Search

Your search keyword '"Lock J"' showing total 1,003 results
Start Over Author "Lock J" Language english
1,003 results on '"Lock J"'

2. Nanomaterials enhance osteogenic differentiation of human mesenchymal stem cells similar to a short peptide of BMP-7

Author

Lock J and Liu H

Subjects
Medicine (General), R5-920
Abstract

Jaclyn Lock, Huinan Liu Department of Bioengineering, University of California, Riverside, CA, USA Background: Nanomaterials have unique advantages in controlling stem cell function due to their biomimetic characteristics and special biological and mechanical properties. Controlling adhesion and differentiation of stem cells is critical for tissue regeneration. Methods: This in vitro study investigated the effects of nano-hydroxyapatite, nano-hydroxyapatite-polylactide-co-glycolide (PLGA) composites, and a bone morphogenetic protein (BMP-7)-derived short peptide (DIF-7c) on osteogenic differentiation of human mesenchymal stem cells (MSC). The peptide was chemically functionalized onto nano-hydroxyapatite, incorporated into a nanophase hydroxyapatite-PLGA composite or PLGA control, or directly injected into culture media. Results: Unlike the PLGA control, the nano-hydroxyapatite-PLGA composites promoted adhesion of human MSC. Importantly, nano-hydroxyapatite and nano-hydroxyapatite-PLGA composites promoted osteogenic differentiation of human MSCs, comparable with direct injection of the DIF-7c peptide into culture media. Conclusion: Nano-hydroxyapatite and nano-hydroxyapatite-PLGA composites provide a promising alternative in directing the adhesion and differentiation of human MSC. These nanocomposites should be studied further to clarify their effects on MSC functions and bone remodeling in vivo, eventually translating to clinical applications. Keywords: human mesenchymal stem cells, osteogenesis, stem cell differentiation, bone morphogenetic protein, peptide delivery, nanocomposites

Published
2011

4. Precision measurement of the specific activity of 39Ar in atmospheric argon with the DEAP-3600 detector

Author

Adhikari, P., Ajaj, R., Alpízar-Venegas, M., Amaudruz, P.-A., Anstey, J., Araujo, G. R., Auty, D. J., Baldwin, M., Batygov, M., Beltran, B., Benmansour, H., Bina, C. E., Bonatt, J., Bonivento, W., Boulay, M. G., Broerman, B., Bueno, J. F., Burghardt, P. M., Butcher, A., Cadeddu, M., Cai, B., Cárdenas-Montes, M., Cavuoti, S., Chen, M., Chen, Y., Choudhary, S., Cleveland, B. T., Corning, J. M., Crampton, R., Cranshaw, D., Daugherty, S., DelGobbo, P., Dering, K., Stefano, P. Di, DiGioseffo, J., Dolganov, G., Doria, L., Duncan, F. A., Dunford, M., Ellingwood, E., Erlandson, A., Farahani, S. S., Fatemighomi, N., Fiorillo, G., Florian, S., Flower, A., Ford, R. J., Gagnon, R., Gallacher, D., Abia, P. García, Garg, S., Giampa, P., Giménez-Alcázar, A., Goeldi, D., Golovko, V. V., Gorel, P., Graham, K., Grant, D. R., Grobov, A., Hallin, A. L., Hamstra, M., Harvey, P. J., Haskins, S., Hearns, C., Hu, J., Hucker, J., Hugues, T., Ilyasov, A., Jigmeddorj, B., Jillings, C. J., Joy, A., Kamaev, O., Kaur, G., Kemp, A., Kuźniak, M., Zia, F. La, Lai, M., Langrock, S., Lehnert, B., Leonhardt, A., LePage-Bourbonnais, J., Levashko, N., Lidgard, J., Lindner, T., Lissia, M., Lock, J., Luzzi, L., Machulin, I., Majewski, P., Maru, A., Mason, J., McDonald, A. B., McElroy, T., McGinn, T., McLaughlin, J. B., Mehdiyev, R., Mielnichuk, C., Mirasola, L., Monroe, J., Nadeau, P., Nantais, C., Ng, C., Noble, A. J., O’Dwyer, E., Oliviéro, G., Ouellet, C., Pal, S., Papi, D., Pasuthip, P., Peeters, S. J. M., Perry, M., Pesudo, V., Picciau, E., Piro, M.-C., Pollmann, T. R., Rad, F., Rand, E. T., Rethmeier, C., Retière, F., Rodríguez García, I., Roszkowski, L., Ruhland, J. B., Santorelli, R., Schuckman II, F. G., Seeburn, N., Seth, S., Shalamova, V., Singhrao, K., Skensved, P., Smith, N. J. T., Smith, B., Sobotkiewich, K., Sonley, T., Sosiak, J., Soukup, J., Stainforth, R., Stone, C., Strickland, V., Stringer, M., Sur, B., Tang, J., Vázquez-Jáuregui, E., Veloce, L., Viel, S., Vyas, B., Walczak, M., Walding, J., Ward, M., Westerdale, S., Willis, J., and Zuñiga-Reyes, A.

