Drugs & Aging最新文献

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.

Background: Osteoporosis (OP) represents a public health challenge, with OP fractures associated with high morbidity, mortality, and economic burden, and fracture risk increasing with age. We evaluated the treatment gap, subsequent fracture rate, and medical costs among patients with OP hip fracture in Italy.

Methods: From two regional administrative databases, our retrospective cohort study included adults aged ≥ 50 years hospitalized for a first OP hip fracture (index fracture; 1 January 2015 to 31 December 2018).

Study outcomes: percentage of patients not prescribed OP treatment in the 6 months following index fracture; fracture and mortality rates (mortality data only available for one region), direct medical costs, persistence and adherence to OP treatment in the 12 months following index fracture (follow-up).

Results: Of 23,961 eligible patients, 87.8% (n = 21,028) were not prescribed OP treatment in the 6 months post-index fracture, with low 12-month persistence (33.7%) and adherence (9.6%) among treated patients. During follow-up, fracture and mortality rates were 36.9 and 280.9 per 1000 patient-years, respectively; higher in non-treated versus treated (39.3 versus 24.0 and 303.7 versus 126.7) patients. Mean (SD) cost per patient was €4963 (€5509); higher in non-persistent versus persistent patients (€5832 versus €4817).

Conclusions: Among patients from two Italian regions experiencing a first hip fracture, we observed a large treatment gap, and high subsequent fracture rates and medical costs. Considering fracture risk increases with age and a globally aging population, these costs are likely to increase and pose a substantial burden on the Italian health service.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) predominantly affect individuals aged 55-75 years, with granulomatosis with polyangiitis (GPA) being diagnosed most often between 55 and 65 years and microscopic polyangiitis (MPA) between 65 and 75 years. Owing to the general increase in life expectancy, the average age at diagnosis increases, encompassing also those over 75 years old. Unfortunately, the exclusion of these older patients from many clinical trials has limited our understanding of the progression of these diseases in older subjects. The role of immunosenescence and aging in AAV pathogenesis and progression is underexplored, despite potential implications in the understanding of the disease, and potentially for disease management. Although AAV manifestations are largely consistent across age groups, certain features, such as renal involvement and the association with interstitial lung disease, may be more prevalent in older patients. Frailty must be a key consideration in therapeutic decision-making, especially when balancing the efficacy of immunosuppressants with potential side effects. Recent evidence supports the use of rituximab in addition to low-dose glucocorticoids for remission induction in life- or organ-threatening AAV, including in older populations. Furthermore, preliminary evidence supports that avacopan might be as efficient as glucocorticoids in these patients. The immunosuppressive treatment of AAV reduces the immune response to environmental pathogens, with rituximab worsening age-related hypogammaglobulinemia. Thus, prophylactic measures, including vaccination and Pneumocystis pneumonia prevention, as well as strategies to mitigate glucocorticoid side effects, should be implemented in AAV management.

Objective: This study complements evidence from randomized controlled trials on the harms (e.g., hypoglycemia) of sulfonylureas compared with dipeptidyl peptidase-4 inhibitors (DPP4i) in the treatment of type 2 diabetes in older adults using real-world data. Existing evidence suggests an increased risk of hypoglycemia, falls, fractures, and cardiovascular events.

Methods: Using target trial emulation, we analyzed a retrospective cohort drawn from German routine claims data. We included patients older than 65 years who initiated DPP4i (sitagliptin, vildagliptin, or saxagliptin) or sulfonylureas (glibenclamid or glimepirid) as add on to metformin between 2011 and 2018. Confounding was adjusted for through overlap weighting, and the average treatment effects were estimated in the overlap population using generalized linear models.

Results: Among 171,318 eligible patients, 111,865 (65%) received DPP4i and 59,453 (35%) sulfonylureas. Patients treated with DPP4i had a higher prevalence of all observed comorbidities. Applying overlap weights to adjust for confounding, patients treated with DPP4i had a higher rate of combined all-cause hospitalizations and outpatient visits compared with those treated with sulfonylureas (rate ratio = 1.03, 95% CI 1.02-1.03) in the total population. In contrast, we found a protective effect of DPP4i on the risk for severe hypoglycemia in the subgroups of new users (ratio rate (RR) = 0.51, 95% CI 0.33, 0.76) and patients with severe renal insufficiency (RR = 0.31, 95% CI 0.16, 0.61).

Conclusions: Deprescribing sulfonylureas and using DPP4i instead may slightly reduce harm in some subgroups of older adults, which supports recommendations of existing lists of potentially inappropriate medications.

Objective: Assess the association of opioids and gabapentinoids with changes in frailty among Medicare beneficiaries who used opioids for 90 or more consecutive days.

Methods: Using a Medicare sample between 2014 and 2020, this study included long-term opioid users who were eligible for Medicare parts A, B, and D for 3 years and had no prior gabapentinoid use. The study was broken into three 1-year periods: lookback, exposure, and outcome. The exposure of interest was gabapentinoid and opioid use measured in period 2. The primary outcome was difference in frailty between periods 1 and 3. Linear regression was used to assess the difference in frailty change by gabapentinoid and opioid use. Multinomial regression was also used to assess the odds of categorical frailty change by gabapentinoid and opioid use.

Results: Overall, the changes in frailty between assessment periods were small. Those who had no continued opioid/no gabapentinoid use showed decreases in frailty (- 0.0005), while each of the other three groups increased in frailty between the assessment periods (opioids only, 0.0040; gabapentinoids only, 0.0136; opioids + gabapentinoids, 0.0142). In addition, each of the drug groups showed increased odds for large increases in frailty compared with those who had no continued opioid/no gabapentinoid use (opioids only, odds ratio (OR): 1.25, 95% confidence interval (CI) 1.04-1.49; gabapentinoids only, OR: 3.12, 95% CI 1.75-5.55; opioids + gabapentinoids, OR: 2.30, 95% CI 1.85-2.87).

Conclusions: Using gabapentinoids, opioids, or a combination of the two showed greater increases in frailty compared with those who used neither drug after long-term opioid use.

Rheumatoid arthritis (RA) is a chronic autoimmune condition disproportionately affecting older adults (> 60 years), who often experience increased disease severity and comorbidities, including cancer. A comprehensive review of the literature was conducted, examining the prevalence of malignancy in patients with RA, associated risk factors, and treatment challenges, including management considerations such as psychological distress and lifestyle modifications. Clinical guidelines and consensus statements were summarized to provide practical insights for optimizing care. Older adults with RA are at an elevated risk for developing cancer due to chronic inflammation, immunosenescence from aging, and shared risk factors such as smoking. Patients with RA tend to have poorer cancer survival rates than individuals without RA, particularly for lung cancer and lymphoma. Immunosuppressive therapies used to treat RA may modestly increase cancer risks but are critical for disease control. Current guidelines emphasize discontinuation or adjustment of RA therapies upon cancer diagnosis, with tailored approaches based on cancer type and stage. Non-pharmacologic interventions, including lifestyle modifications and psychological support, play a vital role in improving quality of life and mitigating disease flares during cancer treatment. The management of RA in older adults with a history of cancer requires a personalized, multidisciplinary approach that balances the need for RA symptom control without affecting cancer outcomes. Shared decision-making, incorporating patient preferences and comorbidities, is critical for optimizing care. Further research is needed to strengthen evidence-based guidelines for this population and address gaps in understanding treatment safety and efficacy.