Improving the prognostic value of multimorbidity through the integration of selected biomarkers to the comprehensive geriatric assessment: An observational retrospective monocentric study.

Background: Multimorbidity (MM) burdens individuals and healthcare systems, since it increases polypharmacy, dependency, hospital admissions, healthcare costs, and mortality. Several attempts have been made to determine an operational definition of MM and to quantify its severity. However, the lack of knowledge regarding its pathophysiology prevented the estimation of its severity in terms of outcomes. Polypharmacy and functional impairment are associated with MM. However, it is unclear how inappropriate drug decision-making could affect both conditions. In this context, promising circulating biomarkers and DNA methylation tools have been proposed as potential mortality predictors for multiple age-related diseases. We hypothesize that a comprehensive characterization of patients with MM that includes the measure of epigenetic and selected circulating biomarkers in the medical history, in addition to the functional capacity, could improve the prognosis of their long-term mortality. Methods: This monocentric retrospective observational study was conducted as part of a project funded by the Italian Ministry of Health titled "imProving the pROgnostic value of MultimOrbidity through the inTegration of selected biomarkErs to the comprehensive geRiatric Assessment (PROMOTERA)." This study will examine the methylation levels of thousands of CpG sites and the levels of selected circulating biomarkers in the blood and plasma samples of older hospitalized patients with MM (n = 1,070, age ≥ 65 years) recruited by the Reportage Project between 2011 and 2019. Multiple statistical approaches will be utilized to integrate newly measured biomarkers into clinical, demographic, and functional data, thus improving the prediction of mortality for up to 10 years. Discussion: This study's results are expected to: (i) identify the clinical, biological, demographic, and functional factors associated with distinct patterns of MM; (ii) improve the prognostic accuracy of MM patterns in relation to death, hospitalization-related outcomes, and onset of new comorbidities; (iii) define the epigenetic signatures of MM; (iv) construct multidimensional algorithms to predict negative health outcomes in both the overall population and specific disease and functional patterns; and (v) expand our understanding of the mechanisms underlying the pathophysiology of MM.

The Possible Impact of Aortic Stiffness on Quality of Late Life: An Exploratory Study.

PURPOSE: Aortic stiffness (AS) is associated with cardiovascular events and all-cause mortality in the older population. AS might also influence the health-related quality of life (HRQOL) as a result of the negative effects of AS on cognitive and physical morbidity. We aimed to investigate the possible association between AS and HRQOL in people aged 75 years and over. PATIENTS AND METHODS: This cross-sectional study was part of the SCOPE study, an international multicenter cohort observational study. The indicators for AS were aortic pulse wave velocity (aPWV) and central pulse pressure (cPP). HRQOL was assessed using the EQ-5D index and the EQ-5D visual analog scale (VAS). ANCOVA and multivariate regression models were used to investigate possible associations. RESULTS: We included 280 Dutch participants of the SCOPE study. Median age was 79 years (IQR 76-83) and 42.1% were women. Participants reporting any problem on the EQ-5D index (n=214) had higher values of aPWV (12.6 vs 12.2 m/s, p = 0.024) than participants not experiencing any problem (n=66) and comparable values of cPP (44.4 vs 42.0 mmHg, p = 0.119). Estimates only slightly changed after adjustments. No association was found between indicators of AS and EQ-5D VAS. CONCLUSION: Aortic stiffness was associated with impaired quality of late life. This association could be mediated by subclinical vascular pathology affecting mental and physical health.

Beyond chronic kidney disease: the diagnosis of Renal Disease in the Elderly as an unmet need. A position paper endorsed by Italian Society of Nephrology (SIN) and Italian Society of Geriatrics and Gerontology (SIGG).

The dramatic increase in prevalence of chronic kidney disease (CKD) with ageing makes the recognition and correct referral of these patients of paramount relevance in order to implement interventions preventing or delaying the development of CKD complications and end-stage renal disease. Nevertheless, several issues make the diagnosis of CKD in the elderly cumbersome. Among these are age related changes in structures and functions of the kidney, which may be difficult to distinguish from CKD, and multimorbidity. Thus, symptoms, clinical findings and laboratory abnormalities should be considered as potential clues to suspect CKD and to suggest screening. Comprehensive geriatric assessment is essential to define the clinical impact of CKD on functional status and to plan treatment. Correct patient referral is very important: patients with stage 4-5 CKD, as well as those with worsening proteinuria or progressive nephropathy (i.e. eGFR reduction > 5 ml/year) should be referred to nephrologist. Renal biopsy not unfrequently may be the key diagnostic exam and should not be denied simply on the basis of age. Indeed, identifying the cause(s) of CKD is highly desirable to perform a targeted therapy against the pathogenetic mechanisms of CKD, which complement and may outperform in efficacy the general measures for CKD.

