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Bas JW van de Steeg,1 Anne C Esselink,2 Hugo AJM de Wit,1 Cornelis Kramers,1 Bart JF van den Bemt3 1Department of Clinical Pharmacy, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands; 2Department of Internal Medicine, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands; 3Department of Pharmacy, Sint Maartenskliniek, Nijmegen, the NetherlandsCorrespondence: Bas JW van de Steeg, Department of Clinical Pharmacy A16, Canisius Wilhelmina Hospital, Nijmegen, 6532 SZ, the Netherlands, Email b.vandesteeg@cwz.nlPurpose: Arterial and venous thromboembolism are a leading cause of mortality. Direct oral anticoagulants (DOACs) are highly effective in both stroke prevention and prevention of venous thrombotic events. Medication adherence is a prerequisite for optimal protection against thromboembolic complications. Recent studies have shown that good adherence cannot be taken for granted by DOACs. In this cross-sectional study adherence among DOAC users was investigated and associations between beliefs about medication, perceived side effects and adherence were explored.Patients and Methods: We included 100 randomly selected adult DOAC users visiting one of the two participating Dutch community pharmacies in the summer of 2020. The self-reported adherence (primary outcome) was assessed with the Medication Adherence Rating Scale-5 (MARS-5) using three different cut-off scores. Beliefs about DOACs were assessed with the Beliefs about Medicine Questionnaire Specific (BMQ-S), while side effects and side effect burden were assessed with a self-developed questionnaire based on the Lareb Intensive Monitoring (LIM) system.Results: Of the participants, 9% reported non-adherence on the primary MARS-5 cut-off score < 24. For the MARS-5 scores < 23 and < 25 non-adherence percentages of, respectively, 3 and 33% were calculated. Associations were found between adherence and both side effects and side effect burden, regardless of the MARS-5 cut-off score. Bruising and minor bleeds were the most reported side effects (both 20%). For all patients, the necessity beliefs outweighed the concern beliefs. No associations were found between adherence and either gender, indication, DOAC or dosage.Conclusion: This study confirms that adherence in patients on DOACs cannot be taken for granted. High necessity beliefs do not guarantee good adherence, as side effects impair adherence even in patients having high necessity beliefs. Therefore, we recommend that both physicians and pharmacists evaluate both adherence and side effects with these patients on a regular base.Plain Language Summary: The issueThrombosis affects many people. Complications like stroke and lung embolism are a major cause of health damage, disability and even death. Direct oral anticoagulants (DOACs) are highly effective drugs at preventing these complications. However, patients need to take their medication properly to get the best protection. Recent studies showed that not all patients consistently take their DOACs.What’s new?In this study, we discovered that patients experiencing bothersome side effect were less likely to stick to their medication schedule. The most common side effects reported were bruising and minor bleeding, by 20% each. There were no differences in how well patients took their medication based on gender, medical condition, type of DOAC or prescribed dosage. Most patients believed their medication was necessary for their health.Why is this important?This study shows that side effects hinder patients taking their medication correctly even when they believe their medication is necessary for their health. This means that patients on DOAC therapy who experience side effects may be less protected against stroke and lung embolism. Therefore, we recommend that doctors and pharmacists regularly check in with patients about any side effects they experience and how consistently they take their DOACs.What’s next?This study highlights the importance of developing, testing, and implementing practical tools to find and help patients who do not take their DOACs correctly, to ensure they are better protected against blood clots.Keywords: DOACs, compliance, MARS-5, beliefs, BMQ-S

Rob Janssen,1 Emiel FM Wouters,2 Wim Janssens,3 Willeke F Daamen,4 Paul Hagedoorn,5 Hugo AJM de Wit,6 Jef Serré,3 Ghislaine Gayan-Ramirez,3 Frits ME Franssen,2 Niki L Reynaert,2 Jan H von der Thüsen,7 Henderik W Frijlink5 1Department of Pulmonary Medicine, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands; 2Department of Respiratory Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands; 3Laboratory of Respiratory Diseases, Department of Chronic Diseases, Metabolism and Ageing (CHROMETA), KU Leuven, Leuven, Belgium; 4Department of Biochemistry, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; 5Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, Groningen, University of Groningen, Groningen, The Netherlands; 6Department of Clinical Pharmacy, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands; 7Department of Pathology, Erasmus Medical Center, Rotterdam, The NetherlandsCorrespondence: Rob JanssenDepartment of Pulmonary Medicine, Canisius-Wilhelmina Hospital, Weg Door Jonkerbos 100, Nijmegen, SZ 6532, The NetherlandsEmail rob.janssen@cwz.nlAbstract: Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration.Keywords: collagen, copper, desmosine, elastin, emphysema, fibulin-5, heparin, lysyl oxidase, lysyl oxidase-like protein 1, tropoelastin

Carlota Mestres Gonzalvo,1 Kim PGM Hurkens,2 Hugo AJM de Wit,3 Brigit PC van Oijen,1 Rob Janknegt,1 Jos MGA Schols,4 Wubbo J Mulder,5 Frans R Verhey,6 Bjorn Winkens,7 Paul-Hugo M van der Kuy1 1Department of Clinical Pharmacology and Toxicology, Orbis Medical Centre, Sittard, 2Department of Internal Medicine, Section of Geriatric Medicine, Academic Medical Centre, Amsterdam, 3Department of Clinical Pharmacy and Toxicology, Atrium Medical Centre, Heerlen, 4Department of Family Medicine and Department of Health Services Research, School for Public Health and Primary Care, Maastricht University, 5Department of Internal Medicine, Maastricht University Medical Centre, 6Department of Psychiatry and Neuropsychology, Alzheimer Centre Limburg/School for Mental Health and Neurosciences, 7Department of Methodology and Statistics, School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands Background: The aim of this study was to evaluate to what extent laboratory data, actual medication, medical history, and/or drug indication influence the quality of medication reviews for nursing home patients. Methods: Forty-six health care professionals from different fields were requested to perform medication reviews for three different cases. Per case, the amount of information provided varied in three subsequent stages: stage 1, medication list only; stage 2, adding laboratory data and reason for hospital admission; and stage 3, adding medical history/drug indication. Following a slightly modified Delphi method, a multidisciplinary team performed the medication review for each case and stage. The results of these medication reviews were used as reference reviews (gold standard). The remarks from the participants were scored, according to their potential clinical impact, from relevant to harmful on a scale of 3 to -1. A total score per case and stage was calculated and expressed as a percentage of the total score from the expert panel for the same case and stage. Results: The overall mean percentage over all cases, stages, and groups was 37.0% when compared with the reference reviews. For one of the cases, the average score decreased significantly from 40.0% in stage 1, to 30.9% in stage 2, and 27.9% in stage 3; no significant differences between stages was found for the other cases. Conclusion: The low performance, against the gold standard, of medication reviews found in the present study highlights that information is incorrectly used or wrongly interpreted, irrespective of the available information. Performing medication reviews without using the available information in an optimal way can have potential implications for patient safety. Keywords: polypharmacy, medication therapy management, decision support systems management, aged, medication review

In this Clinical Lesson, using two illustrating cases, we explain how to do the initial assessment and treatment of an intoxicated patient. An approach aimed at toxidromes can serve as a stepping stone. A toxidrome is a combination of symptoms and clinical features that can occur with the use of certain drugs and substances. The most commonly encountered toxidromes are sympathomimetic, serotonergic, anticholinergic, cholinergic, sedative-hypnotic and opioid. All patients need to be approach according to the ABCDE method. The treatment is based on pharmacokinetics by means of the ADME principle (absorption, distribution, metabolism and excretion) and based on pharmacodynamics, aimed at the toxidrome.

Background: It is estimated that one-third of delirium cases in hospitals could be prevented with appropriate interventions. In Dutch hospitals a manual instrument (VMS-questions) is used to identify patients at-risk for delirium. Delirium Model (DEMO) is an automated model which could support delirium prevention more efficiently. However, it has not been validated beyond the hospital it was developed in., Aim: To externally validate the DEMO and compare its performance to the VMS-questions., Method: A retrospective cohort study between July and December 2018 was conducted. Delirium cases were identified through a chart review, and the VMS-questions were extracted from the electronic health records. The DEMO was validated in patients ≥ 60 years, and a comparison with the VMS-questions was made in patients ≥ 70 years., Results: In total 1,345 admissions were included. The DEMO predicted 59 out of 75 delirium cases (sensitivity 0.79, 95% CI = 0.68-0.87; specificity 0.75, 95% CI = 0.72-0.77). Compared to the VMS-questions, the DEMO showed a lower specificity (0.64 vs. 0.72; p < 0.001) and a comparable sensitivity (0.83 vs. 0.80; p = 0.56). The VMS-questions were missing in 20% of admissions, in which the DEMO correctly predicted 10 of 12 delirium cases., Conclusion: The DEMO showed acceptable performance for delirium prediction. Overall the DEMO predicted more delirium cases because the VMS-questions were missing in 20% of admissions. This study shows that automated instruments such as DEMO could play a key role in the efficient and timely deployment of measures to prevent delirium., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Iron deficiency anaemia is a common problem. The majority of patients are treated with oral iron supplements. The current recommended dosage for oral supplementation of 200 mg ferrous fumarate 3x per day however, is based on a single small study of poor quality. There is no consensus concerning parenteral dosing. In recent years, new insights have been gained regarding both the dosage of oral supplementation and the indication for parenteral supplementation. Oral therapy is preferred. In principle, 100 mg ferrous fumarate once a day is sufficient for the treatment of symptom-free patients with anaemia. In cases of severe anaemia, or in patients with symptoms, 200 mg/day should be prescribed. If side effects appear, it can be dosed every other day. Where oral therapy does not show effectiveness, the anaemia is severe, or rapid increase of haemoglobin is indicated, parenteral supplementation should be chosen. Parenteral supplementation is more effective than oral supplementation in specific conditions, such as dialysis-dependent renal insufficiency, heart failure or active IBD.

Purpose: The chronic use of benzodiazepines and benzodiazepine-related drugs (BZ/Z) in older people is common and not without risks. The objective of this study was to evaluate whether the implementation of a clinical rule promotes the discontinuation of chronically used BZ/Z for insomnia., Methods: A clinical rule, generating an alert in case of chronic BZ/Z use, was created and applied to the nursing home (NH) setting. The clinical rule was a one-off intervention, and alerts did not occur over time. Reports of the generated alerts were digitally sent to NH physicians with the advice to phase out and eventually stop the BZ/Z. In cases where the advice was adopted, a follow-up period of 4 months on the use of BZ/Z was taken into account in order to determine whether the clinical rule alert led to a successful discontinuation of BZ/Z., Results: In all, 808 NH patients were screened. In 161 (19.1%) of the patients, BZ/Z use resulted in a clinical rule alert. From these, the advice to phase out and stop the BZ/Z was adopted for 27 patients (16.8%). Reasons for not following the advice consisted of an unsuccessful attempt in the past (38 patients), patients family and/or patient resistance (37 patients), the non-continuous use of BZ/Z (32 patients) and indication still present (27 patients). Of the 12 NH physicians, seven adopted the advice., Conclusions: The success rate of a clinical rule for discontinuation of chronically used BZ/Z for insomnia was low, as reported in the present study. Actions should be taken to help caregivers, patients and family members understand the importance of limiting BZ/Z use to achieve higher discontinuation rates.

Objectives: Delirium is an underdiagnosed, severe and costly disorder, and 30%-40% of cases can be prevented. A fully automated model to predict delirium (DEMO) in older people has been developed, and the objective of this study is to validate the model in a hospital setting., Setting: Secondary care, one hospital with two locations., Design: Observational study., Participants: The study included 450 randomly selected patients over 60 years of age admitted to Zuyderland Medical Centre. Patients who presented with delirium on admission were excluded., Primary Outcome Measures: Development of delirium through chart review., Results: A total of 383 patients were included in this study. The analysis was performed for delirium within 1, 3 and 5 days after a DEMO score was obtained. Sensitivity was 87.1% (95% CI 0.756 to 0.939), 84.2% (95% CI 0.732 to 0.915) and 82.7% (95% CI 0.734 to 0.893) for 1, 3 and 5 days, respectively, after obtaining the DEMO score. Specificity was 77.9% (95% CI 0.729 to 0.882), 81.5% (95% CI 0.766 to 0.856) and 84.5% (95% CI 0.797 to 0.884) for 1, 3 and 5 days, respectively, after obtaining the DEMO score., Conclusion: DEMO is a satisfactory prediction model but needs further prospective validation with in-person delirium confirmation. In the future, DEMO will be applied in clinical practice so that physicians will be aware of when a patient is at an increased risk of developing delirium, which will facilitate earlier recognition and diagnosis, and thus will allow the implementation of prevention measures., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)