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Abstract Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Abstract Background Delirium is strongly associated with poor health outcomes, yet it is frequently underdiagnosed. Limited research on delirium has been conducted in Nursing Homes (NHs). Our aim is to assess delirium prevalence and its associated factors, in particular pharmacological prescription, in this care setting. Methods Data from the Italian “Delirium Day” 2016 Edition, a national multicenter point-prevalence study on patients aged 65 and older were analyzed to examine the associations between the prevalence of delirium and its subtypes with demographics and information about medical history and pharmacological treatment. Delirium was assessed using the Assessment test for delirium and cognitive impairment (4AT). Motor subtype was evaluated using the Delirium Motor Subtype Scale (DMSS). Results 955 residents, from 32 Italian NHs with a mean age of 84.72 ± 7.78 years were included. According to the 4AT, delirium was present in 260 (27.2%) NHs residents, mainly hyperactive (35.4%) or mixed subtypes (20.7%). Antidepressant treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with lower delirium prevalence in univariate and multivariate analyses. Conclusions The high prevalence of delirium in NHs highlights the need to systematically assess its occurrence in this care settings. The inverse association between SSRIs and delirium might imply a possible preventive role of this class of therapeutic agents against delirium in NHs, yet further studies are warranted to ascertain any causal relationship between SSRIs intake and reduced delirium incidence.

Abstract Background Older subjects are at risk of elevated intestinal permeability (IP) which can lead to immune system activation and low-grade systemic inflammation. Dietary changes are a potential strategy to reduce IP. The MaPLE project evaluated the hypothesis that increasing (poly)phenol intake would beneficially impact on several important markers and pathways related to IP. The objective of the present study was to assess the effects of the MaPLE (poly)phenol-rich diet (PR-diet) on additional IP-related biomarkers and any relationships between biomarker responses. Methods A randomised, controlled, crossover study was performed involving 51 participants (≥ 60 y) with increased IP, as determined by serum zonulin levels. Participants were randomly assigned to one of two intervention groups: a control diet (C-diet) or a PR-diet. Each intervention lasted 8 weeks and was separated by an 8-week washout period. For the present study, serum and faecal samples were used to measure zonula occludens-1 (ZO-1), occludin, adiponectin, calprotectin, faecal calprotectin, soluble cluster of differentiation 14 (sCD14), interleukin-6 receptor (IL-6R), and vascular endothelial-cadherin (VEC) levels using quantitative ELISA assays. Data were analysed using ANOVA, and Spearman and network correlation analysis were performed to identify the relationship among biomarkers at baseline. Results Among the different markers analysed, a significant reduction was observed for faecal and serum calprotectin (p = 0.0378 and p = 0.0186, respectively) following the PR-diet, while a significant increase in ZO-1 was found (p = 0.001) after both the intervention periods (PR-diet and C-diet). In addition, a time effect was observed for VEC levels showing a reduction (p = 0.038) following the PR-diet. Based on network correlation analysis, two clusters of correlations were identified: one cluster with high levels of serum calprotectin, faecal calprotectin, sCD14, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and bacterial DNAemia (16 S rRNA gene copies), with potential inflammatory-induced intestinal permeability. Differently, the other cluster had high levels of serum occludin, IL-6R, soluble intercellular adhesion molecule-1 (sICAM-1) and VEC, with potential inflammatory-induced endothelial dysfunction. Conclusions Overall, this study provides further support to the hypothesis that a (poly)phenol-rich diet may help to ameliorate intestinal permeability-associated conditions. In this regard, calprotectin might represent a promising biomarker since it is a protein that typically increases with age and it is considered indicative of intestinal and systemic inflammation. Further research is needed to develop targeted (poly)phenol-rich diets against age-related gut dysfunction and inflammation. Trial registration 28/04/2017; ISRCTN10214981; https://doi.org/10.1186/ISRCTN10214981 .

Abstract Background Multimorbidity (MM) is generally defined as the presence of 2 or more chronic diseases in the same patient and seems to be frequently associated with frailty and poor quality of life. However, the complex interplay between MM and functional status in hospitalized older patients has not been fully elucidated so far. Here, we implemented a 2-step approach, combining cluster analysis and association rule mining to explore how patterns of MM and disease associations change as a function of disability. Methods This retrospective cohort study included 3366 hospitalized older patients discharged from acute care units of Ancona and Cosenza sites of Italian National Institute on Aging (INRCA-IRCCS) between 2011 and 2017. Cluster analysis and association rule mining (ARM) were used to explore patterns of MM and disease associations in the whole population and after stratifying by dependency in activities of daily living (ADL) at discharge. Sensitivity analyses in men and women were conducted to test for robustness of study findings. Results Out of 3366 included patients, 78% were multimorbid. According to functional status, 22.2% of patients had no disability in ADL (functionally independent group), 22.7% had 1 ADL dependency (mildly dependent group), and 57.4% 2 or more ADL impaired (moderately-severely dependent group). Two main MM clusters were identified in the whole general population and in single ADL groups. ARM revealed interesting within-cluster disease associations, characterized by high lift and confidence. Specifically, in the functionally independent group, the most significant ones involved atrial fibrillation (AF)-anemia and chronic kidney disease (CKD) (lift = 2.32), followed by coronary artery disease (CAD)-AF and heart failure (HF) (lift = 2.29); in patients with moderate-severe ADL disability, the most significant ARM involved CAD-HF and AF (lift = 1.97), thyroid dysfunction and AF (lift = 1.75), cerebrovascular disease (CVD)-CAD and AF (lift = 1.55), and hypertension-anemia and CKD (lift = 1.43). Conclusions Hospitalized older patients have high rates of MM and functional impairment. Combining cluster analysis to ARM may assist physicians in discovering unexpected disease associations in patients with different ADL status. This could be relevant in the view of individuating personalized diagnostic and therapeutic approaches, according to the modern principles of precision medicine.

