Prevalence, country-specific prescribing patterns and determinants of benzodiazepine use in community-residing older adults in 7 European countries.

BACKGROUND: The use of benzodiazepines (BZDs) in older population is often accompanied by drug-related complications. Inappropriate BZD use significantly alters older adults' clinical and functional status. This study compares the prevalence, prescribing patterns and factors associated with BZD use in community-dwelling older patients in 7 European countries. METHODS: International, cross-sectional study was conducted in community-dwelling older adults (65 +) in the Czech Republic, Serbia, Estonia, Bulgaria, Croatia, Turkey, and Spain between Feb2019 and Mar2020. Structured and standardized questionnaire based on interRAI assessment scales was applied. Logistic regression was used to evaluate factors associated with BZD use. RESULTS: Out of 2,865 older patients (mean age 73.2 years ± 6.8, 61.2% women) 14.9% were BZD users. The highest prevalence of BZD use was identified in Croatia (35.5%), Spain (33.5%) and Serbia (31.3%). The most frequently prescribed BZDs were diazepam (27.9% of 426 BZD users), alprazolam (23.7%), bromazepam (22.8%) and lorazepam (16.7%). Independent factors associated with BZD use were female gender (OR 1.58, 95%CI 1.19-2.10), hyperpolypharmacy (OR 1.97, 95%CI 1.22-3.16), anxiety (OR 4.26, 95%CI 2.86-6.38), sleeping problems (OR 4.47, 95%CI 3.38-5.92), depression (OR 1.95, 95%CI 1.29-2.95), repetitive anxious complaints (OR 1.77, 95%CI 1.29-2.42), problems with syncope (OR 1.78, 95%CI 1.03-3.06), and loss of appetite (OR 0.60, 95%CI 0.38-0.94). In comparison to Croatia, residing in other countries was associated with lower odds of BZD use (ORs varied from 0.49 (95%CI 0.32-0.75) in Spain to 0.01 (95%CI 0.00-0.03) in Turkey), excluding Serbia (OR 1.11, 95%CI 0.79-1.56). CONCLUSIONS: Despite well-known negative effects, BZDs are still frequently prescribed in older outpatient population in European countries. Principles of safer geriatric prescribing and effective deprescribing strategies should be individually applied in older BZD users.

Deprescribing potential of commonly used medications among community-dwelling older adults: insights from a pharmacist's geriatric assessment.

Pharmacist's geriatric assessment can provide valuable insights into potential deprescribing targets, while including important information on various health-related domains. Data collected from a geriatric assessment questionnaire, for 388 patients, from the Croatian cohort of the EuroAgeism H2020 ESR 7 international project, along with guideline-based deprescribing criteria, were used to analyse potentially inappropriate prescribing of four medication groups (benzodiazepines (BZN), proton pump inhibitors (PPI), opioids, and non-steroidal anti-inflammatory drugs (NSAID)), and to assess the deprescribing potential. Binary logistic regression was used to explore the effects of age, gender, number of medicines and diagnoses, self-reported health, frailty score, and healthcare utilization on the likelihood of needing deprescribing. More than half of participants (n = 216, 55.2%) are candidates for deprescribing, with 31.1% of PPI, 74.8% of NSAID, 75% of opioid, and 96.1% of BZN users meeting at least one criterion. Most common criteria for deprescribing were inappropriately long use and safety concerns. Women (aOR = 2.58; p < 0.001), those reporting poor self-reported health (aOR = 5.14; p < 0.001), and those exposed to polypharmacy (aOR = 1.29; p < 0.001) had higher odds of needing to have medicines deprescribed. The high rate of deprescribing potential warrants prompt action to increase patient safety and decrease polypharmacy. Pharmacist's geriatric assessment and deprescribing-focused medication review could be used to lead a personalised approach.

Clinical decision-making in benzodiazepine deprescribing by healthcare providers vs. AI-assisted approach.

