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Heat shock proteins (HSPs) are crucial for maintenance of cell homeostasis and survival both during and after various stresses. The capability to cope with stress is believed to affect the chance of health and survival at organismal level. We have investigated whether the gene pool relevant to the (A/C)-110 polymorphism in the promoter region of the HSP70-1 gene changes as the population ages and survival selection occurs. A total of 591 southern Italian subjects were enrolled in the study (263 males and 328 females; age range 18–109 years), free of clinically manifest diseases and with normal haemato-chemical parameters. A significant age-related decrease of the frequency of allele (A)-110 was observed in females. The probability ratio of 0.403 (95% confidence interval [0.163, 0.910]) computed by considering female centenarians as cases and young women (18–49 years old) as controls showed that the (A)-110 allele is unfavorable to longevity in females. [ABSTRACT FROM AUTHOR]

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., (© 2018 Japan Geriatrics Society.)

We review some of the latest approaches to analysing cardiac electrophysiology data using machine learning and predictive modelling. Cardiac arrhythmias, particularly atrial fibrillation, are a major global healthcare challenge. Treatment is often through catheter ablation, which involves the targeted localised destruction of regions of the myocardium responsible for initiating or perpetuating the arrhythmia. Ablation targets are either anatomically defined, or identified based on their functional properties as determined through the analysis of contact intracardiac electrograms acquired with increasing spatial density by modern electroanatomic mapping systems. While numerous quantitative approaches have been investigated over the past decades for identifying these critical curative sites, few have provided a reliable and reproducible advance in success rates. Machine learning techniques, including recent deep-learning approaches, offer a potential route to gaining new insight from this wealth of highly complex spatio-temporal information that existing methods struggle to analyse. Coupled with predictive modelling, these techniques offer exciting opportunities to advance the field and produce more accurate diagnoses and robust personalised treatment. We outline some of these methods and illustrate their use in making predictions from the contact electrogram and augmenting predictive modelling tools, both by more rapidly predicting future states of the system and by inferring the parameters of these models from experimental observations., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To determine whether anticholinergic burden may predict differently 1-year mortality in older patients discharged from acute care hospitals with or without dependency in basic activities of daily living (BADL)., Design: Prospective observational study., Setting and Participants: Our series consisted of 807 patients aged 65 years or older consecutively discharged from 7 acute care geriatric wards throughout Italy between June 2010 and May 2011., Measures: Overall anticholinergic burden was assessed by the anticholinergic cognitive burden (ACB) score. Dependency was rated by BADL, and dependency in at least 1 BADL was considered as a potential mediator in the analysis. The study outcome was all-cause mortality during 12-months of follow-up., Results: Patients included in the study were aged 81.0 ± 7.4 years, and 438 (54.3%) were female. During the follow-up period, 177 out of 807 participants (21.9%) died. After adjusting for potential confounders, discharge ACB score = 2 or more was significantly associated with the outcome among patients with dependency in at least 1 BADL [hazard ratio (HR) 2.25 95% confidence (CI) 1.22‒4.14], but not among independent ones (HR 1.06 95% CI 0.50‒2.34). The association was confirmed among dependent patients after adjusting for the number of lost BADL at discharge (HR 2.20 95% CI 1.18‒4.04) or ACB score at 3-month follow-up (HR 2.18 95% CI 1.20‒3.98), as well as when considering ACB score as a continuous variable (HR 1.28 95% CI 1.11‒1.49). The interaction between ACB score at discharge and BADL dependency was highly significant (P < .001)., Conclusions/implications: ACB score at discharge may predict mortality among older patients discharged from an acute care hospital carrying at least 1 BADL dependency. Hospital physicians should be aware that prescribing anticholinergic medications in this population may have negative prognostic implications and they should try to reduce anticholinergic burden at discharge whenever possible., (Copyright © 2018 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

