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Background rVIII-SingleChain is a recombinant factor VIII (FVIII) with increased binding affinity to von Willebrand factor compared with other FVIII products. rVIII-SingleChain is indicated for the treatment and prevention of bleeding episodes in patients with hemophilia A. Objectives To collect real-world evidence data from patients treated with rVIII-SingleChain to confirm the efficacy and safety established in the clinical trial program and carry out a population pharmacokinetic (PK) analysis. Methods This interim analysis includes data, collected between January 2018 — September 2021, from patients treated with rVIII-SingleChain prophylaxis at French Hemophilia Treatment centers. Data on annualized bleeding rates, dosing frequency, and consumption before and after switching to rVIII-SingleChain were recorded. A population PK analysis was also conducted to estimate PK parameters. Results Overall, 43 patients switched to prophylaxis with rVIII-SingleChain either from a previous prophylaxis regimen or from on-demand treatment. Following the switch to rVIII-SingleChain, patients maintained excellent bleed control. After switching to rVIII-SingleChain, most patients maintained or reduced their regimen. Interestingly, a majority of patients treated >2 ×/weekly with a standard half-life FVIII reduced both injection frequency and FVIII consumption with rVIII-SingleChain. A PK analysis revealed a lower clearance of rVIII-SingleChain (1.9 vs. 2.1 dL/h) and a longer half-life both in adolescents/adults (n = 28) and pediatric (n = 6) patients (15.5 and 11.9 hours, respectively vs. 14.5 and 10.3 hours) than previously reported. Conclusions Patients who switched to rVIII-SingleChain prophylaxis demonstrated excellent bleed control and a reduction in infusion frequency. A population PK analysis revealed improved PK parameters compared with those reported in the clinical trial.

Process-of-care studies participate in improving the efficiency of the care pathway for patient with haemophilia (CPPH) and rationalize the multidisciplinary management of patients. Our objective is to establish a current overview of the different actors involved in the management of patients with haemophilia and to provide an accurate description of the patient trajectory. This is a qualitative exploratory research based on interviews of the principal health professionals of four haemophilia services, between November 2019 and February 2020, in France. Mapping of the CPPH processes within the different institutions and/or services, as well as the rupture zones, were identified. Treatment delivery and biological analyses were carried out exclusively in healthcare institutions. The main liberal health professionals solicited were nurses, physiotherapists and general practitioner. Obstacles and barriers within the specialized service, with other hospital services and external hospital or private services, community health care providers et community environment and individual one was complex and multiples. Our research identified potential concerns that need to be addressed to improve future studies to identify influential elements. Similarly, other qualitative studies will have to be conducted on the perceptions and literacy of patients with haemophilia to develop a global interactive mapping of their trajectories.

Karen Beny,1,2 Benjamin du Sartz de Vigneulles,1 Valerie Chamouard,3,4 Ronald Guilloux,5 Valérie Gay,6 Claude Negrier,3 Claude Dussart1,2 1EA 4129 Laboratory P2S (Health Systemic Process), University of Lyon, University Claude Bernard Lyon 1, Lyon, France; 2Central Pharmacy, Hospices Civils de Lyon, Lyon, France; 3Reference center on hemophilia and other constitutional hemorrhagic diseases, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France; 4Pharmacy, Groupement Hospitalier Est, Hospices Civils de Lyon, Lyon, France; 5Laboratory S2HEP, University of Lyon, University Claude Bernard Lyon 1, Lyon, France; 6Hemophilia Care Center, Centre hospitalier Métropole Savoie, Chambéry, FranceCorrespondence: Karen BenyCentral Pharmacy, Hospices Civils de Lyon, 57 rue Francisque Darcieux, CS 60004, 69563 Saint Genis Laval Cedex, Lyon, FranceTel +33 4 78 86 66 92Fax +33 4 72 67 88 74Email karen.beny@chu-lyon.frBackground: New therapies provide a favorable evolution in the care management of persons with hemophilia. However, the impact of these new therapies on patient care organization remains to be determined. A qualitative study will be implemented to analyze patients’ perception regarding the impact of innovation on the organization of their care management. Secondary objectives will include refining specific factors related to persons with hemophilia (barriers or facilitators, especially the place of treatment) to consider within an organizational impact analysis.Patients and Methods: Semi-structured individual interviews will be conducted via videoconferencing or by phone by two researchers using an interview guide. Participants will be recruited from the Rhône-Alpes region, in France. Physicians from two hemophilia treatment centers will identify eligible patients. Moreover, a call for volunteers will be launched by the Rhône-Alpes committee of the French hemophilia association. Interviews will be conducted with adult patients, adolescent patients or parents of a minor with hemophilia regularly treated prophylactically or on demand. Data analysis will be performed with NVivo® software. Each interview will be analyzed by two researchers using an inductive content analytic method.Discussion: The INNOVHEMO study is an original study analyzing the way patients perceive the impact of an innovation on their care management organization. The resulting patient-specific factors, identified as barriers or facilitators, will need to be integrated into a more comprehensive analysis of the impact of innovation on care management organization.Keywords: therapeutic innovation, hemophilia, care pathway, qualitative research, organizational aspect, patient experience data