AIMS: The aim of this study was to compare the clinical decision-making for benzodiazepine deprescribing between a healthcare provider (HCP) and an artificial intelligence (AI) chatbot GPT4 (ChatGPT-4). METHODS: We analysed real-world data from a Croatian cohort of community-dwelling benzodiazepine patients (n = 154) within the EuroAgeism H2020 ESR 7 project. HCPs evaluated the data using pre-established deprescribing criteria to assess benzodiazepine discontinuation potential. The research team devised and tested AI prompts to ensure consistency with HCP judgements. An independent researcher employed ChatGPT-4 with predetermined prompts to simulate clinical decisions for each patient case. Data derived from human-HCP and ChatGPT-4 decisions were compared for agreement rates and Cohen's kappa. RESULTS: Both HPC and ChatGPT identified patients for benzodiazepine deprescribing (96.1% and 89.6%, respectively), showing an agreement rate of 95% (κ = .200, P = .012). Agreement on four deprescribing criteria ranged from 74.7% to 91.3% (lack of indication κ = .352, P < .001; prolonged use κ = .088, P = .280; safety concerns κ = .123, P = .006; incorrect dosage κ = .264, P = .001). Important limitations of GPT-4 responses were identified, including 22.1% ambiguous outputs, generic answers and inaccuracies, posing inappropriate decision-making risks. CONCLUSIONS: While AI-HCP agreement is substantial, sole AI reliance poses a risk for unsuitable clinical decision-making. This study's findings reveal both strengths and areas for enhancement of ChatGPT-4 in the deprescribing recommendations within a real-world sample. Our study underscores the need for additional research on chatbot functionality in patient therapy decision-making, further fostering the advancement of AI for optimal performance.

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.

Prevalence and Determinants of Multimorbidity, Polypharmacy, and Potentially Inappropriate Medication Use in the Older Outpatients: Findings from EuroAgeism H2020 ESR7 Project in Ethiopia.

Few studies have been conducted on multimorbidity (two or more chronic diseases) and rational geriatric prescribing in Africa. This study examined the prevalence and determinants of multimorbidity, polypharmacy (five or more long-term medications), and potentially inappropriate medication (PIM) use according to the 2019 Beers criteria among the older adults attending chronic care clinics from a single institution in Ethiopia. A hospital-based cross-sectional study was conducted among 320 randomly selected older adults from 12 March 2020 to 30 August 2020. A multivariable logistic regression analysis was performed to identify the predictor variables. The prevalence of multimorbidity, polypharmacy, and PIM exposure was 59.1%, 24.1%, and 47.2%, respectively. Diuretics (10%), insulin sliding scale (8.8%), amitriptyline (7.8%), and aspirin (6.9%) were among the most frequently prescribed PIMs. Older patients experiencing pain flare-ups were more likely to have multimorbidity (adjusted odds ratio (AOR): 1.64, 95% confidence intervals: 1.13-2.39). Persistent anger (AOR: 3.33; 1.71-6.47) and use of mobility aids (AOR: 2.41, 1.35-4.28) were associated with polypharmacy. Moreover, cognitive impairment (AOR: 1.65, 1.15-2.34) and health deterioration (AOR: 1.61, 1.11-2.32) increased the likelihood of PIM exposure. High prevalence of multimorbidity and PIM use was observed in Ethiopia. Several important determinants that can be modified by applying PIM criteria in routine practice were also identified.

The prevalence and prescribing patterns of benzodiazepines and Z-drugs in older nursing home residents in different European countries and Israel: retrospective results from the EU SHELTER study.

