Development of Continuous Assessment of Muscle Quality and Frailty in Older Patients Using Multiparametric Combinations of Ultrasound and Blood Biomarkers: Protocol for the ECOFRAIL Study.

BACKGROUND: Frailty resulting from the loss of muscle quality can potentially be delayed through early detection and physical exercise interventions. There is a demand for cost-effective tools for the objective evaluation of muscle quality, in both cross-sectional and longitudinal assessments. Literature suggests that quantitative analysis of ultrasound data captures morphometric, compositional, and microstructural muscle properties, while biological assays derived from blood samples are associated with functional information. OBJECTIVE: This study aims to assess multiparametric combinations of ultrasound and blood-based biomarkers to offer a cross-sectional evaluation of the patient frailty phenotype and to track changes in muscle quality associated with supervised exercise programs. METHODS: This prospective observational multicenter study will include patients aged 70 years and older who are capable of providing informed consent. We aim to recruit 100 patients from hospital environments and 100 from primary care facilities. Each patient will undergo at least two examinations (baseline and follow-up), totaling a minimum of 400 examinations. In hospital environments, 50 patients will be measured before/after a 16-week individualized and supervised exercise program, while another 50 patients will be followed up after the same period without intervention. Primary care patients will undergo a 1-year follow-up evaluation. The primary objective is to compare cross-sectional evaluations of physical performance, functional capacity, body composition, and derived scales of sarcopenia and frailty with biomarker combinations obtained from muscle ultrasound and blood-based assays. We will analyze ultrasound raw data obtained with a point-of-care device, along with a set of biomarkers previously associated with frailty, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Additionally, we will examine the sensitivity of these biomarkers to detect short-term muscle quality changes and functional improvement after a supervised exercise intervention compared with usual care. RESULTS: At the time of manuscript submission, the enrollment of volunteers is ongoing. Recruitment started on March 1, 2022, and ends on June 30, 2024. CONCLUSIONS: The outlined study protocol will integrate portable technologies, using quantitative muscle ultrasound and blood biomarkers, to facilitate an objective cross-sectional assessment of muscle quality in both hospital and primary care settings. The primary objective is to generate data that can be used to explore associations between biomarker combinations and the cross-sectional clinical assessment of frailty and sarcopenia. Additionally, the study aims to investigate musculoskeletal changes following multicomponent physical exercise programs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05294757; https://clinicaltrials.gov/ct2/show/NCT05294757. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50325.

Muscle mass loss measured with portable ultrasound in hospitalized older adults: The ECOSARC study.

OBJECTIVES: The main objective was to analyze the evolution of muscle of the Quadriceps Rectus Femoris (QRF) between admission and discharge, in older adults hospitalized with an acute medical disease in Acute Geriatric Units (AGUs). DESIGN: Prospective multicentric observational cohort study. SETTING: Seven AGUs from University Hospitals in Spain. PARTICIPANTS: Hospitalized adults ≥ 70 years old, able to ambulate and without severe dementia. MEASUREMENTS: Ultrasound measurements of QRF were acquired at 2/3 distal between anterior-superior iliac spine and patella in both legs by trained Geriatricians. Ultrasound Chison model ECO2 was used. QRF area, thickness, edema, echogenicity, and fasciculations were measured. RESULTS: From the complete sample (n = 143), in 45 (31.5%) participants, ultrasound images were classified as non-valid by an expert radiologist. Mean age was 87.8 (SD 5.4). Mean hospital stay 7.6 days (SD 4.3). From those with valid images, 36 (49.3%), 2 (2.7%), and 35 (47.9%) presented a decrease, equal values, or an increase in QRF area from baseline to discharge, respectively, and 37 (50.0%), 2 (2.7%), and 35 (47.3%) presented a decrease, equal values, or an increase in QRF thickness, respectively. 26 (35.6%) presented a decrease in more than 0.2 cm2 of QRF area, and 23 (31.1%) a decrease in more than 0.1 cm of QRF thickness. Only 4 (5.4%) patients presented new edema, while 13 (17.6%) worsened echogenicity. CONCLUSION: One third of older adults develop significant muscle loss during a hospitalization for acute medical diseases. TRIAL REGISTRATION NUMBER: NCT05113758.

