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In clinical trials, biochemical markers provide useful information on the drug’s mode of action, therapeutic response and side effect monitoring and can act as surrogate endpoints. In pharmacological intervention development for sarcopenia management, there is an urgent need to identify biomarkers to measure in clinical trials and that could be used in the future in clinical practice. The objective of the current consensus paper is to provide a clear list of biochemical markers of musculoskeletal health and aging that can be recommended to be measured in Phase II and Phase III clinical trials evaluating new chemical entities for sarcopenia treatment. A working group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) proposed classifying biochemical markers into 2 series: biochemical markers evaluating musculoskeletal status and biochemical markers evaluating causal factors. For series 1, the group agreed on 4 biochemical markers that should be assessed in Phase II or Phase III trials (i.e., Myostatin-Follistatin, Brain Derived Neurotrophic Factor, N-terminal Type III Procollagen and Serum Creatinine to Serum Cystatin C Ratio – or the Sarcopenia Index). For series 2, the group agreed on 6 biochemical markers that should be assessed in Phase II trials (i.e., the hormones insulin-like growth factor-1 (IGF-I), dehydroepiandrosterone sulphate, and cortisol, and the inflammatory markers C-reactive protein (CRP), interleukin-6 and tumor necrosis factor-α), and 2 in Phase III trials (i.e., IGF-I and CRP). The group also proposed optional biochemical markers that may provide insights into the mode of action of pharmacological therapies. Further research and development of new methods for biochemical marker assays may lead to the evolution of these recommendations.

Prescribing cascades occur when a drug is prescribed to manage side effects of another drug, typically when a side effect is misinterpreted as a new condition. A consensus list of clinically important prescribing cascades that adversely affect older persons' health (i.e., where risks of the prescribing cascade usually exceed benefits) was developed to help identify, prevent, and manage prescribing cascades.Three rounds of a modified Delphi process were conducted with a multidisciplinary panel of 38 clinicians from six countries with expertise in geriatric pharmacotherapy. The clinical importance of 139 prescribing cascades was assessed in Round 1. Cascades highly rated by ≥ 70% of panelists were included in subsequent rounds. Factors influencing ratings in Rounds 1 and 3 were categorized. After three Delphi rounds, highly rated prescribing cascades were reviewed by the study team to determine the final list of clinically important cascades consistent with potentially inappropriate prescribing.After three rounds, 13 prescribing cascades were highly rated by panelists. Following a study team review, the final tool includes nine clinically important prescribing cascades consistent with potentially inappropriate prescribing. Panelists reported that their ratings were influenced by many factors (e.g., how commonly they encountered the medications involved and the cascade itself, the severity of side effects, availability of alternatives). The relative importance of these factors in determining clinical importance varied by panelist.A nine-item consensus-based list of clinically important prescribing cascades, representing potentially inappropriate prescribing, was developed. Panelists' decisions about what constituted a clinically important prescribing cascade were multi-factorial. This tool not only raises awareness about these cascades but will also help clinicians recognize these and other important prescribing cascades. This list contributes to the prevention and management of polypharmacy and medication-related harm in older people.

Patient perspectives are now widely recognized as a key element in the evaluation of health interventions. Therefore, the provision of specific and validated Patient Reported Outcome Measures that emphasize the lived experience of patients suffering from specific diseases is very important. In the field of sarcopenia, the only validated specific health-related quality of life (HRQoL) instrument available is the Sarcopenia Quality of Life questionnaire (SarQoL). This self-administrated HRQoL questionnaire, developed in 2015, consists of 55 items arranged into 22 questions and has currently been translated into 35 languages. Nineteen validation studies performed on SarQoL have consensually confirmed the capacity of SarQoL to detect difference in HRQoL between older people with and without sarcopenia, its reliability and its validity. Two further observational studies have also indicated its responsiveness to change. A short form SarQoL, including only 14 items has further been developed and validated to reduce the potential burden of administration. Research on the psychometric properties of SarQoL questionnaire is still encouraged as the responsiveness to change of SarQoL has not yet been measured in the context of interventional studies, as limited prospective data currently exist and as there is still not cut-off score to define a low HRQoL. In addition, SarQoL has mainly been used in community-dwelling older individuals with sarcopenia and would benefit to be studied in other types of populations. This review aims to provide to researchers, clinicians, regulators, pharmaceutical industries and other stakeholders a clear summary of comprehensive evidence on the SarQoL questionnaire published up to January 2023Query.

(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 healthy dietary patterns have been associated with lower risk for age-related cognitive decline. However, little is known about the specific role of dietary fibre on cognitive decline in older adults. Objective this study aimed to examine the association between dietary fibre and cognitive decline in older adults and to assess the influence of genetic, lifestyle and clinical characteristics in this association. Design and participants the Invecchiare in Chianti, aging in the Chianti area study is a cohort study of community-dwelling older adults from Italy. Cognitive function, dietary and clinical data were collected at baseline and years 3, 6, 9 and 15. Our study comprised 848 participants aged ≥ 65 years (56% female) with 2,038 observations. Main outcome and measures cognitive decline was defined as a decrease ≥3 units in the Mini-Mental State Examination score during consecutive visits. Hazard ratios for cognitive decline were estimated using time-dependent Cox regression models. Results energy-adjusted fibre intake was not associated with cognitive decline during the 15-years follow-up (P > 0.05). However, fibre intake showed a significant interaction with Apolipoprotein E (APOE) haplotype for cognitive decline (P = 0.02). In participants with APOE-ɛ4 haplotype, an increase in 5 g/d of fibre intake was significantly associated with a 30% lower risk for cognitive decline. No association was observed in participants with APOE-ɛ2 and APOE-ɛ3 haplotypes. Conclusions and relevance dietary fibre intake was not associated with cognitive decline amongst older adults for 15 years of follow-up. Nonetheless, older subjects with APOE-ɛ4 haplotype may benefit from higher fibre intakes based on the reduced risk for cognitive decline in this high-risk group.

Purpose STOPP/START is a physiological systems-based explicit set of criteria that attempts to define the clinically important prescribing problems relating to potentially inappropriate medications (PIMs–STOPP criteria) and potential prescribing omissions (PPOs–START criteria). The previous two versions of STOPP/START criteria were published in 2008 and 2015. The present study describes the revised and updated third version of the criteria. Methods A detailed system-by-system review of the published literature from April 2014 to March 2022 was undertaken with the aim of including clinically important new explicit PIM and PPO criteria and removing any criteria considered to be no longer correct or outdated. A panel of 11 academic physicians with recognized expertise in geriatric pharmacotherapy from 8 European countries participated in a Delphi panel with the task of validating the draft criteria. The panel was presented with the draft new criteria using the SurveyMonkey® on-line platform in which panelists were asked to indicate their level of agreement on a five-point Likert scale. Results Two hundred and four evidence-based draft criteria (one hundred and forty-five STOPP criteria, fifty-nine START criteria) were presented to panelists for assessment using the Delphi validation method. Over the course of four rounds of Delphi validation, the panel achieved consensus on 133 STOPP criteria and 57 START criteria, i.e., 190 STOPP/START criteria in total representing a 66.7% increase in the number of criteria compared to STOPP/START version 2 published in 2015. Conclusion A fully revised and updated version of STOPP/START criteria has been validated by a European expert panel using the Delphi consensus process.

ImportanceSeveral ocular biomarkers have been proposed for the early detection of Alzheimer disease (AD) and mild cognitive impairment (MCI), particularly fundus photography, optical coherence tomography (OCT), and OCT angiography (OCTA).ObjectiveTo perform an umbrella review of systematic reviews to assess the diagnostic accuracy of ocular biomarkers for early diagnosis of Alzheimer disease.Data SourcesMEDLINE, Embase, and PsycINFO were searched from January 2000 to November 2021. The references of included reviews were also searched.Study SelectionSystematic reviews investigating the diagnostic accuracy of ocular biomarkers to detect AD and MCI, in secondary care or memory clinics, against established clinical criteria or clinical judgment.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline checklist was followed and the Risk Of Bias in Systematic reviews tool was used to assess review quality.Main Outcomes and MeasuresThe prespecified outcome was the accuracy of ocular biomarkers for diagnosing AD and MCI. The area under the curve (AUC) was derived from standardized mean difference.ResultsFrom the 591 titles, 14 systematic reviews were included (median [range] number of studies in each review, 14 [5-126]). Only 4 reviews were at low risk of bias on all Risk of Bias in Systematic Reviews domains. The imaging-derived parameters with the most evidence for detecting AD compared with healthy controls were OCT peripapillary retinal nerve fiber layer thickness (38 studies including 1883 patients with AD and 2510 controls; AUC = 0.70; 95% CI, 0.53-0.79); OCTA foveal avascular zone (5 studies including 177 patients with AD and 371 controls; AUC = 0.73; 95% CI, 0.50-0.89); and saccadic eye movements prosaccade latency (30 studies including 651 patients with AD/MCI and 771 controls; AUC = 0.64; 95% CI, 0.58-0.69). Antisaccade error was investigated in fewer studies (12 studies including 424 patients with AD/MCI and 382 controls) and yielded the best accuracy (AUC = 0.79; 95% CI, 0.70-0.88).Conclusions and RelevanceThis umbrella review has highlighted limitations in design and reporting of the existing research on ocular biomarkers for diagnosing AD. Parameters with the best evidence showed poor to moderate diagnostic accuracy in cross-sectional studies. Future longitudinal studies should investigate whether changes in OCT and OCTA measurements over time can yield accurate predictions of AD onset.

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© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/., Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration., Open access funding provided by University of Geneva

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.

Background Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty. Methods A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019. Results Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty. Conclusion So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

Herpesviridae reactivation such as cytomegalovirus (CMV) has been described in severe COVID-19 (COronaVIrusDisease-2019). This study aimed to understand if CMV reactivation in older COVID-19 patients is associated with increased inflammation and in-hospital mortality. In an observational single-center cohort study, 156 geriatric COVID-19 patients were screened for CMV reactivation by RT-PCR. Participants underwent a comprehensive clinical investigation that included medical history, functional evaluation, laboratory tests and cytokine assays (TNF-α, IFN-α, IL-6, IL-10) at hospital admission. In 19 (12.2%) of 156 COVID-19 patients, CMV reactivation was detected. Multivariate Cox regression models showed that in-hospital mortality significantly increased among CMV positive patients younger than 87 years (HR: 9.94, 95% CI: 1.66–59.50). Other factors associated with in-hospital mortality were C-reactive protein (HR: 1.17, 95% CI: 1.05–1.30), neutrophil count (HR: 1.20, 95% CI: 1.01–1.42) and clinical frailty scale (HR:1.54, 95% CI: 1.04–2.28). In patients older than 87 years, neutrophil count (HR: 1.13, 95% CI: 1.05–1.21) and age (HR: 1.15, 95% CI: 1.01–1.31) were independently associated with in-hospital mortality. CMV reactivation was also correlated with increased IFN-α and TNF-α serum levels, but not with IL-6 and IL-10 serum changes. In conclusion, CMV reactivation was an independent risk factor for in-hospital mortality in COVID-19 patients younger than 87 years old, but not in nonagenarians.

Comorbidity indexes were designed in order to measure how the disease burden of a patient is related to different clinical outcomes such as mortality, especially in older and intensively treated people. Charlson's Comorbidity Index (CCI) is the most widely used rating system, based on diagnoses, but when this information is not available therapy-based comorbidity indices (TBCI) are an alternative: among them, Drug Derived Complexity Index (DDCI), Medicines Comorbidity Index (MCI), and Chronic Disease Score (CDS) are available.This study assessed the predictive power for 1-year mortality of these comorbidity indices and polypharmacy.Survival analysis and Receiver Operating Characteristic (ROC) analysis were conducted on three Italian cohorts: 2,389 nursing home residents (Korian), 4,765 and 633 older adults admitted acutely to geriatric or internal medicine wards (REPOSI and ELICADHE).Cox's regression indicated that the highest levels of the CCI are associated with an increment of 1-year mortality risk as compared to null score for all the three samples. DDCI and excessive polypharmacy gave similar results but MCI and CDS were not always statistically significant. The predictive power with the ROC curve of each comorbidity index was poor and similar in all settings.On the whole, comorbidity indices did not perform well in our three settings, although the highest level of each index was associated with higher mortality.

A polyphenol-rich diet reduced intestinal permeability (IP) in older adults. Our aim was to evaluate if participants categorized according to urolithin metabotypes (UMs) exhibited different responses in the MaPLE trial. Fifty-one older adults (mean age: 78 years) completed an 8-week randomized-controlled-crossover trial comparing the effects of a polyphenol-rich vs. a control diet on IP, assessed through zonulin levels. Plasma and urinary metabolomics were evaluated with a semi-targeted UHPLC-MS/MS method. Gut microbiota was characterized by 16S rRNA gene profiling. UMs were determined according to urolithin excretion in 24 h urine samples. Multivariate statistics were used to characterize the differences in metabolomic and metataxonomic responses across UMs. Thirty-three participants were classified as urolithin metabotype A (UMA), 13 as urolithin metabotype B (UMB), and 5 as urolithin metabotype 0 (UM0) according to their urinary excretion of urolithins. Clinical, dietary, and biochemical characteristics at baseline were similar between UMs (all p > 0.05). After the polyphenol-rich diet, UMB vs. UMA participants showed a 2-fold higher improvement of zonulin levels (p for interaction = 0.033). Moreover, UMB vs. UMA participants were characterized for alterations in fatty acid metabolism, kynurenine pathway of tryptophan catabolism, and microbial metabolization of phenolic acids. These changes were correlated with the reduction of zonulin levels and modifications of gut microbes (increased Clostridiales, including, R. lactaris, and G. formicilis). In conclusion, urolithin-based metabotyping identified older adults with a higher improvement of IP after a polyphenol-rich diet. Our results reinforce the concept that UMs may contribute to tailor personalized nutrition interventions.

Purpose Aging can be characterized by increased systemic low-grade inflammation, altered gut microbiota composition, and increased intestinal permeability (IP). The intake of polyphenol-rich foods is proposed as a promising strategy to positively affect the gut microbiota-immune system-intestinal barrier (IB) axis. In this context, we tested the hypothesis that a PR-dietary intervention would affect the presence of bacterial factors in the bloodstream of older adults. Methods We collected blood samples within a randomized, controlled, crossover intervention trial in which older volunteers (n = 51) received a polyphenol-enriched and a control diet. We quantified the presence of bacterial DNA in blood by qPCR targeting the 16S rRNA gene (16S; bacterial DNAemia). Blood DNA was taxonomically profiled via 16S sequencing. Results Higher blood 16S levels were associated with higher BMI and markers of IP, inflammation, and dyslipidemia. PR-intervention did not significantly change bacterial DNAemia in the older population (P = 0.103). Nonetheless, the beneficial changes caused by the polyphenol-enriched diet were greatest in participants with higher bacterial DNAemia, specifically in markers related to IP, inflammation and dyslipidemia, and in fecal bacterial taxa. Finally, we found that the bacterial DNA detected in blood mostly belonged to γ-Proteobacteria, whose abundance significantly decreased after the polyphenol-rich diet in subjects with higher bacterial DNAemia at baseline. Conclusions This study shows that older subjects with higher bacterial DNAemia experienced a beneficial effect from a polyphenol-rich diet. Bacterial DNAemia may be a further relevant marker for the identification of target populations that could benefit more from a protective dietary treatment. Registration This trial was retrospectively registered at www.isrctn.org (ISRCTN10214981) on April 28, 2017.

Background Cognitive decline is common in older people. Numerous studies point to the detrimental impact of polypharmacy and inappropriate medication on older people’s cognitive function. Here we aim to systematically review evidence on the impact of medication optimisation and drug interventions on cognitive function in older adults. Methods A systematic review was performed using MEDLINE and Web of Science on May 2021. Only randomised controlled trials (RCTs) addressing the impact of medication optimisation or pharmacological interventions on quantitative measures of cognitive function in older adults (aged > 65 years) were included. Single-drug interventions (e.g., on drugs for dementia) were excluded. The quality of the studies was assessed by using the Jadad score. Results Thirteen studies met the inclusion criteria. In five studies a positive impact of the intervention on metric measures of cognitive function was observed. Only one study showed a significant improvement of cognitive function by medication optimisation. The remaining four positive studies tested methylphenidate, selective oestrogen receptor modulators, folic acid and antipsychotics. The mean Jadad score was low (2.7). Conclusion This systematic review identified a small number of heterogenous RCTs investigating the impact of medication optimisation or pharmacological interventions on cognitive function. Five trials showed a positive impact on at least one aspect of cognitive function, with comprehensive medication optimisation not being more successful than focused drug interventions. More prospective trials are needed to specifically assess ways of limiting the negative impact of certain medication in particular and polypharmacy in general on cognitive function in older patients. publishedVersion

Dietary polyphenols can alter the gut microbiota (GM) and promote the production of bioactive metabolites. Several indoles result of GM metabolism of dietary tryptophan have been associated with intestinal barrier integrity. Our aim is to study the changes in GM-derived indoles during a polyphenol-rich (PR) diet intervention in older adults.Randomized, controlled, crossover trial in adults ≥ 60 years living in a residential care facility during an 8-week PR versus control diet (n = 51). Seven GM-tryptophan metabolites are measured in serum, and metataxonomic analysis of GM is performed on fecal samples. Exploratory subgroup analyses are performed based on renal function (RF). The PR-diet significantly increases serum indole 3-propionic acid (IPA) in subjects with normal RF, but not in subjects with impaired RF. Other GM-tryptophan metabolites are not affected. Comparison of baseline GM composition shows shifts in Bacteroidales order members as well as higher abundance of Clostridiales in participants with normal RF. During the trial, variations of IPA are associated with changes in C-reactive protein (β = 0.32, p = 0.010) and GM, particularly with the Clostridiales (r = 0.35, p0.001) and Enterobacteriales (r = -0.15, p0.05) orders.A PR diet increases the serum concentration of IPA in older adults with normal RF. Our findings may be important when defining appropriate dietary interventions for older adults.ISRCTN10214981 (https://doi.org/10.1186/ISRCTN10214981).

We conducted a systematic review and meta-analysis to investigate whether depression is associated with vision impairment (VI) in population-based studies in adults. MEDLINE and EMBASE were searched, from inception to June 2020. Studies were included if they provided two-by-two data for calculating the OR of association between VI and depression, or crude and/or an adjusted odds ratio (OR) with a corresponding 95% confidence interval (CI) were reported. The proportion of VI and depression was also extracted. ORs were pooled using random-effect models, proportions were pooled using random intercepts logistic regression models. Overall, 29 articles (31 studies) were included: of those, 18 studies used survey data (622,312 participants), 10 used clinical examination data (69,178 participants), and 3 used administrative databases (48,162,290 participants). The proportion of depression (95%CI) was 0.17 (0.13–0.22) overall and 0.27 (0.21–0.33) in VI subjects. The proportion of VI was 0.10 (0.07–0.16) overall and 0.20 (0.13–0.29) in depressed subjects. The association between VI and depression was direct: crude ORs were 1.89 (1.51–2.37) for survey data, 2.17 (1.76–2.67) for clinical examination data, and 3.34 (1.01–11.11) for administrative databases; adjusted ORs were 1.75 (1.34–2.30), 1.59 (1.22–1.96), and 2.47 (0.97–6.33), respectively. In conclusion, VI and depression are prevalent morbidities and should be actively sought when either is identified, especially in older adults.

Background Demographic changes in the western world entail new clinical approaches and challenges in older persons. Low skeletal muscle mass and low physical performance in older persons are both predisposing conditions for disability and obtaining knowledge in this cohort is essential. Aim The primary aim of the study was to analyze a broader spectrum of gait characteristics within this specific population and differentiate them across different test conditions. Methods Two centers participating at the SPRINTT project with hi-tech gait analysis available conducted a cross-sectional descriptive study on N = 115 community-dwelling older persons with low muscle mass and physical performance. Reference values of 13 gait parameters were collected across different conditions: usual gait speed, fast gait speed, and usual gait speed while simultaneously naming animals. Results and discussion This study shows the first spatio-temporal reference values in a community-dwelling older population composed of individuals with low skeletal muscle mass and low physical performance. In comparison to the normative spatio-temporal gait parameters in older persons reported in the literature, this population showed some differences. The mean gait speed was lower than 1 m/s, considered as a cutoff for vulnerable community-dwelling individuals, which corresponds to a greater risk of falls, hospitalization, and mortality. The stride length variability was higher, exposing to a greater risk of falling, and was also associated with a higher risk of developing cognitive decline. Conclusion This study represents the first step in the development of quantitative reference values in community-dwelling older persons with low physical performance and low skeletal muscle mass.

With population ageing, the number of older people is growing, which results in increasing number of people with multimorbidity and related polypharmacy. Polypharmacy in its turn leads to drug-related problems (DRPs) and potentially inappropriate prescribing (IP) in older people. In this commentary, susceptibility of older people to DRPs due to changes in pharmacokinetics and pharmacodynamics, plurality of prescribing physicians, inadequate consideration of patients’ characteristics, polypharmacy and its consequences such as prescribing cascades, drug interactions and potentially IP have been discussed respectively. Consecutively, identifying DRPs and optimizing of IP, including drug reconciliation, application of criteria for identifying and preventing IP, implementation of computer-based prescribing systems, and comprehensive geriatric assessment and management have been elaborated as well. One of the main challenges regarding appropriate and tailored prescribing in older people is to evaluate whether the expected benefits of pharmacotherapy are bigger than the risks in a population with multimorbidity, decreased tolerance to vulnerability and limited life expectancy. Comprehensive geriatric assessment enables informed prescribing decisions in the context of such variables. A challenge for future research is how to integrate important clinical information obtained by existing methods into a comprehensive and wide-reaching approach targeting all potential factors involved in causing DRPs. Good prescribing in late life accommodates the needs of older patients with multimorbidity. Individualized, interactive, multidisciplinary, and multifaceted approach to geriatric pharmacotherapy should be promoted and encouraged. How to optimize pharmacological prescription in complex older patients is a major legacy of geriatrics to contemporary medicine/medical practice.

The stratification of mortality risk in COVID-19 patients remains extremely challenging for physicians, especially in older patients. Innovative minimally invasive molecular biomarkers are needed to improve the prediction of mortality risk and better customize patient management. In this study, aimed at identifying circulating miRNAs associated with the risk of COVID-19 in-hospital mortality, we analyzed serum samples of 12 COVID-19 patients by small RNA-seq and validated the findings in an independent cohort of 116 COVID-19 patients by qRT-PCR. Thirty-four significantly deregulated miRNAs, 25 downregulated and 9 upregulated in deceased COVID-19 patients compared to survivors, were identified in the discovery cohort. Based on the highest fold-changes and on the highest expression levels, 5 of these 34 miRNAs were selected for the analysis in the validation cohort. MiR-320b and miR-483-5p were confirmed to be significantly hyper-expressed in deceased patients compared to survived ones. Kaplan-Meier and Cox regression models, adjusted for relevant confounders, confirmed that patients with the 20% highest miR-320b and miR-483-5p serum levels had three-fold increased risk to die during in-hospital stay for COVID-19. In conclusion, high levels of circulating miR-320b and miR-483-5p can be useful as minimally invasive biomarkers to stratify older COVID-19 patients with an increased risk of in-hospital mortality.

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 p p

To reduce the mortality of COVID-19 older patients, clear criteria to predict in-hospital mortality are urgently needed. Here, we aimed to evaluate the performance of selected routine laboratory biomarkers in improving the prediction of in-hospital mortality in 641 consecutive COVID-19 geriatric patients (mean age 86.6 ± 6.8) who were hospitalized at the INRCA hospital (Ancona, Italy). Thirty-four percent of the enrolled patients were deceased during the in-hospital stay. The percentage of severely frail patients, assessed with the Clinical Frailty Scale, was significantly increased in deceased patients compared to the survived ones. The age-adjusted Charlson comorbidity index (CCI) score was not significantly associated with an increased risk of death. Among the routine parameters, neutrophilia, eosinopenia, lymphopenia, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, procalcitonin, IL-6, and NT-proBNP showed the highest predictive values. The fully adjusted Cox regressions models confirmed that high neutrophil %, NLR, derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), and low lymphocyte count, eosinophil %, and lymphocyte-to-monocyte ratio (LMR) were the best predictors of in-hospital mortality, independently from age, gender, and other potential confounders. Overall, our results strongly support the use of routine parameters, including complete blood count, in geriatric patients to predict COVID-19 in-hospital mortality, independent from baseline comorbidities and frailty.

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.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Correction to: European Journal of Clinical Pharmacology (2021) 77:1–12 https://doi.org/10.1007/s00228-020–02951-8 \ud \ud The article Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials, written by Farhad Pazan, Mirko Petrovic, Antonio Cherubini, Graziano Onder, Alfonso J. Cruz-Jentoft, Michael Denkinger, Tischa J. M. van der Cammen, Jennifer M. Stevenson, Kinda Ibrahim, Chakravarthi Rajkumar, Marit Stordal Bakken, Jean-Pierre Baeyens, Peter Crome, Thomas Frühwald, Paul Gallaghar, Adalsteinn Guðmundsson, Wilma Knol, Denis O’Mahony, Alberto Pilotto, Elina Rönnemaa, José Antonio Serra-Rexach, George Soulis, Rob J. van Marum, Gijsbertus Ziere, Alpana Mair, Heinrich Burkhardt, Agnieszka Neumann-Podczaska, Katarzyna Wieczorowska- Tobis, Marilia Andreia Fernandes, Heidi Gruner, Dhayana Dallmeier, Jean-Baptiste Beuscart, Nathalie van der Velde and Martin Wehling, was originally published electronically on the publisher’s internet portal on 07 August 2020 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 14 May 2021 to © The Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creat iveco mmons. org/ licen ses/ by/4.0. \ud The Original article has been corrected.

Background The aim of our study was to identify independent predictors of functional decline in older nursing home (NH) residents, taking into account both resident and facility characteristics. Methods Longitudinal observational study involving 1,760 older (≥65 y) residents of NH participating in the SHELTER* study (57 NH in eight countries). All residents underwent a comprehensive geriatric assessment using the interRAI LTCF. Functional decline was defined as an increase of at least one point in the MDS Long Form ADL scale during a 1 year follow-up. Facility and country effects were taken into account. Results During the study period 891 (50.6%), NH residents experienced ADL decline. Residents experiencing ADL decline were older, had lower disability at baseline, were more frequently affected by severe dementia and by urinary incontinence, and used more antipsychotics. In the mixed-effect logistic regression model, factors independently associated with a higher risk of functional decline were dementia and urinary incontinence, whereas the presence of a geriatrician was a protective factor. Conclusions Both resident and facility characteristics are associated with the risk of functional decline in NH residents. Increasing the quality of healthcare by involving a geriatrician in residents’ care might be an important strategy to improve the outcome of this vulnerable population.

It is well recognized that poor muscle function and poor physical performance are strong predictors of clinically relevant adverse events in older people. Given the large number of approaches to measure muscle function and physical performance, clinicians often struggle to choose a tool that is appropriate and validated for the population of older people they deal with. In this paper, an overview of different methods available and applicable in clinical settings is proposed. This paper is based on literature reviews performed by members of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) working group on frailty and sarcopenia. Face-to-face meetings were organized afterwards where the whole group could amend and discuss the recommendations further. Several characteristics should be considered when choosing a tool: (1) purpose of the assessment (intervention, screening, diagnosis); (2) patient characteristics (population, settings, functional ability, etc.); (3) psychometric properties of the tool (test–retest reliability, inter-rater reliability, responsiveness, floor and ceiling effects, etc.); (4) applicability of the tool in clinical settings (overall cost, time required for the examination, level of training, equipment, patient acceptance, etc.); (5) prognostic reliability for relevant clinical outcomes. Based on these criteria and the available evidence, the expert group advises the use of grip strength to measure muscle strength and the use of 4-m gait speed or the Short Physical Performance Battery test to measure physical performance in daily practice. The tools proposed are relevant for the assessment of muscle weakness and physical performance. Subjects with low values should receive additional diagnostic workups to achieve a full diagnosis of the underlying condition responsible (sarcopenia, frailty or other).

This systematic review aimed to determine if non-pharmacological interventions can impact upon older stroke survivors quality of life. From 28 trials we identified limited evidence supporting a beneficial impact upon quality of life from additional physiotherapy and occupational therapy. Very limited evidence supported the use of a wide array of other non-pharmacological therapies. Current evidence is limited by low study quality and small sample sizes and more trials specifically involving older stroke survivors are required. The efficacy of non-pharmacological stroke rehabilitation approaches for older stroke survivors is largely unknown, particularly in relation to psychosocial outcomes such as quality of life. 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 ]. Thirteen experts in geriatric medicine, as part of a Delphi panel, agreed quality of life to be a critical outcome of stroke rehabilitation. A comprehensive search strategy was developed and databases were searched for eligible systematic reviews from which trials meeting our criteria were identified. Eligible papers were then double reviewed. Due to heterogeneity, narrative analysis was performed. Cochrane risk of bias and GRADE assessment tools were used to assess bias and quality of evidence. We identified 28 trials, spanning ten types of intervention. Limited evidence supports the use of additional occupational therapy and physiotherapy, with very limited evidence supporting our recommendation to explore caregiver training, constraint-induced movement therapy, device-assisted physiotherapy, and self-management education further. Limited evidence suggests a range of non-pharmacological interventions may improve the quality of life of older stroke survivors. However, evidence is limited by low 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.

Hospitalization for acute SARS-CoV-2 infection confers an almost five-fold higher risk of post-discharge, all-cause mortality compared to controls from the general population. A negative impact on the functional autonomy of older patients, especially in cases of severe disease and prolonged hospitalization, has been recently described. However, little is known about the determinants of cause-specific mortality and loss of independence (LOI) in the activities of daily living (ADL) following COVID-19 hospitalization. Thus, the current prospective, multicenter study is aimed at identifying the determinants of post-discharge cause-specific mortality and the loss of autonomy in at least one ADL function. Older patients hospitalized for a SARS-CoV-2 infection were consecutively enrolled in an e-Registry from 1 March 2020, until 31 December 2020. After at least six months from discharge, patients were extensively re-evaluated according to a common protocol at the outpatient clinic of eight tertiary care Italian hospitals. Of 193 patients [109 (56.4%) men, mean age 79.9 ± 9.1 years], 43 (22.3%) died during follow-up. The most common causes of death were cardiovascular diseases (46.0%), respiratory failure (26.5%), and gastrointestinal and genitourinary diseases (8.8% each). Pre-morbid ADLs qualified as an independent mortality risk factor [adjusted HR 0.77 (95%CI: 0.63–0.95)]. Of 132 patients, 28 (21.2%) lost their independence in at least one ADL. The adjusted risk of LOI declined with a lower frailty degree [aOR 0.03 (95%CI: 0.01–0.32)]. In conclusion, at long-term follow-up after hospitalization for acute SARS-CoV-2 infection, more than 40% of older patients died or experienced a loss of functional independence compared to their pre-morbid condition. Given its high prevalence, the loss of functional independence after hospitalization for COVID-19 could be reasonably included among the features of the “Long COVID-19 syndrome” of older patients.

Ageing is an inevitable process of physical deterioration that impairs functional autonomy and quality of life, becoming a public health issue. Since the percentage of people over 60 years is increasing worldwide, the use of easily detectable biomarkers of ageing is a relevant tool for monitoring of the ageing process and treatment. Among them, Klotho, an ageing suppressor gene because its deficiency leads to ageing like phenotype, seems particularly promising. This systematic review includes the last 10 years clinical studies that evaluated the association between plasma Klotho and body composition, physical performance and frailty in both sedentary and active middle-aged and older adults. Sixteen studies have been found: nine regarding the association between Klotho and body composition, two the association of Klotho and frailty and finally five concerning the effects of physical activity on Klotho. The results of these studies, albeit with some exceptions, point out that Klotho is positively associated with muscle strength and negatively with osteoporosis, frailty, disability and mortality while physical activity generally increases Klotho levels. Moreover, even if there are still few clinical studies, Klotho might be positively associated with bone mineral density, muscle strength, longevity, mobility and robustness during ageing.

ObjectiveTo determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia.DesignEvaluator blinded, randomised controlled trial.Setting16 clinical sites across 11 European countries, January 2016 to 31 October 2019.Participants1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls).InterventionsThe multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months.Main outcome measuresThe primary outcome was mobility disability (inability to independently walk 400 m in ResultsMean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; PConclusionsA multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people.Trial registrationClinicalTrials.gov NCT02582138.

Many studies investigated factors associated with overuse of Emergency Department (ED) by older people. However, there is little evidence of how a better access to long-term care services can affect ED visit rates. Therefore, we estimated the association between ED use and contextual (distance to closest ED), need (priority level at admission and care deprivation), predisposing (socio-economic conditions) and enabling factors (availability of health services) at the municipal level. We investigated ED visit rates by comparing the older population (aged 75 and more) to those aged less than 75 years among 233 municipalities and 13 health districts in the Marche Region, Central Italy. Administrative data were enriched by spatial dimensions. The outcomes were analysed using t-tests and ANOVA, while OLS and multilevel regressions have been used to identify independent correlates of ED visit rates. Mean ED visit rate was 56.3% and 25.3% among older people and the rest of the population (

We would like to thank Chen et al. for their comments on our recently published paper in Ageing Research Reviews (Veronese et al., 2021). In this reply we would like to answer to the points raised in their letter. Regarding the first question, we decided to run our search only in PubMed/Medline and ClinicalTrials.gov since the phase II-III randomized controlled trials of SARS-CoV 2 vaccines, considering the urgency for interventions to ameliorate the pandemic situation, received a great deal of interest. Therefore, they were usually published in high impact factor journals, reported in PubMed, and their protocols were usually reported in clinicaltrials.gov. However, following the suggestion of Chen et al., we did run a similar search in Web of Science (n = 150 articles) and Embase (n = 121 articles), without finding any possible eligible paper. We also searched, as suggested, the WHO ICTRP registry, which includes also the Chinese clinical trial registry, finding 36 ongoing trials, with two eligible out of them (https://trialsearch.who.int/Trial2.aspx? TrialID=ISRCTN79815558; https://trialsearch.who.int/Trial2.aspx? TrialID=RPCEC00000354). However, since both trials are still undergoing, it is not possible to know which percentage of older people will be eventually enrolled, therefore there is no need to modify what was already reported in our systematic review. With regard to the concern related to the language limitation, it should be pointed out that, among the completed trials, four out of ten were performed in China, but still they were published in an English language journal (Xia et al., 2020, 2021; Zhang et al., 2021; Zhu et al., 2020). Furthermore, we added the keywords suggested in the second point of the comments to our article: in this case, limiting the search to the 01st May 2021 as done in our systematic review, we found 547 possible eligible papers, but again, no new work was eligible for our analyses. Even if we recognize that adding these specific keywords might increase sensitivity of the search, they are probably of poor specificity in finding out papers that did not use randomized clinical trial as filter, particularly considering that practically all the papers reporting phase II-III trials on vaccination were published in widely known scientific journals. We also appreciate the comments regarding risk of bias and assessment of the quality of the study, which are a mandatory step in a systematic review. However, we would like to point out that the aim of our systematic review was not to investigate the efficacy/safety of COVID-19 vaccination in older people, but to highlight that older people were usually excluded from these studies. Therefore, this evaluation was not necessary, as we did not want to evaluate the quality of the results provided by the studies, but we aimed only at verifying the inclusion of older people. Finally, we are also grateful for the comments regarding the registration of the protocol and the statistical analysis. Regarding the first point, we agree that pre-publishing the protocol is an essential step in publishing a paper, but at the same time we also believe that the protocol structure is so simple in this case (we practically only extracted data regarding age range, asking to the corresponding authors further information when needed) that pre-publishing of the protocol would have not changed anything in the final results. However, we enclose to this letter as supplementary material the protocol. Moreover, the statistical analyses were so elementary that creating a specific paragraph would not represent an added value and we believe that keeping them in the outcomes section is enough for providing the necessary information to the readers to completely understand our work. In conclusion, we would like to thank Chen et al. for their comments that allowed us to confirm the methodological strengths of our paper. Indeed, as reported in this reply, addressing the points raised did not significantly change our results indicating that our work, even if simple, is correct and the conclusions are sound.

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Background In general, plant protein intake was inversely associated with mortality in studies in middle-aged adults. Our aim was to evaluate the long-term associations of animal and plant protein intake with mortality in older adults. Methods A prospective cohort study including 1 139 community-dwelling older adults (mean age 75 years, 56% women) living in Tuscany, Italy, followed for 20 years (InCHIANTI study) was analyzed. Dietary intake by food frequency questionnaires and clinical information were assessed 5 times during the follow-up. Protein intakes were expressed as percentages of total energy. Time-dependent Cox regression models adjusted for confounders were used to assess the association between plant and animal protein intake, and mortality. Results During the 20 years of follow-up (mean: 12 years), 811 deaths occurred (292 of cardiovascular- and 151 of cancer-related causes). Animal protein intake was inversely associated with all-cause (hazard ratio [HR] per 1% of total energy from protein increase, 95% confidence interval [CI]: 0.96, 0.93–0.99) and cardiovascular mortality (HR per 1% of total energy from protein increase, 95% CI: 0.93, 0.87–0.98). Plant protein intake showed no association with any of the mortality outcomes, but an interaction with baseline hypertension was found for all-cause and cardiovascular mortality (p < .05). Conclusions Animal protein was inversely associated with all-cause and cardiovascular mortality in older adults. Further studies are needed to provide recommendations on dietary protein intake for older adults.

The management of pharmacological therapy in older patients is challenging in clinical practice. Older subjects experience age-related changes that influence pharmacokinetics and pharmacodynamics of drugs, they also usually have multiple diseases, i.e., multimorbidity, and are often cared for, and hence, prescribed by a number of physicians over a long period of time. Therefore, it is not surprising that polypharmacy, literally the use of multiple drugs, is extremely common in older patients and is increasing over time, at least in developed countries. Appropriate geriatric pharmacotherapy, global assessment of patients’ clinical and functional parameters, and integration of skills from different healthcare professionals are needed to address the medical complexity of older adults. In this special issue, the most relevant aspects of geriatric pharmacotherapy are presented and critically discussed. The optimal management of drugs in older patients is a corner stone of the practice of geriatric medicine and one of the most important contributions to the evolution of health care in the direction of adapting contemporary clinical practice to the specific needs of older patients. However, while the tasks are clear, i.e., tailoring drug therapy according to the personal preferences and characteristics, increase patient safety by reducing adverse drug reactions, achieve the most favorable risk benefit ratio for each patient, periodically reviewing pharmacological therapy including deprescribing, as appropriate, the implementation in practice is often difficult, particularly when health care professionals are not geriatricians or clinical pharmacists.

Objectives We aimed to establish an explicit list of potentially clinically significant drug-drug interactions (DDIs) in people aged ≥65 years. Design A preliminary list of potentially clinically significant DDIs was compiled, based on 154 DDIs identified from literature review. Subsequently, a 2-round online Delphi survey was undertaken with a multidisciplinary expert panel. A consensus meeting and a final round were conducted to validate the final DDI list and the scope of information provided. Setting and Participants Twenty nine experts, including geriatricians and clinical pharmacists from 8 European countries. Measures For each DDI, in the first 2 rounds, experts were asked to score the severity of potential harm on a 5-point Likert-type scale. DDIs were directly included on the final list if the median score was 4 (major) or 5 (catastrophic). DDIs with a median score of 3 (moderate) were discussed at a consensus meeting and included if ≥75% of participants voted for inclusion in the final round. Results Consensus was achieved on 66 potentially clinically significant DDIs (28 had a median score of 4/5 and 48 of 3 in the Delphi survey). Most concerned cardiovascular, antithrombotic, and central nervous system drugs. The final list includes information on the mechanism of interaction, harm, and management. Treatment modification is recommended for three-quarters of DDIs. Conclusion and Implications We validated a list of potentially clinically significant DDIs in older people, which can be used in clinical practice and education to support identification and management of DDIs or to assess prevalence in epidemiologic and intervention studies. pre-print 896 KB

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

Background Healthcare professionals are often reluctant to deprescribe fall-risk-increasing drugs (FRIDs). Lack of knowledge and skills form a significant barrier and furthermore, there is no consensus on which medications are considered as FRIDs despite several systematic reviews. To support clinicians in the management of FRIDs and to facilitate the deprescribing process, STOPPFall (Screening Tool of Older Persons Prescriptions in older adults with high fall risk) and a deprescribing tool were developed by a European expert group. Methods STOPPFall was created by two facilitators based on evidence from recent meta-analyses and national fall prevention guidelines in Europe. Twenty-four panellists chose their level of agreement on a Likert scale with the items in the STOPPFall in three Delphi panel rounds. A threshold of 70% was selected for consensus a priori. The panellists were asked whether some agents are more fall-risk-increasing than others within the same pharmacological class. In an additional questionnaire, panellists were asked in which cases deprescribing of FRIDs should be considered and how it should be performed. Results The panellists agreed on 14 medication classes to be included in the STOPPFall. They were mostly psychotropic medications. The panellists indicated 18 differences between pharmacological subclasses with regard to fall-risk-increasing properties. Practical deprescribing guidance was developed for STOPPFall medication classes. Conclusion STOPPFall was created using an expert Delphi consensus process and combined with a practical deprescribing tool designed to optimise medication review. The effectiveness of these tools in falls prevention should be further evaluated in intervention studies.

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 &plusmn, 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.

Background: Interactions between chronic kidney disease (CKD) and several comorbidities may potentially affect prognosis of older hospitalized patients. This study aims at evaluating the prognostic interactions between estimated glomerular filtration rate (eGFR), anemia, sarcopenia, functional and cognitive dysfunction, and 3-year mortality among older patients discharged from acute care hospitals. Methods: Our series consisted of 504 older adults enrolled in a multicenter observational study carried out in twelve Acute Geriatric and Internal Medicine wards throughout Italy. CKD was defined as an eGFR< 60 ml/min/1.73 m2. Anemia, Short Portable Status Mental Questionnaire (SPMSQ), Basic Activities of Daily Living (BADL), sarcopenia, and Charlson index were considered in the analysis. 3-year survival was investigated by Cox regression and prognostic interactions among study variables were assessed by survival tree analysis. Accuracy of different survival models was investigated by C-index. Results: eGFR < 30 mL/min/1.73 m2, anemia, sarcopenia, SPMSQ ≥ 5, and impairment in 1 or more BADL were significantly associated with mortality. Survival tree analysis showed that patients with eGFR < 35.32 ml/min/1.73 m2 and SPMSQ ≥ 5 had the highest risk of mortality [hazard ratio (HR): 5.49, 95%CI: 3.04–9.94] followed by those with eGFR < 35.32 ml/min/1.73 m2, hemoglobin < 11.95 g/dL and SPMSQ < 5 (HR:3.65; 95%CI: 2.21–6.02) and those with eGFR 35.32–47.99 ml/min/1.73 m2 and sarcopenia (HR:3.65; 95%CI: 1.99–6.69). Survival tree leaf node membership had good accuracy in predicting the study outcome (C-index: 0.73, 95%CI:0.70-0.76). Conclusions: Interactions among study risk factors designed distinct risk profiles in older patients discharged from acute care hospitals, that may help identify patients needing targeted interventions and appropriate follow-up after discharge.

Inadequate osteoporosis education can make patients ill-informed concerning preventive and therapeutic interventions and creates misconceptions and unnecessary concerns about the disease. Our study aimed to assess whether patients referred to the DXA exam by their general practitioner are informed about risk factors for osteoporosis, comparing patients who received a diagnosis of osteoporosis before the exam with those without this diagnosis. An observational single-center study was performed among patients who were referred to the DXA exam at the Osteoporosis Service of Marche Nord Hospital (Fano, Italy) between April and July 2019. Socio-demographic and clinical characteristics, awareness of suffering from osteoporosis, femoral and lumbar spine T-score and bone mineral density, risk of fracture and the I-FOOQ score were assessed. A pilot study was carried out to validate the questionnaire in the Italian language (alpha-Cronbach 0.75). After that, a sample of 128 patients was enrolled (response rate 93.3%). Mean age was 66 ± 10.6 years, 95.6% were women. Overall, I-FOOQ mean score was 12 ± 3.5. Age, educational level, menopausal age, body mass index, femoral T-score were not associated with a better knowledge (p > 0.05). A comparison between who know to suffer from osteoporosis and others found no differences (12.2 ± 3.4 and 12 ± 3.5, respectively, p = 0.772). Effect of walking, recommended calcium intake, and familiar predisposition are the less known topics. Patients who undergo the DXA exam are poorly informed about risk factors for osteoporosis, independently of age, education, bone mineral density and risk of fracture. Knowing to suffer from osteoporosis does not increase the likelihood to be informed. It is mandatory to improve the education that is provided to the patients, as there are effective non-pharmacological interventions to prevent and treat osteoporosis.

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.

Anticholinergic burden (ACB) and anemia were found associated with an increased risk of death among older patients. Additionally, anticholinergic medications may contribute to the development of anemia. Therefore, we aimed at investigating the prognostic interplay of ACB and anemia among older patients discharged from hospital. Our series consisted of 783 patients enrolled in a multicenter observational study. The outcome of the study was 1 year mortality. ACB was assessed by an Anticholinergic Cognitive Burden score. Anemia was defined as hemoglobin &lt, 13 g/dL in men and &lt, 12 g/dL in women. The association between study variables and mortality was investigated by Cox regression analysis. After adjusting for several potential confounders, ACB score = 2 or more was significantly associated with the outcome in anemic patients (HR = 1.93, 95%CI = 1.13–3.40), but not non anemic patients (HR = 1.51, 95%CI = 0.65–3.48). An additive prognostic interaction between ACB and anemia was observed (p = 0.02). Anemia may represent a relevant effect modifier in the association between ACB and mortality.