16 research outputs found
Laura Cereta: In defense of a "Republic of Women"
No full textWould exceptional and intellectually talented women be exceptions to the rule? Laura Cereta, an Italian humanist of the 15th century, seeks to answer this question, which accurately reflects a conception of femininity repeatedly presented and defended by philosophers and writers affiliated with various intellectual traditions, in one of her most incisive letters within her collection of epistolary essays. Throughout the lines addressed to a correspondent ironically named Bibolo Semproni, Cereta challenges and aims to refute, using examples from history and mythology, the idea that women are inherently morally and intellectually inferior. This article closely follows the argument developed by the author in the specific letter, highlighting especially her defense of women\u27s right to education and her use of the image of a kind of genealogical tree, a long and noble lineage of celebrated women – a generositas – indicating the existence of a historically documented and constituted “republic of women” [respublica mulierum].Seriam as mulheres notáveis e intelectualmente talentosas exceções à regra? A esta pergunta, que reflete com precisão uma concepção do feminino reiteradamente apresentada e defendida por filósofos e escritores filiados às mais diversas tradições intelectuais, Laura Cereta, uma humanista italiana do século XV, busca responder em uma das cartas mais agudas de seu conjunto de ensaios epistolares. Ao longo das linhas endereçadas a um correspondente que recebe, ironicamente, o nome de Bibolo Semproni, Cereta desafia e busca refutar, com base em exemplos tomados da história e da mitologia, a ideia segundo a qual as mulheres seriam, por natureza, moral e intelectualmente inferiores. Trata-se, neste artigo, de seguir de perto o argumento desenvolvido pela autora na carta em questão, destacando, em especial, sua defesa do direito das mulheres à educação e seu recurso à imagem de uma espécie de árvore genealógica, uma longa e nobre linhagem de mulheres célebres – uma generositas –, que apontaria para a existência de uma república das mulheres [respublica mulierum] documentada e constituída historicamente. 
Microglia Susceptibility to Free Bilirubin Is Age-Dependent
No full textFunding: This work was supported by National Funds (Fundacão para a Ciencia e a Tecnologia—UID/DTP/04138/2015-2019) to iMed.ULisboa. AF had a post-doctoral research position (C2007-FFUL/UBMBE/02/ 2011) and AV a post-doc fellowship (SFRH/BPD/76590/2011), both granted by FCT. CS and ES were Master students from University of Bologna who developed their thesis at Universidade de Lisboa, with fellowships from Erasmus+ Programme. We thank Professor Stefano Girotti from the University of Bologna for establishing such collaborative Program and for the local supervision of the students. The funding organization had no role in data collection and analysis, decision to publish, or preparation of the manuscripIncreased concentrations of unconjugated bilirubin (UCB), namely its free fraction (Bf), in neonatal life may cause transient or definitive injury to neurons and glial cells. We demonstrated that UCB damages neurons and glial cells by compromising oligodendrocyte maturation and myelination, and by activating astrocytes and microglia. Immature neurons and astrocytes showed to be especially vulnerable. However, whether microglia susceptibility to UCB is also age-related was never investigated. We developed a microglia culture model in which cells at 2 days in vitro (2DIV) revealed to behave as the neonatal microglia (amoeboid/reactive cells), in contrast with those at 16DIV microglia that performed as aged cells (irresponsive/dormant cells). Here, we aimed to unveil whether UCB-induced toxicity diverged from the young to the long-cultured microglia. Cells were isolated from the cortical brain of 1- to 2-day-old CD1 mice and incubated for 24 h with 50/100 nM Bf levels, which were associated to moderate and severe neonatal hyperbilirubinemia, respectively. These concentrations of Bf induced early apoptosis and amoeboid shape in 2DIV microglia, while caused late apoptosis in 16DIV cells, without altering their morphology. CD11b staining increased in both, but more markedly in 2DIV cells. Likewise, the gene expression of HMGB1, a well-known alarmin, as well as HMGB1 and GLT-1–positive cells, were enhanced as compared to long-maturated microglia. The CX3CR1 reduction in 2DIV microglia was opposed to the 16DIV cells and suggests a preferential Bf-induced sickness response in younger cells. In conformity, increased mitochondrial mass and NO were enhanced in 2DIV cells, but unchanged or reduced, respectively, in the 16DIV microglia. However, 100 nM Bf caused iNOS gene overexpression in 2DIV and 16DIV cells. While only arginase 1/IL-1β gene expression levels increased upon 50/100 nM Bf treatment in long-maturated microglia, MHCII/arginase 1/TNF-α/IL-1β/IL-6 (>10-fold) were upregulated in the 2DIV microglia. Remarkably, enhanced inflammatory-associated microRNAs (miR-155/miR-125b/miR-21/miR-146a) and reduced anti-inflammatory miR-124 were found in young microglia by both Bf concentrations, while remained unchanged (miR/21/miR-125b) or decreased (miR-155/miR-146a/miR-124) in aged cells. Altogether, these findings support the neurodevelopmental susceptibilities to UCB-induced neurotoxicity, the most severe disabilities in premature babies, and the involvement of immune-inflammation neonatal microglia processes in poorer outcomes.publishersversionpublishe
Proton pump inhibitors and 1-year risk of adverse outcomes after discharge from internal medicine wards: an observational study in the REPOSI cohort.