"SARCOPENIA MEASURED BY ULTRASOUND IN HOSPITALIZED OLDER ADULTS" (ECOSARC): multi-centre, prospective observational study protocol.

BACKGROUND: Measurement of muscle mass and function, and thereafter, screening and diagnosis of sarcopenia, is a challenge and a need in hospitalized older adults. However, it is difficult in complex real-world old patients, because usually they are unable to collaborate with clinical, functional, and imaging testing. Ultrasound measurement of quadriceps rectus femoris (QRF) provides a non-invasive, real-time assessment of muscle quantity and quality, and is highly acceptable to participants with excellent inter-rater and intra-rater variability. However, normative data, protocol standardization, and association with longitudinal outcomes, needs further research and consensus. METHODS: Prospective exploratory multicenter study in older adults admitted to Acute Geriatric Units (AGUs) for medical reasons. 157 subjects from 7 AGUs of Spain were recruited between May 2019 and January 2022. Muscle ultrasound measurements of the anterior vastus of the QRF were acquired on admission and on discharge, using a previously validated protocol, using a Chieson model ECO2 ultrasound system (Chieson Medical Technologies, Co. Ltd, Wimxu District Wuxi, Jiangsu, China). Measurements included the cross-sectional area, muscle thickness in longitudinal view, intramuscular central tendon thickness, echogenicity, and the presence or absence of edema and fasciculations. Functional, nutritional, and DXA measurements were provided. Clinical follow-up was completed at discharge, and 30 and 90 days after discharge. Variations between hospital admission and discharge ultrasound values, and the relationship with clinical variables, will be analyzed using paired t-tests, Wilcoxon tests, or Mc Nemar chi-square tests when necessary. Prevalence of sarcopenia will be calculated, as well as sensitivity and specificity of ultrasound measurements to determine sarcopenia. Kappa analysis will be used to analyze the concordance between measurements, and sensitivity analysis will be conducted for each participating center. DISCUSSION: The results obtained will be of great interest to the scientific geriatric community to assess the utility and validity of ultrasound measurements for the detection and follow-up of sarcopenia in hospitalized older adults, and its association with adverse outcomes. TRIAL REGISTRATION: NCT05113758. Registration date: November 9th 2021. Retrospectively registered.

CAREPATH: Developing Digital Integrated Care Solutions for Multimorbid Patients with Dementia.

CAREPATH project is focusing on providing an integrated solution for sustainable care for multimorbid elderly patients with dementia or mild cognitive impairment. The project has a digitally enhanced integrated patient-centered care approach clinical decision and associated intelligent tools with the aim to increase patients' independence, quality of life and intrinsic capacity. In this paper, the conceptual aspects of the CAREPATH project, in terms of technical and clinical requirements and considerations, are presented.

Psychological and Functional Impact of COVID-19 in Long-Term Care Facilities: The COVID-A Study.

OBJECTIVE: To analyze the psychological and functional sequelae of the COVID-19 pandemic among older adults living in long term care facilities (LTCFs). DESIGN: Cohort longitudinal study SETTING ANT PARTICIPANTS: A total of 215 residents ≥ 65 years without moderate-to-severe cognitive impairment, living in five LTCFs in Albacete (Spain). MEASUREMENTS: Baseline on-site data were collected between March - June 2020 and three-month follow-up between June to September 2020. Symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), and sleep disturbances were measured as psychological variables. Disability in basic activities of daily living (BADL), ambulation and frailty were assessed as functional variables. Differences were analyzed in relation to level of comorbidity and test positivity for COVID-19. RESULTS: At baseline, residents with COVID-19 presented worse functionality, higher frailty levels and malnutrition risk compared to non-COVID-19 residents. At three-month follow-up, higher rates of clinically significant depressive symptoms (57.7%), anxiety symptoms (29.3%), PTSD symptoms (19.1%) and sleep disturbances (93.0%) were found among residents regardless of COVID status. Thus, among 215 residents, 101 (47%) experienced a decline in BADL from baseline to the 3-month follow-up (median functional loss = 5 points in Barthel Index). In multivariate analyses, COVID-19 status did not explain either the functional or the ambulation loss. By contrast, residents with low comorbidity and COVID-19 presented higher PTSD symptoms (effect 2.58; 95% CI 0.93 to 4.23) and anxiety symptoms (effect 2.10; 95% CI 0.48 to 3.73) compared to the low comorbidity/non-COVID19 group. CONCLUSION: COVID-19 pandemic was associated, after three-months, with high psychological impact in older adults in LTCFs., specifically with higher post-traumatic stress and anxiety symptoms. Functional decline did not differ in relation to COVID-19 status but could be related to isolation strategies used for pandemic control.

