French Health Insurance System Research Articles

Cost analysis study comparing the impact of treatment with aprotinin versus tranexamic acid in cardiac surgery under cardiopulmonary bypass

Objectives: An increased risk of mortality and postoperative side effects led to aprotinin (Trasylol®) withdrawal from the market in 2008, but since 2018 aprotinin has again been used in France. The French retrospective multicentre APACHE study (AProtinin versus tranexamic Acid in Cardiac surgery patients with High-risk for Excessive bleeding) compared the efficacy of tranexamic acid versus half-dose aprotinin. The aim of this study, ancillary to the APACHE study, is to carry out a medico-economic analysis of the use of these two antifibrinolytics on an APACHE sub-population.Methods: Economic data on reimbursement by the French health insurance system were extracted from the program for the data processing of medical information, and quantitative data on the cost of healthcare products were obtained from the hospital pharmacy software.Results: The main analysis of costs for the population shows that the global valuation was not significantly different between the two treatment groups (p = 0.60), but the costs of blood products included in the related hospital stay group (Groupe Homogène de séjour [GHS] (whole blood, platelets and plasma) were higher for the tranexamic acid group (p = 0.007). In a sub-analysis of patients alive at discharge, the costs of blood products in addition to GHS (blood-derived medicines) and the costs of blood products in the GHS were higher for the tranexamic acid group (p = 0.04 and 0.001 respectively).Conclusions: The additional cost of aprotinin at the time of purchase is offset by the additional costs of blood products in the tranexamic acid group.

Outcomes and costs with the introduction of robotic-assisted thoracic surgery in public hospitals.

Robotic-assisted thoracic surgery (RATS) is an effective treatment of non-small cell lung cancer (NSCLC) but the effects of its implementation in university hospital networks has not been described. We analyzed the early clinical outcomes, estimated costs, and revenues associated with three robotic systems implemented in the Paris Public Hospital network. A retrospective study included patients who underwent RATS for NSCLC in 2019 and 2020. Ninety-day morbidity, mortality, hospital costs, and hospital revenues were described. Economic analyses were conducted either from the hospital center or from the French health insurance system perspectives. Cost drivers were tested using univariate and multivariable analyses. Sensitivity analyses were performed to assess uncertainty over in-hospital length of stay (LOS), number of robotic surgeries per year, investment cost, operating room occupancy time, maintenance cost, and commercial discount. The study included 188 patients (65.8 ± 9.3years; Charlson 4.1 ± 1.4; stage I 76.6%). Median in-hospital LOS was 6days [5-9.5], 90-day mortality was 1.6%. Mean hospital expenses and revenues were €12,732 ± 4914 and €11,983 ± 5708per patient, respectively. In multivariable analysis, factors associated with hospital costs were body mass index, DLCO, major complications, and transfer to intensive care unit. Sensitivity analyses showed that in-hospital LOS (€11,802-€15,010) and commercial discounts on the list price (€11,458-€12,732) had an important impact on costs. During the first 2years following the installation of three robotic systems in Paris Public Hospitals, the clinical outcomes of RATS for NSCLC have been satisfactory. Without commercial discount, hospital expenses would have exceeded hospital revenues.Clinical registration number CNIL, N°2221601, CERC-SFCTCV-2021-07-20-Num17_MOPI_robolution.

Statin treatment is not associated with an increased risk of adrenal insufficiency in real-world setting.

Statins could reduce the synthesis of steroid hormones, thereby could cause adrenal insufficiency. We investigated this risk in a large nationwide database. We conducted a nested case-control study using a cohort of individuals affiliated to the French health insurance system in 2010, ≥18y and without adrenal insufficiency history. Each case had a first event of adrenal insufficiency between 2015 and 2017 and was matched to up to ten controls on age, sex, and prior treatment with corticosteroids. Statin exposure was measured over the five years preceding the index date, considering a six-month censoring lag-time. Association was estimated using a conditional logistic regression adjusted for confounders included in a disease risk score. Analyses were stratified on age, sex and corticosteroid history of use. 4 492 cases of adrenal insufficiency were compared with 44 798 controls (median age 66y, 58% women), of which 39% vs. 33% were exposed to statins, respectively. No association between statin use and adrenal insufficiency was found when adjusting the model for confounders (adjusted odds ratio 0.98; 95% confidence interval 0.90-1.05). These results were consistent regardless of the exposure definition and stratifications considered. Statin-related adrenal insufficiency risk, if any, seems to be very limited and does not compromise the benefit of statin treatment.

