Vitiligo patient population and disease burden in France: VIOLIN study results from the CONSTANCES cohort.

BACKGROUND: Vitiligo is a chronic autoimmune disease resulting in skin depigmentation. OBJECTIVES: This study assessed the prevalence, disease burden and treatment of vitiligo in France. METHODS: VIOLIN was a cross-sectional study nested in the national CONSTANCES cohort, which consists of randomly selected adults aged 18-69 years in France. In VIOLIN, longitudinal data were collected prospectively from 158,898 participants during 2012-2018 and linked to the National Health Data System (SNDS), a healthcare utilization database. Patients with physician-diagnosed vitiligo were matched (1:3) with control participants based on age, sex, geographic region, year of inclusion and skin phototype. Patients completed a questionnaire in 2022 to collect disease characteristics, disease burden and quality-of-life (QoL) data. RESULTS: Vitiligo prevalence was 0.71% (681/95,597) in 2018. The mean age in the vitiligo population was 51.2 years; 51.4% were women. Most patients (63%) were diagnosed before age 30 years, mainly by dermatologists (83.5%). Most patients (81.1%) had visible lesions (i.e. on face, hands). Vitiligo was limited to <10% of the body surface area (BSA) in 85.8% of patients. Comorbidities including thyroid disease (18.0% vs. 9.0%), psoriasis (13.7% vs. 9.7%), atopic dermatitis (12.4% vs. 10.3%), depression (18.2% vs. 14.6%) and alopecia areata (4.3% vs. 2.4%) were significantly more common in patients with vitiligo versus matched controls (n = 2043). QoL was significantly impaired in patients with >5% BSA involvement or visible lesions, particularly with ≥10% facial involvement. Vitiligo-specific instruments (i.e. Vitiligo Impact Patient scale and Vitiligo-specific QoL instrument) were more sensitive to QoL differences among subgroups versus general skin instruments, and generic instruments were least sensitive. Most patients (83.8%) did not receive any prescribed treatment. CONCLUSIONS: Patients with vitiligo in France have a high disease burden, particularly those with visible lesions or higher BSA involvement. Most patients are not receiving treatment, highlighting the need for new effective treatments and patient/physician education.

Non-tuberculous mycobacterial pulmonary diseases in France: an 8 years nationwide study.

BACKGROUND: The objective of the study was to describe the epidemiology, management and cost of non-tuberculous mycobacteria pulmonary disease (NTM-PD) in France. METHODS: A retrospective analysis was performed using the SNDS ("Système national des données de santé") database over 2010-2017. Patients with NTM-PD were identified based on the ICD10 codes during hospitalizations and/or specific antibiotics treatment regimens. The study population was matched (age, sex and region) to a control group (1:3) without NTM-PD. RESULTS: 5628 patients with NTM-PD (men: 52.9%, mean age = 60.9 years) were identified over the study period and 1433 (25.5%) were treated with antibiotics. The proportion of patients still receiving treatment at 6 and 12 months was 40% and 22%, respectively. The prevalence of NTM-PD was estimated at 5.92 per 100,000 inhabitants and the incidence rate of NTM-PD remained stable over time between 1.025/100,000 in 2010 and 1.096/100,000 in 2017. Patients with NTM-PD had more co-morbidities compared to controls: corticoids (57.3% vs. 33.8%), chronic lower respiratory disease (34.4% vs. 2.7%), other infectious pneumonia (24.4% vs. 1.4%), malnutrition (based on hospitalization with the ICD-10 code reported during a hospital stay as a main or secondary diagnosis) (22.0% vs. 2.0%), history of tuberculosis (14.1% vs. 0.1%), HIV (8.7% vs. 0.2%), lung cancer and lung graft (5.7% vs. 0.4%), cystic fibrosis (3.2% vs. 0.0%), gastro-esophageal reflux disease (2.9% vs. 0.9%) and bone marrow transplant (1.3% vs. 0.0%) (p < 0.0001). The mean Charlson comorbidity index score was 1.6 (vs. 0.2 for controls; p < 0.0001). NTM-PD was independently associated with an increased mortality rate with a hazard ratio of 2.8 (95% CI: 2.53; 3.11). Mortality was lower for patients treated with antibiotics compared to untreated patients (HR = 0.772 (95% CI [0.628; 0.949]). Annual total expenses the year following the infection in a societal perspective were € 24,083 (SD: 29,358) in NTM-PD subjects vs. € 3402 (SD: 8575) in controls (p < 0.0001). Main driver of the total expense for NTM-PD patients was hospital expense (> 50% of the total expense). CONCLUSION: Patients with NTM-PD in France were shown to have many comorbidities, their mortality risk is high and mainly driven by NTM-PD, and their management costly. Only a minority of patients got treated with antibiotics and of those patients treated, many stopped their therapy prematurely. These results underline the high burden associated with NTM-PD and the need for improvement of NTM-PD management in France.

