26 research outputs found
Risk and predictive factors of prolonged viral RNA shedding in upper respiratory specimens in a large cohort of COVID-19 patients admitted to an Italian reference hospital
No full textBackground: Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS).
Methods: A retrospective study including COVID-19 patients admitted to an Italian hospital between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from the upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between VS and clinical outcomes was evaluated through an inverse probability weighted Cox model.
Results: The study included 536 subjects. The median duration of VS from symptoms onset was 18 days. The estimated 30-day probability of VC was 70.2%. Patients with comorbidities, lymphopenia at hospital admission, or moderate/severe respiratory disease had a lower chance of VC. The development of moderate/severe respiratory failure, delayed hospital admission after symptoms onset, baseline comorbidities, or D-dimer >1000ng/mL at admission independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery and reduced the probability of death/mechanical ventilation.
Conclusions: Respiratory disease severity, comorbidities, delayed hospital admission and inflammatory markers negatively predicted VC, which resulted to be associated with better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially where signs of severity or comorbidities are present
Sarilumab plus standard of care vs standard of care for the treatment of severe COVID-19: a phase 3, randomized, open-labeled, multi-center study (ESCAPE study)
No full textBackground: Among interleukin-6 inhibitors suggested for use in COVID-19, there are few robust evidences for the efficacy of sarilumab. Herein, we evaluated the efficacy and safety of sarilumab in severe COVID-19.
Methods: In this phase 3, open-labeled, randomized clinical trial, conducted at 5 Italian hospitals, adults with severe COVID-19 pneumonia (excluding mechanically ventilated) were randomized 2:1 to receive intravenous sarilumab (400 mg, repeatable after 12 h) plus standard of care (SOC) (arm A) or to continue SOC (arm B). Randomization was web-based. As post-hoc analyses, the participants were stratified according to baseline inflammatory parameters. The primary endpoint was analysed on the modified Intention-To-Treat population, including all the randomized patients who received any study treatment (sarilumab or SOC). It was time to clinical improvement of 2 points on a 7-points ordinal scale, from baseline to day 30. We used Kaplan Meier method and log-rank test to compare the primary outcome between two arms, and Cox regression stratified by clinical center and adjusted for severity of illness, to estimate the hazard ratio (HR). The trial was registered with EudraCT (2020-001390-76).
Findings: Between May 2020 and May 2021, 191 patients were assessed for eligibility, of whom, excluding nine dropouts, 176 were assigned to arm A (121) and B (55). At day 30, no significant differences in the primary endpoint were found (88% [95% CI 81-94] in arm A vs 85% [74-93], HR 1.07 [0.8-1.5] in arm B; log-rank p = 0.50). After stratifying for inflammatory parameters, arm A showed higher probability of improvement than B without statistical significance in the strata with C reactive protein (CRP) < 7 mg/dL (88% [77-96] vs 79% [63-91], HR 1.55 [0.9-2.6]; log-rank p = 0.049) and in the strata with lymphocytes <870/mmc (90% [79-96]) vs (73% [55-89], HR 1.53 [0.9-2.7]; log-rank p = 0.058). Overall, 39/121 (32%) AEs were reported in arm A and 14/55 (23%) in B (p = 0.195), while serious AEs were 22/121 (18%) and 7/55 (11%), respectively (p = 0.244). There were no treatment-related deaths.
Interpretation: The efficacy of sarilumab in severe COVID-19 was not demonstrated both in the overall and in the stratified for severity analysis population. Exploratory analyses suggested that subsets of patients with lower CRP values or lower lymphocyte counts might have had benefit with sarilumab treatment, but this finding would require replication in other studies. The relatively low rate of concomitant corticosteroid use, could partially explain our results
Validazione dei dati satellitari di precipitazione per la stima del deflusso nella parte medio-alta del bacino del Fiume Tevere tramite la modellistica semi distribuita in continuo.
