Biochemical Markers of Musculoskeletal Health and Aging to be Assessed in Clinical Trials of Drugs Aiming at the Treatment of Sarcopenia: Consensus Paper from an Expert Group Meeting Organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the Centre Académique de Recherche et d'Expérimentation en Santé (CARES SPRL), Under the Auspices of the World Health Organization Collaborating Center for the Epidemiology of Musculoskeletal Conditions and Aging.

In clinical trials, biochemical markers provide useful information on the drug's mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio - or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

The potential of assessment based on the WHO framework of intrinsic capacity in fragility fracture prevention.

The risk of falls associated with population ageing and the burden of chronic diseases increase the risk of fragility fractures. Globally, a large increase in the numbers of people sustaining fragility fractures is predicted. The management of highly vulnerable older persons who present and/or are at risk of fragility fractures is challenging given their clinical complexity and the fragmentation of the healthcare services. Fragility fractures frequently result in reduced functional ability and quality of life. Therefore, it is essential to implement person-centered models of care to address the individual's priorities and needs. In this context, the multidimensional construct of intrinsic capacity, composed of the critical functions on which the individual's functional ability rely, becomes of particular interest.In this article, the potential of current models to meet the global challenge is considered, particularly where healthcare systems are less integrated and poorly structured. It then describes how assessment of intrinsic capacity might provide the clinician with a holistic picture of an older individual's reserves before and after a fragility fracture and the implications of implementing this approach based on the construct of intrinsic capacity in healthcare systems, in both well-developed and low-resourced settings. It suggests that optimization of intrinsic capacity and functional ability is a credible conceptual model and might support a generally feasible approach to primary and secondary fracture prevention in older people.

Implementation of the frailty assessment to improve liver transplant outcomes.

The majority of patients undergoing Orthotopic Liver Transplantation (OLT) have increased in age, therefore chronological age may have become an unreliable parameter for supporting clinical decisions. The age-related deficit accumulation model measuring frailty proposed by Rockwood et al., may propose an alternative in providing an estimate of an individual's biological age. No Frailty Index (FI) tailored specifically for OLT patients exists to date. Forty-three consecutive OLT patients with ≥ 20 years of survival with a functioning graft were included in our study. The FI was computed taking to account 39 items (FI-39), meeting the standard criteria for internal validation. Endpoints were polypharmacy, and recent Emergency Room admission. The mean age of our population was 69 (sd 9) years. The mean FI-39 was 0.23 (sd 0.1). The FI-39 was associated with polypharmacy [odds ratio (OR) 1.13; Confidence interval (95%CI) 1.03-1.24; p = 0.01], and recent Emergency Room admission [beta coefficient + 1.98; 95%CI + 0.26, + 3.70; p = 0.03], independent for age and sex. This study demonstrates that an FI can be derived from data collected during routine clinical follow-up and allows for improved differentiation related to the OLT clinical complexity in OLT patients, independent of chronological age. This may lead to the adoption of FI-39 to improve personalized OLT patient care.

Last Year of Life, Frailty, and Out-of-Pocket Expenses in Older Adults: A Secondary Analysis of the Mexican Health and Aging Study.

OBJECTIVE: To determine the association of frailty with out-of-pocket expenses (OOPEs) during the last year of life of Mexican older adults. METHODS: Cross-sectional secondary analysis of the Mexican Health and Aging Study (MHAS), a representative population-based cohort study. Health care expenses were estimated, and a probit model was used to estimate the probability that older adults had OOPE. A general linear model was applied to explain OOPE magnitudes. RESULTS: A total of 55.8% of individuals reported having OOPE with a mean of 3,261 USD. Average OOPE for hospitalization during the last year of life was 7,011.9 USD. Older adults taking their own medical decisions during the last year of life expended less than those who did not. CONCLUSION: No affiliation to health services, frailty, and health decision-making by others increased the probability of OOPE. The magnitude is determined by age, hospitalization, medical visits, affiliation, frailty, and health decision-making by others.

Socially desirable responding in geriatric outpatients with and without mild cognitive impairment and its association with the assessment of self-reported mental health.

