Response rates and associated factors after a multicomponent intervention in frail older adults with diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and frailty are associated with functional decline in older population. OBJECTIVE: To explore the individual response to a multimodal intervention on functional performance. DESIGN: A cluster-randomised multicentre clinical trial. SETTING: Outpatients in hospital or primary care. SUBJECTS: 843 (77.83 years, 50.65% men) prefrail and frail individuals ≥70 years with T2DM. METHODS: Participants were allocated to usual care group (UCG) or a multicomponent intervention group (IG): 16-week progressive resistance training, seven nutritional and diabetological educational sessions and achievement of glycated haemoglobin (7-8%) and blood pressure (<150 mmHg) targets. Functional performance was assessed with the Short Physical Performance Battery (SPPB) at 1 year. We used multivariate binomial and multinomial logistic regression models to explore the effect of the IG, and adherence on the outcomes studied, in several adjusted models. RESULTS: 53.7% in the IG versus 38.0% in the UCG improved by at least 1 point in their SPPB score [OR (95% CI): 2.07 (1.43, 2.98), P value <0.001]. Age, SPPB score and number of frailty criteria met decreased the probability of improving the SPPB score. Factors associated with worsening were pertaining to IG (decreased), age, SPPB score and the number of frailty criteria (increased). An adherence ≥84% was needed to achieve benefits, reaching the peak in the probability of improving SPPB when this was ≥85% [OR(95%CI): 2.38 (1.29, 4.79), P value 0.014]. CONCLUSIONS: Factors predicting the likelihood of improvement in a multimodal programme in pre-frail and frail older adults with diabetes are age, basal SPPB score, the number of frailty criteria and adherence.

Frailty Influences the Relationship between the Soluble Receptor for Advanced Glycation-End Products and Mortality in Older Adults with Diabetes Mellitus.

INTRODUCTION: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. METHODS: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried's criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. RESULTS: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962-2,043] pg/mL vs. 1,212 [963-1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36-3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30-4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91-3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.

PKC Inhibition Improves Human Penile Vascular Function and the NO/cGMP Pathway in Diabetic Erectile Dysfunction: The Role of NADPH Oxidase.

Erectile dysfunction (ED) is a frequent and difficult-to-treat condition in diabetic men. Protein kinase C (PKC) is involved in diabetes-related vascular and cavernosal alterations. We aimed to evaluate the role of PKC in endothelial dysfunction and NO/cGMP impairment associated with diabetic ED in the human corpus cavernosum (CC) and penile resistance arteries (PRAs) and the potential mechanisms involved. Functional responses were determined in the CC and PRAs in patients with non-diabetic ED and diabetic ED undergoing penile prosthesis insertion. PKC activator 12,13-phorbol-dibutyrate (PDBu) impaired endothelial relaxations and cGMP generation in response to acetylcholine in the CC from non-diabetic ED. PDBu also impaired responses to a PDE5 inhibitor, sildenafil, in non-diabetic ED patients. Conversely, a PKC inhibitor, GF109203X, improved endothelial, neurogenic, and PDE5-inhibitor-induced relaxations and cGMP generation only in the CC in diabetic ED patients. Endothelial and PDE5-inhibitor-induced vasodilations of PRAs were potentiated only in diabetes. Improvements in endothelial function in diabetes were also achieved with a specific inhibitor of the PKCß2 isoform or an NADPH-oxidase inhibitor, apocynin, which prevented PDBu-induced impairment in non-diabetic patients. PKC inhibition counteracted NO/cGMP impairment and endothelial dysfunction in diabetes-related ED, potentially improving response to PDE5 inhibition.

Differential utility of various frailty diagnostic tools in non-geriatric hospital departments of several countries: A longitudinal study.

