Impact of direct-acting antiviral treatment for hepatitis C on cardiovascular diseases and extrahepatic cancers.

PURPOSE: The impact of direct-acting antivirals (DAAs) on extrahepatic complications in chronic hepatitis C (CHC) patients remains poorly described. We estimated the association of DAAs with cardiovascular events and extrahepatic cancers. METHODS: The prospective ANRS CO22 HEPATHER cohort was enriched with individual data until December 2018 from the French Health Insurance Database (SNDS). CHC patients were enrolled between August 2012 and December 2015 in 32 French hepatology centers. A total of 8148 CHC adults were selected. Cardiovascular events (stroke, acute coronary syndrome, pulmonary embolism, heart failure, arrhythmias and conduction disorders [ACD], peripheral arterial disease [PAD]) and extrahepatic solid cancers were derived from the SNDS. Associations between DAAs and extrahepatic events were estimated using marginal structural models, with adjustments for clinical confounders. RESULTS: Analyses of 12 905 person-years of no DAA exposure and 22 326 person-years following DAA exposure showed a decreased risk of PAD after DAA exposure (hazard ratio [HR], 0.54; 95% CI, 0.33-0.89), a beneficial effect of DAAs on overall cardiovascular outcomes in patients with advanced fibrosis (aHR, 0.58; 95% CI, 0.42-0.79), and an increased risk of ACD (hazard ratio [HR], 1.46; 95% CI, 1.04-2.04), predominant after the first year following DAA initiation. There was no association between DAAs and extrahepatic cancer risk (HR, 1.23; 95% CI, 0.50-3.03). CONCLUSIONS: DAAs were not associated with extrahepatic cancer development or reduction. They were associated with a decreased risk of PAD and an increased risk of ACD, supporting long-term cardiac monitoring after DAA therapy.

Alzheimer's disease and related syndromes and hospitalization: a nationwide 5-year longitudinal study.

BACKGROUND AND PURPOSE: To study the association between Alzheimer's disease and related syndromes (ADRS) and the incidence of short-stay hospitalizations from the year before (Y-1 ) to 4 years after (Y1 -Y4 ) ADRS identification in the healthcare system. METHODS: Among all beneficiaries of the French health insurance general scheme aged 40 years or more, those with an incident ADRS in 2011, identified through long-term disease registry, hospitalization diagnoses or ADRS-specific drug delivery, were matched with beneficiaries without ADRS of the same age, gender and residence area. The annual incidence rates of all-cause hospitalizations (excluding those with a diagnosis code of ADRS) were compared between individuals with or without ADRS using incidence ratios (IRs) globally and by age, gender, deprivation index and modified Charlson score. We also studied cause-specific hospitalizations using patients' diagnoses and procedure codes. RESULTS: A total of 90 871 subjects with and 90 871 subjects without ADRS were included (mean age 79.6 years, 66% females). From Y-1 to Y4 , incidence rates were significantly higher in subjects with ADRS than in those without for all-cause hospitalization [IR(Y-1 ) = 1.73; 95% confidence intervals, 1.71-1.75; IR(Y4 ) = 1.37; 95% confidence intervals, 1.35-1.39], hospitalizations for social reasons [IR(Y-1 ) = 4.28; IR(Y4 ) = 2.70], fall [IR(Y-1 ) = 5.36; IR(Y4 ) = 2.59], injury [IR(Y-1 ) = 2.71; IR(Y4 ) = 2.09] and infection [IR(Y-1 ) = 2.04; IR(Y4 ) = 2.07]. The inverse was observed for hospitalizations for cataract surgery [IR(Y-1 )=0.73; IR(Y4 ) = 0.51] or total hip prosthesis after 2 years [IR(Y4 ) = 0.72]. CONCLUSIONS: Incident ADRS cases were associated with a higher incidence of hospitalization, but these subjects underwent some common non-emergency surgeries less frequently. Future studies need to assess the clinical impact of these differences.

[What place for French morbidity registries in the era of big data?] / Quelle place pour les registres de morbidité à l'ère des données massives de santé ?