BackgroundOnce the pandemic ended, SARS-CoV-2 became endemic, with flare-up phases. COVID-19 disease can still have a significant clinical impact, especially in older patients with multimorbidity and frailty.ObjectiveThis study aims at evaluating the main characteristics associated to in-hospital mortality among data routinely collected upon admission to identify older patients at higher risk of death.MethodsThe present study used data from Gerocovid-acute wards, an observational multicenter retrospective-prospective study conducted in geriatric and internal medicine wards in subjects ≥60 years old during the COVID-19 pandemic. Seventy-one routinely collected variables, including demographic data, living arrangements, smoking habits, pre-COVID-19 mobility, chronic diseases, and clinical and laboratory parameters were integrated into a web-based machine learning platform (Just Add Data Bio) to identify factors with the highest prognostic relevance. The use of artificial intelligence allowed us to avoid variable selection bias, to test a large number of models and to perform an internal validation.ResultsThe dataset was split into training and test sets, based on a 70:30 ratio and matching on age, sex, and proportion of events; 3,520 models were set out to train. The three predictive algorithms (optimized for performance, interpretability, or aggressive feature selection) converged on the same model, including 12 variables: pre-COVID-19 mobility, World Health Organization disease severity, age, heart rate, arterial blood gases bicarbonate and oxygen saturation, serum potassium, systolic blood pressure, blood glucose, aspartate aminotransferase, PaO2/FiO2 ratio and derived neutrophil-to-lymphocyte ratio.ConclusionBeyond variables reflecting the severity of COVID-19 disease failure, pre-morbid mobility level was the strongest factor associated with in-hospital mortality reflecting the importance of functional status as a synthetic measure of health in older adults, while the association between derived neutrophil-to-lymphocyte ratio and mortality, confirms the fundamental role played by neutrophils in SARS-CoV-2 disease.

BackgroundPrognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning.Materials and methodsA retrospective longitudinal study was conducted in a real-world sample of older diabetic patients afferent to the outpatient facilities of the Diabetology Unit of the IRCCS INRCA Hospital of Ancona (Italy). A total of 1,001 T2D patients aged more than 70 years were consecutively evaluated by a multidimensional geriatric assessment, including physical performance evaluated using the Short Physical Performance Battery (SPPB). The mortality was assessed during a 5-year follow-up. We used the automatic machine-learning (AutoML) JADBio platform to identify parsimonious mathematical models for risk stratification.ResultsOf 977 subjects included in the T2D cohort, the mean age was 76.5 (SD: 4.5) years and 454 (46.5%) were men. The mean follow-up time was 53.3 (SD:15.8) months, and 209 (21.4%) patients died by the end of the follow-up. The JADBio AutoML final model included age, sex, SPPB, chronic kidney disease, myocardial ischemia, peripheral artery disease, neuropathy, and myocardial infarction. The bootstrap-corrected concordance index (c-index) for the final model was 0.726 (95% CI: 0.687–0.763) with SPPB ranked as the most important predictor. Based on the penalized Cox regression model, the risk of death per unit of time for a subject with an SPPB score lower than five points was 3.35 times that for a subject with a score higher than eight points (P-value

Abstract Background Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. Results BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65–99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. Conclusions The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.

Abstract Background The Neutrophil-to-lymphocyte ratio (NLR) is a marker of poor prognosis in hospitalized older patients with different diseases, but there is still no consensus on the optimal cut-off value to identify older patients at high-risk of in-hospital mortality. Therefore, in this study we aimed at both validating NLR as a predictor of death in older hospitalized patients and assess whether the presence of specific acute diseases can modify its predictive value. Methods This prospective cohort study included 5034 hospitalizations of older patients admitted to acute care units in the context of the ReportAge study. NLR measured at admission was considered as the exposure variable, while in-hospital mortality was the outcome of the study. ROC curves with Youden’s method and restricted cubic splines were used to identify the optimal NLR cut-off of increased risk. Cox proportional hazard models, stratified analyses, and Kaplan–Meier survival curves were used to analyse the association between NLR and in-hospital mortality. Results Both continuous and categorical NLR value (cut-off ≥ 7.95) predicted mortality in bivariate and multivariate prognostic models with a good predictive accuracy. The magnitude of this association was even higher in patients without sepsis, congestive heart failure, and pneumonia, and those with higher eGFR, albumin, and hemoglobin (p

Abstract Polypharmacy in older adults is associated with multiple negative consequences that may affect muscular function, independently from the presence of medical conditions. The aim of this systematic review and meta‐analysis was to investigate the association of sarcopenia with polypharmacy and higher number of medications. A systematic literature search of observational studies using PubMed, Web of Science, Scopus and Cochrane Library databases was conducted from inception until June 2022. To determine if sarcopenia is associated with a higher risk of polypharmacy and increased number of medications, a meta‐analysis using a random‐effects model was used to calculate the pooled effects (CRD42022337539). Twenty‐nine studies were included in the systematic review and meta‐analysis. Sarcopenia was associated with a higher prevalence of polypharmacy (odds ratio [OR]: 1.65, 95% confidence interval [CI] [1.23, 2.20], I2 = 84%, P

Introduction A prescribing cascade occurs when a drug is prescribed to manage the often unrecognised side effect of another drug; these cascades are of particular concern for older adults who are at heightened risk for drug-related harm. It is unknown whether, and to what extent, gender bias influences physician decision-making in the context of prescribing cascades. The aim of this transnational study is to explore the potential impact of physician implicit gender biases on prescribing decisions that may lead to the initiation of prescribing cascades in older men and women in two countries, namely: Canada and Italy.Methods and analysis Male and female primary care physicians at each site will be randomised 1:1 to a case vignette that features either a male or female older patient who presents with concerns consistent with the side effect of a medication they are taking. During individual interviews, while masked to the true purpose of the study, participants will read the vignette and use the think-aloud method to describe their ongoing thought processes as they consider the patient’s concerns and determine a course of action. Interviews will be recorded, transcribed verbatim and thematic analysis will be conducted to highlight differences in decisions in the interviews/transcripts, using a common analytical framework across the sites.Ethics and dissemination This study has received ethics approval at each study site. Verbal informed consent will be received from participants prior to data collection and all data will be deidentified and stored on password-protected servers. Results of this study will be disseminated through peer-reviewed journal articles and presented at relevant national and international conferences.