Short Physical Performance Battery and all-cause mortality: systematic review and meta-analysis.

BACKGROUND: The Short Physical Performance Battery (SPPB) is a well-established tool to assess lower extremity physical performance status. Its predictive ability for all-cause mortality has been sparsely reported, but with conflicting results in different subsets of participants. The aim of this study was to perform a meta-analysis investigating the relationship between SPPB score and all-cause mortality. METHODS: Articles were searched in MEDLINE, the Cochrane Library, Google Scholar, and BioMed Central between July and September 2015 and updated in January 2016. Inclusion criteria were observational studies; >50 participants; stratification of population according to SPPB value; data on all-cause mortality; English language publications. Twenty-four articles were selected from available evidence. Data of interest (i.e., clinical characteristics, information after stratification of the sample into four SPPB groups [0-3, 4-6, 7-9, 10-12]) were retrieved from the articles and/or obtained by the study authors. The odds ratio (OR) and/or hazard ratio (HR) was obtained for all-cause mortality according to SPPB category (with SPPB scores 10-12 considered as reference) with adjustment for age, sex, and body mass index. RESULTS: Standardized data were obtained for 17 studies (n = 16,534, mean age 76 ± 3 years). As compared to SPPB scores 10-12, values of 0-3 (OR 3.25, 95%CI 2.86-3.79), 4-6 (OR 2.14, 95%CI 1.92-2.39), and 7-9 (OR 1.50, 95%CI 1.32-1.71) were each associated with an increased risk of all-cause mortality. The association between poor performance on SPPB and all-cause mortality remained highly consistent independent of follow-up length, subsets of participants, geographic area, and age of the population. Random effects meta-regression showed that OR for all-cause mortality with SPPB values 7-9 was higher in the younger population, diabetics, and men. CONCLUSIONS: An SPPB score lower than 10 is predictive of all-cause mortality. The systematic implementation of the SPPB in clinical practice settings may provide useful prognostic information about the risk of all-cause mortality. Moreover, the SPPB could be used as a surrogate endpoint of all-cause mortality in trials needing to quantify benefit and health improvements of specific treatments or rehabilitation programs. The study protocol was published on PROSPERO (CRD42015024916).

Impact of hospitalization on modification of drug regimens: Results of the criteria to assess appropriate medication use among elderly complex patients study.

AIM: To assess the impact of hospitalization on modification of drug burden among elderly patients. METHODS: The present prospective cohort study was carried out in acute care hospitals in Italy. The difference in the number of drugs used before hospital admission and those prescribed at discharge was calculated. The prevalence of (i) any increase (1 or more drugs); and (ii) an increase >50% in the number of drugs from admission to discharge was calculated, and the factors associated with these conditions were identified. RESULTS: The mean age of 1082 participants was 81.2 ± 7.3 years and 606 were women (56.0%), an increase in the number of drugs (1 or more drugs) between admission and discharge was observed in 672 participants (62.1% of study sample) and an "increase >50%" was observed in 372 participants (34.3%). "Any increase" was inversely associated with age and the number of drugs used before hospitalization, and it was positively associated with length of stay and diagnoses, including chronic obstructive pulmonary disease, ischemic heart disease and diabetes. "Increase >50%" was inversely associated with female sex, the number of drugs before hospitalization, involuntary loss of weight and intact cognitive status, and was positively associated with length of stay, chronic obstructive pulmonary disease, heart failure and diabetes. CONCLUSIONS: Not only disease, but also demographic factors (age and gender) and geriatric syndromes (weight loss and cognitive status) might influence pharmacological burden. These data might be useful in order to target interventions aimed at improving drug use and reducing iatrogenic illness. Geriatr Gerontol Int 2016; 16: 593-599.

The economic impact of moderate stage Alzheimer's disease in Italy: evidence from the UP-TECH randomized trial.