Use of psychotropic drugs in the elderly in France: Are we condemned to remain at high tide?

Psychotropics are widely used drugs, especially in the elderly, especially in France. This, and the risks associated to their use, logically led to concerns that resulted in numerous studies, reports, and regulatory actions intending to limit this use. This review objective was to provide an overview of psychotropic use in elderly subjects in France for antipsychotics, antidepressants, and benzodiazepines and related drugs. The narrative review performed is structured in two parts. The first reminds the initial steps of psychotropic use monitoring in the general French population. The second provides information on psychotropic use in elderly in France using the latest open data released by the French Health Insurance system and processed using the dedicated DrugSurv tool developed within the DRUGS-SAFE® and DRUGS-SAFE® programs. This was completed examining the most recent studies regarding psychotropic use in elderly in France, whether they consisted in publications or reports. At least before the COVID-19 epidemic, decreases in psychotropic prevalence of use among the elderly in France could be observed, mostly for antipsychotics or benzodiazepines (e.g. antipsychotics, 2006-2013: 10.3% decrease and benzodiazepines 2012-2020: decrease from 30.6% to 24.7% in subjects aged ≥65). Psychotropic prevalence of use remained however very high overall (e.g. antidepressants, 2013: 13% in subjects aged 65-74 and 18% in aged ≥65), exceeding that of most other countries, with a significant proportion of inappropriate use (e.g. in 30% of benzodiazepine users, all ages) carrying a clearly identified risks for uncertain benefit. Initiatives have been multiplied at the national level to reduce psychotropic overuse in the elderly. The reported prevalences demonstrate their effectiveness is obviously insufficient. This limited effectiveness is not specific to psychotropics and might reside in a failure to create strong adherence to messages and recommendations. Other levels should be considered, especially regional, for interventions coupled with pharmacoepidemiologic monitoring allowing impact assessment.

Women's health in migrant populations: a qualitative study in France.

In 2019, there are 6.5 million migrants living in France. Numerous quantitative studies show inequalities in access and quality of care, in particular in women's health. This study aimed to explore migrant women's experience of gynaecological care. We conducted 17 semi-structured in-depth interviews with migrant women in Toulouse (France). We used a Grounded Theory approach to perform the analysis. Although migrant women were generally satisfied with the gynaecological care received, they also reported dysfunctions. Positive elements were the French health insurance system, the human qualities of the healthcare providers and the performance of the health system. Although reassuring, the structured framework was perceived to have little flexibility. This was sometimes felt as oppressive, paternalistic or discriminatory. These obstacles, amplified by the women's lifestyle instability and precariousness, the language barrier and the difficulty to understand a totally new healthcare system, made women's health care and, especially, preventive care, a difficult-to-achieve and low-priority objective for the women. Migrant women's overall satisfaction with the healthcare system contrasted with the known health inequalities in these populations. This is a good example of the concept of acculturation. Healthcare professionals need to make an introspective effort to prevent the emergence of stereotypes and of discriminatory and paternalistic behaviours. A better understanding and respect of the other person's culture is an indispensable condition for intercultural medicine, and thus for reducing the health inequalities that migrant women experience.

Cost of Home Dialysis in France

Summary
 Medico-economic evaluation is defined as economic evaluation applied to the health field. It is a comparative analysis of different diagnostic, therapeutic or preventive strategies, based on their costs and health outcomes. We have only one medico-economic study on the costs of dialysis in France, carried out by the Haute Autorité de Santé, which covered the year 2012 and consisted of cross-referencing 3 databases: the Registre Réseau Épidémiologique et Information en Néphrologie and the Système National d’Informations Inter-régimes de l’Assurance Maladie et de l’Hospitalisation. Analyses focused on prevalent patients, incident patients and key patient characteristics: age, presence of diabetes and care trajectories. The average monthly cost varied considerably according to the management modality, from 3774 euros/month in autonomous continuous ambulatory peritoneal dialysis (CAPD) to 7253 euros/month in center-based hemodialysis. The monthly cost of therapies according to the patient profile appears to be strongly affected by the diabetic status of the patients. This analysis shows the high cost of transport for patients on in-center hemodialysis (20% of total expenditures), and even higher for nursing care in assisted CAPD (37% of total expenditures). The total tariff decreases from 2014 to 2020 were -17.6% for center-based hemodialysis and -9.8% for the low medicalized dialysis unit (LMDU), while the total 2014–2021 tariff increases were +9.3% for CAPD and +9.1% for automated peritoneal dialysis (APD). Paradoxically, these price changes have increased the cost of assisted peritoneal dialysis, which is now almost at the same level of overall cost as in-center hemodialysis for the French health insurance system. The ongoing study of the Physidia Laboratory’s retrospective cohort on daily home hemodialysis (DHH) should allow us to know the current cost of each hemodialysis technique currently practiced in France, including DHH.

