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Abeer Ahmad,1 M Ruth Mast,1 Giel Nijpels,2 Petra JM Elders,2 Jacqueline M Dekker,3 Jacqueline G Hugtenburg1 1Department of Clinical Pharmacology and Pharmacy, 2Department of General Practice, 3Departments of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands Background: Drug-related problems (DRP) following hospital discharge are common among elderly patients using multiple drugs for the treatment of chronic diseases. The aim of this study was to investigate the occurrence of DRP in these patients using a specific tool for the identification of DRP by community pharmacists. Methods: An observational study involving 340 patients aged over 60 years using at least five prescription drugs and discharged from hospital. The occurrence of DRP was assessed by means of an identification tool specifically developed for use by community pharmacists, including a semistructured patient interview and a checklist of common DRP. Results: In total, 992 potential DRP were observed in the 340 patients (mean 2.9 ± 1.7). No drug prescribed but clear indication, an unnecessarily long duration of treatment, dose too low, and incorrect drug selection were the DRP most commonly observed. Ten percent of DRP occurring in 71 patients were drug–drug interactions. The number of DRP was related to the number of drugs prescribed. Frequently occurring DRP found using the patient interview were fear of side effects and no or insufficient knowledge of drug use. Medication of patients discharged from the pulmonary department and of those with type 2 diabetes was particularly associated with occurrence of DRP. Conclusion: Following hospital discharge, DRP occur frequently among elderly patients using five or more drugs for the treatment of chronic disease. The number of DRP increased with the number of drugs used. An important task for community pharmacists is to identify, resolve, and prevent the occurrence of DRP among this patient group. Since DRP are associated with an increased risk of hospital readmissions, morbidity, and mortality, it is very important to develop intervention strategies to resolve and prevent DRP. Keywords: drug-related problems, elderly, discharge from hospital, community pharmacy

Jacqueline G Hugtenburg,1 Lonneke Timmers,1 Petra JM Elders,2 Marcia Vervloet,3 Liset van Dijk31EMGO+ Institute and Department of Clinical Pharmacology and Pharmacy, VU University Medical Center, Amsterdam, 2ANH-VUmc, VU University Medical Center, Amsterdam, 3NIVEL, Netherlands Institute for Health Services Research, Utrecht, The NetherlandsBackground: Nonadherence with medication is a complex and multidimensional health care problem. The causes may be related to the patient, treatment, and/or health care provider. As a consequence, substantial numbers of patients do not benefit optimally from pharmacotherapy, resulting in increased morbidity and mortality as well as increased societal costs. Several interventions may contribute to improved adherence. However, most interventions have only a modest effect. Thus, despite the many efforts made, there has been little progress made as yet in tackling the problem of nonadherence.Methods: This paper summarizes the definitions and taxonomy of adherence with medication, as well as types and causes of nonadherence. In addition, interventions aimed at improvement of adherence are discussed.Conclusion: There is not just one solution for the nonadherence problem that fits all patients. Most interventions to improve adherence are aimed at all patients regardless of whether they are adherent or not. Recently, a number of tailored interventions have been described in the literature. Modern techniques are useful. Electronic pill boxes combined with Short Message Service reminders are specifically designed to improve unintentional adherence and have resulted in an increase in refill adherence in diabetic patients with suboptimal adherence. Tailored Internet interventions are a possibility for influencing patient drug-taking behavior and show promising results. Tailored counseling interventions targeted at the underlying causes of nonadherence seem an attractive method for supporting patients with their use of drugs. However, despite the plausible theoretical framework, data on long-term health effects of the various interventions are not available. To improve adherence effectively, there is a need for a tailored approach based on the type and cause of nonadherence and the specific needs of the patient.Keywords: adherence, compliance, concordance, tailored intervention

Lonneke Timmers,1 Eleonora L Swart,1 Christel CLM Boons,1 Dirk Mangnus,1 Peter M van de Ven,2 Godefridus J Peters,3 Epie Boven,3 Jacqueline G Hugtenburg11Department of Clinical Pharmacology and Pharmacy, 2Department of Epidemiology and Biostatistics, 3Department of Medical Oncology, VU University Medical Center, Amsterdam, The NetherlandsBackground: Adherence to pharmacological therapy is a complex and multifactorial issue that can substantially alter the outcome of treatment. Especially when using long-term medication, cancer patients have adherence rates similar to those of patients with other diseases. The consequences of poor adherence are poor health outcomes and increased health care costs. Only few studies have focused on the use of oral anticancer agents in daily practice. Information about the reasons for nonadherence is essential for the development of interventions that may improve adherence. This report presents the CAPER-capecitabine protocol, which is designed to study the adherence to capecitabine and the influence of patient attitudes towards medication and self-reported side effects. Furthermore, the relationships between patient characteristics, disease characteristics, side effects, quality of life, patient beliefs and attitudes towards disease and medication, dose adjustments, reasons for discontinuation, and plasma concentration of three of the main metabolites, including the active compound 5-fluorouracil, will be explored.Methods: In this multicenter, prospective, observational cohort study, 90 patients aged 18 years or older starting treatment with capecitabine will be included and followed for a period up to five cycles. The main study parameters are adherence, patient attitudes towards medication, and the number and grade of patient-reported side effects. At baseline and during week 2 of cycles 1, 3 and 5, patients will be asked to donate blood and fill out a questionnaire. Blood samples will be analyzed for plasma concentration of the metabolites, 5'-deoxy-5-fluorouridine, 5-fluorouracil, and α-fluoro-β-alanine. The CAPER-capecitabine trial is closely related to the CAPER-erlotinib trial.Discussion: The aim of the present study is to get more insight into patient experiences with the use of capecitabine in daily practice and the various aspects that govern adherence. We hypothesize that patient attitudes towards medication and the side effects experienced play an important role in the way patients use capecitabine. We expect that our findings will be useful for health care professionals in developing interventions to support patients in improving adherence and persistence with the use of capecitabine.Keywords: capecitabine, medication adherence, patients' experiences, medical oncology, oral antineoplastic agents

