Mortality and comorbidities in a Nationwide cohort of HIV-infected adults: comparison to a matched non-HIV adults' cohort, France, 2006-18.

BACKGROUND: Human immunodeficiency virus (HIV) remains a significant cause of morbidity and mortality worldwide. The aim of this study was to describe the mortality rate and associated comorbidities in a nationwide population-based cohort of persons living with HIV (PLWHIV) and to compare it with mortality in an age and gender-matched cohort of non-HIV individuals in France. METHODS: Using data from the French national health data system, we identified and included 173 712 PLWHIV (66.5% men) and 173 712 non-HIV participants (66.5% men) matched for age and gender. PLHIV were identified based on ICD-10 HIV diagnoses, HIV-specific laboratory tests, and/or prescriptions for antiretroviral therapy specific to HIV. Hazard ratios (HRs) of mortality were assessed using multiple Cox regression models. RESULTS: During the 13 years of follow-up (2006-18), we observed 20 018 deaths among PLWHIV compared with 6262 deaths among non-HIV participants (11.52% vs. 3.60%, P < 0.001). The over-mortality of PLWHIV was expressed by univariable HR = 2.135 (2.072-2.199), which remained significant after adjustment for region, Complementary Universal Health Insurance and AME, with multivariable HR = 2.182 (2.118-2.248). The results remained significant after adjusting for comorbidities, including infectious diseases [HR = 1.587 (1.538-1.638)]. Notably, PLWHIV were more importantly associated with mortality in women [HR = 2.966 (2.767-3.180)], compared in men [HR = 1.961 (1.898-2.027)]. CONCLUSION: Although the life expectancy of PLWHIV has globally increased, the causes of death should be prioritized in prevention policies and care management. Gender-specific policies should be highlighted, as we observed a higher impact of HIV mortality in women.

Health status and comorbidities of adult patients with phenylketonuria (PKU) in France with a focus on early-diagnosed patients - A nationwide study of health insurance claims data.

BACKGROUND: This study aimed at evaluating the health status and healthcare consumption of ≥16-year-old patients with phenylketonuria (PKU), with a focus on early-diagnosed patients. METHODS: This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database. Patients with PKU were identified between 2006 and 2018 by ICD-10 diagnosis codes E70.0 (classic PKU) or E70.1 (other causes of hyperphenylalaninemia). They were matched to controls by age, sex, and region. Patients with early-diagnosed PKU were defined as patients born after implementation of nationwide newborn screening in France in 1972. Outcomes were analyzed for the year 2018. RESULTS: Overall, 3549 patients with PKU were identified on January 1st, 2018. Of those, 3469 patients could be matched to 17,170 controls without PKU. Of these patients, 2175 were at least 16 years old and suffered significantly more than controls from specific comorbidities of interest - osteoporosis (28.7% vs 19.8%, p < 0.0001), hypertension (20.9% vs 17.0%, p < 0.0001), hypercholesterolemia (12.8% vs 8.3%, p < 0.0001), diabetes (7.8% vs 4.7%, p < 0.0001), obesity (4.2% vs 1.3%, p < 0.0001), ischemic heart diseases (4.8% vs 2.0%, p < 0.0001), and depression (10.3% vs 8.2%, p = 0.0011). Prescriptions for many medications were also more frequent in patients with PKU than controls. Among ≥16-year-old patients, 1528 were categorized as early-diagnosed. Osteoporosis (0.3% vs 0.01%, p = 0.0035), chronic renal failure (0.6% vs 0.1%, p = 0.0020), hypertension (4.0% vs 2.7%, p = 0.0063), and obesity (2.5% vs 0.8%, p < 0.0001) were significantly more prevalent in early-diagnosed adult patients compared with matched controls. In total, 28.6% of ≥16-year-old patients with PKU and 40.4% of early-diagnosed patients with PKU received dietary amino-acid supplements. Sapropterin was prescribed to 5.0% and 7.0% patients, respectively. CONCLUSION: The results indicate that PKU is associated with a significantly higher comorbidity risk along with increased pharmaceutical prescriptions in adulthood. The comorbidity burden is less distinct in early-diagnosed patients but still present. Few patients are treated specifically for PKU in adulthood. Healthcare of patients with PKU should include prevention and management of comorbidities and especially target PKU-specific treatment adherence and consistent care in specialized medical centers in adulthood.

Health status and comorbidities of adult patients with late-diagnosed phenylketonuria (PKU) born before the newborn screening in France - A nationwide study of health insurance claims data.

