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Article ; Online: Current and Emerging Options for the Management of Inherited von Willebrand Disease.

Heijdra, Jessica M / Cnossen, Marjon H / Leebeek, Frank W G

2017 Volume 77, Issue 14, Page(s) 1531–1547

Abstract: Von Willebrand disease (VWD) is the most common inherited bleeding disorder with an estimated prevalence of ~1% and clinically relevant bleeding symptoms in approximately 1:10,000 individuals. VWD is caused by a deficiency and/or defect of von Willebrand ...

Abstract	Von Willebrand disease (VWD) is the most common inherited bleeding disorder with an estimated prevalence of ~1% and clinically relevant bleeding symptoms in approximately 1:10,000 individuals. VWD is caused by a deficiency and/or defect of von Willebrand factor (VWF). The most common symptoms are mucocutaneous bleeding, hematomas, and bleeding after trauma or surgery. For decades, treatment to prevent or treat bleeding has consisted of desmopressin in milder cases and of replacement therapy with plasma-derived concentrates containing VWF and Factor VIII (FVIII) in more severe cases. Both are usually combined with supportive therapy, e.g. antifibrinolytic agents, and maximal hemostatic measures. Several developments such as the first recombinant VWF concentrate, which has been recently licensed for VWD, will make a more "personalized" approach to VWD management possible. As research on new treatment strategies for established therapies, such as population pharmacokinetic-guided dosing of clotting factor concentrates, and novel treatment modalities such as aptamers and gene therapy are ongoing, it is likely that the horizon to tailor therapy to the individual patients' needs will be extended, thus, further improving the already high standard of care in VWD in most high-resource countries.
MeSH term(s)	Antifibrinolytic Agents/pharmacology ; Antifibrinolytic Agents/therapeutic use ; Aptamers, Nucleotide/therapeutic use ; Deamino Arginine Vasopressin/therapeutic use ; Factor VIII/metabolism ; Genetic Therapy ; Hemorrhage/therapy ; Hemostatic Techniques ; Humans ; Interleukin-11/metabolism ; von Willebrand Diseases/genetics ; von Willebrand Diseases/therapy ; von Willebrand Factor/metabolism
Chemical Substances	Antifibrinolytic Agents ; Aptamers, Nucleotide ; Interleukin-11 ; von Willebrand Factor ; F8 protein, human (839MOZ74GK) ; Factor VIII (9001-27-8) ; Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2017-07-16
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	120316-2
ISSN	1179-1950 ; 0012-6667
ISSN (online)	1179-1950
ISSN	0012-6667
DOI	10.1007/s40265-017-0793-2
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Article ; Online: Desmopressin testing in von Willebrand disease: Lowering the burden.

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

Research and practice in thrombosis and haemostasis

2022 Volume 6, Issue 6, Page(s) e12784

Abstract: Background: Individuals with von Willebrand disease (VWD) require desmopressin testing because of interindividual response differences. However, testing is burdensome, while not all patients may need extensive testing.: Objectives: To provide von ... ...

Abstract	Background: Individuals with von Willebrand disease (VWD) require desmopressin testing because of interindividual response differences. However, testing is burdensome, while not all patients may need extensive testing. Objectives: To provide von Willebrand factor (VWF) cutoffs that predict desmopressin nonresponse and thereby identify individuals who do not need extensive testing in a retrospective cohort. We validated these cutoffs in a prospective cohort. Patients and methods: We included 376 patients (Type 1 VWD with VWF activity [VWF:Act] <0.30 IU/ml: Results: All individuals with Type 1 VWD and Type 2 VWD, respectively, with baseline VWF:Act 0.34 IU/ml or greater or 0.28 IU/ml or greater were responders. In individuals with T1 VWF:Act ≥0.89 IU/ml (Type 1 VWD) or T1 VWF:Act 1.10 IU/ml or greater (Type 2 VWD), response remained at T4. Conclusion: Desmopressin testing is not needed when lowest historical VWF:Act is 0.30 IU/ml or greater. In patients with Type 1 VWD who require testing, measurements after T1 are often not needed. In patients with Type 2 VWD who require testing, we advise performing T1 and T4 measurements.
Language	English
Publishing date	2022-09-26
Publishing country	United States
Document type	Journal Article
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1002/rth2.12784
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Article ; Online: Is pharmacokinetic-guided dosing of desmopressin and von Willebrand factor-containing concentrates in individuals with von Willebrand disease or low von Willebrand factor reliable and feasible? A protocol for a multicentre, non-randomised, open label cohort trial, the OPTI-CLOT: to WiN study.