No full textNell’ambito della Convenzione “contributo per la ricerca applicata nel settore dell’idrologia
operativa, in particolare degli strumenti in tempo reale di previsione e monitoraggio, anche in termini probabilistici, delle risorse idriche e del rischio idrogeologico (frane e alluvioni) a scala regionale” tra il CNR IRPI e il Centro Funzionale Decentrato della Regione Umbria (CFD) la tesi ha come obiettivo la stima della portata all’interno della parte medio-alta del bacino del Fiume Tevere, tramite l’utilizzo di un Modello Idrologico Semi distribuito in continuo (MISDc). Inoltre, è stata effettuata una valutazione della qualità dei dati satellitari di pioggia impiegati nello studio.
Il periodo di analisi è il quadriennio 2016-2019.
Il modello, sviluppato dall’Istituto di Ricerca Per la Protezione Idrogeologica di Perugia (CNR-IRPI), si compone di tre parti: la prima è un modulo di fusione nivale che discerne la
precipitazione totale in parte solida e liquida, la seconda è un modello di bilancio del suolo, che determina il contenuto d’acqua presente in esso in modo continuo e che definisce le condizioni iniziali per la terza parte: un modulo di trasferimento dell’onda di piena per la stima delle portate nelle diverse sezioni del bacino.
La zona che è stata oggetto di tale studio è la parte medio-alta del bacino del Fiume Tevere situata tra la diga di Montedoglio e la sezione di Monte Molino. Tale area presenta una superficie di circa 5200 km2.
All’interno o nelle immediate vicinanze del bacino del Fiume Tevere sono presenti 90 stazioni di monitoraggio pluviometrico, 77 stazioni di monitoraggio termometrico e 17 stazioni di monitoraggio idrometrico. Tali stazioni forniscono dati di pioggia, temperatura dell’aria e livello idrometrico con passo temporale semiorario per il periodo 2004-2020.
Nell’ottica di valutare il comportamento idrologico del bacino mediante la modellistica idrologica semi distribuita in continuo e, sulla base del reticolo idrografico IGM 1: 25.000, l’area di studio stata suddivisa in 98 elementi: 61 aree direttamente drenanti nell’asta fluviale di interesse e 37 bacini di testa.
I dati di input del modello sono: le precipitazioni e le temperature.
Oltre ad essere stati utilizzati i dati di pioggia e temperatura derivanti dalla rete pluviometrica regionale umbra e dalla rete pluviometrica globale (Global Precipitation Climatology Centre, GPCC), ho utilizzato i dati di pioggia provenienti da alcuni prodotti satellitari.
In particolare, ho acquisito i dati di pioggia attraverso tre prodotti derivanti dall’European
Organization for the Exploitation of Meteorological Satellites (EUMETSAT), un prodotto
proveniente dalla National Oceanic and Atmospheric Administration (NOAA) e, per ultimo, i
dati acquisiti dal prodotto proveniente dall’algoritmo “Soil Moisture to Rain” (SM2RAIN), sviluppato dall’Istituto di Ricerca per la Protezione Idrogeologica di Perugia, (CNR-IRPI) il quale stima la pioggia sulla base del contenuto d’acqua nel suolo.
Il modello MISDc, prima di essere stato utilizzato per stimare la portata, è stato calibrato e poi successivamente validato. La calibrazione è stata effettuata tramite la minimizzazione di una funzione obiettivo basata sull’indice di Kling-Gupta e ha riguardato solo alcune sezioni. La validazione è stata, successivamente, applicata alle sezioni rimanenti.
La valutazione per ciascuna sezione si è basata su tre indici di performance: l’indice KGE, l’indice di Nash-Sutcliffe (NS) e il coefficiente di determinazione (R).
Dai risultati che si ottengono attraverso l’applicazione del modello si evince un’ottima capacità di stima del deflusso tramite l’utilizzo della rete pluviometrica regionale con buoni valori degli indici di performance.
