Drugs & Aging最新文献

Metformin, traditionally promoted for its efficacy in diabetes, is increasingly appreciated for its geroprotective potential in the development of vascular aging, a key contributor to cardiovascular morbidity. This review aims at understanding the spectrum of mechanisms that govern the amelioration of degenerative processes associated with vascular aging by metformin. Central to this therapeutic promise is the activation of AMPK, which reduces metabolic dysregulation and hence slows vascular senescence. Oxidative stress has been identified as an important mechanism thought to be enhanced by metformin in the preservation of endothelial function and attenuation of arterial stiffening. Besides, metformin has lipid-lowering and antiinflammatory activity, which is critical for reducing arterial rigidity and the development of atherosclerotic plaque. In recent times, both clinical and preclinical studies revealed empirical data that confirmed the effectiveness of metformin in the improvement of endothelial function and the decreasing of arterial stiffness as a part of a reduction in the rates of cardiovascular events. The therapeutic action of the drug goes beyond glycemic control, rendering it a geroprotector potentially suitable for broader application in age-related vascular decline. In light of these findings, the clinical acceptance of metformin as an intervention in vascular aging should be possible and promising. Carefully monitored follow-up studies are needed to optimize dosing, delineate the broad biological effects, and verify long-term benefits, which will underpin metformin's role in the paradigm against age-associated vascular diseases.

Background: Atrial fibrillation (AF) is common in older adults, and anticoagulation is recommended for those aged 75 years and older. Still, many individuals remain untreated due to concerns about the benefit-risk balance, particularly among the frail. This study examines the association of incident ischemic stroke (IS) and major or clinically relevant nonmajor bleeding (MB/CRNMB) on 1-year mortality in older patients receiving oral anticoagulants (OAC).

Methods: This retrospective multicenter study included individuals aged ≥ 75 years with AF, discharged between 2014 and 2018 from three acute geriatric units. Baseline functional and frailty status were collected. OAC use at discharge was identified through review of clinical charts. Data on 1-year survival, IS, and MB/CRNMB were extracted from a centralized database. Associations with 1-year mortality were analyzed using a multivariable Cox model with IS and MB/CRNMB as time-dependent variables.

Results: The study included 1684 patients with AF, median age 86 years (interquartile range 82-90), of whom 59.8% were female. Most patients were frail (67.2%) or prefrail (24.2%). Within 1 year, 609 (36.2%) patients died; there were 50 (2.9%) cases of IS and 79 (4.7%) cases of MB/CRNMB. Multivariable Cox analysis showed that incident MB/CRNMB (hazard ratio, HR: 3.82, 95% confidence intervals, CI 2.68-5.45) and IS (HR: 1.82, 95% CI 1.14-2.90) were independently associated with increased 1-year mortality.

Conclusions: In total, one third of older adults with AF receiving OAC die within a year of discharge. Incident MB/CRNMB was more strongly associated with reduced survival than incident IS, underscoring the clinical complexity of anticoagulation management in this high-risk population.

Background and objectives: Psychotropic medications are associated with an increased risk of adverse drug events in older adults, yet national data on their use in Australia remain limited. This study aims to estimate the prevalence of psychotropic medication use among older Australians and to examine the sociodemographic factors associated with their use.

Methods: A retrospective cross-sectional study was conducted using national linked data from the 2021 Census and the Pharmaceutical Benefits Scheme (PBS). The study included all individuals aged 65+ years who responded to the 2021 Census and received at least one PBS medication between 1 August and 31 October 2021. Prevalence of psychotropic medication use was calculated across 5-year age groups, and sociodemographic factors associated with each psychotropic subclass were assessed by logistic regression model.