Published
2023
Full Text
View/download PDF

6. Desmopressin testing in von Willebrand disease: Lowering the burden

Author

Heijdra, Jessica M., Atiq, Ferdows, Al Arashi, Wala, Kieboom, Quincy, Wuijster, Esmee, Meijer, Karina, Kruip, Marieke J.H.A., Leebeek, Frank W.G., Cnossen, Marjon H., Fijnvandraat, K., Mathôt, R.A.A., Polinder, S., Coppens, M., Tamminga, R.Y.J., Meijer, K., Laros‐van Gorkom, B.A.P., Brons, P., Schols, S.E.M., van der Meer, F.J.M., Eikenboom, H.C.J., Schutgens, R.E.G., Fischer, K., Heubel‐Moenen, F., Nieuwenhuizen, L., Ypma, P., Driessens, M.H.E., Zwaan, C.M., van Vliet, I., Collins, P.W., Liesner, R., Chowdary, P., Keeling, D., Lock, J., Hazendonk, H.C.A.M., van Moort, I., Preijers, T., de Jager, N.C.B., Goedhart, M.C.H.J., Bukkems, L.H., Cloesmeijer, M.E., and Janssen, A.

Published
2022
Full Text
View/download PDF

9. Developmental asynchrony and host species identity predict variability in nestling growth of an obligate brood parasite: a test of the 'growth-tuning' hypothesis

Author

Winnicki, S.K., Strausberger, B.M., Antonson, N.D., Burhans, D.E., Lock, J., Kilpatrick, A.M., and Hauber, M.E.

Subjects
Cowbirds -- Behavior, Parasitism -- Analysis, Nest building -- Analysis, Animal development -- Analysis, Zoology and wildlife conservation
Abstract

