Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults.

BACKGROUND: Frailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults. METHODS: In non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD. RESULTS: In this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20-3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01-3.12). CONCLUSIONS: This study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD.

An overview of multimorbidity and polypharmacy in older people living with HIV.

The availability of effective antiretroviral therapy (ART) has revolutionized the care of people living with HIV (PLHIV). As a result, PLHIV now have a life expectancy comparable with that of the general population. PLHIV are increasingly confronted with age-related comorbidities and geriatric syndromes, including frailty and polypharmacy, which occur at a higher prevalence and set in at an earlier age compared with their uninfected counterparts. The underlying pathophysiology for multimorbidity and polypharmacy are multifactorial, multidimensional and complex. Therefore, regular review and optimization of risk factors to maintain physical function, social and psychological health is of utmost importance. With an ever-growing population of older PLHIV, there is a pressing need to provide holistic care to address these emerging issues. Accelerated aging observed in PLHIV suggests that early involvement of a multidisciplinary team, including geriatricians, and implementation of integrated models of care can potentially improve the care of older PLHIV, who are at increased risk of frailty and complex multimorbidity. This article reviews the current global situation, discusses the challenges involved and suggests approaches to deliver comprehensive care for older PLHIV. Geriatr Gerontol Int 2024; 24: 49-59.

The patients' perspective on multimorbidity and polypharmacy and how do we accommodate it in the healthcare system.

Patients living with multimorbidity, and polypharmacy can have difficulties handling the treatment burden they face daily. They often experience disjointed treatment courses and demand a more holistic approach to their multimorbidity and to be involved in decisions about their treatments. In the healthcare system, there are examples of new initiatives that go beyond the classic diagnostic silo thinking. However, this review finds that further development of new structures, approaches, and collaboration models in the healthcare system, as well as research, is still necessary to meet the needs of these patients.

Attitudes of Older Adult Patients and Caregivers Towards Deprescribing of Medications in Ethiopia.

Background: Deprescribing is essential for reducing inappropriate medication use and polypharmacy. For a holistic approach, it is essential to know how older adult patients and their caregivers perceive deprescribing. Objective: To assess the attitude of older adult patients and caregivers towards deprescribing medication at Ambo University Referral Hospital. Methodology: Institutional-based cross-sectional study was conducted using the revised Patients' Attitude Towards Deprescribing tool (rPATD). The data was analyzed using the SPSS-25 software. Backward linear regression and logistic regression were used to measure association between outcome and determinant variables. The two-sided P-value ≤0.05 with 95% confidence interval was utilized for reporting significant factors. Results: One hundred fifty-six (81.3%) of the respondents (ie, 85.0% of older adult and 77.2% of caregivers) agreed to stop one or more of their regular medications if the physician said it was possible despite 98 (51.0%) of them (ie, 49.0% of older adult and 53.3% of caregivers) being satisfied with their/their care recipient's medications. On the overall aggregate mean score, the respondents had a neutral position (2.6-3.59) regarding the burden and concerns of stopping medications whereas the majority of them disagree (1.0-2.59) with the inappropriateness of the medication they were taking and agreed (3.6-5.0) with the need for their involvement in treatment decision making. Concerns about stopping medicine scores (AOR = 0.440, 95% CI = 0.262-0.741, P = 0.035) and perceived levels of medication inappropriateness (AOR = 0.653, 95% CI = 0.456-0.936, P = 0.020) was significantly associated with the willingness to discontinue and overall satisfaction with their medicine regimen respectively. Conclusion: The majority of older adult patients and caregivers would like to deprescribe if the physicians recommended it. The perceived concerns of stopping and inappropriateness of the medicines were associated with the willingness to deprescribe and overall satisfaction with their medicine respectively. Healthcare providers should prompt the deprescribing process with older adult patients and caregivers by addressing their concerns about stopping medications.

Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction According to Polypharmacy Status.