Heijdra, Jessica M / Al Arashi, Wala / de Jager, Nico C B / Cloesmeijer, Michael E / Bukkems, Laura H / Zwaan, Christian M / Leebeek, Frank W G / Mathôt, Ron A A / Cnossen, Marjon H

BMJ open

2022 Volume 12, Issue 2, Page(s) e049493

Abstract: Introduction: Von Willebrand disease (VWD) is a bleeding disorder, caused by a deficiency or defect of von Willebrand factor (VWF). In case of medical procedures or bleeding, patients are treated with desmopressin and/or VWF-containing concentrates to ... ...

Abstract	Introduction: Von Willebrand disease (VWD) is a bleeding disorder, caused by a deficiency or defect of von Willebrand factor (VWF). In case of medical procedures or bleeding, patients are treated with desmopressin and/or VWF-containing concentrates to increase plasma VWF and factor VIII (FVIII). However, in many cases these factor levels are outside the targeted range. Therefore, population pharmacokinetic (PK) models have been developed, which aim to quantify and explain intraindividual and interindividual differences in treatment response. These models enable calculation of individual PK parameters by Bayesian analysis, based on an individual desmopressin test or PK profile with a VWF-containing concentrate. Subsequently, the dose necessary for an individual to achieve coagulation factor target levels can be calculated. Methods and analysis: Primary aim of this study is to assess the predictive performance (the difference between predicted and measured von VWF activity and FVIII levels) of Bayesian forecasting using the developed population PK models in four different situations: (A) desmopressin testing (n≥30); (B) medical procedures (n=70; 30 receiving desmopressin, 30 receiving VWF-containing concentrate and 10 receiving a combination of both); (C) bleeding episodes (n=20; 10 receiving desmopressin and 10 receiving VWF-containing concentrate) and (D) prophylaxis with a VWF-containing concentrate (n=3 to 5). Individuals with all types of VWD and individuals with low VWF (VWF 0.30-0.60 IU/mL) will be included. Reliability and feasibility of PK-guided dosing will be tested by assessing predictive performance, treatment duration, haemostasis, patient satisfaction and physician satisfaction. Ethics and dissemination: The OPTI-CLOT:to WiN study was approved by the medical ethics committee of the Erasmus MC, University Medical Centre Rotterdam, the Netherlands. Results of the study will be communicated through publication in international scientific journals and presentation at (inter)national conferences. Trial registration number: NL7212 (NTR7411); Pre-results, EudraCT 2018-001631-46.
MeSH term(s)	Bayes Theorem ; Deamino Arginine Vasopressin ; Humans ; Multicenter Studies as Topic ; Reproducibility of Results ; von Willebrand Diseases/drug therapy ; von Willebrand Factor
Chemical Substances	von Willebrand Factor ; Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2022-02-15
Publishing country	England
Document type	Clinical Trial Protocol ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2021-049493
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Article ; Online: Quantification of the relationship between desmopressin concentration and Von Willebrand factor in Von Willebrand disease type 1: A pharmacodynamic study.

Heijdra, Jessica M / Cloesmeijer, Michael E / de Jager, Nico C B / Leebeek, Frank W G / Kruip, Marieke H J A / Cnossen, Marjon H / Mathôt, Ron A A

Haemophilia : the official journal of the World Federation of Hemophilia

2022 Volume 28, Issue 5, Page(s) 814–821

Abstract: Introduction: Desmopressin can be used to prevent bleeding in von Willebrand disease (VWD), but the relationship between desmopressin and von Willebrand factor activity (VWF:Act) has yet to be quantified.: Aim: To quantify the relationship between ... ...

Abstract	Introduction: Desmopressin can be used to prevent bleeding in von Willebrand disease (VWD), but the relationship between desmopressin and von Willebrand factor activity (VWF:Act) has yet to be quantified. Aim: To quantify the relationship between desmopressin dose, its plasma concentration and the VWF:Act response in type 1 VWD patients. Methods: Forty-seven VWD patients (median age 25 years, IQR: 19-37; median body weight 71 kg, IQR: 59-86) received an IV desmopressin dose of .3 mcg/kg. In total, 177 blood samples were available for analysis. We developed an integrated population pharmacokinetic-pharmacodynamic (PK-PD) model using nonlinear mixed effect modelling. Subsequently, we performed Monte Carlo simulations to investigate the efficacy of the current dosing regimen. Results: A one-compartment PK model best described the time profile of the desmopressin concentrations. In the PD turnover model, the relationship between desmopressin plasma concentration and release of VWF:Act from the vascular endothelium was best described with an Emax model. Typically, VWF:Act increased 452% with an EC50 of .174 ng/ml. Simulations demonstrated that after .3 mcg/kg desmopressin intravenously, >90% patients with a VWF:Act baseline of ≥.20 IU/mL attain a VWF:Act >.5 IU/ml up to ≥4 h after administration. A capped dose of 30 mcg was sufficient in patients weighing over 100 kg. Conclusion: The relationship between desmopressin and VWF:Act was quantified in a PK-PD model. The simulations provide evidence that recently published international guidelines advising an intravenous desmopressin dose of .3 mcg/kg with a capped dose of 30 mcg > 100 kg gives a sufficient desmopressin response.
MeSH term(s)	Adult ; Deamino Arginine Vasopressin/pharmacology ; Deamino Arginine Vasopressin/therapeutic use ; Factor VIII/therapeutic use ; Humans ; von Willebrand Disease, Type 1/drug therapy ; von Willebrand Diseases/drug therapy ; von Willebrand Factor/therapeutic use
Chemical Substances	von Willebrand Factor ; Factor VIII (9001-27-8) ; Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2022-05-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/hae.14582
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Article ; Online: Desmopressin response depends on the presence and type of genetic variants in patients with type 1 and type 2 von Willebrand disease.

Atiq, Ferdows / Heijdra, Jessica / Snijders, Fleur / Boender, Johan / Kempers, Eva / van Heerde, Waander L / Maas, Dominique P M S M / Krouwel, Sandy / Schoormans, Selene C / de Meris, Joke / Schols, Saskia E M / van Galen, Karin P M / van der Bom, Johanna G / Cnossen, Marjon H / Meijer, Karina / Fijnvandraat, Karin / Eikenboom, Jeroen / Leebeek, Frank W G

Blood advances

2022 Volume 6, Issue 18, Page(s) 5317–5326

Abstract: Patients with type 1 and type 2 von Willebrand disease (VWD) can be treated with desmopressin. Although a previous study has shown that the location of the causative VWF gene variant is associated with desmopressin response in type 1 VWD, the association ...

Abstract	Patients with type 1 and type 2 von Willebrand disease (VWD) can be treated with desmopressin. Although a previous study has shown that the location of the causative VWF gene variant is associated with desmopressin response in type 1 VWD, the association between variants in the VWF gene and desmopressin response is not yet fully understood. Our primary aim was to compare desmopressin response in type 1 VWD patients with and without a VWF gene variant. Secondly, we investigated whether desmopressin response depends on specific VWF gene variants in type 1 and type 2 VWD. We included 250 patients from the Willebrand in the Netherlands study: 72 type 1 without a VWF gene variant, 108 type 1 with a variant, 45 type 2A, 16 type 2M, and 9 type 2N patients. VWF gene was analyzed with ion semiconductor sequencing and Multiplex Ligation-dependent Probe Amplification. Complete response to desmopressin was observed in all type 1 VWD patients without a variant, 64.3% of type 1 patients with a variant, and 31.3% of type 2 patients (P < .001). Despite a large interindividual variability in desmopressin response, patients with the same variant had comparable desmopressin responses. For instance, in 6 type 1 patients with exon 4 to 5 deletion, mean VWF activity at 1 hour after desmopressin was 0.81 IU/mL, with a coefficient of variation of 22.9%. In conclusion, all type 1 VWD patients without a VWF gene variant respond to desmopressin. In type 1 and type 2 VWD patients with a VWF variant, desmopressin response highly depends on the VWF gene variants.
MeSH term(s)	Deamino Arginine Vasopressin/pharmacology ; Deamino Arginine Vasopressin/therapeutic use ; Exons ; Humans ; von Willebrand Disease, Type 2/drug therapy ; von Willebrand Disease, Type 2/genetics ; von Willebrand Diseases/genetics ; von Willebrand Factor/genetics
Chemical Substances	von Willebrand Factor ; Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2022-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2021006757
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Article ; Online: A Novel Quantitative Method for Analyzing Desmopressin in Human Plasma Using Liquid Chromatography-Tandem Mass Spectrometry.

de Jager, Nico C B / Heijdra, Jessica M / Pistorius, Marcel / Kruip, Marieke J H A / Leebeek, Frank W G / Cnossen, Marjon H / Mathôt, Ron A A

Therapeutic drug monitoring

2020 Volume 42, Issue 6, Page(s) 880–885

Abstract: Background: Desmopressin (D-amino D-arginine vasopressin: dDAVP) is used for the treatment of patients with hemophilia A and Von Willebrand disease. Studies on the rationale of dosing are scarce and mainly focus on the underlying causes of the vast ... ...

Abstract	Background: Desmopressin (D-amino D-arginine vasopressin: dDAVP) is used for the treatment of patients with hemophilia A and Von Willebrand disease. Studies on the rationale of dosing are scarce and mainly focus on the underlying causes of the vast differences in desmopressin response among individuals. The aim of this study was to develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of desmopressin in human plasma for identifying its pharmacokinetics and its therapeutic effect relationship in patients with bleeding disorder. Methods: The method entails solid-phase extraction with ion exchange for sample clean-up, followed by an LC-MS/MS run. The technique has been validated for analytical selectivity as well as specificity, process efficiency, linearity, accuracy, imprecision, and stability. Results: This method showed good selectivity because no significant chromatographic matrix interferences were observed. The determination coefficient (R) of the calibration curves was ≥0.990. Analyte accuracy ranged from 89.2% to 111.8%, and the between- and within-run imprecision was less than 9.3% in a plasma concentration and range from 60 to 3200 pg/mL. Samples were stable during 3 freeze/thaw cycles with an additional 120 hours of storage at room temperature (21°C-24°C) and 96 hours in the autosampler (10°C). The total run time was approximately 5 minutes. Conclusions: The LC-MS/MS method presented enables quantification of desmopressin in human plasma, and it is sensitive, specific, efficient, accurate, and precise. This analytical technique is a valuable and useful tool to study the interpatient variability of pharmacokinetics.
MeSH term(s)	Chromatography, Liquid ; Deamino Arginine Vasopressin/blood ; Humans ; Reproducibility of Results ; Sensitivity and Specificity ; Solid Phase Extraction ; Tandem Mass Spectrometry
Chemical Substances	Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2020-07-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	424443-6
ISSN	1536-3694 ; 0163-4356
ISSN (online)	1536-3694
ISSN	0163-4356
DOI	10.1097/FTD.0000000000000791
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Article ; Online: Population pharmacokinetics of the von Willebrand factor-factor VIII interaction in patients with von Willebrand disease.

Bukkems, Laura H / Heijdra, Jessica M / de Jager, Nico C B / Hazendonk, Hendrika C A M / Fijnvandraat, Karin / Meijer, Karina / Eikenboom, Jeroen C J / Laros-van Gorkom, Britta A P / Leebeek, Frank W G / Cnossen, Marjon H / Mathôt, Ron A A

Blood advances

2021 Volume 5, Issue 5, Page(s) 1513–1522

Abstract: Recent studies have reported that patients with von Willebrand disease treated perioperatively with a von Willebrand factor (VWF)/factor VIII (FVIII) concentrate with a ratio of 2.4:1 (Humate P/Haemate P) often present with VWF and/or FVIII levels ... ...

Abstract	Recent studies have reported that patients with von Willebrand disease treated perioperatively with a von Willebrand factor (VWF)/factor VIII (FVIII) concentrate with a ratio of 2.4:1 (Humate P/Haemate P) often present with VWF and/or FVIII levels outside of prespecified target levels necessary to prevent bleeding. Pharmacokinetic (PK)-guided dosing may resolve this problem. As clinical guidelines increasingly recommend aiming for certain target levels of both VWF and FVIII, application of an integrated population PK model describing both VWF activity (VWF:Act) and FVIII levels may improve dosing and quality of care. In total, 695 VWF:Act and 894 FVIII level measurements from 118 patients (174 surgeries) who were treated perioperatively with the VWF/FVIII concentrate were used to develop this population PK model using nonlinear mixed-effects modeling. VWF:Act and FVIII levels were analyzed simultaneously using a turnover model. The protective effect of VWF:Act on FVIII clearance was described with an inhibitory maximum effect function. An average perioperative VWF:Act level of 1.23 IU/mL decreased FVIII clearance from 460 mL/h to 264 mL/h, and increased FVIII half-life from 6.6 to 11.4 hours. Clearly, in the presence of VWF, FVIII clearance decreased with a concomitant increase of FVIII half-life, clarifying the higher FVIII levels observed after repetitive dosing with this concentrate. VWF:Act and FVIII levels during perioperative treatment were described adequately by this newly developed integrated population PK model. Clinical application of this model may facilitate more accurate targeting of VWF:Act and FVIII levels during perioperative treatment with this specific VWF/FVIII concentrate (Humate P/Haemate P).
MeSH term(s)	Factor VIII ; Half-Life ; Hemorrhage ; Humans ; von Willebrand Diseases/drug therapy ; von Willebrand Factor
Chemical Substances	von Willebrand Factor ; Factor VIII (9001-27-8)
Language	English
Publishing date	2021-03-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2020003891
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Article ; Online: Population Pharmacokinetic Modeling of von Willebrand Factor Activity in von Willebrand Disease Patients after Desmopressin Administration.

de Jager, Nico C B / Heijdra, Jessica M / Kieboom, Quincy / Kruip, Marieke J H A / Leebeek, Frank W G / Cnossen, Marjon H / Mathôt, Ron A A

Thrombosis and haemostasis

2020 Volume 120, Issue 10, Page(s) 1407–1416

Abstract: Objective: Most von Willebrand disease (VWD) patients can be treated with desmopressin during bleeding or surgery. Large interpatient variability is observed in von Willebrand factor (VWF) activity levels after desmopressin administration. The aim of ... ...

Abstract	Objective: Most von Willebrand disease (VWD) patients can be treated with desmopressin during bleeding or surgery. Large interpatient variability is observed in von Willebrand factor (VWF) activity levels after desmopressin administration. The aim of this study was to develop a pharmacokinetic (PK) model to describe, quantify, and explain this variability. Methods: Patients with either VWD or low VWF, receiving an intravenous desmopressin test dose of 0.3 µg kg Results: The PK model was developed using 951 VWF activity level measurements from 207 patients diagnosed with a VWD type. Median age was 28 years (range: 5-76), median predose VWF activity was 0.37 IU/mL (range: 0.06-1.13), and median VWF activity response at peak level was 0.64 IU/mL (range: 0.04-4.04). The observed PK profiles were best described using a one-compartment model with allometric scaling. While Conclusion: A PK model was developed, describing VWF activity versus time profile after desmopressin administration in patients with VWD or low VWF. Interpatient variability in response was quantified and partially explained. This model is a starting point toward more accurate prediction of desmopressin dosing effects in VWD.
MeSH term(s)	Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Deamino Arginine Vasopressin/pharmacokinetics ; Deamino Arginine Vasopressin/therapeutic use ; Female ; Hemostatics/pharmacokinetics ; Hemostatics/therapeutic use ; Humans ; Male ; Middle Aged ; Models, Biological ; Young Adult ; von Willebrand Diseases/drug therapy ; von Willebrand Diseases/metabolism ; von Willebrand Factor/metabolism
Chemical Substances	Hemostatics ; von Willebrand Factor ; Deamino Arginine Vasopressin (ENR1LLB0FP)
Language	English
Publishing date	2020-08-03
Publishing country	Germany
Document type	Journal Article
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/s-0040-1714349
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Article: A randomized controlled trial studying the effectiveness of group medical appointments on self-efficacy and adherence in sickle cell disease (TEAM study): study protocol.

Madderom, Marlous J / Heijdra, Jessica / Utens, Elisabeth M W J / Polinder, Suzanne / Rijneveld, Anita W / Cnossen, Marjon H

BMC hematology

2016 Volume 16, Page(s) 21

Abstract: Background: Sickle cell disease (SCD) is endemic in non-Western countries. Due to migration, the prevalence of SCD in the Netherlands has increased. Adherence to medical treatment is recognized as a major problem area. Therefore, new effective ... ...

Abstract	Background: Sickle cell disease (SCD) is endemic in non-Western countries. Due to migration, the prevalence of SCD in the Netherlands has increased. Adherence to medical treatment is recognized as a major problem area. Therefore, new effective interventions to increase adherence are urgently needed. Methods/design: The TEAM study is an ongoing randomized controlled trial (RCT) to compare protocolized individual medical appointments (IMA's; care-as-usual) with protocolized group medical appointments (GMA's; novel intervention) in pediatric (n = 40) and adult (n = 60) patients. The study aims to assess the effectiveness of GMA's (over a three year period) on patients' self-efficacy, adherence, quality of life, morbidity, hospital admissions and satisfaction with the treating professional; as well as to test the cost-effectiveness of GMA's. In both the IMA and GMA groups structured assessments will be performed at baseline (start of the study), after 1.5 and after 3 years. Discussion: This is the first RCT to investigate the effectiveness of GMA's on self-efficacy and adherence in pediatric and adult patients with SCD, including a cost-effectiveness analysis. Trial registration: NTR4750 (NL42182.000.12). Registered 13 August 2014.
Language	English
Publishing date	2016-08-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2744433-8
ISSN	2052-1839
ISSN	2052-1839
DOI	10.1186/s12878-016-0058-4
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Article ; Online: Is pharmacokinetic-guided dosing of desmopressin and von Willebrand factor-containing concentrates in individuals with von Willebrand disease or low von Willebrand factor reliable and feasible? A protocol for a multicentre, non-randomised, open label cohort trial, the OPTI-CLOT

Marjon H Cnossen / Frank W G Leebeek / Ron A A Mathôt / M Coppens / MJHA Kruip / S Polinder / K Fischer / R Liesner / K Fijnvandraat / Laura H Bukkems / PW Collins / P Chowdary / K Meijer / A Janssen / MH Cnossen / Jessica M Heijdra / Wala Al Arashi / Nico C B de Jager / Michael E Cloesmeijer /

BMJ Open, Vol 12, Iss

to WiN study

2022 Volume 2

Keywords	Medicine ; R
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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