Generalist obligate brood parasites are excellent models for studies of developmental plasticity, as they experience a range of social and environmental variation when raised by one of their many hosts. Parasitic Brown-headed Cow-birds (Molothrus ater (Boddaert, 1783)) exhibit host-specific growth rates, yet Cowbird growth rates are not predicted by hosts' incubation or brooding periods. We tested the novel 'growth-tuning' hypothesis which predicts that total asynchrony between Cowbirds' and hosts' nesting periods results in faster parasitic growth in nests where host young fledge earlier than Cowbirds. We tested this prediction using previously published and newly added nestling mass data across diverse host species. Total nesting period asynchrony (summed across incubation and brooding stages) predicted Cowbird growth; 8-day-old Cowbirds were heavier in host nests with relatively shorter nesting periods. We further explored the drivers of variation in growth using mass measurements of Cowbirds in Song Sparrow (Melospiza melodia (A. Wilson, 1810)) and Red-winged Blackbird (Agelaius phoeniceus (Linnaeus, 1766)) nests. Our top models included host species (Cowbirds grew faster in Sparrow nests), numbers of nestmates (slowest when raised alone), and sex (males grew faster). These results confirm that multiple social and environmental factors predict directional patterns of developmental plasticity in avian generalist brood parasites. Key words: brood parasitism, growth, offspring, development, Brown-headed Cowbird, Molothrus ater, Red-winged Blackbird, Agelaius phoeniceus, Song Sparrow, Melospiza melodia. Les parasites de nids obligatoires generalistes constituent d'excellents modeles pour l'etude de la plasticite developpementale, puisqu'ils presentent un eventail de variations sociales et environnementales quand ils sont eleves par une de leurs nombreuses especes hotes. Si les vachers a tete brune (Molothrus ater (Boddaert, 1783)), une espece parasite, presentent des taux de croissance dependant de l'hote, la duree des periodes d'incubation ou de soin des oisillons des hotes ne predit toutefois pas ces taux. Nous avons teste l'hypothese de la<< modulation de la croissance >>, qui predit qu'une asynchronie totale entre les periodes de nidification des vachers et de leurs hotes se traduit par une croissance plus rapide des parasites dans les nids ou les jeunes des hotes s'envolent plus tot que les vachers. Nous avons mis cette prediction a l'epreuve en utilisant des donnees nouvelles et deja publiees sur la masse d'oiseaux niais de differentes especes hotes. L'asynchronie totale des periodes de nidification (sommes des periodes d'incubation et de soin des oisillons) predit la croissance des vachers; les vachersde 8 jours sont pluslourdsdansles nids d'hotes caracterises par des periodes de nidification relativement plus courtes. Nous avons en outre explore les facteurs de variation de la croissance en utilisant des mesures de la masse de vachers dans des nids de bruants chanteurs (Melospiza melodia (A. Wilson, 1810)) et de carouges a epaulettes (Agelaius phoeniceus (Linnaeus, 1766)). Nos meilleurs modeles incluent l'espece hote (les vachers croissent plus vite dans les nids de bruants), le nombre d'oisillons dans le nid (les oisillons solitaires croissent le plus lentement) et le sexe (les males croissent plus rapidement). Ces resultats confirment que de multiples facteurs sociaux et environnementaux expliquent les variations de la plasticite developpementale chez les oiseaux parasites de nids generalistes. [Traduit par la Redaction] Mots-cles : parasitisme de nids, croissance, progeniture, developpement, vacher a tete brune, Molothrus ater, carouge a epaulettes, Agelaius phoeniceus, bruant chanteur, Melospiza melodia., Introduction Animals develop and grow at different rates (McCarty 2001; Dmitriew 2011), with often critical impacts on survival and fitness (Mousseau and Fox 1998). These developmental differences can be caused [...]

Published
2021
Full Text
View/download PDF

10. One piece of the puzzle: Population pharmacokinetics of FVIII during perioperative Haemate P®/Humate P® treatment in von Willebrand disease patients

Author

de Jager, Nico C.B., Bukkems, Laura H., Heijdra, Jessica M., Hazendonk, Carolien H.C.A.M., Fijnvandraat, Karin, Meijer, Karina, Eikenboom, Jeroen, Laros - van Gorkom, Britta A.P., Leebeek, Frank W.G., Cnossen, Marjon H., Mathôt, Ron A.A., Collins, P.W., Kruip, M.J.H.A., Polinder, S., Lock, J., van Moort, I., Goedhart, M.C.H.J., Coppens, M., Peters, M., Preijers, T., Brons, P., van der Meer, F.J.M., Schutgens, R.E.G., Fischer, K., Driessens, M.H.E., Zwaan, C.M., van Vliet, I., Liesner, R., Chowdary, P., and Keeling, D.

