279 results on '"Kusters, R."'
Search Results
2. Are the latest point-of-care D-dimer devices ready for use in general practice? A prospective clinical evaluation of five test systems with a capillary blood feature for suspected venous thromboembolism
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Heerink, J.S., Oudega, R., Gemen, E., Hopstaken, R., Koffijberg, H., and Kusters, R.
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- 2023
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3. Active elastohydrodynamics of vesicles in narrow blind constrictions
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Fai, TG, Kusters, R, Harting, J, Rycroft, CH, and Mahadevan, L
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Fluid Mechanics and Thermal Engineering ,Engineering ,cond-mat.soft ,Applied Mathematics ,Classical Physics ,Mechanical Engineering ,Fluid mechanics and thermal engineering - Abstract
Fluid-resistance limited transport of vesicles through narrow constrictions is a recurring theme in many biological and engineering applications. Inspired by the motor-driven movement of soft membrane-bound vesicles into closed neuronal dendritic spines, here we study this problem using a combination of passive three-dimensional simulations and a simplified semianalytical theory for the active transport of vesicles forced through constrictions by molecular motors. We show that the motion of these objects is characterized by two dimensionless quantities related to the geometry and to the strength of forcing relative to the vesicle elasticity. We use numerical simulations to characterize the transit time for a vesicle forced by fluid pressure through a constriction in a channel and find that relative to an open channel, transport into a blind end leads to the formation of a smaller forward-flowing lubrication layer that strongly impedes motion. When the fluid pressure forcing is complemented by forces due to molecular motors that are responsible for vesicle trafficking into dendritic spines, we find that the competition between motor forcing and fluid drag results in multistable dynamics reminiscent of the real system. Our study highlights the role of nonlocal hydrodynamic effects in determining the kinetics of vesicular transport in constricted geometries.
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- 2017
4. Geometric localization in supported elastic struts
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Michaels, T. C. T., Kusters, R., Dear, A. J., Storm, C., Weaver, J. C., and Mahadevan, L.
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- 2019
5. What's in an Attribute? Consequences for the Least Common Subsumer
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Borgida, A. and Kusters, R.
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Computer Science - Artificial Intelligence - Abstract
Functional relationships between objects, called `attributes', are of considerable importance in knowledge representation languages, including Description Logics (DLs). A study of the literature indicates that papers have made, often implicitly, different assumptions about the nature of attributes: whether they are always required to have a value, or whether they can be partial functions. The work presented here is the first explicit study of this difference for subclasses of the CLASSIC DL, involving the same-as concept constructor. It is shown that although determining subsumption between concept descriptions has the same complexity (though requiring different algorithms), the story is different in the case of determining the least common subsumer (lcs). For attributes interpreted as partial functions, the lcs exists and can be computed relatively easily; even in this case our results correct and extend three previous papers about the lcs of DLs. In the case where attributes must have a value, the lcs may not exist, and even if it exists it may be of exponential size. Interestingly, it is possible to decide in polynomial time if the lcs exists.
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- 2011
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6. Additional file 2 of Two point-of-care test-based approaches for the exclusion of deep vein thrombosis in general practice: a cost-effectiveness analysis
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Heerink, J. S., Nies, J., Koffijberg, H., Oudega, R., Kip, M. M. A., and Kusters, R.
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Additional file 2. CHEERS Checklist.
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- 2023
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7. Additional file 1 of Two point-of-care test-based approaches for the exclusion of deep vein thrombosis in general practice: a cost-effectiveness analysis
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Heerink, J. S., Nies, J., Koffijberg, H., Oudega, R., Kip, M. M. A., and Kusters, R.
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Additional file 1. Overview of underlying assumptions for the model in our study.
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- 2023
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8. High pneumococcal DNA load, procalcitonin and suPAR levels correlate to severe disease development in patients with pneumococcal pneumonia
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Loonen, A. J. M., Kesarsing, C., Kusters, R., Hilbink, M., Wever, P. C., and van den Brule, A. J. C.
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- 2017
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9. Control of complexity in virtual organizations: the role of enterprise modelling
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Kusters, R. J. Rob, Wortmann, J. C. Hans, Jagdev, Harinder S., editor, Wortmann, Johan C., editor, and Pels, Henk Jan, editor
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- 2003
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10. How to Realize the Benefits of Point-of-Care Testing at the General Practice: A Comparison of Four High-Income Countries
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Lingervelder, D, Koffijberg, H, Emery, JD, Fennessy, P, Price, CP, van Marwijk, H, Eide, TB, Sandberg, S, Cals, JWL, Derksen, JTM, Kusters, R, IJzerman, MJ, Lingervelder, D, Koffijberg, H, Emery, JD, Fennessy, P, Price, CP, van Marwijk, H, Eide, TB, Sandberg, S, Cals, JWL, Derksen, JTM, Kusters, R, and IJzerman, MJ
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Background In some countries, such as the Netherlands and Norway, point-of-care testing (POCT) is more widely implemented in general practice compared to countries such as England and Australia. To comprehend what is necessary to realize the benefits of POCT, regarding its integration in primary care, it would be beneficial to have an overview of the structure of healthcare operations and the transactions between stakeholders (also referred to as value networks). The aim of this paper is to identify the current value networks in place applying to POCT implementation at general practices in England, Australia, Norway and the Netherlands and to compare these networks in terms of seven previously published factors that support the successful implementation, sustainability and scale-up of innovations. Methods The value networks were described based on formal guidelines and standards published by the respective governments, organizational bodies and affiliates. The value network of each country was validated by at least two relevant stakeholders from the respective country. Results The analysis revealed that the biggest challenge for countries with low POCT uptake was the lack of effective communication between the several organizations involved with POCT as well as the high workload for general practitioners (GPs) aiming to implement POCT. It is observed that countries with a single national authority responsible for POCT have a better uptake as they can govern the task of POCT roll-out and management and reduce the workload for GPs by assisting with set-up, quality control, training and support. Conclusion Setting up a single national authority may be an effective step towards realizing the full benefits of POCT. Although it is possible for day-to-day operations to fall under the responsibility of the GP, this is only feasible if support and guidance are readily available to ensure that the workload associated with POCT is limited and as low as possible.
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- 2022
11. New clinical prediction model for early recognition of sepsis in adult primary care patients: a prospective diagnostic cohort study of development and external validation
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Loots, F.J., Smits, M., Hopstaken, R.M., Jenniskens, K., Schroeten, F.H., Bruel, A. van den, Pol, A.C. van de, Oosterheert, J.J., Bouma, H., Little, P., Moore, M., Delft, S. van, Rijpsma, D., Holkenborg, J., Bussel, B.C.T. van, Laven, R., Bergmans, D.C., Hoogerwerf, J.J., Latten, G.H., Bont, E.G. de, Giesen, P., Harder, A.D., Kusters, R., Zanten, A.R.H., Verheij, T.J., Loots, F.J., Smits, M., Hopstaken, R.M., Jenniskens, K., Schroeten, F.H., Bruel, A. van den, Pol, A.C. van de, Oosterheert, J.J., Bouma, H., Little, P., Moore, M., Delft, S. van, Rijpsma, D., Holkenborg, J., Bussel, B.C.T. van, Laven, R., Bergmans, D.C., Hoogerwerf, J.J., Latten, G.H., Bont, E.G. de, Giesen, P., Harder, A.D., Kusters, R., Zanten, A.R.H., and Verheij, T.J.