BACKGROUND: Socially desirable responding is a potentially relevant issue in older adults and can be evaluated with the Marlowe-Crowne Social Desirability Scale (MCSDS). However, the eight-item MCSDS has never been specifically administered to geriatric subjects, and there is a dearth of literature on the relationship between social desirability and cognitive impairment. Also, the connection between social desirability and subjective measures of psychological well-being is a matter of controversy. This study has three main aims. First, to determine the psychometric properties of the eight-item MCSDS in geriatric outpatients without dementia (i.e. with normal cognition (NC) or mild cognitive impairment (MCI)). Second, to investigate the link between social desirability and cognitive functioning. Third, to determine the association between social desirability and the assessment of self-reported mental health. METHODS: Community-dwelling outpatients (aged ≥ 65) were consecutively recruited and neuropsychologically tested to diagnose NC or MCI (n = 299). Social desirability was assessed with the eight-item MCSDS. Depressive and anxiety symptoms were measured with the short Geriatric Depression (GDS-s) and the State-Trait Personality Inventory Trait Anxiety (STPI-TA) scales. RESULTS: On principal components analysis, the eight-item MCSDS was found to have a multidimensional structure. Of the initial three-component solution, only two subscales had acceptable internal consistency (Cronbach's alpha > 0.6): "Acceptance of responsibility" and "Integrity". The third subscale ("Kindness towards others") appeared to gauge two distinct constructs of formal (i.e. politeness) versus substantive (i.e. forgiveness) compassion. On binary logistic regression, only higher income was a significant predictor of formal compassion. Test-retest reliability was substantial to excellent (Gwet's AC2 ≥ 0.8). There were no meaningful differences in social desirability between the NC and MCI groups. Likewise, negative Spearman's correlations between social desirability and cognitive Z-scores across the whole sample were weak (rs < |0.3|) and confined to one MCSDS item. Although social desirability was an independent predictor of the STPI-TA score in multiple linear regression, it explained only a marginal amount of incremental variance in anxiety symptoms (less than 2%). CONCLUSIONS: Our results suggest that social desirability need not be a major concern when using questionnaires to assess mental health in geriatric outpatients without dementia.

Intrinsic Capacity Assessment by a Mobile Geriatric Team During the Covid-19 Pandemic.

In the autumn of 2020, the second wave of the COVID-19 pandemic hit Europe. In this context, because of the insufficient number of beds in geriatric COVID units, non-geriatric wards were confronted with a significant number of admissions of geriatric patients. In this perspective article, we describe the role of a mobile geriatric team in the framework of the COVID-19 pandemic and specifically how it assisted other specialists in the management of hospitalized geriatric patients by implementing a new approach: the systematic assessment and optimization of Intrinsic Capacity functions. For each patient, assessed by this consultative team, an individualized care plan, including an anticipated end-of-life decision-making process, was established. Intensity of care was most often not stated by considering chronological age but rather the comorbidity burden, the frailty status, and the patient's wishes. Further studies are needed to determine if this mobile geriatric team approach was beneficial in terms of mortality, length of stay, or functional, psychological, and cognitive outcomes in COVID-19 geriatric patients.

Signs and symptoms method in neuropsychology: A preliminary investigation of a standardized clinical interview for assessment of cognitive decline in dementia.

Psychologists usually perform a preliminary assessment of the person's cognitive status through a brief interview conducted before the formal testing. However, this exam has not yet been standardized with ad hoc recommendations in psychology literature. In this work, a standard observational NeuroPsychological Examination (NPE) designed for psychologists was proposed, and its clinical effectiveness evaluated. The NPE was administered to patients referred to a neuropsychological service in a memory clinic over a 2-year period. The NPEs of the patients with Alzheimer dementia (AD), vascular dementia (VaD), and healthy controls (HC) were retrospectively retrieved. Comparisons among the three groups were conducted. Abnormalities/signs identified during the NPE in the AD and VaD groups are more numerous compared to those reported in the HC group. About 80% of HCs show none or only one abnormal sign. Vice versa, 87.5% of both AD and VaD patients show three or more abnormalities. Accordingly, the NPE has 0.88 (95%CI = 0.81-0.95) sensitivity and 0.95 (95%CI = 0.88-1.02) specificity for detecting cognitive decline when a cut-point of three or more signs is applied. Some significant differences also emerge on the number of pathological signs between AD and VaD patients. NPE is a promising tool with demonstrated diagnostic utility in dementia patients.

Unmet needs, health policies, and actions during the COVID-19 pandemic: a report from six European countries.

PURPOSE: The United Nations (UN) has published a Policy Brief on the impact of the Coronavirus Disease 2019 (COVID-19) that identifies policies and responses to protect older adults. Our objective was to summarize actions, health policies and clinical guidelines adopted by six European countries (Belgium, France, Italy, Poland, Spain and United Kingdom) during the pandemic, and to assess the impact of national policies on reducing adverse effects of the COVID-19 pandemic in older populations. METHODS: Reports by geriatricians on the measures and actions undertaken by governmental institutions in each country between March and July 2020, as well as the role of primary care during the pandemic, covered three areas: (a) general health strategies related to the pandemic; (b) impact of COVID-19 on health inequity; and (c) initiatives and challenges for the COVID-19 pandemic and beyond. RESULTS: In the six countries, COVID-19 mortality in nursing homes ranged from 26 to 66%. Although all countries endorsed the World Health Organization general recommendations, the reports identified the lack of harmonized European guidelines and policies for nursing homes, with competencies transferred to national (or regional) governments. All countries restricted visits in nursing homes, but no specific action plans were provided. The role of primary care was limited by the centralization of the crisis in hospital settings. CONCLUSIONS: The older population has been greatly affected by COVID-19 and by the policies initiated to control its spread. The right to health and dignity are transgenerational; chronological age should not be the sole criterion in policy decisions.