Abstract 4101: ADRENALINE, an atlas for drug and breast cancer survival interaction: Comedications at diagnosis and impact on breast cancer mortality of the French breast cancer cohort (n=235,375)

Abstract Background: Breast cancer (BC) incidence increases with age, as well as the incidence of many other chronic diseases. Between 42 and 68% of BC patients suffer from other chronic conditions -comorbidities- at BC diagnosis. Comorbidities may be associated with the intake of chronic medications -comedications. The French health insurance system routinely collects health care reimbursements of almost 98% of the population: hospital abstracts, long-term diseases, outpatient care (medical consults, drug purchases under prescription⋯) and death status. The project ADRENALINE (Atlas for DRug and brEast caNcer survivAL INtEraction) analyzes the impact of comedications at diagnosis on BC survival on a French cohort using data from the French social security system. Methods: We identified all women diagnosed with an incident BC treated with surgery in France from 2011 to 2017 and affiliated to the general health insurance scheme. Women with concomitant cancer or metastases at diagnosis were discarded from the analyses. Comedication intake was defined as the delivery in pharmacy of at least 3 months of full treatment (e.g. 90 pills) the 6 months preceding BC diagnosis. The analysis was restricted to drugs taken by at least 300 women. A Cox proportional hazard model was used to estimate the hazard ratio (HR) for each molecule. The model was adjusted on more than 100 confounding variables: social factors, comorbidities and other comedications. Two adjustment methods were tested: Inverse Probability of Treatment Weighting (IPTW) and matching. We assumed that the adjustment was sufficient to control for confounding if the standardized mean difference of each confounder after adjustment did not exceed 0.1. Molecules which did not pass the adjustment quality test were discarded. Results: 235,375 patients were included in the study. Among 219 selected drugs, 91 and 171 passed the adjustment quality test for IPTW and for matching, respectively. The full set of results is available on a web application. Among main findings, several drugs or drug classes were associated with an improved survival: proton-pump inhibitors (IPTW; HR=0.93; p=0.002); statins (e.g. rosuvastatin, IPTW, HR=0.65, p<0.001); beta-blocking agents (atenolol, IPTW, HR=0.78, p=0.003); alverine (IPTW, HR=0.78, p<0.001). Conversely, imidazoline receptor agonists may be deleterious (moxonidine; matching; HR=2.12; p = 0.001). Conclusion: ADRENALINE reports the impact on BC survival of 219 widely prescribed drugs. It can be used to identify molecules with a potential protective or deleterious effect relative to BC. Some of them are currently under mechanistical investigation within a drug screening program. This atlas highlights candidates to drug-repurposing trials or pharmacovigilance warnings, and will be extended to cancers of other localizations in a near future. Citation Format: Elise Dumas, Beatriz Grandal, Lucie Laot, Eric Daoud, Lidia Delrieu, Marc Espié, Sophie Houzard, Christine Le Bihan-Benjamin, Philippe-Jean Bousquet, Elodie Anthony, Aurélien Latouche, Nadir Sella, Thierry Dubois, Annabelle Ballesta, Amyn Kassara, Elaine Del Nery, Benjamin Marande, Samar Alsafadi, Paul Gougis, Chloé-Agathe Azencott, Fabien Reyal, Anne-Sophie Hamy. ADRENALINE, an atlas for drug and breast cancer survival interaction: Comedications at diagnosis and impact on breast cancer mortality of the French breast cancer cohort (n=235,375) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4101.

First trimester pregnancy exposure to fosfomycin and risk of major congenital anomaly: a comparative study in the EFEMERIS database.