Immunogenicity after 6 months of BNT162b2 vaccination in frail or disabled nursing home residents: The COVID-A Study.

BACKGROUND: There is incomplete information regarding evolution of antibody titers against SARS-CoV-2 after a two-dose strategy vaccination with BNT162b2 in older adults in long-term care facilities (LTCFs) with frailty, disability, or cognitive impairment. We aimed to determine IgG antibody titer loss in older adults in LTCFs. METHODS: This is a multicenter longitudinal cohort study including 127 residents (90 females and 37 males) with a mean age of 82.7 years (range 65-99) with different frailty and disability profiles in two LTCFs in Albacete, Spain. Residents received two doses of BNT162b2 as per label, and antibody levels were determined 1 and 6 months after the second dose. Age, sex, previous history of coronavirus disease 2019 (COVID-19), comorbidity (Charlson Index), performance in activities of daily living (Barthel Index), frailty (FRAIL instrument), and cognitive status were assessed. RESULTS: The mean antibody titers 1 and 6 months after the second vaccine dose were 32,145 AU/ml (SD 41,206) and 6182 AU/ml (SD 13,316), respectively. Across all participants, the median antibody titer loss measured 77.6% (interquartile range [IQR] 23.8%). Notably, the decline of titers in individuals with pre-vaccination COVID-19 infection was significantly lower than in those without a history of SARS-CoV-2 infection (72.2% vs. 85.3%; p < 0.001). The median titer decrease per follow-up day was 0.47% (IQR 0.14%) and only pre-vaccination COVID-19 was associated with lower rate of antibody decline at 6 months (hazard ratio 0.17; 95% confidence interval 0.07-0.41; p < 0.001). Frailty, disability, older age, cognitive impairment, or comorbidity were not associated with the extent of antibody loss. CONCLUSIONS: Older adults in LTCFs experience a rapid loss of antibodies over the first 6 months after the second dose of BNT162b2 vaccine. Only pre-vaccination COVID-19 is associated with a slower rate of antibody decrease. Our data support immunization with a third dose in this vulnerable, high-risk population.

[Frailty prevalence in hospitalized older adults. A systematic review.] / Prevalencia de fragilidad en adultos mayores hospitalizados. Revisión sistemática.

BACKGROUND: Theres is uncertain evidence regarding the prevalence, measurement tools, outcomes, and efficacy of the interventions on frailty in hospitalized older adults. For this reason, we present the results of a systematic review about Frailty and Hospital, following the PRISMA methodology. METHODS: We found 2,050 articles published in PubMed. After an initial assessment of titles and abstracts, complete comprehensive text lecture, and meta-analysis review, we finally included in the systematic review 246 originals. RESULTS: The main result of the systematic review is that from the 246 articles, 179 described frailty prevalence in hospital older adults, with a pooled prevalence of 41.4% (95% CI 38.4% to 44.4%; range 4.7% to 92.5%). The most frequent type of studies were those observational prospectives 166 (67.5%), being the rest observtcional retrospectives or cross-sectional 64 (26.2%) or randomized clinical trials 15 (6.1%). The most frequent healthcare levels where the studies took place were the Hospital/Hospitalization in 125 (50.8%), Geriatric Department in 41 (16.7%), Surgical Units in 23 (9.3%), Cardiology Department in 18 (7.3%), Emergency Department in 15 (6.1%), and other in 24 (9.8%). The most frequent used measurement tolos were the Clinical Frailty Scale in 69 works (28%), the frailty phenotype in 41 (15.9%), the Frailty Index in 39 (15.9%) and the FRAIL scale in 27 (11.0%). In several papers, more than one instrument was used, and in many of them, scales and cut-off points were arbitrarely determined, producing a great results heterogeneity. CONCLUSIONS: The prevalence of frailty in hospitalized older adults is very high. It is necessary to improve frailty measure homogenity and to realize randomized clinical trials in this population.

