Drugs & Aging最新文献

Proton pump inhibitors (PPIs) are amongst the most commonly prescribed medications worldwide. Clinical practice guidelines identify clear indications for short-term and long-term use; however, many older adults are prescribed potentially unnecessary PPIs. Multiple concerns exist with unnecessary PPI therapy, including the potential long-term risk of adverse effects. An association between PPI use and fractures, dementia, and respiratory and gastrointestinal infections has been suggested in observational data; however, there is a paucity of high-quality data supporting a causative relationship. Despite this, PPIs remain a target for medication optimization in older adults because of the high rate of unnecessary use, cost, and contribution to pill burden and polypharmacy. A multidimensional approach is required to reduce unnecessary PPI's, including the alignment of initial prescribing with evidence-based indications, reassessment of existing prescriptions, enhancement of knowledge and resources for patients and prescribers, and support for deprescribing. To increase deprescribing success, barriers to PPI deprescribing must be addressed, including the fear of symptom recurrence, insufficient time and education, and lack of concern regarding long-term use. Deprescribing strategies, such as tapering, can aid in success, as can the utilization of nonpharmacological and lower risk options for managing symptoms of gastric-acid-related disorders.

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.

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: Heart failure with reduced ejection fraction is increasingly prevalent in older adults, yet data on guideline-directed therapies in the oldest age groups remain limited.

Objective: To assess outcomes of sacubitril/valsartan in adults aged ≥75 years, across age strata (≥75, ≥80, ≥85, ≥90 years; 75-79, 80-84, 85- 89 years), focusing on cardiovascular, heart failure, and all-cause hospitalizations, and mortality.

Methods: This retrospective study evaluated all patients aged ≥ 75 years in Belgium with chronic heart failure with reduced ejection fraction who started sacubitril/valsartan between 1 November, 2016 and 31 December, 2018.

Results: A total of 1705 patients were divided into the following age groups: 75-79, 80-84, 85-89, and ≥ 90 years. Cardiovascular hospitalization rates significantly decreased across all age groups after sacubitril/valsartan initiation. Patients aged 75-79 years showed a reduction from 0.74 events/year (95% confidence interval [CI] 0.68-0.81) prior to treatment to 0.54 (95% CI 0.47-0.62, p < 0.001) after initiation. Rates fell from 0.73 (95% CI 0.66-0.80) to 0.53 (95% CI 0.44-0.65, p < 0.001) in those aged 80-84 years, from 0.62 (95% CI 0.52-0.74) to 0.44 (95% CI 0.35-0.57, p < 0.01) in those aged 85-89 years, and from 0.78 (95% CI 0.59-1.03) to 0.42 (95% CI 0.22-0.83, p < 0.01) in patients aged ≥ 90 years. Heart failure-related hospitalization rates also showed consistent reductions: 0.34 (95% CI 0.30-0.39) prior to treatment to 0.28 (95% CI 0.22-0.34) after initiation in patients aged 75-79 years, and from 0.38 (95% CI 0.33-0.43) to 0.30 (95% CI 0.23-0.39) in those aged 80-84 years (all p < 0.05). The rates decreased from 0.35 (95% CI 0.28-0.44) to 0.27 (95% CI 0.20-0.38, p = 0.08) in those aged 85-89 years and from 0.52 (95% CI 0.36-0.76) to 0.29 (95% CI 0.12-0.75, p < 0.05) in the oldest patients aged ≥ 90 years.

Conclusions: Broader application of guideline-directed medical therapy in geriatric heart failure with reduced ejection fraction care should be prioritized.

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.

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".

Background: Gabapentin is increasingly prescribed to older adults, yet prescribing patterns and characteristics of gabapentin initiators remain unclear.

Methods: We conducted a retrospective cohort study of gabapentin initiators using a random sample of age-eligible fee-for-service Medicare beneficiaries (2012-2021) enrolled in Parts A, B, and D. Gabapentin initiators were identified from pharmacy claims. We required 180 days of continuous enrollment (washout period) prior to initiation (index date) for inclusion. We analyzed demographics, healthcare utilization within 3 months of initiation, chronic conditions, medication history during washout period, and patterns of gabapentin use. Subgroup analyses compared initiators by duration of continuous gabapentin use (≤ 90 days, 91-180 days, and > 180 days).

Results: The prevalence of gabapentin prescriptions increased over time, from 6.7% (2013) to 10.2% (2021). Among 247,612 gabapentin initiators (mean age 76.1 years, 61.5% female, 89.2% white), chronic pain (32.6%) was the most commonly documented condition, while epilepsy and postherpetic neuralgia, the approved indications for gabapentin, were documented in fewer than 0.5% of initiators. Among initiators, 38.9% had prior opioid use, and 13.2% were co-prescribed gabapentin and opioids at initiation. About 30% had a history of antidepressant use, predominantly selective serotonin reuptake inhibitors (17.2%). Subgroup analyses showed similar demographics and prescription patterns across subgroups. However, gabapentin initiators with > 180 days continuous use had more neuropathic pain and chronic condition diagnoses documented, fewer opioid co-prescriptions at index, and lower hospitalization rates.

Conclusions: Gabapentin was frequently prescribed, apparently off-label, in older adults with a high burden of chronic pain and comorbidities; initiators often had co-prescriptions of gabapentin with opioids. Future research is needed to investigate factors associated with extended gabapentin use (> 180 days) and its appropriateness in this population.