Fosfomycin trometamol has been recommended as first-line bactericidal antibiotic for urinary tract infections in pregnant women since 2015 in France. However, studies assessing fosfomycin safety in pregnancy are sparse. This study aimed to assess the risk of major Congenital Anomaly (CA) after fosfomycin exposure during the first trimester of pregnancy. We performed a comparative study in EFEMERIS, the French database including expecting mothers covered by the French Health Insurance System of Haute-Garonne from July 1st, 2004 to December 31th, 2018. EFEMERIS contains prescribed and dispensed reimbursed medications during pregnancy and pregnancy outcomes. Logistic regressions have been conducted to compare three groups: (1) pregnancies exposed at least once to fosfomycin; (2) pregnancies exposed at least once to nitrofurantoin; and (3) pregnancies exposed neither to fosfomycin nor to nitrofurantoin, another antibiotic prescribed for urinary infections, before and during pregnancy. A total of 2724 (2.0%) pregnant women received at least one fosfomycin prescription during the first trimester, 650 (0.5%) received nitrofurantoin during the first trimester, and 133,502 (97.5%) pregnant women were not exposed to fosfomycin nor to nitrofurantoin. First trimester pregnancy exposure to fosfomycin was not associated with an increased risk of major CA, compared to first trimester exposure to nitrofurantoin (2.0% versus 2.5%; ORa = 0.80 [0.44-1.47]), or to pregnancies unexposed to fosfomycin and nitrofurantoin (2.0% versus 2.1%; ORa = 0.97 [0.73-1.30]). This is the first large comparative study assessing fosfomycin safety in pregnancy. It does not exhibit an increased risk of major CA after fosfomycin exposure during the first trimester of pregnancy.

Antihypertensive and lipid-lowering drugs usage after primary stroke in a large representative sample of the French population.

The aim of the study is to describe the use of antihypertensive and lipid-lowering drugs in post-stroke secondary prevention in France. This is a prospective cohort study based on a representative sample of the French health insurance system database. All patients aged 45 and over, hospitalized for a first stroke between 1 January 2009 and 31 December 2014 were included. For each drug class, identified using Anatomical Therapeutic Chemical (ATC) codes, patients were followed from the first drug supply after stroke until the end of study period (31 December 2017), or exit date of the database or death. Adherence was defined by the proportion of days covered and persistence by the absence of a treatment gap of more than 91 days. A total of 2674 patients were included, median age was 75.0 years (interquartile range 63.0-83.0) and 51.2% were women. For patients treated with a drug of interest after stroke, median follow-up was 4.8 years (interquartile range 3.4-6.5). Regarding antihypertensive drugs, adherence at 8 years was 84.1% and persistence was 71.0%. For lipid-lowering drugs adherence at 8 years was 68.6% and persistence was 49.4%. Adherence and persistence were lower for patients starting treatment at time of stroke (antihypertensive drugs: 70.9% for adherence and 52.6% for persistence; lipid-lowering drugs: 62.3% and 43.1%) compared to patients already treated (antihypertensive drugs: 87.2% and 75.2%; lipid-lowering drugs: 73.6% and 54.5%). In this large representative sample of patients hospitalized for a first stroke in France, post-stroke therapeutic management remains suboptimal compared to guidelines, notably regarding lipid-lowering drugs. This trend was more pronounced for newly treated patients.

POSA412 Using French National Healthcare Databases (SNDS) to Estimate Economic Burden of Diseases: A Literature Review

The French national medico-administrative database called SNDS (“Système National des Données de Santé”) contains hospital records, primary and secondary care for 66 million people. All dispensed and reimbursed drug prescriptions are collected and these data are individualized and anonymized. The General Beneficiaries Sample (EGB) is a representative sample (1/97) of the SNDS. We aim to provide an overview of cost of illness assessment from medico-administrative databases, focusing on data extracted from SNDS and EGB. A literature review of French and English language publications from 2011 to 2021 was conducted in PubMed, searching keywords related to the SNDS database studies. Only human studies were selected. All publications including a cost analysis conducted through these databases were included. We excluded studies without any cost analysis and studies with cost data extracted from other databases or retrieved from PMSI (hospital database) only. Overall, 43 articles were selected after screening 121 publications, which most of them were published in clinical journals (54%). The EGB database was used more frequently to estimate costs than the SNDS (63% vs 37%). Cardiovascular diseases (16%), cancers (16%) and diabetes (16%) were the three pathologies most studied. Almost half of the studies considered costs over only a 1-year period or less (46.5%). Cost analyses were performed from the French health Insurance System (47%) or societal (35%) perspective, rarely both (9%), when the information was provided. Direct medical (hospitalizations and ambulatory care) or non-medical costs (transportation) were retrieved from French administrative databases, and 8 publications also considered some indirect costs (sick leaves, daily allowances, disability pensions). Discounting was not applied in most cases (79%). The SNDS is an exhaustive medical-administrative database which can provide real world cost data to assess burden of diseases, but also to provide inputs for medico-economic and budget impact models.

