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.

Prognostic Interplay of Functional Status and Multimorbidity Among Older Patients Discharged From Hospital.

OBJECTIVES: The purpose of this study was to investigate the prognostic weight of multimorbidity and functional impairment over long-term mortality among older patients discharged from acute care hospitals. DESIGN: A prospective multicenter observational study. SETTING AND PARTICIPANTS: Our series consisted of 1967 adults aged ≥65 years consecutively admitted to acute care wards in Italy, in the context of the Report-AGE project. METHODS: After signing a written informed consent, all patients underwent comprehensive geriatric assessment by Inter-RAI Minimum Data Set acute care. The primary endpoint of the present study was long-term mortality. Patients were grouped into 3 functional clusters and 3 disease clusters using the K-medians cluster analysis. The association of functional clusters, disease clusters, and Charlson score categories with long-term mortality was investigated through Cox regression analysis and the intercluster classification agreement was further estimated. Finally, the additive effect of either disease clusters or Charlson score on predictive ability of functional clusters was assessed by using changes in Harrell's C-index and categorical Net Reclassification Index (NRI). RESULTS: Functional clusters, disease clusters, and Charlson score were significant predictors of long-term mortality, but the interclassification agreement was poor. Functional clusters predicted mortality with greater accuracy [C-index 0.66, 95% confidence interval (CI) 0.65-0.68] compared with disease clusters (C-index 0.54, 95% CI 0.53-0.56), and Charlson score (C-index 0.58, 95% CI 0.56-0.59). Adding multimorbidity (NRI 0.23, 95% CI 0.14-0.31) or Charlson score (NRI 0.13, 95% CI 0.03-0.20) to functional cluster model slightly improved the accuracy of prediction. CONCLUSIONS AND IMPLICATIONS: Functional impairment may better predict prognosis compared with multimorbidity, which may be relevant to optimally address individuals' needs and to design tailored preventive interventions.

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.

Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study.

BACKGROUND: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016. METHODS/DESIGN: An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months- follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for 'basic' parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months. DISCUSSION: Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people. TRIAL REGISTRATION: This study was registered prospectively on the 25th February 2016 at clinicaltrials.gov ( NCT02691546 ).

Adverse Events of Proton Pump Inhibitors: Potential Mechanisms.

OBJECTIVE: We aimed at summarizing current evidence about mechanisms for potentially harmful effects of Proton Pump Inhibitors (PPIs). METHODS: A Pubmed search was performed, and 207 studies concerning the relationship between use of PPIs and cardiovascular diseases, kidney impairment, nutritional disorders, fractures, infections, functional decline, and mortality were selected and reviewed. RESULTS: PPIs may cause potentially harmful effects by several mechanisms, including endothelial dysfunction, hypomagnesemia, drug interactions, reduced absorption of selected nutrients, increased gastric microbiota and small intestine bacterial overgrowth, reduced immune response, tubular-interstitial inflammation, increased bone turnover, accumulation of amyloid in the brain. Clinical and epidemiologic evidence is not consistent in regard to some negative outcomes during PPI treatment. Data from randomized clinical trials seem to deny most of them, but they are usually designed to investigate efficacy of drugs in ideal conditions and are not powered enough to detect adverse events. Besides being at special risk of experiencing negative outcomes during long-term treatment with PPIs, older and complex patients treated with polypharmacy regimens are persistently excluded from randomized clinical trials. Thus, large observational studies involving real-world patients should be considered as an important informative source about potential risks related to PPIs. CONCLUSIONS: Current evidence suggests that use of PPIs may be associated with negative outcomes by eliciting several different pathophysiologic mechanisms. While short-term PPIs could be considered effective and safe in adult patients with acid-related disorders, their long-term and often inappropriate use in patients carrying vulnerability to adverse events and/or high risk of drug-interactions should be avoided.

Preadmission Functional Decline Predicts Functional Improvement Among Older Patients Admitted to Acute Care Hospital.