Treatment sequence of first and second generation tyrosine kinase inhibitor followed by osimertinib in EGFR-mutated non-small-cell lung cancer: a real life study.

Background: We aimed to assess the effectiveness and cost of patients with first line tyrosine kinase inhibitors (TKIs) sequence of first (1G) and second generation (2G) followed by osimertinib. Materials & methods: Using the French nationwide claims and hospitalization database, we analyzed non-small-cell lung cancer patients who had been treated with osimertinib between April 2015 and December 2017, after a first line treatment with a TKI-1G/2G. Results: The median time on treatment for sequential TKI-1G/2G followed by osimertinib was 34 months (95% CI: 31-46); 13 and 12months, respectively for TKI 1G or 2G and TKI 3G, respectively. The median overall survival for sequential TKI 1G or 2G followed by osimertinib was 37 months (95% CI: 34-42). The mean monthly costs per patient was €5162. Conclusion: These results, in line with those observed during clinical trials, confirm the effectiveness of the sequence TKI-1G/2G followed by osimertinib in EGFR-mutated non-small-cell lung cancer.

Predictors and burden of hospital readmission with recurrent Clostridioides difficile infection: a French nation-wide inception cohort study.

To investigate the predictors and burden of hospital readmission with recurrent Clostridioides difficile infection (rCDI) in a large European healthcare system with a low prevalence of hyper-virulent C. difficile clones. We conducted an inception cohort study based on an exhaustive health insurance database and including all survivors of a first hospital stay with CDI over a one-year period (2015) in France. Readmissions with rCDI were defined as a novel hospital stay with CDI within 12 weeks following discharge of the index hospitalization. Risk factors for readmission with rCDI were investigated through multivariate logistic regression analyses. Among the 14,739 survivors of the index hospital stay (females, 57.3%; median age, 74 [58-84] years), 2135 (14.5%) required at least one readmission with rCDI. Independent predictors of readmission were age ≥ 65 years (adjusted odds ratio (aOR), 1.34, 95% confidence interval (CI), 1.21-1.49, P < 0.0001), immunosuppression (aOR, 1.27, 95% CI, 1.15-1.41, P < 0.0001), chronic renal failure (aOR, 1.29, 95% CI, 1.14-1.46, P < 0.0001), and a previous history of CDI (aOR, 2.05, 95% CI, 1.55-2.71, P < 0.0001). The cumulative number of risk factors was independently associated with the hazard of readmission. Mean acute care costs attributable to rCDI were 5619 ± 3594 Euros for readmissions with rCDI as primary diagnosis (mean length of stay, 11.3 ± 10.2 days) and 4851 ± 445 Euros for those with rCDI as secondary diagnosis (mean length of stay, 16.8 ± 18.2 days), for an estimated annual nation-wide cost of 14,946,632 Euros. Hospital readmissions with rCDI are common after an index episode and drive major healthcare expenditures with substantial bed occupancy, strengthening the need for efficient secondary prevention strategies in high-risk patients.

Xafran, a drug utilization study of rivaroxaban in stroke prevention in atrial fibrillation in France using a claim database.

BACKGROUND: Little is known about the utilization of rivaroxaban in real life treatment settings in France. AIMS: Objectives of this study were to describe the conditions of use and treatment persistence in patients with atrial fibrillation and treated with rivaroxaban for stroke prevention (SP-AF). METHODS: A cohort study was performed using a representative sample of the French nationwide database. All adults who initiated rivaroxaban for SP-AF between 01/08/2012 and 31/12/2014 were included and followed for one year. Inappropriate use of rivaroxaban's was defined as use inconsistent with the summary of product characteristics. RESULTS: In this study, 1278 patients were included, 687 (53.8%) were men and the mean age was 73.4years; 123 patients (9.6%) had a stroke and 78 (6.1%) a major bleeding event in the three years before rivaroxaban initiation. At treatment initiation 236 (18.5%) had chronic congestive heart failure, 991 (77.5%) hypertension, 247 (19.3%) diabetes and 9 (0.7%) HIV, hepatitis B or C infection. No anticoagulant had been administered in the six previous months for 777 patients (60.8%); 160 patients (12.5%) had an inappropriate use of rivaroxaban in SP-AF. At 6 and 12 months after the first delivery with rivaroxaban, 62.8%, and 51.7% (68.5% and 60.5% in sensitivity analyses) of the patients were still treated with rivaroxaban. The proportion of patients with a continuous medication availability above 80% was 96.1%. CONCLUSION: The characteristics of patients in this study are similar to patients treated with this drug in other observational studies. Adherence and persistence with rivaroxaban can be considered good.

Incidence of venous thromboembolism in France: a retrospective analysis of a national insurance claims database.

