Appropriateness of direct oral anticoagulant prescribing in older subjects with atrial fibrillation discharged from acute medical wards.

AIMS: Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards. METHODS: We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug-drug interactions (DDIs). RESULTS: At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin-K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage-17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00-1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02-1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91-0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19-3.13 for missed prescription). CONCLUSIONS: This study showed a suboptimal DOAC prescriptive practice in older in-patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real-life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting.

Serum levels of soluble suppression of tumorigenicity 2 (sST2) and heart-type fatty acid binding protein (H-FABP) independently predict in-hospital mortality in geriatric patients with COVID-19.

Elevation of cardiac damage biomarkers is associated with adverse clinical outcomes and increased mortality in COVID-19 patients. This study assessed the association of admission serum levels of sST2 and H-FABP with in-hospital mortality in 191 geriatric patients (median age 86 yrs., IQR 82-91 yrs.) with COVID-19 and available measures of hs-cTnT and NT-proBNP at admission. Cox proportional hazards models were utilized to predict in-hospital mortality, considering clinical/biochemical confounders as covariates. A composite cardiac score was calculated to improve predictive accuracy. Patients deceased during their hospital stay (26%) exhibited higher levels of all biomarkers, which demonstrated good discrimination for in-hospital mortality. Addition of sST2 and H-FABP significantly improved the discriminatory power of hs-cTnT and NT-proBNP. The composite cardiac score (AUC=0.866) further enhanced the predictive accuracy. Crude and adjusted Cox regressions models revealed that both sST2 and H-FABP were independently associated with in-hospital mortality (HR for sST2 ≥129 ng/mL, 4.32 [1.48-12.59]; HR for H-FABP ≥18 ng/mL, 7.70 [2.12-28.01]). The composite cardiac score also independently correlated with in-hospital mortality (HR for 1-unit increase, 1.47 [1.14-1.90]). In older patients with COVID-19, sST2 and H-FABP demonstrated prognostic value, improving the predictive accuracy of the routinely assessed biomarkers hs-cTnT and NT-proBNP.

Safety and Tolerability of Antimicrobial Agents in the Older Patient.

Older patients are at high risk of infections, which often present atypically and are associated with high morbidity and mortality. Antimicrobial treatment in older individuals with infectious diseases represents a clinical challenge, causing an increasing burden on worldwide healthcare systems; immunosenescence and the coexistence of multiple comorbidities determine complex polypharmacy regimens with an increase in drug-drug interactions and spread of multidrug-resistance infections. Aging-induced pharmacokinetic and pharmacodynamic changes can additionally increase the risk of inappropriate drug dosing, with underexposure that is associated with antimicrobial resistance and overexposure that may lead to adverse effects and poor adherence because of low tolerability. These issues need to be considered when starting antimicrobial prescriptions. National and international efforts have been made towards the implementation of antimicrobial stewardship (AMS) interventions to help clinicians improve the appropriateness and safety of antimicrobial prescriptions in both acute and long-term care settings. AMS programs were shown to decrease consumption of antimicrobials and to improve safety in hospitalized patients and older nursing home residents. With the abundance of antimicrobial prescriptions and the recent emergence of multidrug resistant pathogens, an in-depth review of antimicrobial prescriptions in geriatric clinical practice is needed. This review will discuss the special considerations for older individuals needing antimicrobials, including risk factors that shape risk profiles in geriatric populations as well as an evidence-based description of antimicrobial-induced adverse events in this patient population. It will highlight agents of concern for this age group and discuss interventions to mitigate the effects of inappropriate antimicrobial prescribing.

Association between Sense of Loneliness and Quality of Life in Older Adults with Multimorbidity.

