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1. A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer

Author

ter Heine, Rob, van den Heuvel, Michel M., Piet, Berber, Deenen, Maarten J., van der Wekken, Anthonie J., Hendriks, Lizza E. L., Croes, Sander, van Geel, Robin M. J. M., Jansman, Frank G. A., Boshuizen, Rogier C., Franssen, Eric J. F., Smit, Arthur A. J., Dumoulin, Daphne W., Oude Munnink, Thijs H., Smit, Egbert F., Derijks, Hieronymus J., van der Leest, Cor H., Hendrikx, Jeroen J. M. A., Moes, Dirk J. A. R., and de Rouw, Nikki

Published
2023
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5. Impact of Drug Recalls on Patients in The Netherlands: A 5-Year Retrospective Data Analysis

Author

Annema, Pieter A, Derijks, Hieronymus J, Bouvy, Marcel L, van Marum, Rob J, Annema, Pieter A, Derijks, Hieronymus J, Bouvy, Marcel L, and van Marum, Rob J

Abstract

Drug recalls occur frequently and have the potential to impact considerable numbers of patients and healthcare providers. However, in the absence of a comprehensive overview the extent of conducted recalls and their impact on patients remains unknown. To address this, we developed a comprehensive overview of drug recalls affecting patients. We compiled this overview based on the drug recall registrations from the Jeroen Bosch Hospital (JBZ), the University Medical Center Utrecht (UMCU), and the Royal Dutch Pharmacists Association (KNMP). A retrospective data analysis was conducted to identify drug recalls that affected patients. Specifically, we defined these as drug recalls that required patients to actively switch their drug to a different batch or brand of the same drug or to switch to a drug within the same or a different class of drugs. To quantify the impact, we used real-world drug dispensing data. Between January 1, 2017, and December 31, 2021, we identified 48 drug recalls that necessitated patients to make active changes to their medications an estimated 855,000 times. Most of the affected patients (292,000) were required to switch to a different brand of the same drug, whereas in 95,000 cases patients had to switch to a drug from another drug class. Our study suggests that a significant number of patients are affected by drug recalls. Future efforts are needed to elucidate patients' experiences and preferences regarding drug recalls, which could provide valuable insights to aid decision-making by relevant (national) authorities concerning drug recalls.

Published
2024

6. Adoption of antithrombotic stewardship and utilization of clinical decision support systems —A questionnaire-based survey in Dutch hospitals

Author

Graafsma, Jetske, Klopotowska, Joanna E., Derijks, Hieronymus J., van de Garde, Ewoudt M.W., Hoge, Rien H.L., Kruip, Marieke J.H.A., Meijer, Karina, Karapinar-Carkit, Fatma, van den Bemt, Patricia M.L.A., Graafsma, Jetske, Klopotowska, Joanna E., Derijks, Hieronymus J., van de Garde, Ewoudt M.W., Hoge, Rien H.L., Kruip, Marieke J.H.A., Meijer, Karina, Karapinar-Carkit, Fatma, and van den Bemt, Patricia M.L.A.

Abstract

Antithrombotics require careful monitoring to prevent adverse events. Safe use can be promoted through so-called antithrombotic stewardship. Clinical decision support systems (CDSSs) can be used to monitor safe use of antithrombotics, supporting antithrombotic stewardship efforts. Yet, previous research shows that despite these interventions, antithrombotics continue to cause harm. Insufficient adoption of antithrombotic stewardship and suboptimal use of CDSSs may provide and explanation. However, it is currently unknown to what extent hospitals adopted antithrombotic stewardship and utilize CDSSs to support safe use of antithrombotics. A semi-structured questionnaire-based survey was disseminated to 12 hospital pharmacists from different hospital types and regions in the Netherlands. The primary outcome was the degree of antithrombotic stewardship adoption, expressed as the number of tasks adopted per hospital and the degree of adoption per task. Secondary outcomes included characteristics of CDSS alerts used to monitor safe use of antithrombotics. All 12 hospital pharmacists completed the survey and report to have adopted antithrombotic stewardship in their hospital to a certain degree. The median adoption of tasks was two of five tasks (range 1–3). The tasks with the highest uptake were: drafting and maintenance of protocols (100%) and professional’s education (58%), while care transition optimization (25%), medication reviews (8%) and patient counseling (8%) had the lowest uptake. All hospitals used a CDSS to monitor safe use of antithrombotics, mainly via basic alerts and less frequently via advanced alerts. The most frequently employed alerts were: identification of patients using a direct oral anticoagulant (DOAC) or a vitamin K antagonist (VKA) with one or more other antithrombotics (n = 6) and patients using a VKA to evaluate correct use (n = 6), both reflecting basic CDSS. All participating hospitals adopted antithrombotic stewardship, but the adopted t

Published
2024

7. Impact of Drug Recalls on Patients in The Netherlands: A 5-Year Retrospective Data Analysis

Author

Afd Pharmacoepi & Clinical Pharmacology, PECP – Centre for Clinical Therapeutics, Pharmacoepidemiology and Clinical Pharmacology, Annema, Pieter A, Derijks, Hieronymus J, Bouvy, Marcel L, van Marum, Rob J, Afd Pharmacoepi & Clinical Pharmacology, PECP – Centre for Clinical Therapeutics, Pharmacoepidemiology and Clinical Pharmacology, Annema, Pieter A, Derijks, Hieronymus J, Bouvy, Marcel L, and van Marum, Rob J

Published
2024

9. Sulfamethoxazole-Trimethoprim-Induced Hyperkalemia in Hospitalized Patients Using Potassium-Sparing Drugs: An Observational Study.

