Polypharmacy occurrence and the related risk of premature death among older adults in Denmark: A nationwide register-based cohort study.

BACKGROUND: Polypharmacy, defined as the concurrent use of ≥5 medications, increases the risk of drug-drug and drug-disease interactions as well as non-adherence to drug therapy. This may have negative health consequences particularly among older adults due to age-related pharmacokinetic and pharmacodynamic changes. This study aims to uncover the occurrence of polypharmacy among older adults in Denmark and investigate how polypharmacy relates to mortality. METHOD: This nationwide register-based study included 1,338,058 adults aged 65+ years between January 2013 and December 2017 in Denmark. Polypharmacy prevalence was measured at time of inclusion while incidence and the association between polypharmacy and mortality were measured over the five-year follow-up using Cox regression. In an attempt to adjust for confounding by indication, propensity scores with overlap weighting were introduced to the regression model. RESULTS: At time of inclusion, polypharmacy prevalence was 29% and over the five years follow-up, 47% of the remaining adults transitioned into polypharmacy. Identified risk factors included multimorbidity (2+ morbidities: HR = 3.51; 95% CI = 3.48-3.53), age (95+ years: HR = 2.85; 95% CI = 2.74-2.96), socioeconomic factors (Highest income quartile: HR = 0.81; 95% CI = 0.80-0.81), region of birth region (Non-western migrants: HR = 0.77; 95% CI = 0.75-0.79), marital status (Divorced: HR = 1.10; 95% CI = 1.10-1.12) and year of inclusion (2017: HR = 1.19; 95% CI = 1.19-1.22). Further analyses showed that polypharmacy involves many different drug cocktails with medication for the cardiovascular system (95%), blood and blood-forming organs (69%), alimentary tract and metabolism (61%) and nervous system (54%) contributing the most. After adjustment for propensity scores with OW, both polypharmacy (HR = 3.48, CI95% = 3.41-3.54) and excessive polypharmacy (HR = 3.48, CI95% = 3.43-3.53) increased the risk of death substantially. CONCLUSION: A considerable proportion of older adults in Denmark were exposed to polypharmacy dependent on health status, socio-economic status, and societal factors. The associated three- to four-fold mortality risk indicate a need for further exploration of the appropriateness of polypharmacy among older adults.

Medication-related adverse events in health care-what have we learned? A narrative overview of the current knowledge.

PURPOSE: Although medication-related adverse events (MRAEs) in health care are vastly studied, high heterogeneity in study results complicates the interpretations of the current situation. The main objective of this study was to form an up-to-date overview of the current knowledge of the prevalence, risk factors, and surveillance of MRAEs in health care. METHODS: Electronic databases (PubMed, MEDLINE, Web of Science, and Scopus) were searched with applicable search terms to collect information on medication-related adverse events. In order to obtain an up-to-date view of MRAEs, only studies published after 2000 were accepted. RESULTS: The prevalence rates of different MRAEs vary greatly between individual studies and meta-analyses. Study setting, patient population, and detection methods play an important role in determining detection rates, which should be regarded while interpreting the results. Medication-related adverse events are more common in elderly patients and patients with lowered liver or kidney function, polypharmacy, and a large number of additional comorbidities. However, the risk of MRAEs is also significantly increased by the use of high-risk medicines but also in certain care situations. Preventing MRAEs is important as it will decrease patient mortality and morbidity but also reduce costs and functional challenges related to them. CONCLUSIONS: Medication-related adverse events are highly common and have both immediate and long-term effects to patients and healthcare systems worldwide. Conclusive solutions for prevention of all medication-related harm are impossible to create. In the future, however, the development of efficient real-time detection methods can provide significant improvements for event prevention and forecasting.

Association of healthy lifestyle and all-cause mortality according to medication burden.

BACKGROUND: Healthy lifestyle is associated with reduced all-cause mortality, but it is not known whether this association persists for individuals with high medication burden. We examined the association between healthy lifestyle behaviors and all-cause mortality across different degrees of polypharmacy. METHODS: This was a secondary analysis of 20,417 adults aged ≥45 years from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study. The primary exposure was healthy lifestyle (adherence to Mediterranean diet, physical activity, smoking abstinence, sedentary behavior avoidance, and composite healthy behavior score [HBS]). The primary outcome was all-cause mortality. Strata of medication burden were based on the number of medications taken (no polypharmacy: 0-4, polypharmacy: 5-9, hyperpolypharmacy: ≥10). We used Cox proportional hazards regression models to examine the association between healthy lifestyle behaviors and mortality within each medication burden stratum and examined for interactions with age. RESULTS: The healthiest category of each lifestyle behavior, except sedentary behavior avoidance among the hyperpolypharmacy group, was associated with lower all-cause mortality (hazard ratio [HR]) regardless of medication burden: Mediterranean diet (no polypharmacy: HR 0.77, polypharmacy: HR 0.78, hyperpolypharmacy: HR 0.85), physical activity (no polypharmacy: HR 0.87, polypharmacy: HR 0.82, hyperpolypharmacy: HR 0.79), smoking abstinence (no polypharmacy: HR 0.40, polypharmacy: HR 0.45, hyperpolypharmacy: HR 0.52), and sedentary behavior avoidance (no polypharmacy: HR 0.88, polypharmacy: HR 0.86, hyperpolypharmacy: HR 0.95). Higher HBS was inversely associated with all-cause mortality within each medication burden stratum (no polypharmacy: HR 0.52, polypharmacy: HR 0.55, hyperpolypharmacy: HR 0.69). Although there was an interaction with age among those with no polypharmacy and those with polypharmacy, point estimates for HBS followed a graded pattern whereby higher HBS was incrementally associated with improved mortality across all age strata. CONCLUSION: Greater adherence to a healthy lifestyle was associated with lower all-cause mortality irrespective of medication burden and age.

Antibiotic use and associated factors in adult outpatients from 2000 to 2019.

The aims of the study were to assess the changes in 19-years use of antibiotics (overall, by age, sex and geographical area) and of those classes deemed to be quality indicators for their consumption and to evaluate factors associated to antibiotic use. We analyzed drug prescription data collected in the administrative database of the Lombardy Region (Northern Italy) for outpatients aged 40+ years from 2000 to 2019. Logistic regression analyses were performed to evaluate the association between receiving at least one antibiotic prescription and year of observation, gender, age groups, area of residence, polypharmacy and hospitalizations in the index year. The prevalence of patients prescribed with antibiotics remained high from 2000 (33.8%) to 2019 (32.6%). Prevalence of use of second-line choice antibiotics (penicillin combinations with beta-lactamase inhibitors, third and fourth generation cephalosporins, macrolides) continued to increase, only fluoroquinolones decreased in 2019 (19%) comparing to 2018 (26%), at the time when the Italian Medicines Agency promulgated safety warnings. Females (OR 1.28, 95%CI 1.27-1.28), people living in Brescia (OR 1.24, 95%CI 1.24-1.25), those exposed to polypharmacy (OR 2.57, 95%CI 2.56-2.57) and those hospitalized 1 to 3 (OR 1.86, 95%CI 1.85-1.86) or more than 3 (OR 2.02, 95%CI 2.01-2.03) times a year had a statistically significant higher risk of receiving antibiotics. The high use of antibiotics over the study period further reinforces the need of impactful interventions, in order to improve the rational use of antibiotics and to reduce the risks of antimicrobial resistance. The differences outlined should be considered when monitoring and planning these interventions.

A comparison of anticholinergic burden in older patients with and without cancer.

Aim: To compare anticholinergic burden (ACB) in older patients with and without cancer and evaluate the effects of ACB on geriatric syndromes. Methods: A total of 291 patients from the geriatric clinic and 301 patients from the oncology clinic were evaluated. ACB <2 was categorized as low ACB and ACB ≥2 was categorized as high ACB. A comprehensive geriatric assessment was performed on patients from the geriatric clinic. Results: ACB scores were significantly higher in patients without cancer compared with those with cancer (p < 0.005). Number of falls and Geriatric Depression Scale 15 scores were higher and Mini-Nutritional Assessment and Barthel/Lawton activities of daily living scores were lower in geriatric patients with high ACB scores compared with those with low ACB scores (p < 0.005). Conclusion: It is crucial to understand the potential effects of ACB for rational drug use and optimum cancer management in older patients with cancer.

Lay abstract The elderly population is increasing rapidly worldwide, and most cancer patients are over the age of 65. In this age group, preexisting medical conditions other than cancer lead to the use of multiple drugs, which is defined as polypharmacy. Additionally, the anticholinergic burden (ACB) of the drugs affects cancer treatment in the elderly. This study investigated the frequency of polypharmacy and ACB in elderly patients with and without cancer and their relationship with geriatric syndromes such as depression, falls, nutritional and cognitive impairments. We found that ACB was higher in older patients without cancer than those with cancer and is related to increased falls, depressive symptoms, and impaired nutritional and functional status in older patients. Given the prevalence of cancer among older adults, it is crucial to understand the potential effects of the ACB for rational drug use and optimum cancer management in older patients with cancer.

Antipsychotic Polypharmacy Is Associated With Adverse Drug Events in Psychiatric Inpatients: The Japan Adverse Drug Events Study.

BACKGROUND: Antipsychotic (AP) polypharmacy (APP), the coprescription of more than 1 AP, is frequently practiced in psychiatric inpatients and is considered to be a risk factor for adverse drug events (ADEs). However, the association between APP and ADEs among psychiatric inpatients has not been well investigated. METHODS: The Japan Adverse Drug Events (JADE) study was a series of cohort studies conducted in several clinical settings. In particular, the JADE study for psychiatric inpatients was a retrospective cohort study of 448 psychiatric inpatients with a cumulative 22,733 patient-days. We investigated the relationship between APP, defined as a concurrent prescription of 2 or more APs and ADEs. We also assessed the relationship between potential risk factors for ADEs due to APs. RESULTS: Among the 448 patients included in this study, 106 patients (24%) had APP and the remaining 342 patients were prescribed 1 AP or none. Risperidone was the most frequent drug (25%, 109/442 AP prescriptions) used, and levomepromazine was most frequently prescribed as a concurrent medication with other APs (91%, 29/32). The median number of ADEs among the patients with APP was significantly higher than in those without APP (P = 0.001). Antipsychotic polypharmacy was a risk factor for the occurrence of first (adjusted hazard ratio, 1.54; 95% confidence interval, 1.15-2.04) and second (adjusted hazard ratio, 1.99; 95% confidence interval, 1.40-2.79) ADEs. CONCLUSIONS: Antipsychotic polypharmacy was a risk factor for the occurrence of single and multiple ADEs. Antipsychotic polypharmacy should be conservatively and minimally practiced.

Treating the patient and not just the cancer: therapeutic burden in prostate cancer.

BACKGROUND: Prostate cancer (PC) is a leading cause of death in older men. Androgen deprivation therapy (ADT) is considered the standard-of-care for men with locally advanced disease. However, continuous androgen ablation is associated with acute and long-term adverse effects and most patients will eventually develop castration-resistant PC (CRPC). The recent approval of three, second-generation androgen receptor inhibitors (ARIs), apalutamide, enzalutamide, and darolutamide, has transformed the treatment landscape of PC. Treatment with these second-generation ARIs have produced positive trends in metastasis-free survival, progression-free survival, and overall survival. For patients with non-metastatic CRPC, who are mainly asymptomatic from their disease, maintaining quality of life is a major objective when prescribing therapy. Polypharmacy for age-related comorbidities also is common in this population and may increase the potential for drug-drug interactions (DDIs). METHOD: This review summarizes the multiple factors that may contribute to the therapeutic burden of patients with CRPC, including the interplay between age, comorbidities, concomitant medications, the use of ARIs, and financial distress. CONCLUSIONS: As the treatment landscape in PC continues to rapidly evolve, consideration must be given to the balance between therapeutic benefits and potential treatment-emergent adverse events that may be further complicated by DDIs with concomitant medications. Patient-centered communication is a crucial aspect of alleviating this burden, and healthcare professionals (HCPs) may benefit from training in effective patient communication. HCPs should closely and frequently monitor patient treatment responses, in order to better understand symptom onset and exacerbation. Patients also should be encouraged to participate in exercise programs, and health information and support groups, which may assist them in preventing or mitigating certain determinants of the therapeutic burden associated with PC and its management.