Exploring adherence in patients with advanced breast cancer: focus on CDK4/6 inhibitors.

Treatment adherence is crucial for optimal outcomes in advanced breast cancer, but can be challenging due to various factors, i.e. patients' attitudes and behavior upon diagnosis, and complex therapies with high adverse effect rates. Our aim was to explore the adherence to oral anticancer medications (OAM) in women with advanced breast cancer, focusing on cyclin-dependent kinase 4 and 6 inhibitors (CDKI), and identify factors associated with the adherence. We conducted a cross-sectional study at the University Hospital Centre Zagreb, Croatia, involving women with stage IV advanced breast cancer receiving OAM. Data collection included a questionnaire assessing socio-demographic and clinical information, Beck Depression Inventory-II for depressive symptoms, Medication Adherence Report Scale (MARS-5) for adherence to OAM, and Beliefs about Medicines Questionnaire. Plasma concentrations of CDKI were confirmed by LC-MS/MS in three randomly selected participants. A total of 89 women were included. The most prescribed OAMs were anti-estrogen (71.3 %) and CDKI (60.9 %). MARS-5 scores (mean: 24.1 ± 1.6) correlated with CDKI plasma concentrations. Forgetfulness was the primary reason for non-adherence (25.9 %). Women receiving CDKI (p = 0.018), without depressive symptomatology (p = 0.043), and with more positive beliefs about medicines were more adherent (p < 0.05). This study enhances understanding of medication adherence in advanced breast cancer and identifies influential factors.

Prevalence of potentially inappropriate prescribing in older adults in Central and Eastern Europe: a systematic review and synthesis without meta-analysis.

We aimed to systematically review the prevalence of potentially inappropriate prescribing (PIP) in older adults in Central and Eastern Europe (CEE) in all care settings. We searched Embase and MEDLINE (up to June 2019) and checked the reference lists of the included studies and relevant reviews. Eligible studies used validated explicit or implicit tools to assess the PIP prevalence in older adults in CEE. All study designs were considered, except case‒control studies and case series. We assessed the risk of bias using the Joanna Briggs Institute Prevalence Critical Appraisal Tool and the certainty of evidence using the GRADE approach. Meta-analysis was inappropriate due to heterogeneity in the outcome measurements. Therefore, we used the synthesis without meta-analysis approach-summarizing effect estimates method. This review included twenty-seven studies with 139,693 participants. Most studies were cross-sectional and conducted in high-income countries. The data synthesis across 26 studies revealed the PIP prevalence: the median was 34.6%, the interquartile range was 25.9-63.2%, and the range was 6.5-95.8%. The certainty of this evidence was very low due to the risk of bias, imprecision, and inconsistency. These findings show that PIP is a prevalent issue in the CEE region. Further well-designed studies conducted across countries are needed to strengthen the existing evidence and increase the generalizability of findings.

A Need for Benzodiazepine Deprescribing in the COVID-19 Pandemic: A Cohort Study.

The COVID-19 pandemic has had a negative impact on patients' mental health. The aim of this study was to explore whether the pandemic influenced the use and prescription of benzodiazepines and increased the need for community pharmacist involvement in counselling on deprescribing. Electronic prescription-related data from one pharmacy in Croatia were retrospectively collected for the COVID-19 period (April 2020 to March 2021) and compared with pre-COVID-19 (April 2019 to March 2020) data. Data were collected for patients diagnosed with anxiety disorders who filled out more than one prescription for benzodiazepines, and included age, sex, number of medicines, benzodiazepines, and comorbidities. A total of 1290 benzodiazepine users were identified; of these, 32.87% started using benzodiazepines during the COVID-19 period, while 35.2% continued with benzodiazepine use. More than half of all benzodiazepine users were identified as potential deprescribing candidates (dispensed more than three prescriptions). Women, older patients, multimorbid individuals, and patients with polypharmacy were more likely to use benzodiazepines for a prolonged period. The results show a negative trend of benzodiazepine usage among community-dwelling patients during the pandemic. Community pharmacists can identify potential candidates for deprescribing and initiate a process that ensures more rational use of benzodiazepines and increases the safety of treatment.