Author

Butterhoff, Madelon H., Derijks, Hieronymus J., Hermens, Walter, and van der Linden, Paul D.

Subjects
HOSPITAL patients, HYPERKALEMIA, RENIN-angiotensin system, SCIENTIFIC observation, RESEARCH personnel
Abstract

The objective of this analysis is to investigate the risk of hyperkalemia in hospitalized patients using sulfamethoxazole-trimethoprim (Co-trimoxazole) and a potassium-sparing drug (potassium-sparing diuretic or renin-angiotensin system [RAS]-inhibitor). Researchers conducted a nested case control study within a cohort of hospitalized patients using a potassium-sparing diuretic and/or a RAS-inhibitor from the PHARMO Database Network. Researchers estimated the odds ratios (ORs) and 95% confidence intervals (CI) for the risk of hyperkalemia in patients receiving both Co-trimoxazole and a potassium-sparing drug compared with patients only receiving a potassium-sparing drug. Among a cohort of 25,849 patients, researchers identified 2054 cases of hyperkalemia during hospitalization in patients also using a potassium-sparing drug. Using Co-trimoxazole in addition to a potassium-sparing drug was associated with an increased risk of hyperkalemia in hospitalized patients (ORadj = 1.65, 95% CI 1.26-2.16) compared with using only a potassium-sparing drug. There was a trend of a more pronounced association between hyperkalemia and the co-use of Co-trimoxazole and potassium-sparing drugs in patients with an estimated GFR of 15-29 mL/min (ORadj = 3.15, 95% CI 1.29-7.70). The number needed to harm for hyperkalemia induced by adding Cotrimoxazole to patients receiving a potassium-sparing drug is 19.5. Using the combination of Co-trimoxazole with a potassium-sparing drug in hospitalized patients increases the risk of hyperkalemia compared with using only a potassium-sparing drug. Physicians and other prescribers should be aware of hyperkalemia and routinely monitor serum potassium levels in hospitalized patients using this combination of drugs. [ABSTRACT FROM AUTHOR]

Published
2024
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10. The use of artificial intelligence to optimize medication alerts generated by clinical decision support systems: a scoping review.

Author

Graafsma, Jetske, Murphy, Rachel M, Garde, Ewoudt M W van de, Karapinar-Çarkit, Fatma, Derijks, Hieronymus J, Hoge, Rien H L, Klopotowska, Joanna E, and Bemt, Patricia M L A van den

Abstract

Objective Current Clinical Decision Support Systems (CDSSs) generate medication alerts that are of limited clinical value, causing alert fatigue. Artificial Intelligence (AI)-based methods may help in optimizing medication alerts. Therefore, we conducted a scoping review on the current state of the use of AI to optimize medication alerts in a hospital setting. Specifically, we aimed to identify the applied AI methods used together with their performance measures and main outcome measures. Materials and Methods We searched Medline, Embase, and Cochrane Library database on May 25, 2023 for studies of any quantitative design, in which the use of AI-based methods was investigated to optimize medication alerts generated by CDSSs in a hospital setting. The screening process was supported by ASReview software. Results Out of 5625 citations screened for eligibility, 10 studies were included. Three studies (30%) reported on both statistical performance and clinical outcomes. The most often reported performance measure was positive predictive value ranging from 9% to 100%. Regarding main outcome measures, alerts optimized using AI-based methods resulted in a decreased alert burden, increased identification of inappropriate or atypical prescriptions, and enabled prediction of user responses. In only 2 studies the AI-based alerts were implemented in hospital practice, and none of the studies conducted external validation. Discussion and Conclusion AI-based methods can be used to optimize medication alerts in a hospital setting. However, reporting on models' development and validation should be improved, and external validation and implementation in hospital practice should be encouraged. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Impact of Drug Recalls on Patients in The Netherlands: A 5‐Year Retrospective Data Analysis.

Author

Annema, Pieter A., Derijks, Hieronymus J., Bouvy, Marcel L., and van Marum, Rob J.