Abstract Background Dysphagia is a frequent condition in older nursing home residents (NHRs) which may cause malnutrition and death. Nevertheless, its prevalence is still underestimated and there is still debate about the appropriateness and efficacy of artificial nutrition (AN) in subjects with severe dysphagia. The aim is to assess the prevalence of dysphagia in European and Israeli NHRs, its association with mortality, and the relationship of different nutritional interventions, i.e. texture modified diets and AN—with weight loss and mortality. Methods A prospective observational study of 3451 European and Israeli NHRs older than 65 years, participating in the SHELTER study from 2009 to 2011, at baseline and after 12 months. All residents underwent a standardized comprehensive evaluation using the interRAI Long Term Care Facility (LTCF). Cognitive status was assessed using the Cognitive Performance Scale (CPS), functional status using Activities of Daily Living (ADL) Hierarchy scale. Trained staff assessed dysphagia at baseline by clinical observation. Data on weight loss were collected for all participants at baseline and after 12 months. Deaths were registered by NH staff. Results The prevalence of dysphagia was 30.3%. During the one-year follow-up, the mortality rate in subjects with dysphagia was significantly higher compared with that of non-dysphagic subjects (31.3% vs 17.0%,p = 0,001). The multivariate analysis showed that NHRs with dysphagia had 58.0% higher risk of death within 1 year compared with non-dysphagic subjects (OR 1.58, 95% CI, 1.31–1.91). The majority of NHRs with dysphagia were prescribed texture modified diets (90.6%), while AN was used in less than 10% of subjects. No statistically significant difference was found concerning weight loss and mortality after 12 months following the two different nutritional treatments. Conclusions Dysphagia is prevalent among NHRs and it is associated with increased mortality, independent of the nutritional intervention used. Noticeably, after 12 months of nutritional intervention, NHRs treated with AN had similar mortality and weight loss compared to those who were treated with texture modified diets, despite the clinical conditions of patients on AN were more compromised.

Abstract We evaluated the effect of Acetyl-cholinesterase-inhibitors (AChEIs) on cognitive decline and overall survival in a large sample of older patients with late onset Alzheimer’s disease (LOAD), vascular dementia (VD) or Lewy body disease (LBD) from a real world setting. Patients with dementia enrolled between 2005 and 2020 by the "Alzheimer's Disease Research Centers" were analysed; the mean follow-up period was 7.9 years. A 1:1 propensity score matching was performed generating a cohort of 1.572 patients (786 treated [AChEIs +] and 786 not treated [AChEIs-] with AChEIs. The MMSE score was almost stable during the first 6 years of follow up in AChEIs + and then declined, while in AChEIs− it progressively declined so that at the end of follow-up (13.6 years) the average decrease in MMSE was 10.8 points in AChEIs- compared with 5.4 points in AChEIs + (p

Background: COVID-19 continues to circulate around the world with multiple different strains being active at once. While diagnosis with antigen and molecular testing is more readily available, there is still room for alternative methods of diagnosis, particularly in out-of-hospital settings, e.g., home or nursing homes, and in low–medium income countries, where testing may not be readily available. Study Objectives: To evaluate the performance of two modified corona score methods compared with a traditional corona score approach to identify patients with COVID-19. Methods: This was a retrospective multicenter study performed to compare the ability to predict SARS-CoV-2 test results on a nasopharyngeal swab between the corona scores and two novel corona scores (modified 1 corona score (M1CS) and modified 2 corona score (M2CS)). The M1CS included lung ultrasound (LUS) and chest X-ray (CXR) results, while the M2SC only utilized LUS findings without CXRs. Emergency physicians performed point-of-care LUS and a physical examination upon admission to the emergency department. Results: Subjects positive for SARS-CoV-2 were older and had higher ferritin levels and temperature and lower diastolic blood pressure and oxygen saturation. The two groups differed on corona score and modified corona scores (p < 0.001 for all). SARS-CoV-2-positive patients had fewer pleural line irregularities (p = 0.025) but presented more frequently with an interstitial pattern on CXRs (p < 0.001). Conclusions: In our study, LUS alone provided a valuable contribution to the corona score and improved its performance more than when CXR results were included. These results suggest that resource-limited areas where CXRs may be unavailable or prohibitively expensive can utilize an ultrasound as the sole imaging modality without a loss of diagnostic performance for SARS-CoV-2 pneumonia diagnosis.

