Drugs & Aging最新文献

Background: Inpatient anticholinergic medications have been associated with a higher likelihood of postoperative delirium in older adults. However, it remains unclear whether administering anticholinergic medications after surgery adversely affects long-term cognitive function.

Objective: We aimed to evaluate the relationship between in-hospital anticholinergic medications and time to incident dementia in a cohort of older surgical patients. We also sought to determine whether the association between in-hospital anticholinergic drugs and dementia differed by sex and prehospital anticholinergic exposure.

Methods: This was a retrospective analysis of electronic health record data from a regional health information exchange. The study population included patients aged 50 years and older who underwent major surgery requiring an inpatient stay between 2014 and 2021. Orders for anticholinergic medications were identified using the anticholinergic cognitive burden (ACB) scale. A Cox proportional hazards model was used to estimate the association between inpatient orders for strong anticholinergics and incident dementia after hospital discharge. Cause-specific hazards were modeled. Stratification and relative excess risk due to interaction (RERI) were used to investigate multiplicative and additive interaction, respectively.

Results: In total, 66,420 surgical encounters were analyzed. Approximately 90% of patients received one or more strong anticholinergics during hospitalization, and 3806 patients developed dementia during a median follow-up of 3.4 years. The median time to dementia was 2.2 years. Each one-order increase in inpatient anticholinergic medications was associated with a 0.60% increase in dementia risk (HR 1.006; 95% CI 1.003-1.008). This association was stronger among patients who were prescribed anticholinergics before hospitalization (RERI 0.10; 95% CI 0.08-1.12; p = 0.0122).

Conclusions: Perioperative anticholinergics may increase the risk of dementia after major surgery. Avoiding these medications in hospitalized older adults may improve long-term cognitive outcomes.

Background: Recent guidelines recommend the use of sodium-glucose cotransporter 2 (SGLT-2) inhibitors (SGLT2i) in patients suffering from cardiorenal diseases. However, the safety and efficacy of SGLT2i in older adults with atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and chronic kidney disease (CKD) remain unclear.

Methods: Online databases were queried from inception to 11 July 2023 to identify primary or secondary analyses for inclusion. Efficacy outcomes included all-cause mortality, cardiovascular (CV) death, hospitalization for heart failure (HHF), major adverse cardiac events (MACE), CV death/HHF composite, and cardiorenal composite events. Safety endpoints included acute kidney injury (AKI), serious adverse events, genital infections, limb amputation, fractures, urinary tract infections (UTI), and volume depletion. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs).

Results: Eight trials with 32,541 older adults identified in primary or secondary analyses were included. In older adults, SGLT2i reduced the risk of all-cause mortality (RR 0.88; 95% CI 0.83- 0.95), CV death (RR 0.82; 95% CI 0.74-0.92), HHF (RR 0.72; 95% CI 0.66-0.79), MACE (RR 0.87; 95% CI 0.77-0.99), CV death/HHF composite (RR 0.78; 95% CI 0.70-0.88), and cardiorenal composite events (RR 0.77; 95% CI 0.70-0.85). For safety endpoints, SGLT2i decreased the risk of serious adverse events (RR 0.92; 95% CI 0.89-0.95) and increased the risk of genital infections (RR 3.48; 95% CI 2.58-4.69).

Conclusions: This analysis of randomized trials demonstrates that SGLT2i are efficacious in older adults. However, since older individuals are often underrepresented in most clinical trials, further research targeting this growing demographic is essential.

Chronic itch in older patients is a common problem, with a significant impact on quality of life. Chronic itch in the older population may be attributable to several causes, such as age-related changes, skin conditions, systemic conditions, medications, and psychological conditions. Given the complexity of itch in this population, comorbidities, and polypharmacy in most geriatric patients, treating chronic itch can be challenging for healthcare providers. Therefore, optimized topical treatment regimens are paramount to help these patients and prevent side effects.