BACKGROUND Despite a high prevalence of angiodysplasia, no specific guidelines are available for the modalities of endoscopic exploration of gastrointestinal (GI) bleeding in von Willebrand disease (VWD). Whether VWD patients could benefit from video capsule endoscopy (VCE) looking for angiodysplasia eligible to endoscopic treatment or at high risk of bleeding is unknown. OBJECTIVES To assess the diagnostic efficacy for angiodysplasia and the prognostic value of VCE on top of conventional endoscopy in VWD patients with GI bleeding. PATIENTS/METHODS A survey was sent to the 30 centers of the French-network on inherited bleeding disorders to identify VWD patients referred for endoscopic exploration of GI bleeding from January 2015 to December 2017. Data obtained included patient characteristics, VWD phenotype/genotype, GI bleeding pattern, results of endoscopic investigations, and medical management applied including endoscopic therapy. We assessed by Kaplan-Meier analysis the recurrence-free survival after the first GI bleeding event according to endoscopic categorization and, in patients with angiodysplasia, to the presence of small-bowel localizations on VCE exploration. RESULTS GI bleeding source localization was significantly improved when including VCE exploration (P

Essentials A novel fibrinogen concentrate was evaluated in patients with congenital fibrinogen deficiency. An open-label, phase 2-3 trial studied pharmacology, efficacy, and safety in patients >6 years. The product offers safe and effective therapy in the treatment and prophylaxis of bleeding. Data in recovery show the need of adjusted treatment and further investigation in children. SUMMARY: Background Single-factor replacement therapy is considered the most suitable treatment option for hereditary fibrinogen deficiency. A triple-secured plasma-derived human fibrinogen product was developed to increase the safety of the former fibrinogen concentrate. Objectives This non-randomized, open-label, prospective study investigated pharmacokinetics, efficacy, and safety of a novel fibrinogen concentrate (FibCLOT® /CLOTTAFACT® LFB, France) in inherited deficiency. Patients/Methods Fourteen patients ≥40 kg received fibrinogen concentrate for pharmacology and 16 ≥ 23 kg received treatment for bleeding or surgery. Each treatment was followed by a 3-week safety observation period. Key outcomes included number of infusions, dose, bleeding control, daily assessment, hemoglobin, blood loss, transfusions, and physicians' global assessment of response. Results Incremental recovery was 2.35 mg mL-1 per mg kg-1 and maximal concentration 1.41 g L-1 (geometric mean) after 0.060 g kg-1 infusion in 14 afibrinogenemic patients. Terminal half-life was 69.3 h (non-compartmental analysis). The maximum clot firmness was increased by a mean of 10.3 mm from baseline to maximal effect. Sixteen patients participated to the efficacy phase: 32 bleeding episodes were treated in 9 patients, and 15 patients underwent 38 surgical/invasive procedures. All patients achieved appropriate hemostasis: response to treatment was successful in all bleeds (95% CI, 0.89-1.00) and procedures (95% CI, 0.91-1.00). Most (94%) bleeds were controlled with a single infusion (median 0.050 g kg-1 ). Two patients experienced asymptomatic distal venous thromboses identified by systematic ultrasound. Conclusion FibCLOT® /CLOTTAFACT® showed a pharmacokinetic profile comparable to that of other fibrinogen concentrates and provides safe and clinically effective substitution therapy for fibrinogen-deficient patients.

IntroductionSevere haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.Methods and analysisWe present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14–17 years) with those from a group of young adults (aged 20–29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants’ views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.Ethics and disseminationThe study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.Trial registration numberNCT02866526; Pre-results.

© Springer International Publishing AG, part of Springer Nature 2018. Technologies necessary for the development of pervasive health apps with intensive and seamless interactions with their environments are now widely available. Research studies and experimentations have demonstrated the real ability for health apps to interact with their environment. However, designing, testing and ensuring the maintenance and evolution of pervasive health apps remains very complex. In particular, there is a lack of tools to enable developers to design apps that can adapt to increasingly complex and changing environments (sensors added or removed, failures, mobility etc.). This paper reflects our vision to reduce this complexity and is based on our current research work on smart environment and personalized health monitoring apps. It uses SAM, a smart asthma monitoring app as an illustration to highlight the need for a comprehensive set of new interactions to help health app developers interact with the users’ environment, and more specifically get a smarter access to the data. Some requirements can be on the minimum quality level of the data and the way to adapt to the diversity of the sources (data fusion/aggregation), on the network mechanisms used to collect the data (network/link level) and on the collection of the raw data (sensors). It discusses possible solutions to address these needs.