Inoltre, anche se con performance leggermente inferiori, l’utilizzo dei dati di pioggia derivanti dai prodotti satelliti ha evidenziano buoni risultati.
In particolare, per i dataset che integrano le informazioni derivanti dai satelliti e dai pluviometri si sono osservati i risultati migliori.
Nella seconda parte del lavoro è stata svolta un’analisi sulla qualità del dato di pioggia derivante dai prodotti satellitari. Tale valutazione si è basata sul confronto fra ciascun dataset satellitare con la rete pluviometrica regionale umbra utilizzando, anche in questo caso, tre indici di performance: l’indice di Kling-Gupta (KGE), il coefficiente di determinazione (R) e l’errore relativo quadratico medio (RRMSE).
I dataset satellitari mostrano una buona accuratezza nella stima del dato di pioggia rispetto al dato osservato.
In particolare, tra i prodotti satellitari che ho impiegato, la metodologia che ha presentato le performance migliori è quella relativa ai due prodotti integrati.
Tali prodotti si sono dimostrati essere i più efficienti sulla base di tutti e tre gli indici utilizzati
A 72-h intervention for improvement of the rate of optimal antibiotic therapy in patients with bloodstream infections
No full textAntimicrobial stewardship programs are implemented to optimize the use of antibiotics and control the spread of antibiotic resistance. Many antimicrobial stewardship interventions have demonstrated significant efficacy in reducing unnecessary prescriptions of antibiotics, the duration of antimicrobial therapy, and mortality. We evaluated the benefits of a combination of rapid diagnostic tests and an active re-evaluation of antibiotic therapy 72 h after the onset of bloodstream infection (BSI). All patients with BSI from November 2015 to November 2016 in a 1100-bed university hospital in Rome, where an Infectious Disease Consultancy Unit (Unità di Consulenza Infettivologica, UDCI) is available, were re-evaluated at the bedside 72 h after starting antimicrobial therapy and compared to two pre-intervention periods: the UDCI was called by the ward physician for patients with BSI and the UDCI was called directly by the microbiologist immediately after a pathogen was isolated from blood cultures. Recommendations for antibiotic de-escalation or discontinuation significantly increased (54%) from the two pre-intervention periods (32% and 27.2%, p < 0.0001). Appropriate escalation also significantly increased (22.5%) from the pre-intervention periods (8.1% and 8.2%, p < 0.0001). The total duration of antibiotic therapy decreased with intervention (from 21.9 days [standard deviation, SD 15.4] in period 1 to 19.3 days [SD 13.3] in period 2 to 17.7 days in period 3 [SD 11.5]; p = 0.002) and the length of stay was significantly shorter (from 29.7 days [SD 29.3] in period 1 to 26.8 days [SD 24.7] in period 2 to 24.2 days in period 3 [SD 20.7]; p = 0.04) than in the two pre-intervention periods. Mortality was similar among the study periods (31 patients died in period 1 (15.7%), 39 (16.7%) in period 2, and 48 (15.3%) in period 3; p = 0.90). Rapid diagnostic tests and 72 h re-evaluation of empirical therapy for BSI significantly correlated with an improved rate of optimal antibiotic therapy and decreased duration of antibiotic therapy and length of stay
Rapid ART initiation with bictegravir/emtricitabine/tenofovir alafenamide in individuals presenting with advanced HIV disease (Rainbow study)
No full textBackground: A rapid ART initiation approach can be beneficial in people with advanced HIV disease, in consideration of their high morbidity and mortality. The aim of our study was to evaluate the feasibility, efficacy and safety of rapid ART start with BIC/FTC/TAF in this setting. Methods: Pilot, single-centre, single-arm, prospective, phase IV clinical trial conducted in a tertiary Italian hospital. Thirty ART-naive people presenting with advanced HIV-1 diagnosis (defined as the presence of an AIDS-defining event and/or CD4 cell count 200 cells/mu L at w 48. Two participants developed IRIS and one was diagnosed with disseminated TB and needed an ART switch. Interpretations: Our results support the feasibility, efficacy and safety of BIC/FTC/TAF as a rapid ART strategy in patients with advanced HIV disease. (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/
