Purpose: Adverse drug reactions (ADRs) represent a common and potentially preventable cause of unplanned hospitalization, increasing morbidity, mortality, and healthcare costs. We aimed to review the classification and occurrence of ADRs in the older population, discuss the role of age as a risk factor, and identify interventions to prevent ADRs. Methods: We performed a narrative scoping review of the literature to assess classification, occurrence, factors affecting ADRs, and possible strategies to identify and prevent ADRs. Results: Adverse drug reactions (ADRs) are often classified as Type A and Type B reactions, based on dose and effect of the drugs and fatality of the reaction. More recently, other approaches have been proposed (i.e. Dose, Time and Susceptibility (DoTS) and EIDOS classifications). The frequency of ADRs varies depending on definitions, characteristics of the studied population, and settings. Their occurrence is often ascribed to commonly used drugs, including anticoagulants, antiplatelet agents, digoxin, insulin, and non-steroidal anti-inflammatory drugs. Age-related factors—changes in pharmacokinetics, multimorbidity, polypharmacy, and frailty—have been related to ADRs. Different approaches (i.e. medication review, software identifying potentially inappropriate prescription and drug interactions) have been suggested to prevent ADRs and proven to improve the quality of prescribing. However, consistent evidence on their effectiveness is still lacking. Few studies suggest that a comprehensive geriatric assessment, aimed at identifying individual risk factors, patients’ needs, treatment priorities, and strategies for therapy optimization, is key for reducing ADRs. Conclusions: Adverse drug reactions (ADRs) are a relevant health burden. The medical complexity that characterizes older patients requires a holistic approach to reduce the burden of ADRs in this population.

Chronic diseases and frailty represent the clinical expressions of the accumulations of biological deficits that occur with aging. However, when addressing chronic diseases, the evaluation of frailty is yet far to be part of routine clinical practice. Frailty and chronic diseases are often treated as different identities. However, the two concepts are related and present a certain amount of overlap and the presence of chronic diseases contributes to the onset of frailty. By taking into considerations not only the physical domain and function, but also psychological, socioeconomical and spiritual factors, frailty is a good descriptor of complexity found in older age. Strategies to identify, manage, and prevent frailty at any age in individuals with multimorbidity or chronic conditions are advised. Benefits and harms of pharmacological treatments should be weighted in older people considering the underlying frailty status. In fact, frailty acts as a modifier of the risks and benefits of chronic diseases treatments. Moreover, some treatments could lead to frailty itself (i.e. proton pump inhibitors, diuretics, hypoglycemic drugs, antihypertensive treatments), underlining the need of an individualized and flexible prescribing decision-making in this population. For these reasons, a different pathway of care for older patients with frailty and chronic diseases seems necessary. An assessment of frailty should be simple and not time consuming in order to address patient's needs and expectations, evaluating the social background, lifestyle and priorities. Empowering the patient implies a personalized evaluation and the development of individualized management plans which would ultimately lead to a reorganization of the health care provision and eventually increase quality of life in the elderly multimorbid frail patient.

Background—Patients affected by Long COVID often report shorter times spent doing physical activity (PA) after COVID-19. The aim of the present study was to evaluate potential associations between PA levels and parameters of physical function in a cohort of COVID-19 survivors with post-acute symptoms, with a particular focus on individuals aged 65 and older. Materials and methods—PA levels before and after COVID-19 were assessed in a sample of patients that had recovered from COVID-19 and were admitted to a post-acute outpatient service at the Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Rome, Italy). Participation in PA was operationalized as the engagement in leisure-time PA for at least 150 min per week in the last 3 months. Self-rated health and measures of physical performance and muscle strength were assessed. Results—Mean age of 1846 participants was 55.2 ± 14.4 years and 47% were women. Before COVID-19, inactivity was detected in 47% of the whole study population; only 28% maintained pre-COVID-19 PA engagement. Inactivity was more frequent in women. The stopping of physical activity was associated with increased BMI and CRP levels, lower vitamin D levels and a higher prevalence of post-COVID-19 fatigue, dyspnea, arthralgia, and myalgia. Active participants had higher handgrip strength and performed better on both the six-minute walking test (6MWT) and at the one-minute sit-to-stand test (1MSTST). In particular, at the 6MWT, participants 65 and older that were still active after COVID-19 walked 32 m more than sedentary peers. Moreover, the distance covered was 28 m more than those who were active only before COVID-19 (p = 0.05). Formerly active subjects performed similarly at the 6MWT to inactive participants. PA was associated with better self-rated health. Conclusions—Our findings reveal that inactivity is frequent in the post-acute COVID-19 phase. Stopping physical activity after COVID-19 results in measures of performance that are comparable to those who were never active. Relevant differences in the distance covered at the 6MWT were found between older active subjects and their sedentary peers.

