Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency.

IntroductionHereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available.AimThe aim of this study was to assess safety and efficacy of a new, high‐purity plasma‐derived FX concentrate (pdFX) in subjects with hereditary FX deficiency.MethodsSubjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL−1) received 25 IU kg−1 pdFX as on‐demand treatment or short‐term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end‐of‐study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters.ResultsSixteen enrolled subjects (six aged 12–17 years; 10 aged 18–58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half‐life were 2.00 (2.12; 1.79–2.37) IU dL−1 per IU kg−1 and 29.4 (28.6; 25.8–33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters.ConclusionThese results demonstrate that a dose of 25 IU kg−1 pdFX is safe and efficacious for on‐demand treatment and short‐term prophylaxis in subjects with moderate or severe hereditary FX deficiency

Fibrinogen concentrate for treatment of bleeding and surgical prophylaxis in congenital fibrinogen deficiency patients

Background: Congenital fibrinogen deficiency is an ultra-rare disorder in which patients can experience severe and/or frequent bleeding episodes (BEs). Here, we present the largest prospective study to date on the treatment of this disorder. Methods: Hemostatic efficacy of human fibrinogen concentrate (HFC; FIBRYGA\uae, Octapharma AG) for treatment of bleeding or surgical prophylaxis was assessed by investigators and adjudicated by an independent data monitoring and endpoint adjudication committee (IDMEAC) according to a four-point scale, using objective criteria. Thromboelastometry maximum clot firmness (MCF) was also determined. Results: Twenty-five afibrinogenemia patients were treated with HFC: 24 for on-demand treatment of 89 BEs, and nine as prophylaxis for 12 surgeries. For BEs, treatment success (rating of excellent or good) evaluated by investigators was 96.6% (90% confidence interval [CI], 0.92-0.99; two missing ratings, classified as failures) and by the IDMEAC was 98.9% (90% CI, 0.95-0.999). Mean&nbsp;\ub1&nbsp;standard deviation (SD) increase in MCF was 5.8&nbsp;\ub1&nbsp;2.5&nbsp;mm one hour after the first HFC infusion (mean&nbsp;\ub1&nbsp;SD dose, 61.88&nbsp;\ub1&nbsp;11.73&nbsp;mg/kg). For the 12 surgeries (median [range] HFC dose/surgery, 85.80&nbsp;mg/kg [34.09-225.36]), intraoperative and postoperative treatment success were both rated 100% (90% CI, 0.82-1.00) by investigators and the IDMEAC. Three adverse events were possibly treatment related, including a moderate case of thrombosis. There were no deaths, no severe allergic or hypersensitivity reactions, and no clinical evidence of neutralizing antifibrinogen antibodies. Conclusions: Human fibrinogen concentrate was efficacious for on-demand treatment of bleeding and as surgical prophylaxis, with a favorable safety profile, in patients with congenital afibrinogenemia

Phase 3 study of recombinant von Willebrand factor in patients with severe von Willebrand disease who are undergoing elective surgery

Essentials Recombinant von Willebrand factor (rVWF) is effective in von Willebrand disease (VWD). A phase 3 study of rVWF, with/without recombinant factor VIII (rFVIII) before surgery in VWD. Overall rVWF's efficacy was rated excellent/good; rVWF was administered alone in most patients. rVWF was well-tolerated and hemostasis was achieved in patients with severe VWD undergoing surgery. Summary: Background Recombinant von Willebrand factor (rVWF) has demonstrated efficacy for on-demand treatment of bleeding in severe von Willebrand disease (VWD), warranting evaluation in the surgical setting. Objectives This study (NCT02283268) evaluated the hemostatic efficacy/safety profile of rVWF, with/without recombinant factor VIII (rFVIII), in patients with severe VWD undergoing surgery. Patients/Methods Patients received rVWF 40\u201360\ua0IU\ua0kg 121, VWF ristocetin cofactor activity was measured 12\u201324\ua0h before surgery. If endogenous FVIII activity (FVIII:C) target levels were achieved 3\ua0h before surgery, rVWF was administered alone 1\ua0h before surgery; rVWF was co-administered with rFVIII if target endogenous FVIII levels were not achieved. rVWF was infused postoperatively to maintain target trough levels. Overall and intraoperative hemostatic efficacy, the pharmacodynamics of rVWF administration and the incidence of adverse events (AEs) were assessed. Results All patients treated with rVWF for major (n\ua0=\ua010), minor (n\ua0=\ua04) and oral (n\ua0=\ua01) surgery had overall and intraoperative hemostatic efficacy ratings of excellent (73.3% and 86.7%) or good (26.7% and 13.3%). Most rVWF infusions (89.4%) were administered alone, resulting in hemostatically effective levels of endogenous FVIII within 6\ua0h, which were sustained for 72\u201396\ua0h; 70% (n\ua0=\ua07/10) of major surgeries\ua0were performed without rFVIII co-administration. Six patients reported 12 treatment-emergent AEs. Two\ua0patients each had one serious AE: diverticulitis (not treatment related) and deep vein thrombosis (sponsor-assessed as possibly treatment related). No severe allergic reactions or inhibitory antibodies were reported. Conclusions These data support the efficacy and safety profile of rVWF in patients with severe VWD undergoing elective surgery

A systematic review of protocol studies on conceptual design cognition

This paper reports the first systematic review and synthesis of protocol studies on conceptual design cognition. 47 protocol studies from the domains of architectural design, engineering design, and product de-sign engineering were reviewed towards answering the following re-search question: What is our current understanding of the cognitive processes involved in conceptual design tasks carried out by individual designers? Studies were found to reflect three viewpoints on the cognitive nature of designing, namely: design as search; design as ex-ploration; and design activities. Synthesising the findings of individual studies yielded a classification of cognitive processes involved in con-ceptual design tasks, described in different terms across different viewpoints. Towards a common terminology, these processes are posi-tioned within the cognitive psychology literature, revealing seven basic types of process that appear to be fundamental to designing across all viewpoints: memory (working and long term); visual perception; men-tal imagery; attention; semantic association; cognitive control; and higher-order processes, e.g. analysis and reasoning. The development of common cognitive models of conceptual design, grounded in a sci-entifically rigorous understanding of design cognition, is identified as an avenue for future research

A framework for designing cloud forensic‑enabled services (CFeS)

Cloud computing is used by consumers to access cloud services. Malicious actors exploit vulnerabilities of cloud services to attack consumers. The link between these two assumptions is the cloud service. Although cloud forensics assists in the direction of investigating and solving cloud-based cyber-crimes, in many cases the design and implementation of cloud services falls back. Software designers and engineers should focus their attention on the design and implementation of cloud services that can be investigated in a forensic sound manner. This paper presents a methodology that aims on assisting designers to design cloud forensic-enabled services. The methodology supports the design of cloud services by implementing a number of steps to make the services cloud forensic-enabled. It consists of a set of cloud forensic constraints, a modelling language expressed through a conceptual model and a process based on the concepts identified and presented in the model. The main advantage of the proposed methodology is the correlation of cloud services’ characteristics with the cloud investigation while providing software engineers the ability to design and implement cloud forensic-enabled services via the use of a set of predefined forensic related task

Mental and perceptual feedback in the development of creative flow

Sketching is considered by artists and designers to be a vital tool in the creative process. However, research shows that externalisation during the creative process (i.e., sketching) is not necessary to create effectively. This study examines whether sketching may play a more important role in the subjective experience of creativity by facilitating the deeply focused, optimal state of consciousness termed ‘flow’ (being ‘in the zone’). The study additionally explored whether sketching affects flow by easing cognitive load or by providing a clearer sense of self-feedback. Participants carried out the creative mental synthesis task (combining sets of simple shapes into creative drawings), experimentally simulating the visual creative process. Ideas were generated either mentally before committing to a final drawing, or with external perceptual support through sketching, and cognitive load was varied by using either three- or five-shape sets. The sketching condition resulted in greater experience of flow and lower perceived task difficulty. However, cognitive load did not affect flow and there was no interaction between load and sketching conditions. These findings are the first to empirically demonstrate that sketching increases flow experience, and that this is not dependent on an associated reduction in overall working memory load