Indoor mobility, frailty, and disability in community-dwelling older adults: a mediation model

The general population, but especially older adults, were forced or encouraged to stay home during the recent COVID-19 pandemic. In this context, indoor mobility (IM, the number of steps performed daily at home) may be informative about the general health status of older adults. The present study aimed at evaluating the relationship between IM, frailty (loss of functional reserve including both physical and psychosocial domains), and disability (loss of autonomy measured as activities of daily life, ADLs) in a sample of community-dwelling Italian older adults. Specifically, the primary objective was to investigate IM and disability differences between robust and frail older adults. The secondary objective was to test if frailty is in the causal sequence between IM and disability, i.e., as a mediator in their relationship. Thirty-two participants (mean age = 70 ± 6 years; 56.2% women) were recruited. Frailty and disability were evaluated using the Tilburg Frailty Indicator and the Groningen Activity Restriction Scale, respectively. IM at home was measured via an Adamo wristwatch (a connected accelerometer). One-way analyses of covariance, controlling for age and gender, showed that robust participants, classified according to a score higher than five points in the Tilburg Frailty Indicator, performed significantly more IM (F1,28 = 4.639; p = 0.04) and presented lower disability grade than frail ones (F1,28 = 4.342; p =0.046). Only physical frailty was a mediator in the relationship between IM and disability (F2,29 = 8.538, p < 0.001), with a fully mediated model (z = -2.073, p < 0.04). Conversely, the total frailty score was not a mediator in the same relationship, but with IM accounted for the variance in disability (F2,29 = 8.538, p < 0.001; R2 = 33.7%). Our results suggested that frail older adults restricted their IM more and presented a higher level of disability compared to robust older adults. Moreover, data suggest that IM reduction may have a negative impact on physical frailty and indirectly increase disability

Computed tomography findings and prognosis in older COVID-19 patients

Background: In older and multimorbid patients, chronic conditions may affect the prognostic validity of computed tomography (CT) findings in COVID-19. This study aims at assessing to which extent CT findings have prognostic implications in COVID-19 older patients. Methods: Hospitalized COVID-19 patients aged 60 years or more enrolled in the multicenter, observational and longitudinal GeroCovid study who underwent chest CT were included. Patients were stratified by tertiles of age and pneumonia severity to compare CT findings. Hierarchical clustering based on CT findings was performed to identify CT-related classificatory constructs, if any. The hazard ratio (HR) of mortality was calculated for individual CT findings and for clusters, after adjusting for potential confounders. Results: 380 hospitalized COVID-19 patients, with a mean age of 78 (SD:9) years, underwent chest CT scan. Ground glass opacity (GGO), consolidation, and pleural effusion were the three most common CT findings, with GGO prevalence decreasing from younger to older patients and pleural effusion increasing. More severe the pneumonia more prevalent were GGO, consolidation and pleural effusion. HR of mortality was 1.94 (95%CI 1.24-3.06) for pleural effusion and 13 (95%CI 6.41-27) for cluster with a low prevalence of GGO and a high prevalence of pleural effusion ("LH"), respectively. Out of the three CT based clusters, "LH" was the only independent predictor in the multivariable model. Conclusions: Pleural effusion qualifies as a distinctive prognostic marker in older COVID-19 patients. Research is needed to verify whether pleural effusion reflects COVID-19 severity or a coexisting chronic condition making the patient at special risk of death. Trial registration: ClinicalTrials.gov: NCT04379440

Disentangling the impact of COVID-19 infection on clinical outcomes and preventive strategies in older persons: An Italian perspective

Italy was one of the first western countries to embrace the first wave of COVID-19 and undergo detrimental outcomes in older adults in different clinical settings, especially in those with comorbidity and frailty. In addition, older nursing home (NH) residents had significantly higher mortality rates most likely due to the increased susceptibility of infection due to combined physical vulnerability and risks linked to the NH living environment itself. Different reports throughout Italy have rapidly highlighted selected outcomes related to COVID-19 in older patients being treated in acute and long-term care (LTC) settings. However, the majority of these studies are single center studies. Thus, it remains fundamental to collect large data from prospective based-population studies in order to identify preventive and therapeutic COVID-19 risk/protective factors correlated with COVID-19 health status outcomes. In this commentary paper, we will discuss different Italian reports according to clinical settings and highlight the importance of GeroCovid Observational and GeroCovid Vax, two large population based prospective studies in Italy

Making sense of big data in health research: Towards an EU action plan.

Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health and healthcare for all Europeans

Physical frailty and sarcopenia (PF&S): a point of view from the industry

We have observed over the last 15 years a wide debate both in the medical scientific community and in the public health arena on the definition and operationalization of frailty, typically a geriatric condition, and in particular of physical frailty linked to sarcopenia. Because physical frailty in its initial phase can still be reversed, fighting sarcopenia in elderly persons has the potential to slow or halt progressive decline towards disability and dependency. Quite recently, regulators focused attention on frailty as an indicator of biological age to be measured to characterize elderly patients before their inclusion in clinical trials. A European guidance regarding most adapted evaluation instruments of frailty is currently under public consultation. Does the regulatory initiative imply we should now consider frailty, and particularly physical frailty, primarily as an important risk factor for adverse events and poor response, or mainly as a clinical tool helping the physician to opt for one therapeutic pathway or another? Or is physical frailty above all a specific geriatric condition deserving an effective and innovative therapeutic approach with the objective to curb the incidence of its most common result, e.g., mobility disability? Pharmaceutical industry developers consider both faces of the coin very relevant. We agree with regulators that better characterization of subpopulations, not only in elderly patients, can improve the benefit risk ratio of medicines. At the same time, we believe it is in the public health interest to develop novel drugs indicated for specific geriatric conditions, like osteoporosis in the 1990s and sarcopenia today. We consider it an important therapeutic goal to effectively delay mobility disability and to extend the active, independent, and healthy life years of aging people. The “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” (SPRINTT) collaborative project under IMI is paving the way for adapted methodologies to study the change of physical frailty and sarcopenia in at-risk older persons and to adequately characterize the population that needs to be treated

Fighting against age discrimination in clinical trials

At the American Geriatrics Society 2008 Annual Meeting, representatives of two geriatric societies, the European Union Geriatric Medicine Societies and the American Geriatrics Society, and two regulatory agencies, the U.S. Food and Drug Administration and the European Medicine Agency, conducted a roundtable discussion aimed at reviewing the participation of older people in clinical trials. This article summarizes the important issues discussed at the meeting. Historically, regulatory agencies started to promote the inclusion of older participants in clinical trials in the late 1980s. The identification of the causes of delay in including older participants in clinical trials, as well as of the ongoing bias against including older participants with multiple comorbidities, is important to help geriatricians fight against age discrimination in clinical trials. To overcome this problem, geriatrics societies and regulatory agencies must work together to propose new definitions, study designs, and technologies aimed at improving the evaluation of drugs in older people with multiple comorbidities and polypharmacy

Long-term GAIT speed telemonitoring in older adults with mild cognitive impairment or mild dementia. The DECI study

Non-intrusive telemonitoring of physical activity in Older Adults suffering from Mild Cognitive Impairment (MCI), or Mild Dementia (MD), was implemented as part of a 6-month multicomponent digital intervention in the DECI study (EU Horizon2020 grant No 643588). Methods: To estimate gait speed long-term trajectory, a processing algorithm was applied on individual accelerometry data continuously recorded via the ADAMO wrist-watch accelerometer. Speed Trend Analysis was performed if patients wore the device ≥90 days. Only outdoor activity was analyzed to reflect patients’ own natural gait speed. Only time spent in high or very-high-activity level is used, to eliminate rest periods (e.g. sitting on a bench, on a bus or driving). A raw mean walking speed was computed. Stride was computed from gender and height and walked distance from stride and step count. Mean walking speed was estimated by walking distance and duration. A rolling mean algorithm was applied to the computed mean 15-day baseline series, resulting in a new series representing normalized patient’s gait speed trajectory during the study. Results: Baseline characteristics: F/M=21/19; MCI/MD=36/4; age=75.4\ub16.0 years; BMI= 24.6\ub15,2; MMSE=26.5\ub12.4; education=8.9\ub14.0 years. Monitoring days=147\ub129. Overall three main patterns of gait speed trajectory were identified: “relative stability”, “improving trend” and “progressive decline”: No evident correlation with cognitive status was observed in the sample. Examples of individual patterns are shown. Conclusions: Gait Speed Analysis can describe physical function trajectory over time and identify decliners from stable or improving older adults. Further analyses may clarify the relationship between physical function changes and cognitive status

