Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial.

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.

Boarding in the emergency department: challenges and mitigation strategies.

PURPOSE OF REVIEW: Herein, we conducted a review of the literature to better understand the issue of prolonged emergency department (ED) boarding by providing an overview of the current evidence on the available causes, consequences, and mitigation strategies. RECENT FINDINGS: Severely ill patients awaiting transfer to intensive care units (ICU) imposes additional burdens on the emergency care team from both a clinical and management perspective. The reasons for prolonged ED boarding are multifactorial. ED boarding compromises patients' safety and outcomes, and is associated with increased team burnout and dissatisfaction. Mitigation strategies include the optimization of patients' flow, the establishment of resuscitative care units, deployment of mobile critical care teams, and improvements in training. Staffing adjustments, changes in hospital operations, and quality improvement initiatives are required to improve this situation, while active bed management and implementation of capacity command centers may also help. SUMMARY: Considering the characteristics of healthcare systems, such as funding mechanisms, organizational structures, delivery models, access and quality of care, the challenge of ED boarding of critically ill patients requires a nuanced and adaptable approach. Solutions are complex but must involve the entirety of the hospital system, emergency department, staff adjustment, and education.

Assessment of the components of fluid balance in patients with septic shock: a prospective observational study.

BACKGROUND: The optimal amount for initial fluid resuscitation is still controversial in sepsis and the contribution of non-resuscitation fluids in fluid balance is unclear. We aimed to investigate the main components of fluid intake and fluid balance in both survivors and non-survivor patients with septic shock within the first 72 hours. METHODS: In this prospective observational study in two intensive care units, we recorded all fluids administered intravenously, orally, or enterally, and losses during specific time intervals from vasopressor initiation: T1 (up to 24 hours), T2 (24 to 48 hours) and T3 (48 to 72 hours). Logistic regression and a mathematical model assessed the association with mortality and the influence of severity of illness. RESULTS: We included 139 patients. The main components of fluid intake varied across different time intervals, with resuscitation and non-resuscitation fluids such as antimicrobials and maintenance fluids being significant contributors in T1 and nutritional therapy in T2/T3. A positive fluid balance both in T1 and T2 was associated with mortality (p = 0.049; p = 0.003), while nutritional support in T2 was associated with lower mortality (p = 0.040). The association with mortality was not explained by severity of illness scores. CONCLUSIONS: Non-resuscitation fluids are major contributors to a positive fluid balance within the first 48 hours of resuscitation. A positive fluid balance in the first 24 and 48 hours seems to independently increase the risk of death, while higher amount of nutrition seems protective. This data might inform fluid stewardship strategies aiming to improve outcomes and minimize complications in sepsis.

Contributing Factors for (Non)Adherence to a Physical Exercise Program for People With Neurocognitive Disorder From the Caregivers' Perspective.

BACKGROUND AND PURPOSE: To explore the perception of informal caregivers about the barriers, motivators, and facilitators toward the participation of care recipients with neurocognitive disorder (NCD) in a physical exercise program. METHODS: This is an exploratory qualitative study, including 20 informal caregivers (67.5 ± 13.94 years old; age range: 37-86; 65% male) from the "Body & Brain" community intervention project. Semistructured interviews were performed by a trained researcher; data analysis followed Braun and Clarke's thematic analysis guidelines, under the socioecological framework. RESULTS: Two main barriers, 3 motivators, and 5 facilitators to participation in a physical exercise program were perceived by caregivers, illustrating the relationship between the intrapersonal, interpersonal, and community levels toward individuals' participation. Care recipients' reluctance to participate and physical environment constraints emerged as the main barriers to participation, whereas the health professionals' advice, the need for a stimulating activity, and the potential physical and mental health benefits emerged as motivators. Factors facilitating the involvement and maintenance in the program included care recipients' satisfaction and enjoyment, benefits on their general health, routine, and social connectedness; an overall positive evaluation of the physical exercise program's structure and organization was also highlighted. CONCLUSIONS: Exercise interventions targeting people with NCD should promote a welcoming environment that facilitates individuals' well-being and social interaction. Caregivers have a key role in promoting care recipients' motivation. Health professionals play an important role in recommending participation by raising awareness of potential benefits to recipients and caregivers. Future interventions should be conducted in appropriate community settings and implemented by a specialized professional in small groups. These findings provide insights into the factors that may increase the success rate of exercise interventions specifically designed for individuals with NCD.

A New Global Definition of Acute Respiratory Distress Syndrome.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Balanced crystalloids versus saline for critically ill patients (BEST-Living): a systematic review and individual patient data meta-analysis.

BACKGROUND: The effect of balanced crystalloids compared with that of saline in critically ill patients overall and in specific subgroups is unclear. We aimed to assess whether use of balanced solutions, compared with 0·9% sodium chloride (saline), decreased in-hospital mortality in adult patients in intensive care units (ICUs). METHODS: For this systematic review and individual patient data meta-analysis, we searched PubMed, Embase, and CENTRAL databases from inception until March 1, 2022 (updated Sept 1, 2023) for individually randomised and cluster-randomised trials comparing balanced solutions with saline for adult patients in the ICU. Eligible trials were those that allocated patients to receive balanced solutions or saline for fluid resuscitation and maintenance fluids, or for maintenance fluids only; and administered the allocated fluid throughout ICU admission or, for trials using landmark mortality as their primary outcome, until the timepoint at which mortality was assessed (if ≥28 days). Authors of eligible trials were contacted to request individual patient data. Data obtained from eligible trials were merged, checked for accuracy, and centrally analysed by use of Bayesian regression models. The primary outcome was in-hospital mortality. Prespecified subgroups included patients with traumatic brain injury. This study was registered with PROSPERO (CRD42022299282). FINDINGS: Our search identified 5219 records, yielding six eligible randomised controlled trials. Data obtained for 34 685 participants from the six trials, 17 407 assigned to receive balanced crystalloids and 17 278 to receive saline, were included in the analysis. The mean age of participants was 58·8 years (SD 17·5). Of 34 653 participants with available data, 14 579 (42·1%) were female and 20 074 (57·9%) were male. Among patients who provided consent to report in-hospital mortality, 2907 (16·8%) of 17 313 assigned balanced solutions and 2975 (17·3%) of 17 166 assigned saline died in hospital (odds ratio [OR] 0·962 [95% CrI 0·909 to 1·019], absolute difference -0·4 percentage points [-1·5 to 0·2]). The posterior probability that balanced solutions reduced mortality was 0·895. In patients with traumatic brain injury, 191 (19·1%) of 999 assigned balanced and 141 (14·7%) of 962 assigned saline died (OR 1·424 [1·100 to 1·818], absolute difference 3·2 percentage points [0·7 to 8·7]). The probability that balanced solutions increased mortality in patients with traumatic brain injury was 0·975. In an independent risk of bias assessment, two trials were deemed to be at low risk of bias and four at high risk of bias. INTERPRETATION: The probability that using balanced solutions in the ICU reduces in-hospital mortality is high, although the certainty of the evidence was moderate and the absolute risk reduction was small. In patients with traumatic brain injury, using balanced solutions was associated with increased in-hospital mortality. FUNDING: HCor (Brazil) and The George Institute for Global Health (Australia).

Determinants of fluid use and the association between volume of fluid used and effect of balanced solutions on mortality in critically ill patients: a secondary analysis of the BaSICS trial.

PURPOSE: Fluid use could modulate the effect of balanced solutions (BS) on outcome of intensive care unit (ICU) patients. It is uncertain whether fluid use practices are driven more by patient features or local practices. It is also unclear whether a "dose-response" for the potential benefits of balanced solutions exists. METHODS: The secondary analysis of the Balanced Solution in Intensive Care Study (BaSICS) compared 0.9% saline versus Plasma-Lyte 148® (BS) for fluid therapy in the ICU. The relative contribution of patient features and enrolling site (the random effect) on the volume of fluid used up to day 3 after admission was assessed using different methods, including a Bayesian regression, a frequentist mixed model, and a random forest, all adjusted for relevant patient confounders. Subsequently, a variety of methods were used to assess whether volume of fluid used modulated the effect of BS on 90-day mortality, including a traditional subgroup analysis for patients that remained alive and in the ICU up to 3 days, a Bayesian network accounting for competing risks, and an analysis based on site practices. RESULTS: 10,505 patients were analyzed. Median fluid use in the BS arm and in the 0.9% saline arm were 2500 mL and 2488 mL, respectively. The random effect in the Bayesian regression explained 0.32 (95% credible intervals (CrI) 0.24-0.41) of all model variance (0.33, 95% credible intervals from 0.32-0.35). Frequentist and random forest models produced similar results. In the analysis including only patients alive and in the ICU at 3 days, there was a strong suggestion of interaction between fluid use and the effect of BS, driven mostly by a lower mortality with BS compared to 0.9% saline as fluid use increased for patients with sepsis. These results were consistent in the Bayesian network analysis and in an analysis based on site practices, where septic patients enrolled to BS at high fluid use sites had a lower mortality (absolute risk reduction of - 0.13 [95% credible interval - 0.27 to - 0.01]; 0.98 probability of benefit). CONCLUSION: Baseline patient characteristics collected in the BaSICS trial explain less of the variance of fluid use during the first 3 days than the enrolling site. Volume of fluid used and the effects of BS appear to interact, mostly in the sepsis subgroup where there was a strong association between fluid use after enrollment and the effect of BS on 90-day mortality.

Do physical fitness and cognitive function mediate the relationship between basic activities of daily living and quality of life in older adults with dementia?

PURPOSE: Independence in activities of daily living (ADLs) is associated with quality of life (QoL) in individuals with dementia. However, the contribution of physical and cognitive functions to this relationship needs further examination. This study aims to examine the mediating effect of physical fitness and cognitive function in the relationship between independence in basic ADLs and QoL among older adults with dementia. METHODS: This cross-sectional study included 107 older adults with dementia (74.8% women; age 78.21 ± 7.70 years). Independence in basic ADL and QoL were evaluated using the Barthel Index (BI) and QoL- Alzheimer's Disease Scale, respectively. The Alzheimer's Disease Assessment Scale-Cognitive Subscale and the Mini-Mental State Examination were applied to assess cognitive function. Physical fitness was evaluated using the 30-s chair stand, 2-min step and the Timed-Up and Go tests. A structural equation modelling (SEM) with bootstrapping estimation was conducted to determine the relationship between all variables. RESULTS: Independence in basic ADL positively affected QoL and this association was mediated by physical fitness (ß = 0.242, p = 0.011). No statistically significant results were observed when testing cognitive function as a mediator between BI and QoL (ß = 0.009, p = 0.345). CONCLUSIONS: Physical fitness (i.e., lower body strength, aerobic capacity, and mobility) plays a role in the relationship between basic ADL independence and QoL of older adults with dementia, reinforcing the need to improve and monitor these parameters throughout the disease progression. Future longitudinal studies should explore the temporal relationship between physical and cognitive function and its contribution to basic ADL independence and QoL.

Cardiovascular Safety of Azithromycin in Patients Hospitalized With COVID-19: A Prespecified Pooled Analysis of the COALITION I and COALITION II Randomized Clinical Trials.

The cardiovascular safety from azithromycin in the treatment of several infectious diseases has been challenged. In this prespecified pooled analysis of 2 multicenter randomized clinical trials, we aimed to assess whether the use of azithromycin might lead to corrected QT (QTc) interval prolongation or clinically relevant ventricular arrhythmias. In the COALITION COVID Brazil I trial, 667 patients admitted with moderate COVID-19 were randomly allocated to hydroxychloroquine, hydroxychloroquine plus azithromycin, or standard of care. In the COALITION COVID Brazil II trial, 447 patients with severe COVID-19 were randomly allocated to hydroxychloroquine alone versus hydroxychloroquine plus azithromycin. The principal end point for the present analysis was the composite of death, resuscitated cardiac arrest, or ventricular arrhythmias. The addition of azithromycin to hydroxychloroquine did not result in any prolongation of the QTc interval (425.8 ± 3.6 ms vs 427.9 ± 3.9 ms, respectively, mean difference -2.1 ms, 95% confidence interval -12.5 to 8.4 ms, p = 0.70). The combination of azithromycin plus hydroxychloroquine compared with hydroxychloroquine alone did not result in increased risk of the primary end point (proportion of patients with events at 15 days 17.2% vs 16.0%, respectively, hazard ratio 1.08, 95% confidence interval 0.78 to 1.49, p = 0.65). In conclusion, in patients hospitalized with COVID-19 already receiving standard-of-care management (including hydroxychloroquine), the addition of azithromycin did not result in the prolongation of the QTc interval or increase in cardiovascular adverse events. Because azithromycin is among the most commonly prescribed antimicrobial agents, our results may inform clinical practice. Clinical Trial Registration: NCT04322123, NCT04321278.

Assessment of the components of fluid balance in patients with septic shock: a prospective observational study

Abstract Background: The optimal amount for initial fluid resuscitation is still controversial in sepsis and the contribution of non-resuscitation fluids in fluid balance is unclear. We aimed to investigate the main components of fluid intake and fluid balance in both survivors and non-survivor patients with septic shock within the first 72 hours. Methods: In this prospective observational study in two intensive care units, we recorded all fluids administered intravenously, orally, or enterally, and losses during specific time intervals from vasopressor initiation: T1 (up to 24 hours), T2 (24 to 48 hours) and T3 (48 to 72 hours). Logistic regression and a mathematical model assessed the association with mortality and the influence of severity of illness. Results: We included 139 patients. The main components of fluid intake varied across different time intervals, with resuscitation and non-resuscitation fluids such as antimicrobials and maintenance fluids being significant contributors in T1 and nutritional therapy in T2/T3. A positive fluid balance both in T1 and T2 was associated with mortality (p = 0.049; p = 0.003), while nutritional support in T2 was associated with lower mortality (p = 0.040). The association with mortality was not explained by severity of illness scores. Conclusions: Non-resuscitation fluids are major contributors to a positive fluid balance within the first 48 hours of resuscitation. A positive fluid balance in the first 24 and 48 hours seems to independently increase the risk of death, while higher amount of nutrition seems protective. This data might inform fluid stewardship strategies aiming to improve outcomes and minimize complications in sepsis.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan / Estudo randomizado prospectivo e controlado de avaliação dos efeitos de uma estratégia de limitação da driving pressure em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade (estudo STAMINA): protocolo e plano de análise estatística

ABSTRACT Background: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. Objective: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. Methods: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. Outcomes: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. Conclusion: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

RESUMO Contexto: Em estudos observacionais sobre a síndrome do desconforto respiratório agudo, sugeriu-se que a driving pressure é o principal fator de lesão pulmonar induzida por ventilador e de mortalidade. Não está claro se uma estratégia de limitação da driving pressure pode melhorar os desfechos clínicos. Objetivo: Descrever o protocolo e o plano de análise estatística que serão usados para testar se uma estratégia de limitação da driving pressure envolvendo a titulação da pressão positiva expiratória final de acordo com a melhor complacência respiratória e a redução do volume corrente é superior a uma estratégia padrão envolvendo o uso da tabela de pressão positiva expiratória final baixa do protocolo ARDSNet, em termos de aumento do número de dias sem ventilador em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade. Métodos: O estudo STAMINA (ventilator STrAtegy for coMmunIty acquired pNeumoniA) é randomizado, multicêntrico e aberto e compara uma estratégia de limitação da driving pressure com a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet em pacientes com síndrome do desconforto respiratório agudo moderada a grave devido à pneumonia adquirida na comunidade internados em unidades de terapia intensiva. Esperamos recrutar 500 pacientes de 20 unidades de terapia intensiva brasileiras e duas colombianas. Eles serão randomizados para um grupo da estratégia de limitação da driving pressure ou para um grupo de estratégia padrão usando a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet. No grupo da estratégia de limitação da driving pressure, a pressão positiva expiratória final será titulada de acordo com a melhor complacência do sistema respiratório. Desfechos: O desfecho primário é o número de dias sem ventilador em 28 dias. Os desfechos secundários são a mortalidade hospitalar e na unidade de terapia intensiva e a necessidade de terapias de resgate, como suporte de vida extracorpóreo, manobras de recrutamento e óxido nítrico inalado. Conclusão: O STAMINA foi projetado para fornecer evidências sobre se uma estratégia de limitação da driving pressure é superior à estratégia da tabela de pressão positiva expiratória final baixa do protocolo ARDSnet para aumentar o número de dias sem ventilador em 28 dias em pacientes com síndrome do desconforto respiratório agudo moderada a grave. Aqui, descrevemos a justificativa, o desenho e o status do estudo.

Evidence-Based Checklist to Delay Cardiac Arrest in Brain-Dead Potential Organ Donors: The DONORS Cluster Randomized Clinical Trial.

Importance: The effectiveness of goal-directed care to reduce loss of brain-dead potential donors to cardiac arrest is unclear. Objective: To evaluate the effectiveness of an evidence-based, goal-directed checklist in the clinical management of brain-dead potential donors in the intensive care unit (ICU). Design, Setting, and Participants: The Donation Network to Optimize Organ Recovery Study (DONORS) was an open-label, parallel-group cluster randomized clinical trial in Brazil. Enrollment and follow-up were conducted from June 20, 2017, to November 30, 2019. Hospital ICUs that reported 10 or more brain deaths in the previous 2 years were included. Consecutive brain-dead potential donors in the ICU aged 14 to 90 years with a condition consistent with brain death after the first clinical examination were enrolled. Participants were randomized to either the intervention group or the control group. The intention-to-treat data analysis was conducted from June 15 to August 30, 2020. Interventions: Hospital staff in the intervention group were instructed to administer to brain-dead potential donors in the intervention group an evidence-based checklist with 13 clinical goals and 14 corresponding actions to guide care, every 6 hours, from study enrollment to organ retrieval. The control group provided or received usual care. Main Outcomes and Measures: The primary outcome was loss of brain-dead potential donors to cardiac arrest at the individual level. A prespecified sensitivity analysis assessed the effect of adherence to the checklist in the intervention group. Results: Among the 1771 brain-dead potential donors screened in 63 hospitals, 1535 were included. These patients included 673 males (59.2%) and had a median (IQR) age of 51 (36.3-62.0) years. The main cause of brain injury was stroke (877 [57.1%]), followed by trauma (485 [31.6%]). Of the 63 hospitals, 31 (49.2%) were assigned to the intervention group (743 [48.4%] brain-dead potential donors) and 32 (50.8%) to the control group (792 [51.6%] brain-dead potential donors). Seventy potential donors (9.4%) at intervention hospitals and 117 (14.8%) at control hospitals met the primary outcome (risk ratio [RR], 0.70; 95% CI, 0.46-1.08; P = .11). The primary outcome rate was lower in those with adherence higher than 79.0% than in the control group (5.3% vs 14.8%; RR, 0.41; 95% CI, 0.22-0.78; P = .006). Conclusions and Relevance: This cluster randomized clinical trial was inconclusive in determining whether the overall use of an evidence-based, goal-directed checklist reduced brain-dead potential donor loss to cardiac arrest. The findings suggest that use of such a checklist has limited effectiveness without adherence to the actions recommended in this checklist. Trial Registration: ClinicalTrials.gov Identifier: NCT03179020.

The II Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19 Joint Guidelines of the Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia and Sociedade Brasileira de Reumatologia.

OBJECTIVE: To update the recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. METHODS: Experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. RESULTS: Twenty-one recommendations were generated, including strong recommendations for the use of corticosteroids in patients using supplemental oxygen and conditional recommendations for the use of tocilizumab and baricitinib for patients on supplemental oxygen or on noninvasive ventilation and anticoagulants to prevent thromboembolism. Due to suspension of use authorization, it was not possible to make recommendations regarding the use of casirivimab + imdevimab. Strong recommendations against the use of azithromycin in patients without suspected bacterial infection, hydroxychloroquine, convalescent plasma, colchicine, and lopinavir + ritonavir and conditional recommendations against the use of ivermectin and remdesivir were made. CONCLUSION: New recommendations for the treatment of hospitalized patients with COVID-19 were generated, such as those for tocilizumab and baricitinib. Corticosteroids and prophylaxis for thromboembolism are still recommended, the latter with conditional recommendation. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and to promote resource economy.

Neuropsychiatric Symptoms are Related to Blood-biomarkers in Major Neurocognitive Disorders.

BACKGROUND: Neuropsychiatric symptoms (NPS) are highly prevalent among individuals with major neurocognitive disorders (MNCD). OBJECTIVE: Here, we characterized blood biomarkers (metabolic, inflammatory, neurotrophic profiles and total antioxidant), body composition, physical fitness and quality of life (QoL) in individuals with MNCD according to NPS. METHODS: The sample comprised 34 older adults (71.4% women; 74.06±6.03 yrs, with MNCD diagnosis) categorized according to 50th percentile [Low (≤12) or High (≥13)] for NPS (Neuropsychiatric Inventory Questionnaire). Sociodemographic, clinical data, body composition, anthropometric, cognitive assessment (ADAS-Cog), physical fitness (Senior Fitness Test), QoL (QoL-Alzheimer's Disease scale) were evaluated, and blood samples were collected for biochemical analysis. RESULTS: Low compared to high NPS group showed higher levels of IL-6, IGF-1and neurotrophic zscore (composite of IGF-1, VEGF-1, BDNF). Additionally, low compared to high NPS group have higher QoL, aerobic fitness and upper body and lower body strength. CONCLUSION: The severity of NPS seems to be related to modified neurotrophic and inflammatory outcomes, lower physical fitness, and poor QoL. Strategies to counteract NPS development may preserve the physical and mental health of individuals with MNCD.

A psychometric study of an executive function assessment instrument (TDI-FE).

BACKGROUND: This study aims to present and discuss the psychometric properties of executive functions, which were measured using the TDI-FE instrument. The analysis encompasses its internal structure, potential sensitivity to fatigue factors, relationships with external criteria, and diagnostic accuracy. METHODS: The study sample comprised 382 students from Brazil, aged 6-8 years. Child development variables were screened using the TDI-FE and gold standard tests (Cancellation Attention and Trail Making Tests). The proposed scale comprised four activities: a test with fruit images with three tasks, and one memory game. RESULTS: The one-factor model of EF of the TDI-FE failed to fit to the data. However, fit substantially improved once a latent fatigue factor was controlled in the model. The latent factor of EF assessed by the TDI-FE tasks was coherently associated with a series of external variables, including two popular collateral measures of EF. The diagnostic accuracy was reasonable, and a cut-off of 37 points produced 70% of sensitivity and 60% of specificity. CONCLUSION: Results indicated that the TDI-FE demonstrated sound psychometric properties and diagnostic accuracy, then consisting of an efficient alternative for the assessment of EFs in early childhood education. The study also proved the need to control for response biases such as fatigue in the latent variable models of EF. The TDI-FE is notable because of its low cost and easy application, and it might fulfill a need for instruments for individuals from different contexts at this stage of development in Brazil.

Should Caregivers Also Be Included in Multicomponent Physical-Exercise-Based Interventions for People with a Neurocognitive Disorder? The Caregivers' Perspective.

Informal caregivers of people with neurocognitive disorders (NCDs) may play a decisive role in guaranteeing partners' participation in community-based physical exercise interventions. However, little is still known about their perspective on being involved in such programs that are specifically designed for their partners. This study aimed to explore the views of caregivers of people with NCDs about taking part in a multicomponent physical exercise intervention with their partners and to explore the perceived impact of this program on those caregivers who enrolled in it. An exploratory qualitative study was conducted with 20 caregivers (67.5 ± 13.94 years; seven female) from the "Body & Brain" project. Ten took part in the physical exercise sessions (active-participating caregivers), and the others did not (social-participating caregivers). Data retrieved from semi-structured interviews were analyzed following a thematic analysis approach. Regardless of their participation level, all caregivers reported their inclusion to be important in enhancing their partners' initiation and engagement in the sessions; also, they all identified personal gains. Active-participating caregivers reported exercise-related benefits on general health, enjoyment, and social connectedness. Social-participating caregivers considered this intervention an opportunity for respite and appreciated being involved only occasionally (i.e., occasional gatherings or telephone contacts). The findings support the inclusion of caregivers in physical exercise interventions designed for partners with NCDs, considering their decisive role in the partners' adherence and engagement and due to the perceived gains. Future community-based interventions designed for people with NCDs should consider giving caregivers the opportunity to choose whether they want or not to be actively involved in the exercise sessions. Further studies with larger samples are needed to verify these results, comparing caregivers' point of view at baseline and post-intervention.