Purpose: Delirium has been recognized as an atypical presenting feature of COVID-19 in older adults and is independently associated with mortality. We aimed to perform an updated systematic review of the literature and proportional meta-analysis to assess prevalence and incidence of delirium in older adults with COVID-19, addressing differences according to sex, frailty status, and settings. Methods: We searched databases for English-language articles on prevalence and incidence of delirium in older adults with COVID-19, published between March 2020 and January 2023. Results: Of the 1171 articles identified, 66 met selection criteria and were included in the meta-analysis (n = 35,035 participants, age-range 66–90 years old, 46.6% females). We observed similar pooled prevalence (20.6% [95% Confidence Interval (CI) 17.8–23.8%]) and incidence (21.3% [95% CI 14.7–30%]) of delirium. Pooled occurrence (both prevalence and incidence) of delirium was similar according to sex (females 21.3% [95% CI 16–27.5%] vs. males 23.8%% [95% CI 18.2–30.4%], p-value = 0.55) and study setting (nursing homes 22.5% [95% CI 14.2–33.6%] vs. hospital 20.3% [95% CI 17–24%], p = 0.68), but it was significantly higher in frail versus non-frail patients (37% [95% CI 26.6–48.8%] vs. 12.5% [95% CI 7.8–19.6%], p-value < 0.01). Delirium definitions and assessment tools largely varied across studies. Conclusion: This review delineates delirium as a common feature of COVID-19, particularly in frail older adults, and supports its formal inclusion among COVID-19 symptoms. The considerable heterogeneity in delirium assessment highlights the need for an operational strategy to standardize definitions and tools utilization in the management of frail older adults.

The development of multiple chronic diseases in the same individual (i.e., multimorbidity) results from the loss of homeostasis across several biological systems. Identifying pathophysiological pathways common to multiple diseases, using accessible biomarkers, could increase our understanding of multimorbidity and improve its prognostication and management. We conducted a systematic review of peer-reviewed articles published till September 2024 that investigated biomarkers of multimorbidity. Due to study heterogeneity, a synthesis without meta-analysis was performed on 43 studies employing harvest plots based on direction of effect, sample size and study quality. Findings highlight how inflammatory and metabolic biomarkers, such as interleukin-6 (IL-6) and glycated haemoglobin (HbA1c) especially, but also triglycerides, low-density lipoprotein (LDL) cholesterol and kidney and liver markers, along with markers of neurodegeneration including Neurofilament Light Chain (NfL) and Phospho-Tau 217 (p-tau 217), were directly associated with multimorbidity. Nonetheless, evidence for hormonal and vascular activation markers, as well as more novel geroscience biomarkers, remains limited. These markers could have a key role in identifying individuals at high risk of developing or worsening multimorbidity. The review also highlights how methodological challenges, including heterogeneity in study design, populations, and multimorbidity definitions, impact on comparability and generalizability of findings. Addressing these gaps through standardized, longitudinal studies and multi-omics approaches is crucial to improve our understanding of the pathophysiological mechanisms of multimorbidity. In summary, this review outlines the independent association of diverse biomarkers with multimorbidity, opening to the possibility of identifying specific pathophysiological pathways for risk stratification and possible target of future personalized interventions.

Background—Analgesics could be used to manage painful symptoms during and after COVID-19. Materials and methods—Persistence of painful symptoms was assessed during and after COVID-19 in a sample of patients admitted to a post-acute COVID-19 outpatient service in Rome, Italy. Data on type and frequency of use of first-line analgesics were collected. Pain severity was evaluated with a numeric rating scale (NRS) from 0 to 10. Results—Mean age of 696 participants was 57.1 ± 20.3 years and 61.7% were women. During COVID-19, the most prevalent symptoms were fever, fatigue, arthralgia, myalgia and headache. Acetaminophen was used by 40% of the sample. Only 6.7% needed to continue analgesic therapy after COVID-19. Frequent causes of analgesics consumption were persistent arthralgia and myalgia. The most common analgesics used amongst those who continued taking analgesics in the post-acute phase of COVID-19 were the following: acetaminophen (31%), ibuprofen (31%) and other non-steroidal anti-inflammatory drug (NSAID) (29.5%); in older subjects the most common analgesic used was acetaminophen (54%). Most of the subjects in this group said there was an improvement in pain perception after taking analgesic therapy (84%). Conclusions—Use of analgesics in the post-acute COVID-19 is common in subjects with persistent arthralgia and myalgia, and common analgesics were acetaminophen and ibuprofen. Further research on the safety and efficacy of those medications in COVID-19 is warranted.