Osteoarthritis (OA) is a chronic condition in which pain significantly affects quality of life, often leading to reduced physical activity and disability. Globally, an estimated 595 million people are affected, with the numbers likely to increase owing to an aging population and rising obesity rates. Effective pain management is crucial, yet current treatments, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, often provide limited relief and come with risks. One reason for this limited success is the insufficient recognition of the importance of psychosocial factors and heterogeneity of patients with OA (such as anxiety and depression), which can exacerbate pain and its impacts. The variability in patient pain experiences highlights the potential value of pain phenotyping, which involves a comprehensive assessment of pain characteristics to tailor treatments to individual needs. Antidepressants, particularly serotonin-norepinephrine reuptake inhibitors (SNRIs), show promise in alleviating both psychological symptoms and OA-related pain, but their effectiveness varies among individuals. Therefore, further research into standardized pain phenotyping methods and their integration into antidepressant treatment is needed to improve efficacy and minimize side effects through more personalized approaches.

Introduction: Older adults represent a growing proportion of the general population. Nonsteroidal anti-inflammatory drugs (NSAIDs) constitute a group of medicines that are both necessary, owing to their anti-inflammatory, analgesic, and cardioprotective abilities, and potentially harmful, owing to their side effects.

Objectives: This study provides a comprehensive analysis of NSAID usage patterns among Polish adults aged 60 years and older. It focused on the regular use (≥ three times per week) of two types of NSAIDs: acetylsalicylic acid (ASA) and non-ASA NSAIDs, examining consumption on the basis of age, sex, educational level, and place of residence.

Methods: Data were collected from the PolSenior2 study, a national cross-sectional survey of 5987 Polish individuals aged 60-106 years, conducted from 2018 to 2019.

Results: The study found that 30.7% [95% confidence interval (CI) 28.8-32.7)]of Polish seniors regularly used NSAIDs, with 26.2% (95% CI 24.5-28.0) regularly using ASA, 6.3% (95% CI 5.3-7.2) regularly using non-ASA NSAIDs, and 1.9% (95% CI 1.4-2.3) reporting regular use of both. An age-related increase in regular NSAID use, including ASA, was observed. Women were more likely than men to use non-ASA NSAIDs regularly, whereas men in the 70-79 age group were more likely to use ASA. A lower level of education was associated with more frequent NSAID use.

Conclusions: The findings have implications for healthcare practitioners and policymakers, emphasizing the need for careful management of NSAID use. The study contributes to a more nuanced understanding of NSAID usage and underscores the necessity for tailored healthcare strategies to ensure safe and effective medication use among older adults.

Introduction: Chronic pain is prevalent among older adults with Alzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRD). Memantine and acetylcholinesterase inhibitors (ACHEI; donepezil, rivastigmine, and galantamine) are approved for the treatment of dementia symptoms and may also have analgesic properties. However, findings on the clinical utility of these dementia medications for chronic pain treatment are mixed, and little is known about differences in the use of pain medication according to whether an older adult with AD/ADRD is using dementia medications.

Methods: We selected a 20% national sample of Medicare enrollees with a diagnosis of AD/ADRD and chronic pain in 2020. We calculated the odds of having any pain management prescription (opioids, serotonin and norepinephrine reuptake, gapapentinoids, or non-steroidal anti-inflammatory drugs), having an opioid prescription, and having a long-term (≥ 90 days) opioid prescription, by dementia medication (none, memantine, ACHEI, or memantine and ACHEI).