Epidemiology, Clinical Features, and Outcome in a Cohort of Adolescents With Cerebral Venous Thrombosis.

We aimed to analyze the epidemiologic, clinical, and paraclinical features of adolescents with cerebral venous thrombosis (CVT) and its therapeutic management and outcome. This multicenter retrospective cohort included patients 10 to 18 years of age hospitalized for a first episode of CVT in 2 French regions between 1999 and 2019. The number of cases was compared to the number recorded by the French health insurance system. The CVT registry of the Lariboisière hospital allowed comparisons with adults. One hundred two patients were included (52.9% female; median age 15.1 years). Estimated incidence was 0.37 to 0.38 per 100,000 adolescents per year; 45.5% of patients presented with focal deficits or seizures or in a coma. Male patients were younger than female patients (14.2 vs 15.6 years; p < 0.01) and more often admitted to intensive care (52.1% vs 24.1%; p = 0.0,035). The lateral sinus was the most common CVT location (72.3%), and 29.4% of adolescents had associated venous infarction or hematoma. Most patients (94.1%) received anticoagulation. Treatment also included an endovascular procedure (2.9%), decompressive craniectomy (4.9%), and CSF shunt (6.9%). The most frequently identified CVT-associated condition was local infection in male (18.6%) and systemic disease in female (14.8%; p < 0.001) patients. The proportion of CVTs in adolescents without an identified associated condition or risk factor was low (1.9% vs 11.4% in adults; p < 0.002). Adverse outcome at 1 year was more frequent than in adults (33.3% vs 11.8%; p = 0.0,001). CVT in adolescents is rare and complex with specific epidemiology, including differences in clinical presentation and associated conditions between sexes, and more severe outcomes than in adults. Careful specialized management and follow-up are therefore recommended.

Trajectories of antidepressant drugs during pregnancy: A cohort study from a community-based sample.

The aim of this study was to monitor the trajectories of antidepressant use during pregnancy and the postpartum period among women chronically treated with antidepressants before their pregnancy, and to assess characteristics associated with each trajectory. This cohort study included all pregnant women whose data were included in the General Sample of Beneficiaries (EGB) database affiliated with the French Health Insurance System, from 2009 to 2014. Women were followed up until 6 months after childbirth. Chronic treatment was defined as exposure over the 6-month period preceding pregnancy. A group-based trajectory model (GBMT) was estimated to identify distinctive longitudinal profiles of antidepressant use. Among 760 women chronically treated with antidepressants before their pregnancy, 55.8% stopped their treatment permanently in the first trimester, 20.4% discontinued it for a minimum of 3 months and resumed it postpartum, and 23.8% maintained it throughout pregnancy and postpartum. No sociodemographic or medical characteristics were associated with any trajectory group. Women who maintained treatment presented more frequent obstetric complications and postpartum psychiatric disorders. Among women who interrupted treatment, prescription of benzodiazepines and anxiolytics decreased initially but rose postpartum to a higher level than before pregnancy. Pregnant women treated with antidepressant require a re-evaluation of psychiatric treatment. It is necessary to pay attention to obstetric complications for severely depressed women. Additionally, as relapse was associated with increased benzodiazepine use, it is important to carefully monitor all women who stop antidepressant treatment during pregnancy.

Use of the French healthcare insurance database to estimate the prevalence of exposure to potential drug-drug interactions.

Drug-drug interactions (DDIs) require monitoring in an aging population with increasing polypharmacy exposure. We aimed to estimate the prevalence of exposure to potential DDIs using the French healthcare insurance system database, for six DDIs with various clinical relevance: angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs (ARBs-ACEIs + NSAIDs), antiplatelet agents and NSAIDs (AAP + NSAIDs), serotonergic drugs and tramadol (SD + T), statins and macrolides (S + M), oral anticoagulant and NSAIDs (OAC + NSAIDs), and colchicine and macrolides (C + M). We used exhaustive healthcare data from a 1/97th random sample of the population covered by the French health insurance system (EGB) between 2006 and 2016. Exposure to a DDI was defined as overlapping exposure to two interacting drugs. The prevalence of exposure was estimated by year. Prevalence of exposure in 2016 was estimated at 3.7% for ARBs-ACEIs + NSAIDs, 1.5% for AAP + NSAIDs, 0.76% for SD + T, 0.36% for S + M, 0.24% for AOC + NSAIDs, and 0.02% for C + M. In 26% to 58% of episodes of exposure, the two interacting drugs were prescribed by the same physician and dispensed by the same pharmacy the same day. Between 2006 and 2016, the yearly prevalence was increasing for SD + T and for DDIs involving NSAIDs, and it was decreasing for those involving macrolides. Exposures to potential DDIs in France are not uncommon with a high proportion resulting from a co-prescription by the same physician. Monitoring the prevalence of exposure to DDIs is needed to implement prevention measures. Administrative data enable this surveillance in large and representative cohorts.

