Drugs & Aging最新文献

Cystic fibrosis (CF) is an inherited condition that leads to multiorgan dysfunction, especially in the respiratory, gastrointestinal, and reproductive tracts, with associated conditions including persistent pulmonary infection, liver disease, pancreatic insufficiency, and infertility. Historically, people with CF (pwCF) suffered a shortened lifespan due to complications of the condition, namely respiratory. The emphasis on center-based, multidisciplinary care and the widespread introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has resulted in pwCF living longer and healthier lives. Now they may encounter some of the health and social issues associated with growing older, which previously were not a typical experience for this population. In this article, we review relevant health issues for the aging CF population, including complications that arise from the condition itself, issues encountered due to treatment, and general conditions associated with aging that may manifest earlier or differently in pwCF. We discuss the recommendations for screening and treatment of relevant conditions, and considerations for the integration of healthcare professionals across disciplines into the care of this population.

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: 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: 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 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.

Introduction: Polypharmacy is common in older patients and associated with adverse outcomes. However, the association with outcomes in patients with intertrochanteric fractures remains unclear. This study aimed to investigate associations between polypharmacy and 1-year survival (primary outcome) and postoperative complications (secondary outcome), in older patients undergoing surgical treatment for intertrochanteric fractures.

Patients and methods: This multicenter retrospective study initially identified 1864 patients who underwent surgical treatment for intertrochanteric fractures between 2016 and 2020. We excluded those aged < 65 years, with polytrauma, or with Charlson Comorbidity Index (CCI) > 3 or insufficient data. Patients were classified into polypharmacy (≥ 5 medications) and non-polypharmacy (< 5 medications) groups. We performed two analyses: (1) complete case analysis using 1:1 propensity score matching (498 pairs) with variables including age, sex, body mass index (BMI), CCI, residence before admission, fracture type, American Society of Anesthesiologists (ASA) physical status (PS), and Parker Mobility Score, followed by Kaplan-Meier survival analysis with log-rank test and chi-squared test for complications and (2) multivariate Cox regression analysis using multiple imputation (CART method, five imputed datasets) of the eligible cohort (N = 1608), adjusting for the same variables.

Results: In the matched cohort, the 1-year survival rate was significantly lower in the polypharmacy group (91.3%; 95% CI 87.7-93.8) compared with the non-polypharmacy group (94.0%; 95% CI 90.9-96.1; P = 0.027). Postoperative complications showed no significant differences between groups. Cox regression analysis revealed that advanced age, male sex, ASA-PS, and polypharmacy were associated with decreased survival, while higher Parker Mobility Score and normal and higher BMI showed improved survival.

Conclusions: Polypharmacy was associated with lower postoperative survival in older patients with intertrochanteric fractures and few comorbidities. As a potentially modifiable factor, medication review through multidisciplinary collaboration might contribute to improved outcomes.

Osteoporosis, a chronic metabolic bone disease, increases the predisposition to fragility fractures and is associated with considerable morbidity, high health care cost as well as mortality. An elevation in the rate of incident fragility fractures will be observed proportional with the increase in the number of older people worldwide. Severe osteoporosis is currently defined as having a bone density determined by dual-energy X-ray absorptiometry that is more than 2.5 standard deviations (SD) below the young adult mean with one or more past fractures due to osteoporosis. Nutrition, physical activity and adequate vitamin D are essential for optimal bone strength throughout life. Hormone (oestrogen/sex steroid) status is also a major determinant of bone health. This review explores mechanisms involved in bone homeostasis, followed by the assessment and management of severe osteoporosis, including an overview of several treatment options in older people that range from anti-resorptive to anabolic therapies.

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.

The incidence of patients with late-onset rheumatoid arthritis (LORA) is increasing. The clinical diagnosis of LORA is essentially the same as that of young-onset rheumatoid arthritis (YORA), but special attention should be paid to the differences in clinical features between LORA and YORA. Undertreatment of LORA can lead to reduced physical function and increased societal burden. The treat-to-target strategy has been successfully applied in patients with rheumatoid arthritis (RA), but evidence supporting this strategy is still insufficient for LORA. A wide range of factors should be considered and evaluated in addition to age and RA-related factors, including comorbidity/organ damage, psycho-neurological factors, socio-economic factors and frailty. Considering the proportion of patients with LORA achieving clinical remission or low disease activity in observational studies, the treat-to-target strategy could be stratified by age. Patients with LORA aged < 75 years are treated according to the treat-to-target algorithm used for all patients with RA, with clinical remission as the main target and low disease activity as the alternative target. In patients with LORA aged ≥ 75 years, the initial main target is set at low disease activity, which can be escalated to clinical remission with appropriate adaptation of treatment if a favourable balance of effectiveness and safety is struck at the time of achieving low disease activity by 6 months of treatment. Evidence of the efficacy/effectiveness and safety of methotrexate, biological disease-modifying antirheumatic drugs, Janus kinase inhibitors and glucocorticoids in patients with LORA is accumulating, but further research is warranted.

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].