ICT technologies as new promising tools for the managing of frailty: a systematic review.

OBJECTIVES: Frailty is a major health issue as it encompasses functional decline, physical dependence, and increased mortality risk. Recent studies explored Information and Communication Technology (ICT) interventions as alternatives to manage frailty in older persons. The aim of the present systematic review was to synthesize current evidence on ICT application within the complex models of frailty care in older people. METHODS: Data sources included PubMed, PsycINFO, EMBASE and Web of Science, considering eligible those reviews on ICT application in samples of older persons formally assessed as frail. Records were screened by two independent researchers, who extracted data and appraised methodological quality of reviews and studies. RESULTS: Among the 764 retrieved papers, two systematic reviews were included. Most of the studies analyzed defined frailty considering only few components of the phenotype and used ICT to stratify different levels of frailty or to support traditional screening strategies. Assessment of frailty was the context in which ICT has been mostly tested as compared to intervention. Cost effectiveness evaluations of the ICT technologies were not reported. CONCLUSIONS: The research investigating the use of ICT in the context of frailty is still at the very beginning. Few studies strictly focused on the assessment of frailty, while intervention on frailty using ICT was rarely reported. The lack of a proper characterization of the frail condition along with the methodological limitations prevented the investigation of ICT within complex care models. Future studies are needed to effectively integrate ICT in the care of frailty in orders.

Medication Management in Frail Older People: Consensus Principles for Clinical Practice, Research, and Education.

Frailty is a geriatric condition associated with increased vulnerability to adverse drug events and medication-related harm. Existing clinical practice guidelines rarely provide medication management recommendations specific to frail older people. This report presents international consensus principles, generated by the Optimizing Geriatric Pharmacotherapy through Pharmacoepidemiology Network, related to medication management in frail older people. This consensus comprises 7 principles for clinical practice, 6 principles for research, and 4 principles for education. Principles for clinical practice include (1) perform medication reconciliation and maintain an up-to-date medication list; (2) assess and plan based on individual's capacity to self-manage medications; (3) ensure appropriate prescribing and deprescribing; (4) simplify medication regimens when appropriate to reduce unnecessary burden; (5) be alert to the contribution of medications to geriatric syndromes; (6) regularly review medication regimens to align with changing goals of care; and (7) facilitate multidisciplinary communication among patients, caregivers, and healthcare teams. Principles for research include (1) include frail older people in randomized controlled trials; (2) consider frailty status as an effect modifier; (3) ensure collection and reporting of outcome measures important in frailty; (4) assess impact of frailty on pharmacokinetics and pharmacodynamics; (5) encourage frailty research in under-researched settings; and (6) utilize routinely collected linked health data. Principles for education include (1) provide undergraduate and postgraduate education on frailty; (2) minimize low-value care related to medication management; (3) improve health and medication literacy; and (4) incorporate evidence in relation to frailty into clinical practice guidelines. These principles for clinical practice, research and education highlight different considerations for optimizing medication management in frail older people. These principles can be used in conjunction with existing best practice guidelines to help achieve optimal health outcomes for this vulnerable population. Implementation of the principles will require multidisciplinary collaboration between healthcare professionals, researchers, educators, organizational leaders, and policymakers.

Comprehensive geriatric assessment in older adults with cancer: Recommendations by the Italian Society of Geriatrics and Gerontology (SIGG).

INTRODUCTION: Optimizing the approach to older adults with cancer is now a priority given the increasing frequency of new cancer diagnoses that are made in the older population. The comprehensive geriatric assessment (CGA) represents the gold-standard for (1) defining prognosis and ability to withstand cancer treatments, (2) exploring the multiple aspects that define the complexity of frail older persons, and (3) designing person-tailored interventions. MATERIALS AND METHODS: In this document, based on a comprehensive revision of the literature, the Italian Society for Geriatrics and Gerontology proposes a CGA model (ONCOGER CGA) to be adopted by oncology centers for their routine approach to older patients with cancer. RESULTS AND DISCUSSION: A widespread use of this standardized CGA format will facilitate comparisons across institutions, promote studies based on a multidimensional patient assessment, and foster the inclusion of geriatric endpoints in oncological clinical trials. Furthermore, we predict that the use of a standardized CGA approach will increase the integration of geriatricians into oncology care teams with the final result of improving therapeutic choices and clinical outcomes.

A Comparison of Frailty Assessment Instruments in Different Clinical and Social Care Settings: The Frailtools Project.

OBJECTIVE: To determine which of 8 commonly employed frailty assessment tools demonstrate the most appropriate characteristics to be employed in different clinical and social settings. DESIGN: Cross-sectional multicenter European-based study. SETTING AND PARTICIPANTS: 1440 patients aged ≥75 years evaluated in geriatric inpatient wards, geriatric outpatient clinics, primary care clinics, and nursing homes. METHODS: The frailty instruments used were Frailty Phenotype, SHARE-FI, 3-item Frailty Trait Scale (FTS-3), 5-item Frailty Trait Scale (FTS-5), FRAIL, 35-item Frailty Index (FI-35), Gérontopôle Frailty Screening Tool (GFST), and Clinical Frailty Scale (CFS). The settings were geriatrics wards, outpatient clinics, primary care, and nursing homes. Suitability was evaluated by considering the feasibility (patients with the test fully completed), administration time (time spent for administering the test), and interscale agreement (Cohen kappa index among instruments to detect frailty). RESULTS: The prevalence of frailty varied across settings and adopted tests. The scales with the mean highest feasibility were the FRAIL scale (99.4%), SHARE-FI (98.3%), and GFST (95.0%). The mean shortest administration times were obtained with CFS (24 seconds), GFST (72 seconds), and FRAIL scale (90 seconds). The interscale agreement between most of the tests was fair. CFS followed by FTS-5 agreed at least moderately with a greater number of scales overall and in almost all settings. CONCLUSIONS AND IMPLICATIONS: Based on feasibility, time to undertake the tool, and agreement with other scales, different scales would be recommended according to the setting considered. Our findings suggest that most of the tools evaluated are actually assessing different frailty constructs.

Vitamin D Receptor Polymorphisms in Sex-Frailty Paradox.

The "male-female health-survival paradox" evidences that the survival advantage observed in women is linked to higher rates of disability and poor health status compared to men, a phenomenon also called the "sex-frailty paradox". The depletion of vitamin D seems to play a role in the fragilization of old persons, and genetic polymorphisms of the vitamin D receptor (VDR) gene seem to be involved in regulating the vitamin D pathway. This study correlated the VDR gene polymorphisms (FokI, ApaI, BsmiI, and TaqI) with frailty, computed by frailty index (FI), in 202 persons (127 women and 75 men, aged from 60 to 116 years), aiming to capture the involvement of vitamin D in the sex-frailty paradox. The results showed slightly higher FI (p = 0.05), lower levels of 25(OH)D (p = 0.04), and higher levels of parathyroid hormone PTH (p = 0.002) and phosphorus (p < 0.001) in women than in men. Interestingly, the ApaI minor allele (Aa + aa) showed a significant positive association with FI (p = 0.03) and a negative association with inorganic phosphorus values (p = 0.04) compared to AA genotype only in women, regardless of age. The exact mechanism and the causal role that, in old women, links ApaI polymorphism with frailty are still unclear. However, we could speculate that a specific genetic profiling, other than 25(OH)D levels, play a role in the sex-frailty paradox.

[Dislipidemia and lipid lowering drugs: from guidelines to clinical practice. An updated review of the literature.] / Dislipidemia e terapia ipolipemizzante: dalle linee guida alla pratica clinicaUna rassegna aggiornata della letteratura.

The atherosclerotic cardiovascular disease (ASCVD) represents the leading cause of death and disability not only in countries with a high degree of socio-economic development but also in low- middle-income countries. The study of atherosclerosis and the strategies to control ASCVD are evolving. All strategies emphasize the need to lower LDL cholesterol through an appropriate lifestyle and the use of lipid-lowering drugs. A therapy with statin with or without other lipid lowering drugs is recommended in secondary prevention. In primary prevention, the use of the lipid-lowering drug should instead take into account the cost-benefit ratio. Available evidence coming from clinical trials is useful to inform clinical choices but must be associated with a shared decision-making process between doctor and patient.

The Lisbon patient: exceptional longevity with HIV suggests healthy aging as an ultimate goal for HIV care.

In the context of global aging, HIV infection has become a new chronic disease and requires innovative models of care. Treating isolated comorbidities represents a useless and potentially harmful practice at advanced age. Therefore, a patient-centered approach, in which the interventions are focused on the biology and function of the individual, with understanding of the importance of securing social and home environment that provides psychosocial support, better suits unmet health needs. We present a paradigmatic case of healthy aging: the first reported HIV-infected patient who achieved 100th of life - the Lisbon patient. The construct of healthy aging, recently introduced by the World Health Organization, is the best example of this comprehensive model and could represent the fourth target of UNAIDS agenda of the end of AIDS.