Healthcare professionals' experiences with the use of antipsychotics in dementia.

Background: Antipsychotics are commonly administered to nursing home residents with dementia, despite the associated risk of severe adverse events. Objective: This study aimed to explore healthcare professionals' experiences in caring for nursing home residents with dementia, with a focus on rationales behind the use of antipsychotics. Method: Twelve semi-structured interviews with healthcare professionals' from Danish nursing homes were conducted and analyzed using the method Systematic Text Condensation. Results: Nonpharmacological interventions were reported as the primary approach to care and the first-choice treatment for behavioral and psychological symptoms of dementia (BPSD). Use of antipsychotics was considered to serve as a last resort, reserved for residents with severe symptoms. However, most informants preferred a more limited use. The study identified four main barriers to reduce the use of antipsychotics: "Scarcity of resources", "Perceiving antipsychotic use to provide relieve", "Reluctance towards deprescribing" and "Limited access to medical counseling", and three potential enablers: "Updating knowledge and nonpharmacological competencies", "Management support and clear procedures" and "Regularity in interdisciplinary collaboration". Conclusion: The treatment and care were reported as primarily following guidelines in BPSD. Several barriers were perceived to challenge the healthcare professionals' preference of limited use of antipsychotics. To further reduce the use, this study highlights the importance of understanding the adverse effects caused by limited resources, enhancing employee knowledge and competencies and ensuring regular interprofessional collaboration for assessing and reassessing the need to use antipsychotics.

Establishment of a children's Drugs and Therapeutics Committee to ensure evidence-based and cost-effective medical treatment for children.

The prevalence of undocumented medical treatments among children is a significant issue, as well as many EU countries lack access to newly developed children-friendly medicines. Consequently, there is a pressing need for supplementary resources that can facilitate informed decision-making regarding children's medication. We therefore aim to describe the process of establishing a children's Drug and Therapeutics Committee (cDTC), as well as the preparing and implementation of recommendations for children in the capital region of Denmark. Following the guidelines outlined by the World Health Organization, we established a cDTC, and recommendations for paediatric medication practice were constructed from assessments of medication use patterns among children in the capital region between 2019 and 2021. The recommendations were meticulously crafted based on evaluation of the current marketing authorization landscape and existing best available evidence. In 2019, the capital region established the first cDTC supported by expert councils and an editorial board. A total of 2429 purchase item numbers covering 1 222 846 defined daily doses and 592 088 purchased packages covering 10 200 000 defined daily doses were identified in the secondary and primary sectors, respectively. Three comprehensive lists covering recommendations for newborns and children were published between 2021 and 2020 totaling 331 recommended pharmaceutical products. The recommendations primarily intended for use in the secondary healthcare sector were implemented through the revision of 38 paediatric- and six neonatal product ranges throughout capital region. In conclusion, recommendation lists for children governed by a cDTC provide a rational auxiliary tool that can be immediately implemented in the clinic.

Protocol for DEprescribing and Care to reduce Antipsychotics in Dementia (DECADE)-A hybrid effectiveness-implementation pilot study.

INTRODUCTION: Behavioural and psychological symptoms of dementia (BPSD) should only rarely and briefly be treated with antipsychotics. Despite recommendations to the contrary, the use of antipsychotics in nursing home residents with dementia is widespread and followed by serious adverse effects. Intervention studies on methods to reduce the use of antipsychotics in persons with dementia are few and needed. The aim of this protocol is to describe the rationale and content of the intervention DEprescribing and Care to reduce Antipsychotics in DEmentia (DECADE)-a hybrid effectiveness-implementation pilot study. MATERIALS AND METHODS: This is a protocol of a prospective hybrid effectiveness-implementation pilot study. The primary aim of DECADE is to reduce the use of antipsychotic drugs by 50% in 50% of nursing home residents with dementia while maintaining or improving BPSD. The intervention is implemented in six nursing homes including approximately 190 residents with dementia and consists of Academic Detailing, medication review, education of nursing home staff, and care plans. The evaluation of feasibility and potential effectiveness is an overall assessment of all clinical and process outcomes. Logistic regression analyses will be used to investigate factors characterizing situations with prescription of antipsychotics. BPSD is analysed with a before- and after design using self-controlled case series methods and the use of antipsychotics is analysed as interrupted time series. DISCUSSION: This protocol describes a study that will provide an indication of DECADE effectiveness and a model for upscaling and further evaluation in a controlled design.

