their independence via a third data source. The study ran from 1 July 2014 to 30 June 2016 in 9 French general hospitals. From PMSI, all discharge summaries including a selection of 10th International Classification of Diseases codes related to ADRs were analysed. This selection was based on the results of a previous study. All ADRs corresponding to these codes, spontaneously reported in the FPVDB, were included. RESULTS: In PMSI, 56.9% of hospital stays were related to an ADR (628 out of 1104). In the FPVDB, we retained 115 cases. A total of 43 ADRs were common to the 2 databases. In both sources, the most frequently reported ADRs were cutaneous (33.1 and 19.1%) and renal (25.2% and 11.6%). The most frequently suspected drugs were anti-infectives in PMSI (31.1%) and antineoplastic drugs in the FPVDB (30.4%). Using the capture-recapture method, the estimated number of ADRs was 1657 [95% CI: 1273 to 2040]. CONCLUSION: The use of the PMSI could constitute an additional tool for the estimation of the actual number of ADRs in French hospitals. A model involving a third data source enabled the independence of the 2 sources (PMSI and FPVDB) to be checked before applying the capture-recapture method.

[Pitch perception modification due to antiepileptics: A literature and pharmacovigilance databases review]. / Modification de la perception des sons sous antiépileptiques : une revue de la littérature et des bases de pharmacovigilance.

Pitch perception modifications are among the little-known adverse effects observed with antiepileptics, mainly affecting patients treated with carbamazepine (CBZ). Here, we describe an original French case of pitch perception modification due to CBZ resulting in perfect pitch loss. We also reviewed the literature as well as French and world health organisation global pharmacovigilance database. The case report concerns a 22-year-old patient with perfect pitch with untreated left temporal partial epilepsy. Following a generalized seizure, the introduction of CBZ prolonged release (200mg twice a day) is decided. As soon as CBZ is introduced, the patient notices a change in pitch perception, about a semitone lower. This adverse effect persisted despite a gradual decrease in doses. The patient reported a total recovery of his perfect pitch when CBZ stopped completely 11 years later. In the French pharmacovigilance database, only one other case of pitch perception modification under CBZ was recorded (no cases were found with oxcarbazepine, lacosamide, sodium valproate, lamotrigine, levetiracetam, phenobarbital, phenytoin, primidone, ethosuximide, vigabatrine, felbamate, gabapentin, tiagabine and topiramate). In the literature, 27 cases of pitch perception modification have been published with CBZ, 1 case with oxcarbazepine and 1 case with lacosamide. Pitch perception modification is a very rare adverse effect of CBZ, oxcarbazepine and lacosamide, identified in the literature mainly in the Japanese population, in experienced musicians. A rapid onset after the introduction of treatment, a complete resolution of symptoms, in most cases upon discontinuation of treatment, is observed, with no sequelae reported. Due to the impact on quality of life, especially in patients whose profession is related to music, knowledge of this adverse event seems important to evoke this diagnosis.

Trends in sodium valproate prescriptions among children aged 0 to 14 years between 2010 and 2016: A study based on the French National Health Insurance Database.

PURPOSE: After a huge campaign of information on the teratogenic risk of sodium valproate (VPA) having taken place in France we aimed to evaluate the trend of its prescriptions in young epileptic girls. METHOD: Using the French National Health Insurance Database we searched for patients aged 0-14 years being supplied an antiepileptic drug (AED) between 2010 and 2016. RESULTS: 113,362 children received at least one AED, 61,259 boys and 52,103 girls. Compared to 2010-2014 years, VPA was less prescribed in 2016 as first AED (29% vs 37.3% respectively). The difference between the two periods was greater for girls (-41%) than for boys (-12%). CONCLUSION: The changing trend of VPA as first AED prescribed, particularly in girls, reflects published evidence in terms of safety.