BACKGROUND: Data estimating the annual incidence of venous thromboembolism (VTE) in France, taking into account both hospital and community settings, are very lacking. This study aimed to estimate the annual incidence of VTE (pulmonary embolism (PE) and deep vein thrombosis (DVT)) in France in 2011 in "real world" population. METHODS: This was a longitudinal insurance claims study of the incidence of VTE in France over 2 years (2010 and 2011). The data analysis was performed using the EGB (Echantillon Généraliste des Bénéficiaires) database, a randomly selected sample of the French national insurance database (CNAMTS) which covers 77 % of the population. All adult patients experiencing a VTE event during the study period were analysed. Recurrence rate of VTE and all-cause mortality rate were also estimated over a 12-month follow-up period. RESULTS: The estimated annual incidence of VTE in France was 184.0 per 100 000 subjects, corresponding to a total of 119 670 events countrywide. The estimated incidence of DVT and PE were respectively 119.8 and 64.2 per 100 000 subjects. Annual recurrence of VTE was reported in 5.5 % (n = 99) patients, with a significantly higher recurrence rate in patients with PE than those with DVT (p = 0.02). Overall, 6.2 % (n = 112) of patients had died over the 12-month follow-up (respectively 10.2 and 7.7 % of patients with DVT and PE). DISCUSSION: To our knowledge, this analysis is the first to estimate the annual incidence of VTE in France using exhaustive data from the EGB database. This has allowed the incidence of DVT in the community to be documented, which to date has not been characterised. Previous studies in France have been limited to the hospital setting and have yielded incidence rates comparable to ours. CONCLUSIONS: This analysis is the first to estimate the annual incidence of VTE in France using exhaustive data from the EGB database. This study showed that the incidence and the burden of the disease remains elevated.

Reduced Rate of Hospitalizations for Acute Diabetes Events Before and After FreeStyle Libre® System Initiation in Some People With Type 2 Diabetes on Insulin-Secretagogue Oral Drug Therapy Without Insulin in France.

Objective: Glycemic management in people with type 2 diabetes mellitus (T2DM) on insulin-secretagogue regimens without insulin is of importance, as this group still represents a significant proportion of patients. Risks for acute diabetes events (ADEs), including diabetic ketoacidosis (DKA) or hypoglycemia, using insulin-secretagogue drugs are well established. Few studies have suggested that continuous glucose monitoring (CGM) could be useful for monitoring glucose dynamics associated with the use of such therapies. To document this point an exploratory analysis was conducted in a group of individuals with noninsulin treated T2DM in France who are managed with oral insulin-secretagogues and initiating the FreeStyle Libre® system (FSL). Methods: A retrospective study of the French national SNDS reimbursement claims database (≈66 million French people) was conducted to identify people with T2DM on oral insulin-secretagogues and receiving a first reimbursement of FSL between August 1, 2017 and December 31, 2018. The analysis included data for the 12 months before and up to 24 months after FSL initiation. Hospitalizations for diabetes-related acute events were identified using ICD-10 codes as main or related diagnosis, for: hypoglycemic events; DKA events; comas; and hyperglycemia-related admissions. Results: A total of 1272 people with T2DM on insulin-secretagogues without insulin initiated FSL during the selection period. Of these, 7.15% had at least one hospitalization for any ADE in the year before FSL initiation, compared with 2.52% at 12 months and 2.83% at 24 months following FSL initiation. Reductions in ADEs were driven by -73% fewer admissions for ADEs related to diabetic ketoacidosis (DKA) or other hyperglycemia-related events. These patterns of reduced ADEs persisted after 2 years. Conclusions: This study suggests the value of the FSL system in reducing ADEs in some people with T2DM in France being treated with insulin-secretagogues without insulin. Characteristics of these patients remain to be documented.

Basal Insulinotherapy in Patients Living with Diabetes in France: The EF-BI Study.