Are PrEP services in France reaching all those exposed to HIV who want to take PrEP? MSM respondents who are eligible but not using PrEP (EMIS 2017)

ABSTRACTPre-exposure prophylaxis (PrEP) is fully reimbursed by the French health insurance system since 2016. However, uptake of PrEP is slower than expected and little is known about men who have sex with men (MSM) who are eligible for PrEP according to French guidelines, but not using it. This study aims to (1) assess and describe MSM that are eligible to PrEP but not using it, and (2) identify potential individual and structural barriers of PrEP uptake among eligible MSM who are aware and intend to take PrEP. Data from EMIS-2017, a cross-sectional internet survey among gay, bisexual, and other MSM, were used. Among 7965 respondents without diagnosed HIV, 9.2% were PrEP users. Among 7231 non-PrEP users, 35.2% were eligible to PrEP and 15.2% were eligible, aware and intended to take PrEP. Eligible MSM who are not using PrEP are mostly younger, students, less “out”, living in small cities, using condoms more frequently but still with low self-efficacy regarding safe sex and more distant from preventive health care and information than PrEP users. Despite free PrEP availability in France, results suggest that PrEP is not fully accessible and that there is a need to increase PrEP demand and decentralize PrEP delivery.

Does the take up of public insurance programs improves health care consumption of poor individuals?

Abstract Background The French health insurance system is universal but 95% of the population is also covered by a complementary private health insurance (CHI). The CHI take up is not uniform across the income distribution and health care access is partly conditioned by its coverage. The Complementary Universal Health Coverage (CMU-C) and the Health Insurance Vouchers Scheme (ACS) are mean tested programs providing CHI to the poor. The former is free while the latter takes the form of a voucher to buy private CHI. Our objective is to study and compare the evolution of health care use and consumption associated with the take up of the CMU-C or the ACS. Methods In a nationwide cohort of ACS and CMU-C beneficiaries we compute bi-annual expenditures, out of pockets expenditures and rates of use for different types of care: outpatient, inpatient, dental, optical and audiology. We use panel data regression methods to model the evolution of health care use and expenditures before, during and after the coverage periods of both programs. Results Our population is composed with about 10 million individuals benefiting at least once from either the ACS or the CMU-C on the 2012-2017 period. Preliminary results suggest that inpatient expenditures are increasing concomitantly with the take up of any program whereas outpatient expenditures tend to increase after. Results will be provided for the conference on the variations of the consumption according to the program (CMU-C or ACS), type of care, individual characteristics and health status. Conclusions Free or subsidized complementary health insurance may play an important role in the access to care for poor population, even in the presence of mandatory coverage. The take up of complementary health insurance for the poor population could be partly driven by the use of inpatient services but coverage may impact positively outpatient expenditures. Key messages Unlocking poor individuals financial constraint tends to increase their use of medical services. Generous insurance coverage targeting financially constrained individuals could be a tool to reduce health care use inequalities.

Exposure to Bisphenol A and Bisphenol S and Incident Type 2 Diabetes: A Case-Cohort Study in the French Cohort D.E.S.I.R.