International audience; Introduction: The value and challenges of long-term prophylaxis (LTP) in adolescents and young adults need further characterisation.Aim: To determine the proportions of adolescents and young adults with severe or moderately severe haemophilia in France under LTP and treatment on demand (OD).Methods: Patients 15 to 25 years old with haemophilia A or B, factor VIII/IX ≤ 2% and no current inhibitor could be included if they had been under factor VIII/IX treatment at least 12 months and kept a treatment and bleeding diary.Results: LTP was administered to 169/212 patients (79.7%) and OD treatment to 40/212 patients (18.9%). The most frequent reasons for initiating LTP were joint bleeding, target joints and frequent bleeds; whereas OD treatment was most often selected on the basis of mild bleeding phenotype or because of constraints on LTP. The mean annual bleed rate (ABR) in the OD group (6.33) was higher than in the LTP group (3.07, p 18–21 and > 21–25 years), but was significantly higher for patients with severe haemophilia (4.02) as compared to those with moderate haemophilia (1.97, p = 0.002). No significant difference was observed in mean ABR for joint bleeds between the LTP and OD groups. Physician reported LTP compliance was good or excellent in 97.0% of patients.Conclusion: LTP is the predominant factor VIII/IX treatment among adolescents and young adults with severe or moderately severe haemophilia in France. LTP was associated with low ABR and high compliance. © 2017 The Authors

En traitant majoritairement du déclin de l’Empire ottoman et de l’épopée républicaine, le roman turc du début du XXe siècle se fait amplement l’écho de la vision officielle de l’État kémaliste moderniste et occidentaliste. Mais au fil du temps, conscients qu’il est vital pour une société de connaître son histoire, des écrivains se repenchent sur le passé ottoman. Dans Devlet Ana (1967) et Osmancık (1983), Kemal Tahir et Tarık Buğra prennent pour sujet le début de la fondation d’un ordre étatique par les tribus turkmènes aux XIIIe et XIVe siècles. Vision marxiste pour l’un, plus spiritualiste pour l’autre, tous deux s’attachent à mettre en lumière les aspects positifs qui ont présidé à la fondation de l’Empire ottoman (défense des valeurs humaines, modèle de droit et de justice) et se rejoignent dans une même défense de l’identité nationale.One of the prominent themes of Turkish literature of the 20th century adresses the decline of the Ottoman Empire and the emergence of the Republic. This largely echoes the official view of the western orientated Kemalistic government. Gradually, some writers became conscious of the vital necessity for the country to embrace its history, and started to examine their ottoman past.In Devlet Ana (1967) and in Osmancık (1983), Kemal Tahir and Tarık Buğra took as a subject the beginning of the foundation of a State by the tribes of Turkmen in the 13th and 14th centuries. Despite a marxist vision on one side and a spiritual view on the other, both of them were attached to putting emphasis on the positive aspects of the ottoman Empire’s foundation ( the defense of human values and the model of law and order) ; they both came together to stand up for the defense of a national identity.

The Reference Model of Open Distributed Processing (RM-ODP) is an emerging ISO/ITU-T standard. It provides a framework of abstractions based on viewpoints, and it defines five viewpoint languages to model open distributed systems. This paper uses the viewpoint languages to specify multiparty audio/video exchange in distributed systems. To the designers of distributed systems, it shows how the concepts and rules of RM-ODP can be applied. The ODP ?binding object? is an important concept to model continuous data flows in distributed systems. We take this concept as a basis for multiparty audio and video flow exchanges, and we provide five ODP viewpoint specifications, each emphasising a particular concern. To ensure overall correctness, special attention is paid to the mapping between the ODP viewpoint specifications.

This paper describes a personalised rehabilitation application using a smart phone (PDA) and wireless (bio) sensors. It instructs and motivates patients to follow their exercise programme and keeps track of their progress. It also monitors the relevant biosignals and provides immediate feedback to the patient. Sensors transmit data to the mobile phone where it is analysed locally and the data can also be instantaneously transmitted to a healthcare centre for remote monitoring by a health professional. The rehabilitation application is personalised for each cardiac patient and provides tailored advice (e.g. exercise more, slow down). A trial with a rehabilitation centre is in progress in which we investigate whether the personalised rehabilitation application improves the success of the rehabilitation programme in terms of patient compliance with recommended life style changes (such as increase physical activity or lose weight) and whether use of the system brings peace of mind to cardiac patients. Copyright 2009 ACM.

This paper describes a heart attack self-test application for a mobile phone that allows potential victims, without the intervention of a medical specialist, to quickly assess whether they are having a heart attack. Heart attacks can occur anytime and anywhere. Using pervasive technology such as a mobile phone and a small wearable ECG sensor it is possible to collect the user's symptoms and to detect the onset of a heart attack by analysing the ECG recordings. If the application assesses that the user is at risk, it will urge the user to call the emergency services immediately. If the user has a cardiac arrest the application will automatically determine the current location of the user and alert the ambulance services and others to the person's location.

© Springer-Verlag Berlin Heidelberg 2002. This paper summarizes the research work that has been conducted in the context of the RTIPA project on policy-based QoS (Quality of Service) and security management for distributed multimedia services. It presents an architecture allowing the derivation of policies from the service level down to the network level. It is a step towards an end-to-end QoS and security management for distributed multimedia services running on the new generation of IP networks.