Results: Among the 3,850,281 older adults, 31.1% received at least one psychotropic medication. Prevalence increased with age across all subclasses except antiepileptics. Antidepressants were the most commonly used psychotropics (19.9%). Those needing assistance with core activities (odds ratio, OR 2.05, 95% confidence intervals, CI 2.03-2.06) and living in non-private dwellings (OR 2.02, 95% CI 1.99-2.05) were more likely to receive psychotropics. Conversely, higher educational level, socioeconomic status and non-English speaker were associated with a lower use of all psychotropic subclasses. Aboriginal and Torres Strait Islander people were linked to increased use of benzodiazepines (OR, 1.15; 95% CI 1.10-1.20) and opioids (OR, 1.20; 95% CI 1.16-1.23). Dementia was strongly associated with antipsychotic (OR, 2.59; 95% CI 2.52-2.66) and antidepressant (OR, 1.42; 95% CI 1.40-1.44) use. Arthritis significantly increased the likelihood of opioid use (OR, 2.03; 95% CI 2.02-2.05).

Conclusions: Almost one third of the study population used psychotropic medications between August and October 2021. Aboriginal and Torres Strait Islander people, individuals with dementia and those with arthritis had an increased likelihood of using certain psychotropic medications. Future research should evaluate the clinical appropriateness of psychotropics in these populations, with immediate implementation of strategies to ensure that their use is limited to evidence-based indications.

Transient or permanent cognitive changes among patients experiencing anesthesia, surgery, perioperative sleep disturbances, and the hospital environment in general have become an extensive topic of debate, particularly concerning older adults and individuals with pre-existing cognitive impairment. This narrative review advocates for an updated nomenclature and terminology in the classification of postoperative cognitive changes and summarizes the current understanding of the most important risk factors for postoperative delirium, focusing on patient-specific, anesthetic, and procedural aspects, including the impact of regional versus general anesthesia. Mounting evidence suggests that appropriate anesthetic depth as monitored by processed electroencephalogram (EEG) is important to preserve baseline postoperative cognitive function in vulnerable patients. The potential roles of cognitive prehabilitation, perioperative medications such as dexmedetomidine and antipsychotics, and early mobilization as well as maintenance of sleep quality for mitigating postoperative cognitive alterations are addressed to aid the practitioner in developing comprehensive care plans emphasizing brain health for this at-risk population. Current evidence highlights an urgent need for additional research in this domain of patient care. Targeted clinician education to understand the multifactorial and complex factors contributing to this perioperative conundrum is essential. Improvements in the prevention, monitoring, and treatment of postoperative cognitive alterations, especially in older adults with pre-existing cognitive conditions, remain an unmet need.

Scabies is a common and disabling ectoparasitic infestation of the skin that can clinically present in 'classical' or 'crusted' forms. Diagnosis can often be made on the basis of clinical history and careful dermoscopic examination of the skin. The International Alliance for the Control of Scabies (IACS) diagnostic criteria can support the diagnosis and management of patients with suspected scabies. Older adults are a vulnerable population; the clinical presentation of scabies can be atypical in this group and treatment can be challenging. Institutional scabies outbreaks, such as in care homes, are typically challenging to identify and, therefore, subject to diagnostic delay. These outbreaks are hard to control and an important source of morbidity, requiring simultaneous treatment of those affected, which can be complicated and time consuming. The management of scabies outbreaks involves repeated, contemporaneous (if multiple individuals) treatments with topical scabicide applications to the whole body, with decontamination of the environment(s). In some situations, topical treatment may be inappropriate and delay effective treatment.

The use of drugs with psychedelic and dissociative effects for the treatment of psychiatric illnesses has become increasingly popular in recent years. However, few trials have been conducted to determine the efficacy of these agents in the specific setting of treatment-resistant major depressive disorder (MDD) in older adults. In this paper, we review notable aspects of treatment-resistant MDD in older adults, review classical and nonclassical psychedelic agents and dissociative agents presently being trialed mostly in younger populations for the treatment of depression, and review what is known about trialing these agents in older adults with treatment-resistant MDD. Given the limitations to extant standard treatment and the potential risks associated with first-line pharmacological agents such as selective serotonin reuptake inhibitors (SSRIs) in this population, psychedelic-assisted psychotherapy may offer an important alternative for managing treatment-resistant MDD in older adults. This subset of patients is understudied and stands to benefit significantly from improved treatment regimens. The limited research available that details psychedelic-assisted treatment in this specific group is promising. Here we focus on reviewing those agents with the most controlled data available, beginning with the dissociative anesthetic ketamine/esketamine, and the hallucinogenic agent psilocybin, and concluding with a brief review of related substances including lysergic acid diethylamide (LSD), N,N-dimethyltryptamine (DMT), ayahuasca, ibogaine, 3,4-methylenedioxymethamphetamine (MDMA), and mescaline. Treatment-resistant MDD is highly prevalent among older adults, and while preliminary findings seem promising regarding the safety and tolerability of psychedelics, concerns remain owing to insufficient data, and therefore further research is crucial to establish the safety, efficacy, and applications of psychedelic therapy in this population.