INTRODUCTION: Second-generation basal insulins like glargine 300 U/mL (Gla-300) have a longer duration of action and less daily fluctuation and interday variability than first-generation ones, such as glargine 100 U/mL (Gla-100). The EF-BI study, a nationwide observational, retrospective study, was designed to compare persistence, acute care complications, and healthcare costs associated with the initiation of such basal insulins (BI) in a real-life setting in France. METHODS: This study was conducted using the French healthcare claims database (SNDS). Adult patients living with type 1 or type 2 diabetes mellitus (T1DM or T2DM) initiating Gla-300 or Gla-100 ± other hypoglycemic medications between January 1, 2016 and December 31, 2020, and without any insulin therapy over the previous 6 months were included. Persistence was defined as remaining on the same insulin therapy until discontinuation defined by a 6 month period without insulin reimbursement. Hospitalized acute complications were identified using ICD-10 codes. Total collective costs were established for patients treated continuously with each basal insulin over 1-3 years. All comparisons were adjusted using a propensity score based on initial patient/treatment characteristics. RESULTS: A total of 235,894 patients with T2DM and 6672 patients with T1DM were included. Patients treated with Gla-300 were 83% (T1DM) and 44% (T2DM) less likely to discontinue their treatment than those treated with Gla-100 after 24 months (p < 0.0001). The annual incidence of acute hospitalized events in patients with T2DM treated with Gla-300 was 12% lower than with Gla-100 (p < 0.0001) but similar in patients with T1DM. Comparison of overall costs showed moderate but statistically significant differences in favor of Gla-300 versus Gla-100 for all patients over the first year, and in T2DM only over a 3-year follow-up. CONCLUSION: Use of Gla-300 resulted in a better persistence, less acute hospitalized events at least in T2DM, and reduced healthcare expenditure. These real-life results confirmed the potential interest of using Gla-300 rather than Gla-100.

Respiratory syncytial virus-related hospital stays in adults in France from 2012 to 2021: A national hospital database study.

BACKGROUND: Respiratory syncytial virus (RSV) causes lower respiratory tract infections (LRTI) that may lead to hospitalization or death. The present study aimed to assess the burden of RSV infections in hospitalized adults. METHODS: RSV-related hospitalizations were identified from the nationwide hospital claims database in France (PMSI) from 2012 to 2021 using ICD-10 codes J12.1, J20.5, J21.0 or B97.4, and outcomes assessment focused on 2016-2020. In-hospital outcomes included length of stay, need for intensive care (ICU) and in-hospital all-cause mortality. Post-discharge outcomes included 30-day readmission for decompensation, 90-day RSV-related readmission, and 30 and 60-day in-hospital mortality. RESULTS: A cumulated number of 17 483 RSV-related stays were identified representing a rate of 72.0 cases per million stays. The outcomes assessment included 12,987 patients: 55.8 % were females and the mean age was 74.1 ± 16.4 years, with 57 % ≥ 75 years. Most of patients (78.6 %) had at least one comorbidity, mainly chronic respiratory (56.3 %) and cardiovascular diseases (41.3 %), or diabetes (23.5 %). A co-infection was found in 22.4 %, primarily bacterial (12 %). The mean length of stay was 12.3 ± 13.1 days. Overall, 10.9 % were admitted to an ICU and in-hospital mortality was 7.3 %. In-hospital outcomes were higher in cases of co-infection. Among 12 033 patients alive at discharge from the index stay, 6.5 % were readmitted with RSV within 90 days, 8.1 % for decompensation within 30 days, and 5.6 % died within 60-day. CONCLUSION: This study demonstrated the high burden of RSV infections in older adults and those with chronic conditions, and the need for preventive strategies.

Important Decrease in Hospitalizations for Acute Diabetes Events Following FreeStyle Libre System Initiation in People with Type 2 Diabetes on Basal Insulin Therapy in France.

Aims/Hypothesis: Initiation of insulin therapy in people with type 2 diabetes (T2DM) may be necessary to achieve glycemic targets but is associated with acute diabetes events (ADEs), including severe hypoglycemia (SH) or diabetic ketoacidosis (DKA). We assessed the impact of initiating FreeStyle Libre® system (FSL) on hospitalizations for ADEs in people with T2DM on basal insulin only regimen±noninsulin antidiabetic drugs. Materials and Methods: A retrospective study of the French national Système National des Données de Santé reimbursement claims database (≈66 million French people) identified people with T2DM on basal insulin therapy receiving a first reimbursement of FSL between August 1, 2017 and December 31, 2018. Claims data for the 12 months before, and up to 24 months after FSL initiation, were analyzed. Hospitalizations for ADEs were identified, using ICD-10 codes as main or related diagnosis, for: SH events; DKA events; comas; and hyperglycemia-related admissions. Results: A total of 5933 people with T2DM on basal insulin therapy initiated FSL during the selection period. Of the patients, 78.9% were on basal insulin and other hypoglycemic agents. Among the 5933 patients identified, 2.01% had at least one hospitalization for any ADE in the year before FSL initiation, compared to 0.75% (1 year) and 0.60% (2 years). Reductions in ADEs were driven by 75% fewer DKA admissions, with a 44% reduction in SH admissions. These patterns of reduced ADEs persisted after 2 years, with a further 43% reduction in DKA rates. Conclusions/Interpretation: This study emphasizes the value of the FSL system in reducing ADEs in people with T2DM in France not on intensive insulin therapy and initially treated with basal-only insulin therapy.

Reduced Acute Diabetes Events After FreeStyle Libre System Initiation in People 65 Years or Older with Type 2 Diabetes on Intensive Insulin Therapy in France.