BACKGROUND: Benzodiazepines (BZDs) and Z-drugs have high potential for developing frequent adverse drug events in older adults (e.g., psychomotor sedation, drug-related dementia, deliria, drug dependence, etc.). Knowledge of the prevalence and patterns of the use of BZDs/Z-drugs in vulnerable older patients is important in order to prevent and reduce the burden caused by their drug-related complications. Our study focused on international comparisons of the prevalence, country-specific prescribing patterns and risk factors of regular BZD/Z-drug use in nursing home (NH) residents. METHODS: This cross-sectional study retrospectively analysed data of 4156 NH residents, prospectively assessed in the Services and Health in the Elderly in Long TERm care (SHELTER) project conducted from 2009 to 2014. Residents aged 65+ in 57 NHs in 7 European countries and Israel were assessed by the InterRAI Long-Term Care Facilities instrument. Descriptive statistics and multiple logistic regression models were used to describe the country-specific prevalence, patterns and risk factors of BZD/Z-drug use. RESULTS: The mean age of the participants was 83.4 ± 9.4 years, 73% were female and 27.7% used BZDs/Z-drugs. The prevalence of BZD/Z-drug use differed significantly across countries, ranging from 44.1% in Israel to 14.5% in Germany. The most frequently prescribed were zopiclone (17.8%), lorazepam (17.1%) and oxazepam (16.3%). Lorazepam, oxazepam and diazepam were used in most of the countries. Brotizolam, temazepam and zolpidem showed highest prevalence in Israel (99.4% of all regular users of this medication in the sample), the Netherlands (72.6%) and France (50.0%), respectively. Residing in Israel was the most significant factor associated with the use of BZDs/Z-drugs or BZDs only (odds ratio [OR] 6.7; 95% confidence interval [CI] 4.8-9.2 and OR 9.7, 95%CI 6.5-14.5, respectively). The use of Z-drugs only was most significantly associated with residing in France (OR 21.0, 95%CI 9.0-48.9). CONCLUSIONS: Despite global recommendations and warnings, the preference for and extent of use of individual BZDs and Z-drugs in vulnerable NH residents differ significantly across countries. The strong association with country of residence compared to clinical and functional factors denotes that prescribing habits, social, cultural, behavioural, and regulatory factors still play an important role in the current diverse use of these medications.

Applicability of EU(7)-PIM criteria in cross-national studies in European countries.

BACKGROUND: The European Union (EU)(7)-PIM (potentially inappropriate medication) list presents the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe; however, several country-specific studies have documented lower specificity of this list on pharmaceutical markets of some countries. The aim of our study was to describe approval rates and marketing of PIMs stated by EU(7)-PIM criteria in six EU countries [in comparison with the American Geriatric Society (AGS) Beers 2015 criteria]. METHODS: Research teams of six EU countries (Czech Republic, Spain, Portugal, Serbia, Hungary and Turkey) participated in this study conducted by WG1b EU COST Action IS1402 group in the period October 2015-November 2018. Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drug-regulatory institutes and up-to-date drug compendia. The EU(7)-PIM list and AGS Beers 2015 Criteria (Section 1) were applied. RESULTS: PIMs from EU(7)-PIM list were approved for clinical use more often than those from the AGS Beers 2015 criteria (Section 1). Approval rates for EU(7)-PIMs ranged from 42.8% in Serbia to 71.4% in Spain (for AGS criteria only from 36.4% to 65.1%, respectively). Higher percentages of approved PIMs were documented in Spain (71.4%), Portugal (67.1%) and Turkey (67.5%), lower in Hungary (55.5%), Czech Republic (50.2%) and Serbia (42.8%). The majority of approved PIMs were also currently marketed in all countries except in Turkey (19.8-21.7% not marketed PIMs) and less than 20% of PIMs were available as over-the-counter medications (except in Turkey, 46.4-48.1%). CONCLUSIONS: The EU(7)-PIM list was created for utilization in European studies; however, applicability of this list is still limited in some countries, particularly in Eastern and Central Europe. The EU project EUROAGEISM H2020 (2017-2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits.

Medication use in older patients and age-blind approach: narrative literature review (insufficient evidence on the efficacy and safety of drugs in older age, frequent use of PIMs and polypharmacy, and underuse of highly beneficial nonpharmacological strategies).