Background and objectives: Usual treatment approaches for late-life depression primarily involve selective serotonin reuptake inhibitors (SSRIs). Recently, the potential role of vortioxetine has garnered attention. This study aimed to investigate whether vortioxetine is superior to SSRIs in terms of efficacy and tolerability in older people with moderate-to-severe depression.

Methods: The Vortioxetine in the Elderly versus SSRIs: a Pragmatic Assessment (VESPA) study was an assessor-blinded, randomized, parallel-group, superiority trial, comparing flexible doses of vortioxetine versus SSRIs in older adults with depression. This is a post-hoc analysis that excluded participants with milder symptoms of depression. The primary outcome was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Secondary outcomes included clinical response (MADRS total score reduction of ≥ 50%), remission (a MADRS score < 10), and discontinuation rates. Clinical measures were conducted at baseline and at 1-month, 3-month, and 6-month (endpoint) visits.

Results: In total, 302 individuals (mean age: 73.4 ± 5.9 years; 68.9% females), comprising 152 randomized to vortioxetine and 150 to SSRIs (sertraline N = 92; paroxetine N = 19; escitalopram N = 19; citalopram N = 16; fluoxetine N = 3; fluvoxamine N = 1), were included in this post-hoc analysis. No significant differences in MADRS improvement between vortioxetine and SSRIs were observed at any follow-up visits and 6-month endpoint (-11.8 ± 10.6 versus -14.0 ± 11.6; p = 0.12). This was further confirmed by a subgroup analysis excluding drug discontinuers (-16.8 ± 9.0 versus -17.6 ± 10.3; p = 0.51). In addition, people treated with vortioxetine did not exhibit better rates of response (44.1 versus 53.0%; p = 0.11), remission (25.7 versus 34.7%; p = 0.09), and discontinuation (38.0 versus 30.2%; p = 0.17), including discontinuation owing to either side effects or inefficacy, compared with those treated with SSRIs.

Conclusions: Vortioxetine was not superior to SSRIs in terms of efficacy and tolerability in older adults with moderate-to-severe depression. Additional trials, possibly based on fixed doses of vortioxetine, are needed.

Registration: Clinicaltrials.gov: NCT03779789, registered on 12 Dec 2018; EudraCT number: 2018-001444-66.

Prolonged and repeated exposure of the skin to urine and/or faeces may lead to incontinence-associated dermatitis (IAD). IAD is an irritant contact dermatitis characterised by pain, erythema, maceration, erosion, scaling and very often associated with secondary infection. Older adults who are incontinent are at high IAD risk. Several differential diagnoses must be separated from IAD, with allergic contact dermatitis being the most common in older people. The main prevention and treatment principles are to reduce or to avoid the exposure of the skin to urine and stool. The type of incontinence should be assessed first and strategies to enhance continence implemented. Especially in older adults, high absorbency incontinence products should be used and changed regularly to reduce overhydration of the epidermis. Protective skin care products and mild cleansing should be applied. Weeping erosions, excoriations or infection should be treated with appropriate topical products. The short-term and controlled use of corticosteroids or external urine or stool collection devices or indwelling urinary catheters might be considered in severe cases. Owing to demographic changes, the management of incontinence and associated IAD will become more important. This will be especially relevant in primary care for older adults.