Drugs & Aging最新文献

Background and objective: Despite the increasing use of cannabis by older Canadians, little is known about cannabis safety in this population, particularly in non-clinical settings. The purpose of this study was to describe the self-reported adverse effects experienced by community-dwelling older Canadians who use cannabis.

Methods: Canadians aged 50 years and older completed an online survey regarding their knowledge, perceptions, and experiences with cannabis. Respondents who reported current cannabis use were asked to report any adverse effects experienced in the past year related to their cannabis use. Adverse effects were categorized, and multivariate logistic regressions were performed to assess predictors of adverse effects.

Results: A total of 1615 older adults completed the survey, of whom 503 reported current use of cannabis and were included in this analysis. Adverse effects were reported by 308 participants (61.2%) and included dry mouth (36.2%), feeling high (25.9%), and adverse effects impacting balance (22.1%) and mental alertness (20.3%). Compared with participants aged 50-60 years, those aged 70 years and older had lower odds of reporting any adverse effects (odds ratio (OR) 0.524, 95% confidence interval (CI) 0.303-0.906) or adverse effects impacting mental alertness (OR 0.318, 95% CI 0.172-0.588). Female participants had higher odds of reporting any adverse effect (OR 1.989, 95% CI 1.332-2971) or adverse effects impacting balance (OR 1.930, 95% CI 1.198-3.109).

Conclusions: Adverse effects to cannabis are common amongst community-dwelling older adults. Increased education and guidance regarding adverse effects of cannabis, including the composition and dose of cannabis products, may help increase safe use by this population.

Background: Data on the use of antibody drug conjugates (ADCs) in older patients are scarce.

Objective: The objective was to study the safety and efficacy of ADCs used in early phase clinical trials in patients aged ≥ 65 years compared with younger patients.

Patients and methods: All patients enrolled in early phase clinical trials (phase I or II) of ADCs for solid tumors in our institution between November 2014 and May 2023 were included in this retrospective monocentric study. Safety and efficacy were compared between patients ≥ 65 and < 65 years old (y.o).

Results: A total of 136 patients were included in our study, with 43 (31.6%) patients aged ≥ 65 y.o. In comparison with the younger population, patients aged 65 years or older had similar demographic characteristics. Older patients experienced the same rate of all-grade adverse events (95.3 versus 97.8%) and all-grade related adverse events (65.1 versus 66.7%) but more high-grade adverse events (41.9 versus 30.1%) than younger patients. In the univariate analysis, we identified age, taken as a continuous variable, as associated with high-grade adverse event (p = 0.047). No statistically significant difference was found between older and younger patients in terms of disease control rate (65 versus 54%), median progression-free survival (2.76 months [95% confidence interval, 95% CI 1.64-3.75] compared with 2.56 [95% CI 1.81-2.79], p = 0.34), or median overall survival (6.57 months [95% CI 4.01-13.01] compared to 7.89 [95% CI 6.83-9.36], p = 0.65).

Conclusions: In our cohort, ADC therapy provided comparable survival benefits for the older patients but with a higher risk of high-grade adverse event.

Background: Prescribing cascades occur when a new drug is prescribed to treat an adverse drug event caused by an existing medication, resulting in unnecessary, or potentially hazardous additional drugs. To date, there are no published studies assessing the prevalence of prescribing cascades in older hospitalised adults.

Objective: To investigate the prevalence of prescribing cascades in hospitalised older adults.

Methods: We conducted a prospective observational study of adults aged ≥ 65 years with multimorbidity and polypharmacy presenting to hospital with acute unselected medical or surgical illness. Prescribing cascades were identified using two predefined validated explicit cascade lists, i.e. ThinkCascades, and a list derived from a recently published systematic review of prescribing cascades in community-dwelling adults, referred to here as the 'Doherty list'. Potential prescribing cascades were classified as 'definite', 'probable', 'possible', 'uncertain' or 'indeterminate' according to pre-specified criteria.

Results: The study included 385 consecutive patients (55.1% female, mean age 80.2 years, standard deviation 7.3 years). A total of 281 potential prescribing cascades (drug A → drug B) were identified in 152 patients (39.4%). Probable or possible prescribing cascades were identified in 48 patients (12.4%) using the Doherty list and in 44 patients (11.4%) using ThinkCascades. Patients exposed to potential prescribing cascades experienced greater levels of polypharmacy than patients not exposed to prescribing cascades (median interquartile range [IQR] of 12 [9-14] daily drugs versus 9 [IQR 7-11], p < 0.001).

Conclusions: Potential prescribing cascades were highly prevalent in older hospitalised adults. Practical tools are needed to assist prescribers in prevention, recognition and management of inappropriate prescribing cascades.

Testosterone is the classical male anabolic hormone, involved in sexual development, virilisation and regulation of body composition in adult men. Organic disease involving the hypothalamus, pituitary or testes may interfere with endogenous testosterone production. In such men, testosterone treatment effectively ameliorates symptoms and signs of androgen deficiency. However, non-gonadal factors including age, body mass index and medical comorbidities influence circulating testosterone, and older men have on average lower testosterone concentrations compared with younger men. In these men, testosterone treatment would be a pharmacological intervention requiring stringent justification via high-quality evidence from randomised controlled trials (RCTs). Recent RCTs show benefits of testosterone treatment to improve sexual function, anaemia and bone mineral density in older men, and to prevent or revert type 2 diabetes mellitus in men at high risk. Results from a large cardiovascular safety trial in men with or at risk of cardiovascular disease provide important reassurance as to cardiovascular and prostate safety of testosterone treatment. Key questions remain as to whether testosterone's anabolic and other effects can be used safely to counter reductions in lean mass associated with incretin-based weight loss medications in men with obesity, and whether it might prevent disabilities including frailty, osteoporotic fractures and dementia in older men generally. This last question could be answered by a new testosterone RCT, targeting men in the 65-80 years age bracket, which would necessarily be large and of extended duration. A composite endpoint could be used which integrates potential benefits and risks, such as disability-free survival.

Objective: Lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) significantly impact quality of life in aging men. While monotherapies, including alpha-blockers, 5-alpha reductase inhibitors (5-ARI), or phosphodiesterase type 5 inhibitors (PDE5i), are widely used, the potential benefits and risks of combination pharmacotherapies remain less well-documented. This study reviews and assesses the current evidence regarding the use of combination pharmacotherapies in the management of BPH-related LUTS to provide a comprehensive overview of their efficacy and safety profiles.

Methods: A literature search was conducted in PubMed, including randomized controlled trials (RCTs) published up to June 2024. Studies were selected on the basis of predefined inclusion criteria, focusing on clinical outcomes such as International Prostate Symptom Score (IPSS), urinary flow rate (Q_max), and quality of life. Data from 22 eligible studies were analyzed and summarized.

Results: Combination therapies, particularly those involving alpha-blockers and 5-ARI, demonstrated significant reductions in clinical progression, improvements in urinary flow, and symptom relief compared with monotherapies. Therapies combining alpha-blockers with anticholinergics, beta-3 agonists, or phytotherapeutic agents showed potential for targeting mixed symptoms, though evidence remains limited. Triple therapy studies are scarce, with benefits observed only in highly symptomatic or refractory cases.

Conclusions: Combination therapies for LUTS/BPH offer superior efficacy over monotherapy in certain cases, particularly with alpha-blockers and 5-ARI, which significantly reduce disease progression and symptoms. Other combinations, including alpha-blockers with anticholinergics, beta-3 agonists, or PDE5 inhibitors, provide potential benefits for patients with mixed symptom profiles, though evidence remains heterogeneous. The level of evidence among studies varies significantly, ranging from high-quality RCTs to lower-level observational data, requiring careful interpretation. While combination treatments improve outcomes, they also present challenges in adherence and side effects. A personalized and evidence-based approach is essential to optimize treatment selection and balance efficacy with tolerability.

Cystic fibrosis (CF) is an inherited condition that leads to multiorgan dysfunction, especially in the respiratory, gastrointestinal, and reproductive tracts, with associated conditions including persistent pulmonary infection, liver disease, pancreatic insufficiency, and infertility. Historically, people with CF (pwCF) suffered a shortened lifespan due to complications of the condition, namely respiratory. The emphasis on center-based, multidisciplinary care and the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has resulted in pwCF living longer and healthier lives. Now they may encounter some of the health and social issues associated with growing older, which previously were not a typical experience for this population. In this article, we review relevant health issues for the aging CF population, including complications that arise from the condition itself, issues encountered due to treatment, and general conditions associated with aging that may manifest earlier or differently in pwCF. We discuss the recommendations for screening and treatment of relevant conditions, and considerations for the integration of healthcare professionals across disciplines into the care of this population.

Background: Both bleeding and adverse ischemic events increase with age, compounding the benefit-risk balance of anticoagulants in older patients. We present analyses using benefit-risk methods to better understand the age-dependence of the benefit-risk profile of rivaroxaban in patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE).

Methods: Randomized controlled trial data from the ROCKET-AF (NVAF) and EINSTEIN DVT, EINSTEIN PE, EINSTEIN-Extension, and EINSTEIN CHOICE in (VTE) were used. For ROCKET-AF, benefits and risks were assessed with incidence rates for key thrombotic and bleeding endpoints and a net clinical benefit (NCB) measure. Cumulative incidences (estimated by the Kaplan-Meier method) were estimated at day 185 for EINSTEIN and EINSTEIN Extension and 1 year for EINSTEIN CHOICE. Incidence differences were calculated for the overall population and age subgroups of < 65, 65-75, and > 75 years.

Results: In ROCKET-AF, rate differences in the composite NCB outcome (vascular death, stroke, myocardial infarction, fatal bleeding, critical organ bleeding, and non-CNS systemic embolism) favored rivaroxaban overall and by age < 65, 65-75, and > 75 years (-84, -25, -61, and -150 cases per 10,000 patient-years, respectively). In the pooled EINSTEIN DVT and EINSTEIN PE studies, cumulative incidence differences for the composite NCB outcome (recurrent VTE and major bleeding) were -103, 3, -105, and -544 per 10,000 patients, respectively. For extended VTE treatment with rivaroxaban versus placebo in EINSTEIN-Extension, NCB results were -536, -492, -556, and -601 per 10,000 patients, respectively. In the EINSTEIN CHOICE analysis, NCB favored rivaroxaban 20 mg versus aspirin (-284, -255, -339, and -338, respectively) and rivaroxaban 10 mg versus aspirin (-339, -328, -485, and -80, respectively).

Conclusions: This analysis demonstrated a positive benefit-risk profile with rivaroxaban versus trial comparators in older patients with NVAF or VTE, with benefit-risk increasingly favoring rivaroxaban with increasing age.

Clinical trial registration: http://ClinicalTrials.gov , identifiers: NCT00403767 (ROCKET-AF), NCT00440193 (EINSTEIN DVT), NCT00439777 (EINSTEIN PE), NCT00439725 (EINSTEIN Extension), and NCT02064439 (EINSTEIN CHOICE).

Background: Polypharmacy is associated with reduced health-related quality of life (HRQoL). This study explores the association between prescription and non-prescription medication pill burdens, independent of underlying morbidity, on HRQoL in an older adult population.

Methods: Data from the final intervention year of the ASPirin in Reducing Events in the Elderly (ASPREE) randomized trial in older adults from Australia and the USA, were analyzed cross-sectionally. Participants reported daily prescription and non-prescription pill counts at the final trial visit. HRQoL was assessed using the 12-Item Short-Form instrument (SF-12) and summarized into the physical component summary (PCS) score and mental component summary (MCS) score, where lower scores reflect poorer HRQoL. Multivariable regression, adjusted for covariates, was used to examine the relationships of categorized prescription and non-prescription pill counts with PCS and MCS separately.

Results: 15,165 participants responded to the question about prescription use and 15,727 for non-prescriptions (mean age = 80 years). Compared with non-users of prescription medications, lower mean PCS scores and larger reductions in scores were seen as prescription medication pill burden increased from 1-3, 4-6, 7-9, to ≥ 10 pills (- 1.7, - 4.5, - 7.6, and - 10.9, respectively, p < 0.001). A similar relationship, but of lesser magnitude, was observed with non-prescription medication pill burden, where the mean PCS was lower by - 0.2 for 1-3 pills (p = 0.494), - 1.8 for 4-6 (p < 0.001), and - 1.9 for ≥ 7 pills (p < 0.001), compared with non-users. No significant association was observed between prescription or non-prescription medication pill burdens and MCS.

Conclusions: Prescription and non-prescription medication pill burdens are independently associated with reduced physical, but not mental, HRQoL in older adults.

Background: Deprescribing guidelines reduce the use of potentially inappropriate medications (PIMs) in trial settings; however, their real-world impact remains unclear. Therefore, this study assesses deprescribing trends and the impact of guideline publications (STOPPFrail, proton pump inhibitors [PPIs], and antipsychotics) on these trends among nursing home residents with limited life expectancy in Belgium.

Methods: Deprescribing was assessed using linked healthcare reimbursement data for all residents aged 65 years and older who died between 2014 and 2019. In total, 15 PIMs from STOPPFrail version 1 were selected. Deprescribing was operationalized as discontinuing at least one PIM in the last 4 months of life among those who had been prescribed these medications chronically between 6-12 months prior to death. To identify changes in the trend of deprescribing, we employed a joinpoint linear regression model. We calculated the average quarterly percent change (AQPC) and 95% confidence intervals (CIs). In addition, we used autoregressive integrated moving average (ARIMA) modeling to explore the impact of publication of these guidelines on four commonly used PIMs: PPIs, antipsychotics, lipid modifying agents, and calcium.

Results: Among 244,865 residents, 169,782 (69.3%) were chronically prescribed at least one PIM and 50,487 (29.7%) had at least one discontinued. The prevalence of deprescribing declined from 31.7 to 27.66% between the first quarter of 2014 and the fourth quarter of 2019, with an average quarterly percent change decline of - 0.47% (95% CI - 0.85, - 0.10). No joinpoints were identified, indicating a consistent linear trend with no interruptions or statistically significant shifts in the rate of change in deprescribing prevalence. ARIMA modeling found that the publication of deprescribing guidelines had no impact on deprescribing trends.

Conclusions: Despite the high use of PIMs, and the publication of the STOPPFrail, PPI, and antipsychotic deprescribing guidelines, deprescribing rates remained low and even decreased. These findings emphasize the importance of implementation efforts that go well beyond guideline publications to effectively change deprescribing practices.

Background and objectives: Antipsychotics are used to manage behaviours and psychological symptoms of dementia. While antipsychotics have been associated with increased risk of adverse outcomes, factors associated with these outcomes have been understudied. Thus, the aim of this study was to identify factors associated with risk of hospitalisation and mortality in older people living with dementia using antipsychotics.

Methods: In total, four databases (Embase, Medline, PsycINFO and Web of Science) were searched from 2010 to 30 April 2024 using keywords and Medical Subject Heading (MeSH) terms related to dementia, older adults, antipsychotics and outcomes (hospitalisation or mortality). Studies including older adults (≥ 65 years) with dementia and extractable data on risk measures were eligible. Risk of bias was assessed using the Joanna Briggs Institute's critical appraisal tools and narrative synthesis of results was performed.

Results: Of the 4139 studies identified, 24 were included (Total N [patients] = 587,885) with the majority being cohort studies (N = 23). Antipsychotic-related factors associated with mortality risk included the type of antipsychotic (e.g. typical versus atypical, adjusted hazards ratio [aHR] 1.50, 95% confidence interval [CI] 1.10, 2.10), and dose (high versus low, relative increases ranging from 57 to 155%). Patient-related factors included age (aHR 1.05, 95% CI 1.01, 1.08) and concomitant use of medications (e.g. benzodiazepines, aHR 2.19, 95% CI 1.83, 2.63). Antipsychotic-related factors associated with hospitalisation risk included the type of antipsychotic (e.g. atypical verus typical, aHR 1.17, 95% CI 1.08, 1.27) and dose (high versus low, adjusted odds ratio [aOR] 1.19, 95% CI 1.09, 1.31). Patient-related factors included concomitant benzodiazepine use (aHR 1.55, 95% CI 1.29, 1.86), and new use compared with past use (aOR 3.07, 95% CI 2.84, 3.32).

Conclusions: This review identified several factors associated with risks of hospitalisation and mortality in antipsychotic users with dementia. Clinicians should consider these risk factors when prescribing antipsychotics to people living with dementia.