Abstract Background Dietary biomarkers may complement dietary intake assessment made by dietary questionnaires. We developed an a-posteriori dietary biomarkers score based on Mediterranean diet food groups and evaluated its association with mortality. Methods 642 participants (56% female), aged ≥65 years, with complete data on dietary biomarkers were followed during 20 years in the InCHIANTI cohort study (Tuscany, Italy). The main outcomes were all-cause, cardiovascular, and cancer mortality. Dietary biomarkers were selected from literature and from correlation analyses with dietary intakes of Mediterranean diet food groups in the study. The baseline levels of the following dietary biomarkers were chosen: urinary total polyphenols and resveratrol metabolites, and plasma carotenoids, selenium, vitamin B12, linolenic, eicosapentaenoic and docosahexaenoic acids, and the mono-unsaturated/saturated fatty acid ratio. Associations of the Mediterranean diet score using dietary biomarkers and a validated food frequency questionnaire (FFQ) (as tertiles) with mortality were assessed through Cox regression. Results During the 20-year follow-up [median (Q1–Q3), 14 (8–18) years], and 435 deaths occurred (139 from cardiovascular diseases and 89 from cancer-related causes). In the fully adjusted models, the dietary biomarker-Mediterranean diet score was inversely associated with all-cause (HRT3vs.T1 0.72; 95%CI 0.56–0.91) and cardiovascular (HRT3vs.T1 0.60; 95%CI 0.38–0.93), but not with cancer mortality. Associations between the FFQ-Mediterranean diet score and mortality were not statistically significant. Conclusions A greater adherence at baseline to a Mediterranean diet assessed by a dietary biomarker score was associated with a lower risk of mortality in older adults during a 20-year follow-up. The measurement of dietary biomarkers may contribute to guide individualized dietary counseling to older people. Trial registration NCT01331512

BackgroundMultimorbidity (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.MethodsThis 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.DiscussionThis 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.

Abstract The increased presence of bacteria in blood is a plausible contributing factor in the development and progression of aging-associated diseases. In this context, we performed the quantification and the taxonomic profiling of the bacterial DNA in blood samples collected from forty-three older subjects enrolled in a nursing home. Quantitative PCR targeting the 16S rRNA gene revealed that all samples contained detectable amounts of bacterial DNA with a concentration that varied considerably between subjects. Correlation analyses revealed that the bacterial DNAemia (expressed as concentration of 16S rRNA gene copies in blood) significantly associated with the serum levels of zonulin, a marker of intestinal permeability. This result was confirmed by the analysis of a second set of blood samples collected from the same subjects. 16S rRNA gene profiling revealed that most of the bacterial DNA detected in blood was ascribable to the phylum Proteobacteria with a predominance of the genus Pseudomonas. Several control samples were also analyzed to assess the influence of contaminant bacterial DNA potentially originating from reagents and materials. The data reported here suggest that para-cellular permeability of epithelial (and, potentially, endothelial) cell layers may play an important role in bacterial migration into the bloodstream. Bacterial DNAemia is likely to impact on several aspects of host physiology and could underpin the development and prognosis of various diseases in older subjects.

Abstract Background During aging, alterations of the intestinal microbial ecosystem can occur contributing to immunosenescence, inflamm-aging and impairment of intestinal barrier function (increased intestinal permeability; IP). In the context of a diet-microbiota-IP axis in older subjects, food bioactives such as polyphenols may play a beneficial modulatory role. Methods MaPLE is a project centered on a randomized, controlled cross-over dietary intervention trial [polyphenol-rich diet (PR-diet) versus control diet (C-diet)] targeted to older people (≥ 60 y) living in a well-controlled setting (i.e. nursing home). The 8-week interventions are separated by an 8-week wash-out period. Three small portions per day of selected polyphenol-rich foods are consumed during intervention in substitution of other comparable products within the C-diet. Biological samples are collected before and after each treatment period to evaluate markers related to IP, inflammation, vascular function, oxidative stress, gut and blood microbiomics, metabolomics. A sample size of 50 subjects was defined based on IP as primary outcome. Discussion Evidence that increasing the consumption of polyphenol-rich food products can positively affect intestinal microbial ecosystem resulting in reduced IP and decreased translocation of inflammogenic bacterial factors into the bloodstream will be provided. The integration of data from gut and blood microbiomics, metabolomics and other IP-related markers will improve the understanding of the beneficial effect of the intervention in the context of polyphenols−microbiota−IP interactions. Finally, findings obtained will provide a proof of concept of the reliability of the dietary intervention, also contributing to future implementations of dietary guidelines directed to IP management in the older and other at risk subjects. Trial registration The trial is registered at (ISRCTN10214981); April 28, 2017.

(1) Background: During the COVID-19 pandemic, rapid and reliable diagnostic tools are needed for detecting SARS-CoV-2 infection in urgent cases at admission to the hospital. We aimed to assess the performances of the rapid molecular VitaPCR™ test (Menarini Diagnostics) in a sample of older adults admitted to the Emergency Department of two Italian hospitals (2) Methods: The comparison between the rapid VitaPCR™ and the RT-PCR was performed in 1695 samples. Two naso-pharyngeal swab samplings from each individual were obtained and processed using the VitaPCR™ and the RT-PCR for the detection of SARS-CoV-2 (3) Results: VitaPCR™ exhibited good precision (

Background: Hospitalized older patients are particularly exposed to adverse health outcomes.Objective: In this study, we aimed at investigating the prognostic interactions between disability in basic activities of daily living (BADL), cognitive impairment, low handgrip strength, anticholinergic cognitive burden (ACB), and depression on 1-year mortality.Setting and Subjects: Our series consisted of 503 older patients discharged from acute care hospitals.Methods: Disability in at least one BADL, ACB, depression, cognitive impairment, and low handgrip strength was considered in the analysis. One-year mortality was investigated by Cox regression analysis and prognostic interactions among study variables were assessed by survival tree analysis.Results: Basic activities of daily living disability, ACB, cognitive impairment, and low handgrip strength were significantly associated with 1-year mortality. Survival tree analysis showed that patients with BADL disability and high ACB carried the highest risk of poor survival [hazard ratio (HR): 16.48 (2.63–74.72)], followed by patients with BADL disability and low ACB (HR: 8.43, 95% CI: 1.85–38.87). Patients with cognitive impairment and no BADL disability were characterized by a lower but still significant risk of mortality (HR: 6.61, 95% CI: 1.51–28.97) and those with high ACB scores and good cognitive and functional performance (HR: 5.28, 95% CI: 1.13–24.55).Conclusion: Basic activities of daily living dependency, cognitive impairment, and ACB score were the three main predictors of 1-year mortality among patients discharged from acute care hospitals; the interaction between BADL dependency and ACB score wasfound to significantly affect survival. Early identification of such high-risk patients may help tailor targeted interventions to counteract their detrimental effects on prognosis.