Background and Aims: Older people with type 2 diabetes (T2DM) on insulin are at increased risk of hypoglycemia and associated morbidity. Management of T2DM in older people must optimize glycemic control, while minimizing risks for hypoglycemia and diabetic ketoacidosis (DKA). In France, the FreeStyle Libre® (FSL) system has been reimbursed since June 2017 for T2DM on intensive insulin therapy. We assessed the impact of starting FSL on hospitalizations for acute diabetes events (ADEs) in people ≥65 years old, with T2DM on intensive insulin therapy. Materials and Methods: A retrospective study on the French Système National des Données de Santé (SNDS) claims database was conducted on people ≥65 years old with T2DM, treated with multiple daily injections (MDI) or insulin pump and starting FSL between August 1, 2017, to December 31, 2018. The analysis covered claims data for 12 months before, and up to 24 months after FSL initiation. Hospitalizations for severe hypoglycemia (SH), DKA, comas, and hyperglycemia were identified using ICD-10 codes. Results: We identified 38,312 people with T2DM ≥65 years old on intensive insulin therapy initiating FSL during the selection period. Hospitalizations for ADEs were observed in 1.6% of subjects in the 12 months before FSL initiation, compared to 1.05% after 12 months and 0.96% after 24 months, a -34% and -40% reduction, driven by fewer DKA admissions after 12 months and by fewer SH admissions at 24 months. Conclusions: These results indicate that FSL can reduce hospitalization for ADEs in this vulnerable older population of adults 65 years of age and older with T2DM on intensive insulin therapy, in whom optimal glycemic control must be achieved, while minimizing risk of hypoglycemia and other ADEs.

Patient healthcare trajectories of intrahepatic cholangiocarcinoma in France: A nationwide retrospective analysis.

BACKGROUND: Little is known about the epidemiology and patterns of care of intrahepatic cholangiocarcinoma (iCCA) in daily clinical practice. The aims of this study were to estimate the number of declared cases during the study period 2014-2015 in France from a hospitalization database and to describe the healthcare trajectories of these patients. METHODS: A retrospective analysis was carried out using the French nationwide prospective hospitalization database. All pts with a new diagnosis of "carcinoma of the intrahepatic bile duct" who had a first hospital stay in the Medicine, Surgery and Obstetrics departments (MSO) between 2014 and 2015 with a 2-year follow-up were included. Data related to the first identified stay (S1) in the MSO and on all subsequent stays in the MSO, aftercare and rehabilitation or home hospitalization were analysed. FINDINGS: A total of 3650 new iCCA cases were identified. At S1 (admission via emergency room (ER) in 28%), the median age of the patients was 73 years, 57% were male and 35% had metastases. Jaundice/anaemia/ascites/cholangitis were reported in 17%/16%/12%/7% of patients, respectively. The care of patients at S1 was mainly provided in general hospitals (CHG, 60%). A total of 896 (24%) patients died during S1. They were more frequently hospitalized via the ER (48% vs 23%), metastatic (52% vs 35%) and symptomatic. Subsequent stays were identified for 2507 (69%) patients. Three healthcare pathways were defined: surgery (n = 519; 14%), chemotherapy (CT) without surgery (n = 812; 22%) and best supportive care (BSC) (n = 2319; 63%). CT, surgery and BSC were most frequently performed in the cancer centres, university hospitals and CHG, respectively. INTERPRETATION: This medico administrative study reveals a higher number of iCCA cases than that previously reported by registries and highlights the severity of this disease. FUNDING: This study was sponsored by Incyte Biosciences International Sàrl., Geneva, Switzerland. INCYTE validated the design of the study, the analysis, the interpretation of data and the writing of the manuscript which was first written by the 2 experts and CEMKA.

Long-Term Mortality and State Financial Support in Invasive Meningococcal Disease-Real-World Data Analysis Using the French National Claims Database (SNIIRAM).

OBJECTIVES: Invasive meningococcal disease (IMD) is an uncommon disease known for its acute phase mortality and long-term sequelae. The objective was to assess the impact of IMD on post-discharge mortality risk and dependence on the French state for financial aid. METHODS: A 6-year retrospective analysis in the national insurance database (SNIIRAM) assessed mortality in IMD cases (both during acute phase and post-discharge) and matched controls as well as benefit claims (i.e., for salary loss compensation [SLC], long-term sickness [ALD] and complementary health insurance [CMUc]). Observed survival data were extrapolated to estimate lifetime life expectancy following IMD. RESULTS: Between 2012 and 2017, 3532 incident IMD cases were hospitalised in France (peak in < 2 years and 15-24 year olds), of which 23.3% developed sequelae. With an average follow-up of 2.8 years, 12.9% of cases vs. 3.2% of controls died (p < 0.0001), with significantly more cases than controls dying both during the acute phase and post-discharge. Around a third of these deaths occurred post-discharge. Extrapolation to lifetime life expectancy estimated that having IMD at any age significantly reduces life expectancy in survivors of the acute disease phase, e.g., by around 16 years for cases aged 0-50 years. IMD cases in France were significantly more likely to receive state-funded SLC (relative risk [RR] 3.9, 95% confidence interval [95% CI] 2.3-6.4) and ALD benefits (RR 1.85, 95% CI 1.71-2.00). CONCLUSIONS: IMD has a significant impact on mortality post-discharge, expected to persist over a lifetime. In addition to long-term sequelae, the financial burden extends beyond the healthcare sector. These results highlight the importance of IMD prevention (e.g., vaccination).