Polypharmacy and cross-sectoral collaboration.

Medication review is a pillar in the new recommendations from the Danish Health Authorities regarding patients with multimorbidity and polypharmacy. This review finds that general practitioners should be primary in coordinating medication. Medication reviews can be conducted differently with various co-interventions to try to improve cross-sectoral collaboration. It seems imperative that the interventions involve improved communication for optimal sharing and implementation of changes to the medication with primary care in a key role.

Definition of and delimitation of polyfarmaci.

At present, there is no clear and universal definition of polypharmacy. This review summarises the most common definitions and discusses the challenges in finding one suitable definition. Most of the literature has defined polypharmacy as the simultaneous use of five or more drugs. It is known that polypharmacy can lead to an increased risk of adverse health outcomes. However, a lot of medicine is not necessarily too much medicine. Preferentially, a definition should therefore differentiate between appropriate and inappropriate polypharmacy. As a universal definition has not yet been established, it is important to consider the definition used in the literature describing polypharmacy.

Co-Developing Patient-Centered Information: A Focus Group Study of Asthma Patients' Preferences and Attitudes towards New Medical Treatment Guidelines.

Studies have suggested patient involvement as an important factor when seeking to improve patient-centered information. The objective of this study was to explore asthma patients' preferences regarding information when co-developing patient-centered information and how they evaluate the material as a supportive initiative when they are deciding whether to switch to the new MART approach. The study was performed as a case study involving qualitative semi-structured focus group interviews inspired by the theoretical framework for supporting patient involvement in research. Two focus group interviews were held, with a total of nine interviewees. Three main interview themes were found: the identification of important topics about the new MART approach, feedback on the design and the preferred implementation of written patient-centered information. The asthma patients preferred written patient-centered material to be short and to be presented briefly at the local community pharmacy, and then discussed more thoroughly with their general practitioner (GP) at a consultation. In conclusion, this study identified asthma patients' preferences when co-developing written patient-centered information and how the patients favored the material to be implemented as a support to them in their decision on whether to change asthma treatment.

Patient engagement in pharmaceutical development: Where are we? - Report from a symposium.

In recent years, the term "patient engagement" has found its way into healthcare and specifically into the field of drug development. To better understand the actual status of "patient engagement" in drug development, a symposium was organized by the Drug Research Academy of the University of Copenhagen (Denmark) on November 16, 2022. The symposium brought together experts from regulatory authorities, industry, academia and patients to share their views and experience of and with patient engagement in drug product development. The symposium led to intensive discussions among the speakers and the audience, confirming that viewpoints and experiences of the different stakeholder provide important input into the promoting patient engagement along the entire drug development life cycle.

A Shift in Asthma Treatment According to New Guidelines: An Evaluation of Asthma Patients' Attitudes towards Treatment Change.

The Global Initiative for Asthma (GINA) has presented a shift in pharmacological asthma treatment. The objective of this study was to explore factors influencing a successful switch to a new asthma treatment approach with a focus on asthma patients' attitudes toward treatment change and supportive initiatives. This study was performed as a case study involving a quantitative questionnaire and a qualitative semi-structured interview. A total of 284 responses were collected from the questionnaire, and 141 responses were included. The results showed that asthma patients thought that effectiveness of the new treatment approach, doctor recommendation, and knowledge of the new treatment approach were the most important factors influencing treatment change considerations. Nine interviews were conducted where the main themes were barriers to a shift in asthma treatment, such as effects and side effects of the new treatment, the role of the general practitioner (GP) and conflicts in agreeing on a treatment plan; as well as facilitators to a shift in asthma treatment, such as trust in the GP and easier inhaler use. We found several supportive initiatives, such as consultation with the GP, handing out information leaflets and a consultation at the pharmacy. In conclusion, this study uniquely identified factors that may influence successful treatment shifts in asthma patients that may be instrumental in understanding similar situations in other pharmacological settings.

