Comparative analysis of all-cause health care resource utilization and costs among patients with non-valvular atrial fibrillation and high risk of gastrointestinal bleeding in France: a nationwide cohort analysis.

Aims: This population-based cohort study compared healthcare resource utilization (HCRU) and direct HCRU costs (medical and non-medical) in French patients with non-valvular atrial fibrillation (NVAF) and at high-risk of gastrointestinal bleeding (GIB) after initiating an anticoagulant treatment with vitamin-K antagonists (VKAs) or with direct-oral anticoagulants (DOACs).

Methods: NVAF patients at high risk of GIB who initiated apixaban, rivaroxaban, dabigatran, or VKAs between 2016 and 2019 were identified from the French National Healthcare Data System (SNDS) database. The first anticoagulant reimbursement set the index date and patients were followed-up until drug discontinuation/switch, death, or study end, whichever came first.

Identifying human toxicodynamic variability: A systematic evidence map of the current knowledge.

Current chemical risk assessment uses a default uncertainty factor (UF) of 3.16 for toxicodynamic (TD) variability in humans. The objective was to create a systematic evidence map (SEM) of the human variability in TD by identifying and organizing the available empirical data to assess if a further refinement of the default UF of 3.

Type 2 diabetes in stroke patients: Impact on outcomes, recurrence, resource use, and costs in France.

Introduction: Contemporary estimates of the impact of type 2 diabetes (T2D) on stroke outcomes are important for care planning and resource allocation. This retrospective cohort study compared the incidence of stroke and subsequent clinical and economic outcomes following stroke among people with and without T2D.

Patients And Methods: Data were extracted from a subset of the French Système National des Données de Santé database.

Occurrence and management of thrombosis recurrence and bleeding in low-molecular-weight heparin-treated patients with cancer-associated thrombosis: a French nationwide cohort study.

Background: Rates of venous thromboembolism (VTE) recurrence and bleeding remain high in patients with cancer who are prescribed anticoagulants (ACs) such as low-molecular-weight heparin (LMWH) after an initial VTE event.

Objectives: To identify patient characteristics associated with VTE recurrence and bleeding in patients receiving LMWH for cancer-associated VTE and to explore secondary AC management and clinical outcomes in these patients.

Methods: An observational study was conducted using nationwide French data for adults with active cancer who were hospitalized with VTE in 2013-2018 and were reimbursed for LMWH ≤ 30 days after hospital discharge.

Comparative safety and effectiveness of oral anticoagulants in key subgroups of patients with non-valvular atrial fibrillation and at high risk of gastrointestinal bleeding: A cohort study based on the French National Health Data System (SNDS).

Background: Risk factors and comorbidities can complicate management of non-valvular atrial fibrillation. We describe and compare real-world safety and effectiveness of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) and vitamin K antagonists (VKAs) in subgroups of patients with non-valvular atrial fibrillation at high risk for gastrointestinal (GI) bleeding, utilizing data from a national quasi-exhaustive French database.

Methods: Anticoagulant-naïve adults with non-valvular atrial fibrillation with ≥1 gastrointestinal bleeding risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible.

Comparative safety and effectiveness of oral anticoagulants in patients with non-valvular atrial fibrillation and high risk of gastrointestinal bleeding: A nationwide French cohort study.

Background: This observational study compared effectiveness and safety of direct oral anticoagulants (DOACs; apixaban, rivaroxaban, dabigatran) or vitamin K antagonists (VKAs) in patients with non-valvular atrial fibrillation (NVAF) at high risk for gastrointestinal bleeding (GIB).

Methods: Anticoagulant-naïve adults with NVAF with ≥1 GIB risk factor, initiating anticoagulant treatment January 2016-December 2019, and covered by the French national health data system were eligible. Outcomes included major bleeding (MB) and stroke/systemic embolism (SE).

Clinical burden and healthcare resource utilization associated with managing transfusion-dependent β-thalassemia in France.