The recent opening of massive health databases, as well as the development of methods and tools adapted to their data processing, questions the French model of "morbidity registry". In France in 2019, nearly 61 health registries were operating. As defined by law, these registries identify exhaustively all patients with a given disease in a given territory. Established several decades ago, these registries are part of the French surveillance system that is used for research and evaluation purposes. Since the advent of recent technological progress, large-scale databases are made available to researchers and it is possible with these databases to answer questions initially assigned to the registries. What is the place of such registries in this new context: are they obsolete or still useful? Should they be opposed to the new tools or are they complementary to them, and if so, what is their place in the new French public health ecosystem? The objective of this work was to assess the roles and missions of existing registries and to reflect on their positioning in this new environment. The French model of registry is sometimes questioned because of the complexity of its circuits, requiring a significant amount of human resources. However, the data that constitute them, validated by cross-checking information from several sources, are of very high quality, and make it possible to validate the data in the new databases (National Health Data System (NSDS) or Hospital Data Warehouses). Registries and new databases are in fact complementary, and far from jeopardizing this model, the recent opening of these databases represents an opportunity for registries to modernize their operations and respond to new missions.

[The opening of the French national health database: Opportunities and difficulties. The experience of the Gazel and Constances cohorts]. / L'ouverture du Système national d'information inter-régimes de l'assurance maladie (SNIIRAM) : des opportunités et des difficultés. L'expérience des cohortes Gazel et Constances.

BACKGROUND: In France, the national health database (SNIIRAM) is an administrative health database that collects data on hospitalizations and healthcare consumption for more than 60 million people. Although it does not record behavioral and environmental data, these data have a major interest for epidemiology, surveillance and public health. One of the most interesting uses of SNIIRAM is its linkage with surveys collecting data directly from persons. Access to the SNIIRAM data is currently relatively limited, but in the near future changes in regulations will largely facilitate open access. However, it is a huge and complex database and there are some important methodological and technical difficulties for using it due to its volume and architecture. METHODS: We are developing tools for facilitating the linkage of the Gazel and Constances cohorts to the SNIIRAM: interactive documentation on the SNIIRAM database, software for the verification of the completeness and validity of the data received from the SNIIRAM, methods for constructing indicators from the raw data in order to flag the presence of certain events (specific diagnosis, procedure, drug…), standard queries for producing a set of variables on a specific area (drugs, diagnoses during a hospital stay…). Moreover, the REDSIAM network recently set up aims to develop, evaluate and make available algorithms to identify pathologies in SNIIRAM. CONCLUSION: In order to fully benefit from the exceptional potential of the SNIIRAM database, it is essential to develop tools to facilitate its use.

Management of Neovascular Age-Related Macular Degeneration Treatment in France from 2008-2018: The Nationwide LANDSCAPE Study.

INTRODUCTION: The aim of this study was to describe the management of neovascular age-related macular degeneration (nAMD) in French patients between 2008 and 2018. METHODS: This was a retrospective longitudinal cohort study using exhaustive nationwide health records from the French National Health Information database. Enrollment criteria were adults aged ≥ 50 years, nAMD diagnosis, or reimbursement for nAMD treatments (anti-vascular epithelial growth factor [VEGF] injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and treatments for other macular diseases (dexamethasone implant, laser). Main outcome measures were consumption of medical care and nAMD treatments per calendar year and number of years of follow-up. RESULTS: Between 2008 and 2018, we identified 342,961 patients who have been treated for nAMD. Median duration of ophthalmological follow-up exceeded 7 years (90 months). The median annual number of ophthalmology consultations decreased from nine visits in year 1 after treatment initiation to four visits from year 7 onwards. The median duration of nAMD treatment was 10.1 months for all patients, with 48.5% of patients undergoing treatment for < 1 year. Only 24.4% of patients had maintained treatment at year 11. Patients remaining under treatment had a median of four anti-VEGF treatments per year throughout the 10-year study period. Ranibizumab was the more common first-line treatment (67.5% of patients) compared to aflibercept (32.4%). About 20% of patients who initiated treatment switched treatment at least once. CONCLUSIONS: LANDSCAPE provides exhaustive nationwide data on the real-world management of nAMD in France over a 10-year period. Further investigation into short treatment duration is required, especially in terms of understanding its relation to visual outcomes.

[Performing pharmacoepidemiological studies using the French health insurance data warehouse (SNDS): How to translate guidelines into practice]. / Réalisation d'études pharmacoépidémiologiques à partir du système national des données de santé (SNDS) : application des recommandations dans la pratique.