Tailoring a complex intervention to reduce antidepressants in institutionalized older persons with dementia.

INTRODUCTION: First-line treatment for behavioral and psychiatric symptoms of dementia is non-pharmacological. Still, psychotropic medication is widely used, despite its limited effect and harmful side-effects. More than half of all nursing home residents with dementia receive antidepressants, even though deprescribing is safe and feasible. Interventions to promote deprescribing of antidepressants in nursing homes are few and complex. To optimize the deprescribing process through an intervention, transparency for the development of the intervention is needed. We aim to describe the steps in the development and tailoring of an intervention targeting GPs, nursing home staff, and relatives to enhance collaboration on reducing the use of antidepressants in institutionalized older persons with dementia in Denmark. METHOD: A step-wise process guided by the core elements in the Medical Research Council constituted the tailoring process. Five steps were included; 1) a literature search, 2) interviews with stakeholders, 3) drafting the intervention prototype, 4) professionals' assessment of the intervention, and 5) refinement of the intervention. The steps were conducted from June 2020 to June 2022. RESULTS: Based on the literature search, interviews with stakeholders, and professionals' assessment of the intervention, four main themes were identified; 1) focusing on antidepressants, 2) importance of professional qualifications, 3) collaboration and communication, and 4) patient and relative involvement. They guided intervention development and refinement of the final intervention, which included 1) a case-based training course and 2) a dialog tool including a symptom assessment scale to be used in a structured consultation at the nursing home. CONCLUSION: This study presents a detailed account of the tailoring process for a complex intervention to optimize deprescribing of antidepressants for older persons with dementia at nursing homes. By presenting a thorough development process, we expect to achieve increased adherence to the intervention which is currently being tested in an ongoing cluster randomized controlled trial. The transparency of the process will also increase the future development of other similar complex interventions.

Exploring the value of a multidisciplinary-led medication review for elderly individuals at a long-term care facility performed by four different health-care professions in an equal and closely integrated collaboration.

Background: The increasing population of elderly individuals had led to an increasing number of polypharmacy patients. Polypharmacy increases the risk of adverse drug reactions and hospitalization. One means to combat polypharmacy involves performing medication reviews, which can be conducted by different methods and stakeholders. Objective: The study objective was to explore the value of involving different health-care professions in medication reviews at an equal and closely integrated collaborative physical meeting for elderly individuals at a long-term care facility. A specific focus was to explore the contributions and opinions of the different health-care professionals regarding the medication review process. Materials and Methods: A single case study was applied to perform an in-depth study of a group of health-care professionals performing medication reviews in collaboration. Hence, the study was performed in two settings: 1) the practical execution of medication reviews at a long-term care facility in an interprofessional team and 2) qualitative semi-structured interviews conducted to explore the forms of work done by different professional groups in performing an interdisciplinary medication review. Results: Forty-nine residents from a long-term care facility were included in the study and were offered a medication review. In total, they reported 573 prescriptions, for which 150 changes were recommended by the interprofessional team. At the 3- and 8-month follow-ups, 30.0% and 49.5% of the accepted recommendations had been implemented, respectively. According to the interview, the results reveal that the interdisciplinarity of the interprofessional team was perceived as a great advantage to the results of the medication reviews. Conclusion: The results suggest that performing medication reviews in interprofessional collaboration improves the perceived quality of such reviews with a more complete picture of the residents and their medications, leading to more personalized recommendations and resulting in optimized medication reviews for the individual patients.

[Predictive biomarkers in medical treatment].

Use of predictive biomarkers plays a promising role in stratifying patients to a more effective medical treatment with less side effects. This review provides a brief overview in a Danish context of the potential of applying pharmacogenomics (PGx) including companion diagnostics (CDx) in daily clinical practice based on the current knowledge and regulation from the FDA and EMA, Summary of Product Characteristics (SPC), PharmGKB (pharmacogenomics knowledge resource providing clinical dosing guidelines) and partly promedicin.dk. Also, the barriers to more widespread use are being addressed.

Exploration of Symptom Scale as an Outcome for Deprescribing: A Medication Review Study in Nursing Homes.