Invasive meningococcal disease (IMD) is an uncommon disease mainly affecting children, with severe consequences such as a risk of dying within hours of symptoms and a risk of developing long-term conditions affecting health, learning and ability to work. Little is known of the risk of dying in survivors after discharge from hospital or of survivors' financial support needs. The French national insurance claims database (SNIIRAM) was reviewed for data on IMD patients hospitalised between 2012 and 2017 and matched controls without IMD. Data, available following IMD hospitalisation for an average of around 3 years, were extrapolated to estimate the lifelong impact of the disease. Among 3532 hospitalised IMD cases, the study found that nearly 13% died, of which a third of deaths occurred post-discharge. The cases who survived the acute disease phase were also more likely to require government funds because of loss of salary or to cover long-term healthcare costs. In addition to the well-known acute phase burden of IMD, this study has shown that there is a long-term effect on risk of dying and on need for government support. This demonstrates the importance of prevention, for example, by vaccination.

Trends in postmenopausal osteoporosis treatment in France during the period 2007-2016: A nationwide claims database analysis.

PURPOSE: To describe the trends in the pharmacological management of postmenopausal osteoporosis in France during the period 2007-2016. METHOD: This cross-sectional, yearly repeated study of patients in France used the nationwide claims database 'Échantillon Généraliste de Bénéficiaires' (EGB), covering a 1 in 97 representative sample of approximately 600,000 individuals insured by the main French public insurance scheme. For women aged 50-89 years, prescriptions for all anti-osteoporosis medications (AOMs) marketed in France during the study period (bisphosphonates alone or used in combination with calcium, selective estrogen receptor modulators, strontium ranelate, teriparatide or denosumab) were identified in each calendar year. Initiation of any AOM in a calendar year was defined by the absence of a prescription for any AOM within the 2 previous calendar years. Incidence was calculated for all AOM prescriptions and initial prescriptions for AOM. RESULTS: Marked changes were observed in the rates of women receiving any AOM, with a slight increase from 2007 to 2009 (from 10.22 to 10.42 per 100 patient-years [PY]), then a plateau in 2009-2010, followed by a rapid and more than twofold decrease until 2016 (from 10.39 to 5.02 per 100 PY). The decrease in the overall rate of women initiating an AOM showed a rapid halving from 2007 to 2012 (from 2.56 to 1.15 per 100 PY), followed by a plateau in the range of 0.90-1.0 per 100 PY during the period 2013-2016. In contrast, the use of calcium/vitamin D has been rapidly increasing as the only prevention and exclusive intervention for postmenopausal osteoporosis, from 10.6% of women in 2007 to 47.7% in 2016. The profile of patients initiating AOM changed substantially over the 10-year period. Despite a stable mean age of approximately 69 years, an increasing proportion of women with severe chronic comorbidities (from 34.9% to 43.3%), history of fractures (from 7.8% to 13.3%) or high-dose steroid use (from 2.9% to 8.4%) was observed. The decline of AOM initiation was associated with a marked reduction of prescriptions during the study period: by 64.2% for primary care physicians; by 36.7% for specialty doctors; and by 18.4% for rheumatologists. CONCLUSION: These findings suggest a general trend toward an AOM uptake that is increasingly limited to a fraction of patients who are at high risk of fractures. In the context of an aging population and declining prescription rates for AOM, these data highlight an increasing treatment gap among women in France with osteoporosis, which is similar to that seen in other European countries and in the USA.

Reduced Rate of Acute Diabetes Events with Flash Glucose Monitoring Is Sustained for 2 Years After Initiation: Extended Outcomes from the RELIEF Study.

