Drugs & Aging最新文献

Background: The scientific literature, including systematic reviews and meta-analyses, has frequently described associations between aging, medication use, and frailty, without evaluation of their independent causation. The Bradford Hill Criteria, a framework consisting of nine principles for assessing epidemiological causation, is ideally suited to unconfound and assess the independent causal effect of aging versus medication use, in frailty progression.

Methods: A systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, searched MEDLINE, EMBASE, and CENTRAL with no restrictions on date or study design. Studies were selected based on predefined inclusion criteria and assessed for quality using the Joanna Briggs Institute critical appraisal tool. Where appropriate, meta-analyses of collated data were performed in RStudio, including effect sizes accounting for minimum age and polypharmacy to reduce confounding bias. Causal relationships between aging, medication use, and frailty were then evaluated independently using the nine principles of the Bradford Hill Criteria.

Results: Data from 105 moderate-to-high quality studies based on the Joanna Briggs Institute assessment were extracted, formatted, and compiled to allow evaluation via the Bradford Hill Criteria. Evidence supported a strong independent causal relationship between aging, medication use, and frailty progression across eight of the nine principles. Strength of association, consistency, and a clear biological gradient were observed, with frailty increasing alongside age and medication count, respectively. Temporality was addressed as aging and medication exposure often preceded frailty, while interventions reducing medication supported the experiment criterion. Biological plausibility, biological coherence, and analogy were reinforced by clear biological mechanism, scientific reasoning, and epidemiological patterns. However, specificity could not be fully met, as frailty is influenced by multiple factors beyond aging and medication use, making the relationship inherently non-specific.

Conclusions: An independent causal link between aging and frailty, as well as between medication use and frailty, is well supported by the framework of Bradford Hill Criteria. Given the limited availability of randomized controlled trials or interventional studies in older adults, these findings offer valuable insights where evidence has been lacking and serve as a strategic starting point for future investigations into factors driving frailty progression.

Clinical trial registration: PROSPERO Registration Number CRD42024614144.

Aim: The aim of this repeated cross-sectional study was to estimate polypharmacy prevalence and trends in Australian adults between 2013 and 2024.

Methods: Dispensing records of medicines subsidised by the Australian Pharmaceutical Benefits Scheme (PBS) were analysed for a nationally representative 10% sample of PBS-eligible beneficiaries.

Outcomes: The outcomes for this study were annual polypharmacy and hyperpolypharmacy prevalence, defined as ≥5 and ≥10 regular medicines, respectively, and average annual percentage change (AAPC), overall and by gender-stratified age groups. These groups are defined broadly as adult (18-64 years) and older adult (≥65 years), and as younger adulthood (18-39 years), middle (40-64 years), early older (65-84 years) and later older (85+ years) age.

Results: Polypharmacy prevalence rose from 8.0% in 2013 to 9.2% (AAPC+1.4%), with two million Australians exposed in 2024. Although prevalence was initially higher among women, by 2024 men had surpassed women from middle age onward. Increasing AAPC was observed among adult and older adult men (+1.0%, +1.3%), while remaining stable among women. Finer age strata showed growth among men in middle, early older, and later older age (+1.7%, +1.0%, +3.4%) and divergent trends among women, with increases in younger adulthood (+1.8%) and declines in early older age (- 0.7%).

Conclusion: Shifting gender trends appear driven by stabilising or declining prevalence among women alongside sustained growth among men. By 2024, men exceeded women from middle age onward, suggesting a changing prescribing landscape. These patterns highlight the need for targeted interventions, and gender-stratified monitoring to ensure prescribing is appropriate. The long-term consequences of increasing polypharmacy in younger and middle-aged adults remain unclear and warrant further investigation.

Background: Global aging makes polypharmacy in older adults a critical concern. Pharmacist-led deprescribing shows promise, but lacks routine implementation. Japan introduced "the Medication Adjustment Support Fee (the Adjustment Fee)" in 2018 for deprescribing medications in patients with polypharmacy based on pharmacists' recommendations.

Objective: We aimed to investigate: (1) medication distribution among older patients; (2) medications most frequently deprescribed based on pharmacists' recommendations; and (3) factors associated with successful deprescribing.

Methods: This retrospective study analysed patients aged ≥ 65 years who had prescriptions dispensed for ≥ 60 days from 2069 community pharmacies (April 2020-September 2023). Eligibility for the adjustment fee required six or more oral medications for ≥ 4 weeks, with pharmacists receiving remuneration when two or more medications were deprescribed and sustained for ≥ 4 weeks. We examined: (1) medication distribution in older patients; (2) most frequently deprescribed medications based on pharmacists' recommendations; and (3) factors associated with deprescribing using multi-level logistic regression.