Background: Functional decline from preadmission to admission may represent an important predictor of functional trajectories during hospitalization among older patients. Therefore, we aimed at describing the impact of preadmission decline on functional trajectories among older hospitalized patients. Methods: Our series consisted of 2,011 patients aged 65 years or more consecutively admitted to four acute care wards of Geriatric Medicine participating to a multicenter observational study. Enrolled patients underwent comprehensive geriatric assessment (CGA) by Inter-RAI Minimum Data Set. Main outcomes were functional decline or improvement from hospital admission to discharge based on Activities of Daily Living (ADL) scale. The main exposure variable was ADL decline during the preadmission period (ie, 3 days before the onset of acute illness), and its impact on functional trajectories during stay was investigated by Cox regression models after adjusting for potential confounders. Results: After adjusting for potential confounders, preadmission functional decline was significantly associated with functional improvement during stay (hazard ratio [HR] = 6.65; 95% confidence interval [CI] = 5.01-8.84), but not with functional decline. Severe cognitive impairment (HR = 0.28, 95% CI = 0.13-0.60), visual impairment (HR = 0.60, 95% CI = 0.41-0.89), and weight loss (HR = 0.67, 95% CI = 0.47-0.94) were associated with functional improvement during stay. Hearing impairment (HR = 1.94, 95% CI = 1.17-3.23) and mild (HR = 2.54, 95% CI = 1.41-4.58) or severe cognitive impairment (HR = 2.72, 95% CI = 1.13-6.56) were associated with functional decline during stay. Conclusions: Patients experiencing recent preadmission functional decline should be considered as those for which the geriatric approach may lead to the better functional result in the acute care setting. CGA allows to individuate risk factors to be addressed in the acute care setting.

Coronary flow response to remote ischemic preconditioning is preserved in old cardiac patients.

BACKGROUND: The effect of remote ischemic preconditioning (RIPC) on coronary flow in elderly cardiac patients has not been investigated yet. Thus, we aimed to study the change of coronary flow subsequent to RIPC in old patients with heart diseases and to identify its main correlates. METHODS: Ninety-five elderly patients (aged ≥ 65 years) accessing cardiac rehabilitation ward underwent transthoracic ultrasound evaluation of peak diastolic flow velocity of left anterior descending artery. Measurements of coronary flow velocity were performed on baseline and after an RIPC protocol (three cycles of 5 min ischemia of right arm alternating 5 min reperfusion). Differences between subjects with coronary flow velocity change over or equal the 75° percentile (high-responders) and subjects with a coronary flow velocity change under the 75° percentile (low-responders) were assessed. RESULTS: In enrolled elderly heart patients, coronary flow velocity significantly augmented from baseline after RIPC [0.23 m/s (0.18-0.28) vs 0.27 m/s (0.22-0.36); p < 0.001 by Wilcoxon test]. High-responders to RIPC were significantly younger and in better functional status than low-responders. Heart failure resulted as the main variable associated with impairment of RIPC responsiveness (R 2 = 0.202; p = 0.002)]. CONCLUSIONS: Our sample of old cardiac patients presented a significant median increment of coronary flow velocity after RIPC. The magnitude of the observed change of coronary flow velocity was comparable to that previously described in healthy subjects. The coronary response to RIPC was attenuated by heart failure. Further research should define whether such RIPC responsiveness is associated with cardioprotection and carries prognostic implications.

Special considerations for the treatment of chronic kidney disease in the elderly.

Chronic kidney disease (CKD) is common in older adults, and its burden is expected to increase in older populations. Even if the knowledge on the approach to older patient with CKD is still evolving, current guidelines for pharmacological management of CKD does not include specific recommendations for older patients. Additionally, decision-making on renal replacement therapy (RRT) for older patients is far from being evidence-based, and despite the improvement in dialysis outcomes, RRT may cause more harm than benefit compared with conservative care when prognostic stratification is not carefully assessed. The use of comprehensive geriatric assessment tools could help clinicians in applying a more informed decision-making. Finally, physical exercise and rehabilitation interventions also represents a promising therapeutic strategy.

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.

Treating COPD in Older and Oldest Old Patients.