Background:The question of whether exposure to bisphenol A (BPA) contributes to the development of type 2 diabetes is still unresolved. Most epidemiological evidence on the association between BPA and diabetes is from cross-sectional studies or longitudinal studies with single urinary measurements. No prospective study has examined exposure to BPA analogs such as bisphenol S (BPS) in relation to incident type 2 diabetes.Objectives:We aimed to investigate whether exposure to BPA and BPS, assessed at up to two time points, was associated with the incidence of type 2 diabetes.Methods:We performed a case–cohort study on 755 participants without diabetes at baseline and followed-up over 9 y as part of the French prospective cohort Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.). BPA-glucuronide (BPA-G) and BPS-glucuronide (BPS-G) were assessed in fasting spot urine samples collected during the health examinations at baseline and 3 y later. Associations with incident diabetes were examined using Prentice-weighted Cox regression models adjusted for potential confounders.Results:A total of 201 incident cases of type 2 diabetes were diagnosed over the follow-up, including 30 in the subcohort. Compared with participants with the lowest average BPA exposure (below the first quartile), participants in the second, third, and fourth quartile groups of exposure had a near doubling of the risk of type 2 diabetes, with a hazard ratio 2.56 (95% CI: 1.16, 5.65), 2.35 (95% CI: 1.07, 5.15), and 1.56 (95% CI: 0.68, 3.55), respectively. The detection of BPS-G in urine at one or both time points was associated with incident diabetes, with an 2.81 (95% CI: 1.74, 4.53).Discussion:This study shows positive associations between exposure to BPA and BPS and the incidence of type 2 diabetes, independent of traditional diabetes risk factors. Our results should be confirmed by recent, population-based observational studies in different populations and settings. Overall, these findings raise concerns about using BPS as a BPA substitute. Further research on BPA analogs is warranted. https://doi.org/10.1289/EHP5159

The cost-effectiveness of neonatal versus prenatal screening for congenital toxoplasmosis

BackgroundCongenital Toxoplasmosis (CT) can have severe consequences. France, Austria, and Slovenia have prenatal screening programs whereas some other countries are considering universal screening to reduce congenital transmission and severity of infection in children. The efficiency of such programs is debated increasingly as seroprevalence among pregnant women and incidence of congenital toxoplasmosis show a steady decrease. In addition, uncertainty remains regarding the effectiveness of pre- and postnatal treatments.MethodTo identify cost-effective strategies, prenatal and neonatal screenings were compared using a decision-analytic model based on French guidelines and current knowledge of long-term evolution of the disease in treated children. Epidemiological data were extracted from the scientific literature and clinical data from the French Lyon cohort. Strategies were compared at one year of age, when infection can be definitively evaluated, and at 15 years of age, after which validated outcome data become scarce. The analysis was performed from the French Health Insurance System perspective and included direct medical costs for pregnant women and their children.ResultsThe 1-year Incremental Cost-Effectiveness Ratio showed that prenatal screening would require investing €14,826 to avoid one adverse event (liveborn with CT, fetal loss, neonatal death or pregnancy termination) compared to neonatal screening. Extra investment increased up to €21,472 when considering the 15-year endpoint.ConclusionsPrenatal screening is cost-effective as compared to neonatal screening in moderate prevalence areas with predominant Type II strains. In addition, prenatal screening, by providing closer follow-up of women at risk increases the number of occasions for education avoiding toxoplasmosis.

Risk of Drug-Drug Interactions in Out-Hospital Drug Dispensings in France: Results From the DRUG-Drug Interaction Prevalence Study.

Introduction: Drug interactions could account for 1% of hospitalizations in the general population and 2–5% of hospital admissions in the elderly. However, few data are available on the drugs concerned and the potential severity of the interactions encountered. We thus first aimed to estimate the prevalence of dispensings including drugs Contraindicated or Discommended because of Interactions (CDI codispensings) and to identify the most frequently involved drug pairs. Second, we aimed to investigate whether the frequency of CDI codispensings appeared higher or lower than the expected for the drugs involved.Methods: We carried out a study using a random sample of all drugs dispensings registered in a database of the French Health Insurance System between 2010 and 2015. The distribution of the drugs involved was described considering active principles, detailing the 20 most frequent ones for both contraindicated or discommended codispensings (DCs). To investigate whether the frequency of CDI codispensings appeared higher or lower than the expected for the drugs involved, we developed a specific indicator, the Drug-drug interaction prevalence study-score (DIPS-score), that compares for each drug pair the observed frequency of codispensing to its expected probability. The latter is determined considering the frequencies of dispensings of the individual drugs constituting a pair of interest.Results: We analyzed 6,908,910 dispensings: 13,196 (0.2%) involved contraindicated codispensings (CCs), and 95,410 (1.4%) DCs. For CCS, the most frequently involved drug pair was “bisoprolol+flecainide” (n = 5,036); four out of five of the most represented pairs involved cardiovascular drugs. For DCS, the most frequently involved drug pair was “ramipril+spironolactone” (n = 4,741); all of the five most represented pairs involved cardiovascular drugs. The drug pair involved in the CC with the highest score value was “citalopram+hydroxyzine” (DIPS-score: 3.7; 2.9–4.6); that with the lowest score was “clarithromycin+simvastatin” (DIPS-score: 0.2; 0.2–0.3). DIPS-score median value was 0.4 for CCs and 0.6 for DCs.Conclusion: This high prevalence of CDI codispensings enforces the need for further risk-prevention actions regarding drug-drug interactions (DDIs), especially for arrhythmogenic or anti-arrhythmic drugs. In this perspective, the DIPS-score we develop could ease identifying the interactions that are poorly considered by clinicians/pharmacists and targeting interventions.

