Severity and burden of sickle cell disease in France: a nationwide real-world study.

The burden of sickle cell disease (SCD) in France has been difficult to apprehend due to the paucity of reliable nationwide epidemiological data. We aimed to describe the epidemiology of SCD and evaluate its burden and costs. Patients with SCD and most severely affected patients were identified between 2012 and 2018 from the French National Health Data System database (SNDS, Système national des données de santé). Outcomes of interest included rates of acute and chronic complications, healthcare resource utilization and associated costs, and were compared in subpopulations of patients before and after hematopoietic stem cell transplantation, initiating hydroxyurea or a chronic transfusion program. Between 2012 and 2018, 22,619 patients with SCD were identified, among which 4,270 patients were defined as most severely affected. Rates of vaso-occlusion episodes and acute chest syndrome were 86.29 (95% confidence interval [CI]: 85.75-86.83] and 12.90 (95% CI: 12.69-13.11) per 100 person years in the study population and 166.9 (95% CI: 165.4- 168.4) and 22.71 (95% CI: 22.16-23.27) per 100 person years in most severely affected patients. Median (Q1-Q3) annualized total costs were €5,073.63 (range, €1,633.74-14,000.94) and €13,295.67 (range, €5,754.67-26,385.23) in the study population and most severely affected patients. Median annualized costs were ten times lower after treatment intensification for hematopoietic stem cell transplantation (€29,011.75 vs. €2,465.98; P<0.001), they slightly decreased after hydroxyurea initiation (€13,057.79 vs. €12,752.44; P=0.003) and were five times higher after chronic transfusion program initiation (€4,643.11 vs. €22,715.85; P<0.001). SCD still places a significant demand on health resources, even after therapeutic intensification.

Population characteristics, management, and survival outcomes in muscle-invasive urothelial carcinoma undergoing radical resection: the MINOTAUR study.

PURPOSE: To describe the incidence, management, and survival outcomes of patients with muscle-invasive urothelial carcinoma (MIUC) undergoing radical surgery (RS) in France. METHODS: We relied on a non-interventional real-world retrospective study based on French National Hospitalization Database. Adults with MIUC with a first RS between 2015 and 2020 were selected. Subpopulations of patients with RS performed in 2015 and 2019 (pre-COVID-19) were extracted, according to cancer site: muscle-invasive bladder cancer (MIBC) or upper tract urothelial carcinoma (UTUC). Disease-free and overall survival (DFS, OS - Kaplan-Meier) were assessed on the 2015 subpopulation. RESULTS: Between 2015 and 2020, 21,295 MIUC patients underwent a first RS. Of them, 68.9% had MIBC, 28.9% UTUC, and 2.2% both cancers. Apart from fewer men among UTUC (70.2%) than MIBC patients (90.1%), patients' demographic (mean age ~ 73 years) and clinical characteristics were similar whatever the cancer site or year of first RS. In 2019, RS alone was the most frequent treatment, occurring in 72.3% and 92.6% in MIBC and UTUC, respectively. Between 2015 and 2019, neoadjuvant use rate increased from 13.8% to 22.2% in MIBC, and adjuvant use rate increased from 3.7% to 6.3% in UTUC. Finally, median [95% confidence interval] DFS times were 16.0 [14.0-18.0] and 27.0 [23.0-32.0] months among MIBC and UTUC, respectively. CONCLUSION: Among patients with resected MIUC annually, RS alone remained the main treatment. Neoadjuvant and adjuvant use increased between 2015 and 2019. Nonetheless, MIUC remains of poor prognosis, highlighting an unmet medical need, notably among patients at high risk of recurrence.

Economic burden of in-hospital AKI: a one-year analysis of the nationwide French hospital discharge database.