Subjects
DRUG recall, PATIENTS' attitudes, PATIENT experience, ACADEMIC medical centers, DRUG registration
Abstract

Drug recalls occur frequently and have the potential to impact considerable numbers of patients and healthcare providers. However, in the absence of a comprehensive overview the extent of conducted recalls and their impact on patients remains unknown. To address this, we developed a comprehensive overview of drug recalls affecting patients. We compiled this overview based on the drug recall registrations from the Jeroen Bosch Hospital (JBZ), the University Medical Center Utrecht (UMCU), and the Royal Dutch Pharmacists Association (KNMP). A retrospective data analysis was conducted to identify drug recalls that affected patients. Specifically, we defined these as drug recalls that required patients to actively switch their drug to a different batch or brand of the same drug or to switch to a drug within the same or a different class of drugs. To quantify the impact, we used real‐world drug dispensing data. Between January 1, 2017, and December 31, 2021, we identified 48 drug recalls that necessitated patients to make active changes to their medications an estimated 855,000 times. Most of the affected patients (292,000) were required to switch to a different brand of the same drug, whereas in 95,000 cases patients had to switch to a drug from another drug class. Our study suggests that a significant number of patients are affected by drug recalls. Future efforts are needed to elucidate patients' experiences and preferences regarding drug recalls, which could provide valuable insights to aid decision‐making by relevant (national) authorities concerning drug recalls. [ABSTRACT FROM AUTHOR]

Published
2024
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15. A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer.

Author

Heine, R. ter, Heuvel, M.M. van den, Piet, B., Deenen, M.J., Wekken, A.J. van der, Hendriks, L.E., Croes, S., Geel, R.M.J.M. van, Jansman, F.G.A., Boshuizen, R.C., Franssen, E.J.F., Smit, A.A.J., Dumoulin, D.W., de Munnink, T.H. Ou, Smit, E.F., Derijks, Hieronymus J., Leest, C.H. van der, Hendrikx, J.J., Moes, D.J., Rouw, N. de, Heine, R. ter, Heuvel, M.M. van den, Piet, B., Deenen, M.J., Wekken, A.J. van der, Hendriks, L.E., Croes, S., Geel, R.M.J.M. van, Jansman, F.G.A., Boshuizen, R.C., Franssen, E.J.F., Smit, A.A.J., Dumoulin, D.W., de Munnink, T.H. Ou, Smit, E.F., Derijks, Hieronymus J., Leest, C.H. van der, Hendrikx, J.J., Moes, D.J., and Rouw, N. de

Abstract

Item does not contain fulltext, BACKGROUND: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide. OBJECTIVE: We aimed to develop alternative dosing regimens to reduce drug expenses. METHODS: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan. The alternative dosing regimens were developed by means of modeling and simulation based on the population pharmacokinetic models developed by the license holders. They were based on weight bands and the administration of complete vials to limit drug wastage. The resulting dosing regimens were developed to comply with criteria used by regulatory authorities for in silico dose development. RESULTS: We found that alternative dosing regimens could result in cost savings that range from 11 to 28%, and lead to equivalent pharmacokinetic exposure with no relevant increases in variability in exposure. CONCLUSIONS: Dosing regimens based on weight bands and the use of complete vials to reduce drug wastage result in less expenses while maintaining equivalent exposure. The level of evidence of our proposal is the same as accepted by regulatory authorities for the approval of alternative dosing regimens of other monoclonal antibodies in oncology. The proposed alternative dosing regimens can, therefore, be directly implemented in clinical practice.

Published
2023

16. Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial

Author

Apotheek O&O&O, Cancer, de Rouw, Nikki, Boosman, René J., Burgers, Jacobus A., Huitema, Alwin D.R., Dingemans, Anne Marie C., Derijks, Hieronymus J., Burger, David M., Piet, Berber, Hendriks, Lizza E.L., Biesma, Bonne, Pruis, Melinda A., Dumoulin, Daphne W., Croes, Sander, Mathijssen, Ron H.J., van den Heuvel, Michel M., ter Heine, Rob, Apotheek O&O&O, Cancer, de Rouw, Nikki, Boosman, René J., Burgers, Jacobus A., Huitema, Alwin D.R., Dingemans, Anne Marie C., Derijks, Hieronymus J., Burger, David M., Piet, Berber, Hendriks, Lizza E.L., Biesma, Bonne, Pruis, Melinda A., Dumoulin, Daphne W., Croes, Sander, Mathijssen, Ron H.J., van den Heuvel, Michel M., and ter Heine, Rob

Published
2023

20. Renal function-based versus standard dosing of pemetrexed: a randomized controlled trial

Author

de Rouw, Nikki, primary, Boosman, René J., additional, Burgers, Jacobus A., additional, Huitema, Alwin D. R., additional, Dingemans, Anne-Marie C., additional, Derijks, Hieronymus. J., additional, Burger, David M., additional, Piet, Berber, additional, Hendriks, Lizza E. L., additional, Biesma, Bonne, additional, Pruis, Melinda A., additional, Dumoulin, Daphne W., additional, Croes, Sander, additional, Mathijssen, Ron H. J., additional, van den Heuvel, Michel M., additional, and ter Heine, Rob, additional

Published
2022
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22. The effect of Patient's Own Medication use on patient's self-reported medication knowledge during hospitalisation: a pre-post intervention study