Background: The RELIEF study has previously shown a fall in the rate of acute diabetes events (ADEs) in people living with type 1 diabetes (PwDT1) or people living with type 2 diabetes (PwDT2) in the 12 months after initiation of flash glucose monitoring (FLASH) in France. The 2-year follow-up has provided new insights on the frequency of ADEs, including severe hypoglycemia and diabetic ketoacidosis (DKA), during use of FLASH. Methods: The RELIEF study included 31,446 PwDT1 and 41,027 PwDT2 with a first delivery of FreeStyle Libre (FSL) between August 1 and December 31, 2017. Hospitalizations for DKA, severe hypoglycemia, diabetes-related coma, and hyperglycemia were recorded for the 12 months before and 24 months after FSL initiation. Persistence of the FSL system use was estimated through a Kaplan-Meier survival curve. Change in usual blood glucose monitoring was estimated through acquisition of blood glucose test strips. Results: In the 2 years after FSL initiation, hospitalizations for ADEs were reduced by 49% and by 48% in PwDT1 or PwDT2, respectively, driven by reductions in DKA. After 2 years, 88% of patients persisted with the system and estimated mean consumption of blood glucose test strips had fallen after 2 years by -82% and by -84% in type 1 diabetes mellitus and type 2 diabetes mellitus, respectively. Conclusion: Use of FSL consistently reduces the rates of hospitalization for ADEs, mainly DKA, 2 years after initiation, confirming this is not a transitory effect. Use of FSL also results in a clear and progressive drop in use of blood glucose test strips over the 2-year period.

Care pathways in invasive meningococcal disease: a retrospective analysis of the French national public health insurance database.

Invasive meningococcal disease (IMD) carries a high burden in terms of mortality, long-term complications, and cost, which can be significantly reduced by vaccination. The objectives of this case-control study were to document the care pathways of patients with IMD before, during, and after hospitalization and to assess in-hospital complications and long-term sequelae. Cases consisted of all people hospitalized for IMD in France between 2012 and 2017. Controls were matched by age, gender, and district of residence. Data were extracted from the French national public health insurance database on demographics, hospitalizations, mortality and potential sequelae of IMD. Overall, 3,532 cases and 10,590 controls were assessed and followed up for 2.8 years (median). During hospitalization, 1,577 cases (44.6%) stayed in an intensive care unit, 1,238 (35.1%) required mechanical ventilation, and 43 (1.2%) underwent amputation; 293 cases (8.3%) died in hospital and a further 163 (4.6%) died following discharge; 823 cases (25.4% of survivors) presented ≥1 sequela and 298 (9.2%) presented multiple sequelae. The most frequently documented sequelae were epilepsy (N = 205; 5.8%), anxiety (N = 196; 5.5%), and severe neurological disorders (N = 193; 5.5%). All individual sequelae were significantly more frequent (p < .0001) in cases than controls. Hearing/visual impairment and communication problems were conditions that presented the highest risk for cases compared to controls (risk ratios >20 in all cases). In conclusion, this study highlights the importance of providing optimal medical care for patients with IMD, of minimizing the delay before hospitalization, and of effective prevention through comprehensive vaccination programs.

Benefits of providing optimal medical care for IMD patients.Importance of minimising the delay before hospitalization.IMD remains challenging to diagnose, and vaccination is the most efficient way to prevent the disease and its complications.

Clinical added value of drugs: An empirical survey of French transparency committee opinions.

OBJECTIVES: To identify criteria used by French health authorities to assess the clinical added value (ASMR) of drugs seeking reimbursement. METHODS: We conducted a systematic review of the opinions of the transparency committee (TC) of the French national authority for health (HAS) between March, 2014 and October, 2016 in ten therapeutic areas. TC opinions content was coded and analysed using descriptive statistics and logistic models. RESULTS: The database comprised 160 opinion texts, which included ASMR assessments using a 5 level scale (1=highest ASMR 5=no ASMR). Main elements that were linked with ASMR 1,2,3,4 as compared to ASMR 5 were appraisal of the medical need, population size (<5000 patients), and clinical relevance of the evaluated results. The factors associated with ASMR 4 as compared to ASMR 1-3 were the safety profile and clinical relevance of the results. However, the factors associated with ASMR level varied according to the therapeutic area considered. CONCLUSIONS: The assessment of the drug ASMR conducted by the French transparency commission of the HAS appears to be at least in part determined by criteria (medical need, population size) which reflect the burden of the disease but not reflect the ASMR of the medicine assessed. Other criteria used for the assessment of ASMR are not clearly defined and depend on the therapeutic domain. The lack of sufficient clarity and consistency in assessment of ASMR complicate the decision making process for drug development. Moreover, this situation can be a barrier for a harmonized process of ASMR assessment at European level.

Risk factors for invasive meningococcal disease: a retrospective analysis of the French national public health insurance database.