Published
2020
Full Text
View/download PDF

11. Pulse-shape discrimination against low-energy Ar-39 beta decays in liquid argon with 4.5 tonne-years of DEAP-3600 data

Author

Adhikari, P., Ajaj, R., Alpízar-Venegas, M., Amaudruz, P.-A., Auty, D. J., Batygov, M., Beltran, B., Benmansour, H., Bina, C. E., Bonatt, J., Bonivento, W., Boulay, M. G., Broerman, B., Bueno, J. F., Burghardt, P. M., Butcher, A., Cadeddu, M., Cai, B., Cárdenas-Montes, M., Cavuoti, S., Chen, M., Chen, Y., Cleveland, B. T., Corning, J. M., Cranshaw, D., Daugherty, S., DelGobbo, P., Dering, K., DiGioseffo, J., Di Stefano, P., Doria, L., Duncan, F. A., Dunford, M., Ellingwood, E., Erlandson, A., Farahani, S. S., Fatemighomi, N., Fiorillo, G., Florian, S., Flower, T., Ford, R. J., Gagnon, R., Gallacher, D., García Abia, P., Garg, S., Giampa, P., Goeldi, D., Golovko, V., Gorel, P., Graham, K., Grant, D. R., Grobov, A., Hallin, A. L., Hamstra, M., Harvey, P. J., Hearns, C., Hugues, T., Ilyasov, A., Joy, A., Jigmeddorj, B., Jillings, C. J., Kamaev, O., Kaur, G., Kemp, A., Kochanek, I., Kuźniak, M., Lai, M., Langrock, S., Lehnert, B., Leonhardt, A., Levashko, N., Li, X., Lidgard, J., Lindner, T., Lissia, M., Lock, J., Longo, G., Machulin, I., McDonald, A. B., McElroy, T., McGinn, T., McLaughlin, J. B., Mehdiyev, R., Mielnichuk, C., Monroe, J., Nadeau, P., Nantais, C., Ng, C., Noble, A. J., O’Dwyer, E., Oliviéro, G., Ouellet, C., Pal, S., Pasuthip, P., Peeters, S. J. M., Perry, M., Pesudo, V., Picciau, E., Piro, M.-C., Pollmann, T. R., Rand, E. T., Rethmeier, C., Retière, F., Rodríguez-García, I., Roszkowski, L., Ruhland, J. B., Sánchez-García, E., Santorelli, R., Sinclair, D., Skensved, P., Smith, B., Smith, N. J. T., Sonley, T., Soukup, J., Stainforth, R., Stone, C., Strickland, V., Stringer, M., Sur, B., Tang, J., Vázquez-Jáuregui, E., Viel, S., Walding, J., Waqar, M., Ward, M., Westerdale, S., Willis, J., and Zuñiga-Reyes, A.

Published
2021
Full Text
View/download PDF

12. Efficacy and safety of bexagliflozin compared with dapagliflozin as an adjunct to metformin in Chinese patients with type 2 diabetes mellitus: A 24‐week, randomized, double‐blind, active‐controlled, phase 3 trial.

Author

Xie, Lingding, Han, Jie, Cheng, Zhifeng, Liu, Dexue, Liu, Jie, Xu, Chunrong, Sun, Wenli, Li, Qingju, Bian, Fang, Zhang, Wei, Chen, Jinyu, Zhu, Qian, Thurber, Tara K., Lock, J. Paul, and Zhang, Bo

Subjects
TYPE 2 diabetes, CLINICAL trials, CHINESE people, DAPAGLIFLOZIN, METFORMIN, PHOTOPLETHYSMOGRAPHY
Abstract

Background: Bexagliflozin and dapagliflozin are sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. No direct comparison of SGLT2 inhibitors in a randomized controlled trial has been reported to date. Methods: This was a multicenter, randomized, double‐blind, active‐controlled trial comparing bexagliflozin to dapagliflozin for the treatment of type 2 diabetes mellitus in adults with disease inadequately controlled by metformin. Subjects (n = 406) were randomized to receive bexagliflozin (20 mg) or dapagliflozin (10 mg) plus metformin. The primary endpoint was noninferiority of bexagliflozin to dapagliflozin for the change in glycated hemoglobin (HbA1c) from baseline to week 24. Secondary endpoints included intergroup differences in fasting plasma glucose (FPG), 2‐h‐postprandial glucose (PPG), body weight, and systolic blood pressure (SBP) from baseline to week 24. The trial also evaluated the safety profiles. Results: The model‐adjusted mean change from baseline to week 24 HbA1c was −1.08% for bexagliflozin and −1.10% for dapagliflozin. The intergroup difference of 0.03% (95% confidence interval [CI] −0.14% to 0.19%) was below the prespecified margin of 0.4%, confirming the noninferiority of bexagliflozin. The changes from baseline in FPG, PPG, body weight, and SBP were −1.95 mmol/L, −3.24 mmol/L, −2.52 kg, and −6.4 mm Hg in the bexagliflozin arm and −1.87 mmol/L, −3.07 mmol/L, −2.22 kg, and −6.3 mm Hg in the dapagliflozin arm. Adverse events were experienced in 62.6% and 65.0% and serious adverse events affected 4.4% and 3.5% of subjects in the bexagliflozin and dapagliflozin arm, respectively. Conclusions: Bexagliflozin showed nearly identical effects and a similar safety profile to dapagliflozin when used in Chinese patients on metformin. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

13. Population pharmacokinetics of factor IX in hemophilia B patients undergoing surgery

Author

Preijers, T., Hazendonk, H.C.A.M., Liesner, R., Chowdary, P., Driessens, M.H.E., Hart, D., Keeling, D., Laros‐van Gorkom, B.A.P., van der Meer, F.J.M., Meijer, K., Fijnvandraat, K., Leebeek, F.W.G., Collins, P.W., Cnossen, M.H., Mathôt, R.A.A., Kruip, M.J.A.H., Polinder, S., Lock, J., van Moort, I., Heijdra, J.M., Nederlof, A., de Jager, N., Coppens, M., Peters, M., Tamminga, R.Y.J., Brons, P., Eikenboom, H.C.J., Schutgens, R.E.G., Fischer, K., Zwaan, C.M., and van Vliet, I.

Published
2018
Full Text
View/download PDF

16. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial

Author

El-Khatib, Firas H, Balliro, Courtney, Hillard, Mallory A, Magyar, Kendra L, Ekhlaspour, Laya, Sinha, Manasi, Mondesir, Debbie, Esmaeili, Aryan, Hartigan, Celia, Thompson, Michael J, Malkani, Samir, Lock, J Paul, Harlan, David M, Clinton, Paula, Frank, Eliana, Wilson, Darrell M, DeSalvo, Daniel, Norlander, Lisa, Ly, Trang, Buckingham, Bruce A, Diner, Jamie, Dezube, Milana, Young, Laura A, Goley, April, Kirkman, M Sue, Buse, John B, Zheng, Hui, Selagamsetty, Rajendranath R, Damiano, Edward R, and Russell, Steven J

Published
2017
Full Text
View/download PDF

18. The liquid-argon scintillation pulseshape in DEAP-3600

Author

Adhikari, P., Ajaj, R., Araujo, G. R., Batygov, M., Beltran, B., Bina, C. E., Boulay, M. G., Broerman, B., Bueno, J. F., Butcher, A., Cai, B., Cárdenas-Montes, M., Cavuoti, S., Chen, Y., Cleveland, B. T., Corning, J. M., Daugherty, S. J., Di Stefano, P., Dering, K., Doria, L., Duncan, F. A., Dunford, M., Erlandson, A., Fatemighomi, N., Fiorillo, G., Flower, A., Ford, R. J., Gagnon, R., Gallacher, D., Garcés , E. A., Abia, P. García, Garg, S., Giampa, P., Goeldi, D., Golovko, V. V., Gorel, P., Graham, K., Grant, D. R., Grobov, A., Hallin, A. L., Hamstra, M., Harvey, P. J., Hearns, C., Ilyasov, A., Joy, A., Jillings, C. J., Kamaev, O., Kaur, G., Kemp, A., Kochanek, I., Kuźniak, M., Langrock, S., La Zia, F., Lehnert, B., Levashko, N., Li, X., Litvinov, O., Lock, J., Longo, G., Machulin, I., Majewski, P., McDonald, A. B., McElroy, T., McGinn, T., McLaughlin, J. B., Mehdiyev, R., Mielnichuk, C., Monroe, J., Nadeau, P., Nantais, C., Ng, C., Noble, A. J., Oliviéro, G., Ouellet, C., Pal, S., Pasuthip, P., Peeters, S. J. M., Pesudo, V., Piro, M.-C., Pollmann, T. R., Rand, E. T., Rethmeier, C., Retière, F., García, E. Sanchez, Sánchez-Pastor, T., Santorelli, R., Seeburn, N., Skensved, P., Smith, B., Smith, N. J. T., Sonley, T., Stainforth, R., Stone, C., Strickland, V., Stringer, M., Sur, B., Vázquez-Jáuregui, E., Veloce, L., Viel, S., Walding, J., Waqar, M., Ward, M., Westerdale, S., Willis, J., and Zuñiga-Reyes, A.

Published
2020
Full Text
View/download PDF

19. Meta‐analysis of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin.

Author

McMurray, John J. V., Solomon, Scott D., Lock, J. Paul, Massaro, Joseph M., Zhu, Fang, Zhou, Wenjiong, Skali, Hicham, Lewis, Eldrin F., Freeman, Mason W., and Halvorsen, Yuan‐Di C.

Subjects
MAJOR adverse cardiovascular events, TYPE 2 diabetes, ANGINA pectoris
Abstract

Aim: To explore the risk of major adverse cardiovascular events (MACE) associated with exposure to bexagliflozin. Methods: The analysis included 4090 participants with type 2 diabetes (T2D) enrolled in nine phase 2 and 3 double‐blind randomized controlled trials. All potential MACE were adjudicated by a blinded committee. The primary endpoint for the meta‐analysis was the hazard ratio (HR) for the time to first occurrence of non‐fatal stroke, non‐fatal myocardial infarction (MI), cardiovascular (CV) death or hospitalization for unstable angina (MACE+), tested for non‐inferiority to a ratio of 1.8. The secondary endpoints were time to first occurrence of (i) non‐fatal stroke, non‐fatal MI or CV death (MACE), tested for non‐inferiority to a ratio of 1.3; and (ii) CV death or hospitalization for heart failure, tested for superiority. Results: The HR for the primary endpoint of MACE+ was 0.80 (95% confidence interval [CI] 0.58, 1.09), which fulfilled the non‐inferiority objective with a P value of less than 0.0001. Non‐inferiority for the first key secondary endpoint of MACE was also shown (HR = 0.82; 95% CI 0.59, 1.13; P = 0.0023). Superiority for time to CV death or first hospitalization for heart failure was not shown. Conclusions: Bexagliflozin did not increase the risk of MACE in participants with T2D when compared with placebo or active control. Both the preapproval and postapproval thresholds for CV safety were met and bexagliflozin has been approved by the US Food and Drug Administration. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

28. Strange usurped potentates: Elizabeth I, the papacy and the Indian summer of the medieval deposing power

Author

Lock, J

Subjects
Anti-Catholicism -- England -- History -- 16th century, Great Britain -- Foreign relations -- Catholic Church -- History -- 16th century, Catholic Church -- Foreign relations -- Great Britain -- History -- 16th century
Abstract

This thesis centres on a pivotal event in the development of religious antagonism in England - the papal excommunication and deposition of Elizabeth I - considering its origins and consequences, especially its effect on Protestant thought and writing (since the political thought of Elizabethan Catholics has undergone more recent study). The event appears as a revival of a claim not so antiquated as it is sometimes seen. I survey the medieval precedents for the papal claim to depose secular princes, which have lacked an overall survey, and the (often exaggerated) sixteenth-century views as to its past influence. There was indeed an exceptionally acute sense of this aspect of history during the early English Reformation. The effect of this was that the actual deposition in 1570 served only to confirm Protestants’ preconceptions. In their views of history, they tended towards a conspiracy theory whereby the influence of Pope and prelates lay behind most, if not all, opposition to English and European monarchies. In their views of contemporary foreign affairs, they had, since the beginning of Elizabeth's reign, constantly suspected the machinations of a (fictional) Catholic League, whereby Catholic powers, probably in conjunction with an internal rising, would combine to destroy Protestant England. This would be heralded by the constantly predicted papal sentence against Elizabeth. Demonstrably, this was not the case. Disagreements among Catholic potentates precluded any such agreement in the early part of Elizabeth's reign; and ensured that, when Pius V did issue his sentence, it proved a dangerous embarrassment (in no way mitigated by Gregory XIII's qualification of it). It did serve a pivotal role in actual Catholic plans, which however were unable to overcome conflicting interests; the result was notoriety without efficacy. Nevertheless, a paranoid and pessimistic view predominated in Protestant England, diminishing only Slowly even when overt confrontation late in the reign began to be crowned with success. Constant alertness for conflict had proved something of a self-fulfilling prophecy.

Published
2022

30. One piece of the puzzle

Author

Jager, N.C.B. de, Bukkems, L.H., Heijdra, J.M., Hazendonk, C.H.C.A.M., Fijnvandraat, K., Meijer, K., Eikenboom, J., Laros-van Gorkom, B.A.P., Leebeek, F.W.G., Cnossen, M.H., Mathot, R.A.A., Kruip, M.J.H.A., Polinder, S., Lock, J., Hazendonk, H.C.A.M., Moort, I. van, Goedhart, M.C.H.J., Coppens, M., Peters, M., Preijers, T., Tamminga, R.Y.J., Brons, P., Meer, F.J.M. van der, Eikenboom, H.C.J., Schutgens, R.E.G., Fischer, K., Driessens, M.H.E., Zwaan, C.M., Vliet, I. van, Collins, P.W., Liesner, R., Chowdary, P., Keeling, D., OPTI-CLOT Grp, Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Graduate School, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, Pharmacy, Paediatric Haematology, ACS - Pulmonary hypertension & thrombosis, Amsterdam Reproduction & Development (AR&D), Pediatrics, and Hematology

Subjects
medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Population, 030204 cardiovascular system & hematology, Haemophilia, DIAGNOSIS, Gastroenterology, CLASSIFICATION, surgery, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Von Willebrand factor, Internal medicine, hemic and lymphatic diseases, Von Willebrand disease, MANAGEMENT, Medicine, education, Haemate P, Volume of distribution, education.field_of_study, biology, business.industry, FACTOR-VIII, PSN, Hematology, Perioperative, medicine.disease, NONMEM, individualized medicine, biology.protein, business, von Willebrand disease, pharmacokinetics
Abstract

Contains fulltext : 218302.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Many patients with von Willebrand disease (VWD) are treated on demand with von Willebrand factor and factor VIII (FVIII) containing concentrates present with VWF and/or FVIII plasma levels outside set target levels. This carries a risk for bleeding and potentially for thrombosis. Development of a population pharmacokinetic (PK) model based on FVIII levels is a first step to more accurate on-demand perioperative dosing of this concentrate. METHODS: Patients with VWD undergoing surgery in Academic Haemophilia Treatment Centers in the Netherlands between 2000 and 2018 treated with a FVIII/VWF plasma-derived concentrate (Haemate(R) P/Humate P(R)) were included in this study. Population PK modeling was based on measured FVIII levels using nonlinear mixed-effects modeling (NONMEM). RESULTS: The population PK model was developed using 684 plasma FVIII measurements of 97 VWD patients undergoing 141 surgeries. Subsequently, the model was externally validated and reestimated with independent clinical data from 20 additional patients undergoing 31 surgeries and 208 plasma measurements of FVIII. The observed PK profiles were best described using a one-compartment model. Typical values for volume of distribution and clearance were 3.28 L/70 kg and 0.037 L/h/70 kg. Increased VWF activity, decreased physical status according to American Society of Anesthesiologists (ASA) classification (ASA class >2), and increased duration of surgery were associated with decreased FVIII clearance. CONCLUSION: This population PK model derived from real world data adequately describes FVIII levels following perioperative administration of the FVIII/VWF plasma-derived concentrate (Haemate((R)) P/Humate P((R)) ) and will help to facilitate future dosing in VWD patients.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results