Results: Among 103,564 patients, 5.5% received a memantine prescription, 14.4% received an ACHEI prescription, and 8.6% received a prescription for both. Over 70% of all patients had a pain management prescription. The percentage of patients who had an opioid prescription ranged from 54.5% for those without a dementia medication prescription to 44.0% for those with a prescription for both memantine and ACHEI. Similarly, the percentage of patients who had a long-term opioid prescription was highest for those without a dementia medication prescription (12.2%) and lowest for those with a prescription for both memantine and ACHEI (8.8%). Having a prescription for memantine only was associated with lower odds of any pain management prescription (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.88-1.00; p < 0.05). Having a prescription for either memantine (OR: 0.79; 95% CI 0.75-0.84), ACHEI (OR: 0.85; 95% CI 0.82-0.89), or both (OR: 0.75; 95% CI 0.72-0.79) was associated with lower odds of having an opioid prescription (p < 0.05). Lastly, having a prescription for either memantine (OR: 0.85; 95% CI 0.77-0.94), ACHEI (OR: 0.92; 95% CI 0.86-0.98), or both (OR: 0.83; 95% CI 0.77-0.90) was associated with lower odds of having a long-term opioid prescription.

Discussion: Older adults with co-occurring AD/ADRD and chronic pain who were on dementia medications had lower odds of being prescribed opioid analgesics. Memantine and ACHEIs should be explored as potential opioid-sparing medications for older adults with AD/ADRD, given their relatively safe profiles. Future studies are needed to examine repurposing dementia medications for pain treatment.

IgG4-related disease (IgG4-RD) is an immune-mediated disorder characterized by organ enlargement and dysfunction. The formation of tertiary lymphoid tissues (TLTs) in affected organs is crucial for understanding IgG4-RD, as T follicular helper (Tfh) 2 cells within TLTs drive IgG4+B cell differentiation, contributing to mass formation. Key cytokines IL-4 and IL-10, produced by Tfh2 cells, are essential for this process. Additionally, cytotoxic T cells and M2 macrophages significantly contribute to inflammation and fibrosis in the lesions. These insights into IgG4-RD have led to the development of innovative targeted therapies. While glucocorticoids are effective in many cases, they often cause disease flares during tapering and rarely result in long-term, treatment-free remissions. Long-term glucocorticoid use poses significant challenges owing to potential side effects, particularly in older patients who may already have complications such as diabetes and atherosclerotic diseases. In contrast, targeted therapies offer a promising alternative, potentially providing more effective disease control with fewer side effects. Current research is exploring several exciting approaches, including B-cell depletion, targeted immunomodulation of B cells, Bruton's tyrosine kinase inhibition, disruption of co-stimulation pathways, targeting the SLAMF7 cytokine or its receptor blockade (BAFF, IL-4, or IL-6), and JAK-STAT signaling pathway inhibition. These emerging strategies hold the promise of improving patient outcomes and advancing the management of IgG4-RD.

Background and objective: Quetiapine is a Food and Drug Administration (FDA) approved second-generation antipsychotic. It is also commonly used at low dose for its sedative properties to treat insomnia in the older population. Quetiapine at standard doses has been associated with increased risk of cerebrovascular events, cognitive decline, and mortality in patients with dementia, especially within older adults. However, there are limited data describing its safety at lower doses, especially for the treatment of insomnia in older adults. This study aims to compare the safety of low-dose quetiapine versus trazodone or mirtazapine for insomnia in older adults in the USA.

Methods: This was a retrospective cohort study that included patients aged 65 years or older who started low-dose quetiapine, trazodone, or mirtazapine for the treatment of insomnia from October 2018 to September 2021. The primary outcome was all-cause mortality and secondary outcomes included new incidences of stroke or transient ischemic attack, dementia, and falls with or without traumatic fractures. They were identified from electronic medical records using ICD-10-CM clinical diagnosis codes. Eligible patients were followed from the initiation of the drug until death, end of target drug exposure or escalation of dose, end of health plan membership, or 30 September 30 2022, whichever came first. Patients initiated mirtazapine or trazodone were matched to each patient who initiated quetiapine at a 4:1 ratio using propensity score matching method.