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Item does not contain fulltext, BACKGROUND: Recognising patients who need immediate hospital treatment for sepsis while simultaneously limiting unnecessary referrals is challenging for GPs. AIM: To develop and validate a sepsis prediction model for adult patients in primary care. DESIGN AND SETTING: This was a prospective cohort study in four out-of-hours primary care services in the Netherlands, conducted between June 2018 and March 2020. METHOD: Adult patients who were acutely ill and received home visits were included. A total of nine clinical variables were selected as candidate predictors, next to the biomarkers C-reactive protein, procalcitonin, and lactate. The primary endpoint was sepsis within 72 hours of inclusion, as established by an expert panel. Multivariable logistic regression with backwards selection was used to design an optimal model with continuous clinical variables. The added value of the biomarkers was evaluated. Subsequently, a simple model using single cut-off points of continuous variables was developed and externally validated in two emergency department populations. RESULTS: A total of 357 patients were included with a median age of 80 years (interquartile range 71-86), of which 151 (42%) were diagnosed with sepsis. A model based on a simple count of one point for each of six variables (aged >65 years; temperature >38°C; systolic blood pressure ≤110 mmHg; heart rate >110/min; saturation ≤95%; and altered mental status) had good discrimination and calibration (C-statistic of 0.80 [95% confidence interval = 0.75 to 0.84]; Brier score 0.175). Biomarkers did not improve the performance of the model and were therefore not included. The model was robust during external validation. CONCLUSION: Based on this study's GP out-of-hours population, a simple model can accurately predict sepsis in acutely ill adult patients using readily available clinical parameters.
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- 2022
12. Added Diagnostic Value of Biomarkers in Patients with Suspected Sepsis: A Prospective Cohort Study in Out-Of-Hours Primary Care
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Loots, F.J., Smits, M., Jenniskens, K., Zanten, A.R.H., Kusters, R., Verheij, T.J., Hopstaken, R.M., Loots, F.J., Smits, M., Jenniskens, K., Zanten, A.R.H., Kusters, R., Verheij, T.J., and Hopstaken, R.M.
- Abstract
Contains fulltext : 282886.pdf (Publisher’s version ) (Open Access), BACKGROUND: Point-of-care testing (POCT) has shown promising results in the primary care setting to improve antibiotic therapy in respiratory tract infections and it might also aid general practitioners (GPs) to decide if patients should be referred to a hospital in cases of suspected sepsis. We aimed to assess whether biomarkers with possible POCT use can improve the recognition of sepsis in adults in the primary care setting. METHODS: We prospectively included adult patients with suspected severe infections during out-of-hours home visits. Relevant clinical signs and symptoms were recorded, as well as the biomarkers C-reactive protein, lactate, procalcitonin, high-sensitive troponin I, N-terminal pro b-type natriuretic peptide, creatinine, urea, and pancreatic stone protein. We used a POCT device for lactate only, and the remaining biomarkers were measured in a laboratory from stored blood samples. The primary outcome was sepsis within 72 h of inclusion. The potential of biomarkers to either rule in or rule out sepsis was tested for individual biomarkers combined with a model consisting of signs and symptoms. Net reclassification indices were also calculated. RESULTS: In total, 336 patients, with a median age of 80 years, were included. One hundred forty-one patients (42%) were diagnosed with sepsis. The C statistic for the model with clinical symptoms and signs was 0.84 (95% CI 0.79-0.88). Both lactate and procalcitonin increased the C statistic to 0.85, but none of the biomarkers significantly changed the net reclassification index. CONCLUSIONS: We do not advocate the routine use of POCT in general practice for any of the tested biomarkers of suspected sepsis.
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- 2022
13. The societal impact of implementing an at-home blood sampling device for chronic care patients: patient preferences and cost impact
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Lingervelder, D, Kip, MMA, Wiese, ED, Koffijberg, H, Ijzerman, MJ, Kusters, R, Lingervelder, D, Kip, MMA, Wiese, ED, Koffijberg, H, Ijzerman, MJ, and Kusters, R
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BACKGROUND: Diabetes mellitus, cardiovascular diseases, chronic kidney disease, and thyroid diseases are chronic diseases that require regular monitoring through blood tests. This paper first investigates the experiences of chronic care patients with venipuncture and their expectations of an at-home blood-sampling device, and then assesses the impact on societal costs of implementing such a device in current practice. METHODS: An online survey was distributed among chronic care patients to gain insight into their experience of blood sampling in current practice, and their expectations of an at-home blood-sampling device. The survey results were used as input parameters in a patient-level monte carlo analysis developed to represent a hypothetical cohort of Dutch chronically ill patients to investigate the impact on societal costs compared to usual care. RESULTS: In total, 1311 patients participated in the survey, of which 31% experience the time spent on the phlebotomy appointment as a burden. Of all respondents, 71% prefer to use an at-home blood-sampling device to monitor their chronic disease. The cost analysis indicated that implementing an at-home blood-sampling device increases the cost of phlebotomy itself by €27.25 per patient per year, but it reduces the overall societal costs by €24.86 per patient per year, mainly due to limiting productivity loss. CONCLUSIONS: Patients consider an at-home blood-sampling device to be more user-friendly than venous phlebotomy on location. Long waiting times and crowded locations can be avoided by using an at-home blood-sampling device. Implementing such a device is likely cost-saving as it is expected to reduce societal costs.
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- 2022
14. Blood warming, pump heating and haemolysis in low-flow extracorporeal life support; an in vitro study using freshly donated human blood
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Kusters, R W J, Simons, A P, Lancé, M D, Ganushchak, Y M, Bekers, O, and Weerwind, P W
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- 2017
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15. User-perceptions Of Embedded Software Reliability
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Kusters, R. J., van Solingen, R., Trienekens, J. J. M., Wijnands, H., and Gritzalis, Dimitris, editor
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- 1997
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16. Intelligent Methods for Test and Reliability
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Amrouch, H., primary, Anders, J., additional, Becker, S., additional, Betka, M., additional, Bleher, G., additional, Domanski, P., additional, Elhamawy, N., additional, Ertl, T., additional, Gatzastras, A., additional, Genssler, P., additional, Hasler, S., additional, Heinrich, M., additional, van Hoorn, A., additional, Jafarzadeh, H., additional, Kallfass, I., additional, Klemme, F., additional, Koch, S., additional, Kusters, R., additional, Lalama, A., additional, Latty, R., additional, Liao, Y., additional, Lylina, N., additional, Haghi, Z. Najafi, additional, Pfluger, D., additional, Polian, I., additional, Rivoir, J., additional, Sauer, M., additional, Schwachhofer, D., additional, Templin, S., additional, Volmer, C., additional, Wagner, S., additional, Weiskopf, D., additional, Wunderlich, H.-J., additional, Yang, B., additional, and Zimmermann, M., additional
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- 2022
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17. Supplementary Theory from Puckering and wrinkling in a growing composite ring
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T. C. T. Michaels, Kusters, R., and Mahadevan, L.
