Joint Statement on the Role of Respiratory Rehabilitation in the COVID-19 Crisis: The Italian Position Paper.

Due to the exponential growth of the number of subjects affected by coronavirus disease 2019 (COVID-19), the entire Italian health care system had to respond promptly and in a very short time with the need of semi-intensive and intensive care units. Moreover, trained dedicated COVID-19 teams consisting of physicians were coming from different specialties (intensivists or pneumologists and infectiologists), while respiratory therapists and nurses have been recruited to work on and on without rest. However, due to still limited and evolving knowledge of COVID-19, there are few recommendations concerning the need in respiratory rehabilitation and physiotherapy interventions. The presentation of this paper is the result of a consensus promoted by the Italian societies of respiratory health care professionals who contacted pulmonologists directly involved in the treatment and rehabilitation of COVID-19. The aim was to formulate the more proper and common suggestions to be applied in different hospital settings in offering rehabilitative programs and physiotherapy workforce planning for COVID-19 patients. Two main areas of intervention were identified: organization and treatment, which are described in this paper to face the emergency.

Italian suggestions for pulmonary rehabilitation in COVID-19 patients recovering from acute respiratory failure: results of a Delphi process.

There is a need of consensus about the pulmonary rehabilitation (PR) in patients with COVID-19 after discharge from acute care. To facilitate the knowledge of the evidence and its translation into practice, we developed suggestions based on experts' opinion. A steering committee identified areas and questions sent to experts. Other international experts participated to a RAND Delphi method in reaching consensus and proposing further suggestions. Strong agreement in suggestions was defined when the mean agreement was >7 (1 = no agreement and 9 = maximal agreement). Panelists response rate was >95%. Twenty-three questions from 4 areas: Personnel protection equipment, phenotypes, assessments, interventions, were identified and experts answered with 121 suggestions, 119 of which received high level of concordance. The evidence-based suggestions provide the clinicians with current evidence and clinical experts opinion. This framework can be used to facilitate clinical decision making within the context of the individual patient. Further studies will evaluate the clinical usefulness of these suggestions.

Prevalence and variability of use of home mechanical ventilators, positive airway pressure and oxygen devices in the Lombardy region, Italy.

Few studies have analyzed the prevalence and accessibility of home mechanical ventilation (HMV) in Italy. We aimed to investigate the prevalence and prescription variability of HMV as well as of long-term oxygen therapy (LTOT) and continuous positive airway pressure (CPAP), in the Lombardy Region. Prescribing rates of HMV (both noninvasive and tracheostomies), CPAP (auto-CPAP, CPAP/other sleep machines) and LTOT (liquid-O2, O2-gas, concentrators) in the 15 Local Healthcare districts of Lombardy were gathered from billing data for 2012 and compared. Crude rates (per 100,000 population) and rates for the different healthcare districts were calculated. In 2012, 6325 patients were on HMV (crude prescription rate: 63/100,000) with a high variation across districts (8/100,000 in Milano 1 vs 150/100,000 in Pavia). There were 14,237 patients on CPAP (crude prescription rate: 142/100,000; CPAP/other sleep machines 95.3% vs auto-CPAP 4.7%) with also high intra-regional variation (56/100,000 in Mantova vs. 260/100,000 in Pavia). There were 21,826 patients on LTOT (prescription rate: 217/100,000 rate; liquid-O2 94%, O2-gas 2.08%, O2-concentrators 3.8%), with again high intra-regional variation (100/100,000 in Bergamo vs 410/100,000 in Valle Camonica). The crude rate of HMV prescriptions in Lombardy is very high, with a high intra-regional variability in prescribing HMV, LTOT and CPAP which is partly explainable by the accessibility to specialist centers with HMV/sleep-study facilities. Analysis of administrative data and variability mapping can help identify areas of reduced access for an improved standardization of services. An audit among Health Payer and prescribers to interpret the described huge variability could be welcomed.

The Report-AGE project: a permanent epidemiological observatory to identify clinical and biological markers of health outcomes in elderly hospitalized patients in Italy.

