Drugs & Aging最新文献

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.

Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition that can be particularly challenging to manage in older adults. Dupilumab, a monoclonal antibody targeting the interleukin-4 receptor alpha subunit, has shown promise in treating moderate to severe AD. However, its efficacy and safety in older adults with refractory AD have not been extensively studied.

Objective: The objective of this study is to evaluate the efficacy and safety of dupilumab in treating older adults with refractory atopic dermatitis and to determine its potential as a therapeutic option in this demographic.

Methods: A retrospective, single-center study was conducted involving 73 older adults (aged ≥ 60 years) with moderate-to-severe AD. The Eczema Area and Severity Index (EASI), Pruritus Numerical Rating Scales (P-NRS), and Dermatology Life Quality Index (DLQI) scores were recorded at baseline and at weeks 6 and 16. Adverse events (AEs) were also monitored.

Results: Following dupilumab treatment, a significant reduction in EASI, P-NRS, and DLQI scores was observed compared with baseline (p < 0.0001), indicating improved clinical symptoms and quality of life. Adverse events were mostly mild and did not lead to treatment discontinuation.

Conclusions: Dupilumab demonstrates significant efficacy and a favorable safety profile in managing refractory AD in older adults, suggesting it as a potential effective therapeutic option for this demographic.

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.

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: Both autonomic dysfunction and frailty are common and complex geriatric syndromes with similar negative health outcomes. Both conditions are characterized by a loss of homeostasis that makes individuals more vulnerable to stressors.

Aim: The primary aim of this study is to examine the association between drugs that affect autonomic function and frailty onset in community-dwelling octogenarians. The secondary aim is to investigate the relationship between autonomic dysfunction and frailty onset in this population.

Methods: In total, 372 nonfrail adults aged 80 years and above (mean age 83 ± 3 years) from the BUTTERFLY project were prospectively followed for 2 years (mean follow-up of 22 ± 6 months). The association between autonomic dysfunction (defined as neurogenic orthostatic hypotension and symptoms of orthostatic hypotension), the use of medications affecting autonomic function, and frailty status were examined using binary logistic regression analysis.

Results: The completely adjusted binary logistic regression model showed that the use of drugs affecting autonomic function was associated with frailty {adjusted odds ratio (aOR) = 1.78 [95% confidence interval (CI) 1.06-3.00], p = 0.030}. Furthermore, symptoms of orthostatic hypotension were related to frailty (aOR = 2.98 [95% CI 1.13-7.88], p = 0.027).

Conclusions: Our results show that symptoms of orthostatic hypotension and the use of drugs that affect autonomic function are accompanied with respectively 3-fold and 1.8-fold higher odds of frailty onset in persons aged 80 years and over. Therefore, pharmacological treatment that affects autonomic function should be started with caution and timely discontinued in older persons.

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: 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: Phase II trials and subgroup analyses of clinical studies suggest that bevacizumab plus an oxaliplatin-based chemotherapy doublet is effective and tolerable in fit older patients with metastatic colorectal cancer (mCRC).

Objective: To evaluate the influence of age on the incidence of side effects and efficacy of this combination in patients with mCRC randomized in the prospective phase III OBELICS study.

Methods: In total, 230 patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 out of 1 were retrieved on the basis of age (190 < 70 years and 40 ≥ 70 years). They received bevacizumab 5 mg/kg administered either on the same day as chemotherapy (standard arm) or 4 days before chemotherapy (experimental arm) and oxaliplatin 85 mg/m² on day 1, plus capecitabine 1000 mg/m² twice a day (bid) orally on days 1-10 or levofolinic acid, 200 mg/m², bolus 5-fluorouracil (5-FU) 400 mg/m², and a 46-h intravenous infusion of 5-FU 2400 mg/m², every 14 days; oxaliplatin was discontinued after 12 cycles. The primary end point was the overall response rate (ORR).

Results: Efficacy and toxicity analyses are reported in aggregate form because there were no statistically significant differences between the two arms. Patient characteristics are well balanced between older and younger patients. No difference in ORR was observed between the two groups (50% for the older patients versus 57.9% for the younger ones; p = 0.36). The median PFS was 10.8 (95% confidence interval [CI], 9.9-12.2) and 11.3 (95% CI 8.3-13.0) months, respectively, for subjects younger than 70 years and those aged ≥ 70 years, with an adjusted hazard ratio (HR) of 1.16 (95% CI 0.80-1.68; p = 0.43). The median OS was 26.2 (95% CI 23.3-32.7) for the former and 23.2 (95% CI 17.3-35.3) months for the latter, respectively, with an adjusted HR of 1.60 (95% CI 1.08-2.37; p = 0.027). Considering all forms of toxicity, the most severe ones were not statistically different between the two groups (65% for the older patients and 60.6% for the younger ones, p = 0.61).