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Pattern formation driven by differential strain in constrained elastic systems is a common motif in many technological and biological systems. Here we introduce a biologically motivated case of elastic patterning that allows us to explore the conditions for the existence of local puckering and global wrinkling patterns: a soft growing composite ring adhered elastically to a constraining rigid ring. We explore how differential growth of the soft ring and the elastic resistance to shear and stretching deformations induced by soft adherence leads to a range of phenomena that include uniform aperture-like modes, localized puckers that are Nambu–Goldstone like modes, and global wrinkles in the system. Our analysis combines computer simulations of a discrete rod model with a nonlinear stability analysis of the differential equations in the continuum limit. We provide phase diagrams and scaling relations that reveal the nature and extent of the deformation patterns. Overall, our study reveals how geometry and mechanics conspire to yield a rich phenomenology that could serve both as a guide to the design of programmable localized elastic deformations while being relevant for the mechanical basis of biological morphogenesis.
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- 2021
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18. Health Economic Evidence of Point-of-Care Testing: A Systematic Review
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Lingervelder, D, Koffijberg, H, Kusters, R, IJzerman, MJ, Lingervelder, D, Koffijberg, H, Kusters, R, and IJzerman, MJ
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OBJECTIVE: Point-of-care testing (POCT) has become an essential diagnostic technology for optimal patient care. Its implementation, however, still falls behind. This paper reviews the available evidence on the health economic impact of introducing POCT to assess if poor POCT uptake may be related to lacking evidence. STUDY DESIGN: The Scopus and PubMed databases were searched to identify publications describing a health economic evaluation of a point-of-care (POC) test. Data were extracted from the included publications, including general and methodological characteristics as well as the study results summarized in either cost, effects or an incremental cost-effectiveness ratio. Results were sorted into six groups according to the POC test's purpose (diagnosis, screening or monitoring) and care setting (primary care or secondary care). The reporting quality of the publications was determined using the CHEERS checklist. RESULTS: The initial search resulted in 396 publications, of which 44 met the inclusion criteria. Most of the evaluations were performed in a primary care setting (n = 31; 70.5%) compared with a secondary care setting (n = 13; 29.5%). About two thirds of the evaluations were on POC tests implemented with a diagnostic purpose (n = 28; 63.6%). More than 75% of evaluations concluded that POCT is recommended for implementation, although in some cases only under specific circumstances and conditions. Compliance with the CHEERS checklist items ranged from 20.8% to 100%, with an average reporting quality of 72.0%. CONCLUSION: There were very few evaluations in this review that advised against the implementation of POCT. However, the uptake of POCT in many countries remains low. Even though the evaluations included in this review did not always include the full long-term benefits of POCT, it is clear that health economic evidence across a few dimensions of value already indicate the benefits of POCT. This suggests that the lack of evidence on POCT is not the
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- 2021
19. Puckering and wrinkling in a growing composite ring
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Michaels, T. C. T., primary, Kusters, R., additional, and Mahadevan, L., additional
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- 2021
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20. IT project complexity management based on sources and effects: positive, appropriate and negative
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Stefan Morcov, Pintelon, L., Kusters, R. J., Department of Information Science, RS-Research Line Learning (part of LIRS program), and RS-Research Line Resilience (part of LIRS program)
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project management ,complex IT projects ,structural complexity ,appropriate complexity ,uncertainty ,positive complexity - Abstract
IT project complexity increases continuously, in synchrony with technological complexity, making projects difficult to manage and control. Despitea growing importance and priorityin research, there is still a strong need for solutions to the significant challengesposed by complexity. This paper presents anexploratory qualitative research processbased on design science, that expands the current theoretical foundations of IT project management by providing insights into the positive, appropriate, and negative aspects of complexity, and supports practice with newly designedtools for the analysis and management of complexityandresponse strategy planning, based on complexity sources and effects.The design and validation were performed with semi-structured interviews with experts, based on actual complex IT project cases
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- 2020
21. Preventing overuse of laboratory diagnostics: a case study into diagnosing anaemia in Dutch general practice
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Kip, M.M.A. (Michelle M A), Oonk, M.L.J. (Martijn L J), Levin, M.-D. (Mark-David), Schop, A. (Annemarie), Bindels, P.J.E. (Patrick), Kusters, R. (Ron), Koffijberg, H. (Hendrik), Kip, M.M.A. (Michelle M A), Oonk, M.L.J. (Martijn L J), Levin, M.-D. (Mark-David), Schop, A. (Annemarie), Bindels, P.J.E. (Patrick), Kusters, R. (Ron), and Koffijberg, H. (Hendrik)
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BACKGROUND: More information is often thought to improve medical decision-making, which may lead to test overuse. This study assesses which out of 15 laboratory tests contribute to diagnosing the underlying cause of anaemia by general practitioners (GPs) and determines a potentially more efficient subset of tests for setting the correct diagnosis. METHODS: Logistic regression was performed to determine the impact of individual tests on the (correct) diagnosis. The statistically optimal test subset for diagnosing a (correct) underlying cause of anaemia by GPs was determined using data from a previous survey including cases of real-world anaemia patients. RESULTS: Only 9 (60%) of the laboratory tests, and patient age, contributed significantly to the GPs' ability to diagnose an underlying cause of anaemia (CRP, ESR, ferritin, folic acid, haemoglobin, leukocytes, eGFR/MDRD, reticulocytes and serum iron). Diagnosing the correct underlying cause may require just five (33%) tests (CRP, ferritin, folic acid, MCV and transferrin), and patient age. CONCLUSIONS: In diagnosing the underlying cause of anaemia a subset of five tests has most added value. The real-world impact of using only this subset should be further investigated. As illustrated in this case study, a statistical approach to assessing the added value of tests may reduce test overuse.
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- 2020
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22. Mbo-Schrijfvaardigheidsonderwijspraktijk
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Kusters, R., van den Bergh, H. H. (Thesis Advisor), Westermann, A. J., Kusters, R., van den Bergh, H. H. (Thesis Advisor), and Westermann, A. J.