Reimbursed medication adherence enhancing interventions in 12 european countries: Current state of the art and future challenges.

Background: Medication non-adherence jeopardises the effectiveness of chronic therapies and negatively affects financial sustainability of healthcare systems. Available medication adherence-enhancing interventions (MAEIs) are utilised infrequently, and even more rarely reimbursed. The aim of this paper was to review reimbursed MAEIs across selected European countries. Methods: Data on reimbursed MAEIs were collected from European countries at the ENABLE Cost Action expert meeting in September 2021. The identified MAEIs were analysed and clustered according to their characteristics, direct vs. indirect relation to adherence, and the targeted adherence phase. Results: Out of 12 contributing countries, 10 reported reimbursed MAEIs, 28 in total, of which 20 were identified as MAEIs targeting adherence directly. Reimbursed MAEIs were most often performed by either doctors (n = 6), nurses (n = 6), or pharmacists (n = 3). The most common types of MAEIs were education (n = 6), medication regimen management (n = 5), and adherence monitoring feedback (n = 4). Only seven reimbursed MAEIs were technology-mediated, whereas 11 addressed two interlinked phases of medication adherence, i.e., implementation and persistence. Conclusion: Our review highlights the scarcity of reimbursed MAEIs across the selected European countries, and calls for their more frequent use and reimbursement.

Reimbursed Medication Adherence Enhancing Interventions in European Countries: Results of the EUREcA Study.

Introduction: Current literature lacks detailed understanding of the reimbursement framework of medication adherence enhancing interventions (MAEIs). As part of the ENABLE COST Action, the EUREcA ("EUropen REimbursement strategies for interventions targeting medication Adherence") study aimed to provide an in-depth overview of reimbursed MAEIs currently available in European countries at national and regional levels and to pave the way for further MAEIs to be implemented in the future. Methods: A web-based, cross-sectional survey was performed across 38 European countries and Israel. The survey questionnaire was developed as a result of an iterative process of discussion informed by a desk review. The survey was performed among invited ENABLE collaborators from June to July 2021. Besides descriptive analysis, association between country income and health care expenditure, and the availability of reimbursed MAEIs were also assessed. Results: The survey identified 13 reimbursed MAEIs in nine countries: multi-dose drug dispensing (n = 5), medication review (n = 4), smart device (n = 2), mobile application (n = 1), and patient education (n = 1). The median GDP per capita of countries having ≥1 reimbursed MAEI was significantly higher compared to countries having no reimbursed adherence intervention (33,888 EUR vs 16,620 EUR, respectively; p = 0.05). Conclusions: Our findings highlight that to date only a small number of MAEIs have been reimbursed in European countries. Comprehensive health technology assessment recommendations and multi-stakeholder collaboration could help removing barriers related to the implementation and reimbursement of MAEIs.

Competency (and Beyond): Think Patient. Collaborate. Develop. Evaluate. Improve. Repeat.

The global workforce needs to be competent, flexible, adaptable, sustainable, and patient-focused. A competency approach towards education, development, and professional practice strengthens services and increases better health outcomes. This paper will provide a global perspective on competency approaches from different health care professions. It will focus on two case reports, describing the use of competency methodologies at an undergraduate and postgraduate level, as well as supporting the internship and/or pre-registration training. Challenges and opportunities will be highlighted by addressing some of the key questions posed for this special edition.

Effect of the Mediterranean diet in combination with exercise on metabolic syndrome parameters: 1-year randomized controlled trial.