BACKGROUND: There is consensus that dementia is the most burdensome disease for modern societies. Few cost-of-illness studies examined the complexity of Alzheimer's disease (AD) burden, considering at the same time health and social care, cash allowances, informal care, and out-of-pocket expenditure by families. METHODS: This is a comprehensive cost-of-illness study based on the baseline data from a randomized controlled trial (UP-TECH) enrolling 438 patients with moderate AD and their primary caregiver living in the community. RESULTS: The societal burden of AD, composed of public, patient, and informal care costs, was about €20,000/yr. Out of this, the cost borne by the public sector was €4,534/yr. The main driver of public cost was the national cash-for-care allowance (€2,324/yr), followed by drug prescriptions (€1,402/yr). Out-of-pocket expenditure predominantly concerned the cost of private care workers. The value of informal care peaked at €13,590/yr. Socioeconomic factors do not influence AD public cost, but do affect the level of out-of-pocket expenditure. CONCLUSION: The burden of AD reflects the structure of Italian welfare. The families predominantly manage AD patients. The public expenditure is mostly for drugs and cash-for-care benefits. From a State perspective in the short term, the advantage of these care arrangements is clear, compared to the cost of residential care. However, if caregivers are not adequately supported, savings may be soon offset by higher risk of caregiver morbidity and mortality produced by high burden and stress. The study has been registered on the website www.clinicaltrials.org ( TRIAL REGISTRATION NUMBER: NCT01700556).

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.

Obesity in the Context of Aging: Quality of Life Considerations.

The progressive increase in the prevalence of obesity and aging in the population is resulting in increased healthcare and disability spending. The burden of obesity is particularly relevant in old age, due to accumulating co-morbidities and changes in body composition. Sarcopenic obesity, a mix of over- and under-nutrition, causes frailty, disability, and problems in social and psychological areas, impacting overall health-related quality of life (HR-QOL). The relationship between obesity, aging, and HR-QOL is, however, much more complex than generally acknowledged and is difficult to disentangle. The impact of obesity on HR-QOL is particularly strong in young people, who are free of co-morbidities. It progressively attenuates, compared with the general population, with advancing age, when co-morbid conditions are diffusely present and reduce the perceived health status, independent of obesity. However, even this apparent 'obesity paradox' should not minimize the importance of obesity on HR-QOL, as other obesity-associated limitations and disabilities do impact HR-QOL in older age. A patient-centered approach aimed at reducing the disability and social isolation of advancing age is mandatory to improve HR-QOL in any class of obesity.

The prevention of adverse drug reactions in older subjects.

Adverse drug reactions (ADRs) are a public health problem in older subjects, being responsible for a significant morbidity, disability and mortality. Older subjects are more susceptible to develop ADRs mainly due to polypharmacy, multimorbidity and inappropriate prescribing. The prevention of these drug related negative events represents an important aim for physicians treating older patients. Several strategies could potentially be employed, including state of the art education of medical students and physicians concerning principles of geriatric medicine and appropriate prescription in older subjects, reduction of inappropriate drug use by means of computerized decision support systems, pharmacist involvement and comprehensive geriatric assessment, and finally the identification of at risk older patients. However, there is currently a lack of scientific evidence demonstrating that these strategies can achieve a reduction in ADRs and therefore future intervention studies should be performed to evaluate the best intervention to decrease the burden of drug related problems in the older population.

To grow old in southern Italy: a comprehensive description of the old and oldest old in Calabria.

BACKGROUND: The unprecedented growth of the elderly population is posing important social and medical problems as management of this population is highly demanding in terms of assistance and care. Consequently, many studies are focusing on the elderly subjects in order to better understand their needs by identifying various environmental, social, psychological, and genetic factors determining the quality of ageing. OBJECTIVES: Our aim was to carry out a survey of the elderly Calabrian population in order to highlight the social and medical conditions of this continuously growing population group. METHODS: We have been monitoring the elderly population of Calabria for more than 10 years. For the present study, we collected data regarding 853 subjects by using two specific questionnaires, one for the subjects older than 90 years (400 subjects) and one for the subjects aged between 65 and 85 years (453 subjects). RESULTS: The survey allowed us to carry out an extensive description of the ageing Calabrian population regarding the sociodemographic characteristics, living conditions, cognitive functioning, level of independence in activities of daily living, former and current diseases and health disorders. We could notice that males were in a better condition than females. In fact, male subjects turned out to have better physical performance and lower comorbidity, although their life expectancy is lower. Ultranonagenarians had a lower incidence of serious diseases (such as diabetes, osteoporosis and gastric ulcer), but a higher incidence of non-fatal chronic, debilitating conditions (cataract and bronchitis among others). CONCLUSION: The data we collected and analyzed offer a portrait of elderly Calabrian subjects, on who they are, how they feel, which social and psychological resources they have, and what their health status is. Analysis of the data highlighted that they are characterized by a lower physical performance in comparison to other European populations. Finally, the data presented here may also serve as a valuable source of information to characterize the ageing Calabrian population and improve the care of these subjects.

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.

Environmental and social determinants of aging perception in metropolitan and rural areas of Southern Italy.

The increasing life expectancy is accompanied by a growing request of social and health care services, and social inequalities may contribute to a poor quality of life (QoL) and an increased risk of cognitive impairment and disability. The purpose of the present study was to investigate the role of social, environmental, and economic factors in determining subjective perception of aging in older people coming from two different areas (metropolitan and rural) of Southern Italy. We used data from a survey carried out in three metropolitan and three rural communities in Southern Italy. The cross-sectional descriptive study was performed by conducting structured interviews and assessments during home visits. Life conditions and health at older ages were investigated with a questionnaire. Elderly people were divided into two population cohorts, namely 304 subjects (152 from metropolitan and 152 from rural area) controlling demographic, social, environmental, and health characteristics. For this study we used the multiple correspondence analysis (MCA), a statistical technique used to highlight the interrelationships between qualitative variables describing a population. More significant environmental and social variable categories linked to negative aging perception were poor education, low income, female gender, widowhood, unsatisfactory health perception, perceived high functional disability, life arrangements, difficulty in reaching services, and environmental problems. Social, ecological, and environmental factors could play a relevant role in determining health status and disability with increasing request of social and health care services.

Socioeconomic status and hospitalization in the very old: a retrospective study.

BACKGROUND: Socioeconomic status could affect the demand for hospital care. The aim of the present study was to assess the role of age, socioeconomic status and comorbidity on acute hospital admissions among elderly. METHODS: We retrospectively examined the discharge abstracts data of acute care hospital admissions of residents in Rome aged 75 or more years in the period 1997-2000. We used the Hospital Information System of Rome, the Tax Register, and the Population Register of Rome for socio-economic data. The rate of hospitalization, modified Charlson's index of comorbidity, and level of income in the census tract of residence were obtained. Rate ratios and 95% confidence limits were computed to assess the relationship between income deciles and rate of hospitalization. Cross-tabulation was used to explore the distribution of the index of comorbidity by deciles of income. Analyses were repeated for patients grouped according to selected diseases. RESULTS: Age was associated with a marginal increase in the rate of hospitalization. However, the hospitalization rate was inversely related to income in both sexes. Higher income was associated with lower comorbidity. The same associations were observed in patients admitted with a principal diagnosis of chronic condition (diabetes mellitus, heart failure, chronic obstructive pulmonary disease) or stroke, but not hip fracture. CONCLUSION: Lower social status and associated comorbidity, more than age per se, are associated with a higher rate of hospitalization in very old patients.

From Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines to current clinical practice : an overview of the pharmacological therapy of stable chronic obstructive pulmonary disorder.

BACKGROUND: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines have been promulgated to improve the management of chronic obstructive pulmonary disorder (COPD). OBJECTIVE: To evaluate the extent to which the current therapeutic approach to COPD conforms to GOLD guidelines. METHODS: This was a multicentre observational study of elderly COPD patients enrolled for acute care in general medicine or geriatric wards in tertiary hospitals in Italy in April 2002. Our series consisted of 471 patients >64 years of age consecutively admitted for acute exacerbations of COPD to wards participating in the study. Data describing drugs used prior to exacerbation and prescribed at discharge were collected using a standardised protocol. Changes in prescription at discharge were then compared with home therapy. Demographic variables and indices of COPD severity and co-morbidity were tested as potential correlates for the main outcome measure 'variant prescription', i.e. prescription of a drug considered as a third-line treatment (e.g. methylxanthines) or not recommended (e.g. mucolytics) by GOLD guidelines. The correlation was assessed first by univariate analysis and then by logistic regression analysis. RESULTS: At discharge, prescription of short-acting beta(2)-adrenoceptor agonists had decreased from 26.3% to 14.0%. Conversely, increases in prescription of long-actingbeta(2)-adrenoceptor agonists (from 43.1% to 68.4%), inhaled corticosteroids (50.7% to 69.6%) and anticholinergics (17.2% to 22.3%) were seen. The rate of use of methylxanthines was 49.7% before admission and 44.8% at discharge, with previous use being the main correlate of discharge prescription for this class of drugs (odds ratio [OR] = 4.35; 95% CI 2.88, 6.54). The rate of use of mucolytics was 26.3% before admission and 26.8% at discharge, with use of mucolytics prior to admission being the only correlate of discharge prescription (OR = 4.10; 95% CI 2.47, 6.82). CONCLUSIONS: Hospitalisation resulted in increased adherence to GOLD guidelines in patients with COPD, but the rate of use of anticholinergics was distinctly low and that of methylxanthines and mucolytics surprisingly high. A carry-over effect (i.e. of therapy prescribed by general practitioners on that prescribed by hospital-based physicians) likely accounts for most of the 'variant prescriptions' seen at discharge from the acute care hospital.