Appropriate medication use in Dutch terminal care: study protocol of a multicentre stepped-wedge cluster randomized controlled trial (the AMUSE study).

BACKGROUND: Polypharmacy is common among patients with a limited life expectancy, even shortly before death. This is partly inevitable, because these patients often have multiple symptoms which need to be alleviated. However, the use of potentially inappropriate medications (PIMs) in these patients is also common. Although patients and relatives are often willing to deprescribe medication, physicians are sometimes reluctant due to the lack of evidence on appropriate medication management for patients in the last phase of life. The aim of the AMUSE study is to investigate whether the use of CDSS-OPTIMED, a software program that gives weekly personalized medication recommendations to attending physicians of patients with a limited life expectancy, improves patients' quality of life. METHODS: A multicentre stepped-wedge cluster randomized controlled trial will be conducted among patients with a life expectancy of three months or less. The stepped-wedge cluster design, where the clusters are the different study sites, involves sequential crossover of clusters from control to intervention until all clusters are exposed. In total, seven sites (4 hospitals, 2 general practices and 1 hospice from the Netherlands) will participate in this study. During the control period, patients will receive 'care as usual'. During the intervention period, CDSS-OPTIMED will be activated. CDSS-OPTIMED is a validated software program that analyses the use of medication based on a specific set of clinical rules for patients with a limited life expectancy. The software program will provide the attending physicians with weekly personalized medication recommendations. The primary outcome of this study is patients' quality of life two weeks after baseline assessment as measured by the EORTC QLQ-C15-PAL questionnaire, quality of life question. DISCUSSION: This will be the first study investigating the effect of weekly personalized medication recommendations to attending physicians on the quality of life of patients with a limited life expectancy. We hypothesize that the CDSS-OPTIMED intervention could lead to improved quality of life in patients with a life expectancy of three months or less. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (NCT05351281, Registration Date: April 11, 2022).

Evaluation of a multifaceted medication review in older patients in the outpatient setting: a before-and-after study.

BACKGROUND: The prevalence of medication-related emergency department visits and acute hospital admissions in older patients is rising due to the ageing of the population and increasing prevalence of multimorbidity and associated polypharmacy. AIM: To explore whether a combined medication review performed in the outpatient setting reduces the number of medication-related emergency department visits and hospital (re)admissions. METHOD: All consecutive patients visiting the geriatric outpatient clinic underwent a multifaceted medication review (i.e. evaluation by at least a geriatrician, and/or pharmacist and use of clinical decision support system). Subsequently, we analysed the number of, and reason for, emergency department visits, acute hospital admissions and readmissions in the year prior to and the year following the index-date (date of first presentation and medication review). RESULTS: A multifaceted medication review reduced the number of potentially medication-related emergency department visits (38.9% vs. 19.6%, p < 0.01), although the total number of ED visits or acute hospital admissions per patient in the year before and after medication review did not differ. CONCLUSION: A multifaceted medication review performed in the outpatient clinic reduced the number of potentially medication-related emergency department visits and could therefore reduce negative health outcomes and healthcare costs.

Does formative assessment help students to acquire prescribing skills?

PURPOSE: Formative assessments can help motivate students and ease students' learning through feedback. There is a pressing need for improvement of clinical pharmacotherapy (CPT) education since junior doctors make many prescribing errors. The aim of this study was to determine whether a formative assessment with personalized narrative feedback helps medical students to increase their prescribing skills. METHODS: This retrospective cohort study was conducted among masters' medical students at Erasmus Medical Centre, The Netherlands. Students made a formative and a summative skill-based prescription assessment, both during clerkships as part of their regular curriculum. Errors in both assessments were categorized by type and possible consequence and compared with each other. RESULTS: A total of 388 students made 1964 errors in the formative assessment and 1016 in the summative assessment. Most improvements after the formative assessment were seen for mentioning the weight of a child on the prescription (n = 242, 19%). Most new and repeated errors in the summative assessment were missing usage instructions (n = 82, 16% and n = 121, 41%). CONCLUSIONS: This formative assessment with personalized and individual narrative feedback has helped students to increase the technical correctness of their prescriptions. However, errors repeated after the feedback were predominantly errors showing that only one formative assessment has not yet enhanced the clinical prescribing enough.