BACKGROUND: Multimorbidity has been associated with adverse health outcomes, such as reduced physical function, poor quality-of-life (QoL), poor self-rated health. OBJECTIVE: The association between quality of life, social support, sense of loneliness and sex and age in older adult patients affected by two or more chronic diseases (multimorbidity) was evaluated. METHODS: Patients n. 162 with multimorbidity and living with family members. TESTS: MMSE-Mini-Mental-State-Examination; ADL-Activities of Daily Living; Social Schedule: demographic variables; Loneliness Scale -de Jong Gierveld; Quality-of-Life-FACT-G; WHOQOL-BRIEF Social relationships. STATISTICAL ANALYSIS: Multivariate Regression Analysis. RESULTS: The patients with three or more diseases have worse dimensions of FACT-G total score (p = 0.029), QoL Physical-well-being (p = 0.003), Social well-being (p = 0.003), Emotional-well-being (p = 0.012), Functional-well-being (p < 0.001), than those with two. Multiple linear regression QoL: FACT_G total score, PWB, SWB, EWB, FWB as dependent variables. In the presence of multimorbidity with an increase in the patient's age FACT-G total score (B = -0.004, p = 0.482), PWB (B = -0.024, p = 0.014), SWB (B = -0.022, p = 0.051), EWB (B = -0.001, p = 0.939), FWB (B = -0.023, p = 0.013) decrease by an average of 0.1, and as the sense of solitude increases FACT-G total score (B = -0.285, p < 0.000), PWB (B = -0.435, p < 0.000), SWB(B = -0.401, p < 0.000), EWB(B = -0.494, p < 0.000), FWB(B = -0.429, p < 0.000) decrease by 0.4. CONCLUSIONS: A sense of loneliness and advancing age are associated with bad quality-of life in self-sufficient elderly patients with multimorbidity. IMPLICATIONS FOR PRACTICE: Demonstrating that loneliness, as well as in the presence of interpersonal relations, is predictive of worse quality of life in patients with multimorbidity helps identify people most at risk for common symptoms and lays the groundwork for research concerning both diagnosis and treatment.

Frailty modifies the effect of polypharmacy and multimorbidity on the risk of death among nursing home residents: Results from the SHELTER study.

Background: Frailty, disability, and polypharmacy are prevalent in nursing home (NH) residents, often co-occurring with multimorbidity. There may be a complex interplay among them in terms of outcomes such as mortality. Aims of the study were to (i) assess whether nursing home residents with polypharmacy (5-9 medications) or hyperpolypharmacy (≥10 drugs), have an increased risk of death and (ii) whether any association is modified by the co-presence of frailty or disability. Methods: Cohort study with longitudinal mortality data including 4,023 residents from 50 European and 7 Israeli NH facilities (mean age = 83.6 years, 73.2% female) in The Services and Health for Elderly in Long Term care (SHELTER) cohort study. Participants were evaluated with the interRAI-LongTerm Care assessment tool. Frailty was evaluated with the FRAIL-NH scale. Hazard ratio (HR) of death over 12 months was assessed with stratified Cox proportional hazards models adjusted for demographics, facilities, and cognitive status. Results: 1,042 (25.9%) participants were not on polypharmacy, 49.8% (n = 2,002) were on polypharmacy, and 24.3% (n = 979) on hyperpolypharmacy. Frailty and disability mostly increased risk of death in the study population (frailty: HR = 1.85, 95%CI 1.49-2.28; disability: HR = 2.10, 95%CI 1.86-2.47). Among non-frail participants, multimorbidity (HR = 1.34, 95%CI = 1.01-1.82) and hyperpolypharmacy (HR = 1.61, 95%CI = 1.09-2.40) were associated with higher risk of death. Among frail participants, no other factors were associated with mortality. Polypharmacy and multimorbidity were not associated with mortality after stratification for disability. Conclusions: Frailty and disability are the strongest predictors of death in NH residents. Multimorbidity and hyperpolypharmacy increase mortality only in people without frailty. These findings may be relevant to identify patients who could benefit from tailored deprescription.

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.

A focus on CKD reporting and inappropriate prescribing among older patients discharged from geriatric and nephrology units throughout Italy: A nationwide multicenter retrospective cross-sectional study.

