Clinical prognostic factors for older people: A systematic review and meta-analysis

Objective: To explore the accuracy and precision of prognostic tools used in older people in predicting mortality, hospitalization, and nursing home admission across different settings and timings. Design: Systematic review and meta-analysis of prospective and retrospective studies. Data sources: A systematic search from database inception until 01st February 2023 was run in Medline, Embase, Cinhal, Cochrane Library. Eligibility criteria: Studies were eligible if they reported accuracy (area under the curve [AUC]) and/or precision (C-index) for the prognostic index in relation to any of the following outcomes: mortality, hospitalization, and nursing home admission. Data extraction and synthesis: Two independent reviewers extracted data. Data were pooled using a random effects model. The risk of bias was assessed with the Quality in Prognosis Studies (QUIPS) tool. If more than three studies for the same setting and time were available, a meta-analysis was performed and evaluated using the GRADE tool; other data were reported descriptively. Results: Among 16,082 studies initially considered, 159 studies with a total of 2398856 older people (mean age: 78 years) were included. The majority of the studies was carried out in hospital or medical wards. In the community setting, only two tools (Health Assessment Tool and the Multidimensional Prognostic Index, MPI) had good precision for long-term mortality. In emergency department setting, Barthel Index had an excellent accuracy in predicting short-term mortality. In medical wards, the MPI had a moderate certainty of the evidence in predicting short-term mortality (13 studies; 11,787 patients; AUC=0.79 and 4 studies; 3915 patients; C-index=0.82). Similar findings were available for MPI when considering longer follow-up periods. When considering nursing home and surgical wards, the literature was limited. The risk of bias was generally acceptable; observed bias was mainly owing to attrition and confounding. Conclusions: Several tools are used to predict poor prognosis in geriatric patients, but only those derived from a multidimensional evaluation have the characteristics of precision and accuracy

Loss of p53 Ser18 and Atm Results in Embryonic Lethality without Cooperation in Tumorigenesis

Phosphorylation at murine Serine 18 (human Serine 15) is a critical regulatory process for the tumor suppressor function of p53. p53Ser18 residue is a substrate for ataxia-telangiectasia mutated (ATM) and ATM-related (ATR) protein kinases. Studies of mice with a germ-line mutation that replaces Ser18 with Ala (p53S18A mice) have demonstrated that loss of phosphorylation of p53Ser18 leads to the development of tumors, including lymphomas, fibrosarcomas, leukemia and leiomyosarcomas. The predominant lymphoma is B-cell lymphoma, which is in contrast to the lymphomas observed in Atm−/− animals. This observation and the fact that multiple kinases phosphorylate p53Ser18 suggest Atm-independent tumor suppressive functions of p53Ser18. Therefore, in order to examine p53Ser18 function in relationship to ATM, we analyzed the lifespan and tumorigenesis of mice with combined mutations in p53Ser18 and Atm. Surprisingly, we observed no cooperation in survival and tumorigenesis in compound p53S18A and Atm−/− animals. However, we observed embryonic lethality in the compound mutant animals. In addition, the homozygous p53Ser18 mutant allele impacted the weight of Atm−/− animals. These studies examine the genetic interaction of p53Ser18 and Atm in vivo. Furthermore, these studies demonstrate a role of p53Ser18 in regulating embryonic survival and motor coordination

La renovación de la palabra en el bicentenario de la Argentina : los colores de la mirada lingüística

El libro reúne trabajos en los que se exponen resultados de investigaciones presentadas por investigadores de Argentina, Chile, Brasil, España, Italia y Alemania en el XII Congreso de la Sociedad Argentina de Lingüística (SAL), Bicentenario: la renovación de la palabra, realizado en Mendoza, Argentina, entre el 6 y el 9 de abril de 2010. Las temáticas abordadas en los 167 capítulos muestran las grandes líneas de investigación que se desarrollan fundamentalmente en nuestro país, pero también en los otros países mencionados arriba, y señalan además las áreas que recién se inician, con poca tradición en nuestro país y que deberían fomentarse. Los trabajos aquí publicados se enmarcan dentro de las siguientes disciplinas y/o campos de investigación: Fonología, Sintaxis, Semántica y Pragmática, Lingüística Cognitiva, Análisis del Discurso, Psicolingüística, Adquisición de la Lengua, Sociolingüística y Dialectología, Didáctica de la lengua, Lingüística Aplicada, Lingüística Computacional, Historia de la Lengua y la Lingüística, Lenguas Aborígenes, Filosofía del Lenguaje, Lexicología y Terminología

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Older People Hospitalized for COVID-19: Prognostic Role of Multidimensional Prognostic Index and Other Prognostic Scores

During the SARS-CoV-2 pandemic, frailty and patients’ poor outcomes seem to be closely related. However, there is no clear indication of the significance of this connection and the most adequate risk index in clinical practice. In this study, we compared a short version of MPI (multidimensional prognostic index) and other two prognostic scores for COVID-19 as potential predictors of poor patient outcomes. The patients were consecutively enrolled in the hospital of Palermo for COVID-19. The accuracy of Brief-MPI, 4C score and COVID-GRAM score in points was evaluated using the area under the curve (AUC) with 95% CI, taking mortality or sub-ICU admission as outcome. The study included 112 participants (mean age 77.6, 55.4% males). During a mean of 16 days of hospitalization, Brief-MPI significantly increased by 0.03 ± 0.14 (p = 0.04), whilst COVID-GRAM did not. Brief-MPI, 4C score and COVID-GRAM scores had good accuracy in predicting negative outcomes (AUC > 0.70 for all three scores). Brief-MPI was significantly associated with an increased mortality/ICU admission risk, indicating the importance of multidimensional impairment in clinical decision-making with an accuracy similar to other prognostic scores commonly used in COVID-19 study, providing information regarding domains for which interventions can be proposed

Multidimensional Frailty and Vaccinations in Older People: A Cross-Sectional Study

It is known that influenza, herpes zoster, pneumococcal and pertussis infections may increase morbidity and mortality in older people. Vaccinations against these pathogens are effective in older adults. Frailty seems to be an important determinant of vaccination rates, yet data supporting this association are still missing. Therefore, we aimed to investigate the prevalence of four recommended vaccinations (influenza, herpes zoster, pneumococcal and diphtheria-tetanus-pertussis) and the association with multidimensional frailty assessed using a self-reported comprehensive geriatric assessment tool, i.e., the multidimensional prognostic index (SELFY-MPI). Older participants visiting the outpatient clinic of Azienda Ospedaliera Universitaria, Palermo, Italy were included. The SELFY-MPI questionnaire score was calculated based on eight different domains, while the vaccination status was determined using self-reported information. We included 319 participants from the 500 initially considered (63.8%). Vaccination against influenza was observed in 70.5% of the cases, whilst only 1.3% received the vaccination against diphtheria-tetanus-pertussis. Participants with higher SELFY-MPI scores were more likely to report vaccination against pneumococcus (45.6 vs. 28.3%, p = 0.01), whilst no significant differences were observed for the other vaccinations. In conclusion, the coverage of recommended vaccinations is low. Higher SELFY-MPI scores and vaccination status, particularly anti-pneumococcus, appear to be associated, but future studies are urgently needed for confirming that frailty is associated with vaccination status in older people

Clinical prognostic factors for older people: A systematic review and meta-analysis

Objective To explore the accuracy and precision of prognostic tools used in older people in predicting mortality, hospitalization, and nursing home admission across different settings and timings. Design Systematic review and meta-analysis of prospective and retrospective studies. Data sources A systematic search from database inception until 01st February 2023 was run in Medline, Embase, Cinhal, Cochrane Library. Eligibility criteria Studies were eligible if they reported accuracy (area under the curve [AUC]) and/or precision (C-index) for the prognostic index in relation to any of the following outcomes: mortality, hospitalization, and nursing home admission. Data extraction and synthesis Two independent reviewers extracted data. Data were pooled using a random effects model. The risk of bias was assessed with the Quality in Prognosis Studies (QUIPS) tool. If more than three studies for the same setting and time were available, a meta-analysis was performed and evaluated using the GRADE tool; other data were reported descriptively. Results Among 16,082 studies initially considered, 159 studies with a total of 2398856 older people (mean age: 78 years) were included. The majority of the studies was carried out in hospital or medical wards. In the community setting, only two tools (Health Assessment Tool and the Multidimensional Prognostic Index, MPI) had good precision for long-term mortality. In emergency department setting, Barthel Index had an excellent accuracy in predicting short-term mortality. In medical wards, the MPI had a moderate certainty of the evidence in predicting short-term mortality (13 studies; 11,787 patients; AUC=0.79 and 4 studies; 3915 patients; C-index=0.82). Similar findings were available for MPI when considering longer follow-up periods. When considering nursing home and surgical wards, the literature was limited. The risk of bias was generally acceptable; observed bias was mainly owing to attrition and confounding. Conclusions Several tools are used to predict poor prognosis in geriatric patients, but only those derived from a multidimensional evaluation have the characteristics of precision and accuracy.</p