The French health insurance data warehouse named SNDS is one of the largest medico-administrative in the world allowing for powerful pharmacoepidemiological studies, based on real-life data collected prospectively. In addition to the absolute necessity of a strong pharmacological rationale, recommendations have been thought to improve the quality of pharmacoepidemiological studies. These guidelines emphasize the importance of an accurate definition of the study population, outcome and exposure, especially for studies performed on medico-administrative databases. Compliance with certain guidelines, particularly those concerning the identification of a specific population or an outcome and the definition of risk periods or exposure periods, may be difficult when performing studies on the SNDS because of its structure and the nature of the data recorded. The objective of this article is to provide advice for the conduct of pharmacoepidemiological studies according to the recommendationswhen using the SNDS, given its specificities. The performing of reliable studies from this rich but complex data warehouse requires the expertise of researchers with deep knowledge both in the SNDS and in pharmacological reasoning.

Use of the French national health insurance information system for research in the field of mental health: Systematic review and perspectives.

PURPOSE: This systematic review registered in PROSPERO (CRD42021225296) aimed to describe the use of the French national health insurance information system, which covers the entire French population (67 million inhabitants), for research in the field of mental health. METHODS: Three electronic databases and a journal hand-search identified 15 265 articles from January 1, 2003 (year of creation of the database) to October 31, 2020. Studies of any design were eligible for inclusion provided that they (i) made use of at least one component of the French health insurance database and (ii) focused on a topic in near and far connection with the field of mental health in France. Database used, design and methods, study period, population, key findings, and type of use for medical research were described. RESULTS: A total of 152 studies were included in the review analysis. There was an increase in the number of published articles over time throughout the studied period. Studies focusing on adults (n = 139) largely outnumbered those focusing on children and adolescents (n = 11). Pharmacoepidemiological studies were by far the most frequent (n = 123), followed by methodological studies (n = 23), epidemiological studies (n = 17), and health economics studies (n = 3). The most studied psychotropic drugs were antidepressants (n = 27), anxiolytics (n = 27), and opioids (n = 25) while fewer studies focused on methylphenidate (n = 6) and on mood stabilizers (n = 5). Few studies specifically focused on psychiatric disorders, mainly depression (n = 4), suicide (n = 4), and psychotic disorders (n = 3). CONCLUSION: This systematic review highlighted a relatively poor exploitation of the Système national des données de santé database in the field of psychiatric research with regard to the great possibilities it offers, with a clear lag in certain fields such as epidemiological or health economics studies and in specific populations, in particular children and adolescents.

[Analysis of off-label prescriptions of medicines in hospital in adult patients and feasibility study of their detection using CIM-10 coding]. / Analyse des prescriptions hospitalières hors AMM des médicaments chez l'adulte et étude de la faisabilité de leur détection par le codage CIM-10 du PMSI.

Analysis of off-label prescriptions of medicines in hospital in adult patients and study of feasibility of their detection by use of international disease classification, 10th version (IDC-10 codes). CONTEXT: In order to improve the appropriate use of medicines, a method of detection of off label prescriptions, especially in hospitalised patients, should be available. STUDY OBJECTIVES: Evaluate the performance of the detection of off-label prescriptions in hospitalised patients by use of IDC-10 codes. METHODS: Data prescriptions (excluding those directly taken in charge by the national health care system), clinical history and biological results were extracted from Assistance publique des Hôpitaux de Paris (AP-HP) data-warehouse for 108 in-hospital adults patients' journeys. An adjudication committee established the classification reference for the appropriate or off label drug prescriptions status after analysis of medical information for each patient. IDC-10 codification that is performed after every hospitalisation was crossed with those IDC-10 codes that were to be expected corresponding to the marketing authorisation labelling (section 4.1 of specifications of product characteristics [SPC]). Results of IDC-10 coding were compared to the reference for off label use identification. RESULTS: Out of the 1131 analysed prescriptions, 44 (3.9%) were classified as off label by the adjudication committee. Sensitivity of detection by IDC-10 coding was 87 (95% CI [0.73-0.96]) to 92% (95% CI [0.79-0.98]) and specificity 25 (95% CI [0.22-0.27]) to 41% (95% CI [0.38-0.44]) according to the number of characters of ICD-10 that could be used. CONCLUSIONS: Incidence of in-hospital off label use of drugs (restricted to within drug related groups prescriptions) appeared relatively low (3.9%). Its semi-automatic detection by IDC-10 coding appears feasible with a good sensitivity but a low specificity. Such method could be further assessed as a first step detection focusing on one pharmacological class or on one pathologic condition.