Older hospitalized patients with chronic kidney disease (CKD) are part of the geriatric population with a substantial risk of potentially inappropriate medication (PIM) use. The high rates of multimorbidity and polypharmacy, along with the progressive decline of eGFR, contribute to increasing the risk of drug-drug and drug-disease interactions, overdosing, and adverse drug reactions (ADRs). In this multicenter cross-sectional study, we aimed to evaluate the prevalence of CKD under-reporting and PIMs among older patients discharged from acute geriatric and nephrology units throughout Italy. Renal function was determined by estimated glomerular filtration rate (eGFR) through the Berlin Initiative Study (BIS) equation; the prevalence of PIMs was calculated by revising drug prescriptions at discharge according to STOPP criteria, Beers criteria, and summaries of product characteristics (smPCs). A descriptive analysis was performed to compare the clinical and pharmacological characteristics of patients in the two distinct settings; univariate and multivariate logistic regression models were performed to explore factors associated with CKD under-reporting in the discharge report forms and PIM prevalence. Overall, the study population consisted of 2,057 patients, aged 83 (77-89) years, more commonly women, with a median of seven (5-10) drugs prescribed at discharge. CKD under-reporting was present in 50.8% of the study population, with higher rates in geriatric vs. nephrology units (71.1% vs. 10.2%, p < 0.001). 18.5% of the study population was discharged with at least one renally inappropriate medication; factors associated with at least one contraindicated drug at discharge were the number of drugs (PR 1.09, 95% CI 1.14-1.19); atrial fibrillation (PR 1.35, 95% CI 1.01-1.81); diabetes (PR 1.61, 95% CI 1.21-2.13); being hospitalized in nephrology units (PR 1.62, 95% CI 1.14-2.31), CKD stage 3b (PR 2.35, 95% CI 1.34-4.13), and stage 4-5 (PR 14.01, 95% CI 7.36-26.72). Conversely, CKD under-reporting was not associated with the outcome. In summary, CKD under-reporting and inappropriate medication use were common in older patients discharged from hospital; the relatively high number of PIMs in both nephrology and geriatric settings underlines the need to improve appropriate prescribing during hospital stay and to decrease the risk of ADRs and side effects in this highly vulnerable population.

The relevance of geriatric assessments on the association between chronic kidney disease stages and mortality among older people: a secondary analysis of a multicentre cohort study.

BACKGROUND: age-adapted definition of chronic kidney disease (CKD) does not take individual risk factors into account. We aimed at investigating whether functional impairments influence CKD stage at which mortality increases among older people. METHODS: our series consisted of 2,372 outpatients aged 75 years or more enrolled in a multicentre international prospective cohort study. The study outcome was 24-month mortality. Kidney function was assessed by estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Geriatric assessments included handgrip strength, short physical performance battery (SPPB), cognitive impairment, dependency in basic activities of daily living (BADL) and risk of malnutrition. Analysis was carried out by Cox regression, before and after stratification by individual functional impairments. Survival trees including kidney function and functional impairments were also investigated, and their predictivity assessed by C-index. RESULTS: overall, mortality was found to increase starting from eGFR = 30-44.9 ml/min/1.73 m2 (hazard ratio [HR] = 3.28, 95% confidence interval [CI] = 1.81-5.95) to ACR = 30-300 mg/g (HR = 1.96, 95%CI = 1.23-3.10). However, in survival trees, an increased risk of mortality was observed among patients with impaired handgrip and eGFR = 45-59.9 ml/min/1.73 m2, as well as patients with ACR < 30 mg/g and impaired handgrip and SPPB. Survival tree leaf node membership had greater predictive accuracy (C-index = 0.81, 95%CI = 0.78-0.84 for the eGFR survival tree and C-index = 0.77, 95%CI = 0.71-0.81 for the ACR survival tree) in comparison with that of individual measures of kidney function. CONCLUSIONS: physical performance helps to identify a proportion of patients at an increased risk of mortality despite a mild-moderate impairment in kidney function and improves predictive accuracy of individual measures of kidney function.

Italian guidelines on management of persons with multimorbidity and polypharmacy.