BACKGROUND: There is limited knowledge on the performance of different frailty scales in clinical settings. We sought to evaluate in non-geriatric hospital departments the feasibility, agreement and predictive ability for adverse events after 1 year follow-up of several frailty assessment tools. METHODS: Longitudinal study with 667 older adults recruited from five hospitals in three different countries (Spain, Italy and United Kingdom). Participants were older than 75 years attending the emergency room, cardiology and surgery departments. Frailty scales used were Frailty Phenotype (FP), FRAIL scale, Tilburg and Groningen Frailty Indicators, and Clinical Frailty Scale (CFS). Analyses included the prevalence of frailty, degree of agreement between tools, feasibility and prognostic value for hospital readmission, worsening of disability and mortality, by tool and setting. RESULTS: Emergency Room and cardiology were the settings with the highest frailty prevalence, varying by tool between 40.4% and 67.2%; elective surgery was the one with the lowest prevalence (between 13.2% and 38.2%). The tools showed a fair to moderate agreement. FP showed the lowest feasibility, especially in urgent surgery (35.6%). FRAIL, CFS and FP predicted mortality and readmissions in several settings, but disability worsening only in cardiology. CONCLUSIONS: Frailty is a highly frequent condition in older people attending non-geriatric hospital departments. We recommend that based upon their current feasibility and predictive ability, the FRAIL scale, CFS and FP should be preferentially used in these settings. The low concordance among the tools and differences in prevalence reported and predictive ability suggest the existence of different subtypes of frailty.

Essential steps in primary care management of older people with Type 2 diabetes: an executive summary on behalf of the European geriatric medicine society (EuGMS) and the European diabetes working party for older people (EDWPOP) collaboration.

We present an executive summary of a guideline for management of type 2 diabetes mellitus in primary care written by the European Geriatric Medicine Society, the European Diabetes Working Party for Older People with contributions from primary care practitioners and participation of a patient's advocate. This consensus document relies where possible on evidence-based recommendations and expert opinions in the fields where evidences are lacking. The full text includes 4 parts: a general strategy based on comprehensive assessment to enhance quality and individualised care plan, treatments decision guidance, management of complications, and care in case of special conditions. Screening for frailty and cognitive impairment is recommended as well as a comprehensive assessment all health conditions are concerned, including end of life situations. The full text is available online at the following address: essential_steps_inprimary_care_in_older_people_with_diabetes_-_EuGMS-EDWPOP___3_.pdf.

Upregulation of Orai Channels Contributes to Aging-Related Vascular Alterations in Rat Coronary Arteries.

Vascular territories display heterogeneous sensitivity to the impacts of aging. The relevance of the STIM/Orai system to vascular function depends on the vascular bed. We aimed to evaluate the contribution of the STIM/Orai system to aging-related vascular dysfunction in rat coronary circulation. Vascular function was evaluated according to myography in coronary arteries from young (three-month-old) and older (twenty-month-old) rats. The effects of aging and STIM/Orai inhibition on the contraction and relaxation of the coronary arteries and on the protein expression of STIM-1, Orai1, and Orai3 in these vessels were determined. Aging-related hypercontractility to serotonin and endothelin-1 in arteries from male rats was reversed by STIM/Orai inhibition with YM-58483 or by specifically blocking the Orai1 channel with Synta66. The inhibitory effects of Synta66 on coronary vasoconstriction were also observed in older female rats. YM-58483 relaxed serotonin- but not KCl-contracted arteries from males. STIM/Orai inhibition improved defective endothelial vasodilations in aged arteries, even in the presence of NO synthase and cyclooxygenase inhibitors, but not in KCl-contracted segments. YM-58483 significantly enhanced relaxations to calcium-activated potassium channel stimulation in aged vessels. Increased protein expression of Orai1 and Orai3 was detected in arterial homogenates and sections from older rats. Upregulation of the Orai channel contributes to aging-related coronary dysfunction, revealing a potential target in reducing CVD risk.

STIM/Orai Inhibition as a Strategy for Alleviating Diabetic Erectile Dysfunction Through Modulation of Rat and Human Penile Tissue Contractility and in vivo Potentiation of Erectile Responses.