INTRODUCTION: The importance of rational drug therapy is increasing with the aging of the population. Since one of the main reasons for inappropriate drug prescribing is also the "age-blind" approach, which results in ageist practices, this narrative literature review focuses on the description of the main barriers related to insufficient individualization of drug regimens associated with such age-blind approaches. METHODOLOGY: A narrative literature review using the PubMed, WoS, Embase, and Scopus databases was conducted by the EU COST Action IS1402. Experts in different scientific fields from six countries (the Czech Republic, Spain, Portugal, Hungary, Serbia, and Turkey) worked in four specific areas: (1) underrepresentation of older adults in clinical trials and clinical and ethical consequences; (2) insufficient consideration of age-related changes and geriatric frailty in the evaluation of the therapeutic value of drugs; (3) frequent prescribing of potentially inappropriate medications (PIMs); and (4) frequent underuse of highly beneficial nonpharmacological strategies (e.g., exercise). RESULTS: Older patients are underrepresented in clinical trials. Therefore, rigorous observational geriatric research is needed in order to obtain evidence on the real efficacy and safety of frequently used drugs, and e.g. developed geriatric scales and frailty indexes for claims databases should help to stimulate such research. The use of PIMs, unfortunately, is still highly prevalent in Europe: 22.6% in community-dwelling older patients and 49.0% in institutionalized older adults. Specific tests to detect the majority of age-related pharmacological changes are usually not available in everyday clinical practice, which limits the estimation of drug risks and possibilities to individualize drug therapy in geriatric patients before drug prescription. Moreover, the role of some nonpharmacological  strategies is highly underestimated in older adults in contrast to frequent use of polypharmacy. Among nonpharmacological strategies, particularly physical exercise was highly effective in reducing functional decline, frailty, and the risk of falls in the majority of clinical studies. CONCLUSION: Several regulatory and clinical barriers contribute to insufficient knowledge on the therapeutic value of drugs in older patients, age-blind approach, and inappropriate prescribing. New clinical and observational research is needed, including data on comprehensive geriatric assessment and frailty, to document the real efficacy and safety of frequently used medications.

Challenges and opportunities for ELSI early career researchers.

BACKGROUND: Over the past 25 years, there has been growing recognition of the importance of studying the Ethical, Legal and Social Implications (ELSI) of genetic and genomic research. A large investment into ELSI research from the National Institutes of Health (NIH) Human Genomic Project budget in 1990 stimulated the growth of this emerging field; ELSI research has continued to develop and is starting to emerge as a field in its own right. The evolving subject matter of ELSI research continues to raise new research questions as well as prompt re-evaluation of earlier work and a growing number of scholars working in this area now identify themselves as ELSI scholars rather than with a particular discipline. MAIN TEXT: Due to the international and interdisciplinary nature of ELSI research, scholars can often find themselves isolated from disciplinary or regionally situated support structures. We conducted a workshop with Early Career Researchers (ECRs) in Oxford, UK, and this paper discusses some of the particular challenges that were highlighted. While ELSI ECRs may face many of the universal challenges faced by ECRs, we argue that a number of challenges are either unique or exacerbated in the case of ELSI ECRs and discuss some of the reasons as to why this may be the case. We identify some of the most pressing issues for ELSI ECRs as: interdisciplinary angst and expertise, isolation from traditional support structures, limited resources and funding opportunities, and uncertainty regarding how research contributions will be measured. We discuss the potential opportunity to use web 2.0 technologies to transform academic support structures and address some of the challenges faced by ELSI ECRs, by helping to facilitate mentoring and support, access to resources and new accreditation metrics. CONCLUSION: As our field develops it is crucial for the ELSI community to continue looking forward to identify how emerging digital solutions can be used to facilitate the international and interdisciplinary research we perform, and to offer support for those embarking on, progressing through, and transitioning into an ELSI research career.