Objective: To evaluate, among new users of inhaled corticosteroids that did not persist treatment, knowledge of inhaled corticosteroids' actions and whether they were instructed on the use of their inhaler.Setting: Fifteen community pharmacies in The Netherlands. Methods Patients were interviewed by telephone. Their general practitioners provided diagnostic information and automated dispensing records were retrieved.Main Outcome Measures: Knowledge of patients about the actions of inhaled corticosteroids.Results: 230 (80.1%) of 287 patients were willing to participate. The majority (79.1%) of 230 patients was not aware of the anti-inflammatory actions of inhaled corticosteroids. Most patients were instructed on the use of their inhaler, predominantly by their physician (53%) or pharmacy (35.2%).Conclusions: Although most patients reported inhaler instruction by at least one health care provider, the majority was unaware of inhaled corticosteroids' actions. Physicians and pharmacists should reconsider the instructions they provide especially to patients who should continuously use inhaled corticosteroids. [ABSTRACT FROM AUTHOR]

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., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Objectives: To adapt the 2015 Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) criteria to older nursing home patients with a limited life expectancy of 1.5 to 2 years., Design: A modified Delphi consensus study., Setting and Participants: The study was established in The Netherlands and conducted online. The international panel consisted of 23 experts with experience in medicine for older people., Methods: The expert panel was presented with the 2015 STOPP/START criteria using an online survey program (Survey Monkey). The panelists were asked for their opinion on the appropriateness of the STOPP and START criteria, and adaptations to these criteria for older nursing home patients with a limited life expectancy on 4-point Likert scales. Consensus was defined as ≥70% of the panelists answering (very) inappropriate or (very) appropriate, and (completely) disagree or (completely) agree., Results: Twenty-one panelists completed all 3 Delphi rounds. The final list of "Represcribing for Nursing home residents With A Limited life expectancy (ReNeWAL)" criteria comprises 132 criteria: 98 criteria to stop (70 original STOPP criteria and 28 adapted) and 34 criteria to start (16 original START criteria and 18 adapted) for older nursing home patients with a limited life expectancy. Considerations that panelists mentioned for adapting criteria were mainly prevention and treatment of discomfort., Conclusion and Implications: It is clear that represcribing for older nursing home patients is highly complex and requires the consideration of various elements. The ReNeWAL criteria may be useful in enhancing represcribing for older nursing home patients with a limited life expectancy., Competing Interests: Disclosures The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Online symptom monitoring through patient-reported outcomes can enhance health-related quality of life and survival. However, widespread adoption in clinical care remains limited due to various barriers including the need to reduce health care practitioners' workload., Objective: To report the effects of patient-reported outcome (PRO) symptom monitoring on HRQOL and survival up to 1 year after initiation of any treatment in patients with lung cancer., Design, Setting, and Participants: SYMPRO-Lung is a multicenter stepped-wedge cluster randomized trial including patients with stage I to IV lung cancer. The inclusion period was from October 24, 2019, until September 16, 2021, and data collection ended October 8, 2022. Data analysis was conducted from November 9, 2023, until March 18, 2024., Intervention: Patients in the intervention group reported PRO symptoms weekly using the Patient Reported Outcomes version of the Common Toxicity Criteria for Adverse Events lung cancer subset. If symptoms exceeded a validated threshold, an alert was sent to the health care practitioner (active intervention subgroup) or to the patient (reactive intervention subgroup). Patients in the control group received standard care., Main Outcomes and Measures: Health-related quality of life was measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at baseline, 15 weeks (T1), 6 months (T2), and 1 year (T3), with the summary score (SS) and physical functioning (PF) as primary end points. Linear mixed-effects modeling was used to assess mean differences over time. Effect size (ES) of 0.40 or greater was considered clinically relevant. Cox proportional hazards regression survival analyses were performed to estimate the effect of the intervention on progression-free survival and overall survival (OS). Data were analyzed on an intention-to-treat basis., Results: A total of 515 patients (266 [51.7%] men; mean [SD] age, 65.4 [9.4] years) were included in the study (266 in the control group; 249 in the pooled intervention group). Most baseline characteristics were balanced between groups; however, the most notable exception was the distribution in cancer staging: the intervention group had a higher proportion of patients with stage IV cancer compared with the control group (139 [56%] vs 118 [44%]). The pooled intervention group had a significantly better SS (mean difference T1, 5.22; 95% CI, 2.72-7.73; P < .001; ES = 0.33; mean difference T2, 6.28; 95% CI, 3.65-8.92; P < .001; ES = 0.40; mean difference T3, 3.97; 95% CI, 1.15-6.80; P = .006; ES = 0.25) compared with the control group. Group differences improved more in PF but did not meet the ES greater than or equal to 0.40 threshold (mean difference T1, 7.00; 95% CI, 3.65-10.35; P < .001; ES = 0.27; mean difference T2, 6.79; 95% CI, 3.26-10.31; P < .001; ES = 0.26; mean difference T3, 5.01; 95% CI, 1.23-8.79; P = .009; ES = 0.19). No significant differences in HRQOL were observed between the reactive (n = 89) and active (n = 160) intervention groups. The HR for progression-free survival for the active intervention group compared with the control group was 0.78 (95% CI, 0.58-1.04); the finding was not statistically significant. The HR for overall survival for both interventions groups compared with the control group were not statistically significant.(active: HR, 0.80; 95% CI, 0.55-1.15; reactive: HR, 0.69; 95% CI, 0.42-1.15)., Conclusions and Relevance: In this 1-year follow-up of a stepped-wedge cluster randomized trial, PRO symptom monitoring yielded improvements in long-term HRQOL in patients with lung cancer. The reactive approach proved equally effective as the active approach. A nonsignificant potential survival benefit was observed for the intervention group. These positive results provide further evidence for the usefulness of routine PRO symptom monitoring in lung cancer care., Trial Registration: The Netherlands trial register Identifier: NL7897.