A number of epigenetic studies have demonstrated that DNA methylation patterns exhibit a tissue specificity, but not much has been done to highlight the extent of this phenomenon. Moreover, it is unknown how external factors modulate the plasticity of the tissue specific epigenetic profile. We examined global DNA methylation profiles in tissues from rats of different age, fed with standard or low-calorie diet, and evaluated their association with aging and nutrition. Tissue-specific variations occur during aging with hyper-methylation taking place in all tissues except for liver. The expression of enzymes involved in methylation reactions (DNMTs and TETs) was consistent with the methylation patterns. Nutrition affects global DNA methylation status throughout lifespan. Interestingly, the differences among different tissues are magnified in 96 weeks old rats fed with low calorie diet. Moreover, the low-calorie diet appears to affect the offspring's epigenetic status more strongly if administered during the maternal pre-gestational period than the gestational and lactation time. Therefore, we propose that changes in the global DNA methylation status may represent an epigenetic mechanism by which age and nutrition intersect each other and, in turn, influence the aging plasticity., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Multi-photon laser scanning microscopy provides a powerful tool for monitoring the spatiotemporal dynamics of neural circuit activity. It is, however, intrinsically a point scanning technique. Standard raster scanning enables imaging at subcellular resolution; however, acquisition rates are limited by the size of the field of view to be scanned. Recently developed scanning strategies such as travelling salesman scanning (TSS) have been developed to maximize cellular sampling rate by scanning only select regions in the field of view corresponding to locations of interest such as somata. However, such strategies are not optimized for the mechanical properties of galvanometric scanners. We thus aimed to develop a new scanning algorithm which produces minimal inertia trajectories, and compare its performance with existing scanning algorithms., Approach: We describe here the adaptive spiral scanning (SSA) algorithm, which fits a set of near-circular trajectories to the cellular distribution to avoid inertial drifts of galvanometer position. We compare its performance to raster scanning and TSS in terms of cellular sampling frequency and signal-to-noise ratio (SNR)., Main Results: Using surrogate neuron spatial position data, we show that SSA acquisition rates are an order of magnitude higher than those for raster scanning and generally exceed those achieved by TSS for neural densities comparable with those found in the cortex. We show that this result also holds true for in vitro hippocampal mouse brain slices bath loaded with the synthetic calcium dye Cal-520 AM. The ability of TSS to 'park' the laser on each neuron along the scanning trajectory, however, enables higher SNR than SSA when all targets are precisely scanned. Raster scanning has the highest SNR but at a substantial cost in number of cells scanned. To understand the impact of sampling rate and SNR on functional calcium imaging, we used the Cramér-Rao Bound on evoked calcium traces recorded simultaneously with electrophysiology traces to calculate the lower bound estimate of the spike timing occurrence., Significance: The results show that TSS and SSA achieve comparable accuracy in spike time estimates compared to raster scanning, despite lower SNR. SSA is an easily implementable way for standard multi-photon laser scanning systems to gain temporal precision in the detection of action potentials while scanning hundreds of active cells.

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The transcription of ribosomal RNA genes (rDNA) is subject to epigenetic regulation, as it is abrogated by the methylation of CpG dinucleotides within their promoter region. Here, we investigated, through Sequenom platform, the age-related methylation status of the CpG island falling into the rDNA promoter in 472 blood samples from 20- to 105-year-old humans and in different tissues (blood, heart, liver, kidney, and testis) of 15 rats 3-96 weeks old. In humans, we did not find a consistently significant correlation between CpG site methylation and chronological age. Furthermore, the methylation levels of one of the analyzed CpG sites were negatively associated with both cognitive performance and survival chance measured in a 9-year follow-up study. We consistently confirmed such result in a replication sample. In rats, the analysis of the homologous region in the tissues revealed the existence of increased methylation in old rats. rRNA expression data, in both humans and rats, were consistent with observed methylation patterns, with a lower expression of rRNA in highly methylated samples. As chronological and biological ages in rats of a given strain are likely to be much closer to each other than in humans, these results seem to provide the first evidence that epigenetic modifications of rDNA change over time according to the aging decline. Thus, the methylation profile of rDNA may represent a potential biomarker of aging., (© 2017 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