Incidence and Prevalence of Neovascular Age-Related Macular Degeneration in France between 2008 and 2018: The LANDSCAPE Study.

Purpose: This study aimed to estimate the incidence and prevalence of neovascular age-related macular degeneration (nAMD) in the French population between 2008 and 2018. Design: This was a retrospective, longitudinal population study using health care consumption data from the Système National des Données de Santé (SNDS; the French National Health Information Database), which covers approximately 99% of the French population. Participants: We identified individuals treated for nAMD from the French population 50 years of age and older. Identification criteria were nAMD diagnosis or reimbursement of nAMD treatments (anti-vascular endothelial growth factor intravitreal injection or dynamic phototherapy with verteporfin). Exclusion criteria were high myopia, diagnosis of other retinal diseases, and other treatments for macular diseases (dexamethasone implant, laser therapy, etc.). Methods: We calculated incidence and prevalence based on the age-matched general population in France. Adjustment for age and sex was also performed for incidence. Main Outcome Measures: Incidence and prevalence of nAMD in the French population between 2008 and 2018. Results: Between 2008 and 2018, we identified 342 961 patients with nAMD (67.5% women). Mean ± standard deviation age at nAMD diagnosis or first treatment increased from 78.8 ± 8.1 years in 2008 to 81.2 ± 7.9 years in 2018. In 2018, annual incidence was 0.149% and prevalence was 1.062% for the French population 50 years of age or older. Incidence was stable over the 10-year period. Annual incidence increased with age (0.223%, 0.380%, and 0.603% in those 60 years of age or older, 70 years of age or older, and 80 years of age or older, respectively), with similar trends for prevalence. No major differences were observed among the 14 regions of France for incidence or prevalence. Neovascular age-related macular degeneration incidence in 2018 was not impacted by the availability of primary or ophthalmology care in patients' localities. Conclusions: The LANDSCAPE study provides exhaustive nationwide data on incidence and prevalence of nAMD in France over a 10-year period.

Outcome After Protontherapy for Progression or Recurrence of Surgically Treated Meningioma.

BACKGROUND: To assess the outcome after meningioma surgery and protontherapy (PT). METHODS: We processed the French Système National des Données de Santé database to retrieve appropriate cases of meningiomas operated and irradiated between 2008 and 2017. Survival methods were implemented. RESULTS: One hundred ninety-three patients who received PT after meningioma surgery over a 10-year period were identified. Of the 193 patients, 75.6% were female. Median age at surgery was 50 years (interquartile range [IQR] 41-62). The median number of PT fractions was 31 (IQR 30-39) given over a median duration of 52 days (IQR 44-69). Fourteen patients (7.3%) also received photon radiotherapy and six patients (3.1%) stereotactic radiosurgery. Median follow-up was 4.4 years (IQR 3.86-4.71). Five-year progression-free survival (PFS) rate was 69% (95% confidence interval [CI] 62.1-76.6). For benign, atypical, and malignant meningioma, 5-year PFS rates were 71.5% (95% CI 64.4-79.4), 55.6% (95% CI 32.5-95), and 35.6% (95% CI 12.8-98.9), respectively (p<0.01). In the adjusted regression, tumour location (hazard ratio [HR]=0.1, 95% CI 0.05-0.22, p<0.001), aggressive meningioma (HR=2.26, 95% CI 1.1-4.66, p=0.027), and the need of cerebrospinal fluid (CSF) insertion for hydrocephalus (HR=3.51, 95% CI 1.32-9.31, p=0.012) remained significantly associated to the PFS. All grades considered, 5-year overall survival (OS) rates was 89.7% (95% CI 84.6-95.1). For benign, atypical, and malignant meningioma, 5-year OS rates were 93% (95% CI 88.7-97.4), 76.4% (95% CI 51.4-100), and 44.4% (95% CI 16.7-100), respectively (p<0.01). In the multivariable regression, an older age above 70 years (HR=5.95, 95% CI 2.09-16.89, p<0.001) associated to a high level of comorbidities (HR=5.31, 95% CI 1.43-19.78, p=0.013) and a malignant meningioma (HR=5.68, 95% CI 1.54-20.94, p=0.009) remained significantly associated to a reduced OS. CONCLUSION: Five-year PFS and OS after meningioma surgery and PT is favourable but impaired for older patients with high level of morbidities, tumour of the convexity, malignant histopathology and for those requiring CSF shunting. Further inclusion and prolonged follow-up is required to assess other predictors such as sex, tumour volume, or given dose.