BACKGROUND: Stromal interaction molecule (STIM)/Orai calcium entry system appears to have a role in erectile dysfunction (ED) pathophysiology but its specific contribution to diabetic ED was not elucidated. AIM: To evaluate STIM/Orai inhibition on functional alterations associated with diabetic ED in rat and human penile tissues and on in vivo erectile responses in diabetic rats. METHODS: Rat corpus cavernosum (RCC) strips from nondiabetic (No DM) and streptozotocin-induced diabetic (DM) rats and human penile resistance arteries (HPRA) and corpus cavernosum (HCC) from ED patients undergoing penile prosthesis insertion were functionally evaluated in organ chambers and wire myographs. Erectile function in vivo in rats was assessed by intracavernosal pressure (ICP) responses to cavernous nerve electrical stimulation (CNES). Expression of STIM/Orai elements in HCC was determined by immunofluorescence and immunoblot. MAIN OUTCOME MEASURES: Functional responses in RCC, HCC and HPRA and STIM/Orai protein expression in HCC. In vivo erectile responses to CNES. RESULTS: Inhibition of Orai channels with YM-58483 (20 µM) significantly reduced adrenergic contractions in RCC but more effectively in DM. Thromboxane-induced and neurogenic contractions were reduced by STIM/Orai inhibition while defective endothelial, neurogenic and PDE5 inhibitor-induced relaxations were enhanced by YM-58483 (10 µM) in RCC from DM rats. In vivo, YM-58483 caused erections and attenuated diabetes-related impairment of erectile responses. YM-58483 potentiated the effects of PDE5 inhibition. In human tissues, STIM/Orai inhibition depressed adrenergic and thromboxane-induced contractions in ED patients more effectively in those with type 2 diabetes. Diabetes was associated with increased expression of Orai1 and Orai3 in ED patients. CLINICAL TRANSLATION: Targeting STIM/Orai to alleviate diabetes-related functional alterations of penile vascular tissue could improve erectile function and potentiate therapeutic effects of PDE5 inhibitors in diabetic ED. STRENGTHS AND LIMITATIONS: Improving effects of STIM/Orai inhibition on diabetes-related functional impairment was evidenced in vitro and in vivo in an animal model and validated in human tissues from ED patients. Functional findings were complemented with expression results. Main limitation was low numbers of human experiments due to limited human tissue availability. CONCLUSIONS: STIM/Orai inhibition alleviated alterations of functional responses in vitro and improved erectile responses in vivo in diabetic rats, potentiating the effects of PDE5 inhibition. STIM/Orai inhibition was validated as a target to modulate functional alterations of human penile vascular tissue in diabetic ED where Orai1 and Orai3 channels were upregulated. STIM/Orai inhibition could be a potential therapeutic strategy to overcome poor response to conventional ED therapy in diabetic patients. Sevilleja-Ortiz A, El Assar M, García-Gómez B, et al. STIM/Orai Inhibition as a Strategy for Alleviating Diabetic Erectile Dysfunction Through Modulation of Rat and Human Penile Tissue Contractility and in vivo Potentiation of Erectile Responses. J Sex Med 2022;19:1733-1749.

Healthcare cost expenditures associated to frailty and sarcopenia.

OBJECTIVES: Frailty and sarcopenia have been related with adverse events, including hospitalization. However, its combined effect with hospitalization-related outcomes, including costs, has not been previously investigated. Our purpose was to explore how frailty, sarcopenia and its interaction could impact on healthcare expenditures. METHODS: 1358 community-dwelling older adults from the Toledo Study of Healthy Ageing (TSHA) were included. Sarcopenia was measured using the Foundation for the National Institutes of Health criteria fitted to our cohort. Frailty was defined according to Frailty Trait Scale 5 (FTS5) and the Frailty Index fitted to the cut-off points of TSHA population. Hospitalization costs were taken from hospital records and costs were attributed according to Diagnostic-Related Groups, using as the cost base year 2015. Two-part regression models were used to analyze the relationship between frailty and sarcopenia and hospital admission, number of hospitalizations, length of stay and hospitalization costs. RESULTS: Sarcopenia was associated only with the probability of being admitted to hospital. Frailty was also associated with higher hospital use, regardless of the frailty tool used, but in addition increased hospital admission costs at follow-up by 23.72% per year and by 19.73% in the full model compared with non-frail individuals. The presence of sarcopenia did not increase the costs of frailty but, by opposite, frailty significantly increased the costs in people with sarcopenia, reaching by 46-56%/patient/year at follow-up. Older adults with frailty and sarcopenia had a higher risk of hospitalization, disregarding the tool used to assess frailty, and higher hospitalization costs (FTS5) in the full model, at the cross-sectional and at the follow-up level. CONCLUSIONS: Frailty is associated with increased hospitalization costs and accounts for the potential effects of sarcopenia.

Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging.

Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and cardiovascular system alterations. Aged skeletal muscle mass and strength impairment is related to anabolic resistance, mitochondrial dysfunction, increased oxidative stress and inflammation as well as a reduced antioxidant response and myokine profile. Arterial stiffness and endothelial function stand out as the main cardiovascular alterations related to aging, where increased systemic and vascular oxidative stress and inflammation play a key role. Physical activity and exercise training arise as modifiable determinants of functional outcomes in older persons. Exercise enhances antioxidant response, decreases age-related oxidative stress and pro-inflammatory signals, and promotes the activation of anabolic and mitochondrial biogenesis pathways in skeletal muscle. Additionally, exercise improves endothelial function and arterial stiffness by reducing inflammatory and oxidative damage signaling in vascular tissue together with an increase in antioxidant enzymes and nitric oxide availability, globally promoting functional performance and healthy aging. This review focuses on the role of oxidative stress and inflammation in aged musculoskeletal and vascular systems and how physical activity/exercise influences functional status in the elderly.

Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study.

BACKGROUND: Concerns have been raised about the possibility that inhibitors of the renin-angiotensin-aldosterone system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19. METHODS: In this case-population study, we consecutively selected patients aged 18 years or older with a PCR-confirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case, individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish primary health-care database, in its last available year (2018). We extracted information on comorbidities and prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios (ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation Studies, EUPAS34437. FINDINGS: We collected data for 1139 cases and 11 390 population controls. Among cases, 444 (39·0%) were female and the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62-2·41) and risk factors (1·46, 1·23-1·73) than did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77-1·15). No increased risk was observed with either angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64-1·00) or angiotensin-receptor blockers (1·10, 0·88-1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI 0·34-0·80). The adjusted ORs were similar across severity degrees of COVID-19. INTERPRETATION: RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19. FUNDING: Instituto de Salud Carlos III.

Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease.

INTRODUCTION: The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. METHODS: We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. RESULTS: In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09-2.49, p = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18-3.29, p = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71-3.15, p = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (>1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.

Dexamethasone and oxygen therapy in care home residents with diabetes: a management guide and algorithm for treatment: a rapid response action statement from the European Diabetes Working Party for Older People (EDWPOP) and European Geriatric Medicine Society (EuGMS).

This statement addresses the need to provide clinically relevant and practical guidance for long-term care staff working in care homes and other stakeholders engaged in the care of residents who require consideration for dexamethasone and oxygen therapy. It had been provided following a series of consensus discussions between the EDWPOP and the EuGMS in January and February 2021. Its main aim is to minimise morbidity and mortality from serious acute illnesses including COVID-19 requiring these treatments within the long-term care sector.

Relationship between self-reported visual impairment and worsening frailty transition states in older people: a longitudinal study.

BACKGROUND: Visual impairment (VI) may lead to worsening functional status and disability. Although disability is very difficult to reverse, it is usually preceded by frailty that may be reverted more easily. It is possible that VI is also related to frailty. AIMS: To assess the relationship between VI and worsening of the frailty status. METHODS: Data were taken from the Toledo Study for Healthy Aging (TSHA), a cohort study of community-dwelling people older than 65 years living in one Spanish province who were followed for 5 years. 1181 participants were included. VI was self-reported and frailty was operationalized using the Fried's phenotype adapted to a Spanish population. Models of multivariate logistic regression were built to assess the associations. RESULTS: The mean age was 73.9 (Standard Deviation (SD) = 5 years) and 58.5% were females. Pre-frailty/frailty prevalence at baseline and follow-up were 41.2/5% and 36.2/12.5%, respectively, and VI was reported by 14.1%. After adjusting for age, gender, education level, tobacco consumption, type 2 diabetes mellitus, high blood pressure, cardiovascular disease, depressive symptoms and cognitive status, odds ratios for the development of frailty by VI were 2.5 (95% Confidence Interval (CI) 1.5-4.4) for non-frail, 2.7 (95% CI 1.3-5.7) for pre-frail and 1.9 (CI 0.6-6.00) for robust participants. The frailty domains whose appearance was most increased by VI were slowness, low energy, low physical activity and weakness. DISCUSSION: Our findings support that VI worsens frailty in the early stages of its development (pre-frailty). VI impairs several frailty items at the same time. CONCLUSIONS: Our study highlights the need to assess both VI and frailty for the prevention of frailty and disability in older people.