OBJETIVO: Existe escasa evidencia sobre la prevalencia, herramientas de medición, resultados de salud y eficacia de las intervenciones sobre la fragilidad en adultos mayores en medio hospitalario. Por ello, presentamos los resultados de una revisión sistemática de la Fragilidad en adultos mayores en medio hospitalario, siguiendo la metodología de la declaración PRISMA. METODOS: Se encontraron 2.050 artículos en PubMed. Tras la valoración inicial de los títulos y resúmenes, lectura de texto completo y revisión de los meta-análisis, al final se incluyeron en la revisión sistemática 246 originales. RESULTADOS: El principal resultado fue que, de los 246 originales revisados, 179 describían la prevalencia de fragilidad en adultos mayores en el hospital, siendo el porcentaje combinado del 41,4% (IC 95% 38,4% a 44,4%; rango 4,7% a 92,5%). Por tipo de estudios predominaron los observacionales prospectivos 166 (67,5%), observacionales retrospectivos o transversales 64 (26,2%) y ensayos clínicos 15 (6,1%). Los dispositivos asistenciales más frecuentes fueron el Hospital en general/Hospitalización 125 (50,8%), Geriatría 41 (16,7%), Unidades quirúrgicas 23 (9,3%), Cardiología 18 (7,3%), Urgencias/emergencias 15 (6,1%) y otros dispositivos médicos 24 (9,8%). Las herramientas de valoración de la fragilidad más empleadas fueron la Clinical Frailty Scale en 69 artículos (28%), fenotipo de fragilidad en 41 (16,7%), Frailty Index en 39 (15,9%) y herramienta FRAIL en 27 (11,0%). En varios artículos se emplearon dos o más de las herramientas descritas, y en muchos, las escalas y los puntos de corte fueron arbitrariamente modificados por los autores, generando una gran heterogeneidad en los resultados. CONCLUSIONES: La prevalencia de fragilidad en adultos mayores en el hospital es muy alta, pero es necesaria una mayor uniformidad en su medición y la implementación de ensayos clínicos para evaluar intervenciones.

Baricitinib reduces 30-day mortality in older adults with moderate-to-severe COVID-19 pneumonia.

BACKGROUND: Older adults are at the highest risk of severe disease and death due to COVID-19. Randomized data have shown that baricitinib improves outcomes in these patients, but focused stratified analyses of geriatric cohorts are lacking. Our objective was to analyze the efficacy of baricitinib in older adults with COVID-19 moderate-to-severe pneumonia. METHODS: This is a propensity score [PS]-matched retrospective cohort study. Patients from the COVID-AGE and Alba-Score cohorts, hospitalized for moderate-to-severe COVID-19 pneumonia, were categorized in two age brackets of age <70 years old (86 with baricitinib and 86 PS-matched controls) or ≥70 years old (78 on baricitinib and 78 PS-matched controls). Thirty-day mortality rates were analyzed with Kaplan-Meier and Cox proportional hazard models. RESULTS: Mean age was 79.1 for those ≥70 years and 58.9 for those <70. Exactly 29.6% were female. Treatment with baricitinib resulted in a significant reduction in death from any cause by 48% in patients aged 70 or older, an 18.5% reduction in 30-day absolute mortality risk (n/N: 16/78 [20.5%] baricitinib, 30/78 [38.5%] in PS-matched controls, p < 0.001) and a lower 30-day adjusted fatality rate (HR 0.21; 95% CI 0.09-0.47; p < 0.001). Beneficial effects on mortality were also observed in the age group <70 (8.1% reduction in 30-day absolute mortality risk; HR 0.14; 95% CI 0.03-0.64; p = 0.011). CONCLUSIONS: Baricitinib is associated with an absolute mortality risk reduction of 18.5% in adults older than 70 years hospitalized with COVID-19 pneumonia.