Objective: To describe the clinical burden and healthcare resource utilization associated with managing transfusion-dependent β-thalassemia (TDT) in France.

Methods: We used the French National Health Data System (système national des données de santé) to identify eligible patients from January 1, 2012, to March 1, 2019. Inclusion criteria were a diagnosis of β-thalassemia, ≥8 red blood cell (RBC) transfusion episodes per year in ≥2 consecutive years following the diagnosis, and ≥1 year of follow-up data.

Treatment patterns of patients with HR+/HER2- metastatic breast cancer receiving CDK4/6 inhibitor-based regimens: a cohort study in the French nationwide healthcare database.

Purpose: To assess real-world treatment patterns in patients diagnosed with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC) who received cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with an aromatase inhibitor (AI) or fulvestrant at first line.

Methods: Patient characteristics, treatment history, and outcomes data were extracted from the French 'Système National des Données de Santé' (SNDS) database for patients diagnosed with HR+/HER2- mBC between January 2014 and June 2019 and who received combination therapy with a CDK4/6 inhibitor and endocrine therapy. Kaplan-Meier methodology was used to assess time to next treatment (TTNT) and time to treatment discontinuation (TTTD).

Clinical and Economic Burden Associated With Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation in Germany.

Background: Acute graft-vs-host disease (aGVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT), yet there are limited data on the clinical and economic burden of aGVHD in Germany. This real-world study aimed to evaluate clinical and economic outcomes among patients in Germany with or without aGVHD after allo-HSCT.

Methods: This retrospective cohort study used administrative claims extracted from the German statutory health insurance database.

Healthcare Resource Utilization and Cost Burden of BCG-Treated Non-Muscle Invasive Bladder Cancer Patients in Germany: A Retrospective Claims Analysis.

Background: Intermediate and high-risk non-muscle-invasive bladder cancer (NMIBC) is typically managed with transurethral resection of the bladder tumour (TURBT) followed by intravesical Bacillus Calmette-Guérin (BCG) immunotherapy; however, NMIBC patients can become refractory or unresponsive to BCG treatment, and/or progress to muscle-invasive bladder cancer (MIBC). Healthcare resource utilization (HCRU) and costs in these patient populations are high.

Methods: A retrospective longitudinal cohort design of adult (≥18 years) patients with bladder cancer and BCG treatment (01/01/2012-31/12/2017) was conducted using data from a representative subset of the German statutory health insurance database.

Clinical and economic burden associated with graft-versus-host disease following allogeneic hematopoietic cell transplantation in France.

The real-world clinical and economic burden of graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation has not been comprehensively studied in France. Clinical outcomes, healthcare resource utilization and costs associated with acute GVHD (aGVHD), chronic GVHD (cGVHD), acute plus chronic GVHD (a+cGVHD) versus no GVHD were compared using French administrative claims data. After propensity score matching, 1934, 408, and 1268 matched pairs were retained for the aGVHD, cGVHD, and a+cGVHD cohorts, respectively.

Comparative Analysis of All-Cause Health Care Resource Utilization and Costs Among Venous Thrombosis Patients Without Cancer Prescribed Apixaban or VKAs in France.

Introduction: The direct oral anticoagulant (DOAC) apixaban has shown to have non-inferior efficacy and better safety than vitamin K antagonists (VKAs) in patients with venous thromboembolism (VTE). We determined whether healthcare resource use (HCRU) and direct all-cause medical and non-medical costs in patients with VTE in France differed between VKAs and apixaban.

Methods: A retrospective cohort study was conducted using French national health data from January 2013-June 2018 for anticoagulant-naïve adults hospitalized with VTE.

Exploring the treatment gap among patients with osteoporosis-related fractures in France.

Unlabelled: The use of anti-osteoporosis treatment following a diagnosis of osteoporosis with fracture or a relevant fragility fracture remains low in France. Initiating an anti-resorptive may reduce the incidence of a subsequent fracture by 60%.