No full textProton pump inhibitors are widely prescribed at hospital discharge from internal medicine wards and inappropriate use is common. We retrospectively conducted a survival analysis on data collected from the Registro Politerapie SIMI (REPOSI) registry to evaluate the 1-year risk of hospitalization or mortality associated with the use of PPI, with a particular focus on the appropriateness of use and newly initiated prescriptions at discharge. 7280 patients were discharged from hospital and 4579 (62.9%) had a PPI prescription. The use of PPI was significantly associated with 1-year risk of mortality in the univariate model (hazard ratio (HR) 1.33, p = 0.0012) and also when adjusted for confounders (adjusted HR 1.47, p = 0.0009). In the sensitivity analysis, new PPI prescription use at discharge was associated with an increased risk of mortality (adjusted HR of 1.53, p = 0.006). Inappropriate use was also linked to a nearly 60% higher risk of 1-year mortality and 27% increased risk of 1-year re-hospitalization. Among new PPI users, inappropriate use was associated with nearly 70% increased risk of 1-year mortality (HR 1.69). PPI use was associated with an increased risk of 1-year mortality and re-hospitalization in older adults discharged from hospitals. A higher risk of mortality was observed among new inappropriate PPI users, underscoring the importance of carefully evaluating the unnecessary initiation of new medications at discharge to maintain a favorable benefit-risk ratio.Impact of findings on practice statements. Proton pump inhibitors are among the most commonly prescribed medications. Use of proton pump inhibitors at hospital discharge was associated with a risk of 1-year mortality. Unnecessary PPI use was associated with higher risk of mortality. Patients discharged from internal medicine wards had high rates of inappropriate PPI use. The unnecessary initiation of new drugs at discharge for a favorable benefit-risk ratio was evaluated
Comparison of Anticholinergic Burden Scales and Their Association with Cognitive and Functional Impairment in Older Adults: A Cross-Sectional Study Using the REPOSI Database
No full textBackground: The increasing use of anticholinergic medications in older adults with multiple chronic conditions raises significant concerns regarding their cumulative anticholinergic burden, which is linked to several adverse outcomes. This study aimed to compare existing anticholinergic burden scales to identify those most effective at correlating drug-induced anticholinergic load with cognitive and functional impairment. In addition, we proposed a new classification system on the basis of published scales to optimally correlate total anticholinergic burden with observed clinical deficits.
Methods: This cross-sectional study analyzed data from the REPOSI registry, which collects clinical and therapeutic information on patients aged 65 years and older admitted to internal medicine and geriatric wards across Italy. Anticholinergic exposure was assessed using 20 established anticholinergic burden scales from literature. In addition, seven experimental scales were developed on the basis of published scales and various mathematical functions (maximum, mode, median, and mean) to evaluate potential differences in measuring anticholinergic load. Outcomes included cognitive impairment, assessed using the Short Blessed Test (SBT), and functional independence, measured by the Barthel Index (BI). A zero-inflated negative binomial model was applied to analyze associations between anticholinergic burden and each outcome. Given the variability in drug scoring across published scales, we developed seven experimental scales using different mathematical functions (maximum, mode, median, and mean) to standardize scoring. Three versions included a null-score adjustment to account for drugs omitted in some scales, ensuring a more comprehensive measure of anticholinergic burden.
Results: Among 7735 patients, higher anticholinergic burden was consistently associated with increased cognitive impairment (SBT) and physical dependency (BI) across all existing and proposed scales. The modified Anticholinergic Risk Scale (mARS) scale showed the strongest associations with cognitive (rate ratio [RR] 1.10, 95% confidence interval [CI] 1.06, 1.13; P < 0.0001) and physical impairment (RR 1.18, 95% CI 1.11, 1.24; P < 0.0001), indicating an 18% higher risk of dependency per unit increase, while the CRIDECO Anticholinergic Load Scale (CALS) scale exhibited the best model fit. Our newly developed scales confirmed these associations, with the median with null score and the mean with null score scale showing the strongest link to cognitive impairment (RR 1.07, 95% CI 1.05, 1.09; P < 0.0001) and the strongest association with physical dependency (RR 1.11, 95% CI 1.08, 1.15; P < 0.0001).