Author

Herpen-Meeuwissen, L.J.M. van, Bemt, B.J.F van den, Derijks, Hieronymus J., Bemt, Patricia M. L. A. van den, Maat, B., Onzenoort, H.A.W. van, RS: Carim - V01 Vascular complications of diabetes and metabolic syndrome, Clinical Pharmacy, and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)

Subjects
RISK, animal structures, Health Policy, Hospitals, Patient Discharge, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Hospitalization, All institutes and research themes of the Radboud University Medical Center, ADHERENCE, Surveys and Questionnaires, DRUG-RELATED ADMISSIONS, Humans, Self Report, sense organs
Abstract

Background Improving patient’s medication knowledge and consequently medication use is essential for optimal treatment outcomes. As patient knowledge about medication is currently suboptimal, interventions to optimise medication knowledge are necessary. Implementation of Patient’s Own Medication (POM) in which patients bring their outpatient medication to the hospital, and nurses administer these during admission, may increase medication knowledge. The aim of this study is to explore the impact of POM use on self-reported medication knowledge of hospitalised patients compared to standard care. Patient’s sense of medication safety, attitude to the provision of information, and to inpatient medication use were studied in both standard care and during POM use too. Method In this nationwide intervention study perceived medication knowledge was assessed with a questionnaire pre and post implementing POM use. The questionnaire assessed perceived medication knowledge at admission and discharge, medication safety during hospitalisation, the provision of information during hospitalisation and at discharge, and inpatient medication use during hospitalisation. Patients’ answers were categorised into positive and negative/neutral. The proportion of patients with adequate medication knowledge, in the standard care and POM use group at hospital admission and discharge, were calculated and compared with adjustment for potential confounders. Results Among the 731 patients (393 received standard care and 338 POM) who completed the questionnaire (80.2%), POM use seemed to be positively associated with self-reported knowledge on how to use medication at discharge (adjusted OR: 3.22 [95% CI 2.01–5.16]). However, for the other two knowledge related statements POM use was not associated. Medication knowledge at admission was the most important variable associated with perceived medication knowledge at discharge. The majority perceived POM use to be safer (52.9% of standard care patients versus 74.0% POM users; P P = 0.01), and most patients preferred POM use regardless of having experienced it (68.2% versus 82.2% resp.; P Conclusion POM use positively affects patient’s medication knowledge about how to use medication and patients’ perception of medication safety. With POM use more patients have a positive attitude towards the provision of information. The majority of patients prefer POM use. In conclusion, POM use seems a valuable intervention and requires further investigation.

Published
2022
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23. Dual autoencoders modeling of electronic health records for adverse drug event preventability prediction

Author

Liao, Wenjun, Derijks, Hieronymus J, Blencke, Audrey A, De Vries, Esther, Van Seyen, Minou, J Van Marum, Robert, Liao, Wenjun, Derijks, Hieronymus J, Blencke, Audrey A, De Vries, Esther, Van Seyen, Minou, and J Van Marum, Robert

Abstract

Background Elderly patients are at increased risk for Adverse Drug Events (ADEs). Proactively screening elderly people visiting the emergency department for the possibility of their hospital admission being drug-related helps to improve patient care as well as prevent potential unnecessary medical costs. Existing routine ADE assessment heavily relies on a rule-based checking process. Recently, machine learning methods have been shown to be effective in automating the detection of ADEs, however, most approaches used only either structured data or free texts for their feature engineering. How to better exploit all available EHRs data for better predictive modeling remains an important question. On the other hand, automated reasoning for the preventability of ADEs is still a nascent line of research. Methods Clinical information of 714 elderly ED-visit patients with ADE preventability labels was provided as ground truth data by Jeroen Bosch Ziekenhuis hospital, the Netherlands. Methods were developed to address the challenges of applying feature engineering to heterogeneous EHRs data. A Dual Autoencoders (2AE) model was proposed to solve the problem of imbalance embedded in the existing training data. Results Experimental results showed that 2AE can capture the patterns of the minority class without incorporating an extra process for class balancing. 2AE yields adequate performance and outperforms other more mainstream approaches, resulting in an AUPRC score of 0.481. Conclusions We have demonstrated how machine learning can be employed to analyze both structured and unstructured data from electronic health records for the purpose of preventable ADE prediction. The developed algorithm 2AE can be used to effectively learn minority group phenotype from imbalanced data.