Conclusions: Bevacizumab plus an oxaliplatin-based chemotherapy doublet were effective in older patients randomized in the OBELICS trial, and the adverse event profile was not dissimilar from that of younger patients; no new safety concerns were identified. This post hoc analysis confirms that fit older patients with mCRC should be considered for treatment with this regimen.

Cognitive impairment poses significant challenges for aging populations. Systemic inflammation, a hallmark of rheumatoid arthritis (RA), has been implicated in neurodegeneration through mechanisms including blood-brain barrier disruption, microglial activation, and cytokine-mediated neuronal damage. This review examines the potential impact of disease-modifying antirheumatic drugs (DMARDs) on cognitive function in RA, focusing on the inflammatory pathways linking systemic inflammation to neuroinflammation and cognitive decline. DMARDs, categorized into conventional synthetic (csDMARDs), biologic (bDMARDs), and targeted synthetic (tsDMARDs) classes, modulate immune responses through distinct mechanisms. Evidence suggests that DMARDs, particularly bDMARDs targeting proinflammatory cytokines such as TNF-α and IL-6, may mitigate neuroinflammatory processes and preserve cognitive function. However, the cognitive impact of csDMARDs such as methotrexate is complex, with conflicting reports regarding its role in vascular dementia. Emerging therapies such as Janus kinase inhibitors (JAK-i) offer promise in modulating central inflammation, though clinical evidence remains limited. While some studies highlight protective effects of DMARDs against dementia, findings are inconsistent, hindered by heterogeneity in study design, patient demographics, and cognitive assessment methods. This review underscores the need for personalized treatment strategies, integrating RA management with cognitive health considerations. Future research should prioritize robust, prospective studies with long-term follow-up, incorporating neuroimaging and biomarker analysis to elucidate the mechanisms underpinning DMARD-associated cognitive outcomes. A better understanding of the involved inflammatory pathways in RA and the potential effects of DMARDs could lead to improved therapeutic approaches, enhancing quality of life for patients with RA and potentially benefiting broader strategies in preventing or treating dementia.

Background: Polypharmacy is common amongst older people with dementia or mild cognitive impairment (MCI), increasing the risk of medication-related harm. Medicine optimisation and deprescribing to reduce polypharmacy is considered feasible, safe and can lead to improved health. However, for those living with dementia or MCI, this can be challenging. This systematic review aimed to summarise the evidence on the outcomes of medicine optimisation and deprescribing interventions for older people with dementia or MCI.

Methods: Literature was searched using CINAHL, Embase, Medline, PsychINFO, Web of Science and the Cochrane Library from database inception to January 2024. Papers reporting data specific to people with dementia or MCI from medicine optimisation and deprescribing interventional research studies of any design and in any setting were included. A narrative synthesis was conducted owing to heterogeneity of study designs and outcomes. Quality was assessed using the Mixed Methods Appraisal Tool.

Results: A total of 32 papers reporting on 28 studies were included, with samples ranging from 29 to 17,933 patients and a mean patient age ranging from 74 to 88 years. Of the studies, 60% were undertaken in long-term care settings. Involvement of patients and/or carers in interventions was limited. Papers were grouped as either incorporating a medication review component (n = 13), education component (n = 5) or both (n = 14). Studies primarily focussed on medication-related outcomes, generally showing a positive effect on decreasing the number and improving appropriateness of medications. Fewer papers reported clinical outcomes (behavioural and psychological symptoms of dementia, falls, quality of life and cognition) with mixed findings. A reduction or no change in mortality or hospital attendance demonstrated safety of the interventions in the few papers reporting these outcomes. The quality of the evidence was mixed.

Conclusions: Medicine optimisation and deprescribing interventions generally reduced the number and increased the appropriateness of medications, and although less frequently reported, these interventions seemed to be safe and showed an absence of worsening of clinical outcomes. This review highlights a need for further research, particularly in people with dementia or MCI living at home, with more focus on clinical outcomes and a greater involvement of patients and informal carers.

Protocol registration: The protocol was published in the International Prospective Register of Systematic Reviews (PROSPERO) [Ref: CRD42023398139].