Additional value of a triggerlist as selection criterion in identifying patients at high risk of medication-related hospital admission: a retrospective cohort study.

BACKGROUND: Of all hospital admissions in older patients, 10-30% seem to be medication-related. However, medication-related admissions are often unidentified in clinical practice. To increase the identification of medication-related hospital admissions in older patients a triggerlist is published in the Dutch guideline for polypharmacy. AIM: To assess whether the triggerlist has value as selection criterion to identify patients at high risk of medication-related hospital admissions. METHOD: This retrospective cohort study was carried out in 100 older (≥ 60 years) patients with polypharmacy and having two triggers from the triggerlist. The admissions were assessed as either possibly or unlikely medication-related according to the Assessment Tool for identifying Hospital Admissions Related to Medications. RESULTS: Of all the admissions 48% were classified as possibly medication-related. Patients with a possible medication-related hospital admission were more likely to have an impaired renal function (p = 0.015), but no differences with regard to age, sex, comorbidity or number of medicines were found. CONCLUSION: The high prevalence of medication-related hospital admissions, suggests the triggerlist may have added value as selection criterion in a cohort of older patients with polypharmacy and can be used to improve the identification of a population at high risk of medication-related hospital admissions.

[Adjusting medication at the end of life: towards optimalisation of healthcare in the final fase of life]. / Medicatie aanpassen aan het einde van het leven.

Patients with a limited life expectancy use many medications. Especially medications with a focus on the prevention and treatment of illnesses may be inappropriate in this last phase of life. We present the cases of three patients in which we highlight that such medication reconsideration 1) is quite often done shortly before death, 2) is not without potential disadvantages, and 3) should be accompanied with a patient centered and positive communication style. We argue that the use of medications should be reconsidered in a timely phase, ideally as part of advance care planning.

Medication-related hospital admissions and readmissions in older patients: an overview of literature.

Background The number of medication related hospital admissions and readmissions are increasing over the years due to the ageing population. Medication related hospital admissions and readmissions lead to decreased quality of life and high healthcare costs. Aim of the review To assess what is currently known about medication related hospital admissions, medication related hospital readmissions, their risk factors, and possible interventions which reduce medication related hospital readmissions. Method We searched PubMed for articles about the topic medication related hospital admissions and readmissions. Overall 54 studies were selected for the overview of literature. Results Between the different selected studies there was much heterogeneity in definitions for medication related admission and readmissions, in study population and the way studies were performed. Multiple risk factors are found in the studies for example: polypharmacy, comorbidities, therapy non adherence, cognitive impairment, depending living situation, high risk medications and higher age. Different interventions are studied to reduce the number of medication related readmission, some of these interventions may reduce the readmissions like the participation of a pharmacist, education programmes and transition-of-care interventions and the use of digital assistance in the form of Clinical Decision Support Systems. However the methods and the results of these interventions show heterogeneity in the different researches. Conclusion There is much heterogeneity in incidence and definitions for both medication related hospital admissions and readmissions. Some risk factors are known for medication related admissions and readmissions such as polypharmacy, older age and additional diseases. Known interventions that could possibly lead to a decrease in medication related hospital readmissions are spare being the involvement of a pharmacist, education programs and transition-care interventions the most mentioned ones although controversial results have been reported. More research is needed to gather more information on this topic.

Medication in older patients reviewed multiple ways (MORE) study.