Published
2022

24. Hyperhydration with cisplatin does not influence pemetrexed exposure

Author

de Rouw, Nikki, Derijks, Hieronymus J., Hilbrands, Luuk B., Boosman, René J., Piet, Berber, Koolen, Stijn L.W., Burgers, Jacobus A., Dingemans, Anne Marie C., van den Heuvel, Michel M., Hendriks, Lizza E.L., Aerts, Joachim G.J.V., Croes, Sander, Mathijssen, Ron H.J., Huitema, Alwin D.R., Burger, David M., Biesma, Bonne, ter Heine, Rob, de Rouw, Nikki, Derijks, Hieronymus J., Hilbrands, Luuk B., Boosman, René J., Piet, Berber, Koolen, Stijn L.W., Burgers, Jacobus A., Dingemans, Anne Marie C., van den Heuvel, Michel M., Hendriks, Lizza E.L., Aerts, Joachim G.J.V., Croes, Sander, Mathijssen, Ron H.J., Huitema, Alwin D.R., Burger, David M., Biesma, Bonne, and ter Heine, Rob

Abstract

Pemetrexed is a cytotoxic drug for first-line treatment of lung cancer. It is often combined with other anticancer drugs such as cisplatin or carboplatin. In clinical practice, hyperhydration regimens are applied to overcome cisplatin-related nephrotoxicity. As pemetrexed is almost completely eliminated from the body by the kidneys, hyperhydration can result in augmented clearance. Furthermore, administration of large quantities of fluid may increase the volume of distribution of pemetrexed. Pharmacokinetics and, thus, efficacy and toxicity may be influenced by hyperhydration. This has not yet been properly studied. We performed a population pharmacokinetic analysis to assess hyperhydration as a covariate for pemetrexed clearance and for volume of distribution A relevant change was defined as >25% increase in clearance or volume of distribution. In our extensive dataset of 133 individuals, we found that hyperhydration did not significantly or relevantly explain variability in pemetrexed clearance (unchanged, P =.196) or volume of distribution (+7% change, P =.002), despite a power of >99% to detect a relevant change. Therefore, dose adjustments of pemetrexed are not required during hyperhydration with cisplatin.

Published
2022

25. The Pharmacoeconomic Benefits of Pemetrexed Dose Individualization in Patients With Lung Cancer

Author

HEE, Child Health, JC onderzoeksprogramma Methodology, de Rouw, Nikki, de Boer, Merel, Boosman, René J., van den Heuvel, Michel M., Burger, David M., Lieverse, Joris E., Derijks, Hieronymus J., Frederix, Geert W.J., ter Heine, Rob, HEE, Child Health, JC onderzoeksprogramma Methodology, de Rouw, Nikki, de Boer, Merel, Boosman, René J., van den Heuvel, Michel M., Burger, David M., Lieverse, Joris E., Derijks, Hieronymus J., Frederix, Geert W.J., and ter Heine, Rob

Published
2022

29. Proton Pump inhibitors and Hypomagnesemia in Older inpatients: An Observational Study.

Author

Windsant-van den Tweel, Annemieke M. Anna Vermeulen, Derijks, Hieronymus J., Gadiot, Nadine P. P. M., and Keijsers, Carolina J. P. W.

Subjects
PROTON pump inhibitors, HYPOMAGNESEMIA, OLDER patients, SCIENTIFIC observation
Abstract

PURPOSE: Proton pump inhibitors (PPIs) are prescribed frequently and can cause potentially severe hypomagnesemia. Researchers assessed the prevalence of hypomagnesemia and the association between PPI use and hypomagnesemia in hospitalized older patients. METHODS: Researchers conducted a single-center, observational, retrospective cohort study with patients admitted to a geriatric ward at the Jeroen Bosch Hospital in the period between June 24, 2016, and August 30, 2020. Patients were included if they were 65 years of age or older, had a serum magnesium measurement, and a complete overview of patient's current medication was present at the day of admission. The primary outcome was the occurrence of hypomagnesemia at hospital admission. Exposure to PPIs was the primary determinant investigated. Covariates were studied to identify risk factors and to adjust for potential confounding. The strength of the association between PPI and hypomagnesemia was evaluated with unconditional logistic regression, expressed as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: The prevalence of hypomagnesemia was 21.9% in PPI users and 15.8% in non-PPI users. Overall, the use of PPIs was associated with hypomagnesemia (ORadj = 1.38, 95% CI 1.09-1.76). A trend for this association was most pronounced in male patients (ORadj = 1.88, 95% CI 1.27-2.79), smokers (ORadj = 3.95, 95% CI 1.52-10.28), and in patients using > 7 units alcohol a week (ORadj = 4.44, 95% CI 1.40-14.12). CONCLUSiON: Older patients who are taking a PPI have a higher risk of developing hypomagnesemia than nonusers; additional factors can contribute to the risk. Physicians should be aware of PPI-induced hypomagnesemia and routinely monitor serum magnesium levels in older patients. [ABSTRACT FROM AUTHOR]

Published
2022
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32. Hyperhydration with cisplatin does not influence pemetrexed exposure

Author

de Rouw, Nikki, primary, Derijks, Hieronymus J., additional, Hilbrands, Luuk B., additional, Boosman, René J., additional, Piet, Berber, additional, Koolen, Stijn L. W., additional, Burgers, Jacobus A., additional, Dingemans, Anne‐Marie C., additional, van den Heuvel, Michel M., additional, Hendriks, Lizza E. L., additional, Aerts, Joachim G. J. V., additional, Croes, Sander, additional, Mathijssen, Ron H. J., additional, Huitema, Alwin D. R., additional, Burger, David M., additional, Biesma, Bonne, additional, and ter Heine, Rob, additional

Published
2021
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36. The Pharmacoeconomic Benefits of Pemetrexed Dose Individualization in Patients With Lung Cancer.