BACKGROUND: Patients with heart failure (HF) have a high burden of multimorbidity, often necessitating numerous medications. There may be clinical concern about introducing another medication, especially among individuals with polypharmacy. OBJECTIVES: This study examined the efficacy and safety of addition of dapagliflozin according to the number of concomitant medications in HF with mildly reduced or preserved ejection fraction. METHODS: In this post hoc analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, 6,263 participants with symptomatic HF with left ventricular ejection fraction >40% were randomized to dapagliflozin or placebo. Baseline medication use (including vitamins and supplements) was collected. Efficacy and safety outcomes were assessed by medication use categories ("nonpolypharmacy": <5 medications; "polypharmacy": 5 to 9 medications; and "hyperpolypharmacy": ≥10 medications) and continuously. The primary outcome was worsening HF or cardiovascular death. RESULTS: Overall, 3,795 (60.6%) patients met polypharmacy and 1,886 (30.1%) met hyperpolypharmacy criteria. Higher numbers of medications were strongly associated with higher comorbidity burden and increased rates of the primary outcome. Compared with placebo, dapagliflozin similarly reduced the risk of the primary outcome irrespective of polypharmacy status (nonpolypharmacy HR: 0.88 [95% CI: 0.58-1.34]; polypharmacy HR: 0.88 [95% CI: 0.75-1.03]; hyperpolypharmacy HR: 0.73 [95% CI: 0.60-0.88]; Pinteraction = 0.30). Similarly, benefits with dapagliflozin were consistent across the spectrum of total medication use (Pinteraction = 0.06). Although adverse events increased with higher number of medications, they were not more frequent with dapagliflozin, regardless of polypharmacy status. CONCLUSIONS: In the DELIVER trial, dapagliflozin safely reduced worsening HF or cardiovascular death across a broad range of baseline medication use, including among individuals with polypharmacy (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

Design and statistics of pharmacokinetic drug-drug, herb-drug, and food-drug interaction studies in oncology patients.

Polypharmacy is becoming increasingly prevalent in society. Patients with polypharmacy are at greater risk for drug-drug interactions, which can influence the efficacy of treatment. Especially, in oncology this is a concern since neoplasms are increasing prevalent with age, as well as polypharmacy is. Besides drug-drug interactions, also herb-drug and food-drug interactions could be present. Knowledge of these interactions is of great importance for safe and effective anti-cancer treatment, because the therapeutic window of most of these oncologic drugs are small. To study pharmacokinetic interaction effects, a cross-over pharmacokinetic study is a widely used, efficient and scientifically robust design. Yet, several aspects need to be considered when carrying out an interaction study. This includes the knowledge of the advantages and disadvantages of a cross-over design. Furthermore, determination of the end point and research question of interest, calculation of the required sample size, analysis of the generated data with a robust statistical plan and consideration of the logtransformation for some pharmacokinetic parameters are important aspects to consider. Even though some guidelines exist regarding these key issues, no clear overview exists. In this article an overview of these aspects is provided and their effect is discussed.

Prevalence of Polypharmacy and Potential Drug-Drug Interactions Associated with Risk Factors in the Era of HIV Integrase Inhibitors: A Prospective Clinical Study.

People living with human immunodeficiency virus (PLWH), with the availability of modern antiretroviral drugs, have multiple comorbidities, which increase the risk of polypharmacy and potential drug-drug interactions (PDDIs). This is a particularly important issue for the aging population of PLWH. This study aims to review the prevalence and risk factors for PDDIs and polypharmacy in the era of HIV integrase inhibitors. A cross-sectional, two-center, prospective observational study was conducted on Turkish outpatients between October 2021 and April 2022. Polypharmacy was defined as the use of ≥5 non-HIV medications, excluding over-the-counter (OTC) drugs, and PDDIs were classified using the University of Liverpool HIV Drug Interaction Database (harmful/red flagged and potentially clinically relevant/amber flagged). The median age of the 502 PLWH included in the study was 42 ± 12.4 years and 86.1% were males. Most individuals (96.4%) were given integrase-based regimens (unboosted 68.7% and boosted 27.7%). In total, 30.7% of individuals were taking at least one OTC drug. The prevalence of polypharmacy was 6.8% (9.2% when OTC drugs were included). During the study period, the prevalence of PDDIs was 1.2% for red flag PDDIs and 16% for amber flag PDDIs. CD4+ T cell count >500 cells/mm3, number of comorbidities ≥3, comedication with drugs affecting blood and blood-forming organs, cardiovascular drugs, and vitamin/mineral supplements were associated with red flag or amber flag PDDIs. Drug interaction prevention is still important in HIV care. Individuals with multiple comorbidities should be closely monitored for non-HIV medications to prevent PDDIs.

Prevalence and factors predisposing to potential drug-drug interactions in a Polish community-dwelling geriatric population: An observational, cross-sectional study.