The treatment of older and oldest old patients with COPD poses several problems and should be tailored to specific outcomes, such as physical functioning. Indeed, impaired homeostatic mechanisms, deteriorated physiological systems, and limited functional reserve mainly contribute to this complex scenario. Therefore, we reviewed the main difficulties in managing therapy for these patients and possible remedies. Inhaled long acting betaagonists (LABA) and anticholinergics (LAMA) are the mainstay of therapy in stable COPD, but it should be considered that pharmacological response and safety profile may vary significantly in older patients with multimorbidity. Their association with inhaled corticosteroids is recommended only for patients with severe or very severe airflow limitation or with frequent exacerbations despite bronchodilator treatment. In hypoxemic patients, long-term oxygen therapy (LTOT) may improve not only general comfort and exercise tolerance, but also cognitive functions and sleep. Nonpharmacological interventions, including education, physical exercise, nutritional support, pulmonary rehabilitation and telemonitoring can importantly contribute to improve outcomes. Older patients with COPD should be systematically evaluated for the presence of risk factors for non-adherence, and the inhaler device should be chosen very carefully. Comorbidities, such as cardiovascular diseases, chronic kidney disease, osteoporosis, obesity, cognitive, visual and auditory impairment, may significantly affect treatment choices and should be scrutinized. Palliative care is of paramount importance in end-stage COPD. Finally, treatment of COPD exacerbations has been also reviewed. Therapeutic decisions should be founded on a careful assessment of cognitive and functional status, comorbidity, polypharmacy, and agerelated changes in pharmacokinetics and pharmacodynamics in order to minimize adverse drug events, drug-drug or drug-disease interactions, and non-adherence to treatment.

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.

Advanced technology care innovation for older people in Italy: necessity and opportunity to promote health and wellbeing.

Even though there is a constant and accelerating growth of the aging population worldwide, such a rapid rise is negatively impacting available home and community services not able to encompass the necessities associated with the increased number of older people. In particular, there are increasing demands on e-health care services and smart technologies needed for frail elders with chronic diseases and also for those experiencing active aging. Advanced Technology Care Innovation for older persons encompasses all sectors (assistive technology, robotics, home automation, and home care- and institution-based healthcare monitoring, telemedicine) dedicated to promoting health and wellbeing in all types of living environments. Considering that there is a large concern and demand by older persons to remain in familiar social living surroundings, study projects joined with industries have been currently initiated, especially across Europe to improve health and wellbeing. This article will highlight the latest updates in Europe and, in particular in Italy, regarding scientific projects dedicated to unraveling how diverse needs can be translated into an up-to-date technology innovation for the growing elder population. We will provide information regarding advanced technology designed for those with specific geriatric-correlated conditions in familiar living settings and for individuals aging actively. This is an important action because numerous emerging developments are based on user needs identified by geriatricians, thus, underlining the indispensable role of geriatric medicine toward future guidelines on specific technology.

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.

Estimating renal function to reduce the risk of adverse drug reactions.

The aging process is characterized by relevant changes in pharmacokinetics. Renal function is known to decline with aging. However, as a result of reduced muscle mass, older individuals frequently have a depressed glomerular filtration rate (GFR) despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly on the clearance of hydrosoluble drugs, as well as the risk of adverse drug reactions (ADRs) from hydrosoluble drugs. The assessment of renal function should thus be a mandatory item in the global examination of patient characteristics. Equations for estimating GFR have become very popular in recent years. However, different equations may yield significantly different estimated glomerular filtration rate (eGFR) values, which have important implications in dosing drugs cleared by the kidney. Current knowledge suggests that eGFR based on the Chronic Kidney Disease-Epidemiological Collaboration (CKD-EPI) study equation outperformed eGFR based on the Modification of Diet in Renal Disease (MDRD) study equation and creatinine clearance estimate based on the Cockcroft-Gault formula as a predictor of ADRs from kidney cleared drugs. More recently, the combined creatinine-cystatin C equation was shown to perform better than equations based on either of these markers alone in diagnosing CKD, even in older patients. However, its accuracy in predicting ADRs and usefulness in drug dosing is still to be investigated.

Geriatric conditions and the risk of adverse drug reactions in older adults: a review.

While polypathology and polypharmacy are well known risk factors for adverse drug reactions (ADRs), the association between geriatric conditions (GCs), i.e. a set of clinical and functional problems partly constitutive of and partly related to frailty, and ADRs is suspected but has not been fully elucidated. Several studies have assessed the relationship between single GCs and ADRs, but only a few studies have systematically evaluated the relationship between the whole spectrum of GCs and ADRs. The mechanism by which select GCs increase the risk of developing ADRs during a hospital stay might simply reflect a sort of general predictability of physical disability with respect to adverse outcomes. However, GCs pertaining to the physical dimension of frailty are generally associated with relevant changes in pharmacokinetics and pharmacodynamics of select drugs. While current evidence could not be considered either unequivocal or conclusive, select GCs, e.g. a history of falls and loss of independence in the activities of daily living, seem to define a condition of particular vulnerability of elderly patients to ADRs.

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.

Prognostic significance of the short physical performance battery in older patients discharged from acute care hospitals.