Author

de Rouw, Nikki, de Boer, Merel, Boosman, René J., van den Heuvel, Michel M., Burger, David M., Lieverse, Joris E., Derijks, Hieronymus J., Frederix, Geert W.J., and ter Heine, Rob

Subjects
PEMETREXED, LUNG cancer, MONTE Carlo method, CANCER patients
Abstract

Neutropenia is a dose‐related treatment‐limiting and costly adverse event of pemetrexed. We postulate that individualized dosing reduces the incidence of neutropenia. The aims of this study were (i) to investigate the costs of pemetrexed‐related neutropenia and (ii) to determine the pharmacoeconomic benefits of individualized dosing of pemetrexed in terms of budget impact, yearly cost savings, and reduction in severe neutropenia. Retrospective data on the treatment of grade 3 or higher neutropenia during pemetrexed‐based chemotherapy were collected from three Dutch hospitals to determine the mean healthcare consumption during a neutropenic episode. Subsequently, Monte Carlo simulations were performed using a validated pharmacokinetic/pharmacodynamic model to predict the neutropenia incidence during four cycles for standard dosing of pemetrexed and individualized dosing. The mean costs per neutropenia and the expected neutropenia incidence were combined to calculate the budget impact and cost savings. We found that the average costs per pemetrexed‐associated neutropenic episode to be €1,490 (US $1,674). The neutropenia incidence for the standard and individualized pemetrexed dosing strategies were 12.7% and 9.9%, respectively. This resulted in total expected neutropenia‐related costs of ~ €3.0 million (US $3.372 million) and €2.4 million (US $2.697 million), respectively. Taking the number of patients eligible for pemetrexed treatment into account, individualized dosing could result in saving €686,000 (US $770,995) on a yearly basis in the Netherlands alone. Individualized dosing of pemetrexed can decrease the incidence of neutropenia and thus result in a significant decrease in neutropenia‐related costs and decreased risk of hospitalization or even death while maintaining therapeutic exposure. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Body weight gain in clozapine‐treated patients: Is norclozapine the culprit?

Author

Jessurun, Naomi T., Derijks, Hieronymus J., van Marum, Rob J., Jongkind, Amy, Giraud, Eline L., van Puijenbroek, Eugène P., and Grootens, Koen P.

Subjects
*WEIGHT gain, *BODY weight, *BODY mass index, *WAIST circumference, *SEROTONIN, *DOPAMINE antagonists, *ANTIPSYCHOTIC agents
Abstract

The antipsychotic drug clozapine is associated with weight gain. The proposed mechanisms include blocking of serotonin (5‐HT2a/2c), dopamine (D2) and histamine (H1) receptors. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2) to norclozapine, a metabolite with more 5‐HT2c‐receptor and less H1 blocking capacity. We hypothesized that norclozapine serum levels correlate with body mass index (BMI), waist circumference and other parameters of the metabolic syndrome. We performed a retrospective cross‐sectional study in 39 patients (female n = 8 (20.5%), smokers n = 18 (46.2%), average age 45.8 ± 9.9 years) of a clozapine outpatient clinic in the Netherlands between 1 January 2017 and 1 July 2020. Norclozapine concentrations correlated with waist circumference (r = 0.354, P =.03) and hemoglobin A1c (HbA1c) (r = 0.34, P =.03). In smokers (smoking induces CYP1A2), norclozapine concentrations correlated with waist circumference (r = 0.723, P =.001), HbA1c (r = 0.49, P =.04) and BMI (r = 0.63, P =.004). Elucidating the relationship between norclozapine and adverse effects of clozapine use offers perspectives for interventions and treatment options. [ABSTRACT FROM AUTHOR]

Published
2022
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43. Medicatieoptimalisatie bij psychogeriatrische verpleeghuispatiënten: Succesvol aanpassen van medicatie is mogelijk

Author

Blenke, Audrey A. M., van Marum, Rob J., Vermeulen Windsant-van den Tweel, M. A., Hermens, Walter A. J. J., and Derijks, Hieronymus J.

Subjects
sense organs
Abstract

OBJECTIVE To determine whether advised changes as a result of structured medication reviews in psychogeriatnc patients were implemented and implemented changes were maintained. DESIGN We performed a prospective cohort study in three nursing homes in The Netherlands. METHODS After admission, newly admitted psychogeriatnc residents were subjected to a structured medication review - performed by a pharmacist and physician - resulting in a treatment plan, which was approved by the patient's legal representative and effectuated. Main outcome measures were the percentage of advised changes approved |= approval ratel and the percentage of implemented medication changes still present 90 days after approval != 90-day implementation rate). RESULTS A total of 45 patients were included who used a total number of 333 drugs Imean ± SD = 7.4 ± 3.3 drugs). Changes were advised for 159 medications used by 42 patients. Of these changes 150 were approved (approval rate = 94.3%). Finally, 105 were implemented and 89 were still implemented after 90 days (90-day implementation rate = 84.8%). Overall, 59.7% of the advised changes concerned deprescribing, 22.6% concerned an adjustment of a drug (dose, pharmaceutical form, administration time, frequency of dosing or a combination) and 11.9% concerned starting a drug. The proportion of advised changes implemented was similar for symptom-modifying and risk-modifying drugs, namely, almost 85%. Overall, 55.3% of the recommended changes to deprescribe or reduce dose concerned 10 drug groups. CONCLUSION Medication could be successfully deprescribed from psychogeriatnc patients after structured medication reviews, performed by pharmacists and nursing home physicians. More than 50% of the advised changes to deprescribe or reduce dose involved 10 drug groups, which raises the question whether the structured medication review can be performed more efficiently by focusing on the most common problems.

Published
2019

45. Economic impact of Patient's Own Medication use during hospitalisation: a multicentre pre-post implementation study

Author

van Herpen-Meeuwissen, Loes J M, van den Bemt, Bart J F, Derijks, Hieronymus J, van den Bemt, Patricia M L A, de Vries, Frank, Maat, Barbara, van Onzenoort, Hein A W, van Herpen-Meeuwissen, Loes J M, van den Bemt, Bart J F, Derijks, Hieronymus J, van den Bemt, Patricia M L A, de Vries, Frank, Maat, Barbara, and van Onzenoort, Hein A W

Abstract

Background Medication is frequently thrown away after a patient's discharge from hospital, with undesirable economic and environmental consequences. Because of the rising costs of healthcare, interventions to reduce medication wastage (and associated costs) are warranted. Using Patient's Own Medication during hospitalisation might decrease medication wastage and associated costs. Objective To study the economic impact of patient's own medication use on medication waste and hospital staff's time spent during hospitalisation. Setting In seven Dutch hospitals, of which university, teaching, general, and specialised hospitals, eight different hospital wards, surgical and medical, were selected. Method In this prospective pre-post intervention study data on the economic value of medication waste and time spent by healthcare professionals were collected for a 2 months period each. The economic value of medication waste was defined as the value (€) of wasted medication per 100 patient days. For each ward, time spent on medication process activities was measured 10 times per staff member. The average time spent (in hours) on medication process steps (multiple activities) per staff member per 100 patients and associated salary costs were calculated for both periods. Main outcome measure The primary outcome of the study was the total economic value (€) of wasted medication per 100 patient days. Results Implementation of Patient's Own Medication decreased the economic value of wasted medication by 39.5% from €3983 to €2411 per 100 patient days. The mean time spent on the total medication process was reduced with 5.2 h per 100 patients (from 112.7 to 104.4 h per 100 patients). We observed a shift in professional activities, as physicians and nurses spent less time on the medication process, whereas pharmacy technicians had a greater role in it. When time spent was expressed as salary; €1219 could be saved per 100 patients. Conclusions This study showed that 'Patient's Own Me

Published
2019

46. Economic impact of Patient's Own Medication use during hospitalisation: a multicentre pre-post implementation study

Author

Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, van Herpen-Meeuwissen, Loes J M, van den Bemt, Bart J F, Derijks, Hieronymus J, van den Bemt, Patricia M L A, de Vries, Frank, Maat, Barbara, van Onzenoort, Hein A W, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, van Herpen-Meeuwissen, Loes J M, van den Bemt, Bart J F, Derijks, Hieronymus J, van den Bemt, Patricia M L A, de Vries, Frank, Maat, Barbara, and van Onzenoort, Hein A W

Published
2019

47. Efficiency of computerized clinical decision support systems involving anticoagulants: A flashmob study in Dutch hospital pharmacies.

Author

Graafsma, Jetske, Garde, Ewoudt M. W., Derijks, Hieronymus J., Hoge, Rien H. L., Klopotowska, Joanna E., Karapinar‐Carkit, Fatma, and Bemt, Patricia M. L. A.

Subjects
*CLINICAL decision support systems, *LOW-molecular-weight heparin, *DECISION support systems, *ORAL medication, *ELECTRONIC health records, *DRUGSTORES
Abstract

