Identifying and quantifying potentially problematic prescribing cascades in clinical practice: A mixed-methods study.

BACKGROUND: A prescribing cascade occurs when medication causes an adverse drug reaction (ADR) that leads to the prescription of additional medication. Prescribing cascades can cause excess medication burden, which is of particular concern in older adults. This study aims to identify and quantify potentially problematic prescribing cascades relevant for clinical practice. METHODS: A mixed-methods study was conducted. First, prescribing cascades were identified through literature search. An expert panel (n = 16) of pharmacists and physicians assessed whether these prescribing cascades were potentially problematic. Next, a cohort study quantified potentially problematic prescribing cascades in adults using Dutch community pharmacy data for the period 2015-2020. Additionally, the influence of multiple medications potentially causing the same ADR was evaluated. Prescription sequence symmetry analysis was used to calculate adjusted sequence ratios (aSRs), adjusting for temporal prescribing trends. An aSR >1.0 indicates the occurrence of a prescribing cascade. In a subgroup analysis, aSRs were calculated for older adults. RESULTS: Seventy-six prescribing cascades were identified in literature and three were provided by experts. Of these, 66 (83.5%) were considered potentially problematic. A significant positive aSR for the medication sequence was found for 41 (62.1%) of these prescribing cascades. The highest aSR was found for amiodarone potentially causing hypothyroidism treated with thyroid hormones (4.63 [95% confidence interval 4.40-4.85]), based on 565 incident users. The biggest population (n = 34,645) was found for angiotensin converting enzyme-inhibitors potentially causing urinary tract infections treated with antibiotics. Regarding four potential ADRs, the aSRs were higher for people using multiple medications that cause the same ADR as compared to people using only one of those medications. Among older adults the aSRs remained significant for 37 prescribing cascades. CONCLUSION: An overview was generated of potentially problematic prescribing cascades relevant for clinical practice. These results can support healthcare providers to intervene and reduce medication burden for older adults.

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

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: CDSS efficiency is generally low, both for anticoagulants and any medication, while the time investment is high. Optimization of CDSSs is needed.

Medication adherence to CFTR modulators in patients with cystic fibrosis: a systematic review.

BACKGROUND: In the last decade, a fundamental shift in the treatment of cystic fibrosis (CF) took place due to the introduction of CF transmembrane conductance regulator (CFTR) modulators. Adequate medication adherence is a prerequisite for their effectiveness, but little is known about adherence to CFTR modulators. We aimed to assess the extent of medication adherence to CFTR modulators in patients with CF and assess which characteristics are associated with adherence. METHODS: A systematic review following PRISMA guidelines was performed. Studies needed to report adherence to CFTR modulators. Main outcomes were: 1) level of medication adherence and 2) associations of demographic and/or clinical characteristics with adherence. RESULTS: In total, 4082 articles were screened and 21 full-text papers were assessed for eligibility. Ultimately, seven studies were included. Most studies were retrospective and focused on adherence to ivacaftor or lumacaftor-ivacaftor with only one focusing on elexacaftor-tezacaftor-ivacaftor. The majority used pharmacy refill data with adherence determined with the proportion of days covered (PDC) or the medication possession ratio (MPR). One study additionally used electronic monitoring and patient self-reported adherence. Adherence was 0.62-0.99 based on pharmacy data (PDC or MPR), 61% via electronic monitoring and 100% via self-report. Age <18 years appeared to be associated with good adherence, as was a higher lung function. CONCLUSIONS: Despite the wide variety of adherence methods used, adherence to CFTR modulators is suboptimal, based on objective measures such as pharmacy refill data or electronic monitoring. CFTR modulator adherence measurement and definitions requires more standardisation with a preference for objective and granular methods.

Medication reviews by emergency department pharmacists in patients hospitalised for an adverse drug event: a cost study.

