14 research outputs found
Surgical evaluation of a recombinant factorVIII prepared using a plasma/albumin-free method: Efficacy and safety of Advate in previously treated patients
Evaluation of factor F(V)III replacement in patients with haemophilia A undergoing surgery is critical for FVIII concentrates, yet large scale, multi-center prospective studies, particularly using continuous infusion, are generally lacking for new products. This study evaluated efficacy and safety of a newly developed recombinant FVIII (rAHF-PFM) administered by bolus or continuous infusion in haemophilia A patients undergoing surgery. Subjects >= 5 years of age with baseline FVIII:C = 150 prior FVIII exposure days were included in this prospective, international, open-label, uncontrolled clinical trial. rAHF-PFM was administered perioperatively by bolus infusion (BI) or continuous infusion (CI) according to the standard use at the center to prevent bleeding complication. Both the surgeon and haematologist rated efficacy during hospitalization. Fifty-eight subjects underwent 65 surgical procedures (22 major haemorrhagic risk; 35 minor, 8 dental procedures). Bolus infusion was used exclusively in 47 procedures and continuous infusion, with or without supplemental bolus infusions, in 18. Haemostatic efficacy was assessed as excellent or good for 100% of intraoperative ratings (17 CI, 44 BI, 61 total procedures), and 100% of postoperative ratings performed at time of discharge (18 CI, 44 BI, 62 total procedures). Median total consumption of rAHF-PFM during hospitalization was 822 IU/kg/surgery with CI and 910 IU/kg/surgery with BI. Overall rAHF-PFM was well tolerated, and FVIII inhibitors were not detected. In conclusion, rAHF-PFM administered via continuous infusion or bolus injections is safe, non-immunogenic, and effective for perioperative hemostatic management in previously treated haemophilia A patients
Population pharmacokinetics of recombinant factor VIII: The relationships of pharmacokinetics to age and body weight
Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half-life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PK-based dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling
Integrated analysis of safety and efficacy of a plasma- and albumin-free recombinant factor VIII (rAHF-PFM) from six clinical studies in patients with hemophilia A
Background: Hemophilia A is an X-linked bleeding disorder that results from insufficient levels of factor VIII (FVIII) coagulant activity. Objective: To evaluate the efficacy and safety of ADVATE® rAHF–PFM (Baxter Healthcare Corporation), a recombinant FVIII concentrate manufactured without human or bovine blood-derived additives, and to assess the effect of compliance with prophylactic use in preventing bleeding episodes (BEs). Methods: Clinical data were integrated from six prospective studies. Two hundred thirty-four hemophilia A subjects (FVIII levels ≤ 2%) (median age 14.7 (range: 0.02 – 72.7) years) were included. Results: BEs were managed with one or two infusions and nearly all (1953/1956) responded to treatment. Compliance with a prophylactic treatment regimen significantly reduced the incidence of BEs (p = 0.0061) and prevented non-traumatic joint BEs (median annualized BE rate was 0). One previously treated subject developed an inhibitor; no other safety concerns were observed. Conclusions: These results reinforce the efficacy and safety of rAHF-PFM and suggest that compliance is an essential contributor to the effectiveness of prophylaxis in the treatment of hemophilia A
Evaporation from Fractures Exposed at the Land Surface: Impact of Gas-Phase Convection on Salt Accumulation
Impact of Thrombolysis on Stroke Outcome at 12 Months in a Population: The Bern Stroke Project
Thrombolysis improves outcome of patients with acute ischemic stroke, but it is unknown whether thrombolysis has a measurable effect on long-term outcome in a defined population
Population pharmacokinetics of recombinant factor VIII: the relationships of pharmacokinetics to age and body weight
Comparison of the pharmacokinetics (PK) of a coagulation factor between groups of patients can be biased by differences in study protocols, in particular between blood sampling schedules. This could affect clinical dose tailoring, especially in children. The aim of this study was to describe the relationships of the PK of factor VIII (FVIII) with age and body weight by a population PK model. The potential to reduce blood sampling was also explored. A model was built for FVIII PK from 236 infusions of recombinant FVIII in 152 patients (1-65 years of age) with severe hemophilia A. The PK of FVIII over the entire age range was well described by a 2-compartment model and a previously reported problem, resulting from differences in blood sampling, to compare findings from children and adults was practically abolished. The decline in FVIII clearance and increase in half-life with age could be described as continuous functions. Retrospective reduction of blood sampling from 11 to 5 samples made no important difference to the estimates of PK parameters. The obtained findings can be used as a basis for PK-based dose tailoring of FVIII in clinical practice, in all age groups, with minimal blood sampling
Watershed ‘chemical cocktails’: forming novel elemental combinations in Anthropocene fresh waters
Este artículo contiene 25 páginas, 9 figuras.In the Anthropocene, watershed chemical
transport is increasingly dominated by novel combinations
of elements, which are hydrologically linked
together as ‘chemical cocktails.’ Chemical cocktails
are novel because human activities greatly enhance
elemental concentrations and their probability for
biogeochemical interactions and shared transport
along hydrologic flowpaths. A new chemical cocktail
approach advances our ability to: trace contaminant
mixtures in watersheds, develop chemical proxies
with high-resolution sensor data, and manage multiple
water quality problems. We explore the following
questions: (1) Can we classify elemental transport in
watersheds as chemical cocktails using a new
approach? (2) What is the role of climate and land
use in enhancing the formation and transport of
chemical cocktails in watersheds? To address these
questions, we first analyze trends in concentrations of
carbon, nutrients, metals, and salts in fresh waters over
100 years. Next, we explore how climate and land use
enhance the probability of formation of chemical
cocktails of carbon, nutrients, metals, and salts. Ultimately, we classify transport of chemical cocktails
based on solubility, mobility, reactivity, and dominant
phases: (1) sieved chemical cocktails (e.g., particulate
forms of nutrients, metals and organic matter); (2)
filtered chemical cocktails (e.g., dissolved organic
matter and associated metal complexes); (3) chromatographic
chemical cocktails (e.g., ions eluted from
soil exchange sites); and (4) reactive chemical cocktails
(e.g., limiting nutrients and redox sensitive
elements). Typically, contaminants are regulated and
managed one element at a time, even though combinations
of elements interact to influence many water
quality problems such as toxicity to life, eutrophication,
infrastructure corrosion, and water treatment. A
chemical cocktail approach significantly expands
evaluations of water quality signatures and impacts
beyond single elements to mixtures. High-frequency
sensor data (pH, specific conductance, turbidity, etc.)
can serve as proxies for chemical cocktails and
improve real-time analyses of water quality violations,
identify regulatory needs, and track water quality
recovery following storms and extreme climate
events. Ultimately, a watershed chemical cocktail
approach is necessary for effectively co-managing
groups of contaminants and provides a more holistic
approach for studying, monitoring, and managing
water quality in the Anthropocene.This work was funded by USDA (award
# 2016-67019-25280) and NSF-EPSCoR (#1641157) for
supporting collaborations at the AGU Chapman Conference
on Extreme Climate Events. Significant funding for data
collection/analyses in this paper was provided by NSF
EAR1521224, NSF CBET1058502, NSF Coastal
SEES1426844, NSF DEB-0423476 and DEB-1027188, NSF
RI EPSCoR NEWRnet Grant No. IIA-1330406, EPA ORD,
Chesapeake Bay Trust, and Multi-state Regional Hatch Project
S-1063.Peer reviewe