Purpose: To describe real-world osteoporosis treatment patterns in individuals with a fragility fracture in France and to explore the impact of initiating treatment on the risk of subsequent fracture.

Effectiveness and Safety of Oral Anticoagulants in the Treatment of Acute Venous Thromboembolism: A Nationwide Comparative Cohort Study in France.

Introduction:  Data from clinical trials indicate that direct oral anticoagulants (DOACs) are noninferior and safer than conventional therapy (low-molecular-weight heparin followed by a vitamin K antagonist [VKA]) for treating venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism (PE). This study compared the effectiveness and safety of DOACs and conventional therapy in a real-world setting.

Methods:  This observational study used French national claims data of adult, treatment-naïve patients diagnosed with VTE (majority PE) who were hospitalized and treated for VTE with a DOAC (apixaban or rivaroxaban) or VKAs during 2013 to 2018.

Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France - a cohort study using the French National Healthcare database (SNDS).

Over the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide.

Clinical impact and room for improvement of intensity and adherence to lipid lowering therapy: Five years of clinical follow-up from 164,565 post-myocardial infarction patients.

Background: In patients at risk of cardiovascular (CV) events, the effectiveness of lipid-lowering therapies (LLT) is affected by both intensity and adherence. Our study evaluated the association between LLT intensity (statin and/or ezetimibe) and adherence, and CV events in patients with a history of myocardial infarction (MI) in France.

Methods: Using the French national healthcare database (SNDS), we included patients with a history of MI, an initial LLT prescription in 2011-2013, and a second prescription within one year.

Inter-phenotypic differences in CYP2C9 and CYP2C19 metabolism: Bayesian meta-regression of human population variability in kinetics and application in chemical risk assessment.

Quantifying variability in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. In this context, genetic polymorphisms in cytochromes P450 (CYPs) drive inter-phenotypic differences and may result in reduction or increase in metabolism of drugs or other xenobiotics. Here, an extensive literature search was performed to identify PK data for probe substrates of the human polymorphic isoforms CYP2C9 and CYP2C19.

Investigating combined toxicity of binary mixtures in bees: Meta-analysis of laboratory tests, modelling, mechanistic basis and implications for risk assessment.

Bees are exposed to a wide range of multiple chemicals "chemical mixtures" from anthropogenic (e.g. plant protection products or veterinary products) or natural origin (e.

The Yin-Yang of CYP3A4: a Bayesian meta-analysis to quantify inhibition and induction of CYP3A4 metabolism in humans and refine uncertainty factors for mixture risk assessment.

Quantifying differences in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. Cytochrome P450 (CYP) 3A4-the major hepatic and intestinal human CYP-and the P-glycoprotein (Pgp) transporter share a vast range of common substrates for which PK may be modulated through inhibition or induction in the presence of grapefruit juice (GFJ) or St. John's wort (SJW), respectively.

Generic physiologically-based toxicokinetic modelling for fish: Integration of environmental factors and species variability.

One of the goals of environmental risk assessment is to protect the whole ecosystem from adverse effects resulting from exposure to chemicals. Many research efforts have aimed to improve the quantification of dose-response relationships through the integration of toxicokinetics. For this purpose, physiologically-based toxicokinetic (PBTK) models have been developed to estimate internal doses from external doses in a time-dependent manner.

Toxicokinetic models and related tools in environmental risk assessment of chemicals.

Environmental risk assessment of chemicals for the protection of ecosystems integrity is a key regulatory and scientific research field which is undergoing constant development in modelling approaches and harmonisation with human risk assessment. This review focuses on state-of-the-art toxicokinetic tools and models that have been applied to terrestrial and aquatic species relevant to environmental risk assessment of chemicals. Both empirical and mechanistic toxicokinetic models are discussed using the results of extensive literature searches together with tools and software for their calibration and an overview of applications in environmental risk assessment.