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OBJECTIVE: Frailty has been extensively studied in end-stage kidney disease (ESKD) and kidney transplant (KT) patients. The identification of frailty is useful to predict adverse outcomes among ESKD and KT patients. The recent concept of intrinsic capacity (IC) appears as a good and easy-to-understand tool to screen for and monitor frailty in older adults with ESKD. This study aims to assess the relationships between frailty and IC in older adults with ESKD awaiting KT. DESIGN: Cross-sectional study SETTING AND PARTICIPANTS: 236 patients from a day-care geriatric unit undergoing pre-KT geriatric assessment between 2017 and 2022 were included in the main sample, and 151 patients in an independent multicentric replication sample. MEASUREMENTS: Frailty was evaluated using the physical frailty phenotype (PFP) and IC measures using the World Health Organization's screening (step 1) and diagnostic (step 2) tools for five IC domains (vitality, locomotion, audition, cognition, psychology). Multivariate regressions were run to assess relationships between PFP and IC domains, adjusted for age, sex, and comorbidities. Analyses were replicated using another independent multicenter cohort including 151 patients with ESKD to confirm the results. RESULTS: Impairments in the locomotion, psychology, and vitality IC domains according to WHO screening tools were associated with frailty (odds ratio 9.62 [95% CI 4.09-24.99], 3.19 [95% CI 1.11-8.88], and 3.11 [95% CI 1.32-7.29], respectively). When IC were measured linearly with z-scores, all IC domains except hearing were inversely associated with frailty. In the replication cohort, results were overall similar, with a greater association between psychology domain and frailty. CONCLUSION: This study highlights the relationship between frailty and IC in ESKD patients. We assume that IC may be assessed and monitored in ESKD patients, to predict and prevent future frailty, and post-KT adverse outcomes.
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Fragilidad , Evaluación Geriátrica , Fallo Renal Crónico , Trasplante de Riñón , Humanos , Masculino , Femenino , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Anciano , Fragilidad/complicaciones , Estudios Transversales , Evaluación Geriátrica/métodos , Anciano Frágil , Persona de Mediana Edad , Anciano de 80 o más AñosRESUMEN
There is much public anxiety about how today's students use chatbots to complete assignments. But AI's integration within schools will more deeply impact the next generation of college graduates. The market value of future college degrees is far from certain.
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Instituciones Académicas , Estudiantes , Humanos , Escolaridad , Ansiedad , Trastornos de AnsiedadRESUMEN
OBJECTIVE: The Hospital Frailty Risk Score (HFRS) can be applied to medico-administrative datasets to determine the risks of 30-day mortality and long length of stay (LOS) in hospitalized older patients. The objective of this study was to compare the HFRS with Charlson and Elixhauser comorbidity indices, used separately or combined. DESIGN: A retrospective analysis of the French medical information database. The HFRS, Charlson index, and Elixhauser index were calculated for each patient based on the index stay and hospitalizations over the preceding 2 years. Different constructions of the HFRS were considered based on overlapping diagnostic codes with either Charlson or Elixhauser indices. We used mixed logistic regression models to investigate the association between outcomes, different constructions of HFRS, and associations with comorbidity indices. SETTING: 743 hospitals in France. PARTICIPANTS: All patients aged 75 years or older hospitalized as an emergency in 2017 (n=1,042,234).Main outcome measures: 30-day inpatient mortality and LOS >10 days. RESULTS: The HFRS, Charlson, and Elixhauser indices were comparably associated with an increased risk of 30-day inpatient mortality and long LOS. The combined model with the highest c-statistic was obtained when associating the HFRS with standard adjustment and Charlson for 30-day inpatient mortality (adjusted c-statistics: HFRS=0.654; HFRS + Charlson = 0.676) and with Elixhauser for long LOS (adjusted c-statistics: HFRS= 0.672; HFRS + Elixhauser =0.698). CONCLUSIONS: Combining comorbidity indices and HFRS may improve discrimination for predicting long LOS in hospitalized older people, but adds little to Charlson's 30-day inpatient mortality risk.
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Fragilidad , Multimorbilidad , Humanos , Anciano , Estudios Retrospectivos , Comorbilidad , Fragilidad/epidemiología , Mortalidad Hospitalaria , Factores de Riesgo , HospitalesRESUMEN
Increasing disability-free life expectancy is a crucial issue to optimize active ageing and to reduce the burden of evitable medical costs. One of the main challenges is to develop pragmatic and personalized prevention strategies in order to prevent frailty, counteract adverse outcomes such as falls and mobility disability, and to improve quality of life. Strong evidence reports the effectiveness of exercise interventions to improve various physical parameters and muscle function that are cornerstones of frailty. Other findings also suggest that the interactions between nutrition and physical exercise with or without health behavior promotion prevent the development of frailty. Multimodal programs, including structured exercise, adequate dietary intervention and health behavior promotion, appear increasingly consensual. However, in order for implementation in real-life settings, some pitfalls need to be addressed. In this perspective, structuring and tailoring feasible, acceptable and sustainable interventions to optimize exercise training responses are essential conditions to warrant short, medium and long-term individual benefits. The different components of exercise programs appear to be fairly consensual and effective. However, specific composition of the programs proposed (frequency, intensity, type, time, volume and progressiveness) have to be tailored to individual characteristics and objectives in order to improve exercise responses. The intervention approaches, behavioral strategies and indications for these programs also need to be refined and framed. The main objective of this work is to guide the actions of healthcare professionals and enable them to widely and effectively implement multimodal programs including exercise, nutrition and behavioral strategies in real-life settings.
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Fragilidad , Humanos , Anciano , Fragilidad/prevención & control , Vida Independiente , Calidad de Vida , Ejercicio Físico , Terapia por EjercicioRESUMEN
BACKGROUND: In COVID-19 patients, older age (sixty or older), comorbidities, and frailty are associated with a higher risk for mortality and invasive mechanical ventilation (IMV) failure. It therefore seems appropriate to suggest limitations of care to older and vulnerable patients with severe COVID-19 pneumonia and a poor expected outcome, who would not benefit from invasive treatment. HFNO (high flow nasal oxygen) is a non-invasive respiratory support device already used in de novo acute respiratory failure. The main objective of this study was to evaluate the survival of patients treated with HFNO outside the ICU (intensive care unit) for a severe COVID-19 pneumonia, otherwise presenting limitations of care making them non-eligible for IMV. Secondary objectives were the description of our cohort and the identification of prognostic factors for HFNO failure. METHODS: We conducted a retrospective cohort study. We included all patients with limitations of care making them non-eligible for IMV and treated with HFNO for a severe COVID-19 pneumonia, hospitalized in a COVID-19 unit of the pulmonology department of Lyon Sud University Hospital, France, from March 2020 to March 2021. Primary outcome was the description of the vital status at day-30 after HFNO initiation, using the WHO (World Health Organization) 7-points ordinal scale. RESULTS: Fifty-six patients were included. Median age was 83 years [76.3-87.0], mean duration for HFNO was 7.5 days, 53% had a CFS score (Clinical Frailty Scale) >4. At day-30, 73% of patients were deceased, one patient (2%) was undergoing HFNO, 9% of patients were discharged from hospital. HFNO failure occurred in 66% of patients. Clinical signs of respiratory failure before HFNO initiation (respiratory rate >30/min, retractions, and abdominal paradoxical breathing pattern) were associated with mortality (p = 0.001). CONCLUSIONS: We suggest that HFNO is an option in non-ICU skilled units for older and frail patients with a severe COVID-19 pneumonia, otherwise non-suitable for intensive care and mechanical ventilation. Observation of clinical signs of respiratory failure before HFNO initiation was associated with mortality.
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COVID-19 , Fragilidad , Insuficiencia Respiratoria , Humanos , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/terapia , Oxígeno/uso terapéutico , Respiración Artificial , Estudios Retrospectivos , Anciano Frágil , Fragilidad/epidemiología , Fragilidad/tratamiento farmacológico , Insuficiencia Respiratoria/epidemiología , Insuficiencia Respiratoria/terapiaRESUMEN
Host kinases play essential roles in the host cell cycle, innate immune signaling, the stress response to viral infection, and inflammation. Previous work has demonstrated that coronaviruses specifically target kinase cascades to subvert host cell responses to infection and rely upon host kinase activity to phosphorylate viral proteins to enhance replication. Given the number of kinase inhibitors that are already FDA approved to treat cancers, fibrosis, and other human disease, they represent an attractive class of compounds to repurpose for host-targeted therapies against emerging coronavirus infections. To further understand the host kinome response to betacoronavirus infection, we employed multiplex inhibitory bead mass spectrometry (MIB-MS) following MERS-CoV and SARS-CoV-2 infection of human lung epithelial cell lines. Our MIB-MS analyses revealed activation of mTOR and MAPK signaling following MERS-CoV and SARS-CoV-2 infection, respectively. SARS-CoV-2 host kinome responses were further characterized using paired phosphoproteomics, which identified activation of MAPK, PI3K, and mTOR signaling. Through chemogenomic screening, we found that clinically relevant PI3K/mTOR inhibitors were able to inhibit coronavirus replication at nanomolar concentrations similar to direct-acting antivirals. This study lays the groundwork for identifying broad-acting, host-targeted therapies to reduce betacoronavirus replication that can be rapidly repurposed during future outbreaks and epidemics. The proteomics, phosphoproteomics, and MIB-MS datasets generated in this study are available in the Proteomics Identification Database (PRIDE) repository under project identifiers PXD040897 and PXD040901.
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COVID-19 , Hepatitis C Crónica , Coronavirus del Síndrome Respiratorio de Oriente Medio , Humanos , Antivirales/farmacología , Inhibidores mTOR , Fosfatidilinositol 3-Quinasas , SARS-CoV-2 , Replicación Viral , Coronavirus del Síndrome Respiratorio de Oriente Medio/fisiología , Serina-Treonina Quinasas TORRESUMEN
Extended transition state-natural orbitals for chemical valence (ETS-NOCV)] data were used to rank electron acceptor capacities for several potentially synergistic anionic ligands incorporated into linear d10 [(NH3)Pd(A)]-, square planar d8 [(NN2)Ru(A)]-, and octahedral d6 [(AsN4)Tc(A)]- complexes [A = anionic ligand, NN2 = HN(CH2CH2CH2NH2)2, and AsN4 = [As(CH2CH2CH2NH2)4]-]. It was possible to differentiate between the best acceptors, among them BI2- and B(CF3)2-, and the poorest ones. A sizable fraction of the anionic ligands studied exhibit similar acceptor capacities (backbonding), mostly regardless of d electron count. A number of trends were discerned, including the fact that acceptor capacity decreases down families and across rows but increases down families of the peripheral substituents. The latter appears tied to the ability of the peripheral ligands to compete with the metal in donating electrons to the ligand-binding atom.
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Systematic computational studies of pericyclic Diels-Alder reactions between (H3C)2C=C(CH3)2, 1, and all permutations of substituted cyclopentadienes c-C5R1R2R3R4R5aR5b (R = H, CH3, CF3, F) allowed isolation of substitutional effects on Gibbs free energy barrier heights and reaction Gibbs free energies. "Average Substitution Gibbs Free Energy Correction" ΔG ASC# /ΔG ASC# values for each substituent in each position appeared to be additive. Substituent effects on barriers showed interesting contrasts. Methyl substitution at positions 5a and 5b increased barriers significantly, while substitution at all other positions had essentially no impact. In contrast, fluoro substitution at positions 5a and 5b lowered barriers more than substitution at other positions. Trifluoromethyl substitution mixed these effects, in that substitution at positions 5a and 5b increased barriers, but substitution at other positions lowered them. Despite the variances, ΔG ASC# /ΔG ASC# values allowed reliable prediction of barriers and exergonicities for reactions between 1 and highly substituted cyclopentadienes, and between 1 and cyclopentadienes with random mixtures of CH3/CF3/F substituents. ΔG ASC# /ΔG ASC# values were correlated with steric considerations and quantum theory of atoms in molecules (QTAIM) calculations. Overall, the ASC values provide a resource for predicting which Diels-Alder reactions of this type should occur at rapid rates and/or give stable bicyclic products.
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Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, ß-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and ß-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and ß-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.
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COVID-19 , Selenio , Oligoelementos , Humanos , Anciano , Antioxidantes/análisis , Vitamina A , beta Caroteno , Cobre , Pandemias , Estudios Retrospectivos , Ácido Ascórbico , Suplementos Dietéticos/análisis , Vitaminas/análisis , Minerales , Zinc , Micronutrientes/análisisRESUMEN
OBJECTIVE: To undertake a synthesis of evidence-based research for seven innovative models of care to inform the development of new hospitals. DESIGN: Umbrella review. SETTING: Interventions delivered inside and outside of acute care settings. PARTICIPANTS: Children and adults with one or more identified acute or chronic health conditions. DATA SOURCES: PsycINFO, Ovid MEDLINE and CINAHL. PRIMARY AND SECONDARY OUTCOME MEASURES: Clinical indicators and mortality, healthcare utilisation, quality of life, self-management and self-care and patient knowledge. RESULTS: A total of 66 reviews were included, synthesising evidence from 1272 primary studies across the 7 models of care. Virtual care was the most common model studied, addressed by 47 (73%) of the reviews. Common outcomes evaluated across reviews were clinical indicators and mortality, healthcare utilisation, self-care and self-management, patient knowledge, quality of life and cost-effectiveness. The findings indicate that the innovative models of healthcare we identified in this review may be effective in managing patients with a range of acute and chronic conditions. Most of the included reviews reported evidence of comparable or improved care. CONCLUSIONS: A consideration of local infrastructure and individual patient characteristics, such as health literacy, may be critical in determining the suitability of models of care for patients and their implementation in local health systems. TRIAL REGISTRATION NUMBER: 10.17605/OSF.IO/PS6ZU.
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Aceptación de la Atención de Salud , Calidad de Vida , Adulto , Niño , Humanos , Enfermedad Crónica , AutocuidadoRESUMEN
BACKGROUND: Sarcopenia has a significant medical and economic impact. Serum fibroblast growth factor 19 (FGF19) has recently been described as promoting muscle mass and strength, and could be an interesting marker for early diagnosis of sarcopenia and prevention of its consequences. Ultrasound is a robust non-invasive technique used to measure muscle parameters, which cannot be evaluated by usual body composition measures, but are known to be associated with muscle function. In this cross-sectional cohort study, we aimed to determine whether FGF19 levels were correlated with functional muscle tests and muscle ultrasound parameters. METHODS: Patients over 70 years old with a mobility disability risk were recruited from the cohort of the "well on your feet" mobility loss prevention program. Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older Patients 2 (EWGSOP2) criteria. We have performed functional battery tests, muscle ultrasound measures and bioimpedance spectroscopy. FGF19 levels were measured by the ELISA method. RESULTS: Out of 52 patients involved (34 women, mean age 81.3 years), 30 patients were sarcopenic (15 patients with probable sarcopenia and 15 with certain sarcopenia). Sarcopenic patients were older (mean 82.8 versus 79.6 years, P = 0.033), with higher frailty Fried score (P = 0.006), lower IADL score (P = 0.008), had lower daily protein intakes (P = 0.023) and were less performant to muscle functional tests than non-sarcopenic patients. Serum FGF19 levels were negatively correlated with the SPPB score (rs = 0.28; P = 0.045). FGF19 levels were correlated positively with the pennation angle (rs = 0.31; P = 0.024), but negatively with muscle fiber length (rs = -0.44; P = 0.001). We found no association between FGF19 and muscle thickness (P = 0.243). CONCLUSION: We highlighted in older patients significant correlations between FGF19 levels, pennation angle and muscle fiber length, suggesting that FGF19 could provide an enabling environment for the development of large muscle fibers, as previously suggested in histological studies in mice. However, high FGF-19 levels were unexpectedly associated with a low SPPB score. Further studies are needed to validate and further elucidate these exploratory findings.
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Fragilidad , Sarcopenia , Femenino , Estudios Transversales , Fragilidad/patología , Fuerza de la Mano , Fibras Musculares Esqueléticas/patología , Músculo Esquelético/patología , Sarcopenia/diagnóstico , Humanos , Masculino , Anciano de 80 o más Años , AncianoRESUMEN
AIM: In the present study, we evaluated the triage process particularly for older patients after calls to Emergency Medical Call Centers (ECC), according to the geriatric assessment tool. METHODS: In this observational population-based cross-sectional study in the Rhône (France), we analyzed the audiotapes of all calls received by ECC concerning patients aged ≥75 years, during seven randomly selected days, over a period of 1 year. We analyzed whether information about seven key items, predefined by a panel of experts as essential for quality telephone triage of seniors, was actually collected. RESULTS: Among 4168 calls, 712 (17.1%) concerned patients >75 years (mean ± SD, age 84.6 ± 5.6 years). The mean duration of calls was 3 min 28 s. Information about living arrangements (alone or not), dependency, multiple pathologies, polymedication, ability to walk independently or with help, and hospitalization in the previous 3 months was not collected in 20%, 42%, 40%, 45%, 58% and 61% of calls, respectively. All seven geriatric items were collected for only 54 (7.8%) calls, and only three criteria collected for 277 (40%) calls. Nurse-managed calls were significantly associated with the collection of less geriatric items compared with physician-managed calls. CONCLUSION: Key information is particularly important to guide the orientation, and further management of older patients may be lacking during the telephone triage of patients in ECCs. This may represent an important level of improvement of the triage process, to address the needs of older patients better and avoid inappropriate emergency department visits. Geriatr Gerontol Int 2023; 23: 54-59.
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Teléfono , Triaje , Humanos , Anciano , Estudios Transversales , Servicio de Urgencia en Hospital , HospitalesRESUMEN
BACKGROUND: Emergency Departments (ED) have seen an increasing number of older patients who are mostly referred following a call to the Emergency Medical Services (EMS). Long waiting times in settings, which are not designed to meet older patients' needs, may increase the risk of hospital-acquired complications. Unnecessary visits should therefore be avoided as much as possible. The objective of the study was to evaluate whether a program to provide geriatric knowledge and tools to the dispatching physicians of the EMS could decrease ED referrals of older patients. METHODS: Design: Before-and-after study with two 6-month periods before and after intervention. PARTICIPANTS: All calls received by a dispatching physician of the Rhône EMS from 8 am to 6 pm concerning patients aged 75 years or above during the study period. INTERVENTION: A program consisting of training dispatching physicians in the specific care of older patients and the developing, with a multidisciplinary team, of specific tools for dispatching physicians. OUTCOME: Proportion of ED referrals of patients aged 75 years or above after a call to the EMS. RESULTS: A total of 2671 calls to the Rhône EMS were included corresponding to 1307 and 1364 patients in the pre-and post-intervention phases, respectively. There was no significant difference in the proportion of referrals to the ED between the pre-intervention (61.7%) and the post-intervention (62.8%) phases (p = 0.57). Contact of the patients with their General Practitioner (GP) in the month preceding the call was associated with a 22% reduced probability of being referred to an ED. CONCLUSIONS: No beneficial effect of the intervention was demonstrated. This strategy of intervention is probably not effective enough in such time-constraint environment. Other strategies with a specific parallel dispatching of geriatric calls by geriatricians should be tested to avoid these unnecessary ED referrals. TRIAL REGISTRATION: ClinicalTrials NCT02712450.
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Servicios Médicos de Urgencia , Médicos , Humanos , Anciano , Servicio de Urgencia en Hospital , Derivación y Consulta , GeriatrasRESUMEN
Mitochondria are multifaceted organelles which are important for bioenergetics, biosynthesis and signaling in metazoans. Mitochondrial functions are frequently altered in cancer to promote both the energy and the necessary metabolic intermediates for biosynthesis required for tumor growth. Cancer stem cells (CSCs) contribute to chemotherapy resistance, relapse, and metastasis. Recent studies have shown that while non-stem, bulk cancer cells utilize glycolysis, breast CSCs are more dependent on oxidative phosphorylation (OxPhos) and therefore targeting mitochondria may inhibit CSC function. We previously reported that small molecule ONC201, which is an agonist for the mitochondrial caseinolytic protease (ClpP), induces mitochondrial dysfunction in breast cancer cells. In this study, we report that ClpP agonists inhibit breast cancer cell proliferation and CSC function in vitro and in vivo. Mechanistically, we found that OxPhos inhibition downregulates multiple pathways required for CSC function, such as the mevalonate pathway, YAP, Myc, and the HIF pathway. ClpP agonists showed significantly greater inhibitory effect on CSC functions compared with other mitochondria-targeting drugs. Further studies showed that ClpP agonists deplete NAD(P)+ and NAD(P)H, induce redox imbalance, dysregulate one-carbon metabolism and proline biosynthesis. Downregulation of these pathways by ClpP agonists further contribute to the inhibition of CSC function. In conclusion, ClpP agonists inhibit breast CSC functions by disrupting mitochondrial homeostasis in breast cancer cells and inhibiting multiple pathways critical to CSC function. Significance: ClpP agonists disrupt mitochondrial homeostasis by activating mitochondrial matrix protease ClpP. We report that ClpP agonists inhibit cell growth and cancer stem cell functions in breast cancer models by modulating multiple metabolic pathways essential to cancer stem cell function.
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Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Péptido Hidrolasas/metabolismo , NAD/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Mitocondrias , Homeostasis , Endopeptidasas/metabolismo , Células Madre Neoplásicas , Endopeptidasa Clp/metabolismoRESUMEN
INTRODUCTION: Frailty is characterised by vulnerability to adverse health outcomes and increases with age. Many frailty risk scores have been developed. One important example is the Hospital Frailty Risk Score (HFRS) which has the potential to be widely used and automatically calculated which will provide accurate assessment of frailty in a time/cost-effective manner. This systematic review, therefore, seeks to describe the HFRS use since its publication in 2018. METHODS AND ANALYSIS: The proposed systematic review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will include published original peer-reviewed articles, preprints, conference proceedings and letters to the editor reporting primary data where there is an English language abstract available from 1 January 2018 to 30 June 2022. Databases to be searched are MEDLINE, EMBASE and Web of Science. Additional studies from, for example, the reference of the included studies will be identified and assessed for potential inclusion. Two independent reviewers will perform and assess the following: (1) eligibility of the included studies, (2) critical appraisal using the Cochrane Risk of Bias in Non-randomized Studies of Interventions tool, and (3) data extraction using a predefined form. Disagreements will be resolved through discussions or by involvement of a third reviewer. It may be possible to undertake a meta-analysis if there are sufficient studies reporting effect measures in homogenous populations and/or settings. Effect sizes will be calculated using meta-analysis methods and expressed as risk ratios or ORs with 95% CIs. ETHICS AND DISSEMINATION: No ethical approval is required for this systematic review as it will use secondary data only. The results of the systematic review will be submitted for publication in recognised peer-reviewed journals related to frailty and geriatric care and will be widely disseminated through conferences, congresses, seminars, symposia and scientific meetings.
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Fragilidad , Anciano , Humanos , Fragilidad/diagnóstico , Hospitales , Metaanálisis como Asunto , Proyectos de Investigación , Factores de Riesgo , Revisiones Sistemáticas como AsuntoRESUMEN
Cytomegalovirus (CMV) reactivation from latency following immune dysregulation remains a serious risk for patients, often causing substantial morbidity and mortality. Here, we demonstrate the CMV-encoded G protein-coupled receptor, US28, in coordination with cellular Ephrin receptor A2, attenuates mitogen-activated protein kinase signaling, thereby limiting viral replication in latently infected primary monocytes. Furthermore, treatment of latently infected primary monocytes with dasatinib, a Food and Drug Association-approved kinase inhibitor used to treat a subset of leukemias, results in CMV reactivation. These ex vivo data correlate with our retrospective analyses of the Explorys electronic health record database, where we find dasatinib treatment is associated with a significant risk of CMV-associated disease (odds ratio 1.58, P = 0.0004). Collectively, our findings elucidate a signaling pathway that plays a central role in the balance between CMV latency and reactivation and identifies a common therapeutic cancer treatment that elevates the risk of CMV-associated disease.
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Résumé L'état confusionnel aigu (ECA) est fréquent chez les patients âgés hospitalisés induisant de graves conséquences cliniques. Malgré sa prévalence élevée, l'ECA est souvent sous-diagnostiqué. Un repérage précoce de l'ECA permettrait une prise en charge optimisée, et une diminution de l'incidence des complications. Pour cela, la validation d'outils formalisés et simples d'utilisation est nécessaire.L'objectif de cette revue narrative était de décrire les performances et l'intérêt des outils de repérage de l'ECA les plus fréquemment utilisés en pratique clinique et en recherche, dont ceux ayant une durée de passation rapide (durée inférieure à 3 minutes).Cette revue a permis d'identifier quatre outils, fréquemment utilisés, et validés sur le plan international (CAM, DRS-R-98, DOSS, MDAS), dont trois disposent d'une version française. Les temps de passation de ces outils varient entre 5 et 30 minutes. Bien qu'ils aient un niveau de preuve plus limité, d'autres outils ayant une durée de passation plus rapide, comme la 4AT, la 3D-CAM et l'UB-CAM, semblent prometteurs, notamment en raison d'excellentes performances diagnostiques. De prochaines études devront être menées afin de valider ces outils en langue française, et de mieux préciser leur utilisation et leur impact en pratique clinique. Abstract Delirium is very common in hospitalized older patients and associated with serious clinical outcomes, notably increased risk of functional decline and death. Despite its high prevalence in the hospital setting, delirium is still underdiagnosed. A better identification would allow an early management and a reduction of its complications. To achieve this, the validation of formalized, easy-to-use and quick tools for the identification of delirium and their implementation in our clinical practice are necessary.The objective of this narrative review is to describe the available tools for delirium identification most commonly used in clinical practice and in research, followed by those that are quick to very quick to complete (i.e., less than 3 minutes).This review identified 4 tools frequently used internationally (CAM, DRS-R-98, DOSS, MDAS). Their completion time varies from 5 to 30 minutes. Rapid or very rapid tools exist, with very good diagnostic performance. Among them, the 4AT, the 3D-CAM and the UB-CAM seem particularly promising. These last tools seem interesting for a large-scale implementation at the national level, but a validation in French remains to be done.
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Delirio , Anciano , HumanosRESUMEN
Fatigue is a highly prevalent symptom in both cancer patients and the older population, and it contributes to quality-of-life impairment. Cancer treatment-related fatigue should thus be included in the risk/benefit assessment when introducing any treatment, but tools are lacking to a priori estimate such risk. This scoping review was designed to report the current evidence regarding the frequency of fatigue for the different treatment regimens proposed for the main cancer indications, with a specific focus on age-specific data, for the following tumors: breast, ovary, prostate, urothelium, colon, lung and lymphoma. Fatigue was most frequently reported using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) versions 3 to 5. A total of 324 regimens were analyzed; data on fatigue were available for 217 (67%) of them, and data specific to older patients were available for 35 (11%) of them; recent pivotal trials have generally reported more fatigue grades than older studies, illustrating increasing concern over time. This scoping review presents an easy-to-understand summary that is expected to provide helpful information for shared decisions with patients regarding the anticipation and prevention of fatigue during each cancer treatment.
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The bis(diethyl ether) and 1,2-dimethoxyethane (dme) adducts of molybdenum(IV) chloride and tungsten(IV) chloride are valuable starting materials for a variety of synthetic inorganic and organometallic reactions. Despite the broad utility and extensive use of these 6-coordinate complexes, their syntheses remain unoptimized, and their characterization incomplete after more than three decades. While exploring the ligand exchange behaviour of trans-MoCl4(OEt2)2, we obtained single crystals of this red-orange complex and subsequently compared its structural parameters with those of the recently reported trans-WCl4(OEt2)2. Significantly improved procedures for both MoCl4(dme) and WCl4(dme) were developed, and X-ray diffraction data were obtained and analysed. The magnetic properties of the dme adducts were probed, both with Gouy and SQUID magnetometry measurements. The magnetic moment of WCl4(dme) was smaller than that of MoCl4(dme), an observation that we attribute to the greater spin-orbit coupling of tungsten. Electronic structure studies were also conducted to probe the preferential trans configuration of the diethyl ether adducts and to assign the UV-Vis spectra of the dme adducts.