BACKGROUND: Due to advanced age, multimorbidity and polypharmacotherapy, older patients are predisposed to drug interactions and the adverse effects of inappropriate drug combinations. OBJECTIVES: To provide up-to-date data on predisposing factors and the prevalence of possible drug interactions in the Polish geriatric population and to promote automated analysis programs as part of safe pharmacotherapy. MATERIAL AND METHODS: We used the Lexicomp® Drug Interactions database to assess pharmacological interactions between active substances included in all types of preparations (prescription drugs, over-the-counter drugs, vitamins, nutritional preparations, and dietary supplements) used at least once in the 2 weeks preceding the study, among 2633 home-dwelling people aged >65 years. The variables measured included age, sex, place of residence, level of education, and multimorbidity. Post-stratification was used to weigh the sample structure against the Polish population in 2017. RESULTS: Drug interactions were identified in 81.2% of all individuals. The mean number (with 95% confidence interval (95% CI)) of all drug interactions was 4.24 (4.02-4.46), and the median value (with 1st and 3rd quartiles (Q1-Q3)) was 3 (1-6). At least 1 category C interaction was observed in 75.8% of all study participants, 24.3% had 1 or more category D interaction, and 4.3% had 1 or more category X interaction. The most important predisposing factor to drug interactions was multimorbidity. CONCLUSIONS: This study identified a high prevalence of potential drug interactions in the Polish geriatric population. Automated analysis systems deliver useful information on pharmacological interactions and should be promoted in the Polish healthcare community as tools to support pharmacotherapy.

Potential drug-drug interactions between antiretroviral drugs and comedications, including dietary supplements, among people living with HIV: A clinical survey.

OBJECTIVE: Age-related comorbidities, polypharmacy and thereby the risk of potential drug-drug interactions (PDDIs) among people living with HIV (PLWH) have increased over the years. We estimated the prevalence of comedications, including dietary supplements, and evaluated PDDIs among PLWH receiving antiretroviral therapy (ART) in Denmark in an outpatient setting. METHODS: Information on prescription medication, over-the-counter medication and dietary supplements was obtained from adult PLWH receiving ART attending two outpatient clinics in Denmark. The PDDIs were identified using the University of Liverpool's drug interaction database. Associations between PDDIs and relevant variables were compared using logistic regression models. RESULTS: A total of 337 PLWH receiving ART with a median age of 53 years (interquartile range: 45-61) were included; 77% were male and 96% had a HIV-RNA viral load < 50 copies/mL. Twenty-six per cent of participants received five or more comedications and 56% consumed dietary supplements. Co-administration of drugs requiring dose adjustment or monitoring was identified in the medication lists of 52% of participants, and 4.5% were on drugs that should not be co-administered. Male sex [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.0-3.4], being on a protease inhibitor (OR = 4.3, 95% CI: 1.9-9.7), receiving five or more comedications (OR = 3.3, 95% CI: 1.5-7.2), taking over-the-counter medications (OR = 1.9, 95% CI: 1.1-3.3) and dietary supplements (OR = 2.0, 95% CI: 1.2-3.3) were independent predictors of PDDIs. CONCLUSION: Potential drug-drug interactions were common among our study population Our study confirms that polypharmacy and being on a protease inhibitor-based regimen increase the risk of PDDIs considerably and highlights the importance of questioning PLWH about dietary supplement intake.

Evaluation of polypharmacy among chronic kidney disease patients in Egypt: A cross-sectional study.

OBJECTIVE: To analyze the prevalence and the hazard of polypharmacy in chronic kidney disease (CKD) patients with different CKD stages in an Egyptian nephrology clinic. MATERIALS AND METHODS: A cross-sectional observational study was performed between November and December 2021 in a private nephrology clinic in Egypt. Patients diagnosed with CKD were included in the study. They were classified into 5 stages following KDIGO classification. Medications taken were assessed, classified, and distributed according to CKD stage. RESULTS: 199 patients were included in the study; their ages ranged from 19 to 87 years. Approximately 30% of the patients had stage 5 CKD. Upon medication analysis, all patients were exposed to polypharmacy and had associated comorbidities. Dietary supplements and anti-hypertensive medications were the most frequently used. CONCLUSION: Polypharmacy seems to be inevitable in CKD patients specially those who have associated comorbidities which could be managed through proper clinical pharmacy services to minimize medication hazards.

Can a practice pharmacist improve prescribing safety and reduce costs in polypharmacy patients? A pilot study of an intervention in an Irish general practice setting.