Background Polypharmacy in older patients can lead to potentially inappropriate prescribing. The risk of the latter calls for effective medication review to ensure proper medication usage and safety. Objective Provide insight on the similarities and differences of medication review done in multiple ways that may lead to future possibilities to optimize medication review. Setting This study was conducted in Zuyderland Medical Centre, the second largest teaching hospital in the Netherlands. Method This descriptive study compares the quantity and content of remarks identified by medication review performed by a geriatrician, outpatient pharmacist, and Clinical Decision Support System. The content of remarks is categorized in seven categories of possible pharmacotherapeutic problems: 'indication without medication', 'medication without indication', 'contra-indication/interaction/side-effect', 'dosage problem', 'double medication', 'incorrect medication' and 'therapeutic drug monitoring'. Main outcome measure Number and content of remarks on medication review. Results The Clinical Decision Support System (1.8 ± 0.8 vs. 0.9 ± 0.9, p < 0.001) and outpatient pharmacist (1.8 ± 0.8 vs. 0.9 ± 0.9, p = 0.045) both noted remarks in significantly more categories than the geriatricians. The Clinical Decision Support System provided more remarks on 'double medication', 'dosage problem' and 'contraindication/interaction/side effects' than the geriatrician (p < 0.050), while the geriatrician did on 'medication without indication' (p < 0.001). The Clinical Decision Support System noted significantly more remarks on 'contraindication/interaction/side effects' and 'therapeutic drug monitoring' than the outpatient pharmacist, whereas the outpatient pharmacist reported more on 'indication without medication' and 'medication without indication' than the Clinical Decision Support System (p ≤ 0.007). Conclusion Medication review performed by a geriatrician, outpatient pharmacist, and Clinical Decision Support System provides different insights and should be combined to create a more comprehensive report on medication profiles.

The nocebo effect challenges the non-medical infliximab switch in practice.

BACKGROUND: In clinical practice, non-medical switching of biological medication may provoke nocebo effects due to unexplained deterioration of therapeutic benefits. Indication extrapolation, idiosyncratic reactions, and interchangeability remain challenged in clinical practice after biosimilar approval by the European Medicines Agency. The principle of "first do no harm" may be challenged in a patient when switching from originator to biosimilar biological. AIM: To describe the 1-year results of a pragmatic study on infliximab biosimilar implementation in immune-mediated inflammatory disease patients on the basis of shared decision-making under effectiveness and safety monitoring. METHODS: Inflammatory bowel disease and rheumatology patients on infliximab originator were converted to infliximab biosimilar after providing informed consent. Nocebo response patients were monitored after switch back to originator. Linear mixed models were used to analyze continuous endpoints on effectiveness and laboratory outcomes to determine significance (P ≤ 0.05) of change over time after switching. RESULTS: After inviting 146 patients, a group of 125 patients enrolled in the project over time, respectively, 73 Crohn's disease, 28 ulcerative colitis, nine rheumatoid arthritis, ten psoriatic arthritis, and five ankylosing spondylitis patients. No statistically significant changes in effectiveness and safety were observed in any of the indications after a median of 4 infusions in 9 months of study. An overall nocebo response of 12.8% was found among the patients during a minimal observation period of 6 months after the transition to biosimilar infliximab. The overall nocebo response rate did not differ between the studied indications. CONCLUSIONS: In inflammatory bowel disease and rheumatological patients, similar effectiveness and safety were demonstrated on the transition into infliximab biosimilar. In our series, patient empowerment and registration of treatment outcomes delineated biosimilar transition, an approach that hypothetically could reduce nocebo response rates which are relevant to account for regarding biosimilar implementation.

The use of an electronic clinical rule to discontinue chronically used benzodiazepines and related Z drugs.

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.

Usually Available Clinical and Laboratory Data Are Insufficient for a Valid Medication Review: A Crossover Study.