Immunogenicity of the BNT162b2 vaccine in frail or disabled nursing home residents: COVID-A study.

BACKGROUND/OBJECTIVES: The safety and immunogenicity of the BNT162b2 coronavirus disease 2019 (COVID-19) vaccine in older adults with different frailty and disability profiles have not been well determined. Our objective was to analyze immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in older adults across frailty and disability profiles. DESIGN: Multicenter longitudinal cohort study. SETTING AND PARTICIPANTS: A total of 134 residents aged ≥65 years with different frailty and disability profiles in five long-term care facilities (LTCFs) in Albacete, Spain. INTERVENTION AND MEASUREMENTS: Residents were administered two vaccine doses as per the label, and antibody levels were determined 21.9 days (SD 9.3) after both the first and second dose. Functional variables were assessed using activities of daily living (Barthel Index), and frailty status was determined with the FRAIL instrument. Cognitive status and comorbidity were also evaluated. RESULTS: Mean age was 82.9 years (range 65-99), and 71.6% were female. The mean antibody titers in residents with and without previous COVID-19 infection were 49,878 AU/ml and 15,274 AU/ml, respectively (mean difference 34,604; 95% confidence interval [CI]: 27,699-41,509). No severe adverse reactions were observed, after either vaccine dose. Those with prevaccination COVID-19 had an increased antibody level after the vaccine (B = 31,337; 95% CI: 22,725-39,950; p < 0.001). Frailty, disability, older age, sex, cognitive impairment, or comorbidities were not associated with different antibody titers. CONCLUSIONS: The BNT162b2 mRNA COVID-19 vaccine in older adults is safe and produces immunogenicity, independently of the frailty and disability profiles. Older adults in LTCFs should receive a COVID-19 vaccine.

COVID-19 outbreak in long-term care facilities from Spain. Many lessons to learn.

BACKGROUND/OBJECTIVES: To analyze mortality, costs, residents and personnel characteristics, in six long-term care facilities (LTCF) during the outbreak of COVID-19 in Spain. DESIGN: Epidemiological study. SETTING: Six open LTCFs in Albacete (Spain). PARTICIPANTS: 198 residents and 190 workers from LTCF A were included, between 2020 March 6 and April 5. Epidemiological data were also collected from six LTCFs of Albacete for the same period of time, including 1,084 residents. MEASUREMENTS: Baseline demographic, clinical, functional, cognitive and nutritional variables were collected. 1-month and 3-month mortality was determined, excess mortality was calculated, and costs associated with the pandemics were analyzed. RESULTS: The pooled mortality rate for the first month and first three months of the outbreak were 15.3% and 28.0%, and the pooled excess mortality for these periods were 564% and 315% respectively. In facility A, the percentage of probable COVID-19 infected residents were 33.6%. Probable infected patients were older, frail, and with a worse functional situation than those without COVID-19. The most common symptoms were fever, cough and dyspnea. 25 residents were transferred to the emergency department, 21 were hospitalized, and 54 were moved to the facility medical unit. Mortality was higher upon male older residents, with worse functionality, and higher comorbidity. During the first month of the outbreak, 65 (24.6%) workers leaved, mainly with COVID-19 symptoms, and 69 new workers were contracted. The mean number of days of leave was 19.2. Costs associated with the COVID-19 in facility A were estimated at € 276,281/month, mostly caused by resident hospitalizations, leaves of workers, staff replacement, and interventions of healthcare professionals. CONCLUSION: The COVID-19 pandemic posed residents at high mortality risk, mainly in those older, frail and with worse functional status. Personal and economic costs were high.