OBJECTIVE: To perform a cost study of pharmacist-led medication reviews in patients with an acute hospitalization for adverse drug events. METHOD: Emergency department pharmacists performed medication reviews in patients hospitalized after visiting the emergency department for an adverse drug event (ADE). Control patients were hospitalized after an emergency department visit not related to an ADE and received usual care. The costs of the intervention were labour costs of the junior emergency department pharmacist and the cost savings consisted of costs of medication that was stopped or reduced during six months after the intervention. Sensitivity analyses were performed to evaluate different scenarios. RESULTS: In the intervention group (n = 104) 113 medication changes led to stopping or reducing medication, accounting for averted costs of €22,850. In the control group (n = 112) 39 medication changes led to stopping or reducing medication, accounting for averted costs of €299. The mean labour costs of the intervention were €138 per patient, resulting in saved costs of €61 per patient per six months. Sensitivity analyses showed that if the intervention would be performed by a senior clinical pharmacist, there are no cost savings (€-21), if parts of the intervention would be executed by pharmacy technicians (e.g. administrative tasks), cost savings would be augmented to €87, if outliers in costs associated with medication reduction would be excluded, there are no cost savings (€-35) and if the costs of reduced medication were extrapolated to one year, cost savings would be €260. CONCLUSION: In this study, medication reviews by junior emergency department pharmacists in patients hospitalized after an emergency department visit for an ADE lead to a cost reduction over a six month period. TRIAL REGISTRATION: The main study is registered on the ISRCTN registry with trial ID ISRCTN12506329 on 06-03-2022.

Patient reported medication-related problems, adherence and waste of oral anticancer medication over time.

OBJECTIVES: Patients on oral anticancer therapy regularly experience medication-related problems (MRPs), potentially leading to non-adherence and medication waste. Most studies reporting these experiences have cross-sectional designs. The aim of our study was to explore patient reported MRPs, adherence and waste of oral anticancer medication over time. METHODS: A prospective longitudinal quantitative interview study with 4 months follow-up was performed among patients on oral anticancer medication (mainly tyrosine kinase inhibitors, (anti)hormonal therapy, pyrimidine antagonists) using a semi-structured questionnaire. Patients from two Dutch university medical centres were included from March to December 2022 after informed consent was given. Four interviews were performed with 1 month in between. All interviews were audiotaped, after which the data were entered into an electronic case report form. The primary outcome was the mean number of MRPs per patient per interview round. Secondary outcomes were the proportion of patients with at least one MRP, types of MRPs, perceived non-adherence, medication waste (both in general and specifically for anticancer medication), costs of anticancer medication waste, and factors associated with medication waste as mentioned by the patient. Descriptive statistics were used to analyse the data. RESULTS: Forty patients were included with a mean (SD) age of 64 (9) years; 43% were male. The mean number of MRPs per patient was 2.1 in the first interview and 1.2, 1.0 and 0.9 in the second, third and fourth interviews, respectively. Adverse drug reactions were the most frequently reported type of MRPs (30 (75%) patients in the first interview and 19 (65%) in the last interview). Unintentional non-adherence was regularly reported, especially in the first interview. Medication changes were frequent and associated medication waste was mentioned in all interviews. CONCLUSIONS: Many patients using oral anticancer treatment report MRPs and this number remains substantial over time.

Antithrombotic Questionnaire Tool for Evaluation of Combined Antithrombotic Therapy in Community Pharmacies.

OBJECTIVE: The objective of this paper is to assess the diagnostic value of an antithrombotic questionnaire tool compared with the hospital's medical record information tool. The hypothesis of this study was that the antithrombotic questionnaire tool could identify patients with potentially incorrect antithrombotic therapy. METHODS: This cross-sectional study was conducted in eight community pharmacies in the Netherlands. A standardized questionnaire was developed as antithrombotic questionnaire tool. The pharmacist assessed whether the antithrombotic therapy was correct or potentially incorrect based on answers given by patients and based on the medical record. The primary outcome of the study was the sensitivity and specificity of the antithrombotic questionnaire tool to identify patients with potentially incorrect antithrombotic therapy. RESULTS: For 95 patients, the pharmacist assessed that in 81 (85%) the antithrombotic therapy was correct and in 14 (15%) potentially incorrect. Based on the medical record, 86 patients (91%) were assessed as correct and 9 (9%) as potentially incorrect. The sensitivity of the tool was 100% and the specificity 94%. CONCLUSIONS: This study demonstrated that the antithrombotic questionnaire tool is a suitable tool to assess whether the patient's antithrombotic therapy is potentially incorrect. It can be applied to identify patients with potentially incorrect antithrombotic therapy.

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

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 tasks vary. CDSS alerts used are mainly basic in their logic.