Background: Older patients with type 2 diabetes mellitus (T2D) have an increased risk of hypoglycaemic episodes when using sulphonylureas or insulin. In the Netherlands, guidelines exist for reducing glucose-lowering medication in older patients. However, evidence is lacking that a medication reduction in older patients can be safely pursued. Here, we will examine if promoting the deprescribing of insulin/sulphonylureas with a deprescribing programme (DPP) in general practice affects T2D-complications in older overtreated patients., Methods: We will perform a 1:1 cluster randomised controlled trial in 86 general practices in the Netherlands. The DPP will consist of education sessions with general practitioners and practice nurses about reducing glucose-lowering medication in older patients (≥ 70 years). Topics of the sessions include the necessity of deprescribing, tools to initiate deprescribing and strategies to discuss deprescribing with patients (shared decision making). The DPP further includes a support programme with practice visits. The study will employ a selection tool to identify possibly overtreated older patients from the electronic medical records of the general practitioner. Eligibility for enrolment in the study will be based on HbA1c targets indicated by the Dutch guidelines, which depend on age, diabetes duration, presence of frailty, and life expectancy. The control group will provide usual care. We aim to include 406 patients. The follow-up period will be 2 years. For the primary outcome, the effect of the DPP on T2D-complications will be assessed by counting the cumulative incidence of events related to under- and overtreatment in T2D as registered in the electronic medical records. We shall perform an intention-to-treat analysis and an analysis including only patients for whom deprescribing was initiated. The implementation of the DPP in general practice will be evaluated quantitatively and qualitatively using the Extended Normalisation Process Theory (ENPT) and the Reach, Efficacy - Adoption, Implementation and Maintenance (RE-AIM) model. Other secondary outcomes include quality of life, cognitive functioning, events related to overtreatment or undertreatment, biomarkers of health, amount of blood glucose-lowering medication prescriptions, and cost-effectiveness., Discussion: This study will provide insight into the safety and feasibility of a programme aimed at deprescribing sulphonylureas/insulin in older people with T2D who are treated in general practice., Trial Registration: ISRCTN Registry, ISRCTN50008265 , registered 09 March, 2023., (© 2024. The Author(s).)

Background and Aims: High temperatures may reduce fecal immunochemical test (FIT) positivity and colorectal cancer (CRC) detection sensitivity. We investigated the effect of temperature on hemoglobin concentration [Hb], in the FOB Gold®. Additionally, we examined FIT pick-up, storage, return times and specimen collection., Materials and Methods: In vitro experiments with buffer containing FIT devices, inoculated with Hb-spiked stool. For 7 days, 144 samples were stored in groups of 36 at 4 °C, 22 °C, 30 °C, and 50 °C. Additionally, 54 samples were stored in groups of 18 at 34 °C, 42 °C and 50 °C for 20 h. Paired t-tests and repeated measure ANOVA assessed [Hb] change. Sixty-five screening participants completed a FIT-handling questionnaire., Results: After 7 days, mean [Hb] was stable at 30 °C (0.8 µg Hb/g;95 %CI: -1.5 to 3.1;p = 0.50). For 50 °C, mean [Hb] decreased within 2 days (-21.3 µg Hb/g;95 %CI: -30.2 to -12.5;p < 0.001) and after 20 h (-63.0 µg Hb/g;95 %CI: -88.7 to -37.3;p < 0.001), respectively. All other temperature categories showed significant mean [Hb] increase. Same-day FIT return was reported by 80 %. Eighty-seven percent experienced specimen collection as easy and 33 % kept the FIT refrigerated after collection., Conclusions: The FOB Gold® is suitable for CRC screening in tropical climates. Although most respondents indicated same-day sample return, we recommend avoiding FIT storage above 30 °C for longer than7 days., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Many doctors regularly write a prescription for themselves or for family members or friends. In this article, we discuss the legal and ethical considerations surrounding these prescriptions. We also discuss the role of the pharmacist who receives the prescription. Although there is no legal obstacle, codes of conduct and guidelines state that prescribing to acquaintances or yourself is undesirable, especially because it is often not possible to maintain sufficient professional distance, necessary to provide proper treatment. If the GP or other care providers have no knowledge of the prescription and no medical file is kept, undesirable situations may arise for the patient. A prescription for yourself or acquaintances can be made occasionally and under special circumstances (acute situation, no serious problem, short-term), but then requires a quick transfer of treatment to regular practitioners.

Background: Polypharmacy is common in chronic medication users, which increases the risk of drug related problems. A suitable intervention is the clinical medication review (CMR) that was introduced in the Netherlands in 2012, but the effectiveness might be hindered by limited implementation in community pharmacies. Therefore our aim was to describe the current implementation of CMRs in Dutch community pharmacies and to identify barriers to the implementation., Methods: An online questionnaire was developed based on the Consolidated Framework for Implementation Research (CFIR) and consisted of 58 questions with open ended, multiple choice or Likert-scale answering options. It was sent out to all Dutch community pharmacies (n = 1,953) in January 2021. Descriptive statistics were used., Results: A total of 289 (14.8%) community pharmacies filled out the questionnaire. Most of the pharmacists agreed that a CMR has a positive effect on the quality of pharmacotherapy (91.3%) and on medication adherence (64.3%). Pharmacists structured CMRs according to available selection criteria or guidelines (92%). Pharmacists (90%) believed that jointly conducting a CMR with a general practitioner (GP) improved their mutual relationship, whereas 21% believed it improved the relationship with a medical specialist. Lack of time was reported by 43% of pharmacists and 80% (fully) agreed conducting CMRs with a medical specialist was complicated. Most pharmacists indicated that pharmacy technicians can assist in performing CMRs, but they rarely do in practice., Conclusions: Lack of time and suboptimal collaboration with medical specialists are the most important barriers to the implementation of CMRs., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Background: Previous studies using patient-reported outcomes measures (PROMs) to monitor symptoms during and after (lung) cancer treatment used alerts that were sent to the health-care provider, although an approach in which patients receive alerts could be more clinically feasible. The primary aim of this study was to compare the effect of weekly PROM symptom monitoring via a reactive approach (patient receives alert) or active approach (health-care provider receives alert) with care as usual on health-related quality of life (HRQOL) at 15 weeks after start of treatment in lung cancer patients., Methods: The SYMPRO-Lung trial is a multicenter randomized controlled trial using a stepped wedge design. Stage I-IV lung cancer patients in the reactive and active groups reported PROM symptoms weekly, which were linked to a common alerting algorithm. HRQOL was measured by the EORTC QLQ-C30 at baseline and after 15 weeks. Linear regression analyses and effect size estimates were used to assess mean QOL-C30 change scores between groups, accounting for confounding., Results: A total of 515 patients were included (160 active group, 89 reactive group, 266 control group). No differences in HRQOL were observed between the reactive and active group (summary score: unstandardized beta [B] = 0.51, 95% confidence interval [CI] = -3.22 to 4.24, Cohen d effect size [ES] = 0.06; physical functioning: B = 0.25, 95% CI = -5.15 to 4.64, ES = 0.02). The combined intervention groups had statistically and clinically significantly better mean change scores on the summary score (B = 4.85, 95% CI = 1.96 to 7.73, ES = 0.57) and physical functioning (B = 7.00, 95% CI = 2.90 to 11.09, ES = 0.71) compared with the control group., Conclusions: Weekly PRO symptom monitoring statistically and clinically significantly improves HRQOL in lung cancer patients. The logistically less intensive, reactive approach may be a better fit for implementation., (© The Author(s) 2023. Published by Oxford University Press.)