The aim of the present review was to summarize knowledge about thyroid hormones (THs) and longevity. Longevity is a complex multifactorial phenomenon on which specific biological pathways, including hormonal networks involved in the regulation of homeostasis and survival, exert a strong impact. THs are the key responsible for growth, metabolism rate and energy expenditure, and help in maintaining cognition, bone and cardiovascular health. THs production and metabolism are fine tuned, and may help the organism to cope with a variety of environmental challenges. Experimental evidence suggests that hypothyroid state may favor longevity by reducing metabolism rate, oxidative stress and cell senescence. Data from human studies involving healthy subjects and centenarians seem to confirm this view, but THs changes observed in older patients affected by chronic diseases cannot be always interpreted as a protective adaptive mechanism aimed at reducing catabolism and prolonging survival. Medications, selected chronic diseases and multi-morbidity can interfere with thyroid function, and their impact is still to be elucidated., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: To investigate the prevalence and clinical correlates of overprescribing and underprescribing of low molecular weight heparins (LMWHs) for thromboprophylaxis among older medical inpatients., Methods: Eight hundred seventy six patients (mean age 81.5 ± 7.6 years, female gender 57.2 %) enrolled in a multicenter observational study of seven acute care wards of geriatric medicine in Italy. The risk of venous thromboembolism was ascertained by calculating the Padua score for each patient. Patients receiving appropriate prescription of LMHW during stay were compared to those receiving LMHW with a Padua score <4 (overprescribing group). Similarly, patients with a high thromboembolic risk (Padua score ≥4) but not receiving LMHW (underprescribing group) were compared to patients appropriately not receiving LMHW during stay. Independent correlates of overprescribing and underprescribing were investigated by logistic regression analysis., Results: Overall, 42.8 % of patients had a Padua score ≥4. LMWHs were overprescribed in 7.3 % and underprescribed in 25.2 % of patients. The number of lost basic activities of daily living (BADL) (OR = 0.25; 95 % CI 0.15-0.41) and the number of diagnoses (OR = 0.76; 95 % CI 0.61-0.95) were inversely associated with LMWH overprescription. Conversely, older age (75-84 years: OR = 2.39; 95 % CI 1.10-5.19-85 years or more: OR = 3.25, 95 % CI 1.40-7.61), anemia (OR = 1.80, 95 % CI 1.05-3.16), pressure sores (OR = 4.15, 95 % CI 1.20-14.3), number of lost BADL at the admission (OR = 3.92, 95 % CI 2.86-5.37) and number of diagnoses (OR = 1.29, 95 % CI 1.15-1.44) qualified as significant correlates of LMWH underprescription., Discussion: Underprescription and, to a lesser extent, overprescription still represent an issue among older medical inpatients., Conclusion: Implementing risk-stratifying scores into clinical practice may improve appropriateness of LMWHs prescribing during hospitalization.

Before the last decade, attempts to identify the genetic factors involved in the susceptibility to age-related complex diseases such as cardiovascular disease, diabetes and cancer had very limited success. Recently, two important advancements have provided new opportunities to improve our knowledge in this field. Firstly, it has emerged the concept of studying the molecular mechanisms underlying the age related decline of the organism (such as cellular senescence), rather than the genetics of single disorders. In addition, advances in DNA technology have uncovered an incredible number of common susceptibility variants for several complex traits. Despite these progresses, the translation of these discoveries into clinical practice has been very difficult. To date, several attempts in translating genomics to medicine are being carried out to look for the best way by which genomic discoveries may improve our understanding of fundamental issues in the prediction and prevention of some complex diseases. The successful strategy seems to be testing simultaneously multiple susceptibility variants in combination with traditional risk factors. In fact, such approach showed that genetic factors substantially improve the prediction of complex diseases especially for coronary heart disease and prostate cancer, making possible appropriate behavioural and medical interventions. In the future, the identification of new genetic variants and their inclusion into current risk profile models will probably improve the discrimination power of these models for other complex diseases such as type 2 diabetes mellitus and breast cancer. On the other hand, for traits with low heritability, this improvement will probably be negligible, and this will urge further researches on the role played by traditional and newly discovered non-genetic risk factors.