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

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.

Smaller nadroparin dose reductions required for patients with renal impairment: A multicenter cohort study.

BACKGROUND: Guidelines advise 50 % and 25 % dose reduction of the therapeutic nadroparin dose (86 IU/kg) in patients with eGFR 15-29 and 30-60 ml/min respectively. For monitoring, peak anti-Xa levels are suggested. Data lack whether this results in therapeutic anti-Xa levels or in anti-Xa levels that are comparable to those of patients without renal impairment. AIMS: To determine dose ranges in patients with renal impairment that result in therapeutic anti-Xa levels and to determine the percentage of the 86 IU/kg dose that results in anti-Xa levels normally occurring in patients without renal impairment. METHODS: A retrospective cohort study was conducted in five hospitals. Patients ≥18 years of age, with an eGFR ≥ 15 ml/min were included. The first correctly sampled peak (i.e. 3-5 h after ≥ third administration, regardless of dose per patient) was included. Simulated prediction models were developed using multiple linear regression. RESULTS: 770 patients were included. eGFR and hospital affected the association between dose and anti-Xa level. The doses for peak anti-Xa levels of 0.75 IU/ml differed substantially between hospitals and ranged from 55 to 91, 65-359 and 68-168 IU/kg in eGFR 15-29, 30-60 and > 60 ml/min/1.73m2, respectively. In eGFR 15-29 and 30-60 ml/min/1.73m2, doses of 75 % and 91 % of 86 IU/kg respectively, were needed for anti-Xa levels normally occurring in patients with eGFR > 60 ml/min. CONCLUSION: We advise against anti-Xa based dose-adjustments as long as anti-Xa assays between laboratories are not harmonized and an anti-Xa target range is not validated. A better approach might be to target levels similar to eGFR > 60 ml/min/1.73m2, which are achieved by smaller dose reductions.

Documentation of the Patient Characteristics Morbid Obesity and Bariatric Surgery in the Hospital Information System and the Influence on the Number of Medication-Related Problems.

BACKGROUND: As a result of pharmacokinetic changes, individuals with morbid obesity and/or with bariatric surgery may require dose adjustments, additional monitoring or medication should be avoided. Clinical decision support (CDS) may provide automated alerts enabling correct prescribing but requires documentation of these patient characteristics in the Hospital Information System (HIS) to prevent medication-related problems (MRPs). OBJECTIVE: The primary objective is to determine the proportion of patients with documentation of the patient characteristics morbid obesity and bariatric surgery in the HIS. The secondary objective is to compare the proportion of patients with an MRP in the group with versus without documentation. Also, the type and severity of MRPs and the medication involved are determined. METHODS: A prospective cohort study was performed. Patients admitted to the hospital were identified as morbidly obese and/or with bariatric surgery. In the identified patients, the proportion of patients with documentation of the patient characteristics in the HIS was evaluated as primary outcome. Subsequently, patient records were reviewed for MRPs, which were categorized and associated medication was registered. For the primary objective, descriptive statistics was used. For the secondary outcome, the Fisher's exact test was used. RESULTS: In 43 (21.4%, 95% confidence interval [CI]: 15.7%-27.1%) of 201 included patient (113 morbid obesity, 70 bariatric surgery and 18 both), the patient characteristics were documented. An MRP occurred in 2.3% versus 13.9% (P = 0.032) of patients with and without documentation, respectively. The most common MRP was underdosing in morbid obesity, while in patients with bariatric surgery it was prescription of contra-indicated medication. CONCLUSION AND RELEVANCE: The proportion of patients with documentation of the patient characteristics bariatric surgery and/or morbid obesity in the HIS is low, which appears to be associated with more MRPs. To improve medication safety, it is important to document these patient characteristics.

Prescription Sequence Symmetry Analysis (PSSA) to assess prescribing cascades: a step-by-step guide.

Prescribing cascades occur when patients are prescribed medication to treat the adverse drug reaction of previously prescribed medication. Prescription sequence symmetry analysis (PSSA) can be used to assess the association between two medications in prescription or dispensing databases and thus the potential occurrence of prescribing cascades. In this article, a step-by-step guide is presented for conducting PSSA to assess prescribing cascades. We describe considerations for medication data collection and setting time periods for relevant parameters, including washout window, exposure window, continued exposure interval and blackout period. With two examples, we illustrate the impact of changes in these parameters on the strengths of associations observed. Given the impact seen, we recommend that researchers clearly specify and explain all considerations regarding medication included and time windows set when studying prescribing cascades with PSSA, and conduct subgroup and sensitivity analyses.

A quality improvement study on the effect of electronic transmission of a basic discharge medication report on medication discrepancies in patients discharged from the hospital.

BACKGROUND: Medication discrepancies can occur in transitions of care because of a lack of communication between hospitals and community pharmacies. These discrepancies can lead to preventable adverse drug events (ADEs). AIM: To investigate the effect of electronic transmission of the basic discharge medication report on unintentional medication discrepancies observed between this report and the 28-day post-discharge status in the community pharmacy. METHOD: The study took place in a Dutch teaching hospital and 8 community pharmacies. A quality improvement study with a nonrandomized, historically controlled intervention design was performed. The intervention consisted of the electronic transmission of a basic discharge medication report to the community pharmacies. Unintentional medication discrepancies were identified by comparing the basic discharge medication report to the 28-day post-discharge medication record in community pharmacies. The main outcome measure was the proportion of drugs with one or more unintentional discrepancies compared between the historical control group and intervention group, using the chi-square test. Secondary outcome measure was the proportion of patients with one or more unintentional discrepancies. RESULTS: The participants used a total of 1078 drugs in the control group and 862 in the intervention group. The intervention significantly reduced the proportion of drugs with an unintentional discrepancy from 230 out of 1078 in the control group (21.3%) to 149 out of 862 drugs in the intervention group (17.3%; p = 0.025). At patient level, a non-significant increase was seen (62.4-78.8%; p = 0.41). CONCLUSION: The electronic transmission of the basic discharge medication report reduced the proportion of drugs with an unintentional discrepancy after discharge, but not the proportion of patients.

Prescribing Cascades with Recommendations to Prevent or Reverse Them: A Systematic Review.

BACKGROUND: To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent. OBJECTIVE: This systematic review aims to provide an overview of prescribing cascades, including dose-dependency information and recommendations that healthcare providers can use to prevent or reverse them. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Relevant literature was identified through searches in OVID MEDLINE, OVID Embase, OVID CINAHL, and Cochrane. Additionally, Web of Science and Scopus were consulted to analyze reference lists and citations. Publications in English were included if they analyzed the occurrence of prescribing cascades. Prescribing cascades were included if at least one study demonstrated a significant association and were excluded when the adverse drug reaction could not be confirmed in the Summary of Product Characteristics. Two reviewers independently extracted and grouped similar prescribing cascades. Descriptive summaries were provided regarding dose-dependency analyses and recommendations to prevent or reverse these prescribing cascades. RESULTS: A total of 95 publications were included, resulting in 115 prescribing cascades with confirmed adverse drug reactions for which at least one significant association was found. For 52 of these prescribing cascades, information regarding dose dependency or recommendations to prevent or reverse prescribing cascades was found. Dose dependency was analyzed and confirmed for 12 prescribing cascades. For example, antipsychotics that may cause extrapyramidal syndrome followed by anti-parkinson drugs. Recommendations focused on dosage lowering, discontinuing medication, and medication switching. Explicit recommendations regarding alternative options were given for three prescribing cascades. One example was switching to ondansetron or granisetron when extrapyramidal syndrome is experienced using metoclopramide. CONCLUSIONS: In total, 115 prescribing cascades were identified and an overview of 52 of them was generated for which recommendations to prevent or reverse them were provided. Nonetheless, information regarding alternative options for managing prescribing cascades was scarce.

Implementation of a Patient Questionnaire in Community Pharmacies to Improve Care for Patients Using Combined Antithrombotic Therapy: A Qualitative Study.

For several indications or combinations of indications the use of more than one antithrombotic agent is required. The duration of combined antithrombotic therapy depends on indication and patient characteristics. This study investigated the use of an antithrombotic questionnaire tool that had been developed for pharmacists to detect patients with possible incorrect combined antithrombotic therapy. The objective of this study was to identify potential barriers and facilitators that could influence the implementation of the developed antithrombotic questionnaire tool in daily community pharmacy practice. A qualitative study was conducted at 10 Dutch community pharmacies in which the antithrombotic questionnaire tool had been used with 82 patients. Semi-structured interviews were conducted with pharmacy staff who used the antithrombotic questionnaire tool. The interview questions to identify barriers and facilitators were based on the Consolidated Framework for Implementation Research. The interview data were analysed using a deductive thematic analysis. Ten staff members from nine different pharmacies were interviewed. Facilitators for implementation were that the questionnaire was easily adaptable and easy to use, as well as the relative short duration to administer the questionnaire. A possible barrier for using the questionnaire was a lower priority for using the questionnaire at moments when the workload was high. The pharmacists estimated that the questionnaire could be used for 70-80% of the patient population and they thought that it was a useful addition to regular medication surveillance. The antithrombotic questionnaire tool can be easily implemented in pharmacy practice. To implement the tool, the focus should be on integrating its use into daily activities. Pharmacists can use this tool in addition to regular medication surveillance to improve medication safety in patients who use combined antithrombotic therapy.

Adherence to coprescribing of laxatives with opioids and associated characteristics in general practices in the Netherlands.

BACKGROUND: Guidelines recommend to prescribe a laxative with an opioid to prevent constipation. We aimed to determine the adherence by general practitioners (GPs) to this recommendation and to explore which GP- and patient related factors were associated with it from the perspective of the GP.  METHODS: We conducted an observational study using GPs' prescription data from the Nivel Primary Care Database combined with a questionnaire asking for reasons of non-adherence. The proportion of first opioid prescriptions prescribed together with a laxative was determined as primary outcome. Possible explanatory factors such as the quality of registration, the level of collaboration with the pharmacy, familiarity with the recommendation and use of a clinical decision support system were explored, as were the self-reported reasons for non-adherence (classified as either GP-related or patient-related). We assessed the association of factors with the primary outcome using univariable multilevel logistic regression analysis. RESULTS: The recommendation was measured in 195 general practices. The median proportion of first opioid prescriptions prescribed together with a laxative in these practices was 54% (practice range 18-88%). None of the determinants was consistently associated with the primary outcome. GPs from 211 practices filled out the questionnaire and the most frequently mentioned reason not to prescribe a laxative was that the patient has laxatives in stock, followed by that the patient doesn't want a laxative; both were patient-related factors. CONCLUSION: There was room for improvement in following the guideline on laxative prescribing in opioid use. A main reason seemed to be that the patient refuses a laxative. Improvement measures should therefore focus on communication between GPs and patients on the relevance of co-using a laxative with opioids. Future studies need to establish the effect of such improvement measures, and determine whether reasons for non-adherence to the guideline changed over time.

Feasibility of a protocol for deprescribing antihypertensive medication in older patients in Dutch general practices.

BACKGROUND: Older patients using antihypertensive medication may experience Adverse Drug Events (ADEs), and thus benefit from deprescribing. The lack of a practical protocol may hamper deprescribing. Therefore, we aimed to develop a deprescribing protocol, based on a review of literature, combined with a feasibility test in a small number of patients. METHODS: A deprescribing protocol for general practitioners was drafted and tested in older patients using multiple antihypertensive medication in a single arm intervention. Patients were included if they were 75 years or older, were using two or more antihypertensives, had at least one ADE linked to antihypertensive medication and deprescribing was considered to be safe by their general practitioner. The primary outcome was the percentage of patients for whom one or more antihypertensive drugs were stopped or reduced in dose after 12 months of follow up while maintaining safe blood pressures. Secondary outcomes were the proportion of patients reporting no ADEs after 12 months and the number of deprescribed antihypertensives. Patient's opinions on deprescribing and enablers and barriers for study participation were also collected. RESULTS: Nine general practitioners included 14 patients to deprescribe antihypertensive medication using the deprescribing protocol. After 12 months antihypertensive drug use was lowered in 11 patients (79%). These patients had a mean systolic blood pressure increase of 16 mmHg and a mean diastolic blood pressure increase of 8 mmHg. Nine patients (64%) reported experiencing no ADEs anymore after twelve months. The mean number of deprescribed antihypertensives was 1.1 in all patients and 1.4 (range: 0.5 to 3.5) in patients who successfully lowered their medication. At baseline, being able to use less medication was the most frequently mentioned enabler to participate in this study. The most frequently mentioned positive experience at the end of the study was using less medication, which was in line with the most mentioned enabler to participate in this study. CONCLUSION: A protocol for deprescribing antihypertensives in older patients was considered feasible, as it resulted in a substantial degree of safe deprescribing in this pilot study. Larger studies are needed to demonstrate the effect and safety of deprescribing antihypertensives in older patients.

The Effect of Self-Administration of Medication During Hospitalization on Patient's Self-Efficacy and Medication Adherence After Discharge.

Purpose: The effect of self-administration of medication (SAM), in which capable hospitalized patients administer medication themselves on medication self-efficacy is inconclusive. The aim of this study was to evaluate the effect of SAM on medication self-efficacy, adherence and patient satisfaction. Patients and Methods: A prospective pre-post intervention study on the orthopedic ward of the Sint Maartenskliniek (Nijmegen) was conducted from January 2020 to July 2021. All adults admitted to this ward were eligible for participation. The primary outcome was the level of medication self-efficacy measured by the Self-Efficacy for Appropriate Medication Use Scale (SEAMS) one week after discharge. Secondary outcomes were SEAMS-score three months after hospitalization, medication adherence measured by the Medication Adherence Rating Scale (MARS) one week and three months after hospitalization and patient satisfaction expressed on a five-point Likert scale in patients who experienced SAM. The differences in median SEAMS-scores and non-adherence pre- versus post-implementation of SAM were statistically analyzed. Patients' agreement regarding satisfaction with SAM was calculated as proportion per Likert scale answer. Results: Of the 197 patients participating in the study, 96 were included pre- and 101 post-implementation of SAM. Median SEAMS-scores one week after discharge were 35 [IQR 31-38] and 34 [IQR 30-36] pre- and post-intervention respectively (p = 0.08). There was no difference in the proportion of non-adherent patients at one week and three months after discharge pre- and post-intervention, 52.4%, 53.2%, 57.9% and 64.4% respectively. Of the patients that experienced SAM 32% agreed and 49% strongly agreed that they would like to self-manage medication again during a future hospitalization. Conclusion: In this orthopedic population with high medication self-efficacy scores at discharge, SAM did not affect patients' medication self-efficacy nor medication adherence after hospitalization. Most patients preferred SAM. Additional studies should focus on the effect of SAM in other patient populations.

Optimising the Nadroparin Dose for Thromboprophylaxis During Hemodialysis by Developing a Population Pharmacodynamic Model Using Anti-Xa Levels.

INTRODUCTION: The optimal nadroparin dose in patients undergoing hemodialysis is difficult to determine in clinical practice. Anti-Xa levels ≥ 0.4 IU/mL and < 2.0 IU/mL are suggested to prevent thrombus formation within the extracorporeal circuit whilst minimizing bleeding risk. We aimed to characterize the variability in the association between dose and anti-Xa levels, identify patient and dialysis characteristics that explained this variability, and optimize nadroparin dosing based on the identified characteristics. METHODS: Anti-Xa samples were collected in patients who received intravenous nadroparin as thromboprophylaxis during routine dialysis sessions. A population pharmacodynamic model was developed using non-linear mixed-effects modelling. The percentage of patients ≥ 0.4 IU/mL (efficacy) and < 2.0 IU/mL (safety) was simulated for different doses, patient and dialysis characteristics. RESULTS: Patients (n = 137) were predominantly receiving standard hemodialysis (84.7% vs. hemodiafiltration 15.3%) and had a mean bodyweight of 76.3 kg (± 16.9). Lean body mass (LBM), mode of dialysis, and dialyzer partially explained between-subject variability in anti-Xa levels. Patients on hemodiafiltration and those receiving hemodialysis with a high LBM (≥ 80 kg) had a low probability (< 29%) of anti-Xa levels ≥ 0.4 IU/mL during the entire dialysis session. All patients, except hemodialysis patients with a low LBM (< 50 kg), had a high probability (> 70%) of peak anti-Xa levels < 2.0 IU/mL. CONCLUSION: Mainly patients receiving hemodiafiltration and those receiving hemodialysis with a high LBM can benefit from a higher nadroparin dose than currently used in clinical practice, while having anti-Xa levels < 2.0 IU/mL.