A Randomized Controlled Trial Comparing Crude Versus Heparin-Bonded PTFE Graft in Below the Knee Bypass Surgery for Critical Limb Ischemia (REPLACE Trial): Design and Protocol

Although autogenous venous grafts are preferable for below-the-knee bypass surgery in patients with critical limb ischemia, some 20% of patients will have no suitable vein for grafting, compelling a resort to artificial graft materials. Retrospective subgroup analyses within published studies comparing heparin-bonded polytetrafluoroethylene (PTFE) with crude PFTE graft in below-the-knee bypass suggest that heparin-bonded graft offers superior long-term patency rates, but this has not been prospectively verified in patients with critical limb ischemia. A single-blind randomized controlled trial in 20 French centers has been designed. Patients assessed as having no suitable autologous vein for bypass grafting for critical lower limb ischemia will be randomized to receive either a heparin-bonded PTFE graft or a crude PTFE graft. A literature review suggested expected 1-year patency rates of 53% for the crude ePTFE arm and 74% for the heparin-bonded PTFE arm. On analyzing 1-year patency rate as a binary variable, for a significance level α = 0.05 and a randomization ratio of 1:1, a total of 176 patients (88 in each arm) will be required to obtain approximately 80% power to reject the null hypothesis. Assuming 10% dropout at 1 year and 20% mortality, 228 patients will be randomized (114 patients in each arm). The primary outcome variable will be patency at 1 year assessed by duplex ultrasound color-flow scan. Any intervention to open up or prevent a graft occlusion before 1 year will be classified as loss of patency. Technical success, deaths, complications, major adverse cardiovascular and limb events, length of hospitalization, and quality of life will also be recorded and analyzed as secondary outcome variables. Cost-utility and cost-effectiveness analyses based on standard tariffs in the French health insurance system will be performed. The REPLACE trial is the first randomized controlled trial designed to determine if heparin-bonded PTFE graft is superior to crude PTFE graft in below-the-knee bypass surgery for critical limb ischemia.

A Payer Perspective of the Hospital Inpatient Additional Care Costs of Antimicrobial Resistance in France: A Matched Case-Control Study.

Background and ObjectiveAntimicrobial resistance (AMR) has become one of the biggest threats to global public health given its association with mortality, morbidity and cost of health care. However, little is known on the economic burden of hospitalization attributable to AMR from a public health insurance perspective. We assessed the excess costs to the French public health insurance system attributable to AMR infections in hospitals.MethodsBacterial infectious disease-related hospitalizations were extracted from the National health data information system for all stays occurring in 2015. Bacterial infections, strains, and microbial resistance were identified by specific French ICD-10 codes. Information about health care expenditure, co-morbidities and demographic characteristics (i.e. gender, age) are provided. We used a matched case–control approach to determine the excess of reimbursements paid to stays with AMR compared to stays with an infection without resistance. Cases and controls were matched on gender, age, Charlson comorbidity index, category of infection, infection as principal diagnosis (two classes), microorganism and hospital status. The overall AMR cost was extrapolated to stays with AMR and excluded from the sample (multiple infections), and a second extrapolation was performed to consider stays with unknown resistance status.ResultsThe final sample included 52,921 matched-pairs (98.2% cases). Our results suggest that AMR overall cost reached EUR109.3 million in France with a mean of EUR1103 per stay; extrapolation to the entire database shows that the overall cost could potentially reach EUR287.1 million if all cases would be identified. The mean excess length of hospital stay attributable to AMR was estimated at 1.6 days.ConclusionAMR causes substantial cost burden in France for the public health insurance. Our study confirms the need to reinforce programs to prevent AMR infection and thereby reduce their economic burden.Electronic supplementary materialThe online version of this article (10.1007/s40258-018-0451-1) contains supplementary material, which is available to authorized users.