We investigated the prognostic role of the Short Physical Performance Battery (SPPB) in elderly patients discharged from the acute care hospital. Our series consisted of 506 patients aged 70 years or more enrolled in a multicenter collaborative observational study. We considered three main outcomes: 1-year survival after discharge, functional decline, and hospitalization during follow-up. Independent predictors/correlates of the outcomes were investigated by Cox regression or logistic regression analysis when appropriate. The diagnostic accuracy of SPPB in relation to study outcomes was investigated by receiver operating characteristic (ROC) curve. SPPB score was associated with reduced mortality (hazard ratio [HR]=0.86, 95% confidence interval [CI] 0.78-0.95). When the analysis was adjusted for functional status at discharge, such an association was still near significant only for SPPB values >8 (HR=0.51; 95% CI 0.30-1.05). An SPPB score<5 could identify patients who died during follow-up with fair sensitivity (0.66), specificity (0.62), and area under the ROC curve (0.66). SPPB also qualified as independent correlate of functional decline (odds ratio [OR]=0.82; 95% CI 0.70-0.96), but not of rehospitalization or combined end-point death or rehospitalization. An SPPB score <5 could identify patients experiencing functional decline during follow-up with lower sensitivity (0.60), but higher specificity (0.69), and area under the ROC curve (0.69) with respect to mortality. In conclusion, SPPB can be considered a valid instrument to identify patients at major risk of functional decline and death after discharge from acute care hospital. However, it could more efficiently target patients at risk of functional decline than those at risk of death.

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.

Depression, hypertension, and comorbidity: disentangling their specific effect on disability and cognitive impairment in older subjects.

We aimed to demonstrate that depression and hypertension are associated independently of each other with disability and cognitive impairment in older subjects and that such an association is not attributable to number and severity of comorbidities. An observational study was performed on elderly patients admitted to the Hospital Network of the Italian National Research Center on Aging (INRCA) from January 2005 to December 2006. Depression was defined according to 15-item geriatric depression scale (GDS) score; physical disability according to activities of daily living (ADL) and instrumental activities of daily living (IADL) scores; cognitive impairment on the mini-mental state examination (MMSE) test; the number and severity of comorbidities by means of physician-administered cumulative illness rating scale (CIRS). Among 6180 older subjects (age=79.3 ± 5.8 years; 47% men), 48.3% were normotensive, 21.8% normotensive depressed, 21.7% hypertensive, and 8.2% hypertensive and depressed. Both depression and hypertension remained significantly associated with functional disability and cognitive impairment. When controlling for age, gender, the number and severity of comorbidities, hypertension was associated with a significantly higher likelihood of having functional disability or cognitive impairment only in the presence of depression (odds ratio=OR=2.02, 95% confidence interval=95%CI=1.60-2.54, p<0.001 for functional disability; OR=2.21, 95%CI=1.79-2.74, p<0.001 for cognitive impairment) as compared to normotensive controls without depression. We conclude that depression per se' or co-occurrence of hypertension and depression is associated with higher functional disability and cognitive impairment in older subjects. This effect is not attributable to the number or to the severity of comorbidities.

Comorbidities of chronic obstructive pulmonary disease.

PURPOSE OF REVIEW: Defining the nature of the association between chronic obstructive pulmonary disease (COPD) and other chronic conditions is of primary importance to improve the health status of COPD patients through the optimal care of comorbidities. We aimed at providing a reasoned guide to understand, recognize and treat comorbidity of COPD with the perspective of shifting from comorbidity to multimorbidity. RECENT FINDINGS: Select comorbidities, such as atherosclerotic disease, depression, chronic kidney disease, cognitive impairment, obstructive sleep apnea syndrome, lung cancer, osteoporosis, diabetes, heart failure, sarcopenia, aortic aneurysm, arrhythmias and pulmonary embolism are highly prevalent among older COPD patients. Several concerns may affect the management of older COPD patients with comorbidity (e.g. the use of ß-blockers in patients with COPD and cardiovascular diseases or concerns about the cardiovascular safety of inhaled COPD drugs). SUMMARY: Evidence suggests that systemic inflammation may be the link between COPD and comorbidities, but this issue is still debated. Whatever the mechanism underlying comorbidities in COPD may be, it has an important clinical, prognostic and therapeutic impact. Nevertheless, clinical practice guidelines do not take into account comorbidities in their recommendations. Additionally, clinical trials investigating COPD treatment in the context of multimorbidity and considering geriatric outcomes are also distinctly lacking.