BACKGROUND: Although Acute Kidney Injury (AKI) incidence is increasing worldwide, data investigating its cost are lacking. This population-wide study aimed to describe the characteristics and costs of hospital stays with, and without AKI, and to estimate the AKI-associated increases in costs and length of stay (LOS) in three subgroups (major open visceral surgery (MOV), cardiovascular surgery with extracorporeal circulation (CVEC), and sepsis). METHODS: All hospital stays that occurred in France in 2018 were included. Stay and patient characteristics were collected in the French hospital discharge database and described. Medical conditions were identified using the 10th International Classification of Diseases and the medical acts classification. In each subgroup, the adjusted increase in cost and LOS associated with AKI was estimated using a generalized linear model with gamma distribution and a log link function. RESULTS: 26,917,832 hospital stays, of which 415,067 (1.5%) with AKI, were included. AKI was associated with 83,553 (19.8%), 7,165 (17.9%), and 15,387 (9.2%) of the stays with sepsis, CVEC, and MOV, respectively. Compared to stays without AKI, stays with AKI were more expensive (median [IQR] €4,719[€2,963-€7782] vs. €735[€383-€1,805]) and longer (median [IQR] 9[4-16] vs. 0[0-2] days). AKI was associated with a mean [95%CI] increase in hospitalization cost of 70% [69;72], 48% [45;50], and 68% [65;70] in the sepsis, CVEC, and MOV groups respectively, after adjustment. CONCLUSION: This study confirms the major economic burden of in-hospital AKI in a developed country. Interventions to prevent AKI are urgently needed and their cost should be balanced with AKI-related costs.

Renal Replacement Therapy Modality in the ICU and Renal Recovery at Hospital Discharge.

OBJECTIVES: Acute kidney injury requiring renal replacement therapy is a major concern in ICUs. Initial renal replacement therapy modality, continuous renal replacement therapy or intermittent hemodialysis, may impact renal recovery. The aim of this study was to assess the influence of initial renal replacement therapy modality on renal recovery at hospital discharge. DESIGN: Retrospective cohort study of all ICU stays from January 1, 2010, to December 31, 2013, with a "renal replacement therapy for acute kidney injury" code using the French hospital discharge database. SETTING: Two hundred ninety-one ICUs in France. PATIENTS: A total of 1,031,120 stays: 58,635 with renal replacement therapy for acute kidney injury and 25,750 included in the main analysis. INTERVENTIONS: None. MEASUREMENTS MAIN RESULTS: PPatients alive at hospital discharge were grouped according to initial modality (continuous renal replacement therapy or intermittent hemodialysis) and included in the main analysis to identify predictors of renal recovery. Renal recovery was defined as greater than 3 days without renal replacement therapy before hospital discharge. The main analysis was a hierarchical logistic regression analysis including patient demographics, comorbidities, and severity variables, as well as center characteristics. Three sensitivity analyses were performed. Overall mortality was 56.1%, and overall renal recovery was 86.2%. Intermittent hemodialysis was associated with a lower likelihood of recovery at hospital discharge; odds ratio, 0.910 (95% CI, 0.834-0.992) p value equals to 0.0327. Results were consistent across all sensitivity analyses with odds/hazards ratios ranging from 0.883 to 0.958. CONCLUSIONS: In this large retrospective study, intermittent hemodialysis as an initial modality was associated with lower renal recovery at hospital discharge among patients with acute kidney injury, although the difference seems somewhat clinically limited.

Outcomes, risk factors and health burden of contrast-induced acute kidney injury: an observational study of one million hospitalizations with image-guided cardiovascular procedures.

BACKGROUND: Despite the use of low-osmolar contrast media that have significantly reduced the occurrence of severe adverse reactions, contrast-induced (CI) acute kidney injury (AKI) remains the third cause of AKI in hospitals. We sought to estimate the frequency of CI-AKI among hospitalized patients undergoing image-guided cardiovascular procedures, to quantify the effect of risk factors on the development of this complication and to assess relative organizational and economic burden in healthcare. METHODS: A retrospective cross-sectional population-based study using the extensive French hospital discharge database (PMSI) was carried out. Hospitalizations with image-guided cardiovascular procedures using a contrast media were identified in adults over a 2-year period (2012-2013). Suspected CI-AKI was defined as the presence, during hospitalization, of a diagnostic code of AKI (International Classification of Diseases, 10th revision [ICD-10] codes: N141, 142, N144, N990, N17, N19 or R392) or a code of renal replacement therapy procedure (Classification Commune des Actes Médicaux [CCAM] codes: JVJB001, JVJF002-005 and JVJF008) as creatinine criteria were not available. RESULTS: During 1,047,329 hospitalizations studied, 32,308 suspected CI-AKI were observed, yielding a frequency of 3.1 %. By multivariate analysis, factors that significantly increased the risk of suspected CI-AKI included cardiogenic shock (odds ratio [OR] = 20.5, 95 % confidence interval [95 % CI] [18.7; 22.5]), acute heart failure (OR = 2.5, 95 % CI [2.4; 2.6]) and chronic kidney disease (OR = 2.3, 95 % CI [2.2; 2.3]. Renal replacement therapy was initiated during 6,335 (0.6 %) hospitalizations. The mean length of stay and cost of hospitalizations associated with suspected CI-AKI was higher than in hospitalizations without suspected CI-AKI (20.5 vs 4.7 days, p < 0.00001 and €15,765 vs €3,352, p < 0.0001, respectively). CONCLUSIONS: This is the first large-scale population-based study to estimate frequency and health burden of suspected CI-AKI occurring after image-guided cardiovascular procedures, and the first available data in a French population. We showed that this iatrogenic complication remains of high concern despite prevention efforts and contrast media product improvement. From our results, suspected CI-AKI is associated with particularly high mortality, significantly extends hospitalizations, and leads to additional costs reaching a total of €200M per year.

Acute Ischemic Stroke (AIS) patient management in French stroke units and impact estimation of thrombolysis on care pathways and associated costs.

BACKGROUND: Stroke is the second leading cause of death and a first leading cause of acquired disability in adults worldwide. This study aims to evaluate the current management and associated costs of acute ischemic stroke (AIS) for patients admitted in stroke units in France and over a one-year follow-up period as well as to assess the impact of improved thrombolytic management in terms of increasing the proportion of patients receiving thrombolysis and/or treated within 3 h from the onset of symptoms. METHODS: A decision model was developed, which comprises two components: the first corresponding to the acute hospital management phase of patients with AIS up until hospital discharge, extracted from the national hospital discharge database (PMSI 2011), and the second corresponding to the post-acute (post-discharge) phase, based on national treatment guidelines and stroke experts' advice. Five post-acute clinical care pathways were defined. In-hospital mortality and mortality at 3 months post-discharge was taken into account into the model. Patient journeys and costs were determined for both phases. Improved thrombolytic management was modeled by increasing the proportion of patients receiving thrombolysis from the current estimated level of 16.7 to 25% as well as subsequently increasing the proportion of patients treated within 3 h of the onset of symptoms post-stroke from 50 to 100%. The impact on care pathways was derived from clinical data. RESULTS: Among 202,078 hospitalizations for a stroke or a transient ischemic attack (TIA), 90,528 were for confirmed AIS, and 33% (29,999) of them managed within a stroke unit. After hospitalization, 60% of discharges were to home, 25% to rehabilitative care and then home, 2% to rehabilitative care and then a nursing home, 7% to long-term care, and 6% of stays ended with patient death. Of a total cost over 1 year of €610 million (mean cost per patient of €20,326), 70% concern the post-acute phase. By increasing the proportion of patients being thrombolyzed, costs are reduced primarily by a decrease in rehabilitative care, with savings per additional treated patient of €1,462. By adding improved timing, savings are more than doubled (€3,183 per additional treated patient). CONCLUSIONS: This study confirms that the burden of AIS in France is heavy. By improving thrombolytic management in stroke units, patient journeys through care pathways can be modified, with increased discharges home, a change in post-acute resource consumption and net savings.

Epidemiology and health impact of diabetes in France.

OBJECTIVES: Diabetes is a growing health concern. An update on epidemiology and health outcomes is mandatory to devise strategies to alleviate the burden of diabetes. The objective of this study was to assess the prevalence of diabetes and associated complications in France in 2017. METHODS: Demographics and healthcare data from a representative permanent secondary database were analyzed. Patients with at least 2 national health insurance payments for anti-diabetic drugs in 2017 were selected, with the index date set to the last payment date. Patients were grouped as diabetes treated with insulin only (DTi), diabetes treated with anti-diabetic drugs other than only insulin (DT2) or gestational diabetes. Comorbidities, diabetes-related complications and hospital admissions, healthcare consumption and medical follow-up were extracted for a 5- or 2-year period prior to the index date and summarized using descriptive statistics. RESULTS: Overal, 29,288 patients were included in the study population: 1964 (6.7%) were categorized as DTi and 27,243 (93.0%) as DT2. Patients with gestational diabetes (81 [0.3%]) are not further described here. Prevalence was estimated at 4.9%. For DT2, marked geographic disparities were observed, with prevalence being highest in the northeast France. Diabetes-related complications were more frequent in DTi than in DT2 over a 5-year period (52.2% vs 34.7%). Diabetes-related admissions were also more common in DTi than in DT2 over a 2-year period (29.8% vs 16.9%). In the DT2 category, another antidiabetic drug was added during the 3 months prior to the index date in 16.5% of cases overall and in 25% of patients with recent hospital admission or diabetes-related complications. Although more than 80% of patients in the DTi and DT2 categories had at least 1 healthcare consultation during 2 years prior to the index date, only 10% to 20% of patients complied with guidelines for all 5 recommended examinations. CONCLUSIONS: Prevalence of diabetes is high in the French population, while compliance with recommended healthcare consultations falls short of the 80% goal set by regulations. New strategies are mandatory in order to reduce the burden of diabetes-related complications and admissions, focusing on patient and physician information and education in order to increase proactive treatment adjustment and reduce therapeutic inertia.

