Drugs & Aging最新文献

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.

Background: Prior studies have suggested potential benefits of antihypertensive medication (AHM) in preventing atrial fibrillation. It remains uncertain whether these benefits are uniform across different AHM classes. This study aims to compare the risk of AF across AHM classes in older adults.

Methods: This study included 8942 individuals from a randomized trial of aspirin, who were aged ≥ 65 years, free of cardiovascular disease (CVD) and AF, treated with any AHM at baseline. Exposures of interest included four first-line AHM medications: angiotensin-converting-enzyme inhibitors (ACEIs), angiotensin-receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Participants were assigned a diagnosis of probable, possible or no AF via a clinical algorithm. Possible AF cases were excluded. Cox proportional-hazards model was used to compare risk of probable AF among baseline users of different AHM classes, adjusting for potential confounders and blood pressure.

Results: Over 4.5 years, 535 (6.0%) participants developed probable AF. CCB-based therapy, alone or in combination, showed the lowest AF risk among all classes (HR [95% CI] for CCB-based therapy versus ARB-, ACEI-, and diuretic-based therapy, alone or in combination: 0.74 [0.57-0.98], 0.85 [0.64-1.13], and 0.81 [0.62-1.06], respectively). A lower AF risk was also observed with CCB monotherapy (HR from 0.58-0.71 compared with monotherapy of other classes).

Conclusions: CCB-based AHM therapy was linked to a lower risk of probable AF events compared with non-CCB regimens in older adults who were initially free of CVD and AF and treated with any AHM. Additional studies are warranted to clarify the mechanisms underlying this association.

Sarcopenia and cachexia are two common and overlapping but distinct muscle wasting syndromes that predict adverse outcomes and undermine quality of life among older adults with cancer. Despite their prognostic value and negative effects on older patients' well-being, sarcopenia and cachexia are not routinely or adequately assessed and managed in clinical oncology practice. However, efforts to recognize and manage sarcopenia and cachexia at diagnosis and during follow-up may have beneficial effects on muscle mass, physical function, and quality of life among older adults with cancer, although evidence on long-term clinical outcomes in response to targeted interventions has yet to be established. This comprehensive review attempts to (i) delineate the differences in the pathophysiology and clinical manifestations between sarcopenia and cachexia, (ii) clarify how sarcopenia and cachexia are defined in the geriatric oncology literature, (iii) describe methods for assessing sarcopenia and cachexia in clinical practice, (iv) review the prognostic value of sarcopenia and cachexia among older patients, particularly those undergoing systemic cancer treatment, and (v) discuss evidence-based strategies aimed at managing sarcopenia and cachexia for older adults with cancer.

Early-phase clinical trials (EPCTs) are critical for evaluating the safety, tolerability, efficacy and pharmacokinetics of novel oncology therapies. However, older adults are underrepresented in all phases of oncology clinical trials, including early-phase trials, creating a significant gap in evidence-based cancer management in this population, which translates into clinical practice. This is despite cancer incidence increasing with age, and a substantial proportion of cancer diagnoses occurring in individuals aged ≥ 65 years. Ageing is associated with physiological, physical and psychosocial changes which could underlie the hesitancy to include older adults in early-phase clinical trials, due to concerns of excessively compromising their safety and quality of life. However, the landscape of EPCTs has changed with higher safety and efficacy data. This review explores the current landscape of older adults in early-phase clinical trials, including the participation rate, the outcomes, and the multifaceted challenges contributing to the underrepresentation of older adults, and examines the potential strategies to enhance the inclusivity of older adults for treating older adults with cancer.

Systemic lupus erythematosus (SLE) is widely recognized as a systemic autoimmune disease predominantly affecting young women. However, since the initial report in 1959, cases of late-onset SLE have been increasingly documented. Late-onset SLE, commonly defined as disease onset at or after 50 years of age, sometimes exhibits different clinical characteristics compared with the typical SLE phenotype. There is a higher proportion of male patients and a lower frequency of skin rash, renal involvement, neuropsychiatric manifestations, hypocomplementemia, and anti-DNA antibody seropositivity, whereas serositis is observed more frequently. Furthermore, although disease activity in late-onset SLE is generally lower, it is associated with more severe irreversible organ damage and a poorer prognosis. Data shows that the use of immunosuppressive drugs in late-onset SLE is lower, which may be due to delay in diagnosis, different manifestations, and the presence of comorbidities. However, the clinical situation would have merited their use. Given the aging of the global population, the prevalence of late-onset SLE is expected to increase. A thorough understanding of the characteristics of late-onset SLE may facilitate early diagnosis and appropriate treatment, ultimately improving patient outcomes. This review summarizes the reported characteristics of late-onset SLE and discusses the key considerations for its accurate diagnosis and effective management.