Drugs & Aging最新文献

Background: We previously reported that interventions to optimize medication use reduced adverse drug reactions (ADRs) by 21% and serious ADRs by 36% in older adults. With new evidence, we sought to update the systematic review and meta-analysis.

Method: We searched OVID, Cochrane Library, ClinicalTrials.gov and Google Scholar from 30 April 2017-30 April 2023. Included studies had to be randomized controlled trials of older adults (mean age ≥65 years) taking medications that examined the outcome of ADRs. Two authors independently reviewed all citations, extracted relevant data, and assessed studies for potential bias. The outcomes were any and serious ADRs. We performed subgroup analyses by intervention type and setting. Random-effects models were used to combine the results from multiple studies and create summary estimates.

Results: Six studies are new to the update, resulting in 19 total studies (15,675 participants). Interventions were pharmacist-led (10 studies), other healthcare professional-led (5 studies), technology based (3 studies), and educational (1 study). The interventions were implemented in various clinical settings, including hospitals, outpatient clinics, long-term care facilities/rehabilitation wards, and community pharmacies. In the pooled analysis, the intervention group participants were 19% less likely to experience an ADR (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.68-0.96) and 32% less likely to experience a serious ADR (OR 0.68, 95% CI 0.48-0.96). We also found that pharmacist-led interventions reduced the risk of any ADR by 35%, compared with 8% for other types of interventions.

Conclusion: Interventions significantly and substantially reduced the risk of ADRs and serious ADRs in older adults. Future research should examine whether effectiveness of interventions vary across health care settings to identify those most likely to benefit. Implementation of successful interventions in health care systems may improve medication safety in older patients.

Age-related macular degeneration (AMD) is one of the main causes of visual impairment and severe visual loss, and can progress to two advanced forms-neovascularization and atrophic. The field of anti-AMD drugs has undergone huge developments in recent years, from single-target intravitreal administration to current clinical studies with multi-target and non-invasive agents, offering interesting new pharmacological opportunities for the treatment of this disease. Hence, we summarize some of the approved anti-vascular endothelial growth factor (VEGF) drugs for neovascular AMD, especially their structural characteristics, clinical manifestations, dosing regimens, and safety issues of the anti-VEGF drugs highlighted. In addition, advances in atrophic AMD drug research are also briefly described.

Loop diuretics (LDs) represent the cornerstone treatment for relieving pulmonary congestion in patients with heart failure (HF). Their benefit is well-recognized in the short term because of their ability to eliminate fluid retention. However, long term, they could adversely influence prognosis due to activation of the neurohumoral mechanism, particularly in older, frail patients. Moreover, the advent of new drugs capable of improving outcomes and reducing pulmonary and systemic congestion signs in HF emphasizes the possibility of a progressive reduction and discontinuation of LD treatment. Nevertheless, few studies were aimed at investigating the safety of LDs withdrawal in older patients with chronic stable HF. This current review aims to approach current evidence regarding the safety and effectiveness of LDs discontinuation in patients with chronic stable HF, and is based on the material obtained via the PubMed and Scopus databases from January 2000 to November 2022. Our search yielded five relevant studies, including two randomized controlled trials. All participants presented stable HF at the time of study enrolment. Apart from one study, all the investigations were conducted in patients with HF with reduced ejection fraction. The most common outcomes examined were the need for diuretic resumption or the event of death and rehospitalization after diuretic withdrawal. As a whole, although based on a few investigations with a low grade of evidence, diuretic therapy discontinuation might be a safe strategy that deserves consideration for patients with stable HF. However, extensive investigations in older adults, accounting for frailty status, are warranted to confirm these data in this peculiar class of patients.

Background: The acetylcholinesterase inhibitors (AChEIs) donepezil, galantamine, and rivastigmine are commonly used in the management of various forms of dementia.

Objectives: While these drugs are known to induce classic cholinergic adverse events such as diarrhea, their potential to cause psychiatric adverse events has yet to be thoroughly examined.

Methods: We sought to determine the risk of psychiatric adverse events associated with the use of AChEIs through a systematic review and meta-analysis of double-blind randomized controlled trials involving patients with Alzheimer's dementia and Parkinson's dementia.

Results: A total of 48 trials encompassing 22,845 patients were included in our analysis. Anorexia was the most commonly reported psychiatric adverse event, followed by agitation, insomnia, and depression. Individuals exposed to AChEIs had a greater risk of experiencing appetite disorders, insomnia, or depression compared with those who received placebo (anorexia: odds ratio [OR] 2.93, 95% confidence interval [CI] 2.29-3.75; p < 0.00001; decreased appetite: OR 1.93, 95% CI 1.33-2.82; p = 0.0006; insomnia: OR 1.55, 95% CI 1.25-1.93; p < 0.0001; and depression: OR 1.59, 95% CI 1.23-2.06, p = 0.0004). Appetite disorders were also more frequent with high-dose versus low-dose therapy. A subgroup analysis revealed that the risk of insomnia was higher for donepezil than for galantamine.