Aims Methods Results Conclusion Computerized decision support systems (CDSSs) aim to prevent adverse drug events. However, these systems generate an overload of alerts that are not always clinically relevant. Anticoagulants are frequently involved in these alerts. The aim of this study was to investigate the efficiency of CDSS alerts on anticoagulants in Dutch hospital pharmacies.A multicentre, single‐day, cross‐sectional study was conducted using a flashmob design in Dutch hospital pharmacies, which have CDSSs that operate on both a national medication surveillance database and on self‐developed clinical rules. Hospital pharmacists and pharmacy technicians collected data on the number and type of alerts and time needed for assessing these alerts. The primary outcome was the CDSS efficiency on anticoagulants, defined as the percentage of alerts on anticoagulants that led to an intervention. Secondary outcomes where among other CDSSs efficiency related to any medications and the time expenditure. Descriptive data‐analysis was used.Of the 69 hospital pharmacies invited, 42 (61%) participated. The efficiency of CDSS alerts on anticoagulants was 4.0% (interquartile range [IQR] 14.0%) for the national medication surveillance database alerts and 14.3% (IQR 40.0%) for alerts from clinical rules. For any medication, the efficiency was lower: 1.8% (IQR 7.5%) and 13.4% (IQR 21.5%) respectively. The median time for assessing the relevance of all alerts was 2 (IQR 1:21) h/day for pharmacists and 6 (IQR 5:01) h/day for pharmacy technicians.CDSS efficiency is generally low, both for anticoagulants and any medication, while the time investment is high. Optimization of CDSSs is needed. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Inhibition of CYP2D6 with low dose (5 mg) paroxetine in patients with high 10‐hydroxynortriptyline serum levels‐A prospective pharmacokinetic study.

Author

Jessurun, Naomi T., Vermeulen Windsant, Annemieke, Mikes, Oenone, Puijenbroek, Eugène P., Marum, Rob J., Grootens, Koen, and Derijks, Hieronymus J.

Subjects
PAROXETINE, LONGITUDINAL method, ENZYME inhibitors
Abstract

The antidepressant nortriptyline is metabolized by cytochrome P450 2D6 (CYP2D6) to the less active and more cardiotoxic drug metabolite, 10‐hydroxynortriptyline. High serum levels of this metabolite (>200 μg/L) may lead to withdrawal of nortriptyline therapy. Adding CYP2D6 inhibitors reduce the metabolic activity of CYP2D6 (phenoconversion) and so decrease the forming of hydroxynortriptyline. In this study, 5 mg paroxetine is administered to patients with high hydroxynortriptyline concentrations (>200 μg/L). The shift in number of patients to therapeutic nortriptyline (50–150 μg/L) and safe hydroxynortriptyline (<200 μg/L) concentrations, and the degree of phenoconversion, expressed as the change in ratio nortriptyline/hydroxynortriptyline concentrations before and after paroxetine addition, are prospectively observed and described. After paroxetine addition, 12 patients (80%) had therapeutic nortriptyline and safe hydroxynortriptyline concentrations. Hydroxynortriptyline concentrations decreased in all patients. The average nortriptyline/hydroxynortriptyline concentrations ratio increased from 0.32 to 0.59. This study shows that 5 mg paroxetine addition is able to lower high hydroxynortriptyline serum levels to safe ranges. [ABSTRACT FROM AUTHOR]

Published
2021
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49. Association Between Urinary Tract Infections and Antipsychotic Drug Use in Older Adults

Author

van Strien, Astrid M, Souverein, Patrick C, Keijsers, Carolina J P W, Heerdink, Eibert R, Derijks, Hieronymus J, van Marum, Rob J, van Strien, Astrid M, Souverein, Patrick C, Keijsers, Carolina J P W, Heerdink, Eibert R, Derijks, Hieronymus J, and van Marum, Rob J

Abstract

Antipsychotic drugs are frequently prescribed to older adults, but they may be associated with serious adverse effects. The objective was to investigate the association between use of antipsychotics in older adults and the risk of urinary tract infections (UTIs).This study was designed as a cohort study.Data were obtained from the Clinical Practice Research Datalink from January 1, 2000, to September 29, 2016.Primary care patients 65 years or older in the United Kingdom with a first prescription for an oral antipsychotic were included in the study.Incidence of UTIs was calculated for periods with and without exposure to antipsychotic drugs in one cohort. Cox proportional hazard regression analysis with Andersen-Gill extension for recurrent events was used to calculate hazard ratios (HRs) with 95% confidence interval (CI).During the study period, 191,827 individuals with a first prescription for an oral antipsychotic drug were identified. Current use of antipsychotics was associated with an increased risk of UTI compared with past use (adjusted HR, 1.31; 95% CI, 1.28-1.34). This effect was strongest in the first 14 days of use (adjusted HR, 1.83; 95% CI, 1.73-1.95) and in individuals who used more than one antipsychotic drug concomitantly (adjusted HR, 1.64; 95% CI, 1.45-1.87). The risk was slightly higher for typical antipsychotics than for atypical antipsychotics. Stratification by sex showed that risk estimates were slightly higher in men than in women.Use of antipsychotics was associated with an increased risk of UTIs in both men and women, particularly in the first weeks after the start of treatment.

Published
2018

50. Association Between Urinary Tract Infections and Antipsychotic Drug Use in Older Adults

Author

Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, van Strien, Astrid M, Souverein, Patrick C, Keijsers, Carolina J P W, Heerdink, Eibert R, Derijks, Hieronymus J, van Marum, Rob J, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology, van Strien, Astrid M, Souverein, Patrick C, Keijsers, Carolina J P W, Heerdink, Eibert R, Derijks, Hieronymus J, and van Marum, Rob J

Published
2018

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