Prevalence and cost of sickle cell disease in France: real-world analysis using data from the Echantillon Généraliste des Bénéficiaires.

Sickle cell disease (SCD) is a genetic disorder of the hemoglobin resulting in chronic anemia, hemolysis, and vaso-occlusions. Its treatment mostly relies on hydroxycarbamide, transfusions, and stem cell transplantation. This study aimed at describing the epidemiology and management of SCD in adolescent and adult patients in France. This was a retrospective study performed among SCD patients aged ≥12 years between 2016 and 2018 and controls. SCD patients were matched on a 1:3 ratio with a group of individuals with no diagnosis of SCD, referred as control group. The matching of SCD patients and controls was a direct matching based on age, sex, CMU-c status (which corresponds to free-of-charge complementary coverage for people with low resources) and geographical region of residence. SCD patients and their matched controls were followed-up for the same amount of time by adjusting controls' follow-up period to that of the associated patients. This study used claims data from the French representative 1/97th sample of health data system. The main outcomes were the patients' characteristics and treatments received, healthcare consumptions and related costs among SCD cases and controls. Between 2016 and 2018, 151 patients with ≥6 months of follow-up were identified out of the total population of 732,164 individuals. SCD prevalence extrapolated to the entire population [95% CI] was 19,502 [19,230, 19,778] in 2018. The median (Q1-Q3) age at inclusion date was 37.0 (25.0-48.0) years, with 69.5% of patients being female. The mean (SD) reimbursed cost over follow-up was €24,310 (89,167), mostly represented by hospitalization costs accounting for €21,156 (86,402). A switch in SCD management was observed with age, as younger patients presented more frequent hospitalizations and acute procedures, while older ones had more frequent medical visits and paramedical care. Mean (SD) annual costs were €25,680 (91,843) and vs. €3,227 (23,372) for patients and controls, respectively (p < 0.001), representing an extra cost of almost €150 million over the entire SCD population. This study highlighted the important costs related to SCD and the related medical need with treatment alternatives, which could be filled by the emergence of new therapies.

Childhood cerebral adrenoleukodystrophy (CCALD) in France: epidemiology, natural history, and burden of disease - A population-based study.

BACKGROUND: X-linked adrenoleukodystrophy (ALD) is a rare metabolic and neurodegenerative disorder belonging to the group of leukodystrophies, with an estimated incidence around 1:25 000 newborns worldwide, mostly among men. Childhood Cerebral ALD (CCALD) is the most severe form with a poor prognosis if not properly treated during the first years of life. Currently, only allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely available for CCALD treatment. To date, there is a lack of data regarding CCALD epidemiology, natural history, and current management in France. This knowledge is crucial for the development of new therapies such as gene therapies. In this context, the French National Health Data System (SNDS) is a particularly indicated database to collect information meeting these needs. A non-interventional, national, real-life, retrospective study was performed using secondary data from the national ALD registry (LEUKOFRANCE) and SNDS. CCALD patients detected between 2009 and 2018 and successfully matched between LEUKOFRANCE and SNDS were included in this study. Index date was defined as the first CCALD event detected during study period. Subgroups of patients with sufficient follow-up (6 months) and history (1 year) available around index date were analyzed to assess CCALD burden and natural history. RESULTS: 52 patients were included into the matched cohort. Median annual incidence of CCALD was estimated at 4 patients. Median age at CCALD diagnosis was 7.0 years. Among patients without allo-HSCT, five-year overall survival was 66.6%, with 93.3% of them presenting at least one CCALD symptom and 62.1% presenting a least one major functional disability (MFD). Among patients with allo-HSCT, five-year overall survival was 94.4%, with only 11.1% of patients presenting CCALD symptoms, and 16.7% of presenting a MFD. Mean annualized costs were almost twice as important among patients without allo-HSCT, with 49,211€, 23,117€, respectively. Costs were almost exclusively represented by hospitalizations. CONCLUSIONS: To the best of our knowledge, this is the most up to date study analyzing CCALD epidemiology, clinical and economic burden in France. The necessity of a precocious management with HSCT highlight the potential benefits of including an expanded screening program among newborns, coupled with family screenings when a mutation is detected.

Suboptimal management of rheumatoid arthritis in France: a real-world study based on data from the French National Health Data System.

OBJECTIVES: The emergence of targeted therapy is changing rheumatoid arthritis (RA) management, but real-world data remain limited. This study aimed to describe real-world RA treatment patterns using data from a French national claims database. METHODS: This longitudinal study used the French Permanent Representative Sample (Echantillon Généraliste des Bénéficiaires) claims database. Patients with RA were identified between 2013 and 2017, with treatment patterns, persistence and adherence described. RESULTS: The study population included 2553 patients with RA. Disease-modifying antirheumatic drugs (DMARDs) were prescribed for 1512 (59.2%) patients, of whom 721 (47.6%) did not require discontinuation or treatment switch. There were 377 (24.9%) treatment discontinuations and 114 patients (7.5%) switched to a targeted DMARD (biological and synthetic (Janus kinase inhibitor) DMARDs). Among the 2315 patients with RA in 2017, almost half (n=1102, 47.6%) were not treated with a DMARD. Most (85.7%) received symptomatic treatment (analgesics (81.0%), steroids (49.2%), non-steroidal anti-inflammatory drugs (39.5%)). Of the 1142 treatment initiations identified, 713 (62.4%) were conventional synthetic DMARDs (csDMARDs), with methotrexate being the most frequent (n=553, 48.45%). One-year persistence rates varied between 55.9% (49.2-62.0%) for tumour necrosis factor inhibitors, and 63.4% (59.6-67.0%) for csDMARDs. Treatment adherence, assessed through medication possession ratio, varied between 71.9% and 90.8%, with ≥80% being the adherence cut-off. Almost half of DMARD initiations were associated with long-term (>6 months), high-dose oral steroid use (~7 mg/day prednisone equivalent). CONCLUSION: Despite a diverse therapeutic arsenal, there remains a medical need that is not covered by current RA management, which is frequently compensated for by overprescription of steroids.

A database study of clinical and economic burden of invasive meningococcal disease in France.

OBJECTIVE: Invasive meningococcal disease (IMD) is life-threatening and associated with substantial morbidity and mortality. The study aimed to examine the clinical characteristics and hospital-based healthcare resource use and related costs following IMD diagnosis in France. METHODS: Patients admitted to hospitals due to IMD between 2014 and 2016 were selected from the French hospital discharge database (PMSI). Demographics, clinical outcomes and health utilization (HRU) during index hospitalization were described. HRU and costs during the follow-up period were also examined. A generalized linear model was applied to examine 1-year costs after index hospitalization adjusting for age, type of IMD and presence of sequelae at index hospitalization. RESULTS: A total of 1,344 patients were identified. About 30% cases were in children < 5 years old and 25% aged 10-24 years. Majority of patients presented as meningococcal meningitis (59%), 25% as meningococcaemia, and 9% both. The case fatality rate during the index hospitalization was 6%. About 15% of patients had at least one sequela at index hospital discharge. The median length of stay and the median cost of index hospitalization were 9 days and 8,045€, respectively. Patients with at least one sequela, with clinical manifestation as both meningitis and meningococcaemia, or aged 25 years and older were statistically significantly associated with higher costs than others. CONCLUSION: IMD is unpredictable and can occur in all ages. The study highlights the severity and high health and economic burdens associated with the disease. The data underlines the importance of prevention against IMD through vaccination.

Real-life impact of uncontrolled severe asthma on mortality and healthcare use in adolescents and adults: findings from the retrospective, observational RESONANCE study in France.

OBJECTIVE: To characterise uncontrolled severe asthma and compare the disease burden with the general and asthmatic populations. DESIGN: Retrospective observational study using a national sample of a French healthcare database (Echantillon Généraliste des Bénéficiaires (EGB)). SETTING: The EGB, an anonymised permanent sample of health insurance databases, representing 1/97th of the French population. PARTICIPANTS: Patients (≥12 years) were selected in year 2014 and followed 2 years. A cohort of patients with uncontrolled severe asthma was defined using an algorithm based on peer-reviewed literature and Global Initiative for Asthma recommendations. Index date was the occurrence of the first marker of uncontrolled asthma. This cohort was matched with two control cohorts, general population and asthmatic controls, on baseline characteristics. MAIN OUTCOMES MEASURES: Mortality, healthcare use and associated costs were studied in the 2 years of follow-up. RESULTS: Among 467 716 individuals in the EGB, 16 588 patients with asthma were identified, including 739 (4.5%) with uncontrolled severe disease. The survival probability at 2 years for patients with uncontrolled severe asthma (92.0%) was lower than in the general population cohort (96.6%; relative risk of death: 2.35; 95% CI: 1.70 to 3.29; p<0.0001) and tended to be lower than in the control asthmatic cohort (94.3%; p=0.07). Emergency department visits and hospitalisations were higher in patients with uncontrolled severe asthma than in the general population (64.7% vs 34.9%; p<0.0001) and asthmatic controls (64.7% vs 55.2%; p=0.0002). Other components of healthcare use (medical and paramedical visits, medications) were increased in patients with uncontrolled severe asthma compared with control populations. These increases translated into higher costs (p<0.0001 for both comparisons). CONCLUSIONS: This study demonstrates the huge burden of uncontrolled severe asthma in terms of mortality, morbidity and healthcare resource consumption compared with other patients with asthma and with the general population and emphasises the importance of appropriate management in this high-risk population.

Real-life management of neovascular age-related macular degeneration (nAMD) in France: a nationwide observational study using retrospective claims data.

AIMS: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is standard care for neovascular age-related macular degeneration (nAMD), but the recommended monthly injection regimen is burdensome. Evidence suggests low injection/monitoring frequencies in clinical practice and suboptimal vision outcomes. This observational cohort study uses administrative claims data from the French national healthcare system to assess anti-VEGF treatment patterns and nAMD-specific healthcare resource demands and costs. PATIENTS AND METHODS: nAMD patients ≥50 years initiating intravitreal ranibizumab, aflibercept or bevacizumab treatment (2014‒2015), and propensity score-matched non-nAMD patients (controls), were identified from the Echantillon Généraliste de Bénéficiaires database. Outcomes of interest included anti-VEGF treatment patterns, and healthcare resource utilization and associated costs of patients vis-à-vis controls over 24 months. RESULTS: Study patients (n = 355) received (mean) 5.2 and 2.4 anti-VEGF injections over 0‒12 and 12‒24 months, respectively. Most patients (79.0%) remained on their initial anti-VEGF agent; among treatment switchers, the most common transition was from ranibizumab to aflibercept. During follow-up, nAMD patients were more likely than controls to require ophthalmology visits (99.7% vs. 44.8%), ocular procedures (optical coherence tomography/angiography/fundoscopy) (96.9% vs. 27.2%), cataract surgery (13.0% vs. 6.7%), and medical transports (38.0% vs. 31.9%). Mean numbers of ophthalmology visits (25.1 vs. 1.2) and medical transports (6.0 vs. 3.5) were higher (p<.01) among nAMD patients. Total reimbursed costs were two-fold higher for nAMD patients than controls (mean €16,799 vs. €8,255) due to higher treatment costs (€6,847 vs. €1,156), medical fees (€1,858 vs. €295), hospital fees (€6,396 vs. €5,235), and transport costs (€358 vs. €259). Excess total healthcare cost was (mean) €5,279 and €7,918 over the first 12 and 24 months of treatment, respectively. CONCLUSIONS: Current intravitreal anti-VEGF treatment and monitoring requirements place a considerable economic burden on the French healthcare system. New intravitreal therapies with extended dosing intervals and predictable efficacy might reduce demand for ophthalmology services.

Cervical cancer screening coverage, management of squamous intraepithelial lesions and related costs in France.

Until 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management.

Estimation of the incidence of genital warts and the cost of illness in Germany: a cross-sectional study.

BACKGROUND: Human papillomavirus (HPV) is a necessary cause of cervical cancer. HPV is also responsible for benign condylomata acuminata, also known as genital warts. We assessed the incidence of genital warts in Germany and collected information on their management to estimate the annual cost of disease. METHODS: This was a multi-centre observational (cross-sectional) study of genital warts in Germany. Data were collected from gynecologists, dermatologists, and urologists seeing patients with genital warts between February and April 2005. The number of patients with new and recurrent genital warts was used to estimate the incidence in Germany. We assessed resource use for patients with genital warts seen during a two-month period as well as retrospective resource use twelve months prior to the inclusion visit through a chart review. The mean costs of treatment of patients with genital warts from third-party payer and societal perspectives were estimated, and the total annual cost of genital warts was then calculated. RESULTS: For the incidence calculation 217 specialists provided information on 848 patients and 214 specialists provided resource use data for 617 patients to assess resource consumption. The incidence of new and recurrent cases of genital warts was 113.7 and 34.7 per 100 000, respectively, for women aged 14-65 years consulting gynecologists. The highest incidence was observed in women aged 14-25 years (171.0 per 100 000) for new cases and in women aged 26-45 years (53.1 per 100 000) for recurrent cases. The sample size for males was too small to allow a meaningful estimate of the incidence. The mean direct cost per patient with new genital warts was estimated at 378 euros (95% CI: 310.8-444.9); for recurrent genital warts at 603 euros (95% CI: 436.5-814.5), and for resistant genital warts at 1,142 euros (95% CI: 639.6-1752.3). The overall cost to third-party payers was estimated at 49.0 million euros, and the total societal cost at 54.1 million euros, corresponding to an average cost per patient of 550 euros and 607 euros, respectively. CONCLUSION: The societal burden and costs of managing and treating genital warts in Germany are considerable. A vaccination programme using the quadrivalent human papillomavirus vaccine could provide a substantial health benefit and reduce the costs associated with genital warts in Germany.

Adding a quadrivalent human papillomavirus vaccine to the UK cervical cancer screening programme: A cost-effectiveness analysis.

BACKGROUND: We assessed the cost-effectiveness of adding a quadrivalent (6/11/16/18) human papillomavirus (HPV) vaccine to the current screening programme in the UK compared to screening alone. METHODS: A Markov model of the natural history of HPV infection incorporating screening and vaccination was developed. A vaccine that prevents 98% of HPV 6, 11, 16 and 18-associated disease, with a lifetime duration and 85% coverage, in conjunction with current screening was considered. RESULTS: Vaccination with screening, compared to screening alone, was associated with an incremental cost-effectiveness ratio of pound21,059 per quality adjusted life year (QALY) and pound34,687 per life year saved (LYS). More than 400 cases of cervical cancer, 6700 cases of cervical intraepithelial neoplasia and 4750 cases of genital warts could be avoided per 100,000 vaccinated girls. Results were sensitive to assumptions about the need for a booster, the duration of vaccine efficacy and discount rate. CONCLUSION: These analyses suggest that adding a quadrivalent HPV vaccine to current screening in the UK could be a cost-effective method for further reducing the burden of cervical cancer.

Burden of rotavirus gastroenteritis and potential benefits of a pentavalent rotavirus vaccination in Belgium.

OBJECTIVE AND METHODS: A decision analytic model was built to assess the paediatric rotavirus gastroenteritis (RVGE) burden and potential benefits associated with the introduction of RotaTeq (pentavalent rotavirus vaccine) in Belgium. RESULTS: In the absence of a rotavirus (RV) immunisation programme, paediatric RVGE was estimated to account for about 5,860 hospitalisations, 1,720 cases of nosocomial infections, 9,410 cases treated by general practitioners/paediatricians (GP/P) and 10,790 cases not seeking medical care for a birth cohort followed up to 5 years of age. Paediatric RVGE was estimated to cost about euro9.0 million from the Belgian healthcare provider perspective and euro15.3 million to society. Given a 90% RV vaccination coverage rate, the pentavalent RV vaccine would have a high impact on RV burden by preventing more than 4,850 hospitalisations, 995 cases of nosocomial infections, 7,145 cases treated by GP/P and 8,190 cases not seeking medical care, and reduce RVGE costs by euro7.1 million from the Belgian healthcare provider perspective and euro12.0 million to society.

Health economic evaluation in idiopathic pulmonary fibrosis in France.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic, progressive, fibrosing interstitial pneumonia of unknown cause. To date, there is no specific cure for IPF, and only two treatments (pirfenidone and nintedanib) have marketing authorizations and recommendations in international and French guidelines. OBJECTIVES: A cost-utility analysis (CUA) has been conducted to evaluate the efficiency of nintedanib, in comparison to all available alternatives, in a French setting using the official methodological guidelines. METHODS: A previously developed lifetime Markov model was adapted to the French setting by simulating the progression of IPF patients in terms of lung function decline, incidence of acute exacerbations, and death. Considering the effect of IPF on patients' quality-of-life, a CUA integrating quality adjusted life years (QALY) was chosen as the primary outcome measure in the main analysis. One-way, probabilistic, and scenario sensitivity analyses were performed to evaluate the robustness of the model. RESULTS: Treatment with nintedanib resulted in an estimated total cost of €76,414 (vs €82,665 for pirfenidone). In comparison with all other available options, nintedanib was predicted to provide the most QALY gained (3.34 vs 3.29). This analysis suggests that nintedanib has a 59.0% chance of being more effective than pirfenidone and s 77.3% chance of being cheaper than pirfenidone. Sensitivity analyses showed the results of the CUA to be robust. CONCLUSIONS: In conclusion, this CUA has found that nintedanib appears to be a more cost-effective therapeutic option than pirfenidone in a French setting, due to fewer acute exacerbations and a better tolerability profile.

Epidemiological and economic burden of potentially HPV-related cancers in France.

Human papillomaviruses (HPV) infection is now known to be responsible for almost all cervical cancers, and for a substantial fraction of Head and Neck cancers (HNCs). However, comprehensive epidemiological and economic data is lacking in France, especially for rarer potentially HPV-related cancers, which include anal, vulvar and vaginal cancers. Using the national comprehensive database of French public and private hospital information (PMSI), we assessed prevalence and incidence of patients with in-hospital diagnosis for potentially HPV-related cancers in 2013, and estimated costs related to their management over a 3-year period after diagnosis in France. Concerning female genital cancers, 7,597, 1,491 and 748 women were hospitalized for cervical, vulvar and vaginal cancer in 2013, respectively, with 3,120, 522 and 323 of them being new cases. A total of 4,153 patients were hospitalized for anal cancer in 2013, including 1,661 new cases. For HNCs, 8,794 and 14,730 patients were hospitalized for oral and oropharyngeal cancer in 2013, respectively; 3,619 and 6,808 were new cases. Within the 3 years after cancer diagnosis, the average cost of hospital care per patient varied from €28 K for anal cancer to €41 K for oral cancer. Most expenditures were related to hospital care, before outpatient care and disability allowance; they were concentrated in the first year of care. The total economic burden associated with HPV-potentially related cancers was about €511 M for the French National Health Insurance over a 3 years period (2011 to 2013), ranging from €8 M for vaginal cancer to €222 M for oropharyngeal cancer. This study reported the most up-to-date epidemiological and economic data on potentially HPV-related cancers in France. These results may be used to evaluate the potential impact of new preventive strategies, namely the generalized organized screening of cervical cancer and the nine-valent HPV vaccine, indicated in the prevention of cervical, vaginal, vulvar and anal cancers.

Burden of Idiopathic Pulmonary Fibrosis Progression: A 5-Year Longitudinal Follow-Up Study.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with an unpredictable course. An observational study was set up using the French hospital discharge database to describe the reasons, outcomes and costs of hospitalisations related to this disease. Patients newly hospitalised for idiopathic pulmonary fibrosis (ICD-10 code: J84.1) in 2008 were identified and followed for 5 years. As J84.1 includes other fibrotic pulmonary diseases, an algorithm excluding age<50 years and presence of a differential diagnosis in the following year was defined. Overall, 6,476 patients were identified; of whom 30% were admitted through the emergency unit and 12% died during their first hospitalisation. Most of patients were hospitalised at least once for one or several acute events (n = 5,635; 87.0% of patients), of whom 36.5% of patients with an acute respiratory worsening (in-hospital mortality of 17.0% and median cost of €3,224; interquartile range (IQR €889-6,092)), 43.7% of patients with a respiratory infection (in-hospital mortality of 29.5% and median cost of €5,432 (IQR, €3,620-9,115)) and 51.7% of patients with a cardiac event (in-hospital mortality of 35.7% and median cost of €4,584 (IQR, €2,803-6,399)); 30.2% of these events occurred during the first hospitalisation. Finally, the 3-year in-hospital mortality crude rate was 36.8%. This study is the first providing extensive data on hospitalisations in patients with pulmonary fibrosis, mostly idiopathic, in France, demonstrating high burden and hospital cost.