OBJECTIVES: This study aimed to develop and assess the feasibility and cost impact of an intervention involving a practice pharmacist embedded in general practice to improve prescribing safety, deprescribe where appropriate and reduce costs. SETTING: Four-doctor suburban general practice. PARTICIPANTS: Inclusion criteria: patients receiving 10+ repeat drugs per month. EXCLUSION CRITERIA: deceased, <18 years of age, nursing home resident, no longer attending, late-stage life-limiting condition, unsuitable on clinical/capacity grounds. 137 patients were eligible. 78 were recruited as participants, all of whom completed the study. INTERVENTION: Pharmacist conducting holistic medication reviews in the study group over a 6-month period. PRIMARY OUTCOME MEASURES: Anonymised medication changes, cost, biochemical monitoring and clinical measurements data were collected. Cost analysis of having a pharmacist as part of the general practice team was calculated. RESULTS: In total, 198 potentially inappropriate prescriptions (PIPs), and 163 opportunities for deprescribing were identified; 127 PIPs (64.1%) were actioned; 104 deprescribing opportunities were actioned (63.8%). The pharmacist identified 101 instances in which further investigations were warranted prior to prescription issue, of which 80 were actioned (79.2%). It was calculated that monthly savings of €1252 were made as a result of deprescribing. CONCLUSIONS: This study has shown that the integration of pharmacists within general practice in Ireland is feasible and is an effective means of improving prescribing safety and implementing deprescribing through medication reviews. The combination of safety and cost concerns support taking a holistic approach to deprescribing with the patient. This study highlights the ease with which a pharmacist could integrate into the general practice setting in Ireland and points to how this could be sustainably funded.

Effects of the Atrial Fibrillation Better Care Pathway on Outcomes Among Clinically Complex Chinese Patients With Atrial Fibrillation With Multimorbidity and Polypharmacy: A Report From the ChiOTEAF Registry.

Background Patients with atrial fibrillation commonly have complex clinical backgrounds of multimorbidity and polypharmacy. The Atrial Fibrillation Better Care (ABC) pathway has been developed to help deliver integrated and holistic care for patients with atrial fibrillation. In this ancillary analysis, we assessed the adherence to and the effectiveness of the ABC pathway at reducing adverse outcomes in Chinese patients with atrial fibrillation with a complex clinical background of multimorbidity or polypharmacy. Methods and Results The ChiOTEAF (Optimal Thromboprophylaxis in Elderly Chinese Patients With Atrial Fibrillation) registry is a prospective, multicenter, nationwide study conducted from October 2014 to December 2018. The primary outcomes of interest were the composite end point of all-cause death and thromboembolic events, as well as individual end points of all-cause death, thromboembolic events, and major bleeding. Multimorbidity was defined as the presence of ≥2 comorbidities, and polypharmacy was defined as the concomitant use of ≥5 medications. The eligible cohort included 4644 patients with multimorbidity, of whom 2610 (56.2%) had available data to assess the ABC pathway usage (mean age, 74.4±10.2; 42.8% women). Among patients with polypharmacy (n=2262; mean age, 74.6±10.1; 43.3% women), 1328 (58.7%) had available data to assess the use of the ABC pathway. Adherence to the ABC pathway was associated with a lower risk of the primary composite outcome among patients with multimorbidity (odds ratio, 0.48; 95% CI, 0.29-0.79) and in the polypharmacy group (odds ratio, 0.39; 95% CI, 0.19-0.78). Health-related quality of life was lower in the non-ABC-adherent group compared with the ABC-treated patients. Conclusions This nationwide real-world registry shows that adherence to the ABC pathway is associated with improved clinical outcomes and health-related quality of life in clinically complex Chinese patients with atrial fibrillation with multimorbidity or polypharmacy.

Prevalence of polypharmacy in community-dwelling older adults from seven centres in five European countries: a cross-sectional study of DO-HEALTH.