OBJECTIVES: To establish the quality of medication reviews performed by nursing home physicians, general practitioners and pharmacists. DESIGN AND SETTING: 15 Pharmacists, 13 general practitioners and 18 nursing home physicians performed a medication review for three cases (A, B and C), at three evaluation moments. First, they received the medication list. Secondly, they also received laboratory results and reason for admission and finally, we added medical history. Remarks were divided into 6 categories, i.e. indication without medication, medication without indication, contraindications/ interactions, dosage problems, double medication and wrong medication. Remarks were compared to the remarks made by our expert panel and scored according to our grading model as appropriate (0 to +3) or missed or potentially harmful (-1). For each medication error category, the percentage of participants who made this error was computed. RESULTS: After the first evaluation moment, the overall estimated mean percentage score was -1.7% for case A, 3.9% for case B, and 8.7% for case C. After the second review, this score was 15.0% for case A, 19.8% for case B, and 22.2% for case C. This further increased to 30.0% for case A, 36.7% for case B and 44% for case C at the final evaluation. The absence of medication where there was an indication (indication without medication) was frequently missed and did not improve after adding the extra information regarding laboratory results, reason for admission and finally medical history. CONCLUSION: Increasing clinical information helps physicians and pharmacists to improve their medication reviews, however, additional information was still related with a high margin of error. Detection of certain errors becomes easier with additional information, whereas other errors remain undetected. To achieve a high standard of medication review, we have to change the way medication reviews should be performed.

Hydroxocobalamin, a nitric oxide scavenger, in the prophylaxis of migraine: an open, pilot study.

Drugs which directly counteract nitric oxide (NO), such as endothelial receptor blockers, NO-synthase inhibitors, and NO-scavengers, may be effective in the acute treatment of migraine, but are also likely to be effective in migraine prophylaxis. In the underlying pilot study the prophylactic effect of the NO scavenger hydroxocobalamin after intranasal administration in migraine was evaluated. Twenty patients, with a history of migraine of > 1 year and with two to eight migraine attacks per month, were included in an open trial. A baseline period was followed by an active treatment period of 3 months with 1 mg intranasal hydroxocobalamin daily. Patients were instructed to complete a diary in which details of each attack were described. A reduction in migraine attack frequency of >/ or = 50% was seen in 10 of 19 patients, which corresponds to 53% of the patients (responders). A reduction of > or = 30% was noted in 63% of the patients. The mean attack frequency in the total study population showed a reduction from 4.7 +/- 1.7 attacks per month to 2.7 +/- 1.6 (P < 0.001). For the responders the migraine attack frequency was reduced from 5.2 +/- 1.9 (baseline) to 1.9 +/- 1.3 attacks per month (P < 0.005), while for those who did not respond a non-significant reduction was found: 4.1 +/- 1.4 to 3.7 +/- 1.5 (P > 0.1). A reduction was also observed for the total duration of the migraine attacks per month, the total number of migraine days per month and the number of medication doses for acute treatment used per month. This is the first prospective, open study indicating that intranasal hydroxocobalamin may have a prophylactic effect in migraine. As a percentage of responders in prophylactic trials of > 35-40% is unlikely to be a placebo effect, a double-blind study is warranted.

A quantification of the placebo response in migraine prophylaxis.

To quantify the placebo response of prophylactic therapy in migraine, a meta-analysis of prophylactic, double-blind, placebo controlled migraine studies was performed. The total analysis included 22 studies testing 19 different products, including 2013 patients, of which 828 were treated with placebo. A reduction in migraine attacks of 50% or more (responders) was seen in 23.5%+/-8.0 (95% C.I. 18.3-28.8%) of the patients in the placebo groups and 45.5%+/-15.5 (95% C.I. 37.4-53.6%) in the active groups. A reduction in migraine attacks of 16.8%+/-12.7 (95% C.I. 10.9-22.6%) was observed in the placebo groups and 41.8%+/-11.7 (95% C.I. 36.9-46.6%) in the active groups. We propose that if the percentage of responders in an open-label prophylactic trial in migraine is above 35-40%, or if a reduction in migraine attack frequency is found of 40% or more, further studies are indicated to determine the prophylactic activity of the drug. In all studies included in this analysis, no placebo response was seen above these limits.