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.

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.

The UP-TECH project, an intervention to support caregivers of Alzheimer's disease patients in Italy: preliminary findings on recruitment and caregiving burden in the baseline population.

OBJECTIVES: The paper describes recruitment results and characteristics of the UP-TECH clinical trial sample, including level of care services use, informal caregiver burden and its determinants. METHODS: UP-TECH is designed to test innovative care solutions for community-dwelling patients with moderate stage Alzheimer's disease and their caregivers in Italy. Four hundred and fifty patient-caregiver dyads were randomized into three arms receiving different combinations of services, composed of case management interventions, nurse visits, assistive technology and educational brochures. The research nurses administered a questionnaire comprising an in-depth socio-demographic assessment and several clinical scales, such as Novak's Caregiver Burden Inventory. Analyses of baseline data were conducted using uni- and bi-variate statistics. Linear regressions were computed to identify de-confounded correlates of caregiver burden. RESULTS: Four hundred and thirty-eight patient-caregiver dyads were recruited and randomized. In our sample, patients are predominantly women (71.5%), with an average age of 81.5 years and a mean Mini-Mental State Examination score of 16.2. Caregivers are mostly women (66.2%) and offspring (55.7%), with a mean caregiver burden score of 27.6. They provide more than 50 hours of care per week, while receiving an almost negligible support from public services. Factors associated with caregiver burden are female gender, kinship and the patient's behavioral disturbances. The most important factor associated with lower burden is the employment of a live-in care worker. CONCLUSION: The paper provides a comprehensive description of moderate stage Alzheimer's disease patients and their caregivers, suggesting useful markers of caregiver burden. The well-balanced randomization assures the reliability of the study data-set for prospective evaluation of care strategies.

The economic burden of inappropriate drug prescribing, lack of adherence and compliance, adverse drug events in older people: a systematic review.

Adverse drug events (ADEs) are an increasingly relevant issue for healthcare systems as they are associated with poorer health outcomes and avoidable misuse of resources. The rates of ADEs are higher in the elderly population, as many older patients have comorbidities, multiple drug prescriptions and deteriorated physical and cognitive functioning. The occurrence of ADEs can lead to a perceived lack of therapy efficacy and further underuse or suboptimal adherence in elderly people, with detrimental clinical outcomes. The present article systematically reviews the studies evaluating the economic impact of ADEs occurring as consequence of poor therapy adherence, inappropriate drug use, underuse of effective treatments and poor adherence, medication errors, drug-drug and drug-disease interactions.A Medline systematic literature review of studies evaluating the economic consequences of inappropriate drug prescribing, lack of adherence and compliance, ADEs in older people was performed. English-language articles were screened through a three-step approach (title review, abstract review, full article review) to select pertinent studies quantitatively evaluating costs. We systematically reviewed evidence from767 articles. After title, abstract and full text review, 21 articles were found to measure economic implications ofADEs, inappropriate drug prescribing and poor adherence in elderly patients. Studies suggested that the economic impact of these undesired effects is substantial: hospital costs were the main cost driver, with a relevant part of them being preventable (consequences of inappropriate prescribing). Healthcare costs for unused drug wastage and destruction were also surprisingly high.Although economic evidence in elderly patients is still limited, all studies seemed to confirm that the financial burden due to pharmacological treatment issues is relevant in elderly people. Including economic effects of adverse events in pharmacoeconomic analysis would be beneficial to improve the reliability of results. Preliminary evidence suggests that programmes aimed at comprehensively assessing geriatric conditions, detecting 'high-risk' prescriptions and training patients to comply with prescribed therapies could be costeffective measures to reduce the burden of ADEs.