OBJECTIVE: To investigate the prevalence of polypharmacy and characteristics associated with polypharmacy in older adults from seven European cities. DESIGN: Cross-sectional study of baseline data from DO-HEALTH. SETTING AND PARTICIPANTS: DO-HEALTH enrolled 2157 community-dwelling adults age 70 and older from seven centres in Europe. Participants were excluded if they had major health problems or Mini-Mental State Examination Score <24 at baseline. PRIMARY OUTCOME MEASURES: Extensive information on prescription and over-the-counter medications were recorded. Polypharmacy was defined as the concomitant use of five or more medications, excluding vitamins or dietary supplements. Bivariate and multivariable logistic regression was used to test the association of sociodemographic factors (age, sex, years of education, living situation and city) and health-related indicators (number of comorbidities, cognitive function, frailty status, body mass index (BMI), prior fall, self-rated health and smoking status) with polypharmacy. RESULTS: 27.2% of participants reported polypharmacy ranging from 16.4% in Geneva to 60.8% in Coimbra. In the multivariable logistic regression analyses, older age (OR 1.07; 95% CI 1.04 to 1.10), greater BMI (OR 1.09; 95% CI 1.06 to 1.12) and increased number of comorbidities (OR 2.13; 95% CI 1.92 to 2.36) were associated with polypharmacy. Women were less likely to report polypharmacy than men (OR 0.65; 95% CI 0.51 to 0.84). In comparison to participants from Zurich, participants from Coimbra were more likely to report polypharmacy (OR 2.36; 95% CI 1.56 to 3.55), while participants from Geneva or Toulouse were less likely to report polypharmacy ((OR 0.36; 95% CI 0.22 to 0.59 and OR 0.64; 95% CI 0.42 to 0.96), respectively). Living situation, smoking status, years of education, prior fall, cognitive function, self-rated health and frailty status were not significantly associated with polypharmacy. CONCLUSION: Polypharmacy is common among relatively healthy older adults, with moderate variability across seven European cities. Independent of several confounders, being a woman, older age, greater BMI and greater number of comorbidities were associated with increased odds for polypharmacy. TRIAL REGISTRATION NUMBER: NCT01745263.

Effect of polypharmacy on bleeding with rivaroxaban versus vitamin K antagonist for treatment of venous thromboembolism.

BACKGROUND: Polypharmacy, including use of inhibitors of CYP3A4 and P-glycoprotein (P-gp), is common in patients with venous thromboembolism (VTE) and is associated with increased bleeding. METHODS: In 8246 patients included in the EINSTEIN-VTE studies for acute VTE, we evaluated the effect of polypharmacy on bleeding and on the relative differences between rivaroxaban and enoxaparin/vitamin K antagonist (VKA). We assessed the incidence of clinically relevant bleeding (major and clinically relevant nonmajor bleeding) by number of comedications (none, 1-3, ≥4) at baseline, and by use of CYP3A4 and/or P-gp inhibitors. Interaction between rivaroxaban versus enoxaparin/VKA and comedication was assessed by Cox regression analysis with pinteraction estimates. RESULTS: With increasing number of comedications, the incidence of clinically relevant bleeding rose from 5.7% to 13.3% in rivaroxaban recipients and from 9.1% to 11.1% in enoxaparin/VKA recipients. Whereas rivaroxaban was associated with a reduced bleeding risk compared with enoxaparin/VKA in patients without comedication (hazard ratio [HR] 0.6, 95% confidence interval [CI] 0.4-0.9), the risk was similar in patients with ≥4 comedications (HR 1.2, 95% CI 0.97-1.5, pinteraction .002). Use of CYP3A4 and/or P-gp inhibitors was associated with a doubled bleeding risk compared with no use, without a difference between rivaroxaban and enoxaparin/VKA. CONCLUSION: We conclude that fixed-dose rivaroxaban as compared with enoxaparin followed by dose-adjusted VKA is not associated with an increased bleeding risk in patients with VTE administered polypharmacy in general and CYP3A4 and/or P-gp inhibitors specifically. This implies that the observed increased bleeding risks with polypharmacy and use of CYP3A4 and/or P-gp inhibitors are likely explained by comorbidities and frailty, and not by pharmacokinetic interactions.

Implications for herbal polypharmacy: coumarin-induced hepatotoxicity increased through common herbal phytochemicals astragaloside IV and atractylenolide I.

Hepatotoxicity is a well-known adverse effect of many substances, with toxicity often resulting from interactions of drugs with other drug-like substances. With the increased availability of complementary and alternative medicines, including herbal medicines, the likelihood of adverse interactions between drugs and drug-like substances in herbs increases. However, the impact of potential herb-herb interactions is little understood. To assess the potential of two cytochrome P450 enzyme modulating phytochemicals common to many herbal medicines, atractylenolide I (ATR-I) and astragaloside IV (AST-IV), to interact with coumarin, another phytochemical common in many foods, a hepatocyte function model with a liver carcinoma cell line, HepG2, was exposed to these agents. To determine the effects of cytochrome P450 modulation by these phytochemicals certain cells were induced with rifampicin to induce cytochrome P450. Increasing concentrations of ATR-I combined with a fixed, nontoxic concentration of coumarin (200 µM), demonstrated significant additive interactions. 300 µM ATR-I produced a 31% reduction in cell viability (p < 0.01) with coumarin in rifampicin uninduced cells. In rifampicin-induced cells, ATR-I (100-300 µM) produced a significant reduction in cell viability (p < 0.01) with coumarin (200 µM). AST-IV with fixed coumarin (200 µM) showed 27% toxicity at 300 µM AST-IV in rifampicin uninduced cells (p < 0.05) and 30% toxicity in rifampicin induced cells (p < 0.05). However, when fixed coumarin and AST-IV were combined with increasing concentrations of ATR-I no further significant increase in toxicity was observed (p > 0.05). These results demonstrate the potential toxic interactive capabilities of common traditional Chinese herbal medicine phytochemicals and underline the potential importance of coumarin-mediated toxicity.