Multimorbidity and polypharmacy are emerging health priorities and the care of persons with these conditions is complex and challenging. The aim of the present guidelines is to develop recommendations for the clinical management of persons with multimorbidity and/or polypharmacy and to provide evidence-based guidance to improve their quality of care. The recommendations have been produced in keeping with the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Overall, 14 recommendations were issued, focusing on 4 thematic areas: (1.) General Principles; (2.) target population for an individualized approach to care; (3.) individualized care of patients with multimorbidity and/or polypharmacy; (4.) models of care. These recommendations support the provision of individualized care to persons with multimorbidity and/or polypharmacy as well as the prioritization of care through the identification of persons at increased risk of negative health outcomes. Given the limited available evidence, recommendations could not be issued for all the questions defined and, therefore, some aspects related to the complex care of patients with multimorbidity and/or polypharmacy could not be covered in these guidelines. This points to the need for more research in this field and evidence to improve the care of this population.

Design and methodology of the chronic kidney disease as a dysmetabolic determinant of disability among older people (CKD-3D) study: a multicenter cohort observational study.

BACKGROUND: Chronic kidney disease (CKD) is a common condition in older people and represents a global health issue since it increases the risk of associated comorbidities and all-cause mortality. Furthermore, older people with reduced renal function might be at higher risk for developing functional limitation and disability. Moreover, the current creatinine-based measures of renal function are influenced by several factors in older population. The aims of the CKD-3D project are to perform an observational study to expand the knowledge about CKD-disability relationship and to investigate the use of novel biomarkers of kidney function. METHODS: An observational, multicenter, prospective cohort study will be conducted in 75 + old patients consecutively admitted to acute care wards of geriatric medicine at participating hospitals. The study planned to enroll 440 patients undergoing clinical and laboratory evaluations at baseline and after 12 months. Face-to-face follow-up at 6 months and telephone follow-up at 3 and 9 months will be carried out. Comprehensive Geriatric Assessment (CGA) and the measurement of Cystatin C, Beta-Trace Protein and Beta2-Microglobulin levels will be included. DISCUSSION: This study will provide useful information to prevent CKD-related disability by collecting real-life data over 1-year period. The combined approach of CGA and the investigation of innovative existing biomarkers will make it possible to develop new recommendations and guidelines for a patient-centered approach. It is believed that such a study may lead to an improvement of knowledge on CKD in elderly patients and may also have implications in daily clinical practice and in decision-making process.

Chronic kidney disease in the context of multimorbidity patterns: the role of physical performance : The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Chronic kidney disease (CKD) is known to be associated with several co-occurring conditions. We aimed at exploring multimorbidity patterns associated with CKD, as well as the impact of physical performance and CKD severity on them in a population of older outpatients. METHODS: Our series consisted of 2252 patients enrolled in the Screening of CKD among Older People across Europe multicenter observational study. Hypertension, stroke, transient ischemic attack, cancer, hip fracture, osteoporosis, Parkinson's disease, asthma, chronic obstructive pulmonary disease, congestive heart failure, angina, myocardial infarction, atrial fibrillation, anemia, CKD (defined as GFR < 60, < 45 or < 30 ml/min/1.73 m2), cognitive impairment, depression, hearing impairment and vision impairment were included in the analyses. Physical performance was assessed by the Short Physical Performance Battery (SPPB) and used as stratification variable. Pairs of co-occurring diseases were analyzed by logistic regression. Patterns of multimorbidity were investigated by hierarchical cluster analysis. RESULTS: CKD was among the most frequently observed conditions and it was rarely observed without any other co-occurring disease. CKD was significantly associated with hypertension, anemia, heart failure, atrial fibrillation, myocardial infarction and hip fracture. When stratifying by SPPB, CKD was also significantly associated with vision impairment in SPPB = 5-8 group, and hearing impairment in SPPB = 0-4 group. Cluster analysis individuated two main clusters, one including CKD, hypertension and sensory impairments, and the second including all other conditions. Stratifying by SPPB, CKD contribute to a cluster including diabetes, anemia, osteoporosis, hypertension and sensory impairments in the SPPB = 0-4 group. When defining CKD as eGFR< 45 or 30 ml/min/1.73 m2, the strength of the association of CKD with hypertension, sensory impairments, osteoporosis, anemia and CHF increased together with CKD severity in pairs analysis. Severe CKD (eGFR< 30 ml/min/1.73 m2) contributed to a wide cluster including cardiovascular, respiratory and neurologic diseases, as well as osteoporosis, hip fracture and cancer. CONCLUSIONS: CKD and its severity may contribute significantly to specific multimorbidity patterns, at least based on the cluster analysis. Physical performance as assessed by SPPB may be associated with not negligible changes in both co-occurring pairs and multimorbidity clusters. TRIAL REGISTRATION: The SCOPE study is registered at clinicaltrials.gov ( NCT02691546 ).

Impaired kidney function is associated with lower quality of life among community-dwelling older adults : The screening for CKD among older people across Europe (SCOPE) study.

BACKGROUND: Quality of life (QoL) refers to the physical, psychological, social and medical aspects of life that are influenced by health status and function. The purpose of this study was to measure the self-perceived health status among the elderly population across Europe in different stages of Chronic Kidney Disease (CKD). METHODS: Our series consisted of 2255 community-dwelling older adults enrolled in the Screening for Chronic Kidney Disease (CKD) among Older People across Europe (SCOPE) study. All patients underwent a comprehensive geriatric assessment (CGA), including included demographics, clinical and physical assessment, number of medications taken, family arrangement, Geriatric Depression Scale (GDS), Cumulative Illness Rating Scale, History of falls, Lower urinary tract symptoms, and Short Physical Performance Battery (SPPB). Estimated glomerular filtration rate (eGFR) was calculated by Berlin Initiative Study (BIS) equation. Quality of life was assessed by Euro Qol questionnaire (Euro-Qol 5D) and EQ-Visual Analogue Scale (EQ-VAS). The association between CKD (eGFR < 60, < 45 ml or < 30 ml/min/1.73m2) and low EQoL-VAS was investigated by multivariable logistic regression models. RESULTS: CKD was found to be significantly associated with low EQoL-VAS in crude analysis (OR = 1.47, 95%CI = 1.16-1.85 for eGFR< 60; OR = 1.38, 95%CI = 1.08-1.77 for eGFR< 45; OR = 1.57, 95%CI = 1.01-2.44). Such association was no longer significant only when adjusting for SPPB (OR = 1.20, 95%CI = 0.93-1.56 for eGFR< 60; OR = 0.87, 95%CI = 0.64-1.18 for eGFR< 45; OR = 0.84, 95%CI = 0.50-1.42), CIRS and polypharmacy (OR = 1.16, 95%CI = 0.90-1.50 for eGFR< 60; OR = 0.86, 95%CI = 0.64-1.16 for eGFR< 45; OR = 1.11, 95%CI = 0.69-1.80) or diabetes, hypertension and chronic obstructive pulmonary disease (OR = 1.28, 95%CI = 0.99-1.64 for eGFR< 60; OR = 1.16, 95%CI = 0.88-1.52 for eGFR< 45; OR = 1.47, 95%CI = 0.92-2.34). The association between CKD and low EQoL-VAS was confirmed in all remaining multivariable models. CONCLUSIONS: CKD may significantly affect QoL in community-dwelling older adults. Physical performance, polypharmacy, diabetes, hypertension and COPD may affect such association, which suggests that the impact of CKD on QoL is likely multifactorial and partly mediated by co-occurrent conditions/risk factors.

Association between kidney function, nutritional status and anthropometric measures in older people : The Screening for CKD among Older People across Europe (SCOPE) study.

BACKGROUND: Different mechanisms connect the nutritional status with the occurrence and the course of chronic kidney disease (CKD). The end-stage renal disease is complicated by catabolic inflammatory reactions and cachexia which leads to malnutrition (undernutrition). On the other hand, obesity is an important risk factor for the development and acceleration of CKD. METHODS: In the SCOPE study, community-dwelling persons aged 75 years and over, from 6 European countries and Israel were examined at the baseline phase. We assessed the relationship between anthropometric measures (Body Mass Index (BMI), circumferences of arm (AC), waist (WC), hip (HC), and calf (CC), waist-to-hip ratio - WHR, waist-to-height ratio - WHtR, risk of malnutrition (Mini Nutritional Assessment - MNA), serum albumin) and estimated glomerular filtration rate (eGFR) calculated by Berlin Initiative Study (BIS) equation. RESULTS: We studied 2151 subjects (932 men and 1219 women) with a mean age of 79.5 ± 5.9 years. A total of 1333 (62%) participants had CKD (GRF < 60 ml/min/1.73 m2). Negative correlations between eGFR and weight, AC, WC, HC, CC, BMI, WHtR were observed. Positive correlation occurred between eGFR and MNA score (Spearman's rho = 0.11) and albumin concentration (rho = 0.09). Higher weight, AC, WC, HC, CC, BMI and WHtR increased the odds ratio of CKD; higher MNA (OR = 0.98, 95% CI 0.94-1.0) and higher serum albumin (OR = 0.73, 95% CI 0.53-1.0) were weakly associated with reduced odds. The risk of malnutrition was the highest with eGFR < 30 as compared to eGFR > 60 (OR = 2.95, 95%CI = 1.77-4.94 for MNA < 24; OR = 5.54, 95%CI = 1.66-18.5 for hypoalbuminemia < 3.5 g/dL). CONCLUSION: The population of community dwelling people aged 75+ with CKD shows general features of overweight and obesity with a small prevalence of malnutrition. For anthropometric measures, the strongest association with eGFR and the highest odds of CKD were identified using WC, HC, CC and WHtR. Albumin level and MNA, but not MNA Short Form, indicated an increased odds of malnutrition with a decrease in eGFR.

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.

Cardiovascular risk profiling of long-lived people shows peculiar associations with mortality compared with younger individuals.

AIM: Centenarians represent a biological model of successful aging because they escaped/postponed most invalidating age-related diseases, such as cardiovascular diseases. The aim of the present study was to clarify whether a favorable cardiovascular risk profile increases the survival chances in long-lived people. METHODS: A total of 355 community-dwelling nonagenarians and centenarians living in Southern Italy were recruited in the study. Patients were classified as at low and high cardiovascular risk on the basis of serum cholesterol, diabetes, hypertension and smoking status. The relationship between cardiovascular risk factors and 10-year mortality was investigated by Cox regression analysis. Splines-based hazard ratio curves were also estimated for total cholesterol, low-density lipoprotein cholesterol, and systolic and diastolic blood pressure. RESULTS: Low levels of selected cardiovascular risk factors usually associated with lower mortality in adults do not increase survival chances among oldest-old individuals. In particular, after adjusting for age, sex, and cognitive, functional and nutritional status, serum cholesterol >200 mg/dL increased the survival chances during the follow-up period (hazard ratio 0.742, 95% CI 0.572-0.963). CONCLUSIONS: The present results showed that in nonagenarians and centenarians, the clinical and prognostic meaning associated with traditional cardiovascular risk factors is very different from younger populations. Consequently, considering the increase of this population segment, further studies are required to confirm these results and to translate them into clinical practice/primary care. Geriatr Gerontol Int 2019; 19: 165-170.

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 ).

Estimated glomerular filtration rate and functional status among older people: A systematic review.

BACKGROUND: The association between chronic kidney disease (CKD) and functional status may change as a function of the equation used to estimate glomerular filtration rate (eGFR). We reviewed the predictive value of different eGFR equations in regard to frailty and disability outcomes. METHODS: We searched Pubmed from inception to March 2018 for studies investigating the association between eGFR and self-reported and/or objective measures of frailty or disability. Cross-sectional and longitudinal studies were separately analysed. RESULTS: We included 16 studies, one of which reporting both cross-sectional and longitudinal data. Three out of 7 cross-sectional studies compared different eGFR equations in regard to their association with functional status: two studies showed that cystatin C-based, but not creatinine-based eGFR may be associated with hand-grip strength or frailty; another study showed that two different creatinine-based eGFR equations may be similarly associated with disability. Four out of 10 longitudinal studies provided comparative data: two studies reported similar association with disability for different creatinine-based eGFR equations; one study showed that creatinine-based eGFR was not associated with frailty, but a not significant trend for association was observed with cystatin C-based eGFR; one study showed that cystatin C-based but not creatinine-based eGFR may predict incident mobility disability, while both methods may predict gait speed decline. High heterogeneity was observed in regard to confounders included in reviewed studies. None of them included the most recently published equations. CONCLUSION: Available data do not support the superiority of one of the eGFR equations in terms of measuring or predicting functional decline.

Effects of hyperpolypharmacy and potentially inappropriate medications (PIMs) on functional decline in older patients discharged from acute care hospitals.

AIM: To comparatively investigate the effects of hyperpolypharmacy and potentially inappropriate medications (PIMs) on functional decline in older patients after hospital discharge. METHODS: Our series consisted of 733 patients aged ≥65 consecutively enrolled in a multicenter observational longitudinal study. PIMs were defined on the basis of updated versions of Beers and STOPP criteria. The occurrence of functional decline was defined as the loss of independency in at least 1 basic activity of daily living (BADL) from discharge through 3-month follow-up visit. RESULTS: After adjusting for several potential confounders, hyperpolypharmacy (OR = 2.20; 95%CI = 1.11-4.37) and Beers violations (OR = 1.99; 95%CI = 1.17-3.49) were significantly associated with functional decline, while STOPP (OR = 1.10; 95%CI = 0.64-1.88) and combined Beers + STOPP violations (OR = 1.72; 95%CI = 0.97-3.05) were not. In logistic regression models simultaneously including both hyperpolypharmacy and PIMs, hyperpolypharmacy was always associated with functional decline (OR = 1.98; 95%CI = 1.0-3.97 in the model including Beers violations; OR = 2.19; 95%CI = 1.11-4.35 in the model including STOPP violations; OR = 2.04; 95%CI = 1.02-4.06 in the model including combined Beers and STOPP violations). Beers violations (OR = 1.89; 95%CI = 1.09-3.28) also remained significantly associated with the outcome in this latter analysis, but not STOPP or combined Beers and STOPP violations. CONCLUSIONS: Hyperpolypharmacy, and to a lesser extent Beers violations predict functional decline in older patients discharged from acute care hospitals, whilst STOPP criteria are no longer associated with the outcome after adjusting for potential confounders. Hyperpolypharmacy is associated with functional decline independent of PIMs.

Predicting survival of older community-dwelling individuals according to five estimated glomerular filtration rate equations: The InChianti study.

AIMS: There is uncertainty about which estimated glomerular filtration rate eGFR equation to use in older people with respect to the prediction of prognosis. Our aim was: (i) to compare the discriminative capacity of eGFR estimated by different equations with respect to all-cause mortality; and (ii) to identify the eGFR threshold at which the risk of mortality starts to increase for each equation. METHODS: We used data from 828 community-dwelling older adults aged >65 years enrolled in the InCHIANTI study. The outcome measure was all-cause mortality at 9 years. GFR was estimated by five different equations: Chronic Kidney Disease Epidemiological Collaboration (creatinine equation [CKD-EPIcre ], and creatinine and cystatin C equation [CKD-EPIcre-cys ]), Berlin Initiative Study (BIScre and BIScre-cys ) and full age spectrum. Sensitivity, specificity, areas under receiver operating curve (AUC) and C-statistics were used to compare their predictive capacity. RESULTS: The best mix of sensitivity, specificity, AUC and C-statistic value in predicting mortality was observed with BIS equations. BIScre (AUC 0.65, 95% CI 0.61-0.69) outperformed both CKD-EPIcre (AUC 0.60, 95% CI 0.56-0.64; P = 0.005) and full age spectrum (AUC 0.63, 95% CI 0.59-0.67; P = 0.002) in terms of predictivity. Similarly, BIScre-cys (AUC 0.67, 95% CI 0.63-0.71) outperformed CKD-EPIcre-cys (AUC 0.63, 95% CI 0.59-0.67; P = 0.01). AUC obtained with equations also including cystatin C were not significantly different compared with their creatinine-based counterparts. The risk of long-term mortality began to increase at under 65.6 mL/min/1.73 m2 for CKD-EPIcre-cys , 60.5 for CKD-EPIcre , 60 for BIScre-cys , 56.3 for BIScre and 55.2 for full age spectrum. CONCLUSIONS: The BIS equation discriminates the risk of all-cause mortality better than other equations in older community-dwelling individuals. The eGFR threshold under which mortality starts to increase could change as a function of the equation used. Geriatr Gerontol Int 2018; 18: 607-614.