Results: Amongst 1,458,323 older patients, 36.9% (537,884) met the eligibility criteria for the adjustment fee, but only 0.08% had medications deprescribed based on pharmacist recommendations. At the pharmacy level, 10% of pharmacies (213/2069) claimed the fee at least once. The most frequently deprescribed medications were rebamipide (0.05%), mecobalamin (0.06%) and magnesium oxide (0.02%). Older age, higher number of medications taken, presence of a family pharmacist, and longer evaluation periods were significantly associated with claiming for the adjustment fee (p < 0.001 for all).

Conclusions: Pharmacist-led deprescribing is infrequently implemented. Future studies could investigate the potential of strengthened incentives, enhanced collaboration, and robust protocols to optimize medication management in older adults.

Glaucoma is one of the leading causes of blindness and its prevalence increases with age. The most common form, primary open-angle glaucoma, is a chronic, slowly progressive optic neuropathy characterised by the loss of retinal ganglion cells and their axons, leading to irreversible visual field loss. Elevated intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. Reducing IOP to a level that is safe for the patient's eye has been shown to slow disease progression. Lowering IOP in open-angle glaucoma is achieved by eye drops, selective laser trabeculoplasty (SLT) and/or surgery. Many patients are treated with IOP-lowering eye drops, which require lifelong continuous instillation. However, as with other chronic, asymptomatic diseases, adherence to glaucoma treatment is poor for various reasons and is associated with faster disease progression. The purpose of this review is to discuss several sustained-release systems that have been investigated to reduce IOP over time, to address barriers to adherence and improve quality of life. Among these, non-invasive drug-eluting delivery systems such as contact lenses, punctal plugs, and conjunctival ocular inserts have not reached the market. Currently, only two intracameral implants have been approved by the Food and Drug Administration for single use due to corneal safety issues. The biodegradable bimatoprost implant releases the drug continuously for 4-6 months, and its effect on IOP may extend for up to 2 years in 25% of patients. The non-biodegradable intracameral implant releases travoprost for 36 months, when it needs to be removed. However, additional data are needed to assess safety following repeated administration, as well as in broader patient populations and in combination with other treatment approaches such as SLT. Several other biodegradable intracameral implants that release prostaglandin analogues are undergoing clinical trials. In the future, intraocular implants containing genetically modified cells that secrete neurotrophic factors may potentially offer an IOP-independent neuroprotective strategy, complementing existing IOP-lowering implants in glaucoma management.

Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis and constitutes an important health problem, associated with an increased risk of fractures, significant morbidity and mortality, and long-term decreased quality of life. Aging is linked to extensive multimorbidity, polypharmacy, physical and mental disability, and an increased risk of falls, rendering management of glucocorticoid-induced osteoporosis in the older population particularly challenging. On a pathophysiological level, aging is associated with declining osteoblast activity, increased osteoclast activity, and increased bone marrow adiposity; effects that are all accentuated by glucocorticoids. In this narrative review, we discuss the pathophysiology of glucocorticoid-induced osteoporosis, and focus on the mechanism of action, pharmacokinetics, and pharmacodynamics of the various pharmaceutical agents used in the treatment of glucocorticoid-induced osteoporosis, as well as their efficacy, tolerability and safety, especially in older individuals.

Diabetic peripheral neuropathy (DPN) is one of the most significant chronic complications in people with diabetes. It is a highly heterogeneous condition that affects various parts of the nervous system and presents with a wide range of symptoms. Early diagnosis of diabetic neuropathy is possible if regular screening for this complication is conducted using modern diagnostic methods. Every diabetes clinic should perform annual screening for DPN to identify the risk of diabetic foot disease using a monofilament and tuning fork (or biothesiometer). The treatment of diabetic neuropathy remains limited, as studies on causal therapy have shown conflicting results. In most cases, treatment is restricted to achieving optimal glucose control, symptomatic therapy and the management of the painful form of diabetic neuropathy. Ultimately prevention of complications secondary to neuropathy is paramount and it can lead to foot ulcerations, deformities and amputations.Diabetic neuropathy represents a major health challenge for individuals with diabetes, necessitating ongoing research and public health initiatives aimed at improving screening, prevention and treatment strategies.

Background: Emerging evidence in animal models and humans suggests that statins may provide partial protection against noise-induced and drug-induced hearing loss. However, evidence for protection against age-related hearing loss (ARHL) is mixed, and longitudinal studies in large adult cohorts from the general population are limited. This study examined the association between statin use and ARHL in a diverse, community-based longitudinal cohort of adults across the lifespan.