Abstract Background Delirium is a geriatric syndrome that presents in 1 out of 5 hospitalized older patients. It is also common in the community, in hospices, and in nursing homes. Delirium prevalence varies according to clinical setting, with rates of under 5% in minor elective surgery but up to 80% in intensive care unit patients. Delirium has severe adverse consequences, but despite this and its high prevalence, it remains undetected in the majority of cases. Optimal delirium care requires an interdisciplinary, multi-dimensional diagnostic and therapeutic approach involving doctors, nurses, physiotherapists, and occupational therapists. However, there are still important gaps in the knowledge and management of this syndrome. Main body The objective of this paper is to promote the interdisciplinary approach in the prevention and management of delirium as endorsed by a delirium society (European Delirium Association, EDA), a geriatrics society (European Geriatric Medicine Society, EuGMS), a nursing society (European Academy of Nursing Science, EANS), an occupational therapy society (Council of Occupational Therapists for European Countries, COTEC), and a physiotherapy society (International Association of Physical Therapists working with Older People of the World Confederation for Physical Therapy, IPTOP/WCPT). Short conclusion In this paper we have strongly promoted and supported interdisciplinary collaboration underlying the necessity of increasing communication among scientific societies. We have also provided suggestions on how to fill the current gaps via improvements in undergraduate and postgraduate delirium education among European Countries.

Abstract Background The aim of this trial is to evaluate the effect of SENATOR software on incident, adverse drug reactions (ADRs) in older, multimorbid, hospitalized patients. The SENATOR software produces a report designed to optimize older patients’ current prescriptions by applying the published STOPP and START criteria, highlighting drug-drug and drug-disease interactions and providing non-pharmacological recommendations aimed at reducing the risk of incident delirium. Methods We will conduct a multinational, pragmatic, parallel arm Prospective Randomized Open-label, Blinded Endpoint (PROBE) controlled trial. Patients with acute illnesses are screened for recruitment within 48 h of arrival to hospital and enrolled if they meet the relevant entry criteria. Participants’ medical history, current prescriptions, select laboratory tests, electrocardiogram, cognitive status and functional status are collected and entered into a dedicated trial database. Patients are individually randomized with equal allocation ratio. Randomization is stratified by site and medical versus surgical admission, and uses random block sizes. Patients randomized to either arm receive standard routine pharmaceutical clinical care as it exists in each site. Additionally, in the intervention arm an individualized SENATOR-generated medication advice report based on the participant’s clinical and medication data is placed in their medical record and a senior medical staff member is requested to review it and adopt any of its recommendations that they judge appropriate. The trial’s primary outcome is the proportion of patients experiencing at least one adjudicated probable or certain, non-trivial ADR, during the index hospitalization, assessed at 14 days post-randomization or at index hospital discharge if it occurs earlier. Potential ADRs are identified retrospectively by the site researchers who complete a Potential Endpoint Form (one per type of event) that is adjudicated by a blinded, expert committee. All occurrences of 12 pre-specified events, which represent the majority of ADRs, are reported to the committee along with other suspected ADRs. Participants are followed up 12 (+/− 4) weeks post-index hospital discharge to assess medication quality and healthcare utilization. This is the first clinical trial to examine the effectiveness of a software intervention on incident ADRs and associated healthcare costs during hospitalization in older people with multi-morbidity and polypharmacy. Trial registration number Clinicaltrials.gov NCT02097654, 27 March 2014.

Abstract Background Physical activity (PA) has health benefits for people with type 2 diabetes (T2D). Indeed, regular PA is considered an important part of any T2D management plan, yet most patients adopt a sedentary lifestyle. Exercise referral schemes (ERS) have the potential to effectively promote physical activity among T2D patients, and their effectiveness may be enhanced when they are supported by computer-based technologies. The ‘TRIPL-A’ study (i.e., a TRIal to promote PhysicaL Activity among patients in the young-old age affected by T2D) aims to assess if realizing an innovative ERS, based on a strong partnership among general practitioners, specialist physicians, exercise specialists, and patients, and supported by a web-based application (WBA), can effectively lead sedentary older T2D patients to adopt an active lifestyle. Methods A randomized controlled design will be used, and an ERS, supported by a WBA, will be implemented. 300 physically inactive T2D patients (aged 65–74 years) will be assigned to either an intervention or control arm. Control arm patients will only receive behavioral counseling on physical activity and diet, while intervention arm patients will also undergo an 18-month (3 day/week), discontinuously supervised aerobic exercise training program. The trial will be divided into six three-month periods: during first, third and fifth period, an exercise specialist will supervise the training sessions and, using the WBA, prescribe exercise progression and monitor exercise adherence. Patients will exercise on their own in the other periods. Patients’ sedentary behaviors (primary outcome), PA level, fitness status, metabolic profile, psychological well-being, quality of life, and use of health care services (secondary outcomes) will be assessed at baseline and at 6, 12, and 18 months from baseline. Repeated measure ANCOVAs will be used to compare the intervention and control arm with respect to each study outcome measure. Discussion Primary and secondary outcome results will allow us to evaluate the effectiveness of an ERS, specifically designed for the management of T2D clinical conditions and supported by a WBA, in promoting PA within Italian primary care settings. Trial registration This trial is retrospectively registered under the Australian New Zealand Clinical Trials Registry (reference number: ACTRN12618001164280; registered 13 July 2018).

Summary: Polypharmacy is very common in older adults and increases the risk of inappropriate and unsafe prescribing for older adults. Older adults, particularly women (who make up the majority of this age group), are at the greatest risk for drug-related harm. Therefore, optimising drug prescribing for older people is very important. Identifying potentially inappropriate medications and opportunities for judicious deprescribing processes are intrinsically linked, complementary, and essential for optimising medication safety. This Review focuses on optimising prescribing for older adults by reducing doses or stopping drugs that are potentially harmful or that are no longer needed. We explore how sex (biological) and gender (sociocultural) factors are important considerations in safe drug prescribing. We conclude by providing a practical approach to optimising medication safety that clinicians can routinely apply to the care of their older patients, highlighting how sex and gender considerations inform medication decision making.

The need for major information in meta-research (i.e. the part of medicine interested in systematic reviews [SRs] and meta-analyses [MAs]) is increasing. In the last years we are observing an exponential rate of publications as SRs/MAs in geriatric medicine. In order to better assess the interest in meta-research, we proposed a survey to know the knowledge and the needs in meta-research in geriatrics. A short survey (about 5 minutes) was freely available in the Italian Society of Hospital and Community Geriatrics (SIGOT) website and diffused in social networks. The survey was available during the entire 2019. The survey regards demographic information, previous research activities and the knowledge of the participant on meta-research. Altogether, 148 participants mainly men (=65.5%) and mainly aged 36 to 44 years and working in hospital from all Italian regions completed the survey. Responders read more than 20 articles in the previous year (=58.1%), including 10-20 SRs/MAs (25%). Many respondents (41.9%) had published >20 articles during their life. At the same time, a consistent part of the respondents recognized the importance of metaresearch for clinical practice and almost all the participants recognized that metaresearch has changed their daily clinical approach to the patient. Almost all the participants would like to have more training in meta-research suggesting that SIGOT should organize training courses for metaresearch in geriatric medicine. In conclusion, our survey showed that the interest in SRs/MAs is high, whilst the knowledge is still limited suggesting that education is needed to fill the gap in this field.

Abstract Background All proposed definitions of sarcopenia include the measurement of muscle mass, but the techniques and threshold values used vary. Indeed, the literature does not establish consensus on the best technique for measuring lean body mass. Thus, the objective measurement of sarcopenia is hampered by limitations intrinsic to assessment tools. The aim of this study was to review the methods to assess muscle mass and to reach consensus on the development of a reference standard. Methods Literature reviews were performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis working group on frailty and sarcopenia. Face‐to‐face meetings were organized for the whole group to make amendments and discuss further recommendations. Results A wide range of techniques can be used to assess muscle mass. Cost, availability, and ease of use can determine whether the techniques are better suited to clinical practice or are more useful for research. No one technique subserves all requirements but dual energy X‐ray absorptiometry could be considered as a reference standard (but not a gold standard) for measuring muscle lean body mass. Conclusions Based on the feasibility, accuracy, safety, and low cost, dual energy X‐ray absorptiometry can be considered as the reference standard for measuring muscle mass.

Abstract However, semantics aside, we think that DXA can indeed serve as a reference standard for measuring muscle mass. Obviously, CT and MRI are advanced techniques that can and have been used to obtain important information such as muscle size/volume and more recently amount and distribution of intra‐ and intermuscular adipose tissue. Also individual muscles can be assessed separately. However, with respect to muscle mass, the comparison of DXA with CT/MRI is rather difficult because DXA and QCT/MRI measure different physical parameters

Hypoglycaemia can cause cardiac arrhythmias such as QT interval prolongation and ventricular arrhythmias. Supraventricular arrhythmias and sinus bradycardia were rarely reported. We present the clinical case of an 84- year-old man who developed a persistent bradycardia after a hypoglycaemic episode. After restoration of normoglycaemia, bradycardia persisted for almost eighteen hours, without QT prolongation or any symptoms. Hypoglycaemia is an unusual cause of bradyarrhytmias mainly mediated by neurologic and endocrine systems. Our clinical case supports recent recommendations for more relaxed inpatient glycaemic targets in frail older adults who may be particularly vulnerable to hypoglycaemia and its consequences.

The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects with intestinal permeability enrolled within the MaPLE (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) intervention trial, to evaluate its association with clinical, metabolic and dietary markers. DNA damage in peripheral blood mononuclear cells was assessed by the comet assay in 49 older subjects participating in the study. Clinical and metabolic markers, markers of inflammation, vascular function and intestinal permeability were determined in serum. Food intake was estimated by weighted food diaries. On the whole, a trend towards higher levels of DNA damage was observed in men compared to women (p = 0.071). A positive association between DNA damage and clinical/metabolic markers (e.g., uric acid, lipid profile) and an inverse association with dietary markers (e.g., vitamin C, E, B6, folates) were found and differed based on sex. By considering the importance of DNA stability during aging, the results obtained on sex differences and the potential role of dietary and metabolic factors on DNA damage underline the need for further investigations in a larger group of older adults to confirm the associations found and to promote preventive strategies.