A Phase 1 study for safety and pharmacokinetics of BIO101 (20‐hydroxyecdysone) in healthy young and older adults

Abstract Background Sarcopenia is an age‐related skeletal muscle disorder characterized by loss of muscle mass and strength leading to mobility disability. 20‐Hydroxyecdysone (20E) is a polyhydroxylated plant steroid that demonstrates pharmacological effects in many disease animal models including ageing/sarcopenia. BIO101 is a 20E purified investigational drug (≥97%) that previously demonstrated good toxicology profiles in rat and dog. BIO101 is evaluated in healthy young and older adults in a Phase 1 study. Methods This study is a Single Ascending Dose (SAD) followed by a 14‐day Multiple Ascending Dose (MAD). In SAD, BIO101 was administered orally to 16 young adults at doses from 100 to 1400 mg and to 8 older adults (age ≥65 years) at 1400 mg. In MAD, doses of 350 mg once daily (qd), 350 mg twice daily (bid) and 450 mg bid were administered to 10 older adults. The primary objective was to evaluate safety and pharmacokinetics (PK), including dosing of circulating metabolites. Pharmacodynamic effects were investigated with regard to myostatin, procollagen‐III‐amino‐terminal propeptide (PIIINP), myoglobin, creatine‐kinase Muscle Brain (CKMB), renin and aldosterone plasma/serum levels. Results BIO101 showed a good safety profile with only mild to moderate adverse events and a satisfactory pharmacokinetic profile. In SAD, at 100 mg to 1400 mg, mean Cmax and areas under the curve increased less than dose‐proportionally. Mean half‐life was short (2.4–4.9 h), and mean renal clearance was comparable in all doses (4.05–5.05 L/h). Mean plasma exposure was slightly lower in older adults (22% lower for Cmax and 13%–15% lower for AUCs) compared with young subjects. In MAD, 350 and 450 mg bid led to a slight accumulation over 14 days (mean ratio of accumulation [Rac] of 1.31 in both cohorts). Reduction of biomarkers (myoglobin, CK‐MB) mean serum levels (vs. baseline) was observed at 450 mg bid. Two major metabolites of 20E (14‐deoxy‐20‐hydroxyecdysone and 14‐deoxypoststerone) were identified and quantified. Conclusions BIO101 shows a good safety and pharmacokinetic profile that led to the selection of doses for the subsequent interventional clinical trials of Phase 2 in age‐related sarcopenia (SARA‐INT) and Phase 3 in Covid‐19 (COVA)

Using socially assistive robots for monitoring and preventing frailty among older adults: a study on usability and user experience challenges

Socially assistive robots can play an important role in the monitoring and training of health of older adults. But before their benefits can be reaped, proper usability and a positive user experience need to be ensured. In this study, we tested the usability and user experience of a socially assistive robot (the NAO humanoid robot) to monitor and train the health of frail older adults. They were asked to complete a set of health monitoring and physical training tasks, once provided by the NAO robot, and once provided by a Tablet PC application (as a reference technology). After using each technology, they completed the System Usability Scale for usability, and a set of rating scales for perceived usefulness, enjoyment, and control. Finally, we questioned the participants’ preference for one of the technologies. All interactions were recorded on video and scrutinized for usability issues. Twenty older adults participated. They awarded both technologies ‘average’ usability scores. Perceived usefulness and enjoyment were rated as very positive for both modalities; control was scored positively. Main usability issues for NAO for these tasks were related to speech interaction (e.g., NAO’s limited speech library, NAO’s difficulty to cope with Dutch dialect), older adults’ difficulties with taking their proper role in human-robot interaction, and a lack of affordances of NAO. Seven participants preferred NAO: it was easier to use and more personal. Social robots have the potential to monitor and train the health of frail older adults, but some critical usability challenges need to be overcome first