Conclusions: Scales that identify a greater proportion of patients with at least one anticholinergic drug may provide a more comprehensive assessment of anticholinergic burden in clinical practice. While no single scale demonstrated a definitive advantage across all outcomes, these scales may identify patients at risk. Prioritizing the use of scales with broader coverage could enhance clinical decision-making and optimize management of polypharmacy in older adults and recognize its potential impact on cognitive and functional outcomes
Drug Prescription and Delirium in Older Inpatients: Results From the Nationwide Multicenter Italian Delirium Day 2015-2016
No full textObjective: This study aimed to evaluate the association between polypharmacy and delirium, the association of specific drug categories with delirium, and the differences in drug-delirium association between medical and surgical units and according to dementia diagnosis. Methods: Data were collected during 2 waves of Delirium Day, a multicenter delirium prevalence study including patients (aged 65 years or older) admitted to acute and long-term care wards in Italy (2015-2016); in this study, only patients enrolled in acute hospital wards were selected (n = 4,133). Delirium was assessed according to score on the 4 "A's" Test. Prescriptions were classified by main drug categories; polypharmacy was defined as a prescription of drugs from 5 or more classes. Results: Of 4,133 participants, 969 (23.4%) had delirium. The general prevalence of polypharmacy was higher in patients with delirium (67.6% vs 63.0%, P =.009) but varied according to clinical settings. After adjustment for confounders, polypharmacy was associated with delirium only in patients admitted to surgical units (OR = 2.9; 95% CI, 1.4-6.1). Insulin, antibiotics, antiepileptics, antipsychotics, and atypical antidepressants were associated with delirium, whereas statins and angiotensin receptor blockers exhibited an inverse association. A stronger association was seen between typical and atypical antipsychotics and delirium in subjects free from dementia compared to individuals with dementia (typical: OR = 4.31; 95% CI, 2.94-6.31 without dementia vs OR = 1.64; 95% CI, 1.19-2.26 with dementia; atypical: OR = 5.32; 95% CI, 3.44-8.22 without dementia vs OR = 1.74; 95% CI, 1.26-2.40 with dementia). The absence of antipsychotics among the prescribed drugs was inversely associated with delirium in the whole sample and in both of the hospital settings, but only in patients without dementia. Conclusions: Polypharmacy is significantly associated with delirium only in surgical units, raising the issue of the relevance of medication review in different clinical settings. Specific drug classes are associated with delirium depending on the clinical setting and dementia diagnosis, suggesting the need to further explore this relationship
Correction to: Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register
No full textIn this article the names of a few collaborators and some data in Table 5 were missing. It has been corrected. The original article has been corrected
Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting. evidence from the REPOSI register
No full textDiabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria
Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both
No full textBackground and objective
Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF.
Methods
We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death.
Results
We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009).
Conclusion
In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population
Low serum albumin is associated with mortality and arterial and venous ischemic events in acutely ill medical patients. Results of a retrospective observational study
No full textBackground: In general population hypoalbuminemia is associated with poor survival. Aim of this study was to assess the impact of hypoalbuminemia on mortality and venous and arterial ischemic events in hospitalized acutely ill medical patients.
Patients and methods: Retrospective observational analysis from the "REgistro POliterapie SIMI" (REPOSI). Patients were followed up to 12 months. Serum albumin was obtained in each patient. Mortality and ischemic events were registered throughout the follow-up period.
Results: In the entire population including 4152 patients, median levels of serum albumin were 3.4 g/dL and 2193 patients (52.8 %) had levels ≤3.4 g/dL. Cases with albumin ≤3.4 g/dL were older, frailer, had more comorbidities and were most frequently underweight than those with serum albumin >3.4 g/dL. During the 12-month follow-up, all-cause mortality was 14.8 % (613 patients), with a higher rate in cases with serum albumin ≤3.4 g/dL (459, 20.9 % vs 154, 7.9 % in those with serum albumin >3.4 g/dL; p < 0.0001). During follow-up 121 ischemic events (2.9 %) were registered, 86 (71.1) arterial and 35 (28.9 %) venous. Proportional hazard analysis showed that patients with albumin ≤3.4 g/dL had a higher chance of dying. Furthermore, patients with albumin ≤3.4 g/dL had a higher likelihood of experiencing ischemic events.
Conclusions: Acutely ill hospitalized medical patients with serum levels ≤3.4 g/dL are at higher risk of all-cause mortality and ischemic events, measurement of albumin may help to identify hospitalized patients with a poorer prognosis
Undiagnosed cognitive impairment in older adults hospitalized in internal medicine wards: Data from the REPOSI registry
No full textNo abstract availabl