Diabetes Remission and Relapse After Bariatric Surgery: a Nationwide Population-Based Study.

PURPOSE: The long-term impact of bariatric surgery on the remission of type 2 diabetes (T2DM) remains to be clarified through large nationally representative cohorts. The objectives were to determine the incidence of T2DM remission and relapse after bariatric surgery, to determine the factors associated with remission and to establish a profile for patients at risk for relapse. MATERIALS AND METHODS: We conducted a population-based cohort study using data from the French national health insurance database (Systeme national des données de santé [SNDS]). We had access to exhaustive regional data between 2013 and 2017 and to a national representative sample of the French population (EGB) from 2008 to 2018. Patients were included if they were adults and diabetics with incidental bariatric surgery. RESULTS: This study shows that 50% of patients are in remission from diabetes after bariatric surgery within a median of 2 to 4 months. Diabetes relapse was observed in 13-20% within 10 years. The factors favouring remission already described were noted (non-insulin-dependent diabetes) and original factors were also identified, in particular the advantage of bypass surgery over sleeve gastrectomy, with more remissions and fewer relapses. CONCLUSION: This study highlights a 50% prevalence of remission and a low prevalence of relapse. There are non-modifiable risk factors for remission and relapse (characteristics of diabetes, age, lipid-lowering therapy) and modifiable factors (type of surgery). Identifying these factors is essential for optimal management of patients. Additional data are essential to confirm the results of our analysis of the factors associated with relapse.

[Adaptation of the General Data Protection Regulation (GDPR) to a smartphone app for rhinitis and asthma (MASK-air®)]. / Règlement général sur la protection des données pour MASK-air® (application mobile rhinite et asthme).

The General Data Protection Regulation (GDPR) regulates the processing of personal data in the European Union. The legal context is adapted to follow the evolution of technologies and of society. This new European regulation became mandatory, especially for connected devices, on May 25, 2018. An app originally known as "The Allergy Diary" is available for Android phones and iPhones. Its name was recently changed to MASK-air. The downloading and use of this app are free of charge and there are no adverts. It enables users to record their symptoms and their medications to better track the progress of their allergic rhinitis and/or asthma. It has been developed by public (Foundation FMC VIA-LR, University of Montpellier) and private (KYomed INNOV) organizations based in France and therefore falls under French jurisdiction. This article summarizes the five main principles of personal data protection to be respected during the development of the app: purpose, proportionality and relevance, limited retention period, security and confidentiality, as well as the rights of the people who are involved in the management of the personal data (including withdrawal and modification).

[Individualized Medicine, Electronic Patient File and Further Use of Health Data]. / Individualisierte Medizin, elektronisches Patientendossier und Weiterverwendung von Gesundheitsdaten.

Individualized Medicine, Electronic Patient File and Further Use of Health Data Abstract. The present article is dedicated to the two subject areas 'individualized medicine' and 'electronic patient file'. Both individualised medicine and the electronic patient file generate numerous different health data. The article focuses on the value of health data for human research and discusses the further use of the data according to the Human Research Act. At present, the Human Research Act does not provide for the possibility of making data from the electronic patient file accessible for research. However, efforts are being made to change this legal situation so that data from the patient file can be incorporated into human research for the benefit of (future) patients.

Major ischaemic and bleeding risks following current drug-eluting stent implantation: Are there differences across current drug-eluting stent types in real life?

BACKGROUND: Current drug-eluting stents (c-DESs) reduce the occurrence of ischaemic events, but expose recipients to stent thrombosis and bleeding secondary to preventive antiplatelet therapy. To date, comparative data on the relative effectiveness and safety of the various c-DESs in real life are limited. AIM: To compare ischaemic and bleeding risks across the major c-DESs used in France. METHODS: French national health insurance reimbursement and hospitalization databases were used. Patients implanted with a c-DES in 2014 were followed for 1 year. The risks of ischaemic events (revascularization, myocardial infarction and/or stroke), major bleeding events and death were compared across six c-DESs (XIENCE®, PROMUS®, RESOLUTE®, BIOMATRIX®, NOBORI® and ORSIRO®), using multilevel Cox models adjusted for baseline individual and hospital characteristics. RESULTS: A total of 52,891 subjects were included: 34.4% with XIENCE®; 27.6% with PROMUS®; 24.0% with RESOLUTE®; 8.0% with BIOMATRIX®; 5.0% with NOBORI®; and 1.0% with ORSIRO®. Among them, 9378 had at least one event (ischaemic, 6064; major bleeding, 1968; death, 2411), resulting in an overall incidence rate of 19 per 100 person-years. In the multivariable analysis, the risk of ischaemic events, major bleeding events or death did not differ between the c-DESs overall (adjusted hazard ratios between 0.85 [95% confidence interval 0.68-1.07] and 1.04 [95% confidence interval 0.98-1.10] compared with XIENCE® used as the reference) and when each outcome was considered separately. CONCLUSIONS: In real life, major ischaemic and bleeding risks do not differ across the various c-DESs over the first year following implantation. Future studies are needed to assess comparative c-DES effectiveness and safety longer term.

[Digitization in Swiss veterinary practices]. / Stand der Digitalisierung in Schweizer Tierarztpraxen.

INTRODUCTION: Data on the digitization in Swiss veterinary practices and clinics were collected in a survey from June 2017 to the end of December 2017. Data of 171 practices contributed to the survey. Animal records were filed in 96.5% with a practice management program. Nine out of ten practices operate an x-ray machine whereof 70% digitally record the radiographs. While a moderate diversity of practice management systems is used, numerous different radiographic recording, archiving and viewing systems are utilized. Data exchange with other practices and owners preferably takes place via e-mail, followed by upload servers and digital data carriers. Data protection receives less attention in veterinary medicine than in comparison to human medicine. A protected data exchange platform coupled with AMICUS and ANIS is under construction via standardized DICOM (https://www.dicomstandard.org/current/) and HL7 (https://www.hl7.org/) interfaces.

INTRODUCTION: De juin 2017 à fin décembre 2017, des données relative à la digitalisation ont été collectées dans le cadre d'une enquête auprès de cabinets et cliniques vétérinaires suisses. Au total, 171 pratiques ont participé à l'enquête. 96,5% conservent les antécédents du patient avec un programme de gestion. Neuf cabinets sur dix utilisent un appareil à rayons X, dont 70% enregistrent numériquement les images. Bien que la variété des systèmes de gestion soit modérée, elle est riche en ce qui concerne l'enregistrement, l'archivage et la visualisation des images. L'échange de données avec d'autres pratiques et propriétaires se fait de préférence par courrier électronique, suivi de serveurs de téléchargement et de supports de données numériques. En comparaison avec la médecine humaine, la protection des données a beaucoup moins d'importance en médecine vétérinaire. Afin de pouvoir effectuer l'échange de données numériques de manière pratique, une plate-forme d'échange de données sécurisée couplée à AMICUS et à ANIS via DICOM normalisé (https://www.dicomstandard.org/current/) et HL7 (https://www.hl7.org/) est en construction.

[Health data at local and regional levels: what methods? What benefits for action?]. / Les donnees de sante aux echelons local et regional: quelles methodes? Quels apports pour l'action?

Health data can play a role in health promotion programs either to inform interventions or to raise awareness among health decision makers in their locality. Different tools are available to disseminate health data. Overviews present a snapshot of the social and health situation of a population. They can be carried out at different scales: regional, provincial, municipal or across borders, as was the case in the program 'Générations en Santé' [Generations in Health], which covered the French regions of Champagne-Ardenne, Picardie and Nord Pas-de-Calais; and the Belgian provinces of Luxembourg, Namur and Hainaut. The use of quantitative data encountered two obstacles: between-country comparability on the cross-border level and statistical fluctuation for small populations at the municipal level. Qualitative studies complement statistical data and refine one's knowledge of a situation. They can also enable the inclusion of a participative process.