The economic burden of chronic obstructive pulmonary disease in the elderly: results from a systematic review of the literature.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a high prevalence condition with a significant clinical and economic burden. In elderly people, COPD is often associated with other chronic comorbidities (i.e. cardiovascular diseases), determining clinical complications and requiring frequent acute healthcare interventions. The aim of this article is to review the economic studies evaluating costs and healthcare resource utilization in elderly (≥ 65 years) COPD patients. RECENT FINDINGS: Sixteen of the initial 359 articles retrieved through our research strategy were found to include relevant cost information on elderly COPD patients or to evaluate the effect of older age on healthcare expenditure. Most studies were carried out in the United States and used administrative database claims to determine resource consumption and direct costs (attributable and not). Very few studies focused exclusively on elderly patients. SUMMARY: Results showed a certain variability of cost estimations, mainly due to the different methodologies and adopted cost approach. However, we found a trend of direct cost growth in the elderly population, which can be explained by a more frequent use of acute healthcare services, especially for managing COPD exacerbations. These results cannot be considered definitive and new studies, targeting elderly people, are required in order to confirm these preliminary findings.

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.

The pharmacoeconomic impact of amlodipine use on coronary artery disease.

The most frequent cause of mortality and morbidity in industrialized countries is coronary artery disease (CAD), which in Europe alone is responsible for around two million deaths per year. In 2001 it accounted for about 260,000 hospital discharges in Italy. The costs of CAD treatment in Italy--which were borne by the Italian state, the third-party payer--amounted to 800 million euros. We propose to assess the pharmacoeconomic implications of using amlodipine besylate treatment in Italy for patients with coronary artery disease. The study is based on a post-hoc cost-effectiveness analysis that compared standard care supplemented by amlodipine besylate with ordinary standard care over a 36-month time horizon. The clinical outcome data were based on the prospective randomized evaluation of vascular effect of norvasc trial (PREVENT). Direct medical costs referred to the purchase costs of amlodipine besylate and the cost of National Health Service (NHS) hospitalization. The costs were discounted back at an annual rate of 5%. Patients administered amlodipine besylate exhibited a significant risk reduction with respect to any major vascular event or procedure when compared to the placebo group. The reduction mainly referred to unstable angina events and revascularization procedures. We estimated that the total cost of adding amlodipine besylate to standard care amounted to 139,050 euros per 1000 patients treated for 36 months. This represents a cost of 1780 euros per patient remaining free of any vascular event. Results were sensitive to both clinical and economic variables. The incremental costs of the alternative therapy ranged from 296 euros to 5066 per patient free of any event in, respectively, the best and worst scenario. Amlodipine besylate therapy can be a cost-effective strategy for CAD treatment in Italy. Our economic evaluation demonstrated, first, that by reducing vascular events and the need for revascularization procedures savings were achieved in hospital expenditure, and, second, that such savings could significantly offset drug costs.

Pharmacoeconomic consequences of amlodipine besylate therapy in patients undergoing PTCA.

In Italy, revascularization interventions increased from 44,600 in 1996 to more than 100,000 in 2001. In particular, the occurrence of percutaneous transluminal coronary angioplasty (PTCA) increased from 239 cases per million population in 1994 to about 1300 cases per million population in 2001. This trend has caused a concomitant increase in revascularization costs, which have doubled in few years, rising from Euro 421 millions in 1996 to Euro 850 millions in 2001. In 2001, PTCA amounted to 55% of total cost of revascularizations. The aim of this study was to assess the pharmacoeconomic consequences of amlodipine besylate therapy administered in patients at high risk of restenosis after PTCA. We conducted a cost-effectiveness analysis comparing therapy with amlodipine besylate added to standard care versus standard care alone. Information on clinical outcomes was drawn from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES). Medical costs were estimated with reference to drug therapy and hospitalizations for coronary events and revascularization procedures. The study was conducted from the perspective of the Italian third party payer (National Health Service). The analysis was applied to a time horizon of 4 months. Amlodipine besylate resulted less expensive and more effective than standard care. It reduced mortality, morbidity for coronary reasons and the need of revascularization procedures. The cost per 1000 patients was estimated at Euro 1,166,000 in the placebo and Euro 950,000 in the amlodipine besylate group, resulting into a cost saving of Euro 216,000, that is 18.5% of total cost of standard care. Results are sensitive to the cost of amlodipine besylate and the cost of hospitalizations, but therapy with amlodipine besylate resulted dominant even in the most unfavorable hypothesis.