The use of inappropriate medication is an increasing problem among the elderly, leading to hospitalizations, mortality, adverse effects, and lower quality of life (QoL). Deprescribing interventions (e.g., medication reviews (MRs)) have been examined as a possible remedy for this problem. In order to be able to evaluate the potential benefits and harms of a deprescribing intervention, quality of life (QoL) has increasingly been used as an outcome. The sensitivity of QoL measurements may, however, not be sufficient to detect a change in specific disease symptoms, e.g., a flair-up in symptoms or relief of side effects after deprescribing. Using symptom assessments as an outcome, we might be able to identify and evaluate the adverse effects of overmedication and deprescribing alike. The objective of this study was to explore whether symptom assessment is a feasible and valuable method of evaluating outcomes of MRs among the elderly in nursing homes. To the best of our knowledge, this has not been investigated before. We performed a feasibility study based on an experimental design and conducted MRs for elderly patients in nursing homes. Their symptoms were registered at baseline and at a follow-up 3 months after performing the MR. In total, 86 patients, corresponding to 68% of the included patients, received the MR and completed the symptom questionnaires as well as the QoL measurements at baseline and follow-up, respectively. Forty-eight of these patients had at least one deprescribing recommendation implemented. Overall, a tendency towards the improvement of most symptoms was seen after deprescribing, which correlated with the tendencies observed for the QoL measurements. Remarkably, deprescribing did not cause a deterioration of symptoms or QoL, which might otherwise be expected for patients of this age group, of whom the health is often rapidly declining. In conclusion, it was found that symptom assessments were feasible among nursing home residents and resulted in additional relevant information about the potential benefits and harms of deprescribing. It is thus recommended to further explore the use of symptom assessment as an outcome of deprescribing interventions, e.g., in a controlled trial.

A systematic review of blood eosinophils and continued treatment with inhaled corticosteroids in patients with COPD.

Inhaled corticosteroid (ICS) in patients with chronic obstructive pulmonary disease (COPD) has been debated for 20 years. In our systematic literature review and meta-analysis, we addressed the following: Should patients with COPD and a blood eosinophil count (EOS) of, respectively, a) < 150 cells/µl, b) 150-300 cells/µl, and c) > 300 cells/µl continue treatment with ICS? Protocol registered in PROSPERO (CRD42020178110) and funded by the Danish Health Authority. We searched Medline, Embase, CINAHL and Cochrane Central on 22nd July 2020 for randomized controlled trials (RCT) of ICS treatment in patients with COPD (≥40 years, no current asthma), which analyzed outcomes by EOS count and where >50% of patients used ICS prior. We used the GRADE method. Meta-analyzes for the outcomes were divided into EOS subgroups and analyzed for differences. We identified 11 RCTs with a total of 29,654 patients. A significant difference (p < 0.00001) between the three subgroups' reduction of risk of moderate to severe exacerbation was found. Rate ratios for EOS counts: <150 cells/µL was 0.88 (95%CI: 0.83, 0.94); 150-300 cells/µL was 0.80 (95%CI: 0.69, 0.94); >300 cells/µL was 0.57 (95%CI: 0.49, 0.66). Overall, the certainty of the effect estimates was low to very low due to risk of bias, unexplained heterogeneity, few RCTs, and wide confidence intervals. A clear correlation was demonstrated between effect of continued ICS treatment (number of exacerbations, lung function, and quality of life) and increasing EOS count. Our meta-analyses suggested that treatment with ICS seemed beneficial for everyone except patients with EOS count below 150 cells/µl.

Deprescribing: What is the gold standard? Themes that characterized the discussions at the first Danish symposium on evidence-based deprescribing.

The first Danish symposium on evidence-based deprescribing was held in September 2019. The symposium aimed to increase the awareness of deprescribing in general, to discuss the importance of deprescribing, and, thus, a potential consensus on key issues on a national deprescribing agenda. The invited keynote speaker, Barbara Farrell, from the Bruyére Research Institute, Ottawa, Canada, presented their thorough work on deprescribing guideline development and application. The symposium consisted of two parts: Part 1 concentrated on establishing the need for deprescribing in our society. Part 2 consisted of a panel debate that put the practical application and implementation of deprescribing in perspective to the input from the audience and the structure of the Danish healthcare system. The panelists represented key stakeholders, e.g., clinical pharmacists, general practitioners, hospital doctors, Danish Health Authority representatives, health politicians concerning deprescribing in Denmark. The event allowed 145 participants to discuss the importance of implementing deprescribing in a Danish setting. This commentary highlights and discusses the major themes that characterized the symposium: "why deprescribe?", "deprescribing research" and a theme dedicated to "problems of concern." The emergence of these themes formed the basis for the discussion of new strategies and a proposal for a future gold standard to succeed in deprescribing.

Comparison of Multidrug Use in the General Population and among Persons with Diabetes in Denmark for Drugs Having Pharmacogenomics (PGx) Based Dosing Guidelines.

BACKGROUND: This study measures the use of drugs within the therapeutic areas of antithrombotic agents (B01), the cardiovascular system (C), analgesics (N02), psycholeptics (N05), and psychoanaleptics (N06) among the general population (GP) in comparison to persons with diabetes in Denmark. The study focuses on drugs having pharmacogenomics (PGx) based dosing guidelines for CYP2D6, CYP2C19, and SLCO1B1 to explore the potential of applying PGx-based decision-making into clinical practice taking drug-drug interactions (DDI) and drug-gene interactions (DGI) into account. METHODS: This study is cross-sectional, using The Danish Register of Medicinal Product Statistics as the source to retrieve drug consumption data. RESULTS: The prevalence of use in particular for antithrombotic agents (B01) and cardiovascular drugs (C) increases significantly by 4 to 6 times for diabetic users compared to the GP, whereas the increase for analgesics (N02), psycoleptics, and psychoanaleptics (N06) was somewhat less (2-3 times). The five most used PGx drugs, both in the GP and among persons with diabetes, were pantoprazole, simvastatin, atorvastatin, metoprolol, and tramadol. The prevalence of use for persons with diabetes compared to the GP (prevalence ratio) increased by an average factor of 2.9 for all PGx drugs measured. In addition, the prevalence of use of combinations of PGx drugs was 4.6 times higher for persons with diabetes compared to GP. In conclusion, the findings of this study clearly show that a large fraction of persons with diabetes are exposed to drugs or drug combinations for which there exist PGx-based dosing guidelines related to CYP2D6, CYP2C19, and SLCO1B1. This further supports the notion of accessing and accounting for not only DDI but also DGI and phenoconversion in clinical decision-making, with a particular focus on persons with diabetes.

The Barriers and Facilitators of Different Stakeholders When Deprescribing Benzodiazepine Receptor Agonists in Older Patients-A Systematic Review.

Treatment of older patients with benzodiazepines and Z-drugs (BZRA) is associated with an increased risk of side effects. However, this treatment is still used among these patients. Deprescribing can be a tool to reduce inappropriate medication. This review aims to identify and compare barriers and facilitators of stakeholders involved in BZRA deprescribing in older patients and uncover potential gaps in the research field. The search was conducted in PubMed, EMBASE, PsycINFO, and Cochrane Library. Ten articles based on qualitative data on BZRA deprescribing in older patients (≥65 years) published between 2005-2020 were included. Six articles referred to patients as stakeholders, two referred to physicians, and one to nurses and caregivers, respectively, indicating a need for more studies in the field. More barriers than facilitators were identified. Important findings were the patient willingness to deprescribe BZRA compared to physicians, who did not mention deprescribing to patients due to barriers such as expected patient resistance. Nurses mentioned barriers like lack of knowledge and the feeling that their options were not valued by physicians; education was found to be a shared deprescribing facilitator among the stakeholders. Being aware of deprescribing barriers and facilitators can be helpful in future successful deprescribing interventions.

Use of Clopidogrel and Proton Pump Inhibitors Alone or in Combinations in Persons with Diabetes in Denmark; Potential for CYP2C19 Genotype-Guided Drug Therapy.

BACKGROUND: Clopidogrel and proton pump inhibitors (PPIs) are among the most used drugs in Denmark for which there exists pharmacogenomics (PGx)-based dosing guidelines and FDA annotations. In this study, we further scrutinized the use of clopidogrel and PPIs when prescriptions were redeemed from Danish Pharmacies alone or in combination in the Danish population and among persons with diabetes in Denmark. The focus deals with the potential of applying PGx-guided antiplatelet therapy taking both drug-drug interactions (DDI) and drug-gene interactions (DGI) into account. METHODS: The Danish Register of Medicinal Product Statistics was the source to retrieve consumption data. RESULTS: The consumption of PPIs and clopidogrel in terms of prevalence (users/1000 inhabitants) increased over a five-year period by 6.3% to 103.1 (PPIs) and by 41.7% to 22.1 (clopidogrel), respectively. The prevalence of the use of clopidogrel and PPIs in persons with diabetes are 3.8 and 2.1-2.8 times higher compared to the general population. When redeemed in combination, the prevalence increased to 4.7. The most used combination was clopidogrel and pantoprazole. CONCLUSIONS: The use of clopidogrel and PPIs either alone or in combination is quite widespread, in particular among the elderly and persons with diabetes. This further supports the emerging need of accessing and accounting for not only DDI but also for applying PGx-guided drug therapy in clinical decision making for antiplatelet therapy with clopidogrel having a particular focus on persons with diabetes and the elderly.

Drug Use among Nursing Home Residents in Denmark for Drugs Having Pharmacogenomics Based (PGx) Dosing Guidelines: Potential for Preemptive PGx Testing.

BACKGROUND: Polypharmacy is most prevalent among the elderly population and in particular among nursing home residents. The frequency of the use of drugs with pharmacogenomics (PGx)-based dosing guidelines for CYP2D6, CYP2C9, CYP2C19 and SLCO1B1 were measured among nursing home residents in the Capital Region of Denmark as well as drug-drug interactions. The aim was to evaluate the potential of applying PGx-test as a supportive tool in medication reviews. METHODS: Drug use among nursing home residents during 2017-2018 in the Capital Region of Copenhagen, for drugs with PGx-based dosing guidelines available through the PharmGKB website, were measured. Drug-drug interactions were scored in severity by using drug interaction checkers. RESULTS: The number of residents using drugs with PGx-based actionable dosing guidelines (AG) were 119 out of 141 residents (84.3%). Of these 119 residents, 87 residents used drugs with AG for CYP2C19, 47 residents for CYP2D6, and 42 residents for SLCO1B1. In addition, 30 residents used two drugs with an AG for CYP2C19, and for CYP2D6, it was only seven residents. The most used drugs with AG were clopidogrel (42), pantoprazole (32), simvastatin (30), metoprolol (25), and citalopram (24). The most frequent drug interactions found with warnings were combinations of proton pump inhibitors and clopidogrel underscoring the potential for phenoconversion. CONCLUSION: this study clearly showed that the majority of the nursing home residents were exposed to drugs or drug combinations for which there exist PGx-based AG. This indeed supports the notion of accessing and accounting for not only drug-gene but also drug-drug-gene interactions as a supplement to medication review.

Systematic Medication Review in General Practice by an Interdisciplinary Team: A thorough but Laborious Method to Address Polypharmacy among Elderly Patients.

Polypharmacy increases the risk of hospitalization but may be reduced by medication review. The study objective is to describe and evaluate a method for conducting medication review in general practice by an interdisciplinary medication team of pharmacists and physicians-in this case conducted by a team from the Department of Clinical Pharmacology-based on information concerning medication, diagnosis, relevant laboratory data and medical history supplied by the general practitioner. We discussed the medication review with the patients' general practitioners and received feedback from them regarding acceptance rates of the recommended changes. Ninety-four patients with a total of 1471 prescriptions were included. A medication change was recommended for nearly half of the prescriptions (48%); at least one change of medication was recommended for all patients. The acceptance rate for recommended medication changes was 55%, corresponding to a mean of 4.2 accepted recommendations per patient. For 18% of all 1471 prescriptions, the general practitioner agreed either to discontinue (stop the medication completely) or reduce the dose of the medication. This method is thorough, but since it requires several healthcare professionals, it is rather time-consuming. There is a need to support medication review in general practice, but although this method may be too time consuming in most cases, it may nevertheless prove to be a useful tool managing the most complicated patients.