Methods: The 1239 participants, aged ≥ 55 years, are from the MUSC Longitudinal Cohort Study of Age-Related Hearing Loss (1988-present). Following a comprehensive baseline examination, participants attended annual examinations during which audiometric and statin use data were collected. Multivariable linear regression models were performed on baseline data for cross-sectional analyses, and general linear mixed models were performed on longitudinal data to assess the association between statin use, two types of statins, and hearing over time. Hearing outcomes include four pure-tone averages (PTA): narrow (0.5, 1.0, 2.0, and 4.0 kHz), low frequency (0.25, 0.5, and 1.0 kHz), broad (0.5, 1.0, 2.0, 3.0, 4.0, 6.0, and 8.0 kHz), and high frequency (2.0, 3.0, 4.0, 6.0, and 8.0 kHz). Missing covariate data were imputed with multiple imputation using chain equations (MICE).

Results: Statin use (versus no use) was associated with better hearing at baseline for the broad and high-frequency PTAs for adults aged 55-64 and 65-74 years. However, this statin benefit was not observed for the 75+-year age group and for all participants when hearing was examined over time. Without age stratification, similar results were observed for atorvastatin use but not for simvastatin use.

Conclusions: Overall, the findings suggest statin benefits for mid-to-high frequency hearing for middle-aged to older adults at early stages of ARHL. On the basis of evidence suggesting that some statins have beneficial effects on hearing, well-controlled clinical trials are needed to examine effects of statin use and statin types on ARHL in the general population.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by the accumulation of amyloid-beta (Aβ) and neurofibrillary tangles of hyperphosphorylated tau in the brain. Amyloid-targeting therapies (ATTs) are the first available disease-modifying treatments shown to slow cognitive and functional decline for patients with mild cognitive impairment owing to AD and early symptomatic AD. Currently two ATTs are commercially available, donanemab (Kisunla™) and lecanemab (Leqembi^®). The main potential side effect and safety concern of ATT treatment is amyloid-related imaging abnormalities (ARIA). ARIA can be categorized into two types that can co-occur: ARIA-E (edema/sulcal effusion) and ARIA-H (hemorrhage/superficial siderosis). Although both are often asymptomatic and ARIA-E typically resolves radiographically over time, both forms can be radiologically and/or clinically serious. Treating clinicians should be equipped with a comprehensive understanding of ARIA. This review aims to provide advanced practice providers, who are pivotal to patient care in AD, with critical insights into ARIA to safely identify risk factors, understand treatment guidelines, and gain familiarity with appropriate management strategies. It emphasizes the importance of understanding APOE genotype and vascular factors in ARIA risk and recognizing the clinical and radiographic manifestations of ARIA. Practical recommendations are provided for monitoring and managing ARIA, including dose management strategies and education on symptom awareness. By fostering a comprehensive understanding of ARIA and its monitoring and management, this review aims to support the safe and effective implementation of ATTs, contributing to optimized patient care for those treated with ATTs.

Background: Proton pump inhibitors (PPIs) are commonly used and often prescribed inappropriately, which increases the risk of adverse events. Deprescribing is a health professional-supervised intervention aimed at reducing or discontinuing medications that may cause harm or no longer provide benefits.

Objective: To evaluate the effectiveness of a collaborative intervention involving community pharmacists and general practitioners in deprescribing inappropriate PPIs (ATC/WHO A02BC) among community-dwelling older adults (aged ≥ 65 years).

Methods: This was a pragmatic, multicentre, non-randomised two-arm-controlled trial with 6-month follow-up in Portuguese primary care, involving community pharmacies and family health units (FHUs) to deprescribe long-term PPIs (> 8 weeks). The intervention comprised a pharmacy-based patient awareness and education approach, followed by a clinical assessment by general practitioners to assess inappropriate use and initiate the deprescribing process, along with pharmacy-based follow-up to monitor the withdrawal process. The comparator was usual care. The primary outcome was successful deprescribing, defined as the discontinuation or dose reduction of any PPI at 3 and 6 months. Secondary measurements included clinical and drug-specific outcomes. An intention-to-treat analysis was performed.

Results: The study included 166 patients (mean age 74.2 years (SD 6.0 years), 59.0% female) who had been using PPIs for an average of 10.6 years (SD 7.3 years). The intervention was found to be effective in reducing PPIs use. At 3 months, the adjusted absolute risk difference in deprescribing between the intervention group (IG) and the control group (CG) was 46.3% (95% confidence interval (CI) 32.8-59.9, number needed to treat of 2.2). The relative risk of deprescribing in the IG compared with the CG was 9.6 (95% CI 3.6-25.6). At the 6-month follow-up, the effect remained similar. No significant differences between the IG and CG were observed for secondary outcomes.

Conclusions: This collaborative deprescribing intervention has been effective in reducing inappropriate PPI use, highlighting the need for ongoing multidisciplinary efforts and supportive policies to optimise medication use in older adults. Larger trials with longer follow-ups are necessary for a better assessment of various patient-reported outcomes and the long-term impact of these deprescribing interventions.

Clinical trial registration: ISRCTN49637686, 14/06/2023 "retrospectively registered".