Cognitive outcomes and psychological symptoms in an Italian cohort with post-acute COVID-19 condition (PACC)
No full textBackground: We aim to investigate the proportion of patients (pts) with long-term cognitive outcomes (CO) of PACC and identify associated features. Methods: We assessed participants through a neuropsychological assessment. The chi-square test was used for comparisons according with time of NPA (within or beyond 6 months since COVID19) and with previously hospitalization status (hospitalized patients, PH; not hospitalized patients, nPH). Results: 520 participants: mean age 54 years (SD 12), 53 % female, 14 years of education (SD 3.4), 35 % with >1 comorbidity, 48 % previously hospitalized. Overall, we found CO in 89 % of pts, in particular 88 % evaluated in w6M and 89 % in b6M (p = 0.801) while 90 % and 87 % in nPH and PH, respectively (p = 0.239). By fitting multivariable analysis, PH for COVID19 and female gender were associated with an increased risk of an altered PSQI [Odd Ratio, OR 2.48, 95 % CI 1.54 to 3.99, p < 0.001 and OR 2.59, 95 % CI 1.60 to 4.17, p < 0.001, respectively) and BAI [F vs M: OR 1.67, 95 % CI 1.16 to 2.40, p = 0.005). Conclusions: We show a substantial proportion of PACC-CO; hospitalization leads to impaired memory, anxiety and sleep disorders. Women seem to be at higher risk for anxious-depressive symptoms and worse sleep quality than men
Performance evaluation of the (1,3)-β-D-glucan detection assay in non-intensive care unit adult patients
No full textObjectives: To assess the performance of the (1,3)-β-D-glucan (BDG) detection assay in a large cohort of patients with suspected candidemia who were admitted to non-intensive care unit hospital wards. Methods: This observational, retrospective cohort study was conducted in a 1,100-bed university hospital in Rome, where an infectious disease consultation team has been operational. Two groups of patients were included in the analysis: Group 1, patients with Candida bloodstream infection (BSI) who had at least one BDG test performed ±48 hours from the first positive blood culture (Candida BSI Group) and Group 2, patients with risk factors for candidemia who had at least one BDG test but had negative blood cultures (Control Group). Both Group 1 and Group 2 did not receive prior antifungal therapy. Different BDG cutoff values were considered: 80, 200, 300, 400, and ≥500 pg/mL. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated. Results: A total of 1,296 patients were studied. Of them, 100 patients (candidemic) were in Group 1 and the remaining 1,196 patients (controls) were in Group 2. There were no differences in demographic characteristics between patients of the two groups. According to the above cutoff values, sensitivity (%) and specificity (%) of the BDG assay ranged from 91 to 60.7 and 87.7 to 97.8, respectively, whereas the PPV (%) and NPV (%) ranged from 38.2 to 68.3 and 99.1 to 97.0, respectively. Conclusion: Serum BDG has a very high NPV in a population with~10% prevalence of candidemia. This NPV may support decisions to discontinue antifungal therapy in those patients who were empirically treated because of the suspect of candidemia
Soluble lectin-like oxidized low-density lipoprotein receptor-1 predicts premature death in acute coronary syndromes
No full textAims: The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and its shedding product [soluble LOX-1 (sLOX-1)] are implicated in atherosclerotic cardiovascular disease (ASCVD) pathogenesis. Herein, we examined the relationship of sLOX-1 with both fatal events and plaque progression in patients with acute coronary syndromes (ACS). Methods and results: Plasma sLOX-1 was assessed at baseline in ACS and chronic coronary syndrome (CCS) patients prospectively recruited in the multicentre SPUM-ACS study, with sex- A nd age-matched healthy subjects serving as additional controls (n = 2924). Compared with both CCS and controls, ACS patients showed markedly elevated sLOX-1 levels (median, 2.00 and 2.00 vs. 35.08 pg/mL; P < 0.0001) which were independently associated with