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., (© 2023. The Author(s).)

Background: Despite the abundant availability of effective medication adherence interventions, uptake of these interventions into routine care often lacks. Examples of effective medication adherence interventions include telephone counseling, consult preparation and the teach-back method. Assessing context is an important step in understanding implementation success of interventions, but context is often not reported or only moderately described. This study aims to describe context-specific characteristics in four living labs prior to the implementation of evidence-based interventions aiming to improve medication adherence., Methods: A qualitative study was conducted within four living labs using individual interviews (n = 12) and focus groups (n = 4) with project leaders and involved healthcare providers. The four living labs are multidisciplinary collaboratives that are early adopters of medication adherence interventions in the Dutch primary care system. Context is defined as the environment or setting in which the proposed change is to be implemented. Interview topics to assess context were formulated based on the 'inner setting' and 'outer setting' domains of the Consolidated Framework for Implementation Research (CFIR). Interviews were recorded and transcribed verbatim. Transcripts were deductively analyzed., Results: A total of 39 community pharmacists, pharmacy technicians, general practitioners and a home care employee participated in the (focus group) interviews. All four living labs proved to be pharmacy-driven and characterized by a high regard for innovation by staff members, a positive implementation climate, high levels of leadership engagement and high compatibility between the living labs and the interventions. Two living labs were larger in size and characterized by more formal communication. Two living labs were characterized by higher levels of cosmopolitanism which resulted in more adaptable interventions. Worries about external policy, most notably lack of reimbursement for sustainment and upscaling of the interventions, were shared among all living labs., Conclusions: Contextual characteristics of four living labs that are early adopters of medication adherence interventions provide detailed examples of a positive implementation setting. These can be used to inform dissemination of medication adherence interventions in settings less experienced in implementing medication adherence interventions., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To explore insomnia management in general practice, with a focus on sleep medication prescription., Design: Descriptive analysis of anonymized routine general practice care data extracted from electronic medical records (EMRs), including demographics, free text annotations from sleep consultations and sleep medication prescriptions covering one year before up to two years after the registration of the International Classification for Primary Care (ICPC) code P06 'Sleep disturbance'., Setting: Twenty-one general practices in an urban area of the Netherlands., Patients: Adults (18-85 year) with a first sleep consultation with their GP., Outcomes: Documented non-pharmacological and sleep medication treatment., Results: Of the 1,089 patients who consulted their general practitioner (GP) for sleep disturbance for the first time, about 50% had one more sleep consultation during the two years follow-up. Over two years including the first consultation, GPs documented a non-pharmacological intervention for 48.4% of the patients and prescribed sleep medication to 77.0%. 64.6% of the patients received a sleep medication prescription in the first consultation. Among patients receiving medication ( N  = 838); 59.6% received more than one prescription; 76.8% received one or more short-acting benzodiazepine receptor agonist (BZRA), 39.5% one or more unrecommended drugs and 14.7% >180 pills of BZRAs in two years., Conclusion: Although the guidelines advocate non-pharmacological treatment and warn against unwarranted sleep medication, it is still very common in Dutch general practice to prescribe medication, even at the first sleep consultation. Prescriptions frequently include unrecommended and off-label drugs or repeated BZRA prescriptions.

Background: During the first year of the population based colorectal cancer (CRC) screening program on Curaçao, about 20% of invitees participated. This study explored the target population's perceptions and awareness on CRC (screening), beliefs on the program provision, their preferences and information needs for informed decision-making., Methods: Semi-structured interviews with 23 individuals, who were not yet invited for CRC screening, were recorded, transcribed, coded and analyzed., Results: CRC (screening) was discussed in the context of personal health, where own responsibility and food were important. Cancer was perceived as an unpredictable disease that causes suffering and leads to death and was also associated with fear. Despite being aware of the program, most respondents were not familiar with the screening procedure. Provision of the screening program was regarded positively and as an opportunity to contribute to health improvement. This seemed related to the expressed trust in the Caribbean Prevention Center (program organizer). Respondents preferred to make independent decisions about CRC screening participation. A personal approach, visual aids and media were the preferred sources of information., Conclusion: The results of our interviews suggest that it may be beneficial to provide information on CRC screening in Curaçao within the context of personal health. While including sensitivity to fears and respect for the autonomy of the target population. Finally, electronic media maybe useful in supporting informed decision-making., (© 2023. The Author(s).)

Upscaling of medication adherence interventions to routine care is still challenging. This realist theory-inspired review aimed to assess which intervention aspects are potentially important for the scalability of effective cardiovascular disease (CVD) medication adherence interventions and how they are reported in effectiveness studies. A total of 4097 articles from four databases were screened of which ultimately 31 studies were included. Relevant information on scalability was extracted using a theoretic framework based on the scalability assessment tool used in the QUALIDEC study for the following domains: (i) innovation, (ii) implementers and patients, (iii) adopting organizations and health system, and (iv) socio-political context. Extracted articles were analysed for themes and chains of inference, which were grouped based on commonality and source of evidence to form new hypotheses. Six different domains relevant for scalability of adherence interventions were identified: (1) Complexity of the intervention; (2) training; (3) customization of the intervention; (4) drivers of the intervention; (5) technical interventions; and (6) stakeholder involvement. These six domains might be useful for the development of more scalable interventions by bridging the gap between research and practice. Data relevant for scalability is not well reported on in effectiveness trials for CVD medication adherence interventions and only limited data on scalability has been published in additional papers. We believe the adoption and reach of effective CVD medication adherence interventions will improve with increased awareness for the necessity of scalability in all phases of intervention development., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Purpose: Low dose amitriptyline is prescribed off-label to improve sleep maintenance in patients with insomnia disorder. Data on treatment outcomes are limited. We aimed to assess patient-reported treatment effect and side effects of low dose amitriptyline for insomnia in routine care data., Methods: Cross-sectional study: Seven hundred fifty-two consecutive patients with insomnia disorder having sleep maintenance problems were treated in an outpatient sleep clinic with low dose amitriptyline (10-20 mg based on self-titration). Treatment was intended to improve sleep maintenance. Before the planned follow-up consultation (approximately 6 weeks after start treatment) patients completed an online treatment evaluation questionnaire. Treatment (dose, adherence), sleep, fatigue, satisfaction and side effects were assessed by multiple-choice questions with room for free-text elaboration., Results: 53.7% of the patients reported to use amitriptyline up to 10 mg/day, 42.9% used a self-increased dose of mostly 20 mg/day, while 3.5% had discontinued treatment. 73.9% of the total study population reported improvement of sleep maintenance, 31.3% improved sleep onset, 35.2% improved daytime fatigue, and 45.8% reported to be (very) satisfied with treatment results. 66.1% reported at least one side effect. The reported side effects were generally the already known side effects of amitriptyline., Conclusion: These patient-reported outcomes support the clinical observations that low dose amitriptyline improves sleep maintenance on the short term and that it is generally well tolerated. This further justifies randomized controlled trials in patients with insomnia disorder and sleep maintenance problems to assess the effectiveness and safety of low dose amitriptyline on the short and long term., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

We aimed to assess the validity of an announced telephone pill count in people with type 2 diabetes or cardiovascular disease by comparing this method to a home-visit pill count. We also assessed whether a second telephone pill count improved accuracy. People aged ≥35 years using oral type 2 diabetes or cardiovascular disease medication were included. Thirty-four participants completed a telephone pill count followed by a home-visit pill count, and a subsample of this population (n = 11) completed a second telephone pill count. Scatterplots were used for a visual representation of the number of pills counted with both methods, intraclass correlation coefficients for agreement, and Bland-Altman plots for absolute differences and outliers. A total of 203 pill counts were conducted. The study population consisted of 53% men, with a mean age of 69.6 (±9.2) years and an average of 6.1 (±2.8) medication prescriptions per participant. Scatterplots showed that pills counted with both methods were mostly scattered around the y = x equation. Agreement between the first telephone pill count and home-visit pill count was high, with intraclass correlation coefficients of 0.96 (medication count level) and 0.98 (individual level). No learning effects were observed in the subsample (n = 11), the intraclass correlation coefficient for the first telephone pill count was 0.88 versus 0.89 for the second telephone pill count. Bland-Altman plots indicated high agreement between the two methods. An announced telephone pill count is considered a valid alternative for a home-visit pill count in people with type 2 diabetes or cardiovascular disease. A single pill count appears sufficient., (© 2022 The Authors. Clinical Pharmacology in Drug Development published by Wiley Periodicals LLC on behalf of American College of Clinical Pharmacology.)

Objective: The use of adjuvant endocrine therapy (AET) after primary treatment of hormone receptor-positive breast cancer reduces the risk of recurrence and mortality. However, non-adherence is still common. Limited consideration has been given to how users deal with AET and the role of pharmaceutical care. Therefore, this study aims to obtain insight into the needs and wishes of women using AET regarding pharmaceutical care and eHealth., Methods: This is a qualitative explorative study comprising semi-structured interviews (n = 16) and a focus group (n = 5) among women who use or used AET after primary early-stage breast cancer (EBC) treatment using a thematic analysis approach., Results: Three themes emerged from the interviews and focus group: (1) experiences with AET use, (2) experiences with provided information and (3) needs and wishes regarding pharmaceutical care. Most women were highly motivated to use AET and indicated to have received useful information on AET. However, many expressed a strong need for more elaborate tailored and timely provided information on AET. They acknowledged the accessibility of pharmacists but reported that currently, pharmacists are hardly involved in AET care. Several women considered eHealth useful to obtain counselling and reliable information., Conclusion: Women need more comprehensive information and follow-up in primary setting after initial cancer treatments. A more elaborate role for the pharmacy and eHealth/mHealth, especially with regard to counselling on side effects and side effect management, could potentially improve pharmaceutical care., (© 2022 The Authors. European Journal of Cancer Care published by John Wiley & Sons Ltd.)

Background: Insufficient information transfer is a major barrier in the transition from hospital to home. This study describes the systematic development and evaluation of an intervention to improve medication information transfer between hospital and community pharmacists., Objective: To develop and evaluate an intervention to improve the medication information transfer between hospital and community pharmacists based on patients', community and hospital pharmacists' needs., Methods: The intervention development and evaluation was guided by the six-step Intervention Mapping (IM) approach: (1) needs assessment to identify determinants of the problem, with a scoping review and focus groups with patients and healthcare providers, (2) formulation of intervention objectives with an expert group, (3) inventory of communication models to design the intervention, (4) using literature review and qualitative research with pharmacists and patients to develop the intervention (5) pilot-testing of the intervention in two hospitals, and (6) a qualitative evaluation of the intervention as part of a multicenter before-after study with hospital and community pharmacists., Results: Barriers in the information transfer are mainly time and content related. The intervention was designed to target a complete, accurate and timely medication information transfer between hospital and community pharmacists. A pharmaceutical discharge letter was developed to improve medication information transfer. Hospital and community pharmacists were positive about the usability, content, and comprehensiveness of the pharmaceutical discharge letter, which gave community pharmacists sufficient knowledge about in-hospital medication changes. However, hospital pharmacists reported that it was time-consuming to draft the discharge letter and not always feasible to send it on time. The intervention showed that pharmacists are positive about the usability, content and comprehensiveness., Conclusion: This study developed an intervention systematically to improve medication information transfer, consisting of a discharge letter to be used by hospital and community pharmacists supporting continuity of care., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

What Is Known and Objective: The recently conducted Medication Actions to Reduce hospital admissions through a collaboration between Community and Hospital pharmacists (MARCH) transitional care programme, which aimed to test the effectiveness of a transitional care programme on the occurrence of ADEs post-discharge, did not show a significant effect. To clarify whether this non-significant effect was due to poor implementation or due to ineffectiveness of the intervention as such, a process evaluation was conducted. The aim of the study was to gain more insight into the implementation fidelity of MARCH., Methods: A mixed methods design and the modified Conceptual Framework for Implementation Fidelity was used. For evaluation, the implementation fidelity and moderating factors of four key MARCH intervention components (teach-back, the pharmaceutical discharge letter, the post-discharge home-visit and the transitional medication review) were assessed. Quantitative data were collected during and after the intervention. Qualitative data were collected using semi-structured interviews with MARCH healthcare professionals (community pharmacists, clinical pharmacists, pharmacy assistants and pharmaceutical consultants) and analysed using thematic analysis., Results and Discussion: Not all key intervention components were implemented as intended. Teach-back was not always performed. Moreover, 63% of the pharmaceutical discharge letters, 35% of the post-discharge home-visits and 44% of the transitional medication reviews were not conducted within their planned time frames. Training sessions, structured manuals and protocols with detailed descriptions facilitated implementation. Intervention complexity, time constraints and the multidisciplinary coordination were identified as barriers for the implementation., What Is New and Conclusion: Overall, the implementation fidelity was considered to be moderate. Not all key intervention components were carried out as planned. Therefore, the non-significant results of the MARCH programme on ADEs may at least partly be explained by poor implementation of the programme. To successfully implement transitional care programmes, healthcare professionals require full integration of these programmes in the standard work-flow including IT improvements as well as compensation for the time investment., (© 2022 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd.)

Introduction: Transitional care programs (i.e. interventions delivered both in hospital and in primary care), could increase continuity and consequently quality of care. However, limited studies on the effect of these programs on Adverse Drug Events (ADEs) post-discharge are available. Therefore, the aim of this study was to investigate the effect of a transitional pharmaceutical care program on the occurrence of ADEs 4 weeks post-discharge., Methods: A multicentre prospective before-after study was performed in a general teaching hospital, a university hospital and 49 community pharmacies. The transitional pharmaceutical care program consisted of: teach-back to the patient at discharge, a pharmaceutical discharge letter, a home visit by a community pharmacist and a clinical medication review by both the community and the clinical pharmacist, on top of usual care. Usual care consisted of medication reconciliation at admission and discharge by pharmacy teams. The primary outcome was the proportion of patients who reported at least 1 ADE 4 weeks post-discharge. Multivariable logistic regression was used to adjust for potential confounders., Results: In total, 369 patients were included (control: n = 195, intervention: n = 174). The proportion of patients with at least 1 ADE did not statistically significant differ between the intervention and control group (general teaching hospital: 59% vs. 67%, OR adj 0.70 [95% CI 0.38-1.31], university hospital: 63% vs 50%, OR adj 1.76 [95% CI 0.75-4.13])., Conclusion: The transitional pharmaceutical care program did not decrease the proportion of patients with ADEs after discharge. ADEs after discharge were common and more than 50% of patients reported at least 1 ADE. A process evaluation is needed to gain insight into how a transitional pharmaceutical care program could diminish those ADEs., (Copyright © 2021. Published by Elsevier Inc.)

Introduction: Lung cancer and its treatment cause a wide range of symptoms impacting the patients' health-related quality of life (HRQoL). The use of patient-reported outcomes (PRO) to monitor symptoms during and after cancer treatment has been shown not only to improve symptom management but also to improve HRQoL and overall survival (OS). Collectively, these results favour implementation of PRO-symptom monitoring in daily clinical care. However, these promising outcomes have been obtained under trial conditions in which patients were selected based on stringent inclusion criteria, and in countries with a dissimilar healthcare system than in the Netherlands.The primary aim of the SYMptom monitoring with Patient-Reported Outcomes using a web application among patients with Lung cancer in the Netherlands (SYMPRO-Lung) study is to evaluate the effect of PRO-symptom monitoring during and after lung cancer treatment on HRQoL in daily clinical practice. Secondary objectives include assessing the effect of PRO-symptom monitoring on progression-free survival, OS, the incidence and grade of PRO symptoms, medication adherence, implementation fidelity and cost-effectiveness., Methods and Analysis: The SYMPRO-Lung study is a prospective, multicentre trial with a stepped wedge cluster randomised design. Study participants (n=292 intervention, n=292 controls) include patients with lung cancer (stages I-IV) starting treatment with surgery, systemic treatment, targeted treatment and/or radiotherapy.Every participating centre will consecutively switch from the control period to the intervention period, in which patients report their symptoms weekly via an online tool. In the intervention group, we evaluate two alert approaches: the active and reactive approach. If the symptoms exceed a predefined threshold, an alert is sent to the healthcare provider (active approach) or to the patient (reactive approach). Both the control and intervention group complete HRQoL questionnaires at 4 time points: at baseline, 15 weeks, 6 months and 1-year post treatment). Differences in HRQoL between the groups will be compared using linear mixed modelling analyses, accounting for within-centre clustering, potential time effects and confounding., Ethics and Dissemination: The study protocol was approved by the Institutional Review Board and the Medical Ethics Committee of the Amsterdam UMC (under number NL 68440.029.18) and the institutional review boards of the participating study sites. The dissemination of the results will be conducted through publication in peer-reviewed journals and through scientific conferences., Trial Registration Number: Trial register identifier: Netherlands Trial register Trial NL7897. Date of registration: 24 July 2019. https://www.trialregister.nl/trial/7897., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: For over more than a decade, low-dose amitriptyline and mirtazapine are prescribed off-label for insomnia. However, placebo-controlled evidence on these antidepressants for insomnia is still lacking. Therefore, the present trial aims to assess the effectiveness of low-dose amitriptyline (10-20 mg/day) and mirtazapine (7.5-15 mg/day) in patients with insomnia disorder with difficulty maintaining sleep or early-morning awakening problems in general practice., Methods and Analysis: The Drug REdiscovery: low-dose Amitriptyline and Mirtazapine for INsomnia disorder in General practice (DREAMING) study is a randomised, double-blind, placebo-controlled trial in about 50 general practices. Adults (18-85 years) with insomnia disorder (Diagnostic and Statistical Manual of Mental Disorders-5) who ask their general practitioner (GP) for sleep medication when non-pharmacological treatment is deemed not effective, are eligible., Exclusion Criteria: isolated sleep initiation problem, contraindications for or drug-drug interactions with either amitriptyline or mirtazapine. Participants (n=156) will be randomly assigned to three parallel treatment groups of 16-week treatment with either amitriptyline (one or two tablets of 10 mg/day) or mirtazapine (one or two tablets of 7.5 mg/day) or placebo (one or two tablets) alongside usual GP care. All participants start and end with single dose, but dose can be doubled following GP consultation in week 3. Questionnaire assessments will be conducted at baseline, week 6, 12, 20 and 52. The primary study outcome is self-reported insomnia severity at 6 weeks, measured with the Insomnia Severity Index (ISI) in an intention to treat analysis. Secondary outcomes include subjective sleep quality quantified by sleep indices, daytime functioning and symptoms, safety and treatment evaluation and other sleep care consumption., Ethics and Dissemination: The Medical Ethics Committee of the VU Medical Centre Amsterdam approved this trial. The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences and to key stakeholders., Trial Registration Number: NTR7449., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Overtreatment with cardiometabolic medication in older patients can lead to major adverse events. Timely deprescribing of these medications is therefore essential. Self-reported willingness to stop medication is usually high among older people, still overtreatment with cardiometabolic medication is common and deprescribing is rarely initiated. An important barrier for deprescribing reported by general practitioners is the patients' unwillingness to stop the medication. More insights are needed into the influence of patients' characteristics on their attitudes towards deprescribing and differences in these attitudes between cardiometabolic medication groups., Methods: A survey in older people using cardiometabolic medication using the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire was performed. Participants completed the general rPATD and an adapted version for four medication groups. Linear and ordinal logistic regression were used to assess the influence of age, sex, therapeutic area and number of medications used on the patients' general attitudes towards deprescribing. Univariate analysis was used to compare differences in deprescribing attitudes towards sulfonylureas, insulins, antihypertensive medication and statins., Results: Overall, 314 out of 1143 invited participants completed the survey (median age 76 years, 54% female). Most participants (80%) were satisfied with their medication and willing to stop medications if their doctor said it was possible (88%). Age, sex and therapeutic area had no influence on the general attitudes towards deprescribing. Taking more than ten medicines was significantly associated with a higher perceived medication burden. Antihypertensive medication and insulin were considered more appropriate than statins, and insulin was considered more appropriate than sulfonylureas not favouring deprescribing., Conclusions: The majority of older people using cardiometabolic medication are willing to stop one of their medicines if their doctor said it was possible. Health care providers should take into account that patients perceive some of their medication as more appropriate than other medication when discussing deprescribing.

Purpose: The purpose of this study is to investigate medication intake, perceived barriers and their correlates in adults with type 1 or type 2 diabetes., Methods: In this cross-sectional study, 3,383 Dutch adults with diabetes (42% type 1; 58% type 2) completed the 12-item 'Adherence Starts with Knowledge' questionnaire (ASK-12; total score range: 12-60) and reported socio-demographics, clinical and psychological characteristics and health behaviors. Univariable and multivariable logistic regression analyses were used., Results: Adults with type 1 diabetes had a slightly lower mean ASK-12 score (i.e. more optimal medication intake and fewer perceived barriers) than adults with non-insulin-treated type 2 diabetes. After adjustment for covariates, correlates with suboptimal intake and barriers were fewer severe hypoglycemic events and more depressive symptoms and diabetes-specific distress. In type 2 diabetes, correlates were longer diabetes duration, more depressive symptoms and diabetes-specific distress., Conclusions: Adults with type 1 diabetes showed slightly more optimal medication intake and fewer perceived barriers than adults with non-insulin treated type 2 diabetes. Correlates differed only slightly between diabetes types. The strong association with depressive symptoms and diabetes-specific distress in both diabetes types warrants attention, as improving these outcomes in some people with diabetes might indirectly improve medication intake., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hogervorst, Adriaanse, Hugtenburg, Bot, Speight, Pouwer and Nefs.)

Patients with chronic myeloid leukemia (CML) in deep molecular remission may discontinue tyrosine kinase inhibitor (TKI) treatment without relapse. The present study aims to gain insight into the views of CML patients on TKI treatment discontinuation and identify factors that are associated with their willingness to discontinue treatment. A cross-sectional study, among adult Dutch CML patients was conducted to assess willingness and their views on benefits of and concerns about discontinuation. A total of 185 patients participated of whom 76% were willing to discontinue TKI-treatment. Patients considered the absence of side effects the most important benefit whereas fear of disease recurrence was their most prominent concern. Adequate monitoring was the most important prerequisite for TKI-treatment discontinuation. However, ambiguity with respect to perquisites indicate that patients on long-term TKI treatment should be adequately informed both on the possibility to discontinue treatment and on its benefits, risks, and measures that address risks.

Introduction: This comprehensive observational study aimed to gain insight into adherence to nilotinib and the effect of (non)adherence on exposure (C min ) and treatment outcomes., Methods: Chronic myeloid leukemia (CML) patients using nilotinib were followed for 12 months. Adherence was measured by Medication Event Monitoring System (MEMS), pill count, and Medication Adherence Report Scale (MARS-5). Nilotinib C min and patient-reported outcomes (i.e., quality of life, side effects, beliefs, satisfaction) were measured at baseline, 3, 6, and 12 months., Results: Sixty-eight patients (57.5 ± 15.0 years, 49% female) participated. Median adherence to nilotinib (MEMS and pill count) was ≥ 99% and adherence < 90% was rare. Self-reported nonadherence (MARS-5) increased in the first year of treatment to a third of patients. In line with the strong beliefs in the necessity of taking nilotinib, forgetting to take a dose was more prevalent than intentionally adjusting/skipping doses. Nilotinib C min were generally above the therapeutic target in 95% of patients. Patients reported a variety of side effects, of which fatigue was most frequent. The mean C min was higher in patients who reported severe itching and fatigue. The overall 1-year MMR rate ranged from 47 to 71%., Conclusion: Substantial nonadherence (< 90%) to nilotinib was rare and nilotinib C min were generally above the therapeutic target. Lack of response in our group of patients was not related to nonadherence or inadequate C min . Nevertheless, a considerable number of patients experienced difficulties in adhering to the twice daily fasted dosing regimen, emphasizing the importance of continuous support of medication adherence in CML., Clinical Trial Registration: NTR3992 (Netherlands Trial Register, www.trialregister.nl ).

Background: Deprescribing has been recommended for managing polypharmacy but deprescribing preventive medication in older patients is still uncommon. We aimed to investigate older patients' barriers to and enablers of deprescribing cardiometabolic medication., Methods: Two focus groups were conducted among patients ≥70 years with polypharmacy, including cardiometabolic medication. Purposive sampling through four community pharmacies was used in two regions in the Netherlands. A topic list was developed using literature and the theoretical domains framework (TDF). The meetings were audio recorded, transcribed verbatim and coded using thematic coding, attribute coding and the TDF. In addition, patients were categorized on attitudes towards medication and willingness to stop., Results: The meetings were attended by 17 patients and 1 caregiver (71 to 84 years). In total 15 barriers and 13 enablers were identified within four themes, partly related to beliefs, fears and experiences regarding using or stopping medication, and partly related to the relationship with the health care professional and the conditions to stop. Some patients attributed their wellbeing to their medication and were therefore unwilling to stop. Reducing cardiometabolic medication because of less strict treatment targets confused some patients and was a barrier to deprescribing. Having options to monitor clinical measurements and restart medication were enablers. Patients were only willing to stop cardiometabolic medication when this was proposed by a HCP they trusted. Patients with a positive attitude towards medication varied in their willingness to stop cardiometabolic medication. Patients with a negative attitude towards medication were generally willing to stop medication but still perceived several barriers and may consider some medication as being essential., Conclusion: Fears, beliefs, and experiences regarding using and stopping medication as well as trust in the HCP influence willingness to have medication deprescribed. Attitudes towards medication in general do not necessarily translate into willingness or unwillingness to stop specific medication. For deprescribing cardiometabolic medication, patient involvement when setting new treatment targets and monitoring the effects on short-term outcomes are important., (Copyright © 2020 Crutzen, Baas, Abou, van den Born-Bondt, Hugtenburg, Bouvy, Heringa, Taxis and Denig.)

Objectives: Taking advantage of its food-dependent bioavailability, the present study investigated the effect of a reduced dose taken with real-life meals on the pharmacokinetics (PK) of nilotinib in chronic myeloid leukaemia (CML) patients., Methods: Nilotinib was taken fasted (300 mg BID, days 1-4) or with real-life meals (200 mg BID, days 5-11). Rich sampling (days 1, 3, 8, 11) allowed for non-compartmental PK analysis. Nilotinib exposure (AUC 0-12 h  -C min -C max ) and its intra- and interpatient variability were compared between the two regimens. Adverse events were recorded by means of a patient diary and ECG monitoring., Results: Fifteen patients aged 40-74 years participated. Nilotinib PK following 200 mg BID taken with a meal strongly resembled that of 300 mg BID taken fasted (C min percentile (P)10-P90: 665-1404 ng/mL and 557-1743 ng/mL, respectively). Meals delayed nilotinib absorption. Intra- and interpatient variability were not increased by intake with meals. Nilotinib with food was well tolerated., Conclusion: With support of therapeutic drug monitoring, the use of a reduced 200 mg nilotinib dose with real-life meals seems feasible and safe. Future (confirmatory) studies should further explore the usefulness of nilotinib dosing together with food, including the relationship with treatment efficacy as well as long-term effects on quality of life., Clinical Trial Registration: NTR5000 (Netherlands Trial Register, www.trialregister.nl)., (© 2020 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Some drug safety issues communicated through direct healthcare professional communications (DHPCs) receive substantial media coverage, while others do not., Objectives: The objective of this study was to assess the extent of coverage of drug safety issues that have been communicated through DHPCs in newspapers and social media. A secondary aim was to explore which determinants may be associated with media coverage., Methods: Newspaper articles covering drug safety issues communicated through 387 DHPCs published between 2001 and 2015 were retrieved from LexisNexis Academic™. Social media postings were retrieved from Coosto™ for drugs included in 220 DHPCs published between 2010 and 2015. Coverage of DHPCs by newspapers and social media was assessed during the 2-month and 14-day time periods following issuance of the DHPC, respectively. Multivariate logistic regression was used to assess potential DHPC- and drug-related determinants of media coverage., Results: 41 (10.6%) DHPC safety issues were covered in newspaper articles. Newspaper coverage was associated with drugs without a specialist indication [adjusted odds ratio 5.32; 95% confidence interval (2.64-10.73)]. Negative associations were seen for time since market approval [3-5 years 0.30; (0.11-0.82), 6-11 years 0.18; (0.06-0.58)] and year of the DHPC [0.88; (0.81-0.96)]. In the social media, 180 (81.8%) drugs mentioned in 220 DHPCs were covered. Social media coverage was associated with drugs without a specialist indication [6.92; (1.56-30.64)], and for DHPCs communicating clinical safety issues [5.46; (2.03-14.66)]., Conclusions: Newspapers covered a small proportion of DHPC safety issues only. Most drugs mentioned in DHPCs were covered in social media. Coverage in both media were higher for drugs without a specialist indication.

Background: In accordance with current guidelines, proton pump inhibitors (PPIs) are now generally prescribed as a protective co-medication in patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or low-dose acetylsalicylic acid (LDASA). However, less attention is paid to the corresponding discontinuation of a PPI after cessation of NSAID or LDASA treatment., Objective: The aim of this study was to assess the extent of inappropriate PPI use, as the proportion of patients who started a PPI as a protective co-medication but continued using these drugs after cessation of NSAID and LDASA treatment. We also sought to estimate the potential cost savings and effect gains of discontinuing inappropriate PPI use and the resulting decrease in adverse effects and their detrimental consequences., Methods: Pharmacy dispensing data were used to map inappropriate PPI use in 2014 for community-dwelling patients. Strategies with or without PPI continuation were compared in the cost-utility analysis for a time horizon of 5 years from a healthcare perspective. Subsequently, incremental costs and effects (quality-adjusted life-years) were estimated with a Markov model., Results: Related to NSAID and LDASA treatment, 11.0% and 5%, respectively, of the PPI users were found to inappropriately continue PPI co-treatment. Discontinuation in 71- to 80-year-old patients suggested cost savings of €170.46 (95% confidence interval 75-282) at a 0.003 (95% confidence interval 0.001-0.005) quality-adjusted life-year increase. The total budget impact of stopping inappropriate PPI use related to NSAID/LDASA treatment in the Netherlands would amount to almost €1,050,000 after 1 year. Correspondingly, successful interventions to stop a patient's inappropriate use would cost up to €29 and probably would pay for themselves in the following years., Conclusions: A substantial number of patients inappropriately continue to use a PPI after cessation of NSAID or LDASA treatment. Because adverse effects and their detrimental consequences are avoided, interventions to stop inappropriate PPI use, particularly in older patients, are likely to pay for themselves.