BACKGROUND: Italy is expected to experience the largest growth in persons ≥65 years (>20% by 2020). This demographic shift allows for geriatric research on predictive clinical and biological markers of outcomes related to frailty, re-hospitalization and mortality. AIMS: To describe rationale and methods of the Report-AGE study project of acute care patients in Italian National Research Center on Aging (INRCA) research hospitals. METHODS: Report-AGE study is a large observational study on health conditions and outcomes of hospitalized elderly patients (≥65 years). The primary objective of the study is to create a high-level data resource of demographics, comprehensive geriatric assessments, clinical and diagnostic information, as well as biological and molecular markers in all older patients admitted to INRCA Hospitals. Assessments in physical and nutritional parameters, co-morbid health conditions, and associations with frailty parameters are ongoing in older hospitalized adults following an acute event. Study collection began in September 2011. RESULTS: Up to date, there are 3479 patients ≥65 years (mean age: 85 ± 7years) with 1543 men and 1936 women enrolled. Data have been recorded regarding functional and clinical parameters before, during hospital admission and at discharge. Data collection for primary outcome analyses related to re-hospitalization and mortality is estimated for September 2016. DISCUSSION: This study aims at collecting precise clinical data, comprehensive geriatric assessment, risk factors, and biological data from acute care patients. Data will also be used to identify mechanisms underlying frailty in this specific population. CONCLUSION: This study provides a descriptive epidemiological collection of the health conditions of older in-patients.

Body composition markers in older persons with COPD.

BACKGROUND: Body composition has been shown to be correlated with physical performance, but data in older persons with diverse chronic diseases are lacking. OBJECTIVE: We aimed at investigating the associations of body composition to gait speed and nutritional status of older people in different stages of chronic obstructive pulmonary disease (COPD). DESIGN, SETTING AND SUBJECTS: Cross-sectional analysis of data from Pulmonary Rehabilitation Geriatric Unit at INRCA in Casatenovo, Italy including 132 consecutively admitted COPD patients (mean age: 75 years) with data on body composition, walking speed and respiratory parameters. METHODS: Body mass parameters were assessed using bioelectrical impedance analysis. Pulmonary function tests included spirometry and arterial blood gases. Differences among body composition markers were compared according to gender. Separate multivariate linear regression models with gait speed as the dependent variable were used to test for independent associations with body composition markers after adjusting for multiple confounders. RESULTS: Walking speed deteriorated with increasing severity of COPD. Men were heavier and had more lean mass than women. Participants in the fastest gait tertile were younger, had lower body mass index and fat mass (FM); higher lean-to-fat ratio and albumin levels and better respiratory function (FEV1, FVC) compared with those in the slower tertiles. Total body FM was an independent determinant of walking speed, while fat-free mass and lean-to-fat ratio were not. CONCLUSIONS: Excess body fat may be harmful for physical functioning among elders with COPD.

Analysis of Massaciuccoli Peat after Maturation in Sodium Chloride Water of Undulna Thermae.

In Italy, peat extracted from the peat bogs of Lake Massaciuccoli is the only peat used for therapeutic purposes. Massaciuccoli peat (M-peat) soaked in the salty bromine-iodine water of Undulna Thermae has given positive results in various pathological situations, mainly in dermatological, rheumatological, and traumatological conditions. Morphological and biochemical analysis were performed using base M-peat samples matured in the salty bromine-iodine water of the Undulna Thermae for different times, to evaluate whether maturation time modifies peat chemico-physical properties. The maturation process induced particle aggregation, with an increase in the fractions with larger particle size. The presence of a high number of proteins derived from organic degradation was observed; after 6 months of maturation, a significant increase in proteins was found, suggesting that salty bromine-iodine water plays a role in the clinical action of the peat. The presence of lipids in M-peat was also confirmed, allowing us to draw important considerations on its therapeutic properties possibly deriving from the relevant interactions between lipids and humic acids. Finally, from our observations, it could be reasonably argued that longer periods of maturation do not result in additional advantages regarding clinical activity.

Practical management problems of chronic obstructive pulmonary disease in the elderly: acute exacerbations.