A multi-centre cohort study on healthcare use due to medication-related harm: the role of frailty and polypharmacy.

OBJECTIVES: To determine the association between frailty and medication-related harm requiring healthcare utilisation. DESIGN: Prospective observational cohort study. SETTING: Six primary and five secondary care sites across South East England, September 2013-November 2015. PARTICIPANTS: One thousand and two hundred and eighty participants, ≥65 years old, who were due for discharge from general medicine and older persons' wards following an acute episode of care. Exclusion criteria were limited life expectancy, transfer to another hospital and consent not gained. MAIN OUTCOME MEASURES: Medication-related harm requiring healthcare utilisation (including primary, secondary or tertiary care consultations related to MRH), including adverse drug reactions, non-adherence and medication error determined via the review of data from three sources: patient/carer reports gathered through a structured telephone interview; primary care medical record review; and prospective consultant-led review of readmission to recruiting hospital. Frailty was measured using a Frailty Index, developed using a standardised approach. Marginal estimates were obtained from logistic regression models to examine how probabilities of healthcare service use due to medication-related harm were associated with increasing number of medicines and frailty. RESULTS: Healthcare utilisation due to medication-related harm was significantly associated with frailty (OR = 10.06, 95% CI 2.06-49.26, P = 0.004), independent of age, gender, and number of medicines. With increasing frailty, the need for healthcare use as a result of MRH increases from a probability of around 0.2-0.4. This is also the case for the number of medicines. CONCLUSIONS: Frailty is associated with MRH, independent of polypharmacy. Reducing the burden of frailty through an integrated health and social care approach, alongside strategies to reduce inappropriate polypharmacy, may reduce MRH related healthcare utilisation.

Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review.

Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.

Factors associated to potentially inappropriate prescribing in older patients according to STOPP/START criteria: MoPIM multicentre cohort study.

OBJECTIVES: The objectives of the present analyses are to estimate the frequency of potentially inappropriate prescribing (PIP) at admission according to STOPP/START criteria version 2 in older patients hospitalised due to chronic disease exacerbation as well as to identify risk factors associated to the most frequent active principles as potentially inappropriate medications (PIMs). METHODS: A multicentre, prospective cohort study including older patients (≥65) hospitalized due to chronic disease exacerbation at the internal medicine or geriatric services of 5 hospitals in Spain between September 2016 and December 2018 was conducted. Demographic and clinical data was collected, and a medication review process using STOPP/START criteria version 2 was performed, considering both PIMs and potential prescribing omissions (PPOs). Primary outcome was defined as the presence of any most frequent principles as PIMs, and secondary outcomes were the frequency of any PIM and PPO. Descriptive and bivariate analyses were conducted on all outcomes and multilevel logistic regression analysis, stratified by participating centre, was performed on the primary outcome. RESULTS: A total of 740 patients were included (mean age 84.1, 53.2% females), 93.8% of them presenting polypharmacy, with a median of 10 chronic prescriptions. Among all, 603 (81.5%) patients presented at least one PIP, 542 (73.2%) any PIM and 263 (35.5%) any PPO. Drugs prescribed without an evidence-based clinical indication were the most frequent PIM (33.8% of patients); vitamin D supplement in older people who are housebound or experiencing falls or with osteopenia was the most frequent PPO (10.3%). The most frequent active principles as PIMs were proton pump inhibitors (PPIs) and benzodiazepines (BZDs), present in 345 (46.6%) patients. This outcome was found significantly associated with age, polypharmacy and essential tremor in an explanatory model with 71% AUC. CONCLUSIONS: PIMs at admission are highly prevalent in these patients, especially those involving PPIs or BZDs, which affected almost half of the patients. Therefore, these drugs may be considered as the starting point for medication review and deprescription. TRIAL REGISTRATION NUMBER: NCT02830425.