increased mortality risk over 30-day [tertile (T)3: Adjusted hazard ratio (HR), 3.11; 95% confidence interval (CI), 1.44-10.61; P = 0.0055] and 1-year intervals (T3: Adjusted HR, 2.04; 95% CI, 1.19-3.92; P = 0.0098). Results remained consistent after adjustment for GRACE 2.0 (T3: Adjusted HR, 1.86; 95% CI, 1.04-3.74; P = 0.0391) and were primarily driven by the pronounced relationship of sLOX-1 with cardiovascular mortality at 30 days (T3: Adjusted HR, 3.81; 95% CI, 1.62-19.62; P = 0.0036) and at 1 year (T3: Adjusted HR, 2.29; 95% CI, 1.19-5.34; P = 0.0148). In ACS patients undergoing serial intracoronary imaging and statin therapy, sLOX-1 dropped significantly in those with coronary plaque regression at 1 year (ΔsLOX-1:-4.64 ± 1.80; P = 0.0057), and showed a good discrimination for predicting plaque progression (area under the curve = 0.74; 95% CI, 0.59-0.86; P = 0.0031). Conclusion: Plasma sLOX-1 levels are increased during ACS and predict fatal events beyond traditional and emerging risk factors. Persistently high sLOX-1 associates with coronary plaque progression in patients with established ASCVD. Clinical Trial Registration: NCT01000701. © 2022 The Author(s). Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved
Evolution of SARS‐CoV‐2 variants of concern over a period of Delta and Omicron cocirculation, among patients hospitalized for COVID‐19 in an Italian reference hospital: Impact on clinical outcomes
No full textDespite the higher transmissibility of Omicron Variant of Concern (VOC), several reports have suggested lower risk for hospitalization and severe outcomes compared to previous variants of SARS-CoV-2. This study, enrolling all COVID-19 adults admitted to a reference hospital who underwent both the S-gene-target-failure test and VOC identification by Sanger sequencing, aimed to describe the evolving prevalence of Delta and Omicron variants and to compare the main in-hospital outcomes of severity, during a trimester (December 2021 to March 2022) of VOCs' cocirculation. Factors associated with clinical progression to noninvasive ventilation (NIV)/mechanical ventilation (MV)/death within 10 days and to MV/admission to intensive care unit (ICU)/death within 28 days, were investigated through multivariable logistic regressions. Overall, VOCs were: Delta n = 130/428, Omicron n = 298/428 (sublineages BA.1 n = 275 and BA.2 n = 23). Until mid-February, Delta predominance shifted to BA.1, which was gradually displaced by BA.2 until mid-March. Participants with Omicron VOC were more likely to be older, fully vaccinated, with multiple comorbidities and to have a shorter time from symptoms' onset, and less likely to have systemic symptoms and respiratory complications. Although the need of NIV within 10 days and MV within 28 days from hospitalization and the admission to ICU were less frequent for patients with Omicron compared to those with Delta infections, mortality was similar between the two VOCs. In the adjusted analysis, multiple comorbidities and a longer time from symptoms' onset predicted 10-day clinical progression, while complete vaccination halved the risk. Multimorbidity was the only risk factor associated with 28-day clinical progression. In our population, in the first trimester of 2022, Omicron rapidly displaced Delta in COVID-19 hospitalized adults. Clinical profile and presentation differed between the two VOCs and, although Omicron infections showed a less severe clinical picture, no substantial differences for clinical progression were found. This finding suggests that any hospitalization, especially in more vulnerable individuals, may be at risk for severe progression, which is more related to the underlying frailty of patients than to the intrinsic severity of the viral variant
Predicting respiratory failure in patients infected by SARS-CoV-2 by admission sex-specific biomarkers
No full textBackground: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19.
Methods: Plasma levels of sex hormones (testosterone and 17β-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form.
Results: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males.
Conclusions: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring