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This master thesis looks into the writing education as practised in vocational colleges in The Netherlands: how do teachers in these colleges attempt to get their students to produce written texts at the quality required of the students to graduate; this quality is dictated by law? And how effective are these methods. In summary there are two methods used by these teachers that are apparently quite effective: one method lets students write an assignment, receive feedback and, based on said feedback, rewrite the assignment. The other method is that students observe a finished product written by a professional, and in the process not only read this product but analyse how it was set up and think about the writing process that is needed to make that product, before they start writing their own assignment. It seems this method works best with short texts such as business letters.
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- 2020
23. Preventing overuse of laboratory diagnostics: a case study into diagnosing anaemia in Dutch general practice
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Kip, MMA, Oonk, MLJ, Levin, MD, Schop, A, Bindels, Patrick, Kusters, R, Koffijberg, H, Kip, MMA, Oonk, MLJ, Levin, MD, Schop, A, Bindels, Patrick, Kusters, R, and Koffijberg, H
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- 2020
24. Influence of gas injection on phase inversion in an oil–water flow through a vertical tube
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Descamps, M., Oliemans, R.V.A., Ooms, G., Mudde, R.F., and Kusters, R.
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- 2006
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25. Blood warming, pump heating and haemolysis in low-flow extracorporeal life support; an in vitro study using freshly donated human blood
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Kusters, R. W. J., Kusters, R. W. J., Simons, A. P., Lance, M. D., Ganushchak, Y. M., Bekers, O., Weerwind, P. W., Kusters, R. W. J., Kusters, R. W. J., Simons, A. P., Lance, M. D., Ganushchak, Y. M., Bekers, O., and Weerwind, P. W.
- Abstract
Low-flow extracorporeal life support can be used for cardiopulmonary support of paediatric and neonatal patients and is also emerging as a therapy for patients suffering from exacerbation of chronic obstructive pulmonary disease. However, pump heating and haemolysis have proven to negatively affect the system and outcome. This in vitro study aimed at gaining insight into blood warming, pump heating and haemolysis related to the performance of a new low-flow centrifugal pump. Pump performance in the 400-1,500 ml/min flow range was modulated using small-sized dual-lumen catheters and freshly donated human blood. Measurements included plasma free haemoglobin, blood temperature, pump speed, pump pressure, blood flow and thermographic imaging. Blood warming (T-max=0.5 degrees C) had no relationship with pump performance or haemolysis (R-max(2)=0.05). Pump performance-related parameters revealed no relevant relationships with haemolysis (R-max(2)=0.36). Thermography showed no relevant heat zones in the pump (T-max=36 degrees C). Concerning blood warming, pump heating and haemolysis, we deem the centrifugal pump applicable for low-flow extracorporeal circulation.
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- 2017
26. Influenzasneltests voor de huisartsenpraktijk en SEH. Analytische accuratesse en meerwaarde
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Verhees, Ruud, Lutgens, Suzanne P. M., Kusters, R., Dinant, Geert, Cals, Jochen, Family Medicine, and RS: CAPHRI - R5 - Optimising Patient Care
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Er zijn meerdere sneltests (‘point-of-care’-tests) beschikbaar waarmee de diagnose ‘influenza’ binnen circa 30 min gesteld kan worden Sneltests die gebruikmaken van antigeendetectie zijn makkelijk in gebruik, maar zij hebben een beperkte analytische accuratesse. Sneltests die gebruikmaken van de 'PCR-techniek zijn accuraat, maar zij behoeven directe ondersteuning van het medisch laboratorium; hierdoor zijn deze tests alleen inzetbaar in ziekenhuizen. Er is weinig direct bewijs voor de klinische effectiviteit van influenzasneltests op de SEH en bewijs voor de klinische effectiviteit van influenzasneltests in de huisartsenpraktijk ontbreekt. Influenzasneltests kunnen de ligduur op de SEH verminderen en de doorstroom van patiënten in het ziekenhuis verbeteren, mits capaciteitsproblemen dit niet belemmeren. Op basis van de huidige literatuur is het gerechtvaardigd om influenzasneltests die gebruikmaken van een PCR-techniek in te zetten op de SEH. Implementatie van influenzasneltests in de huisartsenpraktijk is vooralsnog een brug te ver.
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- 2019
27. Ciprofloxacin penetration into infected hepatic cysts in autosomal dominant polycystic kidney disease: a case report
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Bernts, L.H.P., Wallenburg, E., Jonge, H.J. de, Schaap, B., Kusters, R., Overtoom, T.T.C., Bruggemann, R.J.M., Drenth, J.P.H., Lantinga, M.A., Bernts, L.H.P., Wallenburg, E., Jonge, H.J. de, Schaap, B., Kusters, R., Overtoom, T.T.C., Bruggemann, R.J.M., Drenth, J.P.H., and Lantinga, M.A.
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Item does not contain fulltext
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- 2019
28. Point-of-care testing in primary care: A systematic review on implementation aspects addressed in test evaluations
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Lingervelder, D, Koffijberg, H, Kusters, R, IJzerman, MJ, Lingervelder, D, Koffijberg, H, Kusters, R, and IJzerman, MJ
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OBJECTIVES: There are numerous point-of-care tests (POCTs) available on the market, but many of these are not used. This study reviewed literature pertaining to the evaluation/usage of POCTs in primary care, to investigate whether outcomes being reported reflect aspects previously demonstrated to be important for general practitioners (GPs) in the decision to implement a POCT in practice. METHODS: Scopus and Medline were searched to identify studies that evaluated a POCT in primary care. We identified abstracts and full-texts consisting of applied studies (eg trials, simulations, observational studies) and qualitative studies (eg interviews, surveys). Data were extracted from the included studies, such as the type of study, the extent to which manufacturers were involved in the study, and the biomarker/assay measured by the test(s). Studies were evaluated to summarise the extent to which they reported on, amongst others, clinical utility, user-friendliness, turnaround-time and technical performance (aspects previously identified as important). RESULTS: The initial search resulted in 1398 publications, of which 125 met the inclusion criteria. From these studies, 83 POCTs across several disease areas (including cardiovascular disease, venous thromboembolism and respiratory-tract-infections) were identified. There was an inconsistency between what is reported in the studies and what GPs consider important. GPs perceive clinical utility as the most important aspect, yet this was rarely included explicitly in test evaluations in the literature, with only 8% of evaluations incorporating it in their analysis/discussion. CONCLUSIONS: This review showed that, despite the growing market and development of new POCTs, studies evaluating such tests fail to report on aspects that GPs find important. To ensure that an evaluation of a POCT is useful to primary care clinicians, future evaluations should not only focus on the technical performance aspects of a test, but also report o
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- 2019
29. Understanding the adoption and use of point-of-care tests in Dutch general practices using multi-criteria decision analysis
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Kip, MMA, Hummel, JM, Eppink, EB, Koffijberg, H, Hopstaken, RM, IJzerman, MJ, Kusters, R, Kip, MMA, Hummel, JM, Eppink, EB, Koffijberg, H, Hopstaken, RM, IJzerman, MJ, and Kusters, R
- Abstract
BACKGROUND: The increasing number of available point-of-care (POC) tests challenges clinicians regarding decisions on which tests to use, how to efficiently use them, and how to interpret the results. Although POC tests may offer benefits in terms of low turn-around-time, improved patient's satisfaction, and health outcomes, only few are actually used in clinical practice. Therefore, this study aims to identify which criteria are, in general, important in the decision to implement a POC test, and to determine their weight. Two POC tests available for use in Dutch general practices (i.e. the C-reactive protein (CRP) test and the glycated haemoglobin (HbA1c) test) serve as case studies. The information obtained from this study can be used to guide POC test development and their introduction in clinical practice. METHODS: Relevant criteria were identified based on a literature review and semi-structured interviews with twelve experts in the field. Subsequently, the criteria were clustered in four groups (i.e. user, organization, clinical value, and socio-political context) and the relative importance of each criterion was determined by calculating geometric means as implemented in the Analytic Hierarchy Process. Of these twelve experts, ten participated in a facilitated group session, in which their priorities regarding both POC tests (compared to central laboratory testing) were elicited. RESULTS: Of 20 criteria in four clusters, the test's clinical utility, its technical performance, and risks (associated with the treatment decision based on the test result) were considered most important for using a POC test, with relative weights of 22.2, 12.6 and 8.5%, respectively. Overall, the experts preferred the POC CRP test over its laboratory equivalent, whereas they did not prefer the POC HbA1c test. This difference was mainly explained by their strong preference for the POC CRP test with regard to the subcriterion 'clinical utility'. CONCLUSIONS: The list of identified cr
- Published
- 2019
30. A direct proof that sole actin dynamics drive membrane deformations
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Allard A, Pierre Sens, Martin Lenz, Clément Campillo, Jean-François Joanny, Camille Simon, Daniel Lévy, John Manzi, Kusters R, Majdouline Abou-Ghali, Caorsi, Julie Plastino, Di Cicco A, and Cécile Sykes
- Subjects
0303 health sciences ,Tension (physics) ,Chemistry ,Turgor pressure ,Endocytic cycle ,macromolecular substances ,Endocytosis ,Cell membrane ,03 medical and health sciences ,0302 clinical medicine ,Membrane ,medicine.anatomical_structure ,medicine ,Biophysics ,Filopodia ,030217 neurology & neurosurgery ,Actin ,030304 developmental biology - Abstract
Cell membrane deformations are crucial for proper cell function. Specialized protein assemblies initiate inward or outward membrane deformations that turn into, for example, filopodia or endocytic intermediates. Actin dynamics and actin-binding proteins are involved in this process, although their detailed role remains controversial. We show here that a dynamic, branched actin network is sufficient, in absence of any membrane-associated proteins, to initiate both inward and outward membrane deformation. With actin polymerization triggered at the membrane of liposomes, we produce inward filopodia-like structures at low tension, while outward endocytosis-like structures are robustly generated regardless of tension. Our results are reminiscent of endocytosis in mammalian cells, where actin polymerization forces are required when membrane tension is increased, and in yeast, where they are always required to overcome the opposing turgor pressure. By combining experimental observations with physical modeling, we propose a mechanism for actin-driven endocytosis under high tension or high pressure conditions.
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- 2018
- Full Text
- View/download PDF
31. Real-time monitoring of drug-laboratory test interactions with an automated decision support application
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Van Balveren, J., primary, Van De Venne, W. Verboeket-, additional, Erdem-Eraslan, L., additional, De Graaf, A., additional, Musson, R., additional, Oosterhuis, W., additional, Van Der Sijs, I., additional, Verheul, R., additional, Kusters, R., additional, and Hoedemakers, R., additional
- Published
- 2019
- Full Text
- View/download PDF
32. Chapter 8 Lipid involvement in protein translocation
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Kruijff, B. De, primary, Breukink, E., additional, Demel, R.A., additional, T Hof, R. Van, additional, Jongh, H.H.J. De, additional, Jordi, W., additional, Keller, R.C.A., additional, Killian, J.A., additional, Kroon, A.I.P.M. De, additional, Kusters, R., additional, and Pilon, M., additional
- Published
- 1992
- Full Text
- View/download PDF
33. Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients : results from a randomised controlled multicentre trial in the Netherlands
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Kip, Michelle M A, van Oers, J.A., Shajiei, A, Beishuizen, Albertus, Girbes, A.R.J., de Jong, E, de Lange, DW, Nijsten, Maarten W N, IJzerman, M.J., Koffijberg, H, Kusters, R., Kip, Michelle M A, van Oers, J.A., Shajiei, A, Beishuizen, Albertus, Girbes, A.R.J., de Jong, E, de Lange, DW, Nijsten, Maarten W N, IJzerman, M.J., Koffijberg, H, and Kusters, R.
- Published
- 2018
34. Assessing the cost-effectiveness of a routine versus an extensive laboratory work-up in the diagnosis of anaemia in Dutch general practice
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Kip, M.M. (Michelle Ma), Schop, A. (Annemarie), Stouten, K. (Karlijn), Dekker, S. (Soraya), Dinant, G.J., Koffijberg, H. (Hendrik), Bindels, P.J.E. (Patrick), IJzerman, M.J., Levin, M.-D. (Mark-David), Kusters, R. (Ron), Kip, M.M. (Michelle Ma), Schop, A. (Annemarie), Stouten, K. (Karlijn), Dekker, S. (Soraya), Dinant, G.J., Koffijberg, H. (Hendrik), Bindels, P.J.E. (Patrick), IJzerman, M.J., Levin, M.-D. (Mark-David), and Kusters, R. (Ron)
- Abstract
Background Establishing the underlying cause of anaemia in general practice is a diagnostic challenge. Currently, general practitioners individually determine which laboratory tests to request (routine work-up) in order to diagnose the underlying cause. However, an extensive work-up (consisting of 14 tests) increases the proportion of patients correctly diagnosed. This study investigates the cost-effectiveness of this extensive work-up. Methods A decision-analytic model was developed, incorporating all societal costs from the moment a patient presents to a general pra
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- 2018
- Full Text
- View/download PDF
35. Assessing the cost-effectiveness of a routine versus an extensive laboratory work-up in the diagnosis of anaemia in Dutch general practice
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Kip, MMA, Schop, A, Stouten, K, Dekker, S, Dinant, G-J, Koffijberg, H, Bindels, PJE, IJzerman, MJ, Levin, M-D, Kusters, R, Kip, MMA, Schop, A, Stouten, K, Dekker, S, Dinant, G-J, Koffijberg, H, Bindels, PJE, IJzerman, MJ, Levin, M-D, and Kusters, R
- Abstract
Background Establishing the underlying cause of anaemia in general practice is a diagnostic challenge. Currently, general practitioners individually determine which laboratory tests to request (routine work-up) in order to diagnose the underlying cause. However, an extensive work-up (consisting of 14 tests) increases the proportion of patients correctly diagnosed. This study investigates the cost-effectiveness of this extensive work-up. Methods A decision-analytic model was developed, incorporating all societal costs from the moment a patient presents to a general practitioner with symptoms suggestive of anaemia (aged ≥ 50 years), until the patient was (correctly) diagnosed and treated in primary care, or referred to (and diagnosed in) secondary care. Model inputs were derived from an online survey among general practitioners, expert estimates and published data. The primary outcome measure was expressed as incremental cost per additional patient diagnosed with the correct underlying cause of anaemia in either work-up. Results The probability of general practitioners diagnosing the correct underlying cause increased from 49.6% (95% CI: 44.8% to 54.5%) in the routine work-up to 56.0% (95% CI: 51.2% to 60.8%) in the extensive work-up (i.e. +6.4% [95% CI: -0.6% to 13.1%]). Costs are expected to increase slightly from €842/patient (95% CI: €704 to €994) to €845/patient (95% CI: €711 to €994), i.e. +€3/patient (95% CI: €-35 to €40) in the extensive work-up, indicating incremental costs of €43 per additional patient correctly diagnosed. Conclusions The extensive laboratory work-up is more effective for diagnosing the underlying cause of anaemia by general practitioners, at a minimal increase in costs. As accompanying benefits in terms of quality of life and reduced productivity losses could not be captured in this analysis, the extensive work-up is likely cost-effective.
- Published
- 2018
36. Using expert elicitation to estimate the potential impact of improved diagnostic performance of laboratory tests: a case study on rapid discharge of suspected non-ST elevation myocardial infarction patients
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Kip, MMA, Steuten, LMG, Koffijberg, H, IJzerman, MJ, Kusters, R, Kip, MMA, Steuten, LMG, Koffijberg, H, IJzerman, MJ, and Kusters, R
- Abstract
Early health technology assessment can provide insight in the potential cost-effectiveness of new tests to guide further development decisions. This can increase their potential benefit but often requires evidence which is lacking in early test development stages. Then, expert elicitation may be used to generate evidence on the impact of tests on patient management. This is illustrated in a case study on a new triple biomarker test (copeptin, heart-type fatty acid binding protein, and high-sensitivity troponin [HsTn]) at hospital admission. The elicited evidence enables estimation of the impact of using the triple biomarker on time to exclusion of non-ST elevation myocardial infarction compared with current serial HsTn measurement (performed 0, 2, and 6 h after admission). Cardiologists were asked to estimate the effect of the triple biomarker on patient's discharge rates and interventions performed, depending on its diagnostic performance. This elicited evidence was combined with Dutch reimbursement data and published evidence into a decision analytic model. Direct hospital costs and patients' discharge rates were assessed for 3 testing strategies including this triple biomarker (ie, only at admission or combined with HsTn measurements after 2 and 6 h). Direct hospital costs of suspected non-ST elevation myocardial infarction patients using serial HsTn measurements are estimated at €1825 per patient. Combining this triple biomarker with HsTn measurements after 2 and 6 hours is expected to be the most cost-effective strategy. Depending on the diagnostic performance of the triple biomarker, this strategy is estimated to reduce costs with €66 to €205 per patient (ie, 3.6%-11.3% reduction). Expert elicitation can be a valuable tool for early health technology assessment to provide an initial estimate of the cost-effectiveness of new tests prior to their implementation in clinical practice. As demonstrated in our case study, improved diagnostic performance of the triple
- Published
- 2018
37. Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients: results from a randomised controlled multicentre trial in the Netherlands
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Kip, MMA, van Oers, JA, Shajiei, A, Beishuizen, A, Berghuis, AMS, Girbes, AR, de Jong, E, de Lange, DW, Nijsten, MWN, IJzerman, MJ, Koffijberg, H, Kusters, R, Kip, MMA, van Oers, JA, Shajiei, A, Beishuizen, A, Berghuis, AMS, Girbes, AR, de Jong, E, de Lange, DW, Nijsten, MWN, IJzerman, MJ, Koffijberg, H, and Kusters, R
- Abstract
BACKGROUND: Procalcitonin (PCT) testing can help in safely reducing antibiotic treatment duration in intensive care patients with sepsis. However, the cost-effectiveness of such PCT guidance is not yet known. METHODS: A trial-based analysis was performed to estimate the cost-effectiveness of PCT guidance compared with standard of care (without PCT guidance). Patient-level data were used from the SAPS trial in which 1546 patients were randomised. This trial was performed in the Netherlands, which is a country with, on average, low antibiotic use and a short duration of hospital stay. As quality of life among sepsis survivors was not measured during the SAPS, this was derived from a Dutch follow-up study. Outcome measures were (1) incremental direct hospital cost and (2) incremental cost per quality-adjusted life year (QALY) gained from a healthcare perspective over a one-year time horizon. Uncertainty in outcomes was assessed with bootstrapping. RESULTS: Mean in-hospital costs were €46,081/patient in the PCT group compared with €46,146/patient with standard of care (i.e. - €65 (95% CI - €6314 to €6107); - 0.1%). The duration of the first course of antibiotic treatment was lower in the PCT group with 6.9 vs. 8.2 days (i.e. - 1.2 days (95% CI - 1.9 to - 0.4), - 14.8%). This was accompanied by lower in-hospital mortality of 21.8% vs. 29.8% (absolute decrease 7.9% (95% CI - 13.9% to - 1.8%), relative decrease 26.6%), resulting in an increase in mean QALYs/patient from 0.47 to 0.52 (i.e. + 0.05 (95% CI 0.00 to 0.10); + 10.1%). However, owing to high costs among sepsis survivors, healthcare costs over a one-year time horizon were €73,665/patient in the PCT group compared with €70,961/patient with standard of care (i.e. + €2704 (95% CI - €4495 to €10,005), + 3.8%), resulting in an incremental cost-effectiveness ratio of €57,402/QALY gained. Within this time frame, the probability of PCT guidance being cost-effective was 64% at a willingness-to-pay threshold of €80,000/QALY.
- Published
- 2018
38. Toward Alignment in the Reporting of Economic Evaluations of Diagnostic Tests and Biomarkers: The AGREEDT Checklist
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Kip, MMA, IJzerman, MJ, Henriksson, M, Merlin, T, Weinstein, MC, Phelps, CE, Kusters, R, Koffijberg, H, Kip, MMA, IJzerman, MJ, Henriksson, M, Merlin, T, Weinstein, MC, Phelps, CE, Kusters, R, and Koffijberg, H
- Abstract
OBJECTIVES: General frameworks for conducting and reporting health economic evaluations are available but not specific enough to cover the intricacies of the evaluation of diagnostic tests and biomarkers. Such evaluations are typically complex and model-based because tests primarily affect health outcomes indirectly and real-world data on health outcomes are often lacking. Moreover, not all aspects relevant to the evaluation of a diagnostic test may be known and explicitly considered for inclusion in the evaluation, leading to a loss of transparency and replicability. To address this challenge, this study aims to develop a comprehensive reporting checklist. METHODS: This study consisted of 3 main steps: 1) the development of an initial checklist based on a scoping review, 2) review and critical appraisal of the initial checklist by 4 independent experts, and 3) development of a final checklist. Each item from the checklist is illustrated using an example from previous research. RESULTS: The scoping review followed by critical review by the 4 experts resulted in a checklist containing 44 items, which ideally should be considered for inclusion in a model-based health economic evaluation. The extent to which these items were included or discussed in the studies identified in the scoping review varied substantially, with 14 items not being mentioned in ≥47 (75%) of the included studies. CONCLUSIONS: The reporting checklist developed in this study may contribute to improved transparency and completeness of model-based health economic evaluations of diagnostic tests and biomarkers. Use of this checklist is therefore encouraged to enhance the interpretation, comparability, and-indirectly-the validity of the results of such evaluations.
- Published
- 2018
39. Cost-effectiveness of procalcitonin testing to guide antibiotic treatment duration in critically ill patients: results from a randomised controlled multicentre trial in the Netherlands
- Author
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NVIC, MICU, Infection & Immunity, Kip, Michelle M A, van Oers, J.A., Shajiei, A, Beishuizen, Albertus, Girbes, A.R.J., de Jong, E, de Lange, DW, Nijsten, Maarten W N, IJzerman, M.J., Koffijberg, H, Kusters, R., NVIC, MICU, Infection & Immunity, Kip, Michelle M A, van Oers, J.A., Shajiei, A, Beishuizen, Albertus, Girbes, A.R.J., de Jong, E, de Lange, DW, Nijsten, Maarten W N, IJzerman, M.J., Koffijberg, H, and Kusters, R.
- Published
- 2018
40. Biophysical model of the role of actin remodeling on dendritic spine morphology
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Miermans, C A, Kusters, R P T, Hoogenraad, C C, Storm, C., Sub Cell Biology, Celbiologie, Soft Matter and Biological Physics, Sub Cell Biology, and Celbiologie
- Subjects
0301 basic medicine ,Dendritic spine ,Polymers ,lcsh:Medicine ,Actin Filaments ,SDG 3 – Goede gezondheid en welzijn ,Biochemistry ,Actin remodeling of neurons ,Contractile Proteins ,Theoretical ,Polymers/chemistry ,Animal Cells ,Models ,Medicine and Health Sciences ,Classical mechanics ,lcsh:Science ,Cytoskeleton ,Actin Cytoskeleton/metabolism ,Neurons ,Multidisciplinary ,Chemistry ,Physics ,Classical Mechanics ,musculoskeletal system ,Cell biology ,Cell Motility ,Actin Cytoskeleton ,Dendritic Structure ,Physical Sciences ,Cellular Structures and Organelles ,Anatomy ,Cellular Types ,Research Article ,musculoskeletal diseases ,Morphology (linguistics) ,Neuronal dendrites ,Dendritic Spines ,Biophysics ,macromolecular substances ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Animals ,Actin ,lcsh:R ,Dendritic structure ,Biology and Life Sciences ,Proteins ,Actin remodeling ,Cell Biology ,Neuronal Dendrites ,Models, Theoretical ,Actin cytoskeleton ,Actins ,Spine (zoology) ,Cytoskeletal Proteins ,030104 developmental biology ,Cellular Neuroscience ,lcsh:Q ,Actin filaments ,Head ,Neck ,Neuroscience - Abstract
Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. It is well established that the remodeling of spines is strongly dependent upon the actin cytoskeleton inside the spine. A general framework that details the precise role of actin in directing the transitions between the various spine shapes is lacking. We address this issue, and present a quantitative, model-based scenario for spine plasticity validated using realistic and physiologically relevant parameters. Our model points to a crucial role for the actin cytoskeleton. In the early stages of spine formation, the interplay between the elastic properties of the spine membrane and the protrusive forces generated in the actin cytoskeleton propels the incipient spine. In the maturation stage, actin remodeling in the form of the combined dynamics of branched and bundled actin is required to form mature, mushroom-like spines. Importantly, our model shows that constricting the spine-neck aids in the stabilization of mature spines, thus pointing to a role in stabilization and maintenance for additional factors such as ring-like F-actin structures. Taken together, our model provides unique insights into the fundamental role of actin remodeling and polymerization forces during spine formation and maturation.
- Published
- 2017
41. From process improvement to people improvement: enabling learning in software development
- Author
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van Solingen, R, Berghout, E, Kusters, R, and Trienekens, J
- Published
- 2000
- Full Text
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42. Ciprofloxacin penetration into infected hepatic cysts in autosomal dominant polycystic kidney disease: a case report
- Author
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Bernts, L H P, primary, Wallenburg, E, additional, de Jonge, H J M, additional, Schaap, B, additional, Kusters, R, additional, Overtoom, T T C, additional, Brüggemann, R J M, additional, Drenth, J P H, additional, and Lantinga, M A, additional
- Published
- 2018
- Full Text
- View/download PDF
43. Schelden en codewisseling onder tweetaligen in een eentalige samenleving
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Kusters, R., Nortier, J. M. (Thesis Advisor), Corver, N. F. M., Kusters, R., Nortier, J. M. (Thesis Advisor), and Corver, N. F. M.
- Abstract
A lot of research has been done into codeswitching among bilinguals in a bilingual society. Also quite a body of research exists into swearing practices. The number of studies into emotion and bilingualism is significantly smaller. With this small qualitative research, I focus on codeswitching in relation to swearing of bilinguals in a monolingual society – Thai-Dutch bilinguals in The Netherlands to be specific. The findings suggest that Thai-Dutch bilinguals, despite being very reluctant to swear (in line with Thai attitudes towards swearing in Thailand), do – on occasion – codeswitch when they start swearing; both when in conversation with people who do not speak Thai, and in conversation with people who do. I suggest that the former is motivated by exclusion – 'the listener knows I'm angry, but doesn't need to know exactly what I say' – and that the latter is motivated by a desire to be more concise; a Thai native speaker would prefer to swear in Thai and does so when possible. The fact that Thai-Dutch bilinguals are very reluctant to swear, and/or are very reluctant to share information about their swearing practises, needs to be stressed here too.
- Published
- 2017
44. Biophysical model of the role of actin remodeling on dendritic spine morphology
- Author
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Sub Cell Biology, Celbiologie, Miermans, C A, Kusters, R P T, Hoogenraad, C C, Storm, C., Sub Cell Biology, Celbiologie, Miermans, C A, Kusters, R P T, Hoogenraad, C C, and Storm, C.
- Published
- 2017
45. Active elastohydrodynamics of vesicles in narrow blind constrictions
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Fai, T.G., Kusters, R., Harting, J., Rycroft, C.H., Mahadevan, L., Fai, T.G., Kusters, R., Harting, J., Rycroft, C.H., and Mahadevan, L.
- Abstract
Fluid-resistance limited transport of vesicles through narrow constrictions is a recurring theme in many biological and engineering applications. Inspired by the motor-driven movement of soft membrane-bound vesicles into closed neuronal dendritic spines, here we study this problem using a combination of passive three-dimensional simulations and a simplified semianalytical theory for the active transport of vesicles forced through constrictions by molecular motors. We show that the motion of these objects is characterized by two dimensionless quantities related to the geometry and to the strength of forcing relative to the vesicle elasticity. We use numerical simulations to characterize the transit time for a vesicle forced by fluid pressure through a constriction in a channel and find that relative to an open channel, transport into a blind end leads to the formation of a smaller forward-flowing lubrication layer that strongly impedes motion. When the fluid pressure forcing is complemented by forces due to molecular motors that are responsible for vesicle trafficking into dendritic spines, we find that the competition between motor forcing and fluid drag results in multistable dynamics reminiscent of the real system. Our study highlights the role of nonlocal hydrodynamic effects in determining the kinetics of vesicular transport in constricted geometries.
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- 2017
46. Biophysical model of the role of actin remodeling on dendritic spine morphology
- Author
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Miermans, K., Kusters, R., Hoogenraad, C.C., Storm, C., Miermans, K., Kusters, R., Hoogenraad, C.C., and Storm, C.
- Abstract
Dendritic spines are small membranous structures that protrude from the neuronal dendrite. Each spine contains a synaptic contact site that may connect its parent dendrite to the axons of neighboring neurons. Dendritic spines are markedly distinct in shape and size, and certain types of stimulation prompt spines to evolve, in fairly predictable fashion, from thin nascent morphologies to the mushroom-like shapes associated with mature spines. It is well established that the remodeling of spines is strongly dependent upon the actin cytoskeleton inside the spine. A general framework that details the precise role of actin in directing the transitions between the various spine shapes is lacking. We address this issue, and present a quantitative, model-based scenario for spine plasticity validated using realistic and physiologically relevant parameters. Our model points to a crucial role for the actin cytoskeleton. In the early stages of spine formation, the interplay between the elastic properties of the spine membrane and the protrusive forces generated in the actin cytoskeleton propels the incipient spine. In the maturation stage, actin remodeling in the form of the combined dynamics of branched and bundled actin is required to form mature, mushroom-like spines. Importantly, our model shows that constricting the spine-neck aids in the stabilization of mature spines, thus pointing to a role in stabilization and maintenance for additional factors such as ring-like F-actin structures. Taken together, our model provides unique insights into the fundamental role of actin remodeling and polymerization forces during spine formation and maturation.
- Published
- 2017
47. Probing the interplay between dendritic spine morphology and membrane-bound diffusion
- Author
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Adrian, M., Kusters, R., Storm, C., Hoogenraad, C.C., Kapitein, L.C., Adrian, M., Kusters, R., Storm, C., Hoogenraad, C.C., and Kapitein, L.C.
- Abstract
Dendritic spines are protrusions along neuronal dendrites that harbor the majority of excitatory postsynapses. Their distinct morphology, often featuring a bulbous head and small neck that connects to the dendritic shaft, has been shown to facilitate compartmentalization of electrical and cytoplasmic signaling stimuli elicited at the synapse. The extent to which spine morphology also forms a barrier for membrane-bound diffusion has remained unclear. Recent simulations suggested that especially the diameter of the spine neck plays a limiting role in this process. Here, we examine the connection between spine morphology and membrane-bound diffusion through a combination of photoconversion, live-cell superresolution experiments, and numerical simulations. Local photoconversion was used to obtain the timescale of diffusive equilibration in spines and followed by global sparse photoconversion to determine spine morphologies with nanoscopic resolution. These morphologies were subsequently used to assess the role of morphology on the diffusive equilibration. From the simulations, we could determine a robust relation between the equilibration timescale and a generalized shape factor calculated using both spine neck width and neck length, as well as spine head size. Experimentally, we found that diffusive equilibration was often slower, but rarely faster than predicted from the simulations, indicating that other biological confounders further reduce membrane-bound diffusion in these spines. This shape-dependent membrane-bound diffusion in mature spines may contribute to spine-specific compartmentalization of neurotransmitter receptors and signaling molecules and thereby support long-term plasticity of synaptic contacts.
- Published
- 2017
48. The cost-utility of point-of-care troponin testing to diagnose acute coronary syndrome in primary care
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Kip, MMA, Koffijberg, H, Moesker, MJ, IJzerman, MJ, Kusters, R, Kip, MMA, Koffijberg, H, Moesker, MJ, IJzerman, MJ, and Kusters, R
- Abstract
BACKGROUND: The added value of using a point-of-care (POC) troponin test in primary care to rule out acute coronary syndrome (ACS) is debated because test sensitivity is inadequate early after symptom onset. This study investigates the potential cost-utility of diagnosing ACS by a general practitioner (GP) when a POC troponin test is available versus GP assessment only. METHODS: A patient-level simulation model was developed, representing a hypothetical cohort of the Dutch population (>35 years) consulting the GP with chest complaints. All health related consequences as well as cost consequences were included. Both symptom duration, selection of patients in whom the POC troponin test is performed, and test performance at different time points were incorporated. Health outcomes were expressed as Quality-Adjusted Life Years (QALYs). The main outcome parameters involve the effect of POC troponin testing on (in)correct hospital referrals, QALYs, and costs. RESULTS: The POC troponin strategy decreases the referral rate in non-ACS patients from 38.46% to 31.85%. Despite a small increase in non-referral among ACS patients from 0.22% to 0.27%, the overall health effect is negligible. Costs will decrease with €77.25/patient (95% CI €-126.81 to €-33.37). CONCLUSIONS: The POC troponin strategy is likely cost-saving, by reducing hospital referrals. The small increase in missed ACS patients can be partly explained by conservative assumptions used in the analysis. Besides, current developments in POC troponin tests will likely further improve their diagnostic performance. Therefore, future prospective studies are warranted to investigate whether those developments make the POC troponin test to a safe and cost-effective diagnostic tool for diagnosing ACS in general practices.
- Published
- 2017
49. International definition of a point-of-care test in family practice: a modified e-Delphi procedure
- Author
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Schols, A, Dinant, G, Hopstaken, R, Price, C, Kusters, R, Cals, J, Schols, A, Dinant, G, Hopstaken, R, Price, C, Kusters, R, and Cals, J
- Published
- 2017
50. Dynamic phase separation of confined driven particles
- Author
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Kusters, R., primary and Storm, C., additional
- Published
- 2017
- Full Text
- View/download PDF
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