BACKGROUND: Phenylketonuria (PKU) is an inborn error of metabolism. When diagnosed late, it causes developmental delay or severe irreversible intellectual disability. This study aimed at evaluating the health status and healthcare consumption of late-diagnosed PKU patients in France. METHODS: This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database, which contains data from over 66 million French inhabitants. Patients with PKU were identified between 2006 and 2018 by ICD-10 diagnosis codes E70.0 / E70.1 documented as a chronic condition (affection de longue durée - ALD) or in the inpatient setting. Patients with PKU were matched to controls by age, sex, and region. Patients with late-diagnosed PKU were defined as patients born before the nationwide implementation of newborn screening in France in 1972. Outcomes were analyzed for the year 2018. RESULTS: In total, 3549 patients with PKU were identified in the database on January 1st, 2018. Of those, 3469 patients could be matched to 17,170 controls without PKU. Of these, 2175 patients were at least 16 years old of whom 647 patients were categorized as late-diagnosed. The late-diagnosed PKU patients suffered significantly more often from hypertension (60.9% vs. 50.4%, p < 0.0001), hypercholesterolemia (41.7% vs. 26.9%, p < 0.0001), diabetes (24.4% vs. 14.1%, p < 0.0001), depression (20.6% vs. 13.8%, p < 0.0001), ischemic heart disease (16.1% vs. 6.6%, p < 0.0001), obesity (7.9% vs. 2.5%, inpatient diagnoses only, p < 0.0001), and chronic kidney disease (5.2% vs. 1.3%, inpatient diagnoses only, p < 0.0001) compared with their non-PKU controls. Consequently, significantly more patients with late-diagnosed PKU received medication to treat comorbidities associated with the nervous (82.6% vs 77.0%; p = 0.0021) and cardiovascular system (69.5% vs 58.0%; p < 0.0001). Overall, only 3.4% of patients with late-diagnosed PKU received dietary amino-acid supplements and 0.7% received sapropterin. CONCLUSION: The results indicate that PKU is associated with a significantly higher risk of comorbidities along with increased pharmaceutical prescriptions in patients with late-diagnosed PKU, compared with non-PKU controls. The increased risk of comorbidities was more pronounced than in patients with early-diagnosed PKU, as shown in previous research, but these patients are older than those with early-diagnosed PKU. Only few late-diagnosed patients were treated specifically for PKU. Patients with late-diagnosed PKU should be referred to specialized centers to prevent and manage comordities and introduce PKU-specific treatment when it is possible.

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.

Mepolizumab in a population with severe eosinophilic asthma and corticosteroid dependence: results from a French early access programme.

BACKGROUND: Mepolizumab was available in France as part of an early access programme for patients with severe eosinophilic asthma (nominative autorisation temporaire d'utilisation [temporary use authorisation] (nATU)) before its commercialisation. This study aimed to characterise patients who received mepolizumab in the nATU. METHODS: This retrospective, observational study analysed data from the hospital medical records of patients up to 24 months after treatment initiation. Study objectives were to describe patient baseline characteristics, the evolution of disease severity and treatment modifications during follow-up; safety was also investigated. FINDINGS: Overall, 146 patients who received ≥1 dose of mepolizumab were included. At inclusion, patients had a mean age of 58.2 years with a mean severe asthma duration of 13.4 years, and 37.0% had respiratory allergies. Patients experienced, on average, 5.8 exacerbations per patient per year at baseline, 0.6 and 0.5 of which required hospitalisation and emergency department visits, respectively. These values improved to 0.6, 0.1 and 0.1 exacerbations per patient per year, respectively, at 24 months of follow-up. Most patients (92.8%) were using oral corticosteroids at baseline, compared with 34.7% by 24 months of follow-up. Moreover, mean blood eosinophil counts improved from 722 cells·µL-1 at baseline to 92 cells·µL-1 at 24 months of follow-up; lung function and asthma control followed a similar trend. INTERPRETATION: Results confirm findings from clinical trials, demonstrating that mepolizumab is associated with important improvements in several clinically meaningful outcomes and has a favourable safety profile in a population with severe eosinophilic asthma, outside of the controlled environment of a clinical trial.

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.

Outcomes and management costs of peripheral arterial disease in France.

