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- De Vincentis, Antonio, et al.
(author)
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A Polygenic Risk Score to Refine Risk Stratification and Prediction for Severe Liver Disease by Clinical Fibrosis Scores.
- 2022
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In: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - : Elsevier BV. - 1542-7714. ; 20:3, s. 658-673
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Journal article (peer-reviewed)abstract
- A polygenic risk score based on well-known genetic variants in PNPLA3, TM6SF2, MBOAT7 and GCKR predicts hepatic fat content (PRS-HFC). Here we hypothesize that the addition of PRS-HFC to clinical fibrosis scores may improve risk stratification and prediction of severe liver disease (SLD).We used data from 266,687 individuals in the UK Biobank, evaluating the incidence of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation during a median follow-up of 9 years. NAFLD fibrosis score (NFS), FIB-4, APRI, BARD and Forns scores, and PRS-HFC, were computed. All analyses were stratified according to the presence of diabetes, obesity and positive fatty liver index (FLI≥60).Unfavorable genetics (PRS-HFC≥0.396) further stratified the risk of SLD in subjects in intermediate/high risk classes of fibrosis scores, with higher effect in those with metabolic risk factors, and the prediction was improved by integrating PRS-HFC (AUROCs increased for all scores with p∼10-2-10-4, except for APRI in the overall population and in subjects with obesity. PRS-HFC improved diagnostic accuracies and positive predictive values for SLD in intermediate-high clinical score risk classes. Risk stratification and prediction were not/poorly affected by unfavorable genetics in subjects without metabolic risk factors.Integration of genetics with clinical fibrosis scores refines individual risk and prediction for SLD, mainly in individuals at risk for NAFLD. These data provide first evidence from a prospective cohort that common genetic variants capture additional prognostic insights not conveyed by validated clinical/biochemical parameters.
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2. |
- De Vincentis, Antonio, et al.
(author)
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Poor accuracy and sustainability of the first-step FIB4 EASL pathway for stratifying steatotic liver disease risk in the general population.
- 2024
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In: Alimentary Pharmacology and Therapeutics. - 0269-2813. ; 59:11, s. 1402-1412
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Journal article (peer-reviewed)abstract
- The European Association for the Study of the Liver introduced a clinical pathway (EASL CP) for screening significant/advanced fibrosis in people at risk of steatotic liver disease (SLD). We assessed the performance of the first-step FIB4 EASL CP in the general population across different SLD risk groups (MASLD, Met-ALD and ALD) and various age classes.We analysed a total of 3372 individuals at risk of SLD from the 2017-2018 National Health and Nutrition Examination Survey (NHANES17-18), projected to 152.3million U.S. adults, 300,329 from the UK Biobank (UKBB) and 57,644 from the Biobank Japan (BBJ). We assessed liver stiffness measurement (LSM) ≥8kPa and liver-related events occurring within 3 and 10years (3/10year-LREs) as outcomes. We defined MASLD, MetALD, and ALD according to recent international recommendations.FIB4 sensitivity for LSM≥8kPa was low (27.7%), but it ranged approximately 80%-90% for 3-year LREs. Using FIB4, 22%-57% of subjects across the three cohorts were identified as candidates for vibration-controlled transient elastography (VCTE), which was mostly avoidable (positive predictive value of FIB4≥1.3 for LSM≥8kPa ranging 9.5%-13% across different SLD categories). Sensitivity for LSM≥8kPa and LREs increased with increasing alcohol intake (ALD>MetALD>MASLD) and age classes. For individuals aged ≥65years, using the recommended age-adjusted FIB4 cut-off (≥2) substantially reduced sensitivity for LSM≥8kPa and LREs.The first-step FIB4 EASL CP is poorly accurate and feasible for individuals at risk of SLD in the general population. It is crucial to enhance the screening strategy with a first-step approach able to reduce unnecessary VCTEs and optimise their yield.
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- Laudisio, Alice, et al.
(author)
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Association of Pisa Syndrome With Mortality in Patients With Parkinson's Disease
- 2019
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In: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 20:8, s. 1037-
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Journal article (peer-reviewed)abstract
- Objectives: In Parkinson's disease, Pisa syndrom (PS) has been associated with disease stage and severity, combined treatment with levodopa and dopamine agonists, gait disorders, and comorbidities. Some forms of PS are potentially reversible; nevertheless, little is known about the impact of this syndrome on survival. Design: Prospective study with a median follow-up of 2 years. Setting and participants: Patients with Parkinson's disease, age 65 years and older (N = 189), attending a geriatric day hospital. Measurements: According to established criteria, PS was diagnosed in the presence of at least 10 degrees lateral flexion of the trunk reducible by passive mobilization or supine positioning. Cox regression was adopted to assess the association of PS with all-cause mortality. Results: PS was diagnosed in 40 patients (21%); over the follow-up, 21 (11%) subjects died. In Cox regression, PS was associated with higher mortality [hazard ratio (HR) 4.10; 95% confidence interval (CI) = 1.36-12.38], after adjusting; other variables associated with mortality were age (HR = 1.19, 95% CI = 1.08-1.32), beta blockers (HR = 4.35, 95% CI = 1.23-15.39), and albumin levels (HR = 0.05, 95% CI = 0.01-0.33). The association of PS with mortality remained significant also after adjusting for variables associated with this syndrome (HR = 4.04, 95% CI = 1.33-12.25). Conclusions/Implications: PS represents a risk factor for earlier mortality in Parkinson's disease; further studies are needed to ascertain the underlying causes and whether treatment of this condition might improve survival. (C) 2019 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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- Okoye, Chukwuma, et al.
(author)
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Determinants of Cause-Specific Mortality and Loss of Independence in Older Patients following Hospitalization for COVID-19 : The GeroCovid Outcomes Study
- 2022
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In: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:19
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Journal article (peer-reviewed)abstract
- 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.
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- Parrotta, Ilaria, et al.
(author)
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Frailty and hyperactive delirium in hospitalized older patients with COVID-19 : an insight from GeroCovid registry
- 2023
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In: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 35:2, s. 433-442
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Journal article (peer-reviewed)abstract
- Background Delirium is an acute neuropsychiatric condition associated with unfavourable outcomes, frequent in older hospitalized people. In the context of the SARS-CoV-2 pandemic, few studies have specifically focused on the inflammatory status of older, frail patients with hyperactive delirium (HD) hospitalized for COVID-19.Aim To identify biological correlates of HD at hospital admission and to assess the independent effect of delirium and physical frailty on in-hospital mortality.Methods Data were retrospectively extracted by the multicenter registry GeroCovid Observational Study. Individuals aged ≥ 60 years were included if the information on the presence of HD, frailty based on the modified Fried criteria and inflammatory status had been collected. The risk of mortality was evaluated using a Kaplan–Meier estimator, according to frailty and delirium. Logistic and restricted cubic-spline regressions were employed to assess the relationship between inflammatory markers and HD.Results Three-hundred-thirty-seven older adults were included in the analysis [mean age (SD) 77.1 (9.5) years, 50.1% females], and 11.5% presented with HD. A significant association of both PaO2/FiO2 ratio (p = 0.015) and serum lactate dehydrogenase (p = 0.04) with delirium was observed. By Cox multivariable regression, frail and non-frail patients with HD had a 4.42 and 2.85 higher mortality risk compared with non-frail, non-delirious patients.Conclusions Hyperactive delirium at hospital admission is related with markers of lung failure among older adults, especially when physical frailty coexists. Delirium is associated with increased in-hospital mortality risk, which is doubled by the coexistence of physical frailty.
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- Scarlata, Simone, et al.
(author)
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Advancing healthcare through thoracic ultrasound research in older patients
- 2023
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In: Aging Clinical and Experimental Research. - 1594-0667 .- 1720-8319. ; 35:12, s. 2887-2901
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Research review (peer-reviewed)abstract
- This paper reports the proceedings of a meeting convened by the Research Group on Thoracic Ultrasound in Older People of the Italian Society of Gerontology and Geriatrics, to discuss the current state-of-the-art of clinical research in the field of geriatric thoracic ultrasound and identify unmet research needs and potential areas of development. In the last decade, point-of-care thoracic ultrasound has entered clinical practice for diagnosis and management of several respiratory illnesses, such as bacterial and viral pneumonia, pleural effusion, acute heart failure, and pneumothorax, especially in the emergency–urgency setting. Very few studies, however, have been specifically focused on older patients with frailty and multi-morbidity, who frequently exhibit complex clinical pictures needing multidimensional evaluation. At the present state of knowledge, there is still uncertainty on the best requirements of ultrasound equipment, methodology of examination, and reporting needed to optimize the advantages of thoracic ultrasound implementation in the care of geriatric patients. Other issues regard differential diagnosis between bacterial and aspiration pneumonia, objective grading of interstitial syndrome severity, quantification and monitoring of pleural effusions and solid pleural lesions, significance of ultrasonographic assessment of post-COVID-19 sequelae, and prognostic value of assessment of diaphragmatic thickness and motility. Finally, application of remote ultrasound diagnostics in the community and nursing home setting is still poorly investigated by the current literature. Overall, the presence of several open questions on geriatric applications of thoracic ultrasound represents a strong call to implement clinical research in this field.
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- Trevisan, Caterina, et al.
(author)
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Polypharmacy and Antibody Response to SARS-CoV-2 Vaccination in Residents of Long-Term Care Facilities : The GeroCovid Vax Study
- 2023
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In: Drugs & Aging. - 1170-229X .- 1179-1969. ; 40:12, s. 1133-1141
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Journal article (peer-reviewed)abstract
- Background and Objective Polypharmacy is common in older adults, particularly among those living in long-term care facilities. This condition represents a marker of clinical complexity and might directly affect the immunological response. However, there are limited data on the association of polypharmacy with vaccine immunogenicity. This study evaluated the immune response to anti-SARS-CoV-2 vaccines in older residents of long-term care facilities as a function of the number of medications used.Methods In 478 long-term care facility residents participating in the GeroCovid Vax study, we assessed SARS-CoV-2 trimeric S IgG levels through chemiluminescent assays before the vaccination and after 2, 6, and 12 months. A booster dose was administered between 6- and 12-month assessments. Sociodemographic information and data on chronic diseases and medications were derived from medical records. Based on the number of daily medications, residents were classified into the no polypharmacy (zero to four medications), polypharmacy (five to nine medications), and hyperpolypharmacy (ten or more medications) groups.Results In the sample (mean age 82.1 years, 69.2% female), 200 (41.8%) residents were taking five or fewer medications/day (no polypharmacy), 229 (47.9%) had polypharmacy, and 49 (10.3%) had hyperpolypharmacy. Using linear mixed models adjusted for potential confounders, we found that hyperpolypharmacy was associated with a steeper antibody decline after 6 months from the first vaccine dose administration (β = − 0.29, 95% confidence interval − 0.54, − 0.03, p = 0.03) than no polypharmacy, while no significant differences were observed at 12 months.Conclusions The humoral immune response to SARS-CoV-2 vaccination of older residents showed only slight changes as a function of the number of medications taken. Although it seemed less durable among older residents with hyperpolypharmacy, the booster dose administration equalized such a difference.
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- Trevisan, Caterina, et al.
(author)
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The peculiarities of COVID-19 in older people : Considerations after two years
- 2023
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In: European journal of internal medicine. - 0953-6205 .- 1879-0828. ; 117, s. 45-49
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Journal article (other academic/artistic)abstract
- As written by Cicero in De finibus, Aristotle said, “Hominem ad duas res, ad intelligendum et ad agendum, esse natum”, i.e. “Man is born for two things: to understand and to act”. The path of the scientific and medical community dealing with the coronavirus disease 2019 (COVID-19) pandemic reflects precisely this statement, although much remains to be understood and done. This is particularly true for SARS-CoV-2 infection in older people since the complexity of the disease and the related lack of knowledge overlapped with the complexity and vulnerability of this population, which was the most burdened category. In the first pandemic wave, for instance, more than 80% of COVID-19-related deaths occurred in people older than 70 year [1]. Therefore, the only way out of this scenario was to try to understand and plan new actions to improve the prevention and management of the disease.
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9. |
- Virgilio, Enrico, et al.
(author)
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Diabetes Affects Antibody Response to SARS-CoV-2 Vaccination in Older Residents of Long-term Care Facilities : Data From the GeroCovid Vax Study
- 2022
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:12, s. 2935-2942
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Journal article (peer-reviewed)abstract
- OBJECTIVEType 2 diabetes may affect the humoral immune response after vaccination, but data concerning coronavirus disease 19 (COVID-19) vaccines are scarce. We evaluated the impact of diabetes on antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in older residents of long-term care facilities (LTCFs) and tested for differences according to antidiabetic treatment.RESEARCH DESIGN AND METHODSFor this analysis, 555 older residents of LTCFs participating in the GeroCovid Vax study were included. SARS-CoV-2 trimeric S immunoglobulin G (anti-S IgG) concentrations using chemiluminescent assays were tested before the first dose and after 2 and 6 months. The impact of diabetes on anti-S IgG levels was evaluated using linear mixed models, which included the interaction between time and presence of diabetes. A second model also considered diabetes treatment: no insulin therapy (including dietary only or use of oral antidiabetic agents) and insulin therapy (alone or in combination with oral antidiabetic agents).RESULTSThe mean age of the sample was 82.1 years, 68.1% were women, and 25.2% had diabetes. In linear mixed models, presence of diabetes was associated with lower anti-S IgG levels at 2 (β = −0.20; 95% CI −0.34, −0.06) and 6 months (β = −0.22; 95% CI −0.37, −0.07) after the first vaccine dose. Compared with those without diabetes, residents with diabetes not using insulin had lower IgG levels at 2- and 6-month assessments (β = −0.24; 95% CI −0.43, −0.05 and β = −0.30; 95% CI −0.50, −0.10, respectively), whereas no differences were observed for those using insulin.CONCLUSIONSOlder residents of LTCFs with diabetes tended to have weaker antibody response to COVID-19 vaccination. Insulin treatment might buffer this effect and establish humoral immunity similar to that in individuals without diabetes.
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