The impact of the COVID-19 pandemic on multidrug-resistant (MDR) bacteria is unknown. The purpose of this study was to assess prevalence, etiology, and association with mortality of MDR bacteria in older adult patients before and after the first peak of the COVID-19 pandemic in Italy. An observational retrospective study was conducted in two geriatric wards of the Azienda Ospedaliera Ospedali Riuniti Marche Nord, Fano, and of the INRCA, IRCCS, Ancona, in the Marche Region, Italy, from December 2019 to February 2020 and from May to July 2020. A total of 73 patients (mean age 87.4 ± 5.9, 27.4% men) and 83 cultures (36 pre-COVID-19 and 47 post-COVID-19) were considered. Overall, 46 cultures (55.4%) reported MDR bacteria (50% in pre- and 59.6% in post-COVID-19 period, p = 0.384). MDR bacteria in bloodstream significantly increased in post-COVID-19 period (68.8% vs. 40.0% p = 0.038) and MDR bacteria in urine did not change (51.6 vs. 54.8%, p = 0.799). Escherichia coli was the main MDR bacterium in pre-COVID-19, p = 0.082 and post-COVID-19, p = 0.026. Among patients with MDR infection, in-hospital mortality was 37.5% and 68.8% in pre- and post-COVID-19, respectively (p = 0.104), and mortality at 30 days was higher in post-COVID-19 period (78.9% vs. 27.3%, p = 0.012). An increased number of MDR bacteria in bloodstream and mortality after MDR infection have been observed in the post-COVID-19 period.

Atrial fibrillation (AF) and venous thromboembolism (VTE), which includes deep vein thrombosis and pulmonary embolism, are conditions that increase with age. Anticoagulant therapy is strongly recommended both in patients with AF for the prevention of cardioembolic stroke, and for treatment of VTE and prevention of recurrent VTE. Until recently, vitamin K antagonists (VKAs) were the only oral drugs for long-term anticoagulation. In the past decade, four direct oral anticoagulants (DOACs) were approved: a direct thrombin inhibitor (dabigatran) and three factor Xa inhibitors (apixaban, rivaroxaban, edoxaban). Despite increasing evidence demonstrating the efficacy and safety of DOACs in older patients, there are still gray areas where the use of VKAs might be valuable.

Globally, stroke remains a leading cause of death and disability, with older adults disproportionately affected. Numerous non-pharmacological stroke rehabilitation approaches are in use to address impairments, but their efficacy in older persons is largely unknown. This systematic review examined the evidence for such interventions as part of the Optimal Evidence-Based Non-Drug Therapies in Older Persons (ONTOP) project conducted under an European Union funded project called the Software Engine for the Assessment and Optimisation of Drug and Non-Drug Therapies in Older Persons (SENATOR) [http://www.senator-project.eu]. A Delphi panel of European geriatric experts agreed activities of daily living and disability to be of critical importance as stroke rehabilitation outcomes. A comprehensive search strategy was developed and five databases (Pubmed, CINAHL, Embase, PsycInfo and Cochrane Database of Systematic Reviews) searched for eligible systematic reviews. Primary studies meeting our criteria (non-pharmacologic interventions, involving stroke survivors aged ≥65 years, assessing activities of daily living and/or disability as outcome) were then identified from these reviews. Eligible papers were double reviewed, and due to heterogeneity, narrative analysis performed. Cochrane risk of bias and GRADE assessment tools were used to assess bias and quality of evidence, allowing us to make recommendations regarding specific non-pharmacologic rehabilitation in older stroke survivors. In total, 72 primary articles were reviewed spanning 14 types of non-pharmacological intervention. Non-pharmacological interventions based on physiotherapy and occupational therapy techniques improved activities of daily living amongst older stroke survivors. However, no evidence was found to support use of any non-pharmacological approach to benefit older stroke survivors' disability. Evidence was limited by poor study quality and the small number of studies targeting older stroke survivors. We recommend future studies explore such interventions exclusively in older adult populations and improve methodological and outcome reporting.

Despite older adults use emergency department more appropriately than other age groups, there is a significant share of admissions that can be considered potentially preventable.To identify socio-demographic characteristics and health care resources use of older adults admitted to emergency department for a potentially preventable visit.Data come from the Multipurpose Survey "Health conditions and use of health services", edition 2012-2013. A stratified multi-stage probability design was used to select a sample using municipal lists of households.50474 community dwelling Italians were interviewed. In this analysis, 27003 subjects aged 65 years or older were considered.Potentially preventable visits were defined as an emergency department visit that did not result in inpatient admission. Independent variables were classified based on the socio-behavioral model of Andersen-Newman. Descriptive statistics and a logistic regression model were developed.In the twelve months before the interview 3872 subjects (14.3%) had at least one potentially preventable visit. Factors associated with an increased risk of a potentially preventable visit were older age (75-84 years: OR 1.096, CI 1.001-1.199; 85+years: OR 1.022, CI 1.071-1.391), at least one hospital admission (OR 3.869, IC 3.547-4.221), to waive a visit (OR 1.188, CI 1.017-1.389) or an exam (OR 1.300, CI 1.077-1.570). Factors associated with a lower risk were female gender (OR 0.893, CI 0.819-0.975), area of residence (Center: OR 0.850; CI 0.766-0.943; Islands: OR 0.617, CI 0.539-0.706, South: OR 0.560; CI 0.505-0.622), private paid assistance (OR 0.761, CI 0.602-0.962); a better health-related quality of life (PCS score 46-54: OR 0.744, CI 0.659-0.841; PCS score >55: OR 0.746, CI 0.644-0.865).Our study identified several characteristics associated with an increased risk of potentially preventable visits to the emergency department. This might allow the development of specific interventions to prevent the access of at risk subjects to the emergency department.

While the relationship between total cholesterol (TC) and cardiovascular disease (CVD) progressively weakens with aging, several studies have shown that low TC is associated with increased mortality in older individuals. However, the possible additive/synergic contribution of the two most important cholesterol rich fractions (LDL-C and HDL-C) to mortality risk has not been previously investigated. Our study aimed to investigate the relationship between baseline LDL-C and HDL-C, both separately and combined, and 9-years mortality in a sample of community dwelling older individuals from the InCHIANTI study.1044 individuals over 64 years were included. CVD and cancer mortality were defined by ICD-9 codes 390-459 and 140-239, respectively. LDL-C

The inevitable rise of the proportion of people aged [...]

Anemia, a common concern in geriatric population, is associated with several negative outcomes. The aim of this study was to investigate the independent prognostic value of anemia in the year after hospital discharge, analyzing its association with disability and mortality in a sample of older hospitalized patients. We evaluated 896 in-hospital older patients enrolled in the CRiteria to Assess Appropriate Medication Use among Elderly Complex Patients (CRIME) study, with assessment of hemoglobin levels at hospital admission and with follow-up data. We analyzed the risk of developing disability (in patients without pre-existing disability in activities of the daily living) and the likelihood of death (in the entire sample) in the 12 months after discharge according to presence and degree of anemia (defined by sex-specific World Health Organization criteria). Mean age of study participants was 81.2±7.4 years, 57.8% had prevalent anemia. In unadjusted analysis, anemia was strongly associated with functional status and survival. Nevertheless, the increased risk of disability and death was influenced by the coexistence of several clinical conditions associated with anemia. Indeed, using multivariate logistic regression analysis adjusted for potential confounders, the association with disability was strongly attenuated [severe anemia odds ratio (OR) 1.86, 95% confidence interval (CI): 0.96-3.58, mild-moderate anemia OR 1.05, 95% CI: 0.62-1.80] and the relationship with mortality was no longer significant [severe anemia hazard ratio (HR) 1.13, 95% CI: 0.73-1.75, mild-moderate anemia HR 1.14, 95% CI: 0.78-1.67]. In older hospitalized patients, anemia, despite not influencing mortality, might have a significant disabling effect. Anemia should not be considered as an inevitable epiphenomenon of aging but a condition able to worsen the quality of life.

BACKGROUND:Falls are common events in older people, which cause considerable morbidity and mortality. Non-pharmacological interventions are an important approach to prevent falls. There are a large number of systematic reviews of non-pharmacological interventions, whose evidence needs to be synthesized in order to facilitate evidence-based clinical decision making. OBJECTIVES:To systematically examine reviews and meta-analyses that evaluated non-pharmacological interventions to prevent falls in older adults in the community, care facilities and hospitals. METHODS:We searched the electronic databases Pubmed, the Cochrane Database of Systematic Reviews, EMBASE, CINAHL, PsycINFO, PEDRO and TRIP from January 2009 to March 2015, for systematic reviews that included at least one comparative study, evaluating any non-pharmacological intervention, to prevent falls amongst older adults. The quality of the reviews was assessed using AMSTAR and ProFaNE taxonomy was used to organize the interventions. RESULTS:Fifty-nine systematic reviews were identified which consisted of single, multiple and multifactorial non-pharmacological interventions to prevent falls in older people. The most frequent ProFaNE defined interventions were exercises either alone or combined with other interventions, followed by environment/assistive technology interventions comprising environmental modifications, assistive and protective aids, staff education and vision assessment/correction. Knowledge was the third principle class of interventions as patient education. Exercise and multifactorial interventions were the most effective treatments to reduce falls in older adults, although not all types of exercise were equally effective in all subjects and in all settings. Effective exercise programs combined balance and strength training. Reviews with a higher AMSTAR score were more likely to contain more primary studies, to be updated and to perform meta-analysis. CONCLUSIONS:The aim of this overview of reviews of non-pharmacological interventions to prevent falls in older people in different settings, is to support clinicians and other healthcare workers with clinical decision-making by providing a comprehensive perspective of findings.

Non-pharmacological intervention (e.g. multidisciplinary interventions, music therapy, bright light therapy, educational interventions etc.) are alternative interventions that can be used in older subjects. There are plenty reviews of non-pharmacological interventions for the prevention and treatment of delirium in older patients and clinicians need a synthesized, methodologically sound document for their decision making.We performed a systematic overview of systematic reviews (SRs) of comparative studies concerning non-pharmacological intervention to treat or prevent delirium in older patients. The PubMed, Cochrane Database of Systematic Reviews, EMBASE, CINHAL, and PsychINFO (April 28th, 2014) were searched for relevant articles. AMSTAR was used to assess the quality of the SRs. The GRADE approach was used to assess the quality of primary studies. The elements of the multicomponent interventions were identified and compared among different studies to explore the possibility of performing a meta-analysis. Risk ratios were estimated using a random-effects model. Twenty-four SRs with 31 primary studies satisfied the inclusion criteria. Based on the AMSTAR criteria twelve reviews resulted of moderate quality and three resulted of high quality. Overall, multicomponent non-pharmacological interventions significantly reduced the incidence of delirium in surgical wards [2 randomized trials (RCTs): relative risk (RR) 0.71, 95% Confidence Interval (CI) 0.59 to 0.86, I2=0%; (GRADE evidence: moderate)] and in medical wards [2 CCTs: RR 0.65, 95%CI 0.49 to 0.86, I2=0%; (GRADE evidence: moderate)]. There is no evidence supporting the efficacy of non-pharmacological interventions to prevent delirium in low risk populations (i.e. low rate of delirium in the control group)[1 RCT: RR 1.75, 95%CI 0.50 to 6.10 (GRADE evidence: very low)]. For patients who have developed delirium, the available evidence does not support the efficacy of multicomponent non-pharmacological interventions to treat delirium. Among single component interventions only staff education, reorientation protocol (GRADE evidence: very low)] and Geriatric Risk Assessment MedGuide software [hazard ratio 0.42, 95%CI 0.35 to 0.52, (GRADE evidence: moderate)] resulted effective in preventing delirium.In older patients multi-component non-pharmacological interventions as well as some single-components intervention were effective in preventing delirium but not to treat delirium.

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95 x 10(-46)). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78 x 10(-9)) and eicosapentanoic acid (EPA; p = 1.07 x 10(-14)). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; p = 1.1 x 10(-6)). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids.