Interactions between patterns of multimorbidity and functional status among hospitalized older patients: a novel approach using cluster analysis and association rule mining.

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.

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

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

Neutrophil-to-lymphocyte ratio (NLR) predicts mortality in hospitalized geriatric patients independent of the admission diagnosis: a multicenter prospective cohort study.

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 < 0.001). A negative multiplicative interaction was found between NLR and eGFR < 45 (p = 0.001). CONCLUSIONS: NLR at admission is a readily available and cost-effective biomarker that could improve identification of geriatric patients at high risk of death during hospital stay independent of admitting diagnosis, kidney function and hemoglobin levels.

Intrinsic Capacity and Active and Healthy Aging Domains Supported by Personalized Digital Coaching: Survey Study Among Geriatricians in Europe and Japan on eHealth Opportunities for Older Adults.

BACKGROUND: The worldwide aging trend requires conceptually new prevention, care, and innovative living solutions to support human-based care using smart technology, and this concerns the whole world. Enabling access to active and healthy aging through personalized digital coaching services like physical activity coaching, cognitive training, emotional well-being, and social connection for older adults in real life could offer valuable advantages to both individuals and societies. A starting point might be the analysis of the perspectives of different professionals (eg, geriatricians) on such technologies. The perspectives of experts in the sector may allow the individualization of areas of improvement of clinical interventions, supporting the positive perspective pointed out by the intrinsic capacity framework. OBJECTIVE: The overall aim of this study was to explore the cross-national perspectives and experiences of different professionals in the field of intrinsic capacity, and how it can be supported by eHealth interventions. To our knowledge, this is the first study to explore geriatric care providers' perspectives about technology-based interventions to support intrinsic capacity. METHODS: A survey involving 20 geriatricians or clinical experts in the fields of intrinsic capacity and active and healthy aging was conducted in Italy, France, Germany, and Japan between August and September 2021. RESULTS: The qualitative findings pointed out relevant domains for eHealth interventions and provided examples for successful practices that support subjective well-being under the intrinsic capacity framework (the benefits offered by personalized interventions, especially by promoting health literacy but avoiding intrusiveness). Moreover, eHealth interventions could be used as a bridge that facilitates and enables social engagement; an instrument that facilitates communication between doctors and patients; and a tool to enrich the monitoring actions of medical staff. CONCLUSIONS: There is an unexplored and significant role for such geriatric perspectives to help the development process and evaluate the evidence-based results on the effectiveness of technologies for older people. This is possible only when clinicians collaborate with data scientists, engineers, and developers in order to match the complex daily needs of older adults.

Long-term changes in pulmonary function among patients surviving to COVID-19 pneumonia.

PURPOSE: The aim of this study was to assess respiratory function at the time of clinical recovery, 6 weeks, 6 months, and 12 months after discharge in patients surviving to COVID-19 pneumonia. METHODS: Our case series consisted of 13 hospitalized patients with COVID-19 pneumonia. RESULTS: Baseline pulmonary function tests were 55.7 ± 15.6 for FEV1%, 68.6 ± 16.0 for FVC%, and 1.2 ± 0.1 for FEV1/FVC%. Although pulmonary function showed a small improvement after 6 weeks, patients experienced a more significant improvement after 6 and 12 months in FEV1% (95.4 ± 13.7 and 107.2 ± 16.5, respectively; p < 0.001), FVC% (91.3 ± 14.5, and 105.9 ± 15.6, respectively; p < 0.001), and FEV1/FVC% values (1.04 ± 0.04, and 1.01 ± 0.05, respectively; p < 0.001). CONCLUSION: COVID-19 pneumonia may result in significant alterations in lung function, with a mainly restrictive pattern, partly persisting at 6 weeks after recovery from acute phase, but significantly improving during a 12-month follow-up period.

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

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

Pulmonary function in patients surviving to COVID-19 pneumonia.

PURPOSE: The aim of our study was to assess respiratory function at the time of clinical recovery and 6 weeks after discharge in patients surviving to COVID-19 pneumonia. METHODS: Our case series consisted of 13 patients with COVID-19 pneumonia. RESULTS: At the time of clinical recovery, FEV1 (2.07 ± 0.72 L) and FVC (2.25 ± 0.86 L) were lower compared to lower limit of normality (LLN) values (2.56 ± 0.53 L, p = 0.004, and 3.31 ± 0.65 L, p < 0.001, respectively), while FEV1/FVC (0.94 ± 0.07) was higher compared to upper limit of normality (ULN) values (0.89 ± 0.01, p = 0.029). After 6 weeks pulmonary function improved but FVC was still lower than ULN (2.87 ± 0.81, p = 0.014). CONCLUSION: These findings suggest that COVID-19 pneumonia may result in clinically relevant alterations in pulmonary function tests, with a mainly restrictive pattern.

Does trail making test predict long-term prognosis in older patients with COPD?

Executive abilities are frequently impaired in patients with chronic obstructive pulmonary disease (COPD). We aimed at investigating the association between trail making test (TMT) and survival. Our series consisted of 68 stable COPD outpatients followed-up every 6 months for 52.6 ± 27.6 months. Enrolled patients underwent a baseline comprehensive neuropsychological assessment, including mini-mental state exam, attentional matrices, digit span, Rey auditory verbal learning, Rey-Osterrieth complex figure, copy drawing, tokens test, verbal fluency, category fluency, frontal assessment battery, Raven's progressive matrices, TMT-A, -B and -B-A. The association between neuropsychological deficits and overall mortality was investigated by Cox regression. During follow-up period, 41 patients (60.3%) died. After adjusting for potential confounders, TMT-B was significantly associated with mortality (HR = 2.42, 95% CI = 1.10-5.31), along with age (HR = 1.06, 95% CI = 1.0-1.13), overall comorbidity (HR = 1.29, 95% CI = 1.02-1.62) and use of noninvasive ventilation (HR = 2.16, 95% CI = 1.05-4.45). Defective TMT-B may be associated with long-term mortality in patients with stable COPD.

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

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

Neuroinflammaging: A Tight Line Between Normal Aging and Age-Related Neurodegenerative Disorders.

Aging in the healthy brain is characterized by a low-grade, chronic, and sterile inflammatory process known as neuroinflammaging. This condition, mainly consisting in an up-regulation of the inflammatory response at the brain level, contributes to the pathogenesis of age-related neurodegenerative disorders. Development of this proinflammatory state involves the interaction between genetic and environmental factors, able to induce age-related epigenetic modifications. Indeed, the exposure to environmental compounds, drugs, and infections, can contribute to epigenetic modifications of DNA methylome, histone fold proteins, and nucleosome positioning, leading to epigenetic modulation of neuroinflammatory responses. Furthermore, some epigenetic modifiers, which combine and interact during the life course, can contribute to modeling of epigenome dynamics to sustain, or dampen the neuroinflammatory phenotype. The aim of this review is to summarize current knowledge about neuroinflammaging with a particular focus on epigenetic mechanisms underlying the onset and progression of neuroinflammatory cascades in the central nervous system; furthermore, we describe some diagnostic biomarkers that may contribute to increase diagnostic accuracy and help tailor therapeutic strategies in patients with neurodegenerative diseases.

Prevalence, risk factors, and treatment of anemia in hospitalized older patients across geriatric and nephrological settings in Italy.

Anemia is a common but often underdiagnosed and undertreated geriatric syndrome in hospitalized older patients. In this retrospective multicenter study, we aimed at characterizing the prevalence, risk factors, diagnostic and treatment approach to anemia in older patients admitted to acute care hospitals, focusing on differences between nephrology and geriatrics units. Prevalence and risk factors for anemia, diagnostic inertia (lack of iron, vitamin B12, and folate status assessment), replacement inertia (omitted treatment with iron, vitamin B12 or folic acid), and erythropoiesis-stimulating agents (ESA) inertia were explored. 1963 patients aged 82.7 (6.8) years were included in the study; 66.7% of the study population had anemia; among anemic patients, diagnostic inertia and replacement inertia were common with rates of 22-31% and 50-87%, respectively; omitted treatment with ESA affected 67.2% of patients and was more prevalent in geriatric units. In most cases, patients with ESA inertia were not routinely screened for iron tests. COPD, cancer, eGFR 45-60 ml/min were associated with increased tendency to ESA inertia. In conclusion, anemia had a high prevalence in older patients discharged from acute care units, but it is often underdiagnosed and undertreated.

Biomarkers of chronic kidney disease in older individuals: navigating complexity in diagnosis.

Chronic kidney disease (CKD) in older individuals is a matter of growing concern in the field of public health across the globe. Indeed, prevalence of kidney function impairment increases with advancing age and is often exacerbated by age-induced modifications of kidney function, presence of chronic diseases such as diabetes, hypertension, and cardiovascular disorders, and increased burden related to frailty, cognitive impairment and sarcopenia. Accurate assessment of CKD in older individuals is crucial for timely intervention and management and relies heavily on biomarkers for disease diagnosis and monitoring. However, the interpretation of these biomarkers in older patients may be complex due to interplays between CKD, aging, chronic diseases and geriatric syndromes. Biomarkers such as serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria can be significantly altered by systemic inflammation, metabolic changes, and medication use commonly seen in this population. To overcome the limitations of traditional biomarkers, several innovative proteins have been investigated as potential, in this review we aimed at consolidating the existing data concerning the geriatric aspects of CKD, describing the challenges and considerations in using traditional and innovative biomarkers to assess CKD in older patients, highlighting the need for integration of the clinical context to improve biomarkers' accuracy.

Physical performance strongly predicts all-cause mortality risk in a real-world population of older diabetic patients: machine learning approach for mortality risk stratification.

Background: Prognostic risk stratification in older adults with type 2 diabetes (T2D) is important for guiding decisions concerning advance care planning. Materials and methods: A 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. Results: Of 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 <0.001). Conclusion: Assessment of physical performance needs to be implemented in clinical practice for risk stratification of T2D older patients.

Safety and Tolerability of Antimicrobial Agents in the Older Patient.

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

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

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

Toll-like receptors and NLRP3 inflammasome-dependent pathways in Parkinson's disease: mechanisms and therapeutic implications.

Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder characterized by motor and non-motor disturbances as a result of a complex and not fully understood pathogenesis, probably including neuroinflammation, oxidative stress, and formation of alpha-synuclein (α-syn) aggregates. As age is the main risk factor for several neurodegenerative disorders including PD, progressive aging of the immune system leading to inflammaging and immunosenescence may contribute to neuroinflammation leading to PD onset and progression; abnormal α-syn aggregation in the context of immune dysfunction may favor activation of nucleotide-binding oligomerization domain-like receptor (NOD) family pyrin domain containing 3 (NLRP3) inflammasome within microglial cells through interaction with toll-like receptors (TLRs). This process would further lead to activation of Caspase (Cas)-1, and increased production of pro-inflammatory cytokines (PC), with subsequent impairment of mitochondria and damage to dopaminergic neurons. All these phenomena are mediated by the translocation of nuclear factor kappa-B (NF-κB) and enhanced by reactive oxygen species (ROS). To date, drugs to treat PD are mainly aimed at relieving clinical symptoms and there are no disease-modifying options to reverse or stop disease progression. This review outlines the role of the TLR/NLRP3/Cas-1 pathway in PD-related immune dysfunction, also focusing on specific therapeutic options that might be used since the early stages of the disease to counteract neuroinflammation and immune dysfunction.

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

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

Clinical and Prognostic Implications of Estimating Glomerular Filtration Rate by Three Different Creatinine-Based Equations in Older Nursing Home Residents.

Background: According to the international literature, the percentage of nursing home (NH) residents with renal insufficiency is very high, ranging between 22 and 78%. Diminished kidney function represents a risk factor for drug overdosage, adverse drug reactions, end-stage renal disease, disability, morbidity, and mortality. Several studies suggested that screening for chronic kidney disease (CKD) in high-risk and older populations may represent a cost-effective approach to reducing progression to renal failure and CKD mortality. Objective: This study aimed (i) to investigate to what extent CKD may be staged interchangeably by three different creatinine-based estimated glomerular filtration rate (eGFR) equations in a sample of older adults living in long-term care facilities; (ii) to investigate factors explaining differences among eGFR equations; and (iii) to compare the predictivity of different creatinine-based eGFR equations with respect to all-cause mortality. Methods: A total of 522 residents aged 65 years and older participated in a prospective cohort study of 9 long-term care facilities in Calabria. eGFR was calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Berlin initiative study (BIS), and full age spectrum (FAS) equations. Disability in at least one activity of daily living (ADL), depression, cognitive impairment, comorbidity, and malnutrition was considered in the analysis. Statistical analysis was carried out by Bland-Altman analysis, and 2-year mortality was investigated by Kaplan-Meier curves and Cox regression analysis. Results: Depending on the adopted equation, the prevalence of NH residents with impaired renal function (eGFR < 60 ml/min/1.73 m2) ranged between 58.2% for the CKD-EPI and 79.1% for the BIS1 equation. The average difference between BIS and FAS was nearly negligible (0.45 ml/min/1.73 m2), while a significant bias was detected between CKD-EPI and BIS and also between CKD-EPI and FAS (6.21 ml/min/1.73 m2 and 6.65 ml/min/1.73 m2, respectively). Although the eGFR study equations had comparable prognostic accuracy in terms of mortality risk, BIS and FAS were able to reclassify NH residents pertaining to a low-risk group with CKD-EPI, and this reclassification improves the discriminative capacity of CKD-EPI with respect to overall mortality. Conclusion: Despite the relatively good correlation between eGFRs calculated using all adopted equations, the findings in this study reported clearly demonstrated that CKD-EPI and BIS/FAS equations are not interchangeable to assess eGFR among older people and particularly in institutionalized and frail older subjects.

COVID-19 Vaccines: Current and Future Perspectives.

Currently available vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are highly effective but not able to keep the coronavirus disease 2019 (COVID-19) pandemic completely under control. Alternative R&D strategies are required to induce a long-lasting immunological response and to reduce adverse events as well as to favor rapid development and large-scale production. Several technological platforms have been used to develop COVID-19 vaccines, including inactivated viruses, recombinant proteins, DNA- and RNA-based vaccines, virus-vectored vaccines, and virus-like particles. In general, mRNA vaccines, protein-based vaccines, and vectored vaccines have shown a high level of protection against COVID-19. However, the mutation-prone nature of the spike (S) protein affects long-lasting vaccine protection and its effectiveness, and vaccinated people can become infected with new variants, also showing high virus levels. In addition, adverse effects may occur, some of them related to the interaction of the S protein with the angiotensin-converting enzyme 2 (ACE-2). Thus, there are some concerns that need to be addressed and challenges regarding logistic problems, such as strict storage at low temperatures for some vaccines. In this review, we discuss the limits of vaccines developed against COVID-19 and possible innovative approaches.

Improving the prognostic value of multimorbidity through the integration of selected biomarkers to the comprehensive geriatric assessment: An observational retrospective monocentric study.

Background: Multimorbidity (MM) burdens individuals and healthcare systems, since it increases polypharmacy, dependency, hospital admissions, healthcare costs, and mortality. Several attempts have been made to determine an operational definition of MM and to quantify its severity. However, the lack of knowledge regarding its pathophysiology prevented the estimation of its severity in terms of outcomes. Polypharmacy and functional impairment are associated with MM. However, it is unclear how inappropriate drug decision-making could affect both conditions. In this context, promising circulating biomarkers and DNA methylation tools have been proposed as potential mortality predictors for multiple age-related diseases. We hypothesize that a comprehensive characterization of patients with MM that includes the measure of epigenetic and selected circulating biomarkers in the medical history, in addition to the functional capacity, could improve the prognosis of their long-term mortality. Methods: This monocentric retrospective observational study was conducted as part of a project funded by the Italian Ministry of Health titled "imProving the pROgnostic value of MultimOrbidity through the inTegration of selected biomarkErs to the comprehensive geRiatric Assessment (PROMOTERA)." This study will examine the methylation levels of thousands of CpG sites and the levels of selected circulating biomarkers in the blood and plasma samples of older hospitalized patients with MM (n = 1,070, age ≥ 65 years) recruited by the Reportage Project between 2011 and 2019. Multiple statistical approaches will be utilized to integrate newly measured biomarkers into clinical, demographic, and functional data, thus improving the prediction of mortality for up to 10 years. Discussion: This study's results are expected to: (i) identify the clinical, biological, demographic, and functional factors associated with distinct patterns of MM; (ii) improve the prognostic accuracy of MM patterns in relation to death, hospitalization-related outcomes, and onset of new comorbidities; (iii) define the epigenetic signatures of MM; (iv) construct multidimensional algorithms to predict negative health outcomes in both the overall population and specific disease and functional patterns; and (v) expand our understanding of the mechanisms underlying the pathophysiology of MM.