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Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

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Importance: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors improve outcomes in patients with type 2 diabetes, heart failure, and chronic kidney disease, but their effect on outcomes of critically ill patients with organ failure is unknown. Objective: To determine whether the addition of dapagliflozin, an SGLT-2 inhibitor, to standard intensive care unit (ICU) care improves outcomes in a critically ill population with acute organ dysfunction. Design, Setting, and Participants: Multicenter, randomized, open-label, clinical trial conducted at 22 ICUs in Brazil. Participants with unplanned ICU admission and presenting with at least 1 organ dysfunction (respiratory, cardiovascular, or kidney) were enrolled between November 22, 2022, and August 30, 2023, with follow-up through September 27, 2023. Intervention: Participants were randomized to 10 mg of dapagliflozin (intervention, n = 248) plus standard care or to standard care alone (control, n = 259) for up to 14 days or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and ICU length of stay through 28 days, analyzed using the win ratio method. Secondary outcomes included the individual components of the hierarchical outcome, duration of organ support-free days, ICU, and hospital stay, assessed using bayesian regression models. Results: Among 507 randomized participants (mean age, 63.9 [SD, 15] years; 46.9%, women), 39.6% had an ICU admission due to suspected infection. The median time from ICU admission to randomization was 1 day (IQR, 0-1). The win ratio for dapagliflozin for the primary outcome was 1.01 (95% CI, 0.90 to 1.13; P = .89). Among all secondary outcomes, the highest probability of benefit found was 0.90 for dapagliflozin regarding use of kidney replacement therapy among 27 patients (10.9%) in the dapagliflozin group vs 39 (15.1%) in the control group. Conclusion and Relevance: The addition of dapagliflozin to standard care for critically ill patients and acute organ dysfunction did not improve clinical outcomes; however, confidence intervals were wide and could not exclude relevant benefits or harms for dapagliflozin. Trial Registration: ClinicalTrials.gov Identifier: NCT05558098.

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Therapeutic anticoagulation showed inconsistent results in hospitalized patients with COVID-19 and selection of the best patients to use this strategy still a challenge balancing the risk of thrombotic and hemorrhagic outcomes. The present post-hoc analysis of the ACTION trial evaluated the variables independently associated with both bleeding events (major bleeding or clinically relevant non-major bleeding) and the composite outcomes thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, or major adverse limb events). Variables were assessed one by one with independent logistic regressions and final models were chosen based on Akaike information criteria. The model for bleeding events showed an area under the curve of 0.63 (95% confidence interval [CI] 0.53 to 0.73), while the model for thrombotic events had an area under the curve of 0.72 (95% CI 0.65 to 0.79). Non-invasive respiratory support was associated with thrombotic but not bleeding events, while invasive ventilation was associated with both outcomes (Odds Ratio of 7.03 [95 CI% 1.95 to 25.18] for thrombotic and 3.14 [95% CI 1.11 to 8.84] for bleeding events). Beyond respiratory support, creatinine level (Odds Ratio [OR] 1.01 95% CI 1.00 to 1.02 for every 1.0 mg/dL) and history of coronary disease (OR 3.67; 95% CI 1.32 to 10.29) were also independently associated to the risk of thrombotic events. Non-invasive respiratory support, history of coronary disease, and creatinine level may help to identify hospitalized COVID-19 patients at higher risk of thrombotic complications.ClinicalTrials.gov: NCT04394377.

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Lysergic acid diethylamide (LSD) and two phenethylamine classes (NBOHs and NBOMes) are the main illicit drugs found in seized blotter papers. The preliminary identification of these substances is of great interest for forensic analysis. In this context, this work constitutes the inaugural demonstration of an efficient methodology for the selective detection of LSD, NBOHs, and NBOMes, utilizing a fully 3D-printed electrochemical double cell (3D-EDC). This novel 3D-EDC enables the use of two working electrodes and/or two supporting electrolytes (at different pHs) in the same detection system, with the possibility of shared or individual auxiliary and pseudo-reference electrodes. Thus, the selective voltammetric detection of these substances is proposed using two elegant strategies: (i) utilizing the same 3D-EDC platform with two working electrodes (boron-doped diamond (BDD) and 3D-printed graphite), and (ii) employing two pH levels (4.0 and 12.0) with 3D-printed graphite electrode. This comprehensive framework facilitates a fast, robust, and uncomplicated electrochemical analysis. Moreover, this configuration enables a rapid and sensitive detection of LSD, NBOHs, and NBOMes in seized samples, and can also provide quantitative analysis. The proposed method showed good stability of the electrochemical response with RSD <9 % for Ip and <5 % for Ep, evaluating all oxidation processes observed for studied analytes (n = 7) at two pH levels, using the same and different (n = 3) working electrodes. It demonstrates a broad linear range (20-100 and 20-70 µmol L-1) and a low LOD (1.0 µmol L-1) for quantification of a model molecule (LSD) at the two pHs studied. Hence, the 3D-EDC combined with voltammetric techniques using BDD and 3D-printed graphite electrodes on the same platform, or only with this last sensor at two pH values, provide a practical and robust avenue for preliminary identification of NBOHs, NBOMes, and LSD. This method embodies ease, swiftness, cost-efficiency, robustness, and selectivity as an on-site screening tool for forensic analysis.

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Chromoblastomycosis (CBM) and phaeohyphomycosis (FEO) are infections caused by melanized filamentous fungal agents, primarily found in tropical and subtropical regions. Both infections pose significant challenges for the correct identification of the causative agent due to their morphological similarity, making conventional methods of morphological analysis highly subjective. Therefore, molecular techniques are necessary for the precise determination of these species. In this regard, this study aimed to contribute to a new methodology based on PCR-RFLP for the identification of agents causing CBM and FEO. Sequences from the Internal Transcribed Spacer (ITS) region were used to identify potential restriction enzyme sites in silico, followed by in vitro validation using the selected restriction enzymes. The obtained results were compared with species identification through morphological analyses and sequencing. The results demonstrated that the PCR-RFLP applied in this study accurately identified two major agents of chromoblastomycosis, Fonsecaea pedrosoi and Fonsecaea monophora, as well as Cladophialophora bantiana and Exophiala dermatitidis, both causative agents of phaeohyphomycosis. In this context, the proposed assay can complement current methods for identifying these species, aiding in diagnosis, and contributing to the proper management of these infections.

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This study estimated biomass and carbon from components, future carbon values ​​and to obtain economic productive value of carbon fixation of a Seasonal Semideciduous Forest. Biomass and carbon were estimated using adjusted equations and selected using regression statistics. The prognosis of the diametric distribution was performed using the movement ratio method. In the economic evaluation, it was estimated productive value of the stand, referring to the current and future carbon fixation capacity. The coefficients of determination (adjusted R²) of the equations ranged from 0.11 to 0.90 and the standard error of the estimate (Syx) ranged from 41.53% to 141.89% for the biomass of the components, and from 0.03 to 0.87 for adjusted R² and from 46.20% to 143.64% for the error, for stored carbon in the components. The total biomass of the tree component estimated was 56.25 t ha-1 and 25.88 t ha-1 of total carbon. Using the future distributions by the method of the ratio of movements, total stored carbon (aerial + roots) estimated was 14.44 t. ha-1 over the 20-year period. The productive value for the fragment reached R$ 299.95 per ha. year-1.

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This work adopted a green synthesis route using cashew tree gum as a mediating agent to obtain Ni-doped ZnO nanoparticles through the sol-gel method. Structural analysis confirmed the formation of the hexagonal wurtzite phase and distortions in the crystal lattice due to the inclusion of Ni cations, which increased the average crystallite size from 61.9 nm to 81.6 nm. These distortions resulted in the growth of point defects in the structure, which influenced the samples' optical properties, causing slight reductions in the band gaps and significant increases in the Urbach energy. The fitting of the photoluminescence spectra confirmed an increase in the concentration of zinc vacancy defects (VZn) and monovacancies (Vo) as Zn cations were replaced by Ni cations in the ZnO structure. The percentage of VZn defects for the pure compound was 11%, increasing to 40% and 47% for the samples doped with 1% and 3% of Ni cations, respectively. In contrast, the highest percentage of VO defects is recorded for the material with the lowest Ni ions concentration, comprising about 60%. The influence of dopant concentration was also reflected in the photocatalytic performance. Among the samples tested, the Zn0.99Ni0.01O compound presented the best result in MB degradation, reaching an efficiency of 98.4%. Thus, the recovered material underwent reuse tests, revealing an efficiency of 98.2% in dye degradation, confirming the stability of the photocatalyst. Furthermore, the use of different inhibitors indicated that •OH radicals are the main ones involved in removing the pollutant. This work is valuable because it presents an ecological synthesis using cashew gum, a natural polysaccharide that has been little explored in the literature.

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Lysergic acid diethylamide (LSD) is a prevalent psychoactive substance recognized for its hallucinogenic properties, often encountered in blotter papers for illicit consumption. Given that LSD ranks among the most widely abused illicit drugs globally, its prompt identification in seized samples is vital for forensic investigations. This study presents, for the first time, an electrochemical screening method for detecting LSD in forensic samples, utilizing a multi-wall carbon nanotube screen-printed electrode (SPE-MWCNT). The LSD detection process was optimized on SPE-MWCNT in a phosphate buffer solution (0.1 mol L-1, pH 12.0) using square wave voltammetry (SWV). The combined use of SPE-MWCNT with SWV displayed robust stability in electrochemical responses for both qualitative (peak potential) and quantitative (peak current) LSD assessment, with a relative standard deviation (RSD) of less than 5% across the same or different electrodes (N = 3). A linear detection range was established between 0.16 and 40.0 µmol L-1 (R2 = 0.998), featuring a low limit of detection (LOD) of 0.05 µmol L-1. Interference studies with twenty-three other substances, including groups of phenethylamines typically found in blotting papers (e.g., NBOHs and NBOMes) and traditional illicit drugs, were performed, revealing a highly selective response for LSD using the proposed method. Consequently, the integration of SPE-MWCNT with SWV offers a robust tool for qualitative and quantitative LSD analysis in forensic applications, providing rapid, sensitive, selective, reproducible, and straightforward preliminary identification in seized samples.

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Background: COVID-19 progression is associated with an increased risk of arterial and venous thrombosis. Randomised trials have demonstrated that anticoagulants reduce the risk of thromboembolism in hospitalised patients with COVID-19, but a benefit of routine anticoagulation has not been demonstrated in the outpatient setting. Methods: We conducted a randomised, open-label, controlled, multicentre study, evaluating the use of rivaroxaban in mild or moderate COVID-19 patients. Adults ≥18 years old, with probable or confirmed SARS-CoV-2 infection, presenting within ≤7 days from symptom onset with no clear indication for hospitalization, plus at least 2 risk factors for complication, were randomised 1:1 either to rivaroxaban 10 mg OD for 14 days or to routine care. The primary efficacy endpoint was the composite of venous thromboembolic events, need of mechanical ventilation, acute myocardial infarction, stroke, acute limb ischemia, or death due to COVID-19 during the first 30 days. ClinicalTrials.gov: NCT04757857. Findings: Enrollment was prematurely stopped due to sustained reduction in new COVID-19 cases. From September 29th, 2020, through May 23rd, 2022, 660 patients were randomised (median age 61 [Q1-Q3 47-69], 55.7% women). There was no significant difference between rivaroxaban and control in the primary efficacy endpoint (4.3% [14/327] vs 5.8% [19/330], RR 0.74; 95% CI: 0.38-1.46). There was no major bleeding in the control group and 1 in the rivaroxaban group. Interpretation: On light of these findings no decision can be made about the utility of rivaroxaban to improve outcomes in outpatients with COVID-19. Metanalyses data provide no evidence of a benefit of anticoagulant prophylaxis in outpatients with COVID-19. These findings were the result of an underpowered study, therefore should be interpreted with caution. Funding: COALITION COVID-19 Brazil and Bayer S.A.

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BACKGROUND: Nosocomial sepsis is a major healthcare issue, but there are few data on estimates of its attributable mortality. We aimed to estimate attributable mortality fraction (AF) due to nosocomial sepsis. METHODS: Matched 1:1 case-control study in 37 hospitals in Brazil. Hospitalized patients in participating hospitals were included. Cases were hospital non-survivors and controls were hospital survivors, which were matched by admission type and date of discharge. Exposure was defined as occurrence of nosocomial sepsis, defined as antibiotic prescription plus presence of organ dysfunction attributed to sepsis without an alternative reason for organ failure; alternative definitions were explored. Main outcome measurement was nosocomial sepsis-attributable fractions, estimated using inversed-weight probabilities methods using generalized mixed model considering time-dependency of sepsis occurrence. RESULTS: 3588 patients from 37 hospitals were included. Mean age was 63 years and 48.8% were female at birth. 470 sepsis episodes occurred in 388 patients (311 in cases and 77 in control group), with pneumonia being the most common source of infection (44.3%). Average AF for sepsis mortality was 0.076 (95% CI 0.068-0.084) for medical admissions; 0.043 (95% CI 0.032-0.055) for elective surgical admissions; and 0.036 (95% CI 0.017-0.055) for emergency surgeries. In a time-dependent analysis, AF for sepsis rose linearly for medical admissions, reaching close to 0.12 on day 28; AF plateaued earlier for other admission types (0.04 for elective surgery and 0.07 for urgent surgery). Alternative sepsis definitions yield different estimates. CONCLUSION: The impact of nosocomial sepsis on outcome is more pronounced in medical admissions and tends to increase over time. The results, however, are sensitive to sepsis definitions.

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BACKGROUND: Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting. OBJECTIVE: To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients. METHODS: The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests. RESULTS: Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. CONCLUSION: The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

FUNDAMENTO: Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial. OBJETIVO: Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19. MÉTODOS: O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos. RESULTADOS: Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento. CONCLUSÃO: O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

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There is a growing interest in innovative products for eyebrow hair loss treatment with fewer adverse effects. Nevertheless, a fundamental formulation aspect of preventing the fragile skin from the ocular region from being irritated is that the formulations remain restricted to the application region and do not run off. Consequently, the methods and protocols in drug delivery scientific research must be adapted to fulfill such performance analysis demand. Thus, this work aimed to propose a novel protocol to evaluate the in vitro performance of a topical gel formulation with a reduced runoff for minoxidil (MXS) delivery to eyebrows. MXS was formulated with 16% poloxamer 407 (PLX) and 0.4% of hydroxypropyl methylcellulose (HPMC). The sol/gel transition temperature, viscosity at 25 °C, and formulation runoff distance on the skin were evaluated to characterize the formulation. The release profile and skin permeation were evaluated in Franz vertical diffusion cells for 12 h and compared to a control formulation (4% PLX and 0.7% HPMC). Then, the formulation's performance at promoting minoxidil skin penetration with minimum runoff was evaluated in a vertical custom-made permeation template (divided into three areas: superior, middle, and inferior). The MXS release profile from the test formulation was comparable to that from the MXS solution and the control formulation. There was also no difference in the MXS amount that penetrated the skin in the permeation experiments in Franz diffusion cells using the different formulations (p > 0.05). However, the test formulation demonstrated a localized MXS delivery at the application site in the vertical permeation experiment. In conclusion, the proposed protocol could differentiate the test formulation from the control, attesting to its better performance in efficiently delivering MXS to the site of interest (middle third of application). The vertical protocol can be easily employed to evaluate other gels with a drip-free appeal.

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Mephedrone (MEP) is an illicit stimulant drug that belongs to the synthetic cathinone (SC) class, which has been widely used for recreational purposes and reported in forensic analysis. The preliminary identification of MEP and other SCs in seized samples is of great interest for forensic investigation and a fast and simple screening test for these drugs would be useful for on-site and in-house analyses. In this study, we present the electrochemical detection of MEP in forensic samples using, for the first time, independent redox processes of SCs on a graphene screen-printed electrode (SPE-GP). The proposed method for MEP detection on the SPE-GP was optimized in Britton-Robinson buffer solution (0.1 mol L-1) at pH 10.0 with adsorptive stripping differential pulse voltammetry (AdSDPV). The use of the SPE-GP with AdSDPV provides a wide linear range for MEP determination (2.6 to 112 µmol L-1) with a low limit of detection (LOD) (0.3 µmol L-1). The real surface area available for adsorption on the SPE-GP was estimated to be between 3.80 and 5.70 cm2, which provided high sensitivity for the proposed method. Furthermore, good stability of MEP electrochemical responses on the SPE-GP was obtained using the same or different electrodes (N = 3), with relative standard deviation (RSD) < 5.0% for both redox processes. Interference studies for a common adulterant (caffeine) and twelve other illicit drugs (phenethylamines, amphetamines, and other SCs) were performed with a highly selective response for MEP detection. Therefore, the SPE-GP with AdSDPV is demonstrated to be a selective and sensitive screening method to detect MEP and other SCs in forensic analysis, providing a fast and simple preliminary identification of these drugs in seized samples.

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Background: Repurposed drugs for treatment of new onset disease may be an effective therapeutic shortcut. We aimed to evaluate the efficacy of repurposed antivirals compared to placebo in lowering SARS-CoV2 viral load of COVID-19 patients. Methods: REVOLUTIOn is a randomised, parallel, blinded, multistage, superiority and placebo controlled randomised trial conducted in 35 centres in Brazil. We include patients aged 18 years or older admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, symptoms onset 9 days or less and SpO2 94% or lower at room air were eligible. All participants were randomly allocated to receive either atazanavir, daclatasvir or sofosbuvir/daclatasvir or placebo for 10 days. The primary outcome was the decay rate (slope) of the SARS-CoV-2 viral load logarithm assessed in the modified intention to-treat population. This trial was registered with ClinicalTrials.gov, number NCT04468087. Findings: Between February 09, 2021, and August 04, 2021, 255 participants were enrolled and randomly assigned to atazanavir (n = 64), daclatasvir (n = 66), sofosbuvir/daclatasvir (n = 67) or placebo (n = 58). Compared to placebo group, the change from baseline to day 10 in log viral load was not significantly different for any of the treatment groups (0.05 [95% CI, -0.03 to 0.12], -0.02 [95% CI, -0.09 to 0.06], and -0.03 [95% CI, -0.11 to 0.04] for atazanavir, daclatasvir and sofosbuvir/daclatasvir groups respectively). There was no significant difference in the occurrence of serious adverse events between treatment groups. Interpretation: No significant reduction in viral load was observed from the use of atazanavir, daclatasvir or sofosbuvir/daclatasvir compared to placebo in hospitalised COVID-19 patients who need oxygen support with symptoms onset 9 days or less. Funding: Ministério da Ciência, Tecnologia e Inovação (MCTI) - Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ); Cia Latino-Americana de Medicamentos (Clamed); Cia Industrial H. Carlos Schneider (Ciser); Hospital Research Foundation Incorporation, Australia, HCor São Paulo; Blanver Farmoquímica; Instituto de Tecnologia em Fármacos (Farmanguinhos) da Fundação Oswaldo Cruz (Fiocruz); Coordenação Geral de Planejamento Estratégico (Cogeplan)/Fiocruz; and Fundação de apoio a Fiocruz (Fiotec, VPGDI-054-FIO-20-2-13).

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Rationale: Optimal infusion rate for fluid challenges in critically ill patients is unknown. A large clinical trial comparing two different infusion rates yielded neutral results. Conditional average treatment effect (CATE) assessment may aid in tailoring therapy. Objectives: To estimate CATE in patients enrolled in the BaSICS trial and to assess the effects of receiving CATE model-recommended treatment in terms of hospital mortality. Methods: Post hoc analysis of the BaSICS trial assessing the effect of two infusion rates for the fluid challenge (fast, 999 ml/h, control group; vs. slow, 333 ml/h, intervention group) on hospital mortality. CATE was estimated as the difference in outcome for treatment arms in counterfactuals obtained from a Bayesian model trained in the first half of the trial adjusted for predictors hypothesized to interact with the intervention. The model recommended slow or fast infusion or made no recommendation in the second half. A threshold greater than 0.90 probability of benefit was considered. Results: A total of 10,465 patients were analyzed. The model was trained in 5,230 patients and tested in 5,235 patients. A recommendation could be made in the test set in 19% of patients (14% were recommended the control group and 5% the treatment group); for 81% of patients, no recommendation could be made. Slow infusion was more frequently recommended in cases of planned admissions in younger patients; fast infusion was recommended for older patients with sepsis. Slow infusion rate in the subgroup of patients in the test set in which slow infusion was recommended by the model was associated with an odds ratio of 0.58 (95% credible interval of 0.32-0.90; 0.99 posterior probability of benefit) for hospital mortality. Fast infusion in the subgroup in which the model recommended fast infusion was associated with an odds ratio of 0.72 (credible intervals from 0.54 to 0.91; probability of benefit >0.99). Conclusions: Estimation of CATEs from counterfactual probabilities in data from BaSICS provided additional information on trial data. Agreement between treatment recommendation and actual treatment was associated with lower hospital mortality. Clinical trial registered with clinicaltrials.gov (NCT02875873).

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We aimed to assess the prevalence, patient allocation adequacy, and mortality of adults with sepsis in Brazilian emergency departments (ED) in a point-prevalence 3-day investigation of patients with sepsis who presented to the ED and those who remained there due to inadequate allocation. Allocation was considered adequate if the patient was transferred to the intensive care unit (ICU), ward, or remained in the ED without ICU admission requests. Prevalence was estimated using the total ED visit number. Prognostic factors were assessed with logistic regression. Of 33,902 ED visits in 74 institutions, 183 were acute admissions (prevalence: 5.4 sepsis per 1000 visits [95% confidence interval (CI): 4.6-6.2)], and 148 were already in the ED; totaling 331 patients. Hospital mortality was 32% (103/322, 95% CI 23.0-51.0). Age (odds ratio (OR) 1.22 [95% CI 1.10-1.37]), Sequential Organ Failure Assessment (SOFA) score (OR 1.41 [95% CI 1.28-1.57]), healthcare-associated infections (OR 2.59 [95% CI 1.24-5.50]) and low-resource institution admission (OR 2.65 [95% CI 1.07-6.90]) were associated with higher mortality. Accredited institutions (OR 0.42 [95% CI 0.21-0.86]) had lower mortality rates. Allocation within 24 h was adequate in only 52.8% of patients (public hospitals: 42.4% (81/190) vs. private institutions: 67.4% (89/132, p < 0.001) with 39.2% (74/189) of public hospital patients remaining in the ED until discharge, of whom 55.4% (41/74) died. Sepsis exerts high burden and mortality in Brazilian EDs with frequent inadequate allocation. Modifiable factors, such as resources and quality of care, are associated with reduced mortality.

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Anthocyanins are one of the natural pigments that humanity has employed the most and can substitute synthetic food dyes, which are considered toxic. They are responsible for most purple, blue, and red pigment nuances in tubers, fruits, and flowers. However, they have some limitations in light, pH, oxygen, and temperature conditions. Combining biomolecules and inorganic materials such as clay minerals can help to reverse these limitations. The present work aims to produce materials obtained using cetyltrimethylammonium bromide in bentonite clay for incorporation and photostabilization of anthocyanin dye. Characterizations showed that the organic molecules were intercalated between the clay mineral layers, and the dye was successfully incorporated at a different pH. Visible light-driven photostability tests were performed with 200 h of irradiation, confirming that the organic-inorganic matrices were efficient enough to stabilize the quinoidal base form of anthocyanin. The pigment prepared at pH 10 was three-fold more stable than pH 4, showing that the increase in the synthesis pH promotes more stable colors, probably due to the stronger intermolecular interaction obtained under these conditions. Therefore, organobentonite hybrids allow to stabilize the fragile color coming from the quinoidal base form of anthocyanin dyes.

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Resumo Fundamento Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial. Objetivo Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19. Métodos O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos. Resultados Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento. Conclusão O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

Abstract Background Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting. Objective To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients. Methods The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests. Results Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. Conclusion The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

RESUMO

Extended spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae is a medically important pathogen that commonly causes human nosocomial infections. Since veterinary emergency and critical care services have also significantly progressed over the last decades, there are increasing reports of ESBL-producing K. pneumoniae causing hospital-associated infections in companion animals. We present microbiological and genomic analysis of a multidrug-resistant ESBL-positive K. pneumoniae (LCKp01) isolated from a fatal infection in a dog admitted to a veterinary intensive care unit. LCKp01 strain belonged to the sequence type ST392 and displays a KL27 (wzi-187) and O-locus 4 (O4). A broad resistome and presence of the bla CTX-M-15 ESBL gene were predicted. SNP-based phylogenomic analysis, using an international genome database, clustered LCKp01 (60-80 SNPs differences) with K. pneumoniae ST392 from human and animal infections, isolated at 4-year interval, whereas phylogeographical analysis confirmed successful expansion of ST392 as a global clone of One Health concern.

RESUMO

TiO2/Karaya composite was synthesized by the sol-gel method for the photoinactivation of pathogens. This is the first time that we have reported this composite for an antimicrobial approach. The structure, morphology, and optical properties were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-rays (EDS), Fourier transform infrared spectroscopy (FTIR), and diffuse reflectance, and the surface area was characterized by the BET method. The XRD and EDS results showed that the TiO2/Karaya composite was successfully stabilized by the crystal structure and pore diameter distribution, indicating a composite of mesoporous nature. Furthermore, antibacterial experiments showed that the TiO2/Karaya composite under light was able to photoinactivate bacteria. Therefore, the composite is a promising candidate for inhibiting the growth of bacteria.