[The European ADVANTAGE experience for management of frailty: keys to its applicability in Latin AmericaA experiência europeia ADVANTAGE para manejo da fragilidade: apontamentos para sua aplicabilidade na América Latina]. / La experiencia europea ADVANTAGE para el manejo de la fragilidad: claves sobre su aplicabilidad en América Latina.

The European Commission and 22 of its Member States cofinanced, in 2017-2019, the first joint action to address frailty in older persons, known as ADVANTAGE Joint Action. The initiative developed a common strategy, based on the best scientific evidence, to position healthy aging and frailty as priority public health issues in the participating countries and thus contribute to uniformly addressing frailty across Europe. This article details the methodology and main achievements of ADVANTAGE and includes an analysis of the key factors contributing to its success. In the Action's three years, powerful multisectoral networks were formed and developed, both nationally and internationally. ADVANTAGE succeeded in mapping out practical routes for comprehensively addressing frailty and dependency prevention in 22 countries with very heterogeneous political, economic, social, and organizational realities. ADVANTAGE has demonstrated that actions of this type are feasible and effective, and that if the key points of success that have been identified are considered and applied, duly adjusted to each reality, this action can be replicable in any country resolved to promoting the healthy aging of its population, including those of Latin America and the Caribbean.

De 2017 a 2019, a Comissão Europeia e 22 dos seus Estados Membros cofinanciaram a primeira ação conjunta para abordar a fragilidade em idosos, denominada ADVANTAGE Joint Action. No âmbito dessa iniciativa, foi definida uma estratégia comum, baseada nas melhores evidências científicas, para posicionar o envelhecimento saudável e a fragilidade como questões prioritárias de saúde pública nos países participantes, contribuindo, assim, para uma abordagem homogênea à fragilidade em toda a Europa. Este artigo detalha a metodologia do trabalho realizado e as principais conquistas da ADVANTAGE, e inclui uma análise das chaves que contribuíram para seu sucesso. Nos três anos de operação da iniciativa, foram formadas e desenvolvidas poderosas redes multissetoriais, tanto nacional quanto internacionalmente. A iniciativa ADVANTAGE foi capaz de criar roteiros práticos para abordar de maneira global a fragilidade e a prevenção da dependência em 22 países com realidades políticas, econômicas, sociais e organizacionais bastante heterogêneas. A ADVANTAGE mostrou que ações deste tipo são viáveis e eficazes, e que se os principais fatores de sucesso identificados forem levados em consideração e aplicados, devidamente ajustados a cada realidade, esta ação pode ser reproduzida em qualquer país determinado a promover o envelhecimento saudável de sua população, inclusive na América Latina e no Caribe.

Unobtrusive Sensors for the Assessment of Older Adult's Frailty: A Scoping Review.

Ubiquity (devices becoming part of the context) and transparency (devices not interfering with daily activities) are very significant in healthcare monitoring applications for elders. The present study undertakes a scoping review to map the literature on sensor-based unobtrusive monitoring of older adults' frailty. We aim to determine what types of devices comply with unobtrusiveness requirements, which frailty markers have been unobtrusively assessed, which unsupervised devices have been tested, the relationships between sensor outcomes and frailty markers, and which devices can assess multiple markers. SCOPUS, PUBMED, and Web of Science were used to identify papers published 2010-2020. We selected 67 documents involving non-hospitalized older adults (65+ y.o.) and assessing frailty level or some specific frailty-marker with some sensor. Among the nine types of body worn sensors, only inertial measurement units (IMUs) on the waist and wrist-worn sensors comply with ubiquity. The former can transparently assess all variables but weight loss. Wrist-worn devices have not been tested in unsupervised conditions. Unsupervised presence detectors can predict frailty, slowness, performance, and physical activity. Waist IMUs and presence detectors are the most promising candidates for unobtrusive and unsupervised monitoring of frailty. Further research is necessary to give specific predictions of frailty level with unsupervised waist IMUs.

Usability, User Experience, and Acceptance Evaluation of CAPACITY: A Technological Ecosystem for Remote Follow-Up of Frailty.

Frailty predisposes older persons to adverse events, and information and communication technologies can play a crucial role to prevent them. CAPACITY provides a means to remotely monitor variables with high predictive power for adverse events, enabling preventative personalized early interventions. This study aims at evaluating the usability, user experience, and acceptance of a novel mobile system to prevent disability. Usability was assessed using the system usability scale (SUS); user experience using the user experience questionnaire (UEQ); and acceptance with the technology acceptance model (TAM) and a customized quantitative questionnaire. Data were collected at baseline (recruitment), and after three and six months of use. Forty-six participants used CAPACITY for six months; nine dropped out, leaving a final sample of 37 subjects. SUS reached a maximum averaged value of 83.68 after six months of use; no statistically significant values have been found to demonstrate that usability improves with use, probably because of a ceiling effect. UEQ, obtained averages scores higher or very close to 2 in all categories. TAM reached a maximum of 51.54 points, showing an improvement trend. Results indicate the success of the participatory methodology, and support user centered design as a key methodology to design technologies for frail older persons. Involving potential end users and giving them voice during the design stage maximizes usability and acceptance.

Enhanced Contribution of Orai Channels to Contractility of Human Penile Smooth Muscle in Erectile Dysfunction.

BACKGROUND: Store-operated calcium entry and its key players, stromal interaction molecule (STIM) and Orai calcium channels, have been proposed as emergent therapeutic targets in cardiovascular pathophysiology. We hypothesize alteration of STIM/Orai signaling in erectile dysfunction (ED). AIM: To evaluate the contribution of STIM/Orai to human penile tissue contraction and to analyze the influence of ED on STIM/Orai signaling at functional and expression levels in human penile vascular tissues. METHODS: Human penile resistance arteries (HPRA) and human corpus cavernosum (HCC) were dissected from cavernosal specimens from 30 organ donors without history of ED (No ED) and from 48 patients with ED undergoing penile prosthesis insertion and functionally evaluated in wire myographs and organ chambers, respectively. Expression of STIM-1, Orai1, and Orai3 in HCC was localized and quantified by immunofluorescence. MAIN OUTCOME MEASURES: The main outcome measures are functional responses in HCC and HPRA and STIM/Orai channel protein expression in human cavernosal tissue. RESULTS: Inhibition of Orai channels with YM-58483 (20 µM) significantly reduced norepinephrine-induced contractions in both HCC and HPRA from either No ED or ED subjects, but the effects were more marked in ED (-20.1 ± 5.9% vs -45.5 ± 13.2% and -15.9 ± 4.0% vs -31.4 ± 6.9% reduction in Emax to norepinephrine in HCC and HPRA, respectively). Thromboxane-induced contractions were reduced and neurogenic contractile and relaxant responses modulated by Orai inhibition in penile tissues from patients with ED. In fact, addition of YM-58483 concentration dependently relaxed precontracted HPRA and HCC. These relaxations were significantly more pronounced in tissues from patients with ED (EC50 7.5 vs 1.3 µM and 10.5 vs 1.3 µM, for HCC and HPRA, respectively). All HCC specimens displayed expression of STIM-1, Orai1, and Orai3. Significantly increased expression of Orai1 and Orai3 but not STIM-1 was observed in patients with ED. CLINICAL TRANSLATION: Inhibition of enhanced Orai activity in human penile vascular tissue could facilitate erectile responses, alleviating ED. STRENGTHS AND LIMITATIONS: Enhanced STIM/Orai activity contribution to penile smooth muscle tone in ED is demonstrated at functional and structural levels in human tissues from a representative sample of patients with ED and in comparison with healthy tissue. We cannot differentiate the specific contribution of risk factors associated with ED to hyperactivity of the Orai system. CONCLUSIONS: Orai channels significantly contribute to human penile smooth muscle contraction. Orai contribution to penile smooth muscle tone is functionally enhanced in ED accompanied by increased expression of Orai channels in cavernosal tissue. Orai inhibition could be a potential therapeutic strategy to reduce penile smooth muscle contraction in ED. Sevilleja-Ortiz A, El Assar M, García-Rojo E, et al. Enhanced Contribution of Orai Channels to Contractility of Human Penile Smooth Muscle in Erectile Dysfunction. J Sex Med 2020;17:881-891.

European Collaborative and Interprofessional Capability Framework for Prevention and Management of Frailty-a consensus process supported by the Joint Action for Frailty Prevention (ADVANTAGE) and the European Geriatric Medicine Society (EuGMS).

BACKGROUND: Interprofessional collaborative practice (ICP) is currently recommended for the delivery of high-quality integrated care for older people. Frailty prevention and management are key elements to be tackled on a multi-professional level. AIM: This study aims to develop a consensus-based European multi-professional capability framework for frailty prevention and management. METHODS: Using a modified Delphi technique, a consensus-based framework of knowledge, skills and attitudes for all professions involved in the care pathway of older people was developed within two consultation rounds. The template for the process was derived from competency frameworks collected in a comprehensive approach from EU-funded projects of the European Commission (EC) supported best practice models for health workforce development. RESULTS: The agreed framework consists of 25 items structured in 4 domains of capabilities. Content covers the understanding about frailty, skills for screening and assessment as well as management procedures for every profession involved. The majority of items focused on interprofessional collaboration, communication and person-centred care planning. DISCUSSION: This framework facilitates clarification of professionals' roles and standardizes procedures for cross-sectional care processes. Despite a lack of evidence for educational interventions, health workforce development remains an important aspect of quality assurance in health care systems. CONCLUSIONS: The multi-professional capability framework for frailty prevention and management incorporated interprofessional collaborative practice, consistent with current recommendations by the World Health Organization, Science Advice for Policy by European Academies and the European Commission.

Automatic and Real-Time Computation of the 30-Seconds Chair-Stand Test without Professional Supervision for Community-Dwelling Older Adults.

The present paper describes a system for older people to self-administer the 30-s chair stand test (CST) at home without supervision. The system comprises a low-cost sensor to count sit-to-stand (SiSt) transitions, and an Android application to guide older people through the procedure. Two observational studies were conducted to test (i) the sensor in a supervised environment (n = 7; m = 83.29 years old, sd = 4.19; 5 female), and (ii) the complete system in an unsupervised one (n = 7; age 64-74 years old; 3 female). The participants in the supervised test were asked to perform a 30-s CST with the sensor, while a member of the research team manually counted valid transitions. Automatic and manual counts were perfectly correlated (Pearson's r = 1, p = 0.00). Even though the sample was small, none of the signals around the critical score were affected by harmful noise; p (harmless noise) = 1, 95% CI = (0.98, 1). The participants in the unsupervised test used the system in their homes for a month. None of them dropped out, and they reported it to be easy to use, comfortable, and easy to understand. Thus, the system is suitable to be used by older adults in their homes without professional supervision.

Portable Ultrasound-Based Device for Detecting Older Adults' Sit-to-Stand Transitions in Unsupervised 30-Second Chair-Stand Tests.

Lower-limb strength is a marker of functional decline in elders. This work studies the feasibility of using the quasi-periodic nature of the distance between a subjects' back and the chair backrest during a 30-s chair-stand test (CST) to carry out unsupervised measurements based on readings from a low-cost ultrasound sensor. The device comprises an ultrasound sensor, an Arduino UNO board, and a Bluetooth module. Sit-to-stand transitions are identified by filtering the signal with a moving minimum filter and comparing the output to an adaptive threshold. An inter-rater reliability (IRR) study was carried out to validate the device ability to count the same number of valid transitions as the gold-standard manual count. A group of elders (age: mean (m) = 80.79 years old, SD = 5.38; gender: 21 female and seven male) were asked to perform a 30-s CST using the device while a trained nurse manually counted valid transitions. Ultimately, a moving minimum filter was necessary to cancel the effect of outliers, likely produced because older people tend to produce more motion artefacts and, thus, noisier signals. While the intra-class correlation coefficient (ICC) for this study was good (ICC = 0.86, 95% confidence interval (CI) = 0.73, 0.93), it is not yet clear whether the results are sufficient to support clinical decision-making.