BACKGROUND: Little is known about the characteristics and prognosis of patients with peripheral arterial disease (PAD) and related real-life health costs in France. METHODS: A cohort of patients diagnosed with PAD between 2007 and 2011 was extracted from the French Echantillon Généraliste des Bénéficiaires (EGB) claims database. The patients were followed up from the date of PAD diagnosis. Their characteristics, incidence of death and other events, treatments, and costs were analyzed by comparison with age- and gender-matched PAD-free controls. RESULTS: There were 5889 patients with PAD identified. Mean age was 70.8 years, and 68.1% of patients were male. Diabetes was present in 28.9% of patients (13.2% of controls), hypercholesterolemia in 52.9% (28.7%), and hypertension in 46.6% (12.3%); 4.9% of patients had a history of unstable angina or myocardial infarction (0.5%), and 6.0% had a history of stroke or transient ischemic attack (1.4%). At inclusion, 69.3% of patients were receiving antiplatelet drugs (17.3%), 52.3% statins (21.9%), 26.7% angiotensin-converting enzyme inhibitors (13.7%), and 24.2% angiotensin receptor blockers (16.6%). Cumulative mortality rates were 13.2% at 1 year and 19.4% at 2 years (3.2% and 6.5% in controls). Cumulative incidence rates of death and major cardiovascular events (myocardial infarction and ischemic stroke) were 15.7% (95% confidence interval [CI], 14.8%-16.6%) at 1 year and 22.9% (95% CI, 21.9%-24.0%) at 2 years vs 3.9% (95% CI, 3.4%-4.4%) and 7.8% (95% CI, 7.1%-8.5%) in controls. All differences were statistically significant (P < .05). Total annual management costs were €14,949 in the PAD group and €3812 in the control group. CONCLUSIONS: Mortality is elevated and cardiovascular events are frequent among French PAD patients. PAD drug treatment guidelines are not fully implemented in France.

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.

Correction: Medico-economic comparison of two anticoagulant treatment strategies: Vitamin K antagonists vs. direct oral anticoagulants in older adults in nursing homes in France. The "MIKADO" study.

[This corrects the article DOI: 10.1371/journal.pone.0283604.].

Hereditary angioedema with C1 inhibitor deficiency: clinical presentation and quality of life of 193 French patients.

BACKGROUND: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease. New specific treatments are available. OBJECTIVE: To identify patients' features and patients' best therapeutic option. METHODS: A 1-year, multicenter, retrospective study was performed. The primary objective was to examine the clinical presentation of HAE. Secondary objectives included patient characteristics, management of HAE over 12 months, and health-related quality of life using the SF-36v2 questionnaire. RESULTS: One hundred ninety-three patients were included, and 69.4% were women. In the 12-month period, the mean number of HAE attacks was 7.6. Among the 568 reported attacks, localizations were the abdomen (57.1%), peripheral limbs (42.5%), upper airway (7.9%), and face (6.9%); 31.6% of attacks were severe and occurred statistically more often in women (P < .02). Compared with a population of allergic patients, all age- and sex-adjusted scores were significantly lower in patients with HAE (P < .05) except for the physical component summary. Health-related quality of life negatively correlated with the annual number of attacks and was markedly altered for patients having more than 5 attacks per year (P < .05 for all dimensions). CONCLUSION: HAE is a severe disease that places a heavy burden on quality of life.

[Hypoglycemic treatment in type 2 diabetes patients suffering from moderate to severe renal failure in France. Aim of the study]. / Traitements antidiabétiques des patients diabétiques de type 2 atteints d'une insuffisance rénale modérée ou sévère suivis en médecine générale en France.

UNLABELLED: The purpose of this study is to describe the hypoglycemic agents prescribed to type 2 diabetes patients (T2D) with renal impairment (RI). METHOD: Data were extracted from the database LPD-CEGEDIM, based on a sample of 1200 general practitioners. The analysis focused on T2D patients with RI, defined by a glomerular filtration rate (GFR) below 60 mL/min/1.73 m², estimated by the MDRD formula. RESULTS: Of the 36 255 patients identified with T2D, a GFR was calculated for 8 647 patients (23.9%), 1 472 (22%) with a moderate RI (GFR=[30mL/min/1.73 m²-60mL/min/1.73 m²]) and 86 (1.0%) with a severe RI (GFR=[15mL/min/1.73 m-30mL/min/1.73 m²]); 47,6% of T2D patients with a moderate RI and 52,3% of T2D patients with a severe RI were treated with at least one drug contraindicated in patients with moderate or severe RI. CONCLUSION: These findings suggest better informing doctors of these contraindications and show the value of having new hypoglycemic drugs that can be used in case of RI.

Asthma burden according to treatment steps in the French population-based cohort CONSTANCES.

BACKGROUND: Data on health care consumption and costs of asthma in the French population are scarce. OBJECTIVES: The study objective was to describe the burden of asthma according to GINA treatment steps in the CONSTANCES cohort. METHODS: Data from 162,725 participants included between 2012 and 2019 were extracted. Participants were considered as current asthmatics if asthma was reported at inclusion and asthma symptoms and/or treatments were reported in 2019. Participants were classified in three categories according to GINA treatment steps. The results were compared to non-asthmatic participants matched with a propensity score calculated on age, sex, region of residence, precariousness score and year of inclusion. RESULTS: Among 162,725 participants aged 18-69 years, 6783 asthmatics (1566 not treated for asthma, 2444 + 251 GINA steps 1 + 2, 1054 + 1315 GINA steps 3 + 4, and 153 GINA step 5) were matched with 6783 controls. Average annual ambulatory cost and average annual hospitalization cost were respectively €1925 and €719 for asthmatics versus €1376 and €511 for participants without asthma (p < 0,0001). Cardiovascular risk factors, co-morbidities, visits and hospitalizations were higher for asthma participants as compared to controls and increased with GINA steps, as well as inpatient and outpatient costs. However, for cardiovascular risk factors and co-morbidities, differences were non-significant in multivariate analyses. Pharmacy costs were ten times higher for GINA step 5 participants than for GINA steps 1-2 participants: €3187 versus €393 (p < 0,0001). CONCLUSION: mean cost of asthma was estimated at €757 per patient/year and increased with GINA treatment step.

The Place of Immune Reconstitution Therapy in the Management of Relapsing Multiple Sclerosis in France: An Expert Consensus.

The treatment strategy in relapsing multiple sclerosis (RMS) is a complex decision requiring individualization of treatment sequences to maximize clinical outcomes. Current local and international guidelines do not provide specific recommendation on the use of immune reconstitution therapy (IRT) as alternative to continuous immunosuppression in the management of RMS. The objective of the program was to provide consensus-based expert opinion on the optimal use of IRT in the management of RMS. A Delphi method was performed from May 2022 to July 2022. Nineteen clinical assertions were developed by a scientific committee and sent to 14 French clinical experts in MS alongside published literature. Two consecutive reproducible anonymous votes were conducted. Consensus on recommendations was achieved when more than 75% of the respondents agreed or disagreed with the clinical assertions. After the second round, consensus was achieved amongst 16 out of 19 propositions: 13 clinical assertions had a 100% consensus, 3 clinical assertions a consensus above 75% and 3 without consensus. Expert-agreed consensus is provided on topics related to the benefit of the early use of IRT from immunological and clinical perspectives, profiles of patients who may benefit most from the IRT strategy (e.g. patients with family planning, patient preference and lifestyle requirements). These French expert consensuses provide up-to-date relevant guidance on the use of IRT in clinical practice. The current program reflects status of knowledge in 2022 and should be updated in timely manner when further clinical data in IRT become available.

Real-world data and evidence in health technology assessment: When are they complementary, substitutes, or the only sources of data compared to clinical trials?

Within the life-cycle assessment of health technologies, real-world data (RWD) have until now been of secondary importance to clinical trial data. The availability of massive, better quality RWD, particularly with the emergence of connected devices, the improvement of methods for characterizing populations, make it possible to have a better insight into the effects of treatment, sometimes on a national scale the importance of RWD is likely to progress in the eyes of health technology assessors, going from being traditionally complementary to possibly replacing clinical trial data. This is the fundamental question that the round table, involving experts from the academic and/or hospital, institutional, and industrial worlds, set out to answer. This work served first to establish the current role of RWD in health technology assessment, by distinguishing the main purposes of RWD, the timing of the evaluation in relation to the life cycle of the technology, and then according to the party commissioning or receiving the outcomes of RWD-based studies. Secondly, the round table proposed six general recommendations for more intensive and decisive use of RWD in the assessment and decision-making process.

Medico-economic comparison of two anticoagulant treatment strategies: Vitamin K antagonists vs. direct oral anticoagulants in older adults in nursing homes in France. The "MIKADO" study.

OBJECTIVES: Currently, two classes of oral anticoagulants are available in nursing home residents: vitamin K antagonists (VKA) and direct oral anticoagulants (DOAC). DOACs have a higher net clinical benefit than VKAs but DOACs are about 10 times more expensive than VKAs. The objective of our study was to assess and compare the overall costs of anti-coagulant strategy (VKA or DOAC), i.e., including drugs, laboratory costs and time spent in human capital (nurses and medical time) in nursing homes in France. METHODS: This was an observational, multicenter, prospective study including nine nursing homes in France. Among these nursing homes, 241 patients aged 75 years and older and treated with VKA (n = 140) or DOAC (n = 101) therapy accepted to participate in the study. RESULTS: During the 3-month follow-up period, the adjusted mean costs per patient were higher for VKA than DOACs for nurse care (€327 (57) vs. €154 (56), p<.0001) for general practitioner care (€297 (91) vs. €204 (91), p = 0.02), for coordinating physicians care (€13 (7) vs. €5 (7), p < 0.07), for laboratory tests (€23 (5) vs. €5 (5), p<.0001), but were lower for drug costs (€8 (3) vs. €165 (3), p<.0001). The average overall cost for 3 months per patient was €668 (140) with VKA vs. €533 (139) with DOAC (p = 0.02). CONCLUSION: Our study showed that in nursing homes despite a higher drug cost, DOAC therapy is associated with a lower total cost and less time used by nurses and physicians for drug monitoring when compared to VKA.

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.

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.