Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

Measurement of the very rare K+→π+ννˉK^+ \to \pi^+ \nu \bar\nu decay

The decay K+→π+νν¯ , with a very precisely predicted branching ratio of less than 10−10 , is among the best processes to reveal indirect effects of new physics. The NA62 experiment at CERN SPS is designed to study the K+→π+νν¯ decay and to measure its branching ratio using a decay-in-flight technique. NA62 took data in 2016, 2017 and 2018, reaching the sensitivity of the Standard Model for the K+→π+νν¯ decay by the analysis of the 2016 and 2017 data, and providing the most precise measurement of the branching ratio to date by the analysis of the 2018 data. This measurement is also used to set limits on BR(K+→π+X ), where X is a scalar or pseudo-scalar particle. The final result of the BR(K+→π+νν¯ ) measurement and its interpretation in terms of the K+→π+X decay from the analysis of the full 2016-2018 data set is presented, and future plans and prospects are reviewed

The History of the Levant Company, 1581-1605

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Unmet Needs In Obesity Management: From Guidelines To Clinic

Despite the rather slow acceptance of obesity as a disease state, several obesity staging systems and weight-management guidelines have been developed and are in use, along with an ever-growing number of treatment options. Many primary care clinicians, including nurse practitioners (NPs), are at the forefront of clinical efforts to assist individuals with obesity, but face challenges due to lack of alignment and consensus among the various staging systems and guidelines. This is further complicated by shortfalls in clinical training related to obesity management and increasing complexities in reimbursement for obesity-related services. Unmet needs in the management of obesity thus stretch from guidelines to clinic. This article examines the principal barriers to effective management of individuals with obesity and considers how concerns might be overcome, with particular emphasis on the role of the NP

Tecniche statistiche per la previsione del rischio di insolvenza

L'ultimo decennio è stato caratterizzato da una grave crisi economica che ha colpito numerose imprese e ha causato problemi finanziari e di mercato che si sono tradotti in una alta probabilità di insolvenza. Conseguentemente, la gestione del rischio è diventata un tema cruciale poichè una previsione errata della probabilità di insolvenza può produrre rating inadeguati nel supportare gli operatori specializzati come le banche nella concessione di prestiti. Nell’ambito della individuazione del rischio di credito di un’azienda, notevole applicazione trovano le tecniche statistiche (Avery, 1996). Scopo del presente lavoro è quello di comparare le tecniche più opportune, quali il modello logistico, gli alberi di segmentazione e le reti neurali, per valutare la loro efficacia in termini di capacità predittiva del rischio di insolvenza sulla base dei principali indici aziendali

Il calcolo urinario. Proposta di un nuovo metodo di determinazione: dati preliminari

Introduzione: La visualizzazione soggettiva delle reazioni utilizzate per l'identificazione e la quantificazione delle sostanze presenti nel calcolo urinario presentano notevoli problemi. Metodi: Viene descritta una nuova procedura per la determinazione del calcolo urinario. La rilevazione dei carbonati e le concentrazioni di calcio, fosforo, magnesio, ammonio, acido urico (dosaggi quantitativi su analizzatore COBAS 6000 ditta Roche) ed ossalato e cistina (determinazioni adattate su Viva E ditta Siemens) si inseriscono in un foglio Excel per ottenere i possibili principali calcoli urinari (calcio ossalato, acido urico, urato di ammonio, cistina, struvite, brushite, apatite, carbonato apatite) e più in generale "calcio fosfato". Le determinazioni di chimica clinica sono simili a quelle utilizzate effettuate per lo studio metabolico sulle urine delle 24h in cui il dosaggio fotometrico della cistina all'acido fosfotungstico, non essendo commercializzato, è stato costruito ed adattato su analizzatore Viva E. Particolarmente utile risulta l'uso del rapido metodo quantitativo al ferro-solfosalicilico, non commercializzato e costruito nel nostro laboratorio, per la determinazione dell'ossalato nel calcolo. Risultati: Il software proposto converte le concentrazioni degli analiti in mmoli/dL e, partendo dalla struvite, definisce successivamente l'eventuale presenza di calcio ossalato, urato di ammonio ed i diversi calcio fosfato, determinati a seconda del rapporto Ca/P. La conversione finale in concentrazione delle diverse componenti presenti nel calcolo, assieme ad un eventuale residuo inorganico, da la presentazione dei dati in percentuale. Conclusioni: I dati ottenuti, specie se riferiti a concrezioni formate da più componenti, evidenziano buoni risultati se confrontati con la tecnica di riferimento FTIR suggerendo una metodica di laboratorio pratica, rapida ed affidabile. A new laboratory procedure is described for the determination of urinary calculus. The detection of carbonates (production of carbon dioxide with the use of concentrated sulfuric acid) and the concentrations of calcium, phosphorus, magnesium, ammonium, uric acid (quantitative dosages carried out on COBAS 6000 analyzer of the Roche company) and oxalate and cystine (determinations adapted by us on the Siemens Viva E instrument) they are inserted in an Excel sheet created by us in order to obtain the main possible urinary calculations (calcium oxalate, uric acid, ammonium urate, cystine, struvite, brushite, apatite, carbonate apatite and more generally "calcium phosphate." The clinical chemistry determinations are similar to those used for the metabolic study carried out on the urine of 24 hours in which the photometric dosage of cystine with phosphotungstic acid, not being marketed, was built by us and adapted on Viva E analyzer. The use of the rapid quantitative method, with non-commercial sulfosalicylic acid, is particularly useful zato and then built in our laboratory, for the determination of oxalate in the calculation. The software proposed by us converts all the concentrations of the above mentioned analytes to mmoles / dL and, starting from struvite (molecular ratios: 1P - 1Mg - 1NH4), the possible presence of calcium oxalate is subsequently defined (molecular ratios: 1Ca - 1Ox ), that of ammonium urate and the different calcium phosphate (brushite, apatite / carbonate apatite and "calcium phosphate"), the latter determined according to the Ca / P ratio (brushite: <1.155; 1.155≥ "calcium phosphate" <1 , 45; apatite ≥1.45). The final conversion into concentration of the various components present in the calculation, together with any inorganic residue, determines the presentation of the data as a percentage. The data obtained, especially if referring to concretions formed by several components, show good results when compared with the FTIR reference technique

A Pilot Study on Electrical Impedance Tomography During CPAP Trial in Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia: The Bright Side of Non-invasive Ventilation

Background: Different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia phenotypes were described that match with different lung compliance and level of oxygenation, thus requiring a personalized ventilator setting. The burden of so many patients and the lack of intensive care unit (ICU) beds often force physicians to choose non-invasive ventilation (NIV) as the first approach, even if no consent has still been reached to discriminate whether it is safer to choose straightforward intubation, paralysis, and protective ventilation. Under such conditions, electrical impedance tomography (EIT), a non-invasive bedside tool to monitor lung ventilation and perfusion defects, could be useful to assess the response of patients to NIV and choose rapidly the right ventilatory strategy. Objective: The rationale behind this study is that derecruitment is a more efficient measure of positive end expiratory pressure (PEEP)-dependency of patients than recruitment. We hypothesized that patients who derecruit significantly when PEEP is reduced are the ones that do not need early intubation while small end-expiratory lung volume (ΔEELV) variations after a single step of PEEP de-escalation could be predictive of NIV failure. Materials and Methods: Consecutive patients admitted to ICU with confirmed SARS-CoV-2 pneumonia ventilated in NIV were enrolled. Exclusion criteria were former intubation or NIV lasting &gt; 72 h. A trial of continuos positive airway pressure (CPAP) 12 was applied in every patient for at least 15 min, followed by the second period of CPAP 6, either in the supine or prone position. Besides standard monitoring, ventilation of patients was assessed by EIT, and end-expiratory lung impedance (ΔEELI) (%) was calculated as the difference in EELI between CPAP12 and CPAP6. Tidal volume (Vt), Ve, respiratory rate (RR), and FiO2 were recorded, and ABGs were measured. Data were analyzed offline using the dedicated software. The decision to intubate or continue NIV was in charge of treating physicians, independently from study results. Outcomes of patients in terms of intubation rate and ICU mortality were recorded. Results: We enrolled 10 male patients, with a mean age of 67 years. Six patients (60%) were successfully treated by NIV until ICU discharge (Group S), and four patients failed NIV and were intubated and switched to MV (Group F). All these patients died in ICU. During the supine CPAP decremental trial, all patients experienced an increase in RR and Ve. ΔEELI was &lt; 40% in Group F and &gt; 50% in Group S. In the prone trial, ΔEELI was &gt; 50% in all patients, while RR decreased in Group S and remained unchanged in Group F. Conclusion: ΔEELI &lt; 40% after a single PEEP de-escalation step in supine position seems to be a good predictor of poor recruitment and CPAP failure