Conclusions: Our findings suggest that AChEI therapy may negatively impact psychological health, and careful monitoring of new psychiatric symptoms is warranted. Lowering the dose may resolve some psychiatric adverse events, as may switching to galantamine in the case of insomnia.

Clinical trial registration: The study was pre-registered on PROSPERO (CRD42021258376).

Background: Atopic dermatitis presents unique challenges in the older population owing to age-related changes in skin barrier function and immune regulation. However, there is limited evidence on the efficacy and safety of dupilumab, an anti-interleukin-4Rα monoclonal antibody, in patients with atopic dermatitis aged 80 years and above.

Objective: We aimed to assess the clinical efficacy and safety of dupilumab treatment in patients with atopic dermatitis aged 80 years and above.

Methods: Twenty-eight older patients received dupilumab and were evaluated based on several clinical parameters, including the Eczema Area and Severity Index (EASI), Numeric Rating Scale (NRS), Dermatology Life Quality Index (DELI), and AD Control Tool (ACT). Safety assessments and monitoring of concomitant medication use were conducted.

Results: Twenty-six patients completed 16 weeks of treatment, 13 completed 28 weeks, and two completed more than 36 weeks. Dupilumab treatment resulted in a significant improvement in atopic dermatitis symptoms after 16 weeks as demonstrated by reduced EASI, NRS, DLQI, and ADCT scores. Dupilumab had no significant impact on underlying diseases or medication use. No common adverse reactions, such as conjunctivitis and erythema of the face and neck, were identified. Among the 26 patients receiving dupilumab treatment during the COVID-19 pandemic, 17 remained uninfected or experienced milder COVID-19 symptoms than experienced in the general population.

Conclusions: Dupilumab treatment showed significant efficacy in improving atopic dermatitis symptoms in patients aged 80 years and above with a high level of safety. Larger long-term clinical trials are needed to validate these results and provide further evidence for the use of dupilumab in older patients with atopic dermatitis.

Background and objective: Benzodiazepines (including zolpidem and zopiclone) are often associated with higher-than-recommended intake and durations of use, especially in older adults. The objective of this study was to characterize trajectories of benzodiazepine use according to recommended patterns in older adults, and to assess predictors of the risk of developing each of these trajectories.

Methods: Using the French Health Insurance database, we constituted a cohort of adults aged ≥ 65 years who initiated benzodiazepines in 2007 and were followed for up to 8 years. Concordance with benzodiazepine use guidelines was assessed on a quarterly basis according to a "concordance-with-guideline score" with values 1-5. Group-based trajectory modeling was then applied as implemented in the Proc Traj procedure in SAS to define guideline-concordant trajectories based on seven baseline patient-centered characteristics: sex, complementary health insurance coverage, treated alcohol and tobacco use disorder, polypharmacy, hospital stay, and registered chronic diseases.

Results: Among 5080 new users (64.1% women, median age 74 years), six trajectories of benzodiazepine use were identified. Three, representing 70% of users, were concordant with guidelines, whereas three implied non-concordant benzodiazepine use for part or all of the benzodiazepine use follow-up. Polymedicated patients were more prone to develop chronic non-guideline-concordant initially guideline-concordant use, whereas those with a history of long-term disease and hospitalization were more likely to develop chronic non-guideline-concordant use. The number of prescribers during the first quarter, number of daily defined doses, use of loperamide, and use of psychostimulants were associated with a higher risk of developing an initial and persistent non-guideline-concordant use. Treatment initiation by a psychiatrist, initial use of World Health Organization (WHO) step-2 opioids and non-benzodiazepine anxiolytics or sedatives were associated with a higher risk of late non-guideline-concordant use.

Conclusions: Concordance with guidelines varied over time during benzodiazepine use in older adults. A third of these adults will hypothetically follow one of the identified non-guideline-concordant trajectories, consisting of initial and/or late non-guideline concordance. This was associated with modifiable and nonmodifiable factors that clinicians should be aware of for tailoring the monitoring of patients.

Background: Managing hypertension in frail older patients is challenging. Several institutions and organizations have published up-to-date hypertension guidelines suggesting frailty screening among older hypertensive patients, with new recommendations for blood pressure-lowering treatment among the frail population. However, the quality of current hypertension guidelines and the consistency of antihypertension treatment recommendations for frail older patients and their supporting evidence remain unknown.

Objective: In this review, we aimed to systematically collect guidelines with antihypertension treatment recommendations for frail older patients, examine and compare these recommendations, and critically assess reporting and methodology quality of these guidelines.

Methods: A literature search was conducted on two databases and three major websites of guideline development organizations. The AGREE instrument and RIGHT checklist were used to evaluate the methodology and reporting quality of the guidelines, respectively. The consistency of recommendations within the guidelines were compared using descriptive analysis.

Results: We identified 13 hypertension guidelines. The overall methodology quality scores (range 23.35-79.07%) and reporting rates (range 10/35-29/35) varied among these guidelines. Four guidelines provided an explicit definition of frailty. Considering treatment tolerability or increased likelihood of adverse effects while using pharmacotherapy in frail older patients was mentioned in all guidelines. Ten guidelines recommended adjusting blood pressure targets or specific pharmacotherapy programs. Four guidelines recommended using clinical judgment when prescribing. However, the specific recommendations lacked clarity and unity without sufficient evidence.