Objective: To summarize current evidence about mechanisms, clinical features, diagnostic issues, and strategies for prevention of medication-induced nephrotoxicity among older people., Methods: A Pubmed search was performed, and studies concerning age-related changes in kidney structure and function predisposing to nephrotoxicity, pathophysiological mechanisms, kidney drug metabolism enzymes, clinical epidemiology of medication-induced kidney damage, biomarkers for early identification of nephrotoxicity and strategies for prevention of medication-induced nephrotoxicity among older people were selected. Finally, 245 papers were included in the review., Results: Medications may induce nephrotoxicity through several pathophysiological mechanisms. People aged 75 or more are especially exposed to potential nephrotoxic medications or combinations of medications in the context of complex polypharmacy regimens. Estimated glomerular filtration rate (eGFR) may be useful to identify medication-induced alterations in kidney function, but creatinine-based methods have important limitation in older patients. Several innovative biomarkers have been proposed to identify AKI but these methodologies are not standardized and older people have not been evaluated systematically. Factors related to patient, medication, and interactions should be taken into account for effective prevention., Conclusions: Medication-induced nephrotoxicity is a relevant problem in older populations. Nevertheless, several areas of uncertainty remain to be explored, including the impact of nephrotoxicity on functional outcomes relevant to older patients, the reliability of currently recommended methods for diagnosing and staging AKI, the use of innovative biomarkers in such a heterogeneous population, the effectiveness of preventing strategies and treatments and their impact on functional outcomes.

Recording the activity of neural populations at high sampling rates is a fundamental requirement for understanding computation in neural circuits. Two photon microscopy provides one promising approach towards this. However, neural circuits are three dimensional, and functional imaging in two dimensions fails to capture the 3D nature of neural dynamics. Electrically tunable lenses (ETLs) provide a simple and cheap method to extend laser scanning microscopy into the relatively unexploited third dimension. We have therefore incorporated them into our Adaptive Spiral Scanning (SSA) algorithm, which calculates kinematically efficient scanning strategies using radially modulated spiral paths. We characterised the response of the ETL, incorporated its dynamics using MATLAB models of the SSA algorithm and tested the models on populations of Izhikevich neurons of varying size and density. From this, we show that our algorithms can theoretically at least achieve sampling rates of 36.2Hz compared to 21.6Hz previously reported for 3D scanning techniques.

Objectives: To investigate the relationship between use of proton pump inhibitors (PPIs) and incident dependency in older adults discharged from acute care hospitals., Design: Prospective observational study., Setting: Eleven geriatric and internal medicine acute care wards located throughout Italy., Participants: Individuals (mean age 79.2 ± 5.5) who were not completely dependent at the time of discharge from participating wards (N = 401)., Measurements: The outcome of interest was the loss of at least one basic activity of daily living (ADL) from discharge to the end of follow-up (12 months). The relationship between PPI use and functional decline was investigated using logistic regression analysis before and after propensity score matching., Results: Use of PPIs was significantly associated with functional decline before (odds ratio (OR) = 1.75, 95% confidence interval (CI) = 1.17-2.60) and after propensity score matching (OR = 2.44; 95% CI = 1.36-4.41). Other predictors of functional decline were hypoalbuminemia (OR = 3.10, 95% CI = 1.36-7.10 before matching, OR = 2.81, 95% CI = 1.09-7.77 after matching) and cognitive impairment (OR = 4.08, 95% CI = 1.63-10.2 before matching, OR = 6.35, 95% CI = 1.70-24.0 after matching)., Conclusion: Use of PPIs is associated with functional decline during 12 months of follow-up in older adults discharged from acute care hospitals., (© 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.)

Motivation: Present research on gene expression using live cell imaging and fluorescent proteins or tagged RNA requires accurate automated methods of quantification of these molecules from the images. Here, we propose a novel automated method for classifying pixel intensities of fluorescent spots to RNA numbers., Results: The method relies on a new model of intensity distributions of tagged RNAs, for which we estimated parameter values in maximum likelihood sense from measurement data, and constructed a maximum a posteriori classifier to estimate RNA numbers in fluorescent RNA spots. We applied the method to estimate the number of tagged RNAs in individual live Escherichia coli cells containing a gene coding for an RNA with MS2-GFP binding sites. We tested the method using two constructs, coding for either 96 or 48 binding sites, and obtained similar distributions of RNA numbers, showing that the method is adaptive. We further show that the results agree with a method that uses time series data and with quantitative polymerase chain reaction measurements. Lastly, using simulated data, we show that the method is accurate in realistic parameter ranges. This method should, in general, be applicable to live single-cell measurements of low-copy number fluorescence-tagged molecules., Availability and Implementation: MATLAB extensions written in C for parameter estimation and finding decision boundaries are available under Mozilla public license at http://www.cs.tut.fi/%7ehakkin22/estrna/ CONTACT: andre.ribeiro@tut.fi., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

We aimed at reviewing age-related changes in kidney structure and function, methods for estimating kidney function, and impact of reduced kidney function on geriatric outcomes, as well as the reliability and applicability of equations for estimating glomerular filtration rate (eGFR) in older patients. CKD is associated with different comorbidities and adverse outcomes such as disability and premature death in older populations. Creatinine clearance and other methods for estimating kidney function are not easy to apply in older subjects. Thus, an accurate and reliable method for calculating eGFR would be highly desirable for early detection and management of CKD in this vulnerable population. Equations based on serum creatinine, age, race, and gender have been widely used. However, these equations have their own limitations, and no equation seems better than the other ones in older people. New equations specifically developed for use in older populations, especially those based on serum cystatin C, hold promises. However, further studies are needed to definitely accept them as the reference method to estimate kidney function in older patients in the clinical setting.

Objectives: To investigate the relationship between clinical conditions typically observed in the geriatric patients (geriatric conditions) and adverse drug reactions in older patients admitted to acute care hospitals., Design and Setting: Prospective observational study conducted in 11 acute care medical wards throughout Italy., Participants: Five hundred six patients aged 65 years or older consecutively admitted to participating wards., Measurements: The outcome of the study was the occurrence of any adverse drug reactions during the hospital stay. Geriatric conditions considered in the analysis were basic activities of daily living, history of falls, slow walking speed, malnutrition, dementia, depression, 1 or more unplanned admissions in the previous 3 months, history of stroke, unintentional weight loss, and exhaustion. The relationship between risk factors and outcomes was assessed using logistic regression., Results: Female gender (odds ratio [OR] 2.29; 95% confidence interval [CI] 1.18-4.45) and number of medications taken during hospitalization (OR 1.12; 95% CI 1.06-1.18), but not individual Geriatric conditions, were associated with the outcome after correction for potential confounders. However, the simultaneous presence of history of falls and dependency in at least 1 activities of daily living (OR 2.18; 95% CI 1.13-4.19) was associated with adverse drug reactions during stay., Conclusion: The simultaneous presence of history of falls and dependency in at least one activity of daily living defines a condition of particular vulnerability of elderly hospitalized patients to adverse drug reactions. Physicians should be aware of this high-risk condition when prescribing new drugs to disabled older people., (Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.)

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.

Background: Glomerular filtration rate (GFR) is directly associated with survival. However, the prognostic significance of GFR might be different according to the formula used to estimate it. We aimed at comparing the association between GFR estimated using three different formulas and 1-year survival in elderly patients discharged from acute care hospitals., Methods: Our series consisted of 439 patients aged 65 and older admitted to 11 acute care medical wards enrolled in a multicentre prospective observational study. GFR was estimated by body surface area-adjusted Cockcroft-Gault (CG-BSA), Modification of Diet in Renal Disease study (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulas. The relative risk of mortality in patients with estimated GFR = 30-59.9 or < 30 mL/min/1.73 m(2) compared to people with estimated GFR ≥ 60 mL/min/1.73 m(2) was calculated using Cox regression analysis., Results: Participants with reduced GFR showed an increased mortality, regardless of the equation used, and the highest one was associated with CG-BSA-estimated GFR < 30 mL/min/1.73 m(2). After adjusting for potential confounders, CKD-EPI-estimated GFR remained significantly associated with the outcome [30-59.9 mL/min/1.73 m(2), hazard ratio (HR) = 1.70, 95% confidence interval (95% CI) = 1.02-2.98; < 30 mL/min/1.73 m(2), HR = 2.60, 95% CI = 1.20-5.66], while the strength of the association was clearly reduced for MDRD (30-59.9 mL/min/1.73 m(2), HR = 1.47, 95% CI = 0.83-2.38; < 30 mL/min/1.73 m(2), HR = 2.07, 95% CI = 1.01-4.30) and CG-BSA (30-59.9 mL/min/1.73 m(2), HR = 1.79, 95% CI = 0.67-4.53; < 30 mL/min/1.73 m(2), HR = 2.68, 95% CI = 0.92-7.55)., Conclusion: GFR adds to the list of prognostic indicators in elderly and frail people, and CKD-EPI-derived GFR, which outperforms to some extent MDRD and CG-BSA-derived GFR in a multivariable predictive model, seems worthy of testing in wider populations.

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

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

Balanced and safe prescribing is difficult to achieve in frail older adults with multiple comorbid diseases. This issue is of particular concern, especially in elderly hospitalized patients because hospitalization exposes such individuals to an increased risk of adverse drug reactions (ADRs). The avoidance of medications that are considered to be inappropriate is among the interventions for treatment options in elderly patients. A potentially inappropriate medication (PIM) is a drug in which the risk of an adverse event outweighs its clinical benefit, particularly when there is a safer or more effective alternative therapy for the same condition. Explicit criteria have been developed to identify PIMs and among these, Beers' criteria are the most frequently applied in the literature. However, evidence suggests that such criteria cannot easily be applied to elderly hospitalized people in European countries; approximately 20% of drugs listed in Beers' criteria are rarely prescribed or are not available in Europe, and Beers' listed PIMs are not associated with inhospital mortality, length of hospital stay and/or ADRs in Italian studies. On the contrary, ADRs can contribute to accelerated functional decline in elderly hospitalized patients independently of the use of Beers' listed PIMs. Therefore, we will review the evidence pertaining to the application of Beers' criteria in elderly hospitalized patients, while focusing on Italian studies that have investigated the role of PIMs as potential predictors of negative hospital outcomes. In addition, we will also review the available evidence regarding new European criteria on identifying PIMs, because clinical application in elderly hospitalized Europeans is still under investigation.

Objectives: To verify whether the use of potentially inappropriate medications (PIMs) is associated with loss of independence in elderly in-patients by promoting adverse drug reactions (ADRs)., Design: Prospective observational study., Participants: Five hundred six patients aged 65 and older admitted to 11 acute care medical wards., Measurements: In-hospital loss of one or more activities of daily living (ADLs) and three or more ADLs. PIMs were identified according to diagnosis-independent Beers criteria and ascertained by study physicians based on daily review of medical and nurse records. The relationship between risk factors and outcomes was assessed using logistic regression., Results: Overall, 104 patients (20.6%) were taking at least one PIM at the time of admission (baseline users), and 49 (9.7%) were newly prescribed at least one PIM during their hospital stay. The loss of one or more ADLs occurred in 9.6% of baseline users, 16.3% of new users, and 8.5% of nonusers (P=.21) and that of three or more ADLs in 7.7% of baseline users, 12.2% of new users, and 4.8% of nonusers (P=.10). The lack of association was confirmed after correction for potential confounders, including ADRs. The occurrence of ADRs was strongly associated with both outcomes (odds ratio (OR)=7.80, 95% confidence interval (CI)=3.53-17.3 for the loss of > or =1 ADLs; OR=3.98, 95% CI=1.50-10.5 for the loss of > or =3 ADLs), but PIMs caused only six of 106 ADRs., Conclusions: ADRs to any drugs more than the use of PIMs might be associated with functional decline in elderly hospitalized patients, but because the power of this study was too limited to definitively exclude a direct relationship between PIMs and functional decline, this merits further investigation.

Objective: To assess whether the number of daily administrations of individual drugs, as a measure of regimen complexity, contributes to the profile of an elderly patient who adheres poorly to the prescribed therapy., Population: Six hundred ninety patients over 64 years who were consecutively admitted to 11 acute medical care and three long term/rehabilitation wards in Italy., Main Outcome Measure: Self-reported adherence to drugs taken at home before admission was measured by a single question assessment for each listed drug supplemented with a latter question about the circumstances of the missed administration. For cognitively impaired patients the question was put to patients' relatives or caregivers., Methods: A structured multidimensional assessment was performed to identify nonadherence and its potential correlates. Correlates of nonadherence were identified by multivariable logistic regression., Results: We recorded 44 cases (6.4%) of nonadherence to at least one drug. Being assisted by foreign caregivers (OR 2.17; 95% CI 1.02-4.63) and the use of at least one multiple daily dosing drug (OR 2.99; 95% CI 1.24-7.17) were significant independent correlates of medication nonadherence, while age, selected indexes of frailty and the cumulative number of prescribed drugs were not., Conclusion: Regimen complexity and type of assistance are independent correlates of medication nonadherence.

Background: In studies on the genetics of human aging, we observed an age-related variation of the 3'APOB-VNTR genotypic pool (alleles: Short, S, <35 repeats; Medium, M, 35-39 repeats; Long, L, >39 repeats) with the homozygous SS genotype showing a convex frequency trajectory in a healthy aging population. This genotype was rare in centenarians, thus indicating that the S alleles are unfavorable to longevity, while common in adults, thus indicating a protective role at middle age. This apparent paradox could be due to possible effects exerted by the above polymorphism on lipidemic parameters. Aim of the work was to get insights into these puzzling findings, Methods: We followed a double strategy. Firstly, we analyzed the average effects of S (alphaS), M (alphaM), and L (alphaL) alleles on lipidemic parameters in a sample of healthy people (409 subjects aged 20-102 years) recruited in Calabria (southern Italy). The (alphaS), (alphaM), and (alphaL) values were estimated by relating 3'APOB-VNTR genotypes to lipidemic parameters, after adjustment for age, sex and body mass index (multiple regression). Then, we analyzed the S alleles as susceptibility factors of Cardiovascular Atherosclerotic Disease (CD) in CD patients characterized either by low serum HDL-Cholesterol or by high serum LDL-Cholesterol (CD-H and CD-L patients, 40 and 40 subjects respectively). The Odds Ratios (OR) were computed for carriers of S alleles in CD-H and CD-L patients matched for origin, sex and age with controls extracted from the sample of healthy subjects., Results: By the analysis of the healthy sample group we found that the S alleles lower the average values of serum Total Cholesterol (alphaS = -5.98 mg/dL with [-11.62/-0.74] 95% confidence interval) and LDL-Cholesterol (alphaS = -4.41 mg/dL with [-8.93/-0.20] 95% confidence interval) while the alleles M and L have no significant effect on the lipidemic phenotype. In line with these findings, the analysis of CD patients showed that the S alleles are protective as for CD-L (O.R. = 0.55 with [0.21/0.98] 95% confidence interval) while neutral as for CD-H (O.R. = 0.75 with [0.32/1.60] 95% confidence interval)., Conclusion: On the whole, the S alleles would be advantageous in adults (by protecting from CD-L) while dangerous in the elderly, probably by lowering serum cholesterol below a critical threshold. This could explain the convex frequency trajectory of SS genotypes previously observed in a healthy aging population.