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.

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.

Comorbidities in people living with HIV: An epidemiologic and economic analysis using a claims database in France.

OBJECTIVES: As people living with HIV (PLHIV) age, the burden of non-HIV related comorbidities increases resulting in additional healthcare costs. The present study aimed to describe the profile, the prevalence and the incremental costs of non-HIV related comorbidities in PLHIV compared to non-HIV matched controls (1:2 ratio) in France. METHODS: The French permanent sample of health beneficiaries (Echantillon généraliste de bénéficiaires [EGB]), a claims database representative of the national population, was used to assess comorbidities in PLHIV which were identified by the ICD-10 diagnosis codes of hospitalization, full healthcare coverage, and drug reimbursements between 2011 and 2014. The control group was matched by year of birth, gender, region of residence, and economic status. Total costs of outpatient care and hospitalizations were analysed from a societal perspective. A general linear model was used to assess the incremental cost per patient in PLHIV. RESULTS: A total of 1,091 PLHIV and 2,181 matched controls were identified with a mean ± standard deviation age of 46.7 ± 11.5 years. The prevalence of alcohol abuse (5.8% vs 3.1%; p<0.001), chronic renal disease (1.2% vs 0.3%; p = 0.003), cardiovascular disease (7.4% vs 5.1%; p = 0.009), dyslipidaemia (22% vs 15.9%; p<0.001), hepatitis B (3.8% vs 0.1%; p<0.001) and hepatitis C (12.5% vs 0.6%; p<0.001) was significantly higher in PLHIV compared with non-HIV controls. Other comorbidities such as anaemia, malnutrition, psychiatric diseases, and neoplasms were also more prevalent in PLHIV. Hospitalizations were significantly increased in PLHIV compared to controls (33.2% vs 16%; p<0.001). Mean total cost was 6 times higher for PLHIV compared to controls and 4 times higher after excluding antiretroviral drugs (9,952€ vs. 2,593€; p<0.001). Higher costs per person in PLHIV were significantly associated to aging (42€ per patient/year), chronic cardiovascular disease (3,003€), hepatitis C (6,705€), metastatic carcinoma (6,880€) and moderate or severe liver disease (6,299€). CONCLUSION: Our results demonstrated an increase in non-HIV related comorbidities among PLHIV compared to matched controls. This study contributes to raise awareness on the burden of chronic comorbidities.

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.

Survey of Clinical Practice Patterns in the Management of 992 Hyperthyroid Patients in France.

BACKGROUND: Considerable variations in diagnosis and therapeutic practices are reported for hyperthyroidism (HT) between countries. METHODS: A clinical study was conducted among a representative sample of 263 endocrinologists in France. All consecutive patients seen for HT during the study period were included. Diagnosis and treatment modalities were recorded from hyperthyroid patients with Graves disease (GD, n = 802), multinodular goiter (MNG, n = 121), and toxic adenoma (TA, n = 69). RESULTS: Antithyroid antibodies were measured in half of the population (anti-TPO in 48.5% and anti-TSH receptor in 57.8%). Patients had thyroid ultrasonography and scintigraphy in 93.8 and 40.3%, respectively. Therapeutic management depended on the etiology: for the first episode of GD, antithyroid drugs (ATDs) were the first-line treatment in 91% of the patients, combined with surgery in 6.1% and with radioiodine in 2.9%. Surgery was preferred to radioiodine in MNG (52.6 vs. 22.4%) and TA (59.1 vs. 24.2%). Euthyroid status was achieved after 3 months in 64.4% of GD. A "block and replace" protocol was used in 41.2% of patients. After 3 months, 73% of patients were euthyroid in the "block and replace" group compared to 56.2% in the group with ATDs alone (p = 0.009). For MNG and TA, more than 75% of patients were euthyroid at the 3-month follow-up. CONCLUSIONS: Large discrepancies remain between clinical practice and international guidelines. These results should boost efforts to improve adherence to these guidelines.

An observational study of the initial management of hypothyroidism in France: the ORCHIDÉE study.

OBJECTIVE: To document the initial management of hypothyroidism in France with respect to diagnostic setting, investigations, and therapeutic approach. DESIGN: Observational study of the management by primary care practitioners (PCPs) and endocrinologists of patients diagnosed with, and treated for, hypothyroidism during the enrollment period or the previous 6 months. METHODS: A representative sample of PCPs and endocrinologists enrolled up to five consecutive patients and reported sociodemographic, clinical, therapeutic, and laboratory data. Data were submitted at baseline and at the first measurement of TSH after starting the treatment. RESULTS: The analysis population comprised 1255 patients (mean (s.d.) age 52.8 (16.3) years; 84% female). Hypothyroidism was suspected on clinical grounds in 77% of patients, with goiter in 16%. Autoimmune thyroiditis, supported by positive anti-thyroid antibodies, was the most frequent diagnosis (59%), followed by iatrogenic causes (28%), of which thyroidectomy was the most common. The median baseline TSH was 8.6 mIU/l, suggesting a high incidence of subclinical hypothyroidism. Imaging studies were requested in over 75% of patients, with ultrasound performed in 98% and scintigraphy performed in 19% of these patients. Both groups of physicians treated their patients almost exclusively with levothyroxine. Endocrinologists were more likely than PCPs to provide counseling on how to take medication correctly. CONCLUSIONS: This observational study of a large cohort of patients with newly diagnosed hypothyroidism in France illustrates current practice and indicates some areas where physician education may be required to optimize adherence to guidelines and cost-effectiveness.

[Budget impact analysis of Pradaxa thromboprophylaxis after total hip or total knee replacement]. / Bénéfice économique de Pradaxa en thromboprophylaxie après prothèse totale de hanche ou de genou.

Venous thromboembolism is a serious disease that can be life-threatening in case of pulmonary embolism or induce major sequelae. Patients undergoing major orthopaedic surgery represent a population at high risk of venous thromboembolism. Recently Pradaxa has demonstrated its efficacy and safety versus enoxaparin in 2 pivotal trials. Beyond these clinical benefits on the treatment duration observed, the budget impact model's objective was to assess, from the French Sickness Funds perspective for retail market, the consequence of the introduction of this new drug on French setting for a theoretical, representative sample of 1,000 patients in each indication. The cost saving estimated by the model was in excess of 36,000 Euros per 1,000 procedures for total hip replacements. A univariate sensitivity analysis showed that the budget impact was robust and remained positive with the utilisation of Pradaxa in all cases tested.

[Evaluation of a screening programme for diabetic retinopathy (DODIA study)]. / Dépistage de la rétinopathie diabétique par des photographies do fond d'oeil. Evaluation d'un programme en médecine libérale (étude DODIA).

CONTEXT: In France, 43% to 63% of diabetics have an annual fundoscopy. Do the new screening tools, coupled with teletransmission of the images, allow for satisfying ophthalmological screening? It is an important matter given the foreseeable reduction in the number of French ophthalmologists in the forthcoming years. OBJECTIVES: To measure the quality of screening for diabetic retinopathy (DR), in the framework of a network, by the provision of a retinograph by numeric camera (with teletransmission of the images and centralised interpretation), in a screening centre located in town. METHOD: The study evaluated the quality of screening obtained in two comparable groups of general practitioners, one using the retinograph and the other using the classical method of screening by ophthalmologist. The screening was targeted at diabetics who had not had a fundoscopy in the preceding year, nor had known DR or a treating ophthalmologist (for the retinography group only). RESULTS: 667 patients were sampled in the retinography group (456 included) and 707 in the control group (426 included) between 1/04/02 and 1/11/02; 417 patients were followed until the end of the study in the 2 groups. A screening examination was considered effective if it was performed within the six months following its request, and by the presence of a report in the file of the general practitioner. The percentage of patients thus screened was 74% in the retinography group and 71,5% in the other group (not significant). 16% of diabetics in the retinography group had DR compared with 10% of patients in the control group. The analysis of the level of satisfaction of patients tended to show a preference for the system of screening by fundal photography. CONCLUSION: In the framework of a healthcare network, the availability of a retinograph by numeric camera, with the interpretation of photos by teletransmission of the images, obtained a high level of quality of screening for diabetic retinopathy that was at least as good as that obtained by a healthcare network using the classical ophthalmological screening method.

[Invasive cervical cancer treatment costs in France]. / Coût de la prise en charge du cancer invasif du col de l'utérus en France.

The objective of this study was to estimate the direct costs of invasive cervical cancer (ICC) management to the French national health insurance system the 1st year after ICC diagnosis. A retrospective survey was conducted in three centres in 2005, including 42 patients admitted for ICC between 2001-2003. Medical records were examined for data relating to treatments and to determine the management costs. To estimate the annual cost of ICC management in France, data were extrapolated to the general population. The number of new ICC cases in France was estimated at 3,247 in 2003. The mean hospitalisation cost increased with ICC severity at diagnosis: 9,164 euros for stage I, 15,999 euros for stage II, 22,697 euros for stage III, and 26,886 euros for stage IV. The annual cost associated with the medical management of ICC patients was estimated at 43,862,125 euros (sensitivity range 32,973,461 euros-54,748,422 euros) corresponding to a mean patient cost of 13,509 euros. Recent HPV vaccination studies have shown 100 % for a quadrivalent (6,11,16,18) HPV vaccine against HPV-induced carcinoma in situ (FIGO stage 0/CIN3), a precursor lesion that may develop into ICC. Thus, it is expected that this vaccine will significantly reduce the socio-economic burden associated with this disease.