Vaccination of at-risk populations against Neisseria meningitidis is an important strategy to prevent invasive meningococcal disease (IMD). The objective of this study was to characterize preexisting risk factors in patients with IMD and to compare their relative importance. This case-control analysis was performed in the French national public health insurance database (SNDS). Cases consisted of all people hospitalized for IMD in France over a six-year period (2012-2017). Controls were matched by age, gender, and district of residence. Medical risk factors were identified from ICD-10 codes in the SNDS. Socioeconomic risk factors studied were low household income and social deprivation of the municipality of residence. Associations of these risk factors with hospitalization for IMD were quantified as odds ratios (ORs) between cases and controls with their 95% confidence intervals (95%CI). The medical risk factors showing the most robust associations were congenital immunodeficiency (OR: 39.1 [95%CI: 5.1-299], acquired immunodeficiency (10.3 [4.5-24.0]) and asplenia/hyposplenia (6.7 [3.7-14.7]). In addition, certain chronic medical conditions, such as autoimmune disorders (5.4 [2.5-11.8]), hemophilia (4.7 [1.8-12.2]) and severe chronic respiratory disorders (4.3 [3.1-6.2]) were also strongly associated, as was low household income (1.68 [1.49-1.80]). In conclusion, this study has documented potential risk factors associated with hospitalization for IMD in a large and comprehensive sample of individuals with IMD in France. Several of the risk factors identified may help identify groups who could benefit from targeted prevention measures (such as vaccination) in order to reduce the burden of IMD.

Healthcare Resource Consumption and Cost of Invasive Meningococcal Disease in France: A Study of the National Health Insurance Database.

INTRODUCTION: Invasive meningococcal disease (IMD) is an uncommon but serious infectious disease. Its economic burden is known to be high but is poorly characterised. The objective of this study was to determine costs, as captured in the healthcare claims database, incurred by all patients hospitalised for IMD in France over a 6-year period. METHODS: This case-control study was performed using the French national public health insurance database (SNDS). Cases comprised all individuals hospitalised with acute IMD in France between 2012 and 2017 inclusive. For each case, three controls were identified, matched for age, gender and region of residence. All healthcare resource consumption by cases and controls during the follow-up period was documented. Costs were analysed for the index hospitalisation in cases, 1 year following the index date and then for 5 years following the index date. Costs were assigned from national tariffs. The analysis was performed from a societal perspective. IMD sequelae were identified from hospital discharge summaries. RESULTS: A total of 3532 cases and 10,590 controls were evaluated. The mean per capita cost of the index IMD hospitalisation was €11,256, and increased with age and with the presence of sequelae. In the year following the index date, mean per capita direct medical costs were €6564 in cases and €2890 in controls. Annual costs were €4254 in cases without sequelae, €10,799 in cases with one sequela and €20,096 in cases with more than one sequela. In the fifth year of follow-up, mean per capita costs were €2646 in cases and €1478 in controls. The excess cost in cases was principally due to the management of sequelae. Amputation, skin scarring and mental retardation generated per capita costs in excess of €20,000 in the first year and in excess of €10,000 for subsequent years. CONCLUSION: The economic burden of IMD in France is high and, over the long-term, is driven by sequelae management.

Important Drop in Rate of Acute Diabetes Complications in People With Type 1 or Type 2 Diabetes After Initiation of Flash Glucose Monitoring in France: The RELIEF Study.

OBJECTIVE: The RELIEF study assessed rates of hospitalization for acute diabetes complications in France before and after initiation of the FreeStyle Libre system. RESEARCH DESIGN AND METHODS: A total of 74,011 patients with type 1 diabetes or type 2 diabetes who initiated the FreeStyle Libre system were identified from the French national claims database with use of ICD-10 codes, from hospitalizations with diabetes as a contributing diagnosis, or the prescription of insulin. Patients were subclassified based on self-monitoring of blood glucose (SMBG) strip acquisition prior to starting FreeStyle Libre. Hospitalizations for diabetic ketoacidosis (DKA), severe hypoglycemia, diabetes-related coma, and hyperglycemia were recorded for the 12 months before and after initiation. RESULTS: Hospitalizations for acute diabetes complications fell in type 1 diabetes (-49.0%) and in type 2 diabetes (-39.4%) following FreeStyle Libre initiation. DKA fell in type 1 diabetes (-56.2%) and in type 2 diabetes (-52.1%), as did diabetes-related comas in type 1 diabetes (-39.6%) and in type 2 diabetes (-31.9%). Hospitalizations for hypoglycemia and hyperglycemia decreased in type 2 diabetes (-10.8% and -26.5%, respectively). Before initiation, hospitalizations were most marked for people noncompliant with SMBG and for those with highest acquisition of SMBG, which fell by 54.0% and 51.2%, respectively, following FreeStyle Libre initiation. Persistence with FreeStyle Libre at 12 months was at 98.1%. CONCLUSIONS: This large retrospective study on hospitalizations for acute diabetes complications shows that a significantly lower incidence of admissions for DKA and for diabetes-related coma is associated with use of flash glucose monitoring. This study has significant implications for patient-centered diabetes care and potentially for long-term health economic outcomes.