Results: We included 375 patients initiated on low-dose quetiapine, who were matched to 1500 patients started on trazodone and 1500 patients started on mirtazapine. Comparing patients who received quetiapine with trazodone, the quetiapine group had an increased risk of mortality (hazard ratio (HR) 3.1, 95% confidence interval (CI) 1.2-8.1; P < 0.05), dementia (HR 8.1, 95% CI 4.1-15.8; P < 0.05), and falls (HR 2.8, 95% CI 1.4-5.3; P < 0.05). When comparing quetiapine with mirtazapine, quetiapine group had an increased risk of dementia (HR 7.1, 95% CI 3.5-14.4; P < 0.05). No significant differences were detected in other outcomes.

Conclusions: Caution should be taken in practice when using low-dose quetiapine for insomnia in older adults. It is associated with significantly higher rates of mortality, dementia, and falls when compared with trazodone and a higher dementia rate when compared with mirtazapine.

Background and objectives: Despite their limited benefits and serious adverse effects, psychotropics remain frequently prescribed for neuropsychiatric symptoms (NPS) of dementia. Psychotropic polypharmacy, the use of two or more concomitant psychotropic medications, is therefore not recommended for people with dementia. The objectives of this study were to investigate the prevalence of psychotropic polypharmacy in Australians living with dementia whose caregivers sought external NPS support from Dementia Support Australia (DSA; the national provider of NPS support) and the association of psychotropic polypharmacy with their demographics and NPS characteristics.

Methods: A retrospective cross-sectional study of a subset of DSA referrals at baseline (i.e., yet to receive psychosocial intervention(s)) between 2016 and 2020 was conducted. Referrals with and without psychotropic polypharmacy were compared on the basis of demographic characteristics (e.g., sex, dementia subtype), NPS type (e.g., agitation), NPS severity and associated caregiver distress as measured by the Neuropsychiatric Inventory (NPI), using Pearson's chi-square test and Welch's t-test for categorical and continuous data, respectively. Logistic regression models were used to examine the relationship between individual NPI domains and exposure to psychotropic polypharmacy.

Results: A total of 421 referrals (mean age 81.5 (standard deviation 8.5) years, 52.3% males, 46.8% Alzheimer's disease) were analysed. Of those, over 90% (n = 383) were prescribed at least one psychotropic, with 214 referrals (50.8%) prescribed psychotropic polypharmacy. The medication types most associated with psychotropic polypharmacy were antipsychotics (n = 162, 75.7%), opioids (n = 104, 48.6%), anxiolytics (n = 93, 43.5%), sedative/hypnotics (n = 52, 24.3%) and antidepressants (n = 47, 22.0%). No relationship between psychotropic polypharmacy and any variable tested was identified, including age, sex, dementia subtype and NPI severity.

Conclusions: Psychotropic polypharmacy is highly prevalent in Australians living with dementia referred to external dementia-specific behaviour support programs, but no factors were associated with its presence in this cohort.

There are several pharmacologic agents that have been touted as guideline-directed medical therapy for heart failure with preserved ejection fraction (HFpEF). However, it is important to recognize that older adults with HFpEF also contend with an increased risk for adverse effects from medications due to age-related changes in pharmacokinetics and pharmacodynamics of medications, as well as the concurrence of geriatric conditions such as polypharmacy and frailty. With this review, we discuss the underlying evidence for the benefits of various treatments in HFpEF and incorporate key considerations for older adults, a subpopulation that may be at higher risk for adverse drug events. Key considerations for older adults include: the use of loop diuretics, mineralocorticoid receptor antagonists (MRAs), and sodium glucose co-transporter-2 (SGLT2) inhibitors for most; angiotensin receptor blockers/ angiotensin receptor-neprilysin inhibitors (ARB/ARNIs) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) as add-on therapies for some, though risk of geriatric conditions such as falls, malnutrition, and/or sarcopenia must be considered; and beta blockers for a smaller subset of patients (with consideration of deprescribing for some, though data are lacking on this approach). Naturally, when making clinical decisions for older adults with cardiovascular disease, it is critical to consider the complexity of their conditions, including cognitive and physical function and social and environmental factors, and ensure alignment of care plans with the patient's health goals and priorities.