Conclusions: There were considerable variations in methodology and reporting quality across the 13 included hypertension guidelines. Furthermore, the depth and breadth of antihypertension treatment recommendations for frail older patients were varied and inconsistent. Further trials exploring optimal treatment are urgently required to promote the development of specific guidelines for managing frail older hypertensive patients.

Lower urinary tract (LUT) symptoms are a common presentation of autonomic dysfunction in Parkinson's disease (PD). Symptoms significantly impact quality of life and are associated with worsening of motor symptoms and increased risk for falls. Different medical co-morbidities can often contribute to LUT symptoms, and a thorough evaluation therefore becomes essential. The effects of medications used for Parkinson's disease and other co-existing medical co-morbidities on LUT symptoms is often underestimated. Treatment options include behavioural therapy, oral agents such as antimuscarinic and beta-3 receptor agonist agents, botulinum toxin and neuromodulation. The first-line oral agents cause adverse effects that may exacerbate pre-existing Parkinson's disease-related symptoms. Furthermore, these oral agents can interact with other medications used in Parkinson's disease, and the challenges posed by interactions on pharmacological effects and metabolism are discussed. Knowledge about drug interactions can help in effective management of such patients and mitigate the risks for developing adverse effects.

Background: Data comprehensively examining trends in central nervous system (CNS)-active polypharmacy are limited. The objective of this cross-sectional study was to characterize the composition of and trends in CNS-active medication use in US adults.

Methods: We included all participants ≥ 18 years old in the National Health and Nutrition Examination Study (NHANES), 2009-2020. The primary outcome was the percent of adults with CNS-active polypharmacy. This was defined as ≥ 3 medications among antidepressants [tricyclic, selective and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs), opioids, antiepileptics, antipsychotics, benzodiazepines, and nonbenzodiazepine receptor agonists ("Z-drugs")]. Secondary outcomes included prevalence of any CNS-active medication and specific medications and classes over time, and their indications. Percentages were weighted according to NHANES's nationally representative sampling frame. log binomial regressions evaluated the relative risk (RR) for each outcome, comparing the last (2017-2020) versus the first (2010-2011) survey cycle.

Results: We included 34,189 adults (18.8% at least 65 years old) from five serial cross-sections (survey cycles). The prevalence of CNS-active polypharmacy was 2.1% in 2009-2010 and 2.6% in 2017-2020 [RR 1.18, 95% confidence interval (CI) 0.94-1.47]. The prevalence of CNS-active polypharmacy did not significantly change within any specific age group (e.g., age at least 65 years: RR 1.29, CI 0.74-2.24). The prevalence of any CNS-active medication was 21.0% in 2009 and 24.6% in 2017-2020 (RR] 1.12, 95% CI 1.02-1.25). A substantial increase occurred for antiepileptics (5.1-8.3%), specifically among participants aged 65 years and older (8.3-13.7%). This was largely driven by increasing gabapentin prevalence (1.4-3.6% overall; 3.3-7.9% age 65 years and older). Anticholinergic, SSRIs/SNRIs, antiepileptics, and benzodiazepines were elevated in most cycles for participants at least 65 years old compared with participants less than 65 years, and opioid use was increased in several cycles for older participants as well. Alprazolam was the most common benzodiazepine and third most common medication for anxiety/depression. Gabapentin was the most common CNS-active medication (3.6% of all participants in 2017-2020), followed by sertraline, citalopram, and acetaminophen-hydrocodone (each ~2%). The most common categories were antidepressants (13.7% in 2017-2020), followed by opioids (5.1% in 2017-2020).

Conclusions: CNS-active medications are increasingly common, particularly gabapentin, and use of any CNS-active medication increased by 12%. Numerous CNS-active classes also increased in older adults throughout the years. Increasing suboptimal medication use highlight the need for further investigation into causes for potentially inappropriate prescribing, particularly for older adults.

Dysphagia is increasingly common in older adults; it is especially prevalent in long-term care settings. Patients with dysphagia likely require pharmacologic treatment for multiple comorbidities but may find it difficult or impossible to swallow oral medications. Administering crushed medications mixed with a soft food or liquid vehicle, or via a feeding tube, is a common strategy to circumvent swallowing difficulties in patients with dysphagia. However, inappropriate medication use and improper crushing technique can reduce the medication dose a patient receives, alter medication pharmacokinetics and pharmacodynamics, and compromise treatment efficacy and patient safety. Clinical judgment is needed to identify medications that can and cannot be crushed, select a crushing methodology and vehicle for administering crushed medications, and create a strategy for administering multiple medications. A coordinated effort from the entire care team-including physicians, pharmacists, nurses, advanced practice providers, speech therapists, patients, and caregivers-is necessary to develop and implement an individualized plan for administering medications to patients with dysphagia. This review details the current literature regarding the administration of medications that have been altered, such as by crushing tablets or opening capsules, for patients with dysphagia or who are receiving enteral feeding and provides recommendations on best practices.