This work aimed to evaluate and compare the benefits of the energy restricted Mediterranean diet (MD) and Standard hypolipemic diet (SHD) accompanied by exercise on metabolic syndrome parameters. A 12-month, randomized, single-blinded, diet-controlled study was conducted on 124 obese participants in the University Hospital Dubrava. Participants were assigned to the MD (n = 63) or the SHD (n = 61) and received the same amount of nutritional education and guidance on physical activity. The completion rate was 67.7 %. Both diets produced significant beneficial changes in body weight and waist circumference (P < 0.001 for MD and SHD). Compared with the SHD, HDL cholesterol increased (P = 0.031) and systolic blood pressure (SBP) decreased (P = 0.020) in the MD group. Fasting plasma glucose decreased significantly in both diet groups (P < 0.001 for MD; P = 0.026 for SHD). Although both diets accompanied by physical activity yielded similar weight reduction results, adherence to the MD was associated with more prominent reduction of the MetS components, namely HDL level elevation and SBP reduction.

Pharmacist's interventions improve time in therapeutic range of elderly rural patients on warfarin therapy: a randomized trial.

Background Community pharmacists can play an important role in optimizing warfarin treatment, which is very important in vulnerable patient groups such as the elderly patients in rural areas. Objective To evaluate the impact of a community pharmacist's interventions on the quality of anticoagulation in elderly rural patients receiving warfarin. Setting A community pharmacy in Donji Miholjac in Croatia's province of Slavonia. Method We conducted a prospective randomized trial. Eligible patients were recruited at the pharmacy and randomized into two groups. All participants were followed up monthly for a period of 6 months. Repeated education and a follow up plan were provided to the participants in the intervention group, and their general practitioners were contacted to correct the warfarin dose or to avoid drug interactions. Main outcome measure Time in therapeutic range (TTR) calculated by the Rosendaal method. Results A total of 140 patients were randomized and 131 patients finished the study, 65 patients in the intervention group. Median age was 73 years. At the end of the follow-up period, the median TTR was significantly higher in the intervention group (93 vs. 31.2% for intervention and control, respectively; P < 0.001). The proportion of patients with TTR ≥ 65% was also significantly higher in the intervention group (86.2 vs. 7.6% for intervention and control, respectively; P < 0.001). Factors independently associated with TTR ≥ 65% were intervention (P < 0.001), less frequent dose change (P = 0.005), better adherence (P < 0.001) and less variable vitamin K intake (P = 0.010).

Potentially inappropriate medicines in elderly hospitalised patients according to the EU(7)-PIM list, STOPP version 2 criteria and comprehensive protocol.

PURPOSE: The aim of this study was to measure the prevalence of potentially inappropriate medications (PIMs) by using the EU(7)-PIM list, STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) version 2 criteria and the new comprehensive protocol. METHODS: This prospective study involved a sample of 276 consecutive elderly patients discharged from the university teaching hospital. Age, gender, diagnoses, medication history and medicines at discharge were recorded. The main outcome measure was the prevalence of PIMs according to each set of criteria: EU(7)-PIM list, STOPP version 2 criteria and comprehensive protocol. RESULTS: The median patient age (range) was 74 (65-92) years. The median number of prescribed medications was 7 (1-17). STOPP identified 393 PIMs affecting 190 patients (69%), EU(7)-PIM list identified 330 PIMs in 184 patients (66.7%) whilst the comprehensive protocol identified 134 PIMs in 102 patients (37%). STOPP version 2 criteria identified significantly more PIMs per patient than the other two protocols (p < 0.001). Gender (p = 0.002), glomerular filtration rate (p = 0.039) and number of comorbidities (p = 0.001) were associated with the proportion of PIMs for the STOPP version 2 criteria only. CONCLUSION: A very high PIM prevalence at discharge was reported suggesting the urgent need for actions to reduce them. STOPP version 2 criteria identified significantly more PIMs than the EU(7)-PIM list and the comprehensive protocol and was found as a more sensitive tool for PIM detection.

Level of minerals and trace elements in the urine of the participants of mountain ultra-marathon race.

The aim of the present study was to explore impact of endurance exercise on urinary level of minerals and trace elements as well as on some oxidative stress and biochemical parameters. Urine samples were collected from participants (n=21) of mountain ultra-marathon race (53km; Medvednica, Zagreb, Croatia), before (baseline value), immediately after, 12h and 24h after the race. In urine samples level of minerals (Ca, P, K and Na) and trace elements (Se, Zn, Mn, Cu, Fe and Co) were assessed using the bench top Total reflection X-ray Fluorescence (TXRF) spectrometer. Oxidative stress was determined as level of malondialdehyde (MDA). Immediately after the race level of minerals, trace elements, MDA, creatinine, ketones, erythrocytes and specific gravity increased compared to their baseline value. In 24h follow-up trace elements involved in antioxidant defence, MDA and biochemical parameters returned to their baseline values, Cu and Co remained increased as after the race, Fe and K tended to return to baseline values while Ca, P and Na continued to increase. Mountain ultra-marathon resulted in alteration of physiologically important minerals and trace elements that for some minerals and trace elements persist, indicating their involvement in recovery processes. However, due to their loss in urine, level of minerals and trace elements in athletes participating in endurance exercise should be monitored.

The Development of the Croatian Competency Framework for Pharmacists.

Objective. To adjust and validate the Global Competency Framework (GbCF) to be relevant for Croatian community and hospital pharmacists. Methods. A descriptive study was conducted in three steps: translation, consensus development, and validation by an expert panel and public consultation. Panel members were representatives from community pharmacies, hospital pharmacies, regulatory and professional bodies, academia, and industry. Results. The adapted framework consists of 96 behavioral statements organized in four clusters: Pharmaceutical Public Health, Pharmaceutical Care, Organization and Management, and Personal and Professional Competencies. When mapped against the 100 statements listed in the GbCF, 27 matched, 39 were revised, 30 were introduced, and 24 were excluded from the original framework. Conclusions. The adaptation and validation proved that GbCF is adaptable to local needs, the Croatian Competency Framework that emerged from it being an example. Key amendments were made within Organization and Management and Pharmaceutical Care clusters, demonstrating that these issues can be country specific.

Individualized education and competency development of Croatian community pharmacists using the general level framework.

OBJECTIVES: To measure Croatian community pharmacists' progress in competency development using the General Level Framework (GLF) as an educational tool in a longitudinal study. METHODS: Patient care competencies of 100 community pharmacists were evaluated twice, in 2009 and in 2010 in a prospective cohort study. During this 12-month period, tailored educational programs based on the GLF were organized and conducted, new services and standard operating procedures were implemented, and documentation of contributions to patient care in the pharmacist's portfolio became mandatory. RESULTS: Pharmacists' development of all GLF patient care competencies was significant with the greatest improvements seen in the following competencies: patient consultation, monitoring drug therapy, medicine information and patient education, and evaluation of outcomes. CONCLUSIONS: This study, which retested the effectiveness of an evidence-based competency framework, confirmed that GLF is a valid educational tool for pharmacist development.

The antioxidative protecting role of the Mediterranean diet.

Recent meta-analysis shows that adherence to a Mediterranean diet (MD) can significantly decrease the risk of overall mortality, mortality from cardiovascular diseases, as well as incidence of mortality from cancer, and incidence of Parkinson's and Alzheimer's disease. All of these diseases could be linked to oxidative stress (OS) as antioxidative effect of MD is getting more attention nowadays. Although a lot of research has been done in this area and it suggests antioxidative protective role of MD, the presented evidence is still inconclusive. The aim of this paper is to review studies investigating the effect of MD on OS, as well as to identify the areas for further research.

Evaluation of Croatian community pharmacists' patient care competencies using the general level framework.

OBJECTIVES: To assess Croatian community pharmacists' patient care competencies using the General Level Framework (GLF). METHODS: The competencies of 100 community pharmacists working in 38 community pharmacies were evaluated using an adapted version of the GLF. RESULTS: Pharmacists demonstrated the best performance in the competency areas drug specific issues and provision of drug products; the poorest performance was in the competency areas evaluation of outcomes and monitoring drug therapy. Pharmacists' behavior varied the most in the following areas: ensuring that the prescription is legal, prioritization of medication management problems, and identification of drug-drug interactions. CONCLUSIONS: Competencies were identified that need to be developed to improve pharmacist interventions in community settings. This study provides the first data on pharmacists' performance in Croatia and serves as a starting point for future studies and actions.