PURPOSE OF REVIEW: Acute exacerbations of chronic obstructive pulmonary disease (ECOPDs) have numerous causes and are associated with increased mortality and hospitalization, especially in older patients. The urgent need to identify and enable timely treatment of ECOPDs is a necessity for physicians worldwide. This review will highlight the causes and optimal combinations of available treatments for such events in older populations. RECENT FINDINGS: The exact definition of exacerbations is lacking; however, it is agreed that such events are considered episodes of worsening of symptoms, leading to morbidity and death. The aging process is a consistent determinant for ECOPD events and is associated with worsening of COPD stages. The incidence of ECOPD rises across the worsening stages of COPD. Studies have shown that the frequency of exacerbations increases with age and correlated clinical outcomes are poorer than in younger patients. The risk of mortality has also been shown to be significantly higher after a hospital admission following an acute exacerbation. At the moment, the need to rapidly and correctly treat acute exacerbations is crucially important in the rapidly growing elderly population. SUMMARY: ECOPDs are extremely dangerous events for older patients with severe stages of COPD. There is an urgent need to identify risk factors, identify tolerable treatment guidelines and manage acute exacerbations in older patients with COPD.

Long-term azithromycin use in patients with chronic obstructive pulmonary disease and tracheostomy.

Patients with Chronic Obstructive Pulmonary Disease (COPD) and tracheostomy are at high risk for exacerbations and hospitalizations. Macrolide treatment has shown to reduce exacerbations in moderate-to-severe COPD. To evaluate the safety and the efficacy of long-term azithromycin use in outpatients with severe COPD and tracheostomy. A multicenter, randomized, uncontrolled, pilot trial evaluating the safety and the efficacy of azithromycin 500 mg three day-a-week for 6 months (AZI) vs. standard of care (SC) in severe COPD outpatients with tracheostomy. Patients were monitored for six months of treatment plus six months of follow up. The primary outcome was the reduction in the number of exacerbations and hospitalizations. A total of 22 patients was randomized (11 to SC and 11 to AZI). Patients in AZI had a significant lower cumulative number of exacerbations after the first 3 months of treatment when compared to patients in SC (p = 0.001), as well as hospitalizations (p = 0.02). Kaplan-Meier survival curves for time to first exacerbation showed a significant reduction in AZI of the rates of first exacerbation when compared to SC (log rank test = 12.14, p < 0.001), as well as to first hospitalization (log-rank = 4.09, p = 0.04). Azithromycin significantly improved the quality of life in comparison to SC. No serious adverse events in the AZI group were reported. Long-term azithromycin treatment seems to be safe and effective in severe COPD outpatients with tracheostomy in reducing exacerbations, hospitalizations, as well as in improving quality of life.

Targeting inflammation to slow or delay functional decline: where are we?

The role of inflammation in the pathophysiology of chronic age-related diseases is increasingly recognized, and inflammation could represent the common pathway linking diseases and disability. Thus, targeting inflammation could represent a useful strategy at preventing or delaying functional decline. In this paper we review recent evidence suggesting that selected drugs, such as statins, fibrates, angiotensin converting enzyme-inhibitors and angiotensin receptor blockers, and physical exercise may be able to contrast functional decline by blunting inflammation. Results from randomized trials investigating the effects of physical activity programs on inflammation and functional decline is still limited, and further investigations are warranted.

Gait analysis in patients with chronic obstructive pulmonary disease: a systematic review.

BACKGROUND: Gait instability is a major fall-risk factor in patients with chronic obstructive pulmonary disease (COPD). Clinical gait analysis is a reliable tool to predict fall onsets. However, controversy still exists on gait impairments associated with COPD. RESEARCH QUESTION: Thus, the aims of this review were to evaluate the current understanding of spatiotemporal, kinematic and kinetic gait features in patients with COPD. METHODS: In line with PRISMA guidelines, a systematic literature search was performed throughout Web of Science, PubMed Medline, Scopus, PEDro and Scielo databases. We considered observational cross-sectional studies evaluating gait features in patients with COPD as their primary outcome. Risk of bias and applicability of these papers were assessed according to the QUADAS-2 tool. RESULTS: Seven articles, cross-sectional studies published from 2011 to 2017, met the inclusion criteria. Sample size of patients with COPD ranged 14-196 (mean age range: 64-75 years). The main reported gait abnormalities were reduced step length and cadence, and altered variability of spatiotemporal parameters. Only subtle biomechanical changes were reported at the ankle level. SIGNIFICANCE: A convincing mechanistic link between such gait impairments and falls in patients with COPD is still lacking. The paucity of studies, small sample sizes, gender and disease status pooling were the main risk of biases affecting the results uncertainty. Two research directions emerged: stricter cohorts characterization in terms of COPD phenotype and longitudinal studies. Quantitative assessment of gait would identify abnormalities and sensorimotor postural deficiencies that in turn may lead to better falling prevention strategies in COPD.

COPD management as a model for all chronic respiratory conditions: report of the 4th Consensus Conference in Respiratory Medicine.

BACKGROUND: Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions. METHODS: These issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3-4 November 2016. RESULTS AND CONCLUSIONS: Regarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role.

Laparoscopic repair of ventral hernia in a laparoscopic experienced surgical center: low recurrence rate, morbidity, and chronic pain are achievable.

PURPOSE: Recurrence rate and the perioperative outcome evaluation through laparoscopic approach for ventral (primary and incisional) hernia repair. MATERIALS AND METHODS: A retrospective evaluation of a series of patients treated through a minimally invasive approach for ventral hernia was performed. A standardized surgical technique was adopted. All the patients were evaluated through a clinical follow-up. RESULTS: From July 2004 to June 2011, 150 videolaparoscopic ventral hernia repairs were performed. The median follow-up was 40 months. One hernia recurrence (0.7%) was detected after 55 months. The intraoperative and postoperative complication rate was 2.6% (1 conversion to open surgery) and 5.3%, respectively. Chronic pain nonresponsive to drug was registered in 2 patients (1.3%). CONCLUSIONS: The videolaparoscopic approach to ventral hernia repair is a safe technique that can guarantee a low recurrence rate; moreover, if it is performed in an experienced laparoscopic surgical center, it can be a valid alternative to the traditional open approach.

Feasibility and effectiveness of an educational program in Italian COPD patients undergoing rehabilitation.

BACKGROUND: Self-management education is associated with improvement in quality of life and reduction of hospital admissions. Nevertheless, the data are insufficient to formulate clear recommendations regarding the type and content of education programs for COPD patients, and few data are available on knowledge of the disease itself. OBJECTIVE: To test the level of patients' knowledge of their disease and therapy at baseline and after an educational program (COPD-EP); the feasibility of structured educational sessions; the influence of clinical status (degree of severity of disease, presence of comorbidities, oxygen use), demographics status (age, sex), previous knowledge level, previous lessons attendance and adherence of COPD-EP to the variation of knowledge after program. METHODS: Selected COPD in-patients and out-patients referred to rehabilitative hospital departments were enrolled. The study was divided into 2 parts: a pre-study phase (educational materials and health team preparation) and a study phase. All COPD subjects received one educational brochure and were invited to attend seven 30-min group lessons to complete the educational program. Learning effect was evaluated by a 20-questions multiple choice learning questionnaire (LQ). RESULTS: We enrolled 158 subjects, of whom 44.9% had previous formal education lessons on COPD management and 69.6% had previous rehabilitative hospitalizations. At baseline, the LQ total score was 15.2 ± 3.5 points, which increased to 16.9 ± 3.0 points post COPD-EP (P < .001). Pre-to-post change of LQ scores significantly correlated with adherence (R = 0.24, P = .002) and Severity Index of Cumulative Illness Rating Scale score (R = -0.22, P = .001). Subjects with low baseline knowledge were more likely to have improved LQ scores than subjects with greater levels of knowledge. Subjects without prior educational COPD lessons improved more than subjects who had attended previous education. CONCLUSIONS: A formal COPD-EP is feasible and effective in improving subject knowledge and self-management. Specific learning instruments to follow up this population should be validated.

Explicit criteria for potentially inappropriate medications to reduce the risk of adverse drug reactions in elderly people: from Beers to STOPP/START criteria.

Balanced and safe prescribing is difficult to achieve in frail older adults with multiple comorbid diseases. For this reason, great efforts have been made in the search for interventions to improve efficacy, safety and appropriateness of prescriptions in this vulnerable population. Among these interventions, the avoidance of medications that are considered to be inappropriate, i.e. potentially inappropriate medications (PIMs), has been considered a valuable treatment option. The aim of the present review was to summarize evidence about the use of explicit criteria for PIMs to reduce the risk of adverse drug reactions (ADRs) in older people. A PIM is a drug in which the risk of an adverse event outweighs its clinical benefit, particularly when there is evidence in favour of a safer or more effective alternative therapy for the same condition. Explicit criteria have been developed to identify PIMs, and among these, the Beers criteria have been the most frequently applied until recently. However, evidence suggests that such criteria can not easily be applied in European countries: several drugs listed in the 2003 Beers criteria were rarely prescribed or were not available in Europe and 2003 Beers-listed PIMs were not associated with ADRs in some studies. In the past few years, START/STOPP criteria have been developed and applied in several different studies and populations showing a greater ability to predict ADRs with respect to Beers criteria and to prevent potentially inappropriate prescribing. In 2012, Beers criteria have been updated using an evidence-based approach and future studies will investigate the impact of these and other criteria coming from ongoing studies on clinical outcomes relevant to geriatric populations.

Cu to Zn ratio, physical function, disability, and mortality risk in older elderly (ilSIRENTE study).

Associations between copper to zinc ratio (CZr) and mortality have suggested CZr as a biomarker of aging. Nevertheless, very limited data exist on the association between serum CZr and physical or functional status of very old people. We examined the relationship between serum CZr and physical performance, muscle strength, functional status, and survival from the ilSIRENTE Study: a longitudinal study of persons aged 80 years or older (n = 346). An adjusted linear regression model was subsequently performed to calculate the regression coefficients of the associations between baseline physical and functional measures (dependent variable) with CZr or "Cu and Zn" alone taking also into account the influence of other relevant factors, including hematological (albumin, cholesterol, and urea) and inflammatory biomarkers (IL-6 and CRP) that were significantly different across CZr tertiles. CZr showed significant and stronger relationships than Cu or Zn alone with all baseline physical and functional measures in models that did not include adjustments for inflammatory parameters. CZr was also associated with physical decline, measured as "SPPB% decline" at 2 years of follow-up and mortality at 4 years of follow-up. Subjects in the high CZr tertile had a higher risk of death with an adjusted hazard ratio of 1.92 (95% CI, 1.12-3.29; p = 0.02). In conclusion, we have confirmed the role of CZr as a predictor of mortality, whereas the role of CZr as a biomarker or predictor of physical or functional performance seems to be the consequence of its strict relationships with inflammatory parameters. In this context, further investigations need to be carried out.

Development and validation of the HOPE prognostic index on 24-month posthospital mortality and rehospitalization: Italian National Research Center on Aging (INRCA).

BACKGROUND: A fast and simple tool is needed to test for the risk of mortality and rehospitalization in older patients. OBJECTIVE: The aim of this study was to construct and validate a prognostic index using specific items from the Comprehensive Geriatric Assessment (CGA) in a large population of older hospitalized adults. METHOD: This was a prospective study of a 24-month follow-up period, between 2005 to 2008 in 3,043 elderly patients (mean age, 81 ± 6) discharged from three acute geriatric wards in the Marche region of Italy. Baseline predictors of demographics and 25 items from the CGA regarding functional and cognitive status, depression, co-morbidity, social isolation, and quality of life were used to build a summary score, the Hospitalized Older Patient Examination (HOPE) Index. The HOPE index was developed in 1,533 patients and validated in 1,510 consecutively hospitalized patients. Outcome measures were 24-month mortality and rehospitalization. RESULTS: Three risk categories of HOPE based on the best sensitivity and specificity for mortality and rehospitalization were: Low (≤4), moderate (4-8), and high (≥8). Categorizing data across the HOPE index, mortality ranged from 7.9% to 14.5% in the development cohort and 6.2% to 14.0% in the validation cohort, whereas rehospitalization ranged from 68.3% to 79.4% and 69.8% to 79.8%, respectively. Kaplan-Meier survival curves demonstrated that risk for mortality increased with a worsening across the HOPE index (p < 0.001). In the development and validation cohorts, a close agreement was found for HOPE on mortality and rehospitalization with a receiver operating characteristic (ROC) of 0.69 (95% confidence interval [CI] 0.61-0.74) vs. 0.67 (95% CI 0.57-0.70) and rehospitalization of 0.62 (95% CI 0.58-0.66) vs. 0.60 (95% CI 0.56-0.63), respectively. In the development and validation cohorts, Cox proportional hazard models showed that a high HOPE index predicted risks of 2.38 (1.34-4.23) and 2.86 (1.24-6.61) on mortality and 1.27 (1.09-1.44) and 1.37 (1.10-1.64) on rehospitalization, respectively. CONCLUSIONS: HOPE may be useful for long-term clinical planning, discharge, and follow-up.

Does concealed chronic kidney disease predict survival of older patients discharged from acute care hospitals?

We aimed at verifying whether unrecognized chronic kidney disease (CKD) (i.e., reduced estimated glomerular filtration rate in spite of normal serum creatinine) has prognostic significance in an unselected population of older patients discharged from 11 acute care hospitals located throughout Italy. Our series consisted of 396 participants aged 70 and older. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) study equation. We compared three groups: Normal renal function (normal serum creatinine levels and normal eGFR), concealed (normal serum creatinine levels and reduced eGFR), or overt (increased creatinine levels and reduced eGFR) renal failure. The relationship between renal function and 1-year mortality was evaluated using Kaplan-Meier curves and Cox regression analysis including potential confounders. Overall, 56 patients died over a cumulative follow-up time of 335 months, with an estimated incidence rate of 16.7/100 person-year (PY). The corresponding figures in patients with normal renal function, concealed CKD, and overt CKD were 9.8/100 PY (95% CI, 5.7-15.7), 28.3/100 PY (95% CI, 13.6-52.1), and 23.0 (95% CI, 15.4-33.0), respectively (log rank test p = 0.006). According to the fully adjusted model, both concealed (hazard ratio [HR], 2.35; 95% CI, 1.09-6.01) and overt CKD (HR, 2.09; 95% CI, 1.05-5.34) were significantly associated with the outcome. Concealed CKD contributes to profile the elderly patient at greater risk of death after being discharged from acute care medical wards. If confirmed in broader populations, this finding might have both clinical and epidemiological implications.

Pharmacoeconomics and aging.

The aging of the general population in industrialized countries has brought to public attention the increasing incidence of age-related clinical conditions, because the long-term impact of diseases on functional status and on costs are greater in older people than in any other age group. With the aging of the population, it is becoming increasingly important to quantify the burden of illness in the elderly; this will be vital not only in planning for the necessary health services that will be required in coming years, but also in order to measure the benefit to be expected from interventions to prevent disability in older people. The management of multiple and chronic disorders has become a more important issue for healthcare authorities because of increasing requests for medical assistance and healthcare interventions. Among these, pharmacological treatments and drug utilization in older people are pressing issues for healthcare managers and politicians; indeed, a relatively small proportion of the population accounts for a substantial part of public drug costs. Two key sources of pressure are well known: the growing number of elderly persons, who are the highest per-capita users of medicines, and the introduction of new, often more expensive, medicines. On the other hand, the development of strategies for controlling costs, while providing the elderly with equitable access to needed pharmaceuticals, should be based on an evaluation of the economic impact of pharmacological care in older people, taking into account the burden of illness, drug utilization data, drug technology assessment evidence and results. Furthermore, there are major factors affecting pharmacological care in older people: for example inappropriate prescribing, lack of adherence and compliance, and the burden of adverse drug events. The assessment of these factors should be considered a priority in pharmacoeconomic evaluations in the aging population, and the most relevant evidence will be reviewed in this paper with examples referring to particular